19 S1

Contents

Cystic Fibrosis Research Topics Featured at the CFTR processing, trafficking and interactions 16th ECFS Basic Conference, Dubrovnik, M.D. Amaral, D.M. Hutt, V. Tomati, H.M. Botelho, Croatia, 27-30 March, 2019 N. Pedemonte (Portugal, USA, Italy) S33 Guest Editors: Cliff Taggart, Isabelle Callebaut, Alternative chloride transport pathways as Carlos Farinha and Martin Mense pharmacological targets for the treatment of cystic Journal of Cystic FibrosisJournal Journal of Cystic Fibrosis Journal Journal of Exploring the basic mechanisms in Cystic Fibrosis: fibrosis Promoting data presentation and discussion at the R. Quesada, R. Dutzler (Spain, Switzerland) S37 16th ECFS Basic Science Conference Regeneration of airway epithelial cells to study rare cell I. Callebaut, M. Mense, C.M. Farinha states in cystic fibrosis (France, USA, Portugal) S1 P. Barbry, A. Cavard, M. Chanson, A.B. Jaffe, L.W. Plasschaert (France, Switzerland, USA) S42 Cystic Fibrosis The and genomics of cystic fibrosis N. Sharma, G.R. Cutting (USA) S5 Interplay between host-microbe and microbe-microbe Genetic variation in CFTR and modifier loci may interactions in cystic fibrosis The Official Journal of the European Cystic Fibrosis Society modulate cystic fibrosis disease severity C.R. Armbruster, T. Coenye, L. Touqui, A. Paranjapye, M. Ruffin, A. Harris, J.M. Bomberger (USA, Belgium, France) S47 H. Corvol (USA, France) S10 New approaches to genetic therapies for cystic fibrosis The influence of CFTR complex alleles on precision A. Christopher Boyd, S. Guo, L. Huang, therapy of cystic fibrosis B. Kerem, Y.S. Oren, A.J. Walker, B. Chevalier, A. Hinzpeter (France) S15 S.L. Hart (UK, USA, Israel) S54 CFTR: New insights into structure and function and Intestinal organoids for Cystic Fibrosis research implications for modulation by small molecules E. de Poel, J.W. Lefferts, J.M. Beekman B. Kleizen, J.F. Hunt, I. Callebaut, T.-C. Hwang, (the Netherlands) S60 I. Sermet-Gaudelus, S. Hafkemeyer, D.N. Sheppard

(the Netherlands, USA, France, Germany, UK) S19 ECFS Cystic Fibrosis Research Towards next generation therapies for cystic fibrosis: Folding, function and pharmacology of CFTR S.J. Bose, G. Krainer, D.R.S. Ng, M. Schenkel, H. Shishido, J.S. Yoon, P.M. Haggie, M. Schlierf, D.N. Sheppard, W.R. Skach (UK, Germany, USA) S25 Pages S1–S186 Supplement:

Cystic Fibrosis Research Topics Featured at the Volume 19 Suppl. 12

Pages S1 – Abstracts of the 16th43rd EuropeanECFS Basic CysticScience Fibrosis Conference, Conference Dubrovnik, – 2020 MarchJune 2020 2020 S64 Croatia, 27-30 March, 2019 ISSN 1569-1993

Guest Editors: Cliff Taggart, Isabelle Callebaut,

ELSEVIER Carlos Farinha and Martin Mense

Publication of this Abstract Book was supported by the European Cystic ELSEVIER Publication of this Supplement is supported by The European Cystic Fibrosis 4.290 SocietyFibrosis (ECFS)Society

www.ECFS.eu Editorial Board Editor-in-Chief: Scott Bell, Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Queensland, Australia Deputy Editors: Carlo Castellani, IRCCS Istituto Giannina Gaslini, Cystic Fibrosis Centre, Genoa, Italy Patrick Flume, Medical University of South Carolina, Charleston, South Carolina, USA Founding Editor: Harry Heijerman, Dept. of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands Editorial Board: Scott Blackman, USA Geraint Rogers, Australia Pierre-Régis Burgel, France Steven Rowe, USA Neelkamal Chaudhary, USA Laura Sherrard, UK Aleksander Edelman, France Anne Stephenson, Canada Pascale Fanen, France Cliff Taggart, UK Niels Høiby, Denmark Daan Touw, The Netherlands Paul McCray, USA Michael Tunney, N. Ireland Marianne Muhlebach, USA Donald Van Devanter, USA Gerald Pier, USA Michael Wilschanski, Israel Felix Ratjen, Canada Jeffrey Wine, USA Kristin A. Riekert, USA Susannah King, Australia Statistical Advisers: Christine Etherington, Christoph Meisner, Germany Editor In Chief, Cystic Fibrosis Research News: Harry Heijerman, Dept. of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands

Amsterdam — Boston — — New York — Oxford — Paris — Philadelphia — San Diego — St. Louis — Tokyo Volume 19, Supplement 12 (2020)

Cystic Fibrosis Research TopicsAbstracts Featured of the at the 16th ECFS Basic Science Conference,43rd European Dubrovnik, Cystic Fibrosis Croatia, Conference 27-30xx–xx March,June – 2020 2020 2019

Guest Editors:

Cliff Taggart, Isabelle Callebaut, Carlos Farinha, and Martin Mense

Publication of this Supplement is supported by The European Cystic Fibrosis Society (ECFS)

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Abstracts of thethe 43rd40th European CysticCystic FibrosisFibrosis Conference Conference – 2020 Seville, Spain, 7–10 June 2017

Workshops ����������������������������������������������������������������������������������������������������������������������������������������������������������������������S1S1

WorkshopWS01 Airways: 1. Old improving and new clinical thoughts care on ��������������������������������������������������������������������������������������������������������������������������������� antibiotics ...... S1 S1 WorkshopWS02 Equality 2. : and diversity from in daily CF: engaging practice tothe enzymes disengaged for ���������������������������������������������������������������������������������������� the future ...... S2 S3 WorkshopWS03 Liver 3. disease/gut New therapies inflammation targeting ����������������������������������������������������������������������������������������������������������������������������������� the airway surface ...... S4 S4 WorkshopWS04 Role 4.of Newnew biomarkers insights from �������������������������������������������������������������������������������������������������������������������������������������������������� inflammation and immunology...... S6 S6 WorkshopWS05 CFTR 5. structure Anxiety and and trafficking depression: �������������������������������������������������������������������������������������������������������������������������������������� a family affair ...... S8 S7 WorkshopWS06 LCI - 6.Old CFTR Method dysfunction: but new data what ������������������������������������������������������������������������������������������������������������������������������������ happens where? ...... S9 S9 WorkshopWS07 Physiotherapy 7. Microbiome at home analysis ������������������������������������������������������������������������������������������������������������������������������������������������� in CF: what’s new in lung and gut?...... S11 S11 WorkshopWS08 The CF 8. CTairway and microbiome: MRI, where areomics-based we? Ready detection yet for theand clinics? monitoring...... ������������������������������������������������������������S13 S12 WorkshopWS09 Improving 9. Exercise the diagnosis and correlations of CF ������������������������������������������������������������������������������������������������������������������������������������ with other outcomes...... S15 S14 WorkshopWS10 Moving 10. beyond The impact body of mass CF: index high mountains to assess nutritional – deep valleys status...... in CF ��������������������������������������������������������������S16 S16 WorkshopWS11 The link 11. Newbornbetween CFTR screening modulators and diagnostic and mutations advances ���������������������������������������������������������������������������������������������...... S18 S17 WorkshopWS12 Immunology 12. Bone - health,targets glucosefor therapy metabolism ����������������������������������������������������������������������������������������������������������������������������� and CFRD ...... S19 S19 WS13 CFTR Modulators: to have and to have not �������������������������������������������������������������������������������������������������������������S21 Workshop 13. Rescuing CFTR: new developments ...... S20 WS14 When the going gets tough: improving multidisciplinary team working ��������������������������������������������������� S23 Workshop 14. Basic pathogenesis: Pseudomonas, microbiota interaction and viruses...... S22 WS15 Cystic Fibrosis-Related Diabetes: improved diagnosis and prevention of complications ���������������������� S25 Workshop 15. New lung function methods to monitor disease and treatment ...... S24 WS16 The role of physical exercise: impacts on health ��������������������������������������������������������������������������������������������������S27 Workshop 16. Understanding and teaching, a knowledge network...... S26 WS17 Beyond modulators: approaches involving gene editing or alternative channels ������������������������������������ S28 Workshop 17. CF related liver disease and pancreatic insufficiency: can we do better?...... S28 WS18 Nontuberculous mycobacterial infection: outcomes, transmission and treatment ��������������������������������� S30 Workshop 18. CFTR: Functional tests for therapeutic interventions ...... S29 WS19 New insights into CFTR-modulating therapies ������������������������������������������������������������������������������������������������������S31 Workshop 20. Evolving and risk factors for lung infection...... S31 WS21 CFTR gene: from regulation to phenotype ������������������������������������������������������������������������������������������������������������� S33 Workshop 21. How to personalise chest physiotherapy? ...... S32 WS23 CF Disease is evolving: latest data from Registries ��������������������������������������������������������������������������������������������� S34 Workshop 23. Insights from registries and cohorts...... S34 ePS01.E-Posters Screening ������������������������������������������������������������������������������������������������������������������������������� and Diagnosis ...... ������������������������������������������ S37 S36 ePS02. The CF team in development ...... S39 ePoster Session 1: Multiple challenges in physiotherapy ����������������������������������������������������������������������������������������������S37 ePS03. New treatments ...... S41 ePoster Session 2: Adult complications ������������������������������������������������������������������������������������������������������������������������������ S40 ePS04. Multi-tasking physiotherapists: managing , pain, exercise, ...... S43 ePoster Session 3: Inflammation goes wild ����������������������������������������������������������������������������������������������������������������������� S43 ePoster Session 4: Highs and lows of nutritional status evaluation �������������������������������������������������������������������������� S46 ePoster Session 5: Measuring what people with cystic fibrosis think ���������������������������������������������������������������������� S49 ePoster Session 6: Cystic fibrosis airway infection: novel methods for detection and treatment ������������������� S52

Posters ���������������������������������������������������������������������������������������������������������������������������������������������������������������������� S55

Genetics ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� S55 Diagnosis/Screening ������������������������������������������������������������������������������������������������������������������������������������������������������������������ S58 Epidemiology/Registry ������������������������������������������������������������������������������������������������������������������������������������������������������������� S64 Microbiology/Antibiotics ����������������������������������������������������������������������������������������������������������������������������������������������������������S76 Pulmonology/Inflammation/Immunology ����������������������������������������������������������������������������������������������������������������������� S102 Cell /Physiology/Clinical Trials/New Therapies �������������������������������������������������������������������������������������������������S113 Gastroenterology/Liver Disease//Metabolic Complications ����������������������������������������������������������� S122 Nutrition/Growth ��������������������������������������������������������������������������������������������������������������������������������������������������������������������� S131 Physiotherapy ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������� S137 Nursing/Psychosocial Issues ������������������������������������������������������������������������������������������������������������������������������������������������� S149

Author Index ����������������������������������������������������������������������������������������������������������������������������������������������������������� S169

This abstract book has been produced electronically by Elsevier B.V., and is also available on USB.

Every effort has been made to faithfully reproduce the abstracts as submitted. However, no responsibility is assumed by the organisers and the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of the rapid advances in the medical sciences, we recommend that independent verification of diagnoses and drug dosages should be made. Journal of Cystic Fibrosis 19S2 (2020) S1–S36

Workshops

only as a support to airways clearance, in palliative care and as a bridge to WS01 Airways: improving clinical care lung transplantation. Aim: To analyse NIV use in CF adults. WS01.1 Methods: We conducted a retrospective observational study on the use of Low frequency of confirmed hypersensitivity to antibiotics in cystic NIV in CF patients (pts) at the Orbassano Adult Centre from 1996 to 2019. fibrosis patients We collected data at the beginning of NIV, after 6 months and 1–3 years 1,2 1,3 4 4 4 (yrs) of chronic use. C. Braun ,P.Reix , I. Durieu , R. Nove-Josserand , S. Durupt , 1 1 2,5 2,5 1 1 Results: 22 pts (12 F - 54.6%) were adapted to NIV. Clinical characteristic at C. Ohlmann , C. Mainguy , J.-F. Nicolas , A. Nosbaum , V. Jubin . Hospices the enrollment were: mean age 34.2 yrs (22–59); 21/22 (95%) pancreatic Civils de Lyon, Pediatric Pulmonology and Allergology Department, Pediatric 2 2 insufficient, mean BMI 19.99 Kg/m (15.7–25.7); chronic P. Aeruginosa Cystic Fibrosis Center, Hôpital Femme Merè Enfant, Bron, France; CIRI - Centre infection in 12/22 (54%); mean ppFEV 31.3 (15–46); mean arterial pH 7.39 International de Recherche en Infectiologie (International Center for 1 3 (7.30–7.44), mean arterial pCO2 48.75 mmHg (33–80); in the previous year Infectiology Research), INSERM U 1111, CNRS UMR 5308, Lyon, France; UMR 4 pts received each a mean of 3.76 cycles of intravenous antibiotics (iv atb). 5558 (EMET), CNRS, LBBE, University of Lyon, Villeurbanne, France; Internal PSV was the most common mode of ventilation (86.4%). The main and Vascular Pathology Department, Adult Cystic Fibrosis Center, indication for NIV was respiratory exacerbation with acute respiratory Groupement Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, 5 failure (77.3%). Even in advanced disease a positive trend in lung function France; Allergology and Clinical Immunology Department, Groupement and nutritional status was observed with trend in reduction in antibiotics Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France use. At 6 months mean ppFEV1 was 30.05%. Objectives: Cystic fibrosis (CF) patients receive many antibiotic treatments (15–44), mean arterial pCO2 48.67 mmHg (36.6–63), mean BMI 20.26 Kg/ 2 – – 2 for recurrent respiratory infections and frequently report antibiotic m (16.1 26). At 1 yr: mean ppFEV1 32.4% (18 49), mean BMI 20.38 Kg/m hypersensitivity reactions (HSRs). The aim of this study was to define the (15.7–26.5), mean arterial pCO2 45.32 mmHg (32.5–64), 3.54 cycles iv atb/ prevalence and clinical features of antibiotic HSRs in the CF population, yr/pt. At 3 yr, 6 pts were still on NIV: mean ppFEV1 32.5%. according to a complete allergy work-up. (24–40), mean BMI 19.58 Kg/m2 (16.9–21.45), mean arterial pCO2 44.68 Methods: In this retrospective study, medical records of CF patients were mmHg (35.4–69),. reviewed to clarify the clinical features, the culprit antibiotics and the 3.33 cycles ev atb/yr/pt. 13 (59%) pts were transplanted. prevalence of antibiotic HSRs in the CF population. Conclusions: NIV in adults CF with respiratory failure is a good option, Results: From 601 CF patients, 95 “suspected antibiotic HSRs” occurred which preserves lung function and nutritional status even in pts with (prevalence of 10.0%). severe disease. β-lactams were the most common inducers but cotrimoxazole was also frequently involved. 76 of 95 suspected HSRs were assessed by allergy WS01.3 work-up including skin tests (43/76 reactions) and/or drug reintroduction Сhronic rhinosinusitis with nasal polyps (CRSwNP) in adult cystic as a full course of the culprit antibiotic (73/76 reactions). From the 43 HSRs fibrosis patients: optimal medical and surgical strategies that were skin tested, only 3 were “allergic” based on positive skin tests and G. Shumkova1, E. Amelina1, V. Svistushkin2, S. Krasovskiy1, E. Sinkov2. were not subjected to drug readministration. All the other 73 “suspected 1Pulmonology Research Institute under FMBA of Russia, Moscow, Russian HSRs” received a full course of the culprit antibiotic: HSR symptoms Federation; 2First Moscow State Medical University of the Ministry of Health of recurred in 10/73 cases and therefore were considered as “confirmed the Russian Federation (Sechenov University), Moscow, Russian Federation antibiotic HSRs”; for the remaining 63 “suspected HSRs” that did not relapse after drug readministration, the diagnosis of antibiotic HSRs was Background: CRSwNP is diagnosed in more than 25% of CF patients, but excluded. In summary, 13/76 suspected HSRs were confirmed as antibiotic there is no evidence-based approach to its treatment. HSRs among which 3 were allergic. Aim: To assess the outcome of Functional Endoscopic Sinus Surgery (FESS) Conclusion: The prevalence of suspected and confirmed antibiotic HSRs followed by 1 year of medical treatment (MT) in CF adults. and antibiotic allergy in CF patients appears similar to that reported in the Methods: 28 CF patients with CRSwNP aged 18–32 were divided into two general population. Of note, most of the suspected antibiotic HSRs are not treatment groups. 14 patients in group1 had FESS, followed by 1 year of MT, confirmed after allergology work-up. A complete allergy work-up appears in group2 MT only. Complains by SNOT-20 scale, endoscopic symptoms, CT therefore crucial to make a correct diagnosis and to avoid unnecessary scan by Lund-Mackay scale, anterior active rhinomanometry, spirometry, contra-indication of major antibiotics. respiratory exacerbation rate, oxygen saturation were assessed. Results: In 6 months there was decrease in SNOT-20 scale in both groups WS01.2 (p < 0,001). Non-invasive ventilation in adult cystic fibrosis patients with severe (group1 from 76 ± 6,7 to 22 ± 6,2; group2 - from 71 ± 6,5 to 65,71 ± 7,1). lung disease Endoscopic symptoms decreased also (p < 0,001) (group1 - from 33 ± 1,2 to 1 1 1 2 1 1 1 4 ± 3,4; group2 - from 32 ± 1,7 to 25 ± 3,3). CT picture by Lund-Mackay scale C. Biglia , S. Demichelis , R. Di Tria , C. Bena , M. Sciolla , B. Messore . AOU 2 and anterior active rhinomanometry improved in group1 (p < 0,001) after San Luigi Gonzaga, Adult Cystic Fibrosis Centre, Orbassano, Italy; AOU San FESS and 6 months of MT, oxygen saturation increased by 2–3% in group1 Luigi Gonzaga, Pneumology, Orbassano, Italy (from 92,3 ± 2,3 to 95,9 ± 1,9, p < 0,001), in group2 no significant changes Background: In Cystic Fibrosis (CF) respiratory disease is responsible of were seen. Decrease of respiratory exacerbation rate was seen in group1 morbidity and mortality. Non-Invasive Ventilation (NIV) in CF is considered S2 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 during the year from 6,1 ± 1,9 to 3,6 ± 1,1 (p < 0,001), while in group2 no the review (e.g. change of device, addition of a spacer device). All patients significant change was seen. who received training were able to demonstrate improved technique at the Conclusions: FESS in combination with MT is more effective in CRSwNP end of the consultation and said they would use their inhalers differently in treatment than MT alone in CF adults, it also improves oxygen saturation the future. and decreases respiratory exacerbation rate. Conclusion: The data shows that inadequate inhaler technique is common in adults with CF, highlighting the need for regular review of technique. WS01.4 Training provided by a healthcare professional improves inhaler technique Survival after pulmonary re-transplantation in cystic fibrosis patients: and provides the opportunity for interventions such as changing devices or 10-year single centre experience the addition of spacer devices to further optimise inhaler use. The types of F.F. Rönsholt1, K. Jensen1, T.K. Lund1, H.H.L. Schultz1, T. Pressler2, M. Perch1. errors are consistent with studies in COPD and asthma. The project is 1Rigshospitalet, University Hospital Copenhagen, Dept. of Cardiology, Section ongoing and further findings will be presented. for Lung Tranplantation, Copenhagen Ø, Denmark; 2Rigshospitalet, University Hospital Copenhagen, Dept. of Infectious Diseases and Cystic Fibrosis, WS01.6 Copenhagen Ø, Denmark Antifibrinolytics therapy for treatment of hemoptysis in adults with cystic fibrosis; does it affect lung function? Background and Objective: At Rigshospitalet (national lung transplant- 1,2 1,2 1, 2 3,4 1 1, 2 L. Cardoni , R. Perkins , K. Shin , H. Al-Samkari , E. Pighetti , S. Rits , ation center, Denmark) pulmonary retransplantation (re-LTX) has been 1, 2 3,4 1,2 1 L. McMahon , J. Connors , A. Uluer . Boston Children’s Hospital, Harvard performed since the initiation of the pulmonary transplantation program Medical School, Division of Pulmonary and Respiratory Disease, Boston, in the 1990s, but disappointing outcomes led to a cessation of this practice 2 United States; Brigham and Women’s Hospital, Harvard Medical School, for the following decade. In the beginning of 2010 reports of successful re- Division of Pulmonary and Critical Care Medicine, Boston, United States; LTX encouraged the reintroduction of re-LTX in highly selected patients 3 Massachusetts General Hospital, Division of Hematology and Oncology, with bronchiolitis obliterans syndrome (BOS). 4 Boston, United States; Brigham and Women’s Hospital, Harvard Medical The objective of this abstract was to assess survival of CF patients after re- School, Division of Hematology, Boston, United States LTX in our centre. Methods: Data was obtained from the transplant registry. Specific patient Objectives: Hemoptysis in patients with cystic fibrosis (CF) is a major cause related data was collected from hospital records and patients’ charts. of morbidity and mortality. Use of antifibrinolytic therapy (AFT) has Survival statistics were performed using Kaplan-Meier charts, where previously been shown to reduce hospitalisations when used as a surviving patients were censored at December 31st,2019. treatment of hemoptysis in adults with CF and without significant Results: Since 2010, 303 pulmonary transplantations were performed at adverse events. Its effect on lung function is unknown. This study aims to Rigshospitalet; 50 due to CF. assess the impact of AFT on lung function in a cohort of CF adults with Out of the 303 pulmonary transplantations, nine were re-LTX. Of these, four hemoptysis. were CF patients and five had other diagnoses. Methods: A retrospective review was performed evaluating the rate of lung Median age at re-LTX was 41,4 years (41,3 years among CF patients). function decline in CF adults with hemoptysis treated with systemic AFT. Median time from first LTX to re-LTX overall was 2154 days (1738 days Serial ppFEV1 measurements from time of first hemoptysis documentation among CF patients). were collected. Systemic AFT administration date was determined. Rate of By January 1st, 2020, five of the nine re-LTX patients were deceased; four lung function decline was obtained by calculating ppFEV1 slope pre-AFT were CF patients. The deceased CF patients’ median survival time from re- and post-AFT. A minimum of six months of pre and post lung function data LTX was 927 days (2,5 years), range 242–1975 days. were required in analysis. When considering all re-LTX patients, 2-year survival was 77% and 3-year Results: 21 patients were reviewed with 17 included in the analysis (mean survival was 62,2%. age 30.8 years, 59% male, F508del homozygous 59%, F508del heterozygous CF patients had a 2-year survival of 75% vs. 80% among other patients, 41%, mean BMI 20.2, no modulator 76.5%, Pseudomonas colonisation 82%). however numbers are too small for prognostic value. 65% (n = 11) of patients were treated with tranexamic acid and 35% (n = 6) Conclusion: Median survival time among four CF patients who have with ε- aminocaproic acid. The mean rate of decline before AFT undergone re-LTX was 2,5 years. Re-LTX is a treatment option in highly administration was −0.341 and− 0.035 following AFT administration. selected patients with BOS. National data are too sparse to determine There was a significant difference in rate of decline between the two groups prognostic factors. (p = 0.0395 by Wilcoxon signed-rank test). The rate of decline was not significantly different based upon AFT used (post TXA slope 0.05, post ε- WS01.5 aminocaproic acid slope − 0.20; p = 0.37). Assessment of inhaler technique in inpatients on an adult cystic Conclusion: Our study characterised the effect of AFT on the rate of lung fibrosis ward function decline in a cohort of adult CF patients with hemoptysis. Early E.J. Williams1. 1Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom systemic antifibrinolytic treatment for hemoptysis is effective in slowing the rate of lung function decline in adult CF patients and is independent of Objectives: Inhalers are an integral part of treatment for many people AFT agent used. Future evaluation accounting for modulator usage, living with cystic fibrosis (CF). Correct technique is essential to optimise bacterial colonisation, age, and BMI is being undertaken. drug delivery to the lungs. The aim of the project was to evaluate inhaler technique in adults with CF who are prescribed inhalers for the administration of bronchodilators or corticosteroids. The aim was then to provide training to help patients optimise their inhaler technique. WS02 Equality and diversity in CF: engaging Methods: During inpatient admission, patients with at least one inhaler on their repeat prescription were invited to have an inhaler technique review the disengaged with a pharmacist. Patients were asked to demonstrate how they usually use their inhalers. A discussion then took place and training was provided WS02.1 by the pharmacist if technique was sub-optimal. A questionnaire was CF BOOST - engaging the disengaged completed before and after the consultation. H. Green1, M. Clegg1, J. Hildage1, V. Kendall1, L. Kinsey1, H. Oxley1, J. Pickles1, Results: 20 patients have had their technique assessed so far. 19 (95%) A. Tansinda1, A. Jones1. 1Manchester University NHS Foundation Trust, patients demonstrated inadequate technique for at least one of their Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom prescribed inhaler devices, 14 (74%) of whom had received some form of training in the past. The most common errors were inhaling too quickly Objectives: Our large adult CF centre has a cohort of patients that (84%), not exhaling before use (42%) and not holding their breath deteriorate rapidly despite standard care as per national CF guidelines. afterwards (21%). Nine patients had their prescriptions changed during These patients often have psychological difficulties and struggle to Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S3 communicate verbally with the MDT. They are typically non-adherent to Methods: Based on a qualitative model using the Grounded Theory medications and physiotherapy, have low BMIs, accelerated lung function methodology; data retrieved from interviews conducted with 16 adoles- decline and rely on frequent courses of IV antibiotics. We aimed to develop cents with CF, aged between 11 and 23 years old, recruited by using the an outpatient based service to provide intensive MDT support to these ‘snowball’ technique. patients with key aims being to improve: communication and engagement Results: Following the protocol of data analysis of Strauss and Corbin with the CF MDT; adherence; nutrition; lung function and to give enhanced (2008), the emerged categories in this study were grouped according to psychosocial support. their properties: the discovery of the disease was considered as causal Methods: The CF BOOST (Cystic Fibrosis Better Outpatient Outcome conditions; the social interaction and information categories were Support Team) service was developed consisting of 1 consultant, 2 identified as intervening conditions; the category building autonomy specialist nurses, 2 physiotherapists, 1 dietician and the psychosocial reacts as the strategic approach of the study and we identified future team. Each enrolled patient receives intensive home support using a perspectives as the consequential dimension. By interpreting all the combination of texts, emails and home visits. Weekly MDT meetings are acknowledged categories through subcategories, we considered them an held to discuss progress, problems and patient feedback. A summary of influence to the construction of the central phenomenon: THE SEARCH FOR discussions and weekly individualised action plan is immediately NORMALITY. discussed with the patient. Conclusion: Following the central phenomenon sustained by the assump- Results: 9 patients have enrolled in the service. The first patient to enrol tions of Meleis (1994, 2000), by recognizing the transition and its has graduated from 12 months of CF BOOST support and is now taking all properties as being experienced by the participants, the nurse will be oral and nebulised medication for the first time in their life and has had a able to implement interventions targeting the stability and well-being of ’ sustained 14% (absolute) increase in FEV1. BMI has risen from 16.2 to 22.2 the adolescent with CF. Hence the suggestion of guidelines to plan a nurses (without enteral feeding) and only 2 weeks of emergency IV antibiotics appointment as an asset to identify the focal point of the nurse, the were required in the past 6 months compared to 18 weeks of emergency IV development of diagnosis and corresponding interventions, always taking antibiotics in the year prior to enrolment. All 8 more recently enrolled into account the uniqueness of each adolescent and family. As a result of patients are also showing favourable outcomes e.g. improved lung the data analysis from the interviews, it is clear the demand for a binding function, BMI, adherence and engagement and decreased IV antibiotic element to the entire multidisciplinary team with the holistic knowledge of frequency. the adolescent and parents. Conclusion: Using an alternative approach with rapidly deteriorating, non- adherent, disengaged patients can result in significant improvements in WS02.4 patient outcome and satisfaction. Developing an enhanced transition pathway for young people with additional needs at the Manchester Adult Cystic Fibrosis Centre WS02.2 (MACFC) Specific psychological symptoms of cystic fibrosis patients following E. Shaw Núñez1, A. Myrtle2, D. McKenna1,L.Brown1, J. Fauset-Jones2, lung transplantation M. McKenna1. 1Manchester Adult Cystic Fibrosis Centre, Manchester, United O. Poletaeva1. 1‘Ostrova’ Charitable Foundation, Saint-Petersburg, Russian Kingdom; 2Royal Manchester Children’s Hospital, Manchester, Federation United Kingdom

Objectives: To identify psychological symptoms specific for cystic fibrosis Objectives: Transitional care is a planned process addressing the medical (CF) patients after lung transplantation. and psychosocial needs of adolescents with CF as they move from Methods: We observed 14 CF patients, six boys and eight girls aged 12–37 paediatric to adult care. Young people with additional needs such as co- y.o. Patients’ psychological symptomatology was assessed using individual morbid health conditions, learning disabilities, neurodevelopmental and family counselling, testing as well as using projective, bodily, and difficulties, or communication difficulties can face challenges associated “bridge” methods. with this reorganisation of care. To improve the current transition process Results: CF patients awaiting lung transplantation displayed symptoms, between local CF paediatric services and MACFC, an enhanced pathway has common for patients with other chronic, life-threatening diseases that been developed outlining the transition process for patients with require surgical therapy. Such symptoms included anxiety (14 patients), additional needs, their family and/or carers, and CF services involved in depression (10 patients), panic attacks nine patients), fear of unsuccessful their care. surgery (14 patients), fear of life after the surgery (12 patients), loneliness Methods: The collaborative development of the enhanced transition (10 patients), poor socialization (13 patients). We also identified specific pathway included a literature review, a review of current good practice psychological symptoms in CF patients after lung transplantation: between CF paediatric services and MACFC, benchmarking with CF services psychological rejection of transplant (seven patients), loss of signal in the United Kingdom, stakeholder engagement and consultation. system of transplanted lungs (four patients), and unformed gender Results: The enhanced transition pathway outlines four phases with identity (six patients, five of which died). flexible steps, encompassing pre-transfer preparation, transition proced- Conclusion: Psychological rejection of transplant, loss of signal system of ure, transfer procedure and post-transition care. Examples of additional transplanted lungs, and unformed gender identity were specific psycho- input differentiating this enhanced transition from MACFC’s standard logical symptoms for CF patients after lung transplantation. Identification transition process include the use of person-centred resources, additional and treatment of these symptoms aided psychophysiological rehabilitation home and clinic visits, continuity of key staff, multiagency liaison (e.g. of CF patients after lung transplantation, and their psychosocial adaptation working with social and education services), capacity assessments, and in new life. As five out of six patients with unformed gender identity died, it best interest decision-making. may be a significant psychological factor contributing to CF patients’ Conclusion: It is important that services provide a planned, person- survival and disease treatment. Thus, further studies of effects of gender centred transition for young people and their families. Young people with identity in CF patients, and its relation to disease are needed. additional needs can face challenges during their transition from CF paediatric care to CF adult care. The development of an enhanced CF WS02.3 transition pathway improves service delivery by supporting young people, Cystic fibrosis in adolescence: the experience in first person their family and/or carers, and CF multidisciplinary teams during this M.C. Reisinho1. 1Escola Superior de Enfermagem, Porto, Portugal process. Objectives: Understand the adolescents’ experience living with Cystic Fibrosis; contribute to the excellence of the nurse’s care provided to adolescents with CF. S4 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

WS02.5 delivering the news of an adult diagnosis have the appropriate training and Setting up a therapeutic education course for male patients presenting support, they adequately assess individual’s information needs and provide cystic fibrosis infertility appropriate and relevant information. Implications for psychosocial S. Ramel1, D. Beauvillard2, J. Le Bihan1, A. Valeri3, M.-T. Le Martelot4, practice include providing educative training, reflective practice and A. Caroff1, F. Touilin5, M. Kerbrat1. 1Fondation Ildys, CF Center, Roscoff, France; supervision to healthcare professionals and supporting patients to help 2Regional University Hospital Brest, Department of Medical Genetics and make sense of the diagnosis, develop adaptive coping strategies and adjust Reproductive Biology, Brest, France; 3Regional University Hospital Brest, to living with a chronic condition. Future research would benefit from a Urology Department, Brest, France; 4Regional University Hospital Brest, more diverse UK wide sample. Gynecology-Obstetrics Department, Brest, France; 5Fondation Ildys, CF Patient, Roscoff, France 98% of male CF patients have Congenital Bilateral Absence of the Vas WS03 Liver disease/gut inflammation Deferens leading to hypofertility. CF patients’ life expectancy and have improved and access to paternity is increasing. Several publica- WS03.1 tions underline that despite patient’s strong interest concerning fertility Do blood biomarkers perform better than traditional methods for and sexuality, they have poor knowledge and some misconceptions. Care identifying adults with cystic fibrosis and liver fibrosis? givers are also reticent to discuss the subject. We decided to work on a 1 1 1 1 2 1 program to support this aspect of patient management. D. Amaxilati , M. Allenby , T. Daniels , M. Carroll , J. Patel . University Methods and objectives: A working group with an adult CF patient Hospital Southampton NHS Foundation Trust, Wessex Adult Cystic Fibrosis 2 partner, pulmonologist, biologist, urologist and nurses from our CF centre Service, Southampton, United Kingdom; University Hospital Southampton and from our local medically assisted reproduction centre met regularly for NHS Foundation Trust, Hepatology, Southampton, United Kingdom ’ 2 years. We identified patients needs and gave the CF team a sound Objectives: CF-Related Liver Disease (CFLD) is associated with increased theoretical training on male hypofertility. Then we built an educational mortality. Early detection of CFLD may allow implementation of interven- program for the patient to enable him to understand hypofertility, the tions to prevent progression to irreversible fibrosis. Non-invasive compos- process of spermatozoa preservation and the advantage of an early sample. ite biomarker scores to assess liver fibrosis are validated in other liver Results: disease. The Enhanced Liver Fibrosis (ELF) test is composed of hyaluronic Tools for care givers: a filmed interview of MD biologist who explains the acid (HA), Procollagen III amino terminal peptide (P3NP) and Tissue mechanisms leading to hypofertility in male CF patients, how to diagnose it Inhibitor of metalloproteinase (TIMP-1), and is recommended for use in and the different steps to fatherhood. other liver diseases by the UK National Institute for Clinical Excellence. Tools for the patient: A slideshow about CF hypofertility. A booklet with 9 Fibrosis-4 (Fib-4) consists of age, platelet count, AST and ALT. points about the process of spermatozoa preservation. An interactive aid Methods: ELF and Fib-4 were used to assess liver fibrosis in adults with CF about the surgical procedure with sketches of male reproductive tract. A including those suspected to have CFLD. CFLD patients were defined as filmed testimony of our partner patient explaining his management course those having any level of abnormal liver function tests or abnormal liver starting from the spermogram to the surgical collection of spermatozoa. A findings on ultrasound scan (US), in keeping with international guidelines. tool on genetic inheritance patterns. Patients with US evidence of cirrhosis were excluded. Transient elasto- Discussion: This collaborative work has benefited from the strong graphy (TE, Fibro Scan)® was performed on some patients with ELF ≥9. implication of our partner patient. We started the program in June 2019. Results: Of 299 CF patients under our service, 153 have CFLD and 9 have We proposed it to our male CF patients aged 18/20 years, always respecting cirrhosis based on traditional identification methods. their wish to receive this information. Next projects are to evaluate this 72 patients had ELF and Fib-4 assessed. 24 patients (33.4%) had ELF score program, to share it with the other CF teams and to develop an E-Learning ≥9, thought to reflect a raised Kleiner score indicative of moderate to severe program for a wider distribution. fibrosis. No patients had a raised Fib-4 score. 14 patients with ELF score ≥9 proceeded to have Fibro Scan® performed. WS02.6 Two patients had Liver Stiffness Measurement (LSM) >7 kPa supporting ’ Living with cystic fibrosis: patients experiences of diagnosis in presence of liver fibrosis. Only one of these patients was previously adulthood considered to have CFLD. 1 1 1 2 1 N. Sharma , D. Harcourt , E. Jenkinson , A. Pearce . University of the West of Conclusion: Most CF patients tested had low ELF and Fib-4 scores. ELF may 2 , Bristol, United Kingdom; Southern Health NHS Foundation Trust, be able to identify a population at risk of liver fibrosis, missed by traditional Southampton, United Kingdom modalities, offering the possibility of more targeted screening for CFLD. Objectives: There is a paucity of research investigating what it is like to be diagnosed and to live with cystic fibrosis (CF) in adulthood. Understanding WS03.2 patients’ experiences and the impact of the condition can provide A multicentre cohort study on ursodeoxycholic acid and liver disease information to help healthcare professionals deliver appropriate support. associated with cystic fibrosis 1 2 3 4 5 6 This research aimed to address this literature gap. C. Colombo , G. Alicandro , H. Evans , M. Oliver , C.Y. Ooi , F. Alghisi , 7 7 8 9 10 Methods: An experiential qualitative approach using semi-structured N. Kashirskaya , E. Kondratyeva , G. Ramm , I. de Monestrol , R. Padoan , 11 12 1 interviews was undertaken. Sixteen individuals diagnosed with CF in I. Asherova , A. Lindblad , CF UDCA Study Group. Fondazione IRCCS Ca’ adulthood who received their care from a regional UK CF centre were Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 2 3 recruited. Italy; Italian National Institute of Statistics, Rome, Italy; Starship Children’s 4 Results: Using inductive thematic analysis, four themes were identified Health, Auckland, ; Royal Children’s Hospital, Melbourne, 5 “No, you can’t possibly have CF,” emotions around diagnosis, “It did kind of Australia; Sydney Children’s Hospital & University of New South Wales, 6 7 take over my life” and “I no longer wish to argue with it” These themes Sydney, Australia; Ospedale Pediatrico Bambino Gesù, Rome, Italy; Federal described participants’ frustrations regarding contact with healthcare State Budgetary Institution, Research Centre for Medical Genetics, Mosocw, 8 professionals before diagnosis, ambivalence around diagnosis, the chal- Russian Federation; Royal Children’s Hospital, Queensland, Australia; 9 10 lenges faced with day-to-day living and acceptance and adjustment to their Karolinska University Hospital, Stockholm, Sweden, ASST Spedali Civili 11 CF. A key finding was the mismatch between patient need and healthcare Brescia, Brescia, Italy; City Children’s Hospital N1, Yaroslavl, Russian 12 provision. Federation; Queen Silvia Children’s Hospital, Gothenburg, Sweden Conclusions: This research found that the experiences of people diagnosed Objectives: To evaluate if the incidence of severe liver disease (LD) differs and living with CF in adulthood can be broad and diverse. between CF centres where prescription of ursodeoxycholic acid (UDCA) Recommendations involved awareness raising of the possibility of was a common practice as compared to centres where UDCA was not receiving a CF diagnosis in adulthood, ensuring CF healthcare professionals routinely prescribed. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S5

Methods: We carried out a historical multicentre cohort study including CF WS03.4 patients born between 1990 and 2007 and followed up to the age of 20 Lumacaftor/ivacaftor improves the intestinal inflammation in children years or the end of the study (31 December 2016), whichever came first. with cystic fibrosis The study outcome was the development of severe LD defined by the first C. Tetard1, M. Mittaine2, F. Beaufils1, S. Bui1, H. Clouzeau1, F. Galodé1, documented event of portal hypertension, need for liver transplantation or C. Collet1,M.Fayon1, T. Lamireau1, P.-R. Burgel2, L. Delhaes1, E. Mas2, death due to LD. We computed the crude cumulative incidence (CCI) of R. Enaud1. 1CRCM Pédiatrie, Bordeaux, Bordeaux, France; 2CRCM Pédiatrie, severe LD at the age of 20 years in the two groups and we estimated the Toulouse, Toulouse, France subdistribution hazard ratio (sHR) through a Fine and Gray model. Results: The study included 1606 patients followed-up in 11 centres (1204 Objectives: The morbi-mortality of Cystic fibrosis is conditioned by lung from UDCA-prescribing centres and 402 from centres which did not involvement, but other organs can be affected, including the digestive tract. routinely prescribe UDCA). Over the follow-up, 108 patients developed Chronic intestinal inflammation is present in more than half of the patients, severe LD [84 (7.0%) among patients followed-up in UDCA prescribing for which no treatment is currently proposed. Protein therapies have been centres and 24 (6.0%) in centres which did not routinely prescribe UDCA]. developed in recent years to modulate the defective CFTR protein. Severe LD occurred at a median age (interquartile range) of 11 (9–13) and Although treatment with lumacaftor/Ivacaftor has been shown to be 10 (7–14) years in UDCA prescribing and non-prescribing centres, effective at the pulmonary level, no data are available on its effect on respectively. The CCI of severe LD at 20 years was 10.1% (95% CI: 7.9–12.3) digestive inflammation. in UDCA prescribing centres and 7.7% (95%: 4.6–10.7) in centres which did Methods: We studied the evolution of intestinal inflammation under not routinely prescribe UDCA. The sHR among patients followed in UDCA lumacaftor/Ivacaftor in children with cystic fibrosis aged less than 18 years prescribing centres indicated no significant difference in the rate of severe and followed at the CRCMs of Bordeaux and Toulouse, having started LD either in the unadjusted model (sHR: 1.14, 95% CI: 0.64–2.03) or in the treatment between January 2016 and July 2018. Faecal calprotectin model adjusted for pancreatic insufficiency (sHR: 1.20, 95% CI: 0.71–2.03). measurement was performed at the beginning of treatment with Conclusions: Patients with CF followed-up in UDCA prescribing centres did lumacaftor/Ivacaftor and after at least 3 months of treatment. not have a lower incidence of severe LD as compared to those followed in Results: Fifteen patients were included in the study (median age; 12 years, centres which did not routinely prescribe UDCA. IQR: 12; 14.5). At treatment initiation, the median calprotectin concentra- tion was 713 μg/g (IQR: 148; 852) and 9 patients (60%) had a concentration WS03.3 higher than 250 μg/g. Compared to baseline, faecal calprotectin concen- A review of ursodeoxycholic acid prescribing in an adult cystic fibrosis trations decreased significantly after at least 3 months of treatment with population lumacaftor/Ivacaftor (median (IQR): 102 μg/g (69; 210) respectively, 1 1 2 1,3 1,4 p = 0.001). Only four patients (27%) maintained calprotectin levels higher C. Bradley , C. Rutherford , C. McParland , C. Addy , D.G. Downey , 2 1 1 than 250 μg/g and two patients (13%) had an increase in calprotectin levels C. McKeown , S. Caskey . Belfast Health and Social Care Trust, Adult CF 2 after lumacaftor/Ivacaftor. No significant differences were observed in the Centre, Belfast, United Kingdom; Belfast Health and Social Care Trust, Z-score changes in weight, height, BMI or FEV1. Pharmacy Department Belfast City Hospital, Belfast, United Kingdom; 3 Conclusion: To our knowledge, this study shows for the first time that Queen’s University Belfast, Centre for Medical Education, Belfast, 4 intestinal inflammation associated with cystic fibrosis decreases under United Kingdom; Queen’s University Belfast, Centre for Experimental lumacaftor/Ivacaftor. The short-term consequences on digestive symptoms Medicine, Belfast, United Kingdom and the long-term consequences on the risk of intestinal cancer are still to Objectives: Ursodeoxycholic acid (UDCA) is used for the prevention or be determined. treatment of CF‐related liver disease. Recommendations regarding UDCA usage are inconsistent, lacking robust evidence. Detection and monitoring WS03.5 of CF liver disease (CFLD) is difficult. Often at diagnosis, portal hypertension Gut microbiome and intestinal inflammation in infants in the FIRST is present. Clinicians face a dilemma; commence UDCA early to potentially cohort through 6 years of age prevent liver involvement or later as a therapeutic “rescue” option in H. Lai1, S. Murali1, S. Sudakaran1, FIRST Study Group. 1Universityof Wisconsin - established disease. Madison, Madison, United States Methods: Electronic care records for 296 adult patients with CF were reviewed. Baseline demographics and clinical outcomes such as liver Objectives: We aim to characterise gut microbiome (GM) and intestinal enzymes (LFTs), liver imaging (USS) and dosage of UDCA are reported. inflammation in infants with CF, how they evolve with age in comparison to Results: Ninety-three percent had LFTs in the past 12 months of which 20% their siblings without CF, and whether they vary by CF phenotypes [n = 63] demonstrated abnormalities. Imaging of the liver/biliary tract was [meconium ileus (MI), pancreatic insufficiency (PI) or sufficiency (PS)] and performed in 21% [n = 68] and 6% [n = 19] had a formal diagnosis of CFLD. In breastfeeding. total, 24% (n = 76) were prescribed UDCA. Review by hepatology occurred in Methods: We utilised data from the ongoing longitudinal FIRST (Feeding 23% (n = 74). Liver transplantation for CFLD was performed in < 1% [n = 2]. Infants Right…from the STart) study initiated in 2012 in 6 CF centres in the Of the 19 PWCF with CFLD, 32% [n = 6] were prescribed UDCA. Dosage US. A total of 671 faecal samples over age 0–6 yr from 163 CF subjects and varied, with a mean of 719 mg daily [range 250–1500 mg]. Fourteen were 57 samples over age 2–8 yr from 41 siblings without CF were analysed for F508 del homozygotes and 21% [n = 4] were currently prescribed a CFTR GM using 16 s rRNA and calprotectin as a marker of intestinal inflamma- modulator. Cirrhosis was present in 26% [n = 5], 10% [n = 2] had oesopha- tion. GM diversity was assessed by relative abundance and Shannon index geal varices and 26% [n = 5] were thrombocytopenic. One PWCF stopped at taxonomic ranks from phylum to genus. Faecal calprotectin (ug/g stool) CFTR modulation due to hepatic dysfunction. was classified as normal (< 50), borderline (50–120) and high (>120). Of those prescribed UDCA without confirmed CFLD [n = 70], 20% [n = 14] Results: CF children had lower GM diversity (median Shannon index 3.05 had abnormal LFTs, 20% [n = 14] had abnormal USS findings (fatty liver and vs. 4.27, p < 0.0001) and higher prevalence of intestinal inflammation (high gallstones most common 13% [n = 9]). Hepatology review occurred in 71% calprotectin 29% vs. 3%, p = 0.004) compared to their siblings without CF. [n = 50]. Within CF children, Shannon index increased from birth to 2 yr and Conclusion: Insufficient evidence exists to recommend routine use of plateaued by 4–6 yr of age. Dramatic shifts in the relative abundance of the UDCA in PWCF. A wide variation of prescribed doses exists within our 4 major phyla were noted: Firmicutes doubled from 21% at 3 mo to 41% at population. There is an urgent need for well‐designed, adequately age 2 yr, Actinobacteria and Proteobacteria both halved from 15–20% at 3 powered, multicentre RCTs to assess the effectiveness of UDCA in CF and mo to 8–10% at age 3 yr, and Bacteroidetes emerged from < 1% before 12 mo clarify its role in the prevention and treatment of CFLD. to 25% by 6 yr of age. Shannon index was lower in MI and PI compared to PS S6 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 patients (p = 0.005), and higher among those with high faecal calprotectin (p = 0.014). Exclusive breastfeeding >2 mo was associated with higher WS04 Role of new biomarkers abundance of Bifidobacterium than formula feeding in the first 3 yr of life, p = 0.001. WS04.1 Conclusion: MI and PI in CF reduce gut microbiome diversity and increase Inflammatory markers in BronchoAlveolar Lavage as risk factors for intestinal inflammation. More analyses are being conducted to examine early cystic fibrosis Lung disease: the I-BALL study how antibiotics and proton pump inhibitors modify these relationships. 1 2,3 1 2,3 2,3 H. Horati , J.D. Chandler , D. Caudri , C. Margaroli , M.B. Kilgore , (Funded by NIH & CFF). 4 5 2,3 1 1 M. Veltman , L. Peng , L. Guglani , H.A.M.W. Tiddens , B.J. Scholte , R. Tirouvanziam2,3, H.M. Janssens1. 1Erasmus MC-Sophia Children’s Hospital, WS03.6 University Hospital Rotterdam, Department of , Division of Does the cystic fibrosis diet contribute to intestinal dysbiosis? 2 Respiratory Medicine and Allergology, Rotterdam, Netherlands, Children’s 1 1 1, 2 3 4 1 J. van Dorst , I. McKay , M. Coffey , M. Doumit , L. Bramley , K. Paida , Healthcare of Atlanta, Center for CF and Airways Disease Research, Atlanta, 1,5,6 7, 8 4 5,9,10 1 A. Jaffe , T. Thomas ,T.Katz , C.Y. Ooi . University of New South United States, 3Emory University School of Medicine, Department of Pediatrics, Wales, School of Women’s and Children’s Health, Medicine, Randwick, Atlanta, United States, 4Erasmus MC, Rotterdam, Department of Cell Biology, 2 Australia; Sydney Children’s Hospital Randwick, Randwick, Australia; Rotterdam, Netherlands, 5Emory University School of , 3 Sydney Children’s Hospital Randwick, Department of Physiotherapy, Department of and Bioinformatics, Atlanta, United States Randwick, Australia; 4Sydney Children’s Hospital Randwick, Department of Nutrition and Dietetics, Randwick, Australia; 5Molecular and Integrative Cystic Inflammation plays an important role in early cystic fibrosis (CF) lung Fibrosis (miCF) Research Centre, Randwick, Australia; 6Sydney Children’s disease. We previously reported that higher neutrophil elastase (NE) and Hospital, Department of Respiratory, Randwick, Australia; 7University of New myeloperoxidase (MPO) activities in bronchoalveolar lavage fluid (BALF) South Wales, Biological, Earth and Environmental Sciences, Randwick, associate with more severe structural lung damage in a cross-sectional Australia; 8University of New South Wales, Centre for Marine Science and study of CF infants. In this longitudinal study, we aimed to identify Innovation, Randwick, Australia; 9Evaluating the Alimentary and Respiratory candidate inflammatory markers as risk factors for lung damage 2 years Tracts in Health and Disease (EARTH) Research Program, Randwick, Australia; later, with potential use in clinical monitoring. 10Sydney Children’s Hospital, Department of Gastroenterology, Randwick, Methods: Inclusion criteria: infants with CF (n = 37), age 1, 3 and 5 years, Australia with 2 consecutive chest computed tomography scans (CTs) and bronchoscopies. CTs were scored for %disease (%Dis) and %bronchiectasis Background: The mechanisms behind intestinal dysbiosis and inflamma- (%Bx) using PRAGMA-CF score. Analyses in BALF were: MPO (n = 25), free tion in cystic fibrosis (CF) are likely to be multifactorial. The high-calorie, NE (n = 26), an array (Olink) targeting 92 inflammatory and tissue high-fat CF diet is an underexplored microbial modulator. This study aims remodelling proteins (n = 26) and neutrophil percentage (neutro%) to explore the interplay between the gut microbiota, inflammation and (n = 36). diet. Results: None of the markers were significantly correlated with change in % Methods: This is a prospective, cross-sectional, observational cohort study Dis. Spearman correlations with change in %Bx over 2 years were at Sydney Children’s Hospital, Australia. CF children, 0–18yrs were age and significant for neutro%, MPO and inducible T-cell costimulator ligand gender matched to healthy controls (HC), and completed a clinical survey, (ICOSLG) (p < 0.01), and p < 0.1 for interleukin-8 (IL-8) and hepatocyte food frequency questionnaire (ACAES), and provided stool samples. Stools growth factor (HGF) (p = 0.07, 0.06, respectively), and non-significant for underwent microbiata analysis via 16 s rRNA sequencing (V4 region) and NE. We investigated the prognostic value for >0.5% change in %Bx with ROC calprotectin was measured. curves and estimated cut-off with optimal sensitivity/specificity using Results: 33 CF (17 female (52%); median age (IQR) = 9.58 (5.28–12.51) and Youdens Index. ICOSLG and IL-8 had the best sensitivity/specificity (0.82/ 33 HC (17 female (52%); median age (IQR) = 8.87 (4.91–13.8) subjects were 0.67 and 0.82/0.73, respectively). Odds ratios for >0.5% change in %Bx was recruited. The relative abundances of Enterobacter, Enterococcus and significant (p < 0.05) for high neutro%, ICOSLG, IL-8 and HGF 9 and p < 0.1 Rhodococcus were higher in CF compared to HC, whilst Ruminococcaceae, for MPO, and non-significant for NE. Lachnospiraceae, Akermansia, Subdoligranulum and Alistipes were lower Conclusions: MPO, ICOSLG, IL-8, HGF, and neutro% in BALF were candidate (ANCOM analysis; FDR< 0.05). Dietary analysis revealed the CF diet had: (i) risk factors for progression of bronchiectasis in 2 years in this cohort, higher relative fat and lower relative carbohydrate and fibre intake whereas free NE was not. Markers for neutrophil activation, tissue compared to HC (P < 0.05; Table 1), (ii) significant correlations between remodelling and immune modulation may be of use in clinical monitoring fat, sugar, and intestinal microbiota elevated in CF. and intervention. In CF, calprotectin was significantly correlated with the percentage of non- Funding: NIH R01, Sophia Foundation, NCFS core foods (R = 0.488, P = 0.039) and percentage takeaway (R = 0.491, P = 0.032), and negatively correlated with the percentage intake of grains WS04.2 (R = −0.806, p = 0.0006) and wholegrains (R = -0.568, p = 0.001). Electronic nose (E-nose) analysis of systemic volatile organic compounds (VOCs) pattern distinguishes paediatric patients with cystic fibrosis (CF) from healthy controls (HC) and depicts disease status Macronutrients Median CF (g/ Median HC P value F. Lucca1, L. Tenero2, S. Volpi3, M. Piazza2, A. Borruso3, L. Menin3, M. Sandri4, 1000kj) (g/1000kj) M. Cipolli3, G. Piacentini2. 1University of Verona, Pediatrics School, Verona, 2 Fat (total, (10.3, 4.6, 0.2) (8.4, 1.1, 0.1) (0.004, 0.0001, 0.0005) Italy, Azienda Ospedaliera Universitaria Integrata, Pediatric Department, 3 saturated, Verona, Italy, Cystic Fibrosis Center, Azienda Ospedaliera Universitaria trans) Integrata, Verona, Italy, 4University of Brescia, Data Methods and Systems CHO (total, fibre, (26.0, 0.9, 2.8, 0.2) (28.3, 1.4, 4.5, 0.5) (0.03, 0.002, 0.006, 0.007) Statistical Laboratory, Brescia, Italy wholegrains, resistant Objectives: VOCs originating from metabolic processes can be assessed on starch) different matrices, and have already been shown to reflect pathophysio- logical processes at respiratory level and systemic level. VOCs pattern has [Macronutrients with different relative intakes (g/1000kj) for CF and HC previously been analysed with the E-nose on exhaled air in asthma, COPD children.] and CF and on urine in various inflammatory systemic diseases. The application of the E-nose to urinary VOCs analysis in CF could help to depict Conclusions: The altered CF microbiota (demonstrated by dysbiosis and disease progression and clinical status. Our aim was to evaluate urinary inflammation) is likely to be associated with dietary intake. A modified CF VOCs expression with E-nose in HC and in CF patients (pts); to compare diet may provide a promising therapeutic target. urinary VOCs in stable CF pts (StCF) and in pts with respiratory exacerbation (ExCF). Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S7

Methods: A cross-sectional experimental study was approved by Verona WS04.4 and Rovigo Ethic Committee. Clinical data, spirometry, N2multiple breath Guidance on the use of sputum biomarkers to monitor treatment washout (MBW) and urine samples were collected from 29 CF pts (age response and act as trial outcomes in cystic fibrosis 12.56 ± 4.08; 23 StCF, 6 ExCF) and 15 HC (age 13.36 ± 4.13). Urine VOCs A. Lepissier1, C. Addy2,3, D. Downey2,3,K.Hayes4, I. Sermet5. 1Service de ® analysis was performed with Cyranose320 . The output data were Pneumologie et Allergologie Pédiatriques, Centre de Ressources et de elaborated through multivariate analysis and Principal Component Compétence de la Mucoviscidose, Hôpital Necker Enfants Malades, INSERM Analysis (PCA). U1151, Institut Necker Enfants Malades, Université Paris Sorbonne, Paris, ® Results: A number of Cyranose320 sensors (S5-7, S9, S12, S14, S17, S23) France; 2The Queen’s University of Belfast, Belfast, United Kingdom, 3Belfast significantly distinguished between HC and CF pts; also, StCF could be City Hospital, Belfast, United Kingdom; 4Wellcome Wolfson Centre for discriminated from ExCf (S6, S7, S9, S11, S12, S14, S16, S17, S21, S23, S29). Experimental Medicine, Clinical Research Facility, The For sensors distinguishing HC from CF pts, AUC of ROC was more than Queen’s University of Belfast, Belfast, United Kingdom; 5Centre de Ressources et accurate for S14 (0.82), good for S9 (0.75) and S17 (0.73). PCA identified de Compétence de la Mucoviscidose, Hôpital Necker Enfants Malades, INSERM PC2, which proved the best PC in predicting between HC and CF subsets. U 1151, Institut Necker Enfants Malades, Université Paris Sorbonne, Service de Spirometry distinguished HC from ExCF, but not from St CF, while N2MBW Pneumologie et Allergologie Pédiatriques, Paris, France distinguished also StCF from HC. Conclusion: We here report the first use of E-nose on urine samples from Objectives: Targeting inflammatory pathways is an increasing area of CF pts to measure VOCs profiles: the latter could distinguish HC from CF pts, clinical research and investigative trials in cystic fibrosis. Measurement of the impact of therapeutic interventions on inflammation is essential to the and among CF pts, StCF from ExCF. N2MBW distinguished all 3 populations, while spirometry only distinguished ExCF from HC. Further analyses development of future CF therapies. Measurement of lung inflammation in and studies are needed to evaluate systemic VOCs role as a clinical outcome respiratory specimens is one method to measure treatment response. This in CF. ongoing study highlights the need for reliable biomarkers to provide evidence of effectiveness, to develop and guide future therapies. Objectives WS04.3 included identification of which sputum biomarkers can discriminate Changes in symptom scores as a potential clinical endpoint for studies between people with cystic fibrosis (PWCF), healthy controls (HC) and of pulmonary exacerbation treatment other respiratory disorders. To demonstrate which biomarkers demon- 1 2,3 4 5 3 strate evidence of convergent validity with established clinical parameters D. VanDevanter , S. Heltshe , D. Sanders , N. West , M. Skalland , 6 3,7 1 of response and identify which biomarkers demonstrate responsiveness to P. Flume , C. Goss , on behalf of the STOP-OB Study. Case Western Reserve 2 therapeutic interventions. University, Cleveland, United States; University of Washington, Pediatrics, 3 Methods: A literature search was conducted identifying potential sputum Seattle, United States; Seattle Children’s Research Institute, Seattle, 4 biomarkers. The ECFS CTN Biomarker Working Group consensus selected United States; Indiana University School of Medicine, Indianapolis, 5 6 key biomarkers for further analysis. United States; Johns Hopkins University, Baltimore, United States; Medical 7 Results: Results were collated to provide an overview of discriminate and University of South Carolina, Charleston, United States; University of convergent validity and responsiveness for each biomarker. This ongoing Washington, Medicine and Pediatrics, Seattle, United States study demonstrates discriminate validity between PWCF and HC, asthma Objectives: Assessment of symptoms is commonly used to determine need and other respiratory diseases as well as by sample type and bacterial for and response to antibiotic treatment for pulmonary exacerbation (PEx). status. Convergent validity is demonstrated with FEV1 and other selected The Standardized Treatment of Pulmonary Exacerbations Observational clinical parameters. Responsiveness is also demonstrated by treatment study (STOP-OB; NCT02109822) was a prospective observational study of type for antibiotic, anti-inflammatory, CFTR modulator therapies and patient response to IV antibiotic PEx treatment, intended to provide airway clearance therapies. information to design future PEx intervention studies. In a secondary Conclusion: Inflammatory biomarkers can be reliably measured from analysis of STOP-OB data, we assessed changes in daily respiratory induced or spontaneously expectorated sputum, in both adult and symptoms during PEx treatment. paediatric populations. This increases the potential use of sputum as a Methods: 220 individuals with CF ≥1 2 years of age were treated at 11 sites sampling method within paediatric populations and PWCF with less severe with IV antibiotics for PEx. Subjects’ symptoms, captured using the Chronic lung disease. This ongoing study will provide recommendations on the Respiratory Infection Symptom Score (CRISS), were measured daily for 28 reliability, validity and responsiveness of key biomarkers. days (lower score = fewer symptoms). Daily CRISS scores and changes from admission were assessed. WS04.5 Results: The mean (SD) age at admission was 26.3 (9.5) years. Mean Urinary clusterin in children with cystic fibrosis: a novel biomarker of absolute FEV1 increase from admission was 9% predicted at end of IV lung disease? antibiotic treatment (mean = 15.9 (6.0) days), but only 7% predicted at Day S. Boardman1, M. Coffey1,2,K.Taylor3, J. Erlich3,4, A. Jaffé1,2,5, Z. Endre3,4, – 28. Mean CRISS at admission was 47.6 [95% CI: 46.0, 49.1; range 0 73]. The C. Ooi1,2,6, S. Kennedy1, 7. 1Discipline of Paediatrics, School of Women’s and − − − greatest mean CRISS reduction was 26.2 [95%CI 28.7, 23.7] at Day 17. Children’s Health, University of New South Wales, Sydney NSW, Australia; Mean time to minimal clinically important CRISS difference (-11), achieved 2Molecular and Integrative Cystic Fibrosis (miCF) Research Centre, High Street, − by 91.8% of patients, was 4.7 days [4.2, 5.2]; mean time to 26 CRISS change Randwick, NSW, Australia; 3Australian Kidney Biomarker Reference was 9.9 days [9.0, 10.8], achieved by 74.5% of patients. Higher admission Laboratory, Prince of Wales Clinical School, University of New South Wales, CRISS was significantly associated with probability of >26-point CRISS Sydney, Australia; 4Department of Nephrology, Prince of Wales Hospital, High 5 reduction. Age, sex, admission FEV1, and of oral antibiotics Street, Randwick NSW, Australia; Department of Respiratory, Sydney preceding admission were not associated with probability of a 26-point Children’s Hospital, High Street, Randwick NSW, Australia; 6Department of CRISS reduction. Gastroenterology, Sydney Children’s Hospital, High Street, Randwick, NSW, Conclusion: Symptom response measured by the CRISS is a viable clinical Australia; 7Department of Nephrology, Sydney Children’s Hospital, High Street, endpoint for PEx interventional trials. Further analyses will provide Randwick, Australia estimates of clinically relevant changes to power future studies. This work was supported by the Cystic Fibrosis Foundation. The authors Objectives: Clusterin is a multifunctional protein involved in immune acknowledge TDN sites, CF patients and families. regulation and DNA repair. In idiopathic pulmonary fibrosis, clusterin may be involved in both epithelial regeneration and fibrotic lung repair, through intracellular and extracellular (secretory) forms, respectively. Clusterin S8 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 expression may also be altered in the respiratory epithelium of cystic fibrosis (CF) patients, which may contribute to a dysregulated immune WS05 CFTR structure and trafficking response, causing chronic airway inflammation and progression of CF- related lung disease. We evaluated urinary clusterin levels in CF patients WS05.1 and healthy controls (HC) and determined if there was a relationship AVX-770 binding site within CFTR membrane spanning domain 2 between urinary clusterin and pulmonary function in CF. enables ATP-independent channel activation Methods: A single-centre cross-sectional study of children with CF and age 1 2 2 1 1 1 N. Baatallah , A. Elbahnsi , J.-P. Mornon , B. Chevalier , I. Pranke , N. Servel , and sex matched healthy controls (HC). Urine was assayed for clusterin 1 1 2 1 1 A. Edelman , I. Sermet-Gaudelus , I. Callebaut , A. Hinzpeter . Institut using an immunobead-based assay. Lung function testing was performed 2 Necker Enfants Malades, Paris, France; Institut de Minéralogie, de Physique in CF subjects. Results are expressed as median [IQR]. des Matériaux et de Cosmochimie, Paris, France Results: 25 CF and 25 HC subjects were included (52% male, median age 9.5 years [5.9–12.3] and 9.4 years [5.2–12.8] respectively). Urinary clusterin Objectives: Cystic Fibrosis is an autosomal recessive genetic disease caused levels were significantly lower in CF subjects compared with HC, (2.5 ng/ by mutations of the CFTR gene. mL [1.0–8.1] and 7.9 ng/mL [2.6–25.1] respectively, p = 0.011) and also During these last years, modulators of CFTR channel have been developed when corrected for creatinine (2.8 ng/mg Cr [1.7–5.4] and 6.7 ng/mg Cr to target some defects associated with specific mutations, affecting the [2.7–15.6] respectively, p = 0.019). There was no correlation between folding of CFTR protein (correctors; e.g. VX809) or the opening probability clusterin and FEV1% (n = 21), however, there was a strong positive of the channel (potentiators; e.g. VX-770). Our aim is to understand the correlation between clusterin (ng/mg Cr) and LCI, (n = 5, r = 0.997, mechanistic basis of VX-770 potentiation`. p < 0.001), suggesting that higher clusterin levels are associated with Methods: We combined a structural approach including molecular worse pulmonary function. dynamics simulations with site directed mutagenesis of key amino acids Conclusion: Urinary clusterin may be a potential novel biomarker of lung and functional assays. disease in children with CF. Further investigation to explore the potential Results: The identification of a point mutation insensitive to VX-770 led us role of extracellular (secreted) clusterin potentiating lung disease in to search for a possible binding site in the second membrane spanning children with CF is warranted. The overall reduction in urinary clusterin domain of CFTR. Structural data currently available, combined with in CF compared to HC also warrants further investigation. molecular dynamics simulations, allowed us to identify a pocket able to accommodate the potentiator. WS04.6 Mutation of key amino acids was realized in order to confirm their Dynamic Chest Radiography (DCR) in cystic fibrosis: initial experience implication in VX-770 binding. T.S. FitzMaurice1,2, R. Bedi3,S.Hawkes1, R. Peat1, S. Lomax4, C. McCann4, Moreover, we identified a gain of function mutation (GOF) which allow to D. Nazareth1,2, M. Walshaw1,2. 1Liverpool Heart & Chest Hospital, Adult CF rescue CFTR activity in a G551D background following an ATP-independent Unit, Liverpool, United Kingdom; 2University of Liverpool, Liverpool, mechanism. United Kingdom; 3University of Washington, Department of Bioengineering, Finally, the sensitivity of VX-770-resistant mutations to other CFTR Seattle, United States; 4Liverpool Heart & Chest Hospital, Department of potentiators was evaluated. Radiology, Liverpool, United Kingdom Conclusion: Altogether, these results give new insights into our funda- mental understanding of the mode of action of potentiators and open new Objectives: DCR is a novel technology that uses real-time low-dose X-ray to perspectives for CFTR-specific, structure-based drug design. obtain sequential chest radiographs to assess moving structures such as the chest wall and diaphragm. It is quick to perform and carries a similar WS05.2 radiation dose to a PA chest X-ray. It has previously demonstrated good Role of cholesterol in the function of current cystic fibrosis medications correlation between diaphragm motion with vital capacity (VC) and FEV in 1 1 2 1 1 D. Ravamehr-Lake , T.A. Stone , C.M. Deber . University of Toronto, non-CF healthy volunteers (Hida et al, EJR, 2019), and with the severity of 2 Biochemistry, Toronto, Canada; Research Institute, Hospital for Sick Children, lung disease in COPD (Hida et al, EJR, 2019). For the first time, we report its Molecular Medicine, Toronto, Canada use in assessing pulmonary physiology in people with CF (pwCF). Methods: 11 pwCF (age range 17–56, 6 male) with stable lung function Objectives: Despite their importance, the mechanisms of action of – (ppFEV1 range 26 101) underwent DCR as part of their scheduled CF clinically approved Cystic Fibrosis (CF) drugs remain unclear. VX-809 is a annual review. DCR was performed during a tidal/deep breathing corrector of CFTR, while VX-770, a CFTR potentiator, works by binding to manoeuvre using a dynamic imaging system (Konica Minolta®) that CFTR at a protein-lipid interface. CFTR resides in regions of membrane that applies real-time sequential PA X-ray in the standing position at 15fps. are highly enriched in cholesterol, yet a possible integral role of cholesterol Software localisation of the mid-diaphragm image was performed, and in facilitating drug-CFTR interactions has not been specifically investigated. excursion (mm) and speed (mm/s) over a time of up to 20 s were recorded. Accordingly, we sought to explore the role of cholesterol in: Spirometry was performed on the same day. 1) the interaction of VX-770 and VX-809 with the mammalian membrane;, Results: DCR was well tolerated with no adverse events during image and capture. Time to perform DCR was similar to that of a standard PA chest 2) stabilizing and folding of hairpin constructs of the CFTR transmembrane X-ray, as was image quality. Hemi-diaphragm maximum speed and domain. excursion during deep breathing correlated with FVC (maximum speed: Methods: The interaction(s) of VX-770 and VX-809 with the lipid bilayer right r = -0.701, p = 0.001; left r = -0.638, p = 0.003; maximum excursion: were assayed by several biophysical techniques. right r = -0.627, p = 0.004; left r = -0.0524, p = 0.034), with a trend towards i. A terbium-based liposome disruption assay was used to determine FEV1 with right hemi-diaphragm speed (right p = 0.061, r = -0.437, left p = 0.126, r = -0.364). drug effects on the membrane. Conclusion: This imaging system is promising in clinical settings, as it ii. To explore the effect of cholesterol on secondary structure/protein provides physiological and functional information, and is quick to perform. folding, circular dichroism (CD) spectroscopy was performed on WT and Further work to correlate larger sample sizes with more detailed CF-phenotypic mutant hairpin constructs consisting of the transmembrane pulmonary function tests is warranted. segments 3 and 4 of CFTR in lipid bilayers, in the presence and absence of cholesterol. CD experiments were also conducted on hairpins in the presence of VX-809. iii. Förster Resonance Energy Transfer spectroscopy was used to explore the general role of cholesterol in membrane protein folding and stabilization. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S9

Results: We show that cholesterol influences the extent of folding of CFTR of HspB5 was determined in F508del- and WT-CFTR-CFBE41o- cells. Cell helical hairpins in response to VX-809. Our experiments further establish surface expression of F508del-CFTR after HspB5 and phosphomimetics that the interaction of both drugs with the lipid bilayer is highly increased expression was assessed by different technics including cell surface ELISA in the presence of cholesterol, with the effect more prominent in HEK293 MSR Grip Tite cells expressing F508del-CFTR (Rotin’s Lab, in VX-770. Toronto, Canada). Function of F508del-CFTR after HspB5 and phosphomi- Conclusions: Our studies suggest an important role played by cholesterol metics expression was measured by YFP assay in HEK293MSR-GT. in the functioning of CF drugs. The impact of our findings will not only Results: Endogenous HspB5 protein is detected in HNEC from CF and non- bridge the gap in knowledge relating to existing CF drugs, but also provide a CF patients and increased in the lungs of CF mice model compared to platform for the design of novel CF therapeutics. control. Phosphorylation status of HspB5 was altered in F508del-CFTR- CFBE41o-. Using HspB5 and phosphomimetic-HspB5 mutants, we estab- WS05.3 lished that one of the phosphomimetic has the highest ability to restore Characterisation of the molecular mechanisms underlying F508del-CFTR at the plasma membrane. PI3Kγ-dependent stabilisation of CFTR at the plasma membrane Conclusion: Our study demonstrates that a phosphomimetic of HspB5 A. Murabito1,M.Li1, A. Raimondi2, A. Loffreda2, C. Tacchetti2, E. Hirsch1,3, increases the transport, function and stability of the F508del-CFTR. These A. Ghigo1, 3. 1University of Torino, Department of Molecular Biotechnology and activities are enhanced in presence of VX-770, VX-809 and VX-770 + VX- Health Sciences, Torino, Italy; 2Experimental Imaging Center, San Raffaele 809. Moreover, in CF disease we have shown that HspB5 acts in a very Scientific Institute, Ospedale San Raffaele, Milano, Italy; 3Kither Biotech Srl, different way compared to HspB1 and HspB4. Overall, this study pinpoints Torino, Italy the therapeutic potential of HspB5 spB5 in cystic fibrosis.

Objectives: Cystic fibrosis (CF) is caused by mutations in the gene encoding WS05.5 the cystic fibrosis transmembrane conductance regulator (CFTR). The most Examining the CFTR interactome upon mutation and drug exposure frequent mutation in patients (F508delCFTR) results in a trafficking defect M. Iazzi1, G.D. Gupta1. 1Ryerson University, Chemistry and Biology, Toronto, of the channel, that is retained in the endoplasmic reticulum (ER) and Canada degraded without reaching the plasma membrane (PM). To restore CFTR trafficking, several correctors have been developed but their efficacy is still Objectives: Despite extensive study, there are significant gaps in our unsatisfactory. Preliminary results from our lab suggest that PI3Kγ understanding of how CFTR is synthesized and processed and how CFTR is regulates CFTR stabilisation at the PM. Inhibition of PI3Kγ scaffold function, regulated and functions at the apical membrane. CFTR associates with a which is responsible for cAMP modulation, increases the amount of CFTR number of proteins that facilitate its trafficking or function, but our on the PM. understanding of these interactions and how they are altered in CF is Methods: To unravel how PI3Kγ controls CFTR stability, we exploited a cell- relatively poor. Furthermore, it is likely that additional proteins associate permeable peptide targeting its scaffold activity (Patent n° WO/2016/ with CFTR. The long-term objective of my research program is to fully 103176). characterize the molecular interaction landscapes of wild type and mutant Results: Immunogold staining and biotinylation assays demonstrated that CFTR proteins, and decipher the molecular defects of CFTR mutants. the PI3Kγ-peptide increases the amount of wild-type and F508del CFTR at Methods: Affinity-purification mass spectrometry (AP-MS) combined with the PM. Moreover, endoglycosidase H sensitivity assays revealed that the proximity labelling techniques such as BioID are a novel and effective compound specifically elevates the core-glycosylated F508del-CFTR. Of means of mapping stable and transient protein-protein interactions in note, this effect was independent on the peptide ability to modulate cAMP/ living cells. This study will utilize BioID to map the CFTR interactome and PKA signaling since PKA and phoshodiesterases (PDEs) inhibitors, but also examine how patient mutations and current frontline CF therapeutics cAMP analogues, did not affect peptide-mediated CFTR stabilisation. modify this interactome. Conversely, knock-down of GRASP proteins fully abolished the peptide Results: To date, we have generated the interactome for wild-type CFTR ability to stabilise the CFTR at the PM suggesting the potential involvement and the most common disease-causing mutations, ΔF508del and G551D, in of the unconventional trafficking route. a embryonic kidney cell line. These experiments are currently being Conclusion: We validated PI3Kγ as a new pivotal regulator of CFTR stability. replicated in a bronchial epithelial cell line, which is more representative of A better understanding on how the PI3Kγ-peptide mediates CFTR the human airway. stabilisation will strengthen the possibility to develop the compound Conclusion: A complete understanding of how the CFTR mutation into a CF therapeutic agent. Ongoing work will clarify how this activity interactomes change upon mutation or during drug treatments can might be exploited to augment therapeutic effects of CFTR potentiator and provide better insight on how this disease can be better treated. Subunits corrector drugs. of early endocytic clathrin machinery were lost in the G551D mutant but This work was supported by grants from the Italian Cystic Fibrosis Research appeared to be restored upon VX-770/VX-809 treatment. We propose that Foundation and Cariplo Foundation. these proteins may be involved in coupling CFTR channel conformation to its endocytosis from the PM and would therefore be novel regulators of WS05.4 CFTR PM density and activity. HspB5 is a phospho-regulated corrector of F508del-CFTR S. Simon1, 2, F. Degrugillier1, 2, B. Simonneau1, A. Aissat1, 2, V. Pruliere-Escabassè 1,2,3, P. Fanen1, 2. 1INSERM U955, Créteil, France; 2Université Paris-Est Créteil (UPEC), Créteil, France; 3Centre Hospitalier WS06 LCI - Old Method but new data Intercommunal de Créteil, Service d’ORL et de Chirurgie Cervico-Faciale, Créteil, France WS06.1 Objectives: Molecular chaperones are needed to assist newly synthesized Clinical value of Lung Clearance Index among patients with cystic proteins in order to adopt their functional 3D structures. The role of heat fibrosis 1 1 1 1 2 shock proteins (Hsp70, Hsc70 and Hsp90) in the processing of WT- or E. Hatziagorou , C. Mantsiou , E. Kouroukli , I. Lialias , P. Talimtzi , 1 1 1 F508del-CFTR, have been extensively studied besides the small Heat Shock S. Kirvassili , J. Tsanakas . School of Medicine, Aristotle University of 2 Proteins (sHSPs) HspB1 (Hsp27) and HspB4 (αA-crystallin), which favour Thessaloniki, CF Unit, Hippokration Hospital, Thessaloniki, Greece; School of the degradation of F508del-CFTR. HspB5, also called αB-crystallin, is a Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, ubiquitous protein including the lung. The aim of this study was to evaluate Department of Hygiene, Social-Preventive Medicine & Medical Statistics, the impact of HspB5 expression and phosphorylation on the maturation, Thessaloniki, Greece transport at the plasma membrane, stability and function of F508del-CFTR. Aim: To investigate the role of age, different types of bronchial infection Methods: Control and CF mice lungs and primary human nasal epithelial and pulmonary exacerbations upon lung clearance index (LCI) cells (HNEC) to assess HspB5 expression by ELISA. Phosphorylation status deterioration. S10 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

Methods: 76 children and adults with CF (mean (range) age (years): 10.58 WS06.3 (1.75 to 23.75)) performed 1272 serial Multiple Breath Washout Lung Clearance Index in infants with cystic fibrosis may predict lung (MBW) measurements and 1047 spirometries over a 7-year period. 289 function in preschoolers pulmonary Exacerbations (PEx) were recorded. Pseudomonas aeruginosa, V. Koucky1, 2, V. Skalicka1, 2, P. Pohunek1, 2. 12nd Faculty of Medicine, Charles Staphylococcus aureus infection, as well as aspergillus, candida, University, Department of Paediatrics, Prague, Czech Republic; 2University Achromobacter, Acinetobacter, Serratia and Stenotrophomonas Hospital Motol, Department of Paediatrics, Prague, Czech Republic Maltophilia isolated from cough swabs/ sputum cultures were recorded. Patients were divided into 5 age-groups: < 5 years, 5 to 10 years, 11 to 15 Objectives: Nitrogen multiple breath washout test (N2-MBW) with Lung years, 16 to 20 years and >20 years. Clearance Index (LCI2.5) has been shown to be a sensitive marker of small Results: Most lung function parameters showed significant progression airway disease in patients with cystic fibrosis (CF). Recently the safety and with age (FRC, LCI, Scond, M1/M0, M2/M0, FEV1% predicted, FEF50% feasibility of N2-MBW has been confirmed also in infants. However the predicted). LCI deteriorated significantly among the older age groups: ΔLCI predictive value of LCI2.5 for later lung function remains to be investigated. ((95% CI)) = 0.38 (-0.24 to 1.01), p = 0.228, 5–10 years; 1.14 (0.40 to 1.87), The aim of our prospective longitudinal study was to investigate the p = 0.002, 11–15 years; 3.02 (2.11 to 3.94), p < 0.001, 16 to 20 years and 3.92 relationship between ventilation inhomogeneity in infancy and spirometry (2.87 to 4.97), p < 0.001, over 20 years. in preschool age. LCI deteriorated significantly during pulmonary exacerbations, ΔLCI ((95% Methods: We enrolled 28 infants with CF. N2-MBW was performed at the CI)) = 1.11 (0.83 to 1.39), p < 0.001. New Pseudomonas colonisation caused a mean age 1.33 ± 0.49 years. Patients were followed prospectively until significant increase in LCI; ΔLCI 95% CI)) = 0.35 (0.01 to 0.69), p = 0.019. New preschool age. The first successful spirometry was performed at the age Stenotrophomonas colonisation caused a significant increase in LCI; ΔLCI 4.1 ± 0.6. The quality criteria for preschool spirometry by ATS/ERS (2006) 95% CI)) = 1.19 (0.45 to 1.94), p < 0.001. were adopted. We used reference data by Zapletal et al. (2003). The Conclusion: The LCI demonstrates progression of lung disease and relationship between LCI2.5 and the respective spirometry parameters corresponds to changes in bacterial infections and pulmonary exacerba- (FEV1 - forced expiratory volume at 1 second; FVC - forced vital capacity; tions among patients with CF. LCI may be a useful marker to track disease MEF25 - maximal forced expiratory flow where 25% of the FVC remains to deterioration and may have a role in the routine clinical care of patients be expired) were studied using Spearman’s rank correlation (r). Preschool with CF. FEV1%, FVC% and MEF25% were compared between groups of infants with LCI2.5 higher and lower than 10.0 by using t-test. WS06.2 Results: Successful N2-MBW measurements were available in 24 infants, Evaluation of LCI during pulmonary exacerbation in children with mean LCI2.5 = 10.6 ± 1.5. At preschool age, spirometry was available in 22 cystic fibrosis patients, FEV1% = 88.9 ± 14.5%, FVC% = 91.1 ± 13.9%, MEF25% = 76.4 ± 18.8%. 1,2 1,2 1,2 1, 2 1 Mean FEV % and FVC% was significantly higher in 14 infants with LCI < K. Walicka-Serzysko , M. Postek , J. Milczewska , D. Sands . Institute 1 2.5 2 10.0 than in 8 infants with LCI >10.0 (both p = 0.001). MEF % did not of Mother and Child, Cystic Fibrosis Department, Warsaw, Poland; Pediatric 2.5 25 differ (p = 0.196). LCI significantly and negatively correlated with FEV % Hospital, Cystic Fibrosis Centre, Dziekanow Lesny, Poland 2.5 1 (r = −0.485, p = 0.022) and FVC% (r = −0.613, p = 0.002).

Objectives: Pulmonary exacerbation (PEx) in cystic fibrosis is one of the Conclusion: Ventilation inhomogeneity in infancy measured by N2-MBW main factors affecting life expectancy. The Lung Clearance Index (LCI) is may predict preschool spirometry in CF patients. LCI2.5 at 16 months is sensitive to early CF lung disease and it is increasingly used to assess lung significantly and negatively correlated 7FEV1% and FVC% at 49 months. function in stable condition as well as during exacerbations. The aim of our study was to check the variability of selected pulmonary function WS06.4 parameters in patients with cystic fibrosis who were diagnosed with PEx. Early Pseudomonas aeruginosa (Pa) isolation impacts on N2-Multiple Methods: Forty paediatric CF patients median age 13 [10,5–15] had Breath Washout (MBW) and body mass index (BMI) percentile in performed a spirometry and Multiple Breath Nitrogen Washout (MBNW) children with cystic fibrosis tests when they have been clinically stable, at the beginning and at the end F. Lucca1, G. Paiola2, G. Cucchetto2, A. Borruso2, L. Menin2, E. Pintani2, of treatment of PEx. S. Volpi2, M. Cipolli2. 1University of Verona, Pediatrics School, Verona, Italy; Results: We found weak negative correlation between percentage change 2Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, in LCI and FEV1 values obtained in their stable state and those obtained at Verona, Italy the beginning of the PEx (r = -0,3849 p < 0,05). An average change in LCI between stable state and the beginning of PEx amounted of 0.98 (± 1.86) Objectives: Since early events in CF patients’ life can determine disease units, which represented 10.64% (± 18.06). However, the LCI response was progression and burden in later years, there is increasing interest regarding − these events. The aim of our study was to evaluate the effect of Pa first not uniform in all patients. FEV1 values decreased 8,075% (±11,24) and − identification in preschoolers. 0,57 z-score (±1,069). After treatment the FEV1 parameter increased by an average of 11.13% (± 9.11) while the LCI decreased of 1.22 ± 1.57 units, which Methods: We retrospectively evaluated data regarding 150 2003–2013 represented an average of 9.52% ± 11.275 compared to the value at the birth cohort CF patients with regular follow-up. Mean spirometries and th beginning of the exacerbation. We had no significant difference between auxology measurements in the 6 year of life and first time ever N2-MBW Sacin and Scond values. were extracted. Conclusion: The obtained results suggest that an increase in LCI up to 11% Results: We identified 3 groups: 61 patients with first Pa identification compared to the stable state may indicate PEx. Moreover, early treatment of before 2 years of age (group A); 47 patients with first Pa at 2–6 years of age PEx can help prevent deterioration of lung function. The correlation (group B); 42 patients without Pa up until 7 years of age (group C). Class I or II mutations on both alleles and pancreatic insufficiency were between FEV1 and LCI implies that LCI could be one of the factors useful in the diagnosis of PEx in cystic fibrosis patients. This parameter could be more frequent in groups A and B than in group C (79% and 72.3% vs 36% and handy especially in young children with early lung disease who often can 91.8% e 85.1% vs 40.48%, respectively). Chloride at sweat test was higher in not perform spirometry. group A and B (97.84 ± 10.89 vs 97.2 ± 2.7 vs 84.2 ± 19.84, p < 0.004). BMI percentile was higher in group C (p < 0.01). Examining spirometries in the 6th year of life, percent predicted (pp) FVC

was higher in group C, as was ppFEV1%, though not significantly. LCI 2.5% was worse in groups A and B than in group C (9.45 [8.93–12.6] and 10.82 [8.47–13.52] vs 7.91 [7.24–11.13], p = 0.011); analysis of ppLCI 2.5%

was consistent with absolute values; LCI5% and Scond were also significantly worse in groups A and B; Sacin was no different between groups. No significant difference was shown between groups A and B for all examined parameters. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S11

Chronic colonisation developed in 19.67% of group A and in 21.28% of group we used data from 118 healthy infants age 2–22 months (unpublished data, B. MRSA was found in 3.3% of A, 8.5% of B, 4.8% of C. P. M. Gustafsson). Conclusion: Early Pa isolation impacts on BMI and respiratory function in Results: Ninety-five longitudinal MBW test occasions were accomplished CF preschool children. While spirometry does not show a clear difference in in 17 children. The first 21 test (before July 2018) were excluded due to face the considered subsets, first N2MBW was significantly worse in patients masks with an undesirable large dead space. Two tests (2.7%) were with early Pa isolation, apparently anticipating effects on spirometry. excluded due to poor quality. The mean (range) number of test occasions per child was 4.2 (3–6). Mean LCI was 7.75 (test = 19, N = 8, mean age 7.9 WS06.5 months, age-specific upper limit of normal (asULN) 8.03) in infants < 1 Adding a Slow Vital Capacity (SVC) manoeuvre to the methodology of year, 7.80 in infants 1–2 years (test = 26, N = 13, mean age 18.7 months,

Multiple Breath Nitrogen Washout (MBWN2) can enhance the asULN 7.54) and 8.40 (test = 27, N = 10, mean age 29.7 months, asULN NA, sensitivity of the Lung Clearance Index (LCI) but expected ≤7.3) in children >2 years. Number of tests above the asULN C. Short1,2, C. Saunders1,2, S. Irving1, 2, J. Tuyindi1, T. Semple1, 2, J. Davies1, 2. increased with age - 5/19 (26%) in children < 1 year, 17/26 (65%) in children 1Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom; 1–2 years and 23/27 (85%) in children >2 years of age. A linear mixed model 2Imperial College London, National Heart and Lung Institute, London, analysis demonstrated a significant annual increase in LCI of 0.45 units/ United Kingdom year (CI 95% 0.1–0.8). Conclusion: Our preliminary data indicate that longitudinally SF6 MBW Objectives: There is much enthusiasm for measuring LCI from MBWN2 may detect and be useful in monitoring CF lung disease from infancy. The owing to its sensitivity and effort independent technique. However, there’s pathological trend in LCI in children with CF receiving best standard care a limitation which, if addressed, could enhance sensitivity. With the highlights the need for strategies to prevent or slow down progressive CF addition of an SVC, signal from poorly ventilated lung units (PVLU) can be lung disease from infancy and may depend on the use of CFTR modulators. incorporated into LCI. Methods: Ten healthy controls (HC) and 37 cystic fibrosis (CF) subjects ‘ ’ performed MBWN2 according to Jensen et al. 2013. After the end of test subjects performed an SVC followed by tidal breathing until the ‘end of test’ WS07 Physiotherapy at home criteria were again met. Quantification of PLVU relies on a 3-part calculation, a value we termed LCI . Part 1- the change in Nitrogen X WS07.1 concentration [N ], between SVC and its preceding breath, multiplied by 2 Evaluation of video conferencing consultations in the West of Scotland the volume (L) of the expiration of the SVC. Part 2- if the [N ] of the breaths 2 Adult Cystic Fibrosis unit following the SVC remain higher than the target [N2], the additional L. Morrison1, D. McTavish1. 1West of Scotland Adult CF Unit, Glasgow, volume is included. Part 3- the SVC with the largest [N2] delta is added to the mean LCI. United Kingdom Results: Subjects young as five were able to perform the SVC. For HC, LCIX Objectives: To assess the value of video conferencing (VC) for people with – was similar to LCI (median [IQR] difference 0.22 [0.02 0.51], NS). For CF Cystic Fibrosis (pwCF). – subjects, LCIX was 1.17 [0.34 2.01] greater than LCI (P < 0.0001). LCIX was Methods: 17pwcf were invited to attend an AHP(Physiotherapy/Dietitian) – repeatable between stable visits for CF subjects (8.3 [7.51 10.27] vs 8.0 specific VC clinic. They evaluated the benefit of VC in place of standard face – [7.5 10.3] n = 11) and was sensitive to pulmonary exacerbations (PeX) (8.0 to face clinic appointments using anonymised online questionnaires. – – [7.6 11.6] vs PeX-10.7 [9.0 14.5] P < 0.0001; n = 17). In this paired data set, Results: – – a significant increase was also seen in LCI (7.7 [7.3 10.0] vs PeX-9.7 [8.3 • 17pwCF completed the pre-clinic survey. 12.0] P < 0.0001), but the relative difference in LCIX was greater (34.4% vs 62% had no previous experience of VC, 94% considered this useful for 26.7%). communicating with AHPs. Specific concerns raised related to the required Conclusions: The variability in LCIX between CF subjects suggests this technology and accuracy of exacerbation management with no access to measure may provide additional information over standard LCI, potentially auscultation or spirometry. Some preferred face to face consultations and informing on proximal vs distal disease. The greater difference between others felt VC would reduce travel time. HC/CF and stable/PeX values could mean superior sensitivity as an outcome • 11 people attended the VC clinic and completed the post clinic survey. measure. Future work will compare LCIX with sensitive imaging techni- • 6 failed to attend the VC with no reasons given. ques, and study changes with clinical interventions. Responses were extremely positive with 100% finding VC useful and willing to consult with other MDT members this way.100% stated the AHP was able WS06.6 to resolve all issues raised and 80% reported that if necessary, follow up Longitudinal SF6 Multiple Breath Washout measurements in infants occurred. and young children with cystic fibrosis born after implementation of 80% preferred VC over standard telephone calls, however this would newborn screening depend on the nature of the discussion. Technical issues were experienced 1 1 1 1 1 R.M. Sandvik , M.N. Schmidt , C. Voldby , T. Pressler , F. Buchvald , but the use of smart phones appeared to resolve data issues and syncing of 2 1 1 1 P. Gustafsson , M. Skov , K. Nielsen . Rigshospitalet, University Hospital sound and vision. Benefits highlighted were: reduction in consultation Copenhagen, CF Centre Copenhagen, Paediatric Pulmonary Service, time (80%), convenience of not travelling/parking at hospital site (90%), Department of Paediatrics and Adolescent Medicine, Copenhagen, Denmark; seeing both AHP’s together (60%) and benefits of reduction in cross 2 Skaraborgs Sjukhus, Barn-och Ungdomsmedicin, Skövde, Sweden infection (70%). Specific comments were; ability to fit VC into lunch time thus not requiring time off work, a more relaxed, less rushed discussion of Objectives: Multiple Breath Washout (MBW) is a potentially valuable tool more relevant issues. for measuring airway impairment in young children with CF. With Conclusion: Overall VC proved to be well received and a viable option to implementation of new born screening (NBS) for CF in Denmark May increase appointments when clinical space is limited. The benefit of face to 2016, we aimed to describe longitudinal trend in the lung clearance index face consultations is recognised but VC could be used by the full MDT for (LCI) in this NBS cohort. alternating appointments to minimise travel time and cross infection risks Methods: From Nov. 2017, SF -MBW (Exhalyzer® D, EcoMedics AG, 6 whilst maintaining optimal clinical management of the pwcf. Duernten, Switzerland) was performed every 3 months (on days without acute pulmonary symptoms) in 19 children. Intranasal dexmedetomidin was used as sedative during testing. All children were followed by our standard care CF regime with monthly clinical visits. As reference material S12 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

WS07.2 Table 1. Respiratory Admission Avoidance Physiotherapy (RAAP) pilot for Participant Demographics. Median (Range) children with cystic fibrosis via Hospital in the Home (HITH) Group Gender Age Baseline Pre Distance from 1,2 1, 2 1 3 1, 2 1 ’ A. Elliott , M. Wallace , A. Middleton , M. Doumit , C. Benz . Children s (m/f) ppFEV1 ppFEV1 Hospital Hospital at Westmead, Physiotherapy, Westmead, Australia; 2Sydney Children’s Hospital Network, Hospital in the Home, Sydney, Australia; 3Sydney Hybrid 8/23 13 (10–16) 87 (80–95) 77 (68–83) 21kms (11–27) Children’s Hospital, Physiotherapy, Sydney, Australia Standard 11/14 12 (10–15) 83 (68–98) 75 (57–87) 122kms (21–377) Airway clearance is a cornerstone of treatment for young people with CF. There is potential to reduce the severity of health decline (reducing Conclusion: This study provides important preliminary information hospitalised bed days, IVABs, burden of care and reductions in respiratory supporting a hybrid telehealth physiotherapy model as an alternative to function) through early intensive physiotherapy (PT). Early community- standard care for young people with CF during an exacerbation. Safety of based PT has been shown to decrease hospitalisation and ED presentations the hybrid model was high. Future research in telehealth should include in CF populations. Hospital in the Home (HITH) may be a pathway for prospective studies of clinical outcomes during respiratory exacerbations, children with CF to avoid hospitalisation. its impact on families, and opportunities to bring physiotherapy care closer Objectives: Pilot study to assess effectiveness of an early, home based PT to home for remote patients. HITH admission at WS07.4 i. avoiding hospitalisation and Pre-visit planning with a mobile patient support system in a paediatric ii. reducing admission related costs (to patient and hospital) for patients cystic fibrosis centre deemed at risk. H. Abdulahi1, K. Wallin1, M. Mårtensson1, C. Hansen1, M. Montan2. 1Barnkliniken Lund, Lund, Sweden; 2Genia Upstream Dream, Stockholm, Method: Patients deemed at imminent risk of hospitalisation for Sweden respiratory exacerbation between April 2017- June 2018 were considered. A 2-week RAAP physiotherapy only HITH admission was provided to Objectives: The Lund paediatric Cystic Fibrosis (CF) centre uses a optimise airway clearance, inhalation therapy and exercise. Twice daily mobile patient support system (PSS) developed by a CF father in Sweden. sessions in week 1, daily in week 2 with medical reviews pre, mid and post. The PSS is an app used by all CF centres in the country and is integrated Treatment provided at home or school. with the National CF Quality Registry. The purpose of the app is to help Outcomes: Hospitalisation avoided (no readmission 6 weeks post young patients and their families to manage CF and to support self-care discharge), time to next admission, estimated hospital bed days/days of activities. Patients can keep track of key treatments, such as antibiotics, and IVABs saved and satisfaction survey. record daily health and quality of life observations. The PSS also supports Results: Nine of 12 patients avoided hospitalisation. Three were hospita- communication with the CF centre and enables pre-visit planning to lised before or on day 14. Average time to next admission was 219 days support healthcare appointments and shared decision-making. (range 49–476) or 7.2 months; 2 patients have not been hospitalised. Based Methods: Physiotherapists introduce the app to CF families during on a 14-day admission, 126 estimated bed days were saved. Patient/Carer appointments and encourage them to fill in and send pre-visit reports. satisfaction and perceived effectiveness with RAAP was a median 10/10. They also support families with practical aspects such as training on how to Conclusion: This pilot was shown to be a successful pathway to avoid use the app. During weekly team meetings the multidisciplinary care team hospitalisation for respiratory exacerbation in the majority of patients. An reviews pre-visit reports for the week to plan for upcoming appointments estimated 126 bed days/days of IV antibiotics were saved. RAAP was well together. received with overall satisfaction, perceived effectiveness and benefits Results: As of December 2019, 51 out of the total 61 paediatric patients had rated highly. These results are encouraging and we have begun a follow up downloaded the app and 73% used the support system in 2019. The PSS has investigation. positively affected the way the team works. Patient appointments are better prepared for with pre-visit reports. Requested prescriptions and equipment can be prepared in advance. The team can also schedule WS07.3 multidisciplinary professionals that patients have requested to meet during Managing exacerbations in young people with cystic fibrosis through their visit, saving time and costs for the patient. Patient reported Hospital in the Home physiotherapy via Telehealth information helpsto assess patients during meetings and to get an overview 1,2 3 1 1, 2 1 ’ C. Benz , A. Harvey , A. Middleton , A. Elliott . Children s Hospital at of their status over time. 2 ’ Westmead, Physiotherapy, Westmead, Australia; Sydney Children s Hospital Conclusion: The use of a mobile patient support system for pre-visit 3 Network, Hospital in the Home, Sydney, Australia; Monash University, planning supports multidisciplinary team coordination and preparation Physiotherapy, Melbourne, Australia for efficient patient appointments. Further research is needed to measure The demand for Hospital in the Home (HITH) in Australia has increased the benefits accrued for both the healthcare system and patients. significantly, however a limiting factor of HITH efficiency is excessive travel WS07.5 distances and time. Telehealth has potential to increase in-home access to Pilot study - exercise response and enjoyment of virtual reality in an specialist care and HITH physiotherapy treatment capacity. inpatient stay Objectives: To examine Telehealth for HITH physiotherapy in the 1 1 1 1 1 1 management of respiratory exacerbations in young people with CF. K. Setchell , F. Cathcart , Z. Beverley , S. Cunningham , A. Jones . Royal Methods: An observational benchmarking study examined a hybrid model Brompton and Harefield NHS Trust, London, United Kingdom (1xTelehealth,1x face-to-face home visit) vs standard care (2x face-to-face) Background: Exercise is an important part of CF care and is well provided by HITH physiotherapy during exacerbations requiring IVABs documented. VR can reduce perceived amount of exercise and is used between Jan 2017 - June 2019. Patients were allocated according to distance widely in the general population for exercise. VR could be an attractive from hospital, with a 35 km limit for home visits in hybrid model. Primary alternative during an inpatient stay to allow exercise sessions in a confined outcome: Frequency of return to 0.95 of baseline ppFEV1 (best in previous space and to engage patients in a novel format. 12 months). Secondary outcomes: adverse events, change in FEV1, Objective: To assess if Virtual Reality (VR) can be used as a form of exercise Telehealth travel time and distance saved. in an inpatient hospital stay to achieve an appropriate exercise response Results: HITH physiotherapy provided 84 episodes of care: hybrid (N = 42); and to assess patient enjoyment and satisfaction. standard care (N = 42); participant demographics shown in Table 1. Return Methods: VR was offered with an active rhythm-based game as an to 0.95 of baseline was achieved in 48% of hybrid group vs. 33% in standard alternative to usual exercise sessions. Heart rate (HR) was recorded through – care. Median ppFEV1 change was +6% in hybrid group vs +2.5% in standard each session using a finger probe and HR targets set to reach 60 80% of an care. There were no adverse events with Telehealth. Travel time and individual’s predicted HR max. Time to HR target was also recorded. distance saved were estimated at 16,706 min and 12,448.8 km. A feedback questionnaire was completed on the last session of VR. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S13

Results: 10 patients (7 males, median FEV1 52%) were offered VR sessions.1 selective growth media. Molecular microbiology, based on PCR, is known to patient declined. Patients completed 2.5 sessions (range 1–5) during their be more sensitive and detects a wider range of organisms in cross-sectional admission. comparisons. Here we compared molecular- and culture-based microbiol- 1 patient reached 60% HR max and all reached at least 40%. Of the 8 patients ogy on longitudinal respiratory samples from Pa-free paediatric patients. who did not achieve HR max, 7 achieved their highest HR in the last Methods: 44 paediatric patients with mild CF provided samples at regular session. 8/10 feedback forms were returned with 7/8 reporting VR as intervals over a period of 3 years. Patients with at least 7 samples were enjoyable and that they would use VR again. 4 participants reported subjec- included in this analysis. All patients were considered free of chronic Pa at tively working harder than previous exercise sessions. Subjective reports study entry. High-throughput sequencing (HTS) of the 16S rRNA gene was included finding it a fun distraction from hospital and helping reduce compared to routine microbial culture performed on samples collected at anxiety. the same time. Patients with ≥50% isolation of Pa were deemed to be Conclusion: Patients showed high enjoyment of VR for exercise sessions. chronically infected. However, reaching HR targets needed more sessions to allow an element of Results: 17 patients (9M/8F) were included, average age 10.4yrs and mean learning for both the therapist and the patient. Further research would FEV1 98.7% predicted. Median follow-up was 850 days (2.3 years). 103 need to explore varying games and comparison with other exercise paired samples were compared, (40 cough swabs and 63 sputum samples). methods. 14 patients (82%) had no Pa on clinical micro at any point, 1 patient had intermittent infection, and 2 patients had chronic Pa infection. In contrast, WS07.6 6 patients (35%) had chronic Pa by PCR, 7 were intermittently infected, and Getting a ‘handle’ on nebuliser compliance in young children only 4 (24%) remained free of Pa throughout. PCR sequencing also isolated C. Lord1, P. Singleton1, F. Lindsay1,R.Jayaraj1, A. Murad1. 1James Cook Burkholderia spp. as a chronic colonisation in 2 patients (none isolated by University Hospital, Teesside Cystic Fibrosis Service, Middlesbrough, culture) and high rates of H. influenzae infection United Kingdom (58% chronic, 30% intermittent). Conclusion: HTS identified substantially greater levels of infection with Pa, Objectives: Time taken to nebulise medication multiple times a day affects Burkholderia spp. and H. influenzae than conventional microbiological quality of life for families. Little is known about the stress and anxiety for culture. Based on PCR,10/17 (59%) of children with mild disease in a non-Pa parents administering these therapies in young children compared to clinic would be re-classified. This has significant implications for patient evidence for those caring for an adolescent. Nebulisation times in our segregation and treatment options. Analysis of a corresponding longitu- cohort varied from 5–20 minutes, those taking longer had decreased dinal adult population is ongoing. compliance and increased apprehension around treatment. Our objective was to find a solution to improve technique therefore decreasing WS08.2 nebulisation time, reducing physical support parents give the child thus The first time point of Pseudomonas aeruginosa identification in the achieving better adherence. respiratory tract microbiome of newborns and infants with cystic Methods: Informal discussion by the physiotherapist highlighted the fibrosis challenges parents face with nebulised therapies on a daily basis using the 1,2 1 1,2 1 1, 2 PARI eFlow®.One idea was that a ‘handle’ might make it easier to hold the M.-M. Pust , I. Rudolf , A.-M. Dittrich , L. Wiehlmann , B. Tümmler . 1Medizinische Hochschule Hannover, Clinic for Paediatric Pneumology and nebuliser in the correct position to optimise drug delivery therefore reduce 2 time taken to administer treatment. In collaboration with the CF team, local Neonatology, Hannover, Germany; German Center for Lung Research (DZL), families and Medical Physics at James Cook University Hospital, a ‘handle’ Hannover, Germany attachment was developed that clips onto the nebuliser handset without Objectives: Locate the first time point of Pseudomonas aeruginosa (Pa) in changing how it works. Families then trialled the handle and completed an the respiratory tract of infants with cystic fibrosis (CF), identify bacterial, anonymised questionnaire. viral or environmental patterns influencing an early detection, and Results: Results from the questionnaires showed an increased level of evaluate the practical feasibility of culture-independent sequencing tools acceptance of nebulised treatments. Parents found it quicker to complete as potential routine diagnostics. therapy; children were able to manage it independently without parents Methods: Cough swabs were collected from healthy (n = 52) and CF- holding the nebuliser and had a free hand to play games, keeping them diagnosed children (n = 48) up to the age of six. Longitudinal sampling of distracted. Overall an increase in compliance and acceptability was found twelve CF patients still continues, starting from the date of diagnosis for both children and parents. (newborn screening), ending with the first detection of Pa. High-resolution Conclusion: Following positive feedback from our families, the ‘Handle’ shotgun metagenomic sequencing and a reference-based assembly has since become commercially available under the name Nebigrip. It has approach were applied for taxonomic and functional investigations. been commended in innovation North Bright Ideas in Health Awards. This Results: Pa was detected in 24% of CF-infants and in 21% of healthy children highlights that for parents struggling with daily problems, a small change with the youngest child being three weeks old. In all cases, Pa was part of can have a big impact and emphasises the importance of listening and the rare biosphere and did not affect alpha diversity of abundant or rare involving parents with innovative ideas. species. A hierarchical clustering method revealed three profiles of microbial community composition. The first two groups were similar, including diseased and healthy children with and without Pa. The third group appeared separate during cluster analysis, containing only healthy WS08 The CF airway microbiome: omics-based and PA-negative children. The latter profile was characterised by an detection and monitoring increased bacterial load of abundant (epsilon-squared effect size (e2) = 0.57) and rare species (e2 = 0.39), as well as increased alpha diversity of rare species (e2 = 0.20) and more rare species in general WS08.1 (e2 = 0.21). Comparison of longitudinal sputum microbiology culture with Conclusion: Healthy and diseased infants come in contact with Pa early on. high-throughput PCR-based sequencing 1 1 2 1 2 3 The presence of Pa as a rare species in the respiratory tract is not necessarily H. Gavillet , L.R. Hatfield , B. Bianco , D.W. Rivett , A. Jones , A. Maitra , disease-associated. A Pa-negative microbial signature was identified, A. Horsley2,4, C. van der Gast1. 1Manchester Metropolitan University, 2 which was characterised by increased bacterial load of abundant and Manchester, United Kingdom; Manchester Adult CF Centre, Manchester, rare species, increased alpha diversity and number of rare species, 3 ’ United Kingdom; Royal Manchester Children s Hospital, Manchester, contributing to the functional diversity of the respiratory tract microbiome. United Kingdom; 4University of Manchester, Division of Infection, Immunity and Respiratory Medicine, Manchester, United Kingdom Objectives: Culture-based microbiology is used to inform treatment of lung infection in CF by growing key pathogens, such as P. aeruginosa (Pa), on S14 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

− WS08.3 (p = 2.07*10 8) when compared to donor tissue, while in CF tissue − Novel characterisation of the lung microbiome in cystic fibrosis community dominance was significantly higher (p = 1.20*10 8). For both patients and longitudinal changes associated with Pseudomonas CF and donor tissue, significant intra- and inter-patient variability in aeruginosa early colonisation ecological parameters was observed (p < 0.05). No significant relationships L. Velo-Suarez1, 2, S. Schutz1, S. Gouriou1, R. Le Berre1,3, G. Héry-Arnaud1, 4. were observed between ecological parameters and pre-transplant Brody 1Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France; 2Association Gaétan score, or presence of features of end-stage lung disease on MicroCT Saleün, Brest, France; 3CHRU La Cavale Blanche, Département de Médecine (p > 0.05). Interne et Pneumologie, Brest, France; 4Unité de Bactériologie, Pôle de Conclusions: The end-stage CF lung is characterised by a low diversity Biologie-Pathologie, Centre Hospitalier Régional et Universitaire de Brest, microbiota, which differs markedly within and between individual CF Hôpital de la Cavale Blanche, Blvd Tanguy Prigent, Brest, France patients. Moreover, diversity and richness in the deeper airway tissue is underestimated by analysis of sputum. There was no clear relationship Objectives: Our knowledge of species and functional composition of the between regional variation and structural lung damage. Larger, longitu- cystic fibrosis (CF) lung microbiome is rapidly increasing. However, how dinal ‘omics’-based studies may facilitate increased insight into the microbiome structure evolves over time, and whether changes within it relationship between microbiota composition and structural damage in CF. impact Pseudomonas aeruginosa (Pa) colonisation remains uncertain. Methods: We assessed the microbial community structure of 188 serial WS08.5 sputa and subsequent disease course of 47 patients collected over a span of Omics-based surveillance of Pseudomonas aeruginosa infection 3 years using 16S rRNA sequencing. Samples were separated into “never” identifies clonal persistence despite ‘eradication’ (patient has never been infected with Pa) or “free” (patient shows no Pa 1 2 3 4 5 1 J. Bartell , L. Sommer , R. Marvig ,M.Skov , T. Pressler , S. Molin , cultures in a year) according to Lee’s criteria. 2,6 1 H. Krogh Johansen . Technical University of Denmark, Novo Nordisk Results: All CF lung samples were characterised by an outgrowth of the 2 Foundation Center for Biosustainability, Kgs. Lyngby, Denmark; Rigshospitalet phyla Proteobacteria and Actinobacteria, mainly explained by higher (Copenhagen University Hospital), Department of Clinical Microbiology, relative abundances of species associated to Haemophilus (14% of total 3 Copenhagen, Denmark; Rigshospitalet (Copenhagen University Hospital), reads) and Neisseria (12%). Streptococcus was the most abundant (24%) and 4 Center for Genomic Medicine, Copenhagen, Denmark; Rigshospitalet prevalent (n = 188 samples) genus. Patients who remained uninfected with (Copenhagen University Hospital), Department of Pediatrics, Copenhagen, Pa, whether never or free, maintained intra-individual stable microbiome 5 Denmark; Rigshospitalet (Copenhagen University Hospital), Cystic Fibrosis communities. However, they showed a substantial inter-individual 6 Center, Copenhagen, Denmark; University of Copenhagen, Department of heterogeneity in their microbiota composition and structure. None of the Clinical Medicine, Copenhagen, Denmark bio-clinical metadata collected during the study such as infection stage, age, sex, antibiotic intake and cftr mutation explained any of the variation Objectives: Eradication of bacteria from the lungs is a primary goal in the in the bacterial community observed between patients. Pa first infections treatment of cystic fibrosis (CF) patients, and early eradication therapy remained consistently associated with reduced microbial richness, the (EET) is relied on to clear initial infection in a majority of patients. In lowest values being observed in subjects with the highest Pa loads. general, infection eradication is determined by a lack of positive cultures of Conclusions: Microbiome stability suggests that CF bacterial communities the pathogenic bacteria; however, surveillance via whole genome can remain unchanged over prolonged periods. Inter-patient heterogeneity sequencing (WGS) can provide critical insight regarding the true clearance may reflect the inherent difference among individuals due to genetic and/ of strains. or environmental backgrounds. Links between Pa colonisation and CF lung Methods: We selected 80 patients for which we had complete bacterio- microbiome in early infections will be discussed as they may help identify logical records at the Copenhagen CF Center from the date of first alternative strategies to maintain lung health into adulthood for CF Pseudomonas aeruginosa (Pa) positive culture within the monitoring patients. period (2002–2018). Seventy-two patients had at least one isolate sequenced and clone typed. After calculating Pa-free intervals (PFI), we WS08.4 applied phylogenetic analysis and multivariate statistical modelling of Microbial community composition in explanted cystic fibrosis and phenotypic data to examine isolate relatedness over time. unused donor lungs Results: 86% of patients exhibited an eradication period (PFI of at least 6 G.G. Einarsson1, B. Vanaudenaerde2, C.D. Spence3, A.J. Lee1, M. Boon4, months). However, within 42 patients with consistently sequenced G.M. Verleden2, J.S. Elborn1, L.J. Dupont2, D. Van Raemdonck2, D.F. Gilpin3, positive Pa cultures, 43% retained the same clone type over their R. Vos2, S.E. Verleden2, M.M. Tunney3. 1Halo Research Group, School of maximum ‘eradication’ period (mean length: 1.4 years, range: 0.52–3.6 Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, years). Combined phylogenetic and phenomic evaluation suggests that Belfast, United Kingdom; 2Leuven Lung Transplant Unit, Department of post-eradication samples of the same clone type are not re-infections from Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium; 3Halo the environment, but re-emergence of the same persisting bacterial strain. Research Group, School of Pharmacy, Queen’s University Belfast, Belfast, We show examples of maintained phylogenetic and phenomic similarity United Kingdom; 4Pediatics Unit, UZ Leuven, Leuven, Belgium over eradication periods, between lower and upper airways, and during transmission cases, which contrast with examples of colonisation by new Objectives: To determine if the microbiota in the lungs of people with end- clone types. stage cystic fibrosis (CF) is spatially heterogeneous and related to localised Conclusions: Most CF patients experience a Pa eradication period. structural damage. However, close to half of patients cleared according to positive culture Methods: Tissue (n = 131) and luminal mucus plugs (n = 20) samples were are not truly cleared according to WGS, an important tool to identify the extracted from explanted lungs of people with CF (n = 11) and unused persistently infected. This distinct cohort would likely benefit from donor lungs (n = 4 patients). Microbial community composition was additional monitoring and customised treatment. determined by Illumina MiSeq sequencing and related to the Brody score and features of end-stage lung disease assessed on MicroCT. WS08.6 Results: Ninety-eight CF tissue samples (n = 11 patients), 20 CF luminal Pseudomonas aeruginosa phage gene expression changes in co-culture mucus plug samples with Streptococcus and Rothia spp. in an artificial sputum model (n = 8 patients) and 33 donor tissue samples (n = 4 patients) were analysed. 1 1 1 2 1 L.L. Wright , A. Cazares , W. Figueroa , M. Walshaw ,S.O’Brien , Significant differences in microbial community composition were seen 1 1 1 2 C. Winstanley , J.L. Fothergill . University of Liverpool, Liverpool, between the 3 groups (R = 0.12; p = 0.001). However, there was 2 United Kingdom; Liverpool Heart and Chest Hospital, Liverpool, some overlap between the three communities, particularly between CF United Kingdom and donor tissue and between a subset of CF tissue and CF sputum samples. CF tissue demonstrated a significantly lower community richness Objectives: Chronic bacterial lung infections with Pseudomonas aeruginosa − − (p = 2.73*10 5), Shannon-Wiener diversity (p = 2.06*10 8 and evenness are common in people with cystic fibrosis (CF) but interactions with other Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S15 commonly seen members of the CF lung community, such as Streptococcus WS09.2 and Rothia spp., are not well understood. The aim of this study was to Automated image analyses of cystic fibrosis transmembrane determine the impact of other species on P. aeruginosa using an artificial conductance regulation-dependent, β-adrenergically-evoked sweat sputum medium (ASM) model designed to mimic the conditions in the CF secretion driven by iontophoresis lung. A. Reynaerts1, F. Vermeulen2, P.Melotti3, S. Gohy4, R. Frédérick5, M. Nietert6, Methods: P. aeruginosa LESB58, representing a CF strain, was T. Leal7. 1Université catholique de Louvain, Louvain Center for Toxicology and inoculated into ASM either alone or in co-culture with Streptococcus Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, anginosus, Streptococcus vestibularis, Rothia mucilaginosa or Rothia dento- Brussels, Belgium; 2Université catholique de Louvain, Cystic Fibrosis Center, cariosa. Gene expression was assessed using RNAseq at 72 and 96 h Leuven, Belgium; 3Azienda Ospedaliera Universitaria Integrata, Cystic Fibrosis timepoints. Free phage numbers were assessed by plaque assay and qPCR. Center, Verona, Italy; 4Université Catholique de Louvain, Cystic Fibrosis Center, Results: Differential expression of P. aeruginosa genes, including those Bruxelles, Belgium; 5Université catholique de Louvain, Medicinal Chemistry, related to virulence factors such as prophage, type III secretion, Louvain Drug Research Institute, Bruxelles, Belgium; 6University of Goettingen, exopolysaccharides and pyochelin production, was seen in co-culture Institut fuer Medizinische Bioinformatik, Goettingen, Germany; 7Université conditions compared with single-species culture. In particular, at 72 h, catholique de Louvain, Louvain Center for Toxicology and Applied there was lower expression of most LES prophage genes under co-culture Pharmacology, Institut de Recherche Expérimentale et Clinique, Bruxelles, conditions, and this corresponded with lower overall free phage at the Belgium same timepoint. Specifically, during co-culture, there was a reduction in the levels of a D3112-like transposable phage, previously shown to have the Objectives: An image-based test allowing dissecting Cystic Fibrosis (CF) ability to drive CF-like adaptations in an experimental evolution model, Transmembrane Conductance Regulator-independent and -dependent and an increase in levels of Pf1-like filamentous phage, associated with sweat secretion was previously validated in small cohorts using intradermal altered biofilm formation and immune responses. injections and laborious operator-dependent image analysis. The test was Conclusion: Gene expression changes during co-culture with Streptococcus reported to better define diagnosis, prognosis and efficacy of CF-directed and Rothia spp. were identified affecting key P. aeruginosa virulence factors therapies. The aim of this work is to evaluate, in larger cohorts, the auto- including phage. Further work indicated changes to free phage levels of mated analysis of images reflecting cholinergic or β-adrenergic stimulated two important P. aeruginosa LESB58 prophage with the potential to affect P. sweat secretion obtained during a non-invasive version of the test. aeruginosa adaptation, antibiotic resistance and host immune response in Methods: Cholinergically- or β-adrenergically-stimulated sweat secretion the CF lung. was obtained by iontophoresis of pilocarpine solution or by electroosmosis of solution with atropine, isoproterenol and aminophylline. Both solutions were conducted using Macroduct device (Wescor). Efficacy of drug delivery was previously evaluated by evaporimetry. Images of sweat droplets were WS09 Improving the diagnosis of CF recorded during cholinergic and β-adrenergic phases. A software was developed to automatically measure droplet circumferences and their time-dependent changes. WS09.1 Results: 40 healthy controls and 15 patients with CF were tested. ICM and NPD diagnostics of cases with inconclusive CFTR genetics and Iontophoresis/electroosmosis delivery of drugs was achieved after asses- sweat test: a single-centre 10-year experience sing different drug concentrations and pH solutions. After filtering and 1 1 1 1 1, 2 1 R. Minso , A. Schulz , C. Dopfer , N. Alfeis , G. Hansen , S. Junge , elimination of non-specific signals, statistical image analysis performed by 1 2,3 3 1, 2 1 C. Müller , F. Ringshausen , A. Sauer-Heilborn , F. Stanke , C. Stolpe , the AutoBuSTeD software showed that droplets formed during β- 1 2,3 1,2 1, 2 1 S. Tamm , T. Welte , A.-M. Dittrich , B. Tümmler . Medizinische adrenergic phase in CF did not grow over time in contrast to controls. Hochschule Hannover, Klinik für Pädiatrische Pneumologie, Allergologie und Conclusion: Our work confirms that iontophoresis/electroosmosis is 2 Neonatologie, Hannover, Germany; Biomedical Research in Endstage and adequate for delivery into the skin of non-ionized or poorly ionized Obstructive Lung Disease Hannover, German Center for Lung Research, drugs needed for β-adrenergic stimulation of sweat and that the non- 3 Hannover, Germany; Klinik für Pneumologie, Medizinische Hochschule invasive test allows good discrimination between CF and controls. The new Hannover, Hannover, Germany automated software allows circumventing limitations of manual image Objectives: Nasal potential difference (NPD) and intestinal current analysis. measurements (ICM) are CFTR biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and CFTR genetics and WS09.4 a clinical suspicion for CF or CFTR-related disorder. Next generation sequencing in newborn screening for cystic fibrosis 1, 2 1, 3 1 1 Methods: NPD and ICM were measured according to standard operating J. Vinohradská , I. Valaskova , R. Gaillyová . University Hospital, Brno, 2 procedures (SOPs) of the ECFS Diagnostic Network Working Group. Czech Republic; Masaryk University, Faculty of Science, Brno, Czech Republic; 3 Results: We assessed 236 individuals who had been referred to our Masaryk University, Faculty of Medicine, Brno, Czech Republic laboratory due to clinical symptoms suggestive of CF, but inconclusive Objectives: In the Czech Republic, newborn screening for cystic fibrosis sweat test and CFTR genetics (median age: 18 years, range 1–65 years). NPD (CF) is performed by the IRT/DNA algorithm. Currently, CFTR molecular and/or ICM profiles were normal in 167 patients and in the CF range in 69 analysis is based on ARMS™ using Elucigene® CF-EU2v1 panel of 50 patients. CF or CFTR-related disorder was diagnosed in 15 of 22 patients mutations (the mutation detection rate is approximately 92% for the Czech with a CFTR genotype of unknown or variable clinical significance (68%), 11 population). One of the key challenges for newborn screening for CF is of 22 carriers of one (50%) and 43 of 192 patients with no identified CFTR designing a protocol that does not discriminate against a small, but mutation (22%). If two CFTR sequence variants had been identified, the significant number of CF infants with low incidence pathogenic variants, outcome of NPD and ICM was consistent with the classification of the mainly from ethnically diverse populations. This can be addressed using CFTR2 database. Six individuals exhibited discordant tracings of ICM and extended CFTR gene analysis by next generation sequencing (NGS) to NPD, with one measurement being in the CF range, the other in the normal identify rarer variants. range. Methods: We analysed 24 samples of DNA extracted from dry blood spots Conclusions: NPD and ICM are valuable tools to provide functional of infants or from peripheral blood. The amplicon library for NGS was information on individuals with yet uncharacterized sequence variants and prepared by Devyser CFTR kit. Sequencing was performed on MiSeq to diagnose CF in patients with wild type CFTR coding sequence on at least (Illumina) and subsequent bioinformatic analysis was done with one of their CF alleles. This group should strongly benefit from disease- AmpliconSuite software (SmartSeq). Devyser CFTR kit enables full modifying approaches by CFTR modulation. sequence determination of all coding exons (LRG_663t1) and adjacent exon/intron boundaries, poly-T,TG-repeat region in intron 9 as well as deep intronic mutations in introns 7,11,12 and 22, 144 bp of the promoter region S16 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 and quantitative CNVs detection (8 common exon spanning CNVs directly, (called normal weight obesity - NWO), and to examine the relationship rest of CNVs indirectly). with clinical parameters. Results: We successfully verified the results obtained from analysis by Methods: BIA data collected as part of dietetic clinic assessment from 2017 Elucigene® CF-EU2v1. The test reliably detects all sequence variants, which to 2019 using TANITA 780 model. BIA measurements included FFM, body were found in our samples. The indirect detection of CNVs has limitations fat (BF)%, BF kg, phase angle (PA). Clinical data was also collected. NWO has caused by amplicon based access mainly in single exon CNVs, but could be been defined as BMI < 25 kg/m2 and body fat >30% women, >23% men. used as screening for the potential presence of CNVs, which should be Results: Data for 174 AWCF (53% male) aged 17–72 years were analysed. verified by MLPA analysis. Based on BMI alone, 26/174 were classified as overweight (BMI>25 kg/m2) Conclusion: Our pilot study successfully demonstrated that CFTR muta- and 5/174 were classified as obese (BMI>30 kg/m2). 25/174(14%) had NWO. tions could be detected from dried blood spots using NGS in our lab. This Statistical analysis was performed to compare those with NWO and AWCF approach could be beneficial concerning the context of the global who had normal weight and normal FFM; mean BMI 20.3 v 22.75 (p = 0.7). increasing ethnic diversity of populations. FEV1% 74 v 63% ± 0.24 v 0.24 (p = 0.04); Phase angle (PA) 6.25 v 5.82 ± 0.91 v 0.67 (p = 0.03). WS09.5 Conclusion: This data suggests that current standard anthropometric Penetrance is a critical parameter for assessing the disease liability of measures are missing a substantial number of AWCF who are obese, and CFTR variants that this is associated with worse clinical outcomes. Results show NWO is A. Boussaroque1, M.-P. Audrézet2,3, C. Raynal4, I. Sermet5, T. Bienvenu1, associated with both lower lung function and phase angle (a measure of C. Férec2,3, A. Bergougnoux4, M. Lopez1, V. Scotet3, A. Munck5,6, E. Girodon7. overall body health). Currently a third of our CF population have excess 1APHP.Centre Université de Paris, Cochin Hospital, Molecular Genetics body fat (combination of overweight, obese and NWO). With the advent of Laboratory, Paris, France; 2CHRU Brest, Molecular Genetics Laboratory, Brest, CFTR modulator therapies, nutrition in PWCF will improve and obesity and France; 3Inserm UMR 1078, Génétique, Génomique Fonctionnelle et its complications are likely to increase in prevalence. Dietetic practice Biotechnologies, Brest, France; 4CHU Montpellier, EA 7402 Université de needs to adapt to the evolving CF population, however reversing long-term Montpellier, Molecular Genetics Laboratory, Montpellier, France; 5APHP.Centre dietary habits may prove challenging. Université de Paris, Necker Enfants Malades Hospital, Cystic Fibrosis Center, Paris, France; 6Société Francaise de Dépistage Néonatal, Paris, France; 7Hopital WS10.2 Cochin, APHP, Paris, France Normal weight obesity in cystic fibrosis is associated with glucose tolerance irregularities in cystic fibrosis at a UK adult cystic fibrosis Objectives: A major issue of newborn screening (NBS) in CF is accurate centre assessment of disease liability of variants. We aimed to get insight into the 1 1 1 1 1 penetrance of CF for CFTR variants identified through NBS in France, D. Sills , M. Mitchell-Whyte ,J.Dewar, H. Barr . Nottingham University notably in inconclusive diagnosis. Hospitals Trust, Nottingham, United Kingdom Methods: Fifteen CFTR variants were selected: 5 frequent CF-causing and Objectives: To evaluate and compare body composition measures using 10 classified as of varying clinical consequence (VCC) or associated with a bioelectrical impedance analysis in people with people with CF. CFTR-related disorder (CFTR-RD) in CFTR2 or CFTR-France databases. The Methods: In 2018 bioelectrical impedance analysis was introduced as part penetrance was evaluated by: 1) comparison of variant allelic frequencies of standard practice during annual assessment for adults with at a UK adult in CF patients (CFTR2) and in the general population; 2) estimation of the CF specialist Centre. We performed bioelectrical impedance analysis using likelihood of a positive NBS test for the 14 compound heterozygous with multi frequency a whole-body bioelectrical impedance analyser, Tanita MC F508del and F508del homozygous genotypes, defined as the ratio of 780 MA, (Tanita Corporation, Tokyo-Japan). At annual assessment absolute detected/expected number of neonates with a given genotype in the 2002- FEV1, weight, height, phase angle, body fat percentage and fat free mass to-2017 period. were measured and diabetes status were recorded. Normal weight obesity Results: While a full penetrance was observed for severe CF-causing was defined as a BMI < 25 kg/m2 and body fat >30% in women or >23% in variants, 5 variants were more frequently found in the general population men. than in CF patients: TG11T5, TG12T5, TG13T5, L997F and R117H;T7. The Results: One hundred and twenty-four sets of data were available from 103 likelihood of a positive NBS test was as low as 0.03% for TG11T5, 0.3% for patients. We found normal weight obesity in nine (8.7%) of the 103 patients. TG12T5, 1.9% for TG13T5, 0.6% for L997F, 11.8% for D1152H, and 17.8% for In those with normal weight obesity 89% of those had glucose tolerance R117H;T7. It greatly varied for variants labelled as CF in CFTR2 but VCC or irregularities (impaired glucose tolerance or cystic fibrosis diabetes). CFTR-RD in CFTR-France: 5.1% for R117C, 12.3% for T338I, 43.5% for D110H Absolute FEV1 was negatively associated with body fat percentage and 52.6% for L206W. (r = 0.2, p = 0.03). Conclusion: These results illustrate that genetics population data are of Conclusion: Excess adiposity, particularly in the form of normal weight major importance to accurately assess the disease liability of CFTR variants obesity (normal weight BMI with elevated body fat percentage) has been for diagnosis and genetic counselling purposes in the context of NBS. shown to have a negative association with lung function. In this small study we noted higher frequency of normal weight obesity in people with glucose tolerance irregularities. This finding may benefit from larger prospective studies to confirm these findings and determine the long-term WS10 Moving beyond body mass index to assess clinical consequences in CF. nutritional status in CF WS10.3 Associations of protein intake and muscle strength with fat-free mass WS10.1 (index) in adult cystic fibrosis patients Prevalence of hidden obesity in adults with cystic fibrosis 1, 2 3 2,4 3 1, 2 1 1, 2 1 F. Hollander-Kraaijeveld , I. Winter , M. Burghard , N. de Roos , K. Ballinger , T. Daniels , C. Pearson . University Hospital Southampton H. Heijerman2,5. 1University Medical Centre Utrecht, Department of Dietetics, NHS Foundation Trust, Wessex Adult Cystic Fibrosis Centre, Southampton, 2 2 Utrecht, Netherlands; University Medical Centre Utrecht, Cystic Fibrosis United Kingdom; University Hospital Southampton NHS Foundation Trust, Center, Utrecht, Netherlands; 3Wageningen University & Research, Division of Department of Dietetics, Southampton, United Kingdom and Health, Wageningen, Netherlands; 4University Medical Objectives: Current clinical practice relies heavily on BMI and weight, but Centre Utrecht, Department of Rehabilitation, Nursing Science and Sports, these alone will fail to identify adults with CF (AWCF) with excess or Utrecht, Netherlands; 5University Medical Centre Utrecht, Division Heart and depleted fat mass (FM) or fat free mass (FFM). This service evaluation aims Lung, Department of Pulmonology, Utrecht, Netherlands to describe the body composition of AWCF at a UK CF centre using Objectives: In healthy adults, protein intake is positively associated with bioelectrical impedance analysis (BIA), to examine the prevalence of fat-free mass (FFM). We investigated the association between protein previously undetectable anthropometric states including ‘hidden obesity’ Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S17 intake and FFM or its height-corrected index (FFMI) in adult cystic fibrosis WS10.5 (CF) patients. Additionally, the association between muscle strength and Dietary patterns and body composition in paediatric cystic fibrosis FFM(I) was investigated. patients: preliminary study 2 Methods: FFM(I) (kg, kg/m ) was determined by whole body single M. Mielus1,2, P. Madej2, M. Surowiecka2, K. Zybert1, 2, frequency bioelectrical impedance analysis (Bodystat 500) in 105 adult CF U. Borawska-Kowalczyk1, 2,M.Ołtarzewski3, D. Sands1, 2. 1Institute of Mother patients. Protein intake was estimated from a dietary history and expressed and Child, Cystic Fibrosis Department, Warsaw, Poland; 2Dziekanow Lesny as % of energy intake (EN%). Muscle strength expressed as isometric knee Hospital, Cystic Fibrosis Center, Dziekanow Lesny, Poland; 3Institute of Mother extension strength (%pred) (n = 71) was determined by a Cybex or MicroFET and Child, Department of Screening and Metabolic Diagnostic, Warsaw, Poland II dynamometer. Associations were tested by multiple linear . Objectives: The optimal nutritional status with the proper balance Results: Protein intake ranged from 10.9 to 31.0 EN%. Mean FFM across between the fat free mass (FFM) and the fat mass (FM), along with the tertiles of protein intake (EN%) was 50.7 kg, 48.4 kg and 52.9 kg (P = 0.401) quality of the diet become the current trends in cystic fibrosis (CF) whereas mean FFMI was 16.5 kg/m2, 16.1 kg/m2 and 17.2 kg/m2, respect- nutrition. The aim of our study is to determine the impact of food group ively (P = 0.132). A low FFM and FFMI was observed in 7 and 21 patients, frequency consumption on body composition of paediatric CF patients. respectively. Adjusted for age and gender, protein intake was significantly Methods: In Warsaw Cystic Fibrosis Centre, from January to December associated with FFM (B = 0.507 kg per 2EN%, P = 0.047) and with FFMI 2019, CF patients aged 8–18, in stable condition, during annual assessment, (B = 0.165 kg/m2 per 2EN%, P = 0.012). Muscle strength was significantly were included into the study. Patients with at least one of the listed associated with FFM (B = 0.893 kg per 5%, P = 0.000) and FFMI condition: FEV1%< 40%, enteral nutrition and CFRD were excluded from the (B = 0.167 kg/m2 per 5%, P = 0.000). study. Patients or their parents fulfilled Polish validated non-quantitative Conclusion: A higher protein intake and higher muscle strength were food frequency questionnaire (FFQ-6). A body composition was deter- significantly associated with a higher FFM(I). Further research should focus mined by multi frequency segmental body composition analyzer. The fat on protein intake and muscle strength improvement in CF patients with free mass index (FFMI) and the fat mass index (FMI) were calculated low FFM(I). according to the following formula: FFMI = FFM/height2, FMI = FM/ height2, respectively. WS10.4 Results: Seventy-five CF subjects (45% male), with mean age 13,2 ± 2,8 Association of energy intake, physical activity and sedentary behaviour years were assessed. 50% of the group were homozygotes F508del and 84% with growth and pulmonary function in children with cystic fibrosis were pancreatic insufficient. None of the patients were malnourished. Two 1, 2 2 1 3 3 patients had BMI >2 z-score. The mean values for FFMI and FMI were as C. Katsagoni , M. Yannakoulia , I. Tokou , M. Moustaki , A. Petrocheilou , 3 1 follow: 14,48 ± 1,92 and 4,26 ± 1,61. Patients had significantly higher FFMI I. Loukou . Agia Sofia Children’s Hospital, Clinical Nutrition Department, 2 when consume less often (no more than few times a month) different kind Athens, Greece; Harokopio University, School of Health Science and 3 of: chocolate sweets (F = 4,55; p = 0,036); low quality sausages and bacon Education, Department of Nutrition and Dietetics, Kallithea, Greece; Agia (F = 8,64; p = 0,004); salty snacks (F = 5,71; p = 0,02). In the contrast, FMI Sofia Children’s Hospital, Cystic Fibrosis Department, Athens, Greece was observed lower when patients consume more frequently (at least Objectives: Cystic fibrosis (CF) patients are advised to follow a high calorie/ several times a week): all kinds of oils (F = 13,95; p = 0,0004); milk and high fat diet and engage with physical activity (PA), although little is known natural dairy drinks (F = 3,97; p = 0,05). about sedentary behaviour (SB) in this population. The present study Conclusion: The quality of the diet influences body composition in CF aimed to explore the associations of several lifestyle factors with growth children and adolescents. Less frequent consumption of processed food and pulmonary function of CF-children. had a positive impact on FFMI. More regular eating of natural diary drinks Methods: The study involved 100 children and adolescents (37% boys-63% and oils promotes lower FMI. girls) with CF from Greece, with mean age of 10 ± 4years. Dietary assessment was based on 4 24-hour recalls. At the same time information WS10.6 on pancreatic enzyme replacement therapy was obtained. The duration Refeeding risk in cystic fibrosis (Part 2): a survey of practice of the (minutes/day) of PAwas assessed before, during and after children’s school British Dietetic Association Cystic Fibrosis Group (BDA CFG) members using a self-reported questionnaire. Duration of leisure time, such as TV D. Sills1, M. Mitchell-Whyte1,J.Dewar1, H. Barr1, viewing, video games etc. was also estimated and SB was defined as >2 British Dietetic Association Cystic Fibrosis Group. 1Nottingham University hours/d spent on those activities. Hospitals Trust, Nottingham, United Kingdom Results: Almost 80% of adolescents and 95.5% of children performed at least 60 min of PA/day. Energy intake of active pupils was more than 144% Objectives: To examine practice of refeeding syndrome assessment within 1 of the Estimated Average Requirement (EAR), deriving mainly from CF in the UK using NICE criteria. proteins (3.5 ± 1.2 g/Kg vs. 2.2 ± 1.0 g/Kg, p = 0.002) compared to 115% of Methods: A survey was distributed to the BDA CFG. The survey was created EAR found in non-active students. Nevertheless, SB was as high as 25% in using Survey Monkey and distributed via email to BDA CFG members. both children and adolescents. Spending more than 60 min per day in PA Questions aimed to assess how relevant each part of criteria was felt to be within CF, how Dietitians treated people with CF who were deemed at risk was positively associated with FEV1 (OR = 1.14, CI:1.03–1.26, p = 0.009), but negatively with BMI (OR = 0.59, of refeeding syndrome CI:0.38–0.93, p = 0.02), after adjusting for age, sex, total energy intake and Results: Twenty one surveys were submitted not all questions were pancreatic function compared to less time. In contrast, SB was negatively completed, with a response rate of 16%. All responders were aware of NICE – refeeding guidelines with 86% using this guideline, but 80% (16/20) also associated with FEV1 (OR = 0.96, CI:0.92 0.99, p = 0.04) even though total PA was taken into account and after adjusting for the same factors, but not had local guidelines. with BMI. When responding to the question ‘how relevant do you find the criteria Conclusion: At least 60 min of physical activity per day is a health- with NICE 2006 guidelines on Refeeding Syndrome within cystic fibrosis’, promoting behaviour in children, including those with cystic fibrosis, while using a five point Likert scale, 52% answered BMI was highly important, 31% sedentary activities should be avoided. Close monitoring of their energy felt it was unimportant and 19% neither important or unimportant. Weight intake is also needed in order to avoid problems in their weight status. loss and biochemistry were weighted more towards being important factors (60% and 76% respectively). Of responses to ‘how do you approach providing nutrition in terms of energy target S18 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

(i.e. kcals/kg/day)’, ten provided kcal/kg/d answers; two answered 5– WS11.2 10kcals/kg/d, one answered Initial evaluation of the ex vivo response to the CFTR potentiator 5–20kcals/kg/d, six answered 10kcals/kg/d and one answered 20kcals/kg. dirocaftor, corrector posenacaftor and amplifier nesolicaftor in Responses to ‘what time period would you usually build up the feed to organoids derived from cystic fibrosis subjects with ultra-rare meet full nutritional requirements?’ two responded 2–3days, eight mutations responded 3–4days and 7 responded 4–5days. P. van Mourik1, M. Bierlaagh1, A. Vonk1,2, A. Santo Ramalho3, I. A.L. Silva4, Conclusion: Despite the importance of nutrition in CF, where people are J. Beekman1, 2, C. K. van der Ent1, G. Gilmartin5. 1Wilhelmina Children’s deemed at risk of refeeding syndrome there appears to be a high level of Hospital, Department of Pediatric Pulmonology, Utrecht, Netherlands; 2Utrecht caution around initiating nutrition. Response rate may be low as ‘centres’ University, University Medical Center Utrecht, Utrecht, Netherlands; may have responded rather than individuals. 3Katholieke Universiteit Leuven, Dept. of Development and Regeneration, We acknowledge the British Dietetic Association Cystic Fibrosis Group. Leuven, Belgium; 4Universidade de Lisboa, BioISI-Biosystems and Integrative 5 Reference Sciences Institute, Lisboa, Portugal; Proteostasis Therapeutics, Inc., Boston, United States [1] National Collaborating Centre for Acute Care 2006. Nutrition support in adults Oral nutrition support, enteral tube feeding and Objectives: To determine the ex vivo swelling of CF subject-derived parenteral nutrition. organoids in response to the investigational CFTR modulators dirocaftor (DIR), posenacaftor (POS) and nesolicaftor (NES). Background: Approved CFTR modulators were developed using precision medicine with product labels restricted to specific CF genotypes. This limits WS11 The link between CFTR modulators and accounting for response heterogeneity among patients with the same genotype and prevents prediction of potential benefit for patients with mutations others. DIR and POS represent a novel potentiator and corrector, respectively. NES, a first-in-class CFTR amplifier, selectively increases the WS11.1 amount of immature CFTR protein and thus provides additional substrate Response to CFTR modulators in organoids from patients with cystic boost. Patient-derived cells such as rectal organoids have been demon- fibrosis as a tool to select candidates to treatment strated to accurately predict a donor’s clinical benefit from approved CFTR 1 A. Santo Ramalho1, S. Cuyx1, 2,M.Boon1,2, L. Dupont1,3, M. Proesmans1,2, modulators . This informs the pursuit for personalised therapies that are I. Sarouk4, C. V. Cordero5, F. Vermeulen1,2, K. De Boeck1, 2. 1Catholic University based on an individual’s theratype, as opposed to their genotype, for of Leuven (KULeuven), Department of Development and Regeneration, Leuven, modulators currently in clinical development. This strategy is being Belgium; 2University Hospital of Leuven, Department of Pediatrics, Leuven, pioneered by HIT-CF (www.hitcf.org), a collaborative consortium to Belgium; 3University Hospital of Leuven, Department of Pulmonology, Leuven, realise personalised medicine for the treatment of CF. Belgium; 4Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Methods: Up to 500 of the approximately 2,300 adults across Europe with Pulmonology Pediatrics and National CF Center, Tel Hashomer, Israel; 5Cruces CF, ineligible for approved CFTR modulators, and with ultra-rare genotypes, University Hospital, Pulmonology and Cystic Fibrosis Unit, Barakaldo, Spain are planned to be enrolled in the study. Subjects will donate rectal tissue that will be cultured into intestinal organoids, an ex vivo model of CF. The Advances in CFTR modulators created the need for biomarkers of CFTR response to the modulators DIR/POS/NES is determined in a CFTR- function with good correlation to clinical data. dependent assay. The results from this assay will be used to identify Objective: Analysing rescue of CFTR function using approved CFTR potential responders for clinical study inclusion. modulators in intestinal organoids derived from CF patients. Results: Initial ex vivo organoid data with the modulators DIR/POS/NES will Methods: CFTR function was measured in 230 patient-derived intestinal be available and presented at the 2020 European Cystic Fibrosis organoids using the FIS (Forskolin Induced Swelling) assay using CFTR Conference. modulators ivacaftor, lumacaftor, and tezacaftor. A wide spectrum of CFTR Conclusions: Based on their response in the organoid test assay a subset of genotypes were represented being, 61 F508del homozygotes, 98 F508del subjects will be invited to participate in a study to confirm clinical efficacy. heterozygotes and 71 having no F508del mutation. Results: Comparing the average responses in F508del/F508del organoids 1. Berkers G. et al., Cell Rep. 2019 (1689 ± 704, AUC using 0.8 μM forskolin), we divided modulators responses in 3 groups: none, low (< 1700) and average/high (≥ 1700). In WS11.3 this study, 42% of patients had average/high responses, 41% had low The last 10%: small molecule screening for correctors of rare CFTR responses and 17% none. Results were in agreement to what was expected processing mutations for characterized mutations. Among F508del homozygous patients a range 1 1 2 3 4 M. Ensinck , L. De Keersmaecker ,M.Nijs , A.S. Ramalho , K. De Boeck , of responses was observed mimicking clinical trials results. Several 5 6 1 1 1 1 S. Munck , H. Klaassen , F. Christ , Z. Debyser , M.S. Carlon . KU Leuven, patients, with rare mutations not yet characterized, had promising 2 Pharmaceutical and Pharmacological Sciences, Leuven, Belgium; Cistim- results. However, due to the high cost of modulators and difficulty to get 3 CD3 - Centre for Drug Design and Discovery, Leuven, Belgium; KU Leuven, reimbursement, treatment approval for rare mutations remains difficult. 4 Development and Regeneration, Leuven, Belgium; UZ Leuven, Leuven, For two patients (one Q359K_T360 K homozygous and one E60 K/I507del), 5 Belgium; KU Leuven, VIB Center for Brain & Disease Research, Leuven, based on the organoid responses (1956 ± 222 AUC and 3417 ± 199 AUC, 6 Belgium; Cistim-CD3 - Centre for drug Design and Discovery, Leuven, Belgium respectively), was possible to start a short period of treatment. The first patient received OrkambiTM treatment, 2 weeks after starting his FEV1 rose Objectives: The last 10% of CFTR mutations remain in need of causal from 49% to 65% predicted and sweat chloride decreased from 86 to therapies. We hypothesised that small molecules identified by high 33 mmol/L. For the second, 6 weeks after starting Symkevi, sweat chloride throughput screening for F508del might not act optimally for other dropped from 73 to 36 mmol/L and FEV1 improved from 32% to 47% mutations. We therefore set up a high content imaging assay (HCA) to predicted. specifically screen for compounds that restore trafficking of two refractory Conclusion: FIS assay results in organoids mimic clinical results and may mutations, N1303 K and G85E. serve as biomarker for prescribing CFTR modulator therapy. Methods: Monoclonal human lung adenocarcinoma cell lines were Acknowledgement to all participating patients and the Mucovereniging for generated expressing mutant extracellular tagged 3HA-CFTR. PM CFTR financial support. was detected via its 3HA-tag. Fluorescent images (9 fields/well) were taken Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S19 at 20x with the Perkin Elmer Operetta CLS and analysed using Harmony WS11.5 software. PM CFTR fold increase over DMSO was determined. Compounds Evaluation of combinations of the CFTR potentiator dirocaftor, (20 μM) with highest fold increase and low visual toxicity were selected for corrector posenacaftor and amplifier nesolicaftor in cystic fibrosis retesting and their efficacy and toxicity assessed. The most promising hits subjects with two copies of the F508del mutation are being tested in human intestinal organoids by Forskolin Induced D. G Downey1,I.Fajac2, P. Flume3,M.O’Carroll4, T. Pressler5, M. Proesmans6, Swelling (FIS) +/− VX-809 and VX-770. B. Quon7, C. Schwarz8, S. Sutharsan9, J. Jiang10, G. Gilmartin10. 1Queens Results: We optimised an HCA in 96-well. WT served as positive control. University Belfast, Belfast, United Kingdom; 2Université de Paris, 2AP-HP PM CFTR of WT was ∼9.1- and ∼19.6-fold higher than N1303 K and G85E. Z’ Centre, Paris, France; 3Medical University of South Carolina, Charleston, averaged 0.64, confirming assay robustness. For N1303 K, VX-809 was United States; 4Auckland City Hospital, Auckland, New Zealand; included, increasing PM CFTR minimally (∼1.7-fold). Next, a repurposing 5Rigshospitalet Copenhagen, Copenhagen, Denmark; 6University Hospital library containing 2.960 compounds was screened for both. Retesting Leuven, Leuven, Belgium; 7St. Paul’s Hospital, Vancouver, Canada; 8Charité ∼ ∼ 9 yielded 11 hits rescuing PM N1303 K 1.8- to 6.7-fold, most with an EC50 Universitätsmedizin Berlin, Berlin, Germany; Universitätsmedizin Essen, in the low μM range. Confirmed hits were also tested on F508del. Currently, Essen, Germany; 10Proteostasis Therapeutics, Inc., Boston, United States top hits are being tested by FIS in N1303 K/N1303 K and F508del/F508del organoids. Preliminary results show at least one compound additive to Objectives: To determine the safety, tolerability, PK and effect of co- combined VX-809 and VX-770 in F508del/F508del organoids. administration of the novel CFTR modulators dirocaftor (DIR), posenacaftor Conclusion: We aimed at screening compounds directly on refractory (POS) and nesolicaftor (NES), based on initial results from a 4-week phase 2 mutations N1303 K and G85E. Currently, we have identified several hits study. with corrector efficacy in the low μM range for N1303 K. FIS experiments Background: DIR and POS represent novel CFTR potentiators and are ongoing to confirm if positive hits can rescue CFTR trafficking and correctors, respectively. NES, a CFTR amplifier, selectively increases the possibly function in organoids. amount of immature CFTR protein and provides additional substrate for correctors and potentiators to act upon. In vitro, in human bronchial WS11.4 epithelial cells from F508del homozygous donors, the combination of DIR/ Relationship between organoid swelling and improvement of CFTR POS/NES increased CFTR chloride transport activity to levels comparable to function in patients with cystic fibrosis homozygous for the F508del that elicited by the elexacaftor/tezacaftor/ivacaftor combination. The mutation receiving lumacaftor-ivacaftor potential for a clinical response was evaluated in this phase 2 study. 1,2,3 4 5 3 1,2,3 Methods: The combination of DIR/POS/NES was evaluated in a rando- S.Y. Graeber , P. van Mourik , A.M. Vonk , S. Hirtz , M.A. Mall , 5,6 1 mised, double blinded, placebo-controlled phase 2 clinical study in J. Beekman . Charité Universitätsmedizin Berlin, Department of Pediatric subjects with CF, homozygous for the F508del CFTR mutation, age ≥18 Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis 2 years, with FEV 40–90% predicted. Treatment period was 4 weeks followed Center, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany; 1 3 by a 2-week follow-up visit. Primary objectives were safety and tolerability University of Heidelberg, Department of Translational Pulmonology, and secondary objectives were PK, change in FEV and sweat chloride. Translational Lung Research Center (TLRC), German Center for Lung Research 1 4 Results: Initial data suggest a generally well-tolerated safety profile and (DZL), Heidelberg, Germany; Utrecht University, Department of Pediatric clinical benefit with DIR/POS/NES. In the preliminary analysis, mean Pulmonology, Wilhelmina Children’s Hospital, University Medical Center 5 absolute changes in percent predicted FEV of 8 percentage points (95% CI; Utrecht, Utrecht, Netherlands; Utrecht University, Regenerative Medicine 1 6 3,12) (p ≤0 .01, n = 11) versus placebo were observed following a treatment Center, University Medical Center, Utrecht, Netherlands; Utrecht University, period of 4 weeks. Reduction in sweat chloride of −29 mmol/L (95% CI; −42, Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, −16) (p < 0.0005, n = 10) versus placebo were observed at week 4. University Medical Center, Utrecht, Netherlands Conclusions: Dirocaftor, posenacaftor and nesolicaftor represent novel Objectives: Lumacaftor-ivacaftor (lum-iva) improves cystic fibrosis (CF) CFTR modulators in clinical development. transmembrane conductance regulator (CFTR) function in F508del homo- zygous patients with CF. However, clinical response in individual patients is highly heterogeneous. Organoid swelling has been shown to differentiate treatment responses among different genotypes and CFTR modulator WS12 Immunology - targets for therapy treatments. However, it is unknown if organoid swelling can predict treatment response to lum-iva in individual patients homozygous for the WS12.1 F508del mutation. Potential action of phages as immunomodulators in cystic fibrosis Methods: We investigated the relationship between forskolin-induced M. Cafora1,2, F. Forti3, A. Brix1, N. Loberto1, M. Aureli1, F. Briani3, A. Pistocchi1. swelling (FIS) of patient-derived organoids stimulated with lum-iva and 1Università degli Studi di Milano, Dipartimento di Biotecnologie Mediche e improvement in in vivo CFTR function measured by sweat chloride, nasal Medicina Traslazionale, Milano, Italy; 2Università degli Studi di Milano, potential difference (NPD), and intestinal current measurements (ICM) in Dipartimento di Scienze Cliniche e Comunità, Milano, Italy; 3Università degli 21 F508del homozygous patients with CF treated with lum-iva for 8 to 16 Studi di Milano, Dipartimento di Bioscienze, Milano, Italy weeks. Results: In all organoids of F508del homozygous patients, stimulation with Objectives: Chronic inflammation caused by bacterial infections is a lum-iva induced substantial FIS. In addition, all patients improved in at common feature of patients with Cystic Fibrosis (CF). However, new pieces least one biomarker of in vivo CFTR function. However, no correlation was of evidence suggest that constitutive inflammation is present in CF patients observed between the degree of FIS and the in vivo improvement of CFTR even in the absence of bacterial infection. Surprisingly, we also found that function measured by sweat chloride testing, NPD or ICM in F508del phages mitigate the hyper-inflammation of the CF zebrafish model not homozygous patients receiving lum-iva. In addition, neither FIS nor infected by bacteria. We are investigating the mechanism through which improvement of CFTR function correlated with short-term clinical out- phages act as anti-inflammatory agents using the CF zebrafish model and comes in F508del homozygous patients treated with lum-iva. primary and immortalized human bronchial epithelial cells homozygous Conclusion: In vitro and in vivo CFTR function measurements of F508del for the CFTR mutation F508del. homozygous patients treated with lum-iva detect a treatment effect in all Methods: In the CF zebrafish embryos we are characterizing the subjects. However, organoid swelling alone might not be suitable to predict immunomodulatory effects of the phage-cocktail used in our previous the level of improvement in CFTR function by lum-iva in individual work by dissecting the action of each single phage in the cocktail and of one patients. This is most likely due to the low range of CFTR correction by lum- or the other of the two phage components, DNA or virion proteins. To iva and a fairly homogenous effect on CFTR function. Our results suggest investigate the possible mechanisms through which phages modulate the that biomarkers measuring the in vivo CFTR function might still be inflammation, we are studying the TOLL-like receptor pathway. In human, supportive in evaluating treatment responses in individual patients. we will administer the phage cocktail to the CuFi-1 cell line characterized by a high basal proinflammatory state, and primary bronchial epithelial S20 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 cells obtained from the “Servizio Colture Primarie” of the Italian Cystic a treatment with anti IL5-R monoclonal antibodies may help to control the Fibrosis Research Foundation. As a read-out of the action of phages as symptoms and the lung function decline. immunomodulators, we are assessing the expression of pro- and anti- Objectives: To assess clinical and biological evolution of CF patients inflammatory cytokines by means of qPCR and ELISA techniques. presenting with asthma and/or ABPA and eosinophilia and treated with Results: In CF zebrafish embryos phages act as immuno-modulators in the anti IL5-R (benralizumab). absence of bacterial infection and this effect is similar for each phage of the Methods: We run an observational prospective study including all cocktail. Moreover, we showed that the DNA component of the phage is not consecutive CF patients treated with benralizumab, since July 2019. necessary for the immunomodulatory response. Patients were all included in a multicentre cohort (MABCF, ethical Conclusions: The research of new anti-inflammatory agents in a cheap and committee approval: 2019_IRB-MTP_12-07). Follow up for patients easy-of-use CF zebrafish model, together with the studies on the effects of treated with benralizumab consists in a monthly consultation for 3 phages on CF human cells could speed-up the translational potential of this months, and then a visit every 8 weeks. We present data from patients research. treated up to 3 months. Results: Seven patients (5 ABPA, 2 asthma), with average age of 23,5 (12 to WS12.2 36 years old) were included in this study. Median eosinophilia at V0 was Antigen-specific T cell response in Aspergillus fumigatus conditions in 440 G/L [300;1220] and 4 G/L [0;12] after 3 months of treatment. There was cystic fibrosis no significant difference in the evolution of FEV1 (median is 0 for delta FEV1 P. Eschenhagen1, C. Grehn1, P. Bacher2, A. Scheffold2, C. Schwarz1. 1Charité - in % between 0 and 3 months), and number of pulmonary exacerbation. The Universitätsmedizin Berlin, Department of Pediatric Pneumology, Immunology SNOT is improving for most of the patients. For CFQ-R, we have an and Intensive Care Medicine, Cystic Fibrosis Center, Berlin, Germany; heterogeneous response but all patients improve in most items, mainly for 2University Hospital Schleswig-Holstein, Campus Kiel, Department of the health item. One patient dropped out since he claimed the treatment Immunology, Kiel, Germany was not showing any relevant clinical effect (even though his level of eosinophils normalised after the first month of therapy). No adverse event Objectives: The most frequently detected mould in the respiratory tract in was recorded in any of the 7 patients. CF is Aspergillus fumigatus (Af). Aspergillus diseases are associated with Conclusion: CF hyper-eosinophilic patients with ABPA or asthma may significant morbidity and mortality. The most common clinical picture benefit from a treatment with anti IL5-R monoclonal antibodies (benra- caused by Af in CF is allergic bronchopulmonary aspergillosis (ABPA), lizumab). Further studies are needed to better appreciate the clinical effect which is triggered by an immunological reaction to Af allergens. Af of this therapy in this group of patients. Bronchitis or invasive aspergillosis rarely occur in CF as a result of spore proliferation. Since pulmonary mycoses and exacerbations by other WS12.4 pathogens overlap in clinical, radiological and immunological character- Tezacaftor/ivacaftor therapy induces increased airway neutrophilia and istics, diagnosis remains a challenge. Novel biomarkers could help to gain circulating neutrophil activation in cystic fibrosis diagnostic certainty. 1 1 1 1 1 G.R. Hardisty , N.J. Robinson , J.L. Gillan , R.D. Gray . University of Methods: In our prospective single centre study (2017–2019), we analysed Edinburgh, Centre for Inflammation Research, Edinburgh, United Kingdom Af-specific T helper cell responses of patients with CF as potential biomarkers of Af conditions. According to their clinical, radiological and Objectives: This project aims to determine the therapeutic impact of the immunological findings, the patients were identified as three groups of CFTR modulator Tezacaftor/ivacaftor (TEZ/IVA) on neutrophils isolated from acute Af disease conditions: ABPA, bronchitis, and pneumonia In initial blood and sputum in people with CF. Inherent neutrophil dysfunction and analyses, the groups were compared in terms of the frequencies of T helper inflammation driven by excessive neutrophil recruitment are a hallmark of cell subsets defined by their characteristic cytokine levels (IFNγ, IL-4, IL-10, CF disease. With the increasing availability of CFTR modulators, we asked IL-5, IL-17A, IL-21, IL-22). what impact modulator therapy has on neutrophil responses in CF. Results: 216 patients with CF were included. Of those, three cases were Methods: Collection of patient samples is ongoing. Circulating neutrophils classified as Af-bronchitis, five as Af-pneumonia and 13 as acute ABPA. were characterised by multi-parameter flow cytometry for markers of There was a significant difference in Af-specific Th2 response in the acute activation, aging and adhesion and sputum samples were analysed for ABPA group compared to the other groups and to the control group. neutrophil content prior treatment and at 1 and 3 months following CFTR Furthermore, there was a significant difference in the Af-specific Th17 modulator therapy. response in the acute ABPA and Af pneumonia group, whereas the Af Results: TEZ/IVA therapy induces a significant increase in sputum bronchitis group showed no significant difference. neutrophils within 1 month of treatment. Circulating CF neutrophils Conclusion: Acute Af conditions (ABPA, bronchitis, pneumonia) in CF can remain elevated compared with non-CF controls and have increased be identified based on their Af-specific T helper cell responses. expression of activation markers, including complement receptor 1 (CD35) and integrin associated protein (CD47). Markers for cell maturity in WS12.3 neutrophils (CD66b, CD11b) were significantly upregulated in comparison May eosinophilic cystic fibrosis patients benefit from anti IL5-R to non-CF controls and failed to decrease in response to CFTR modulator monoclonal antibodies? Preliminary results of the MABCF cohort. therapy. IL-8 receptor (CXCR2) expression was significantly decreased on M. Drevait1, D. Caimi1, A. Coudrat1, J. Moreau1, R. Chelabi1, B. Camara2, CF neutrophils in comparison to non-CF controls and also failed to increase S. Quetant2, S. Ramel3, R. Chiron1,4. 1Centre de Ressources et de Compétences in response to treatment (current N = 22). de la Mucoviscidose (CRCM), Centre Hospitalier Universitaire de Montpellier, Conclusion: Airway neutrophilia contributes to CF pathogenesis. Despite 34, Montpellier, France; 2CHU Grenoble, 38, Grenoble, France; 3Centre de significant improvements in lung function TEZ/IVA treatment is associated Perharidy, 29, Roscoff, France; 4Equipe PHySE, HydroSciences Montpellier, with sputum increased neutrophil numbers. Furthermore, circulating CNRS, IRD, Université de Montpellier, 34, Montpellier, France neutrophils show increased markers of activation and maturity which are not corrected by TEZ/IVA. A better understanding of the effects of CFTR Allergic bronchopulmonary aspergillosis (ABPA) or uncontrolled severe (and CFTR modulation) on innate immune cell function in CF is required. asthma may be persistent in CF patients, despite optimal treatment. In a Sample collection is on-going at the time of submission. subgroup of these patients, presenting with persistent hyper-eosinophilia, Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S21

WS12.5 tezacaftor/ivacaftor were assessed at baseline, one month and three Plasma human epididymis protein 4 (HE4) levels correlate with the months. Lung function, weight, C-reactive protein, white blood count, β improvement of FEV1 in cystic fibrosis patients treated with serum IL-1 , IL-18, IL-6, IL-10, and TNF were measured at each assessment. lumacaftor/ivacaftor Cytokine quantification, caspase-1 and mRNA levels of pro-IL-1β, TNF, IL-6, Z. Fejes1, A. Balla1, Z.A. Mezei1, Z. Bene2, M. Macek, Jr. 3, M.D. Amaral4, IL-10 were measured following stimulation of peripheral blood mono- I. Balogh1,5, B. Nagy, Jr. 1. 1University of Debrecen, Faculty of Medicine, nuclear cells (PBMCs) with LPS and ATP. IL-1β and IL-18 secretion was also Department of Laboratory Medicine, Debrecen, Hungary; 2University of measured in monocytes of drug-naïve patients and healthy controls. Debrecen, Faculty of Medicine, Department of Pediatrics, Debrecen, Hungary; Results: Patients in both groups remained stable over the study period. 3Charles University and Motol University Hospital, Department of Biology and lumacaftor/ivacaftor decreased serum IL-18 (p < 0.0001) and TNF (p = Medical Genetics, Prague, Czech Republic; 4University of Lisboa, Faculty of 0.0004) but had no effect on IL-1β. There was a reduction in IL-18 Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal; (p < 0.0001), TNF (p < 0.0005) and caspase-1 activity (p = 0.03), increased 5University of Debrecen, Faculty of Medicine, Division of Clinical Genetics, IL-10 (p < 0.0001) but no change in IL-1β or in pro-IL-1β mRNA post-PBMC Debrecen, Hungary stimulation. Tezacaftor/ivacaftor reduced serum IL-18 (p < 0.0001), TNF (p = 0.02), IL-1β (p < 0.0003) levels and decreased IL-18 (p = 0.0002), IL-1β Objectives: We previously documented that elevated plasma HE4 levels (p < 0.0001) and pro-IL-1β mRNA (p < 0.0001) post-PBMC stimulation. In decreased in CF patients bearing the CFTR Gly551Asp variant under vitro application of lumacaftor/ivacaftor. ivacaftor, and HE4 inversely correlated with FEV1. Although the PROSPECT or tezacaftor/ivacaftor to monocytes derived from stable CF adults showed ® study has evaluated the effectiveness of lumacaftor/ivacaftor (Orkambi )in a significant reduction in IL-18 whereas IL-1β were only reduced with CF patients homozygous for the CFTR F508del variant, blood biomarkers tezacaftor/ivacaftor following stimulation with LPS/ ATP. have not been used to monitor treatment efficacy in this context so far. Conclusion: This study demonstrates that CFTR modulators have potent Aim: We have retrospectively analysed plasma HE4 levels in a randomly anti-inflammatory properties which could contribute to improved clinical selected subcohort of the PROSPECT study cases in order to validate our outcomes. tezacaftor/ivacaftor appears to be superior to lumacaftor/ previous observations. ivacaftor at downregulating inflammation. Methods: Plasma HE4 levels were examined in 68 CF patients before treatment and at 1, 3, 6 and 12 months after Orkambi® administration.

Delta FEV1 (% predicted) were correlated with delta HE4. Results: The absolute mean change of FEV1 was 2.6 ± 8.0% by 6 months WS13 CFTR Modulators: to have and to have not together with improved sweat chloride concentrations and nutritional status in this cohort. Plasma HE4 concentrations were significantly reduced WS13.1 below baseline (p < 0.001) following Orkambi® administration during the Disease progression in F508del homozygous (F/F) persons with cystic entire study period. Importantly, delta HE4 values indicated improving or fibrosis treated with lumacaftor/ivacaftor (LUM/IVA): interim results of decreasing pulmonary function compared to baseline data at 6 months a long-term safety study using data from the US Cystic Fibrosis (−17.9 ± 16.9 vs. 12.6 ± 27.5 pmol/L; p < 0.0001). A significant inverse Foundation Patient Registry (CFFPR) correlation between the mean change of HE4 and delta FEV (r = -0.6603; 1 1 1 1 2 2 2 1 p < 0.0001) was observed with an independent association of delta HE4 J.K. Bower , S. Tian , R. Zahigian ,A.Sewall ,R.Wu , A. Elbert . Vertex 2 β Pharmaceuticals Incorporated, Boston, United States, US CF Foundation, with FEV1 improvement by multiple regression analysis ( = -0.61, p = 0.0001). Substantial ROC-AUC value was determined for delta HE4 with a Bethesda, United States − cut-off value of 7,4 pmol/L when 3% mean absolute change of FEV1 at 6 Objectives: This ongoing 5-year safety surveillance study evaluates CF – months was used as classifier (0.832 [95% CI 0.732 0.931]; p < 0.0001). disease progression in F/F persons with CF treated with LUM/IVA in the Conclusion: Our data provide evidence that improved CF lung disease in real-world setting. cases treated with lumacaftor/ivacaftor can be reliably assessed by Methods: This interim analysis focused on 2,287 F/F persons with CF in the evaluating plasma levels of HE4. Samples were supplied by CFF and the US CFFPR treated with LUM/IVA for an average of 2.9 years (range: 1.2 to 4.0 study was supported by UID/MULTI/04046/2013 centre grant (to BioISI). years) by the end of Study Year 3 (2018). Outcomes were compared to a concurrent comparator (COMP) population of 3,527 phenotypically similar WS12.6 persons with CF (genotype F508del/minimal function) with no prior Different CFTR modulator combinations downregulate inflammation history of CFTR modulator use. Outcomes included percent predicted FEV1 differently in cystic fibrosis (ppFEV1), BMI, and pulmonary exacerbations (PEx). Means and percen- H. Jarosz-Griffiths1, 2, T. Scambler2,3,4, C. Wong2,3, S. Lara-Reyna2,3, tages were compared between LUM/IVA and COMP cohorts as appropriate; J. Holbrook2,3, F. Martinon2,5, S. Savic2,3,6, P. Whitaker7, C. Etherington7, for continuous outcomes, change from pretreatment baseline in 2014 (BL) G. Spoletini7, I. Clifton7, A. Mehta8, M. McDermott2,3, D. Peckham1,2,7. through 2018 was calculated. 1 ’ University of Leeds, Leeds Institute of Medical Research at St James s, Leeds, Results: Mean change from BL (95% CI) in ppFEV1 was smaller in the LUM/ United Kingdom; 2University of Leeds, Leeds Cystic Fibrosis Trust Strategic IVA vs COMP cohort (-3.7 percentage points [pp] [−4.2 to −3.3 pp] vs −6.9 Research Centre, Leeds, United Kingdom; 3University of Leeds, Leeds Institute of pp [−7.2 to −6.5 pp], respectively). Among those < 18 years old, BMI Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom; 4New York percentile increased by 1.7 pp (95% CI: 0.5 to 2.8 pp) in LUM/IVA but University School of Medicine, Department of Pathology, New York, declined by 3.8 pp (95% CI: 2.9 to 4.7 pp decline) in COMP cohort. Among United Kingdom; 5University of Lausanne, Department of Biochemistry, adults, BMI (95% CI) increased more in the LUM/IVA vs COMP cohort Epalinges, Switzerland; 6University of Leeds, Department of Clinical (+0.8 kg/m2 [0.7 to 0.9 kg/m2] vs +0.2 kg/m2 [0.1 to 0.3 kg/m2], respect- Immunology and Allergy, St James’s University Hospital, Leeds, ively). The percentage of LUM/IVA persons with CF with at least one PEx United Kingdom; 7University of Leeds, Adult Cystic Fibrosis Unit, St James’s remained stable (≈37%) but increased among the COMP cohort (39.8% in University Hospital, Leeds, United Kingdom; 8University of Dundee, Division of 2014 to 48.3% in 2018). The mean number of PEx/year/person also Medical Sciences, Dundee, United Kingdom remained stable among the LUM/IVA cohort (≈0.6) but increased among the COMP cohort (0.7 in 2014 to 1.0 in 2018). Objectives: Inflammation plays a critical role in the pathogenesis of cystic Conclusion: This interim analysis identified no new safety concerns with fibrosis. We assessed the effectiveness of CFTR modulators on down- LUM/IVA and showed that, relative to untreated COMP, LUM/IVA persons regulating serum and innate-immune cell-derived IL-1β and IL-18, two with CF had favourable changes over time in lung function, BMI, and PEx. pro-inflammatory cytokines which drive local and systemic inflammation These data support the potential for LUM/IVA to modify CF disease in CF. progression with long-term use. Methods: The clinical status of adults with CF, homozygous for F508del, Sponsor: Vertex Pharmaceuticals Incorporated. entering a compassionate use program for lumacaftor/ivacaftor and S22 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

WS13.2 Conclusion: Smoke exposure blunts the therapeutic effect of tezacaftor/ The Swedish cystic fibrosis Registry facilitates the evaluation of ivacaftor in CF patients ages 12–18 years. Future analysis will assess the Orkambi® treatment consequence of smoke exposure in the recently FDA-approved triple- ® P. Ericson1, A. Hedborg2, I. de Monestrol2, L. Hjelte2, U. Lindberg3, combination agent (elexacaftor/tezacaftor/ivacaftor, Trikafta ). Although C. Hansen3, C. Krantz4, M. Gilljam1, A. Lindblad1. 1Sahlgrenska University findings need to be validated with biomarkers of smoke exposure and in Hospital, Gothenburg CF Center, Gothenburg, Sweden; 2Karolinska University other cohorts, these data suggest that limiting smoke exposure may help Hospital, Stockholm CF Center, Stockholm, Sweden; 3Skåne University enhance the benefit of CFTR modulators. Hospital, Lund CF Center, Lund, Sweden; 4Akademiska University Hospital, Uppsala CF Center, Uppsala, Sweden WS13.4 Distribution of cystic fibrosis patients not eligible to studied CFTR Objectives: Starting July 1, 2018, the Dental and Pharmaceutical Benefits modulators in Europe ® Agency decided that Orkambi was to be subsidized by the Swedish state. 1 1 2 3 4 A. Zolin , A. Orenti , A. Barbier , J. van Rens , L. Naehrlich , The decision was accompanied by the following restrictions: 1. Treatment 1 2 On Behalf of the ECFSPR. University of Milan, Milano, Italy; Translate Bio, initiated at a CF Centre with close follow-up of effect and adverse events 3 Inc, Lexington, United States; University Hospital Leuven, Leuven, Belgium; 2. Set treatment goals evaluated after one year 3. Follow-up via the Swedish 4 Justus-Liebig-University Giessen, Giessen, Germany CF Registry. The aim was to investigate whether the registry could facilitate the Studied Cystic Fibrosis (CF) modulators have been announced to cover 90% evaluation of Orkambi® treatment. of all CF patients. A genotype-agnostic novel therapy for CF is under Methods: A national follow-up program for the first year of Orkambi® development, which will focus on people with CF who have mutations that treatment was established by The Swedish CF Working Group. Extra fields are not eligible for the approved small molecule modulators and triple were added to the registry to fit the program and staff was hired to ensure combination therapies. The data in the European Cystic Fibrosis Society that data was entered correctly. Mandatory check-ups were at treatment Patient Registry (ECFSPR) are used to provide a quantitative overview of start and after 1, 3, 6, 9 and 12 months. eligible patients. Results: The registry is used by all 4 centres and all patients that initiated Patients who are alive and seen during the 2017, or alive and not seen were Orkambi® are included in the follow-up program. Up to July 31, 2019, 190 considered (excluding France who delivered the data directly to the patients entered the program. 25 (13%) patients stopped treatment due to sponsor). Not considered were patients F508del homozygotes eligible for adverse events. Mean age (SD) at start was 22.9 (12.7) yrs with FEV1pp of elexacaftor/tezacaftor/ivacaftor, tezacaftor/ivacaftor, lumacaftor/ivacaftor, 77 (22)% and LCI (< 18 yrs) 8.89 (1.99). BMI in adults was 21.9 (2.51) and BMI or heterozygotes eligible for elexacaftor/tezacaftor/ivacaftor. Neither were z-score in children −0.35 (0.82). patients with at least one of the following mutations: E56 K, P67L, R74W, 87 patients (35 children) had been on treatment for >6 months July 31, D110E, D110H, R117C, E193 K, L206W, R347H, R352Q, A455E, D579G, 711 2019. The sweat test decreased in average 18 mmol/l (range −48 to +3A->G, E831X, S945L, S977F, F1052 V, K1060 T, A1067 T, R1070W, F1074L, +14 mmol/l) after 3 months. After 6 months, FEV1 showed a trend of D1152H, D1270N, 2789+5G->A, 3272-26A->G, 3849+10kbC->T (eligible for improvement in the adult population while it was stable in the paediatric tezacaftor/ivacaftor, ivacaftor) and R117H, G178R, S549N, S549R, G551D, population (6–18 yrs) where a decrease of LCI (0.7 units) was seen. Both G551S, G1069R, R1070Q, G1244E, S1251N, S1255P, G1349D (eligible for BMI and BMI z-score showed a slight increase. Comparing the 180 days ivacaftor). before starting Orkambi® to the180 days after treatment start, the mean From the 41,264 patients registered in the ECFSPR for the 2017, 4,798 number of days on iv antibiotics per patient decreased from 7.2 to 3.1 days. patients (12%) carry a genotype that is not eligible to the currentlyapproved Conclusions: The follow-up program for Orkambi® shows that the Swedish modulators or the triple combo. The percentage of non-eligible patients CF-registry is a useful tool for evaluation of new therapies. Longer follow- varies from 2,3% in Ireland to 71,9% in Armenia. 2,954 of these patients are up time will be presented in June 2020. 11 years or older, 1,561 have a FEV1% of predicted value between 40% and 90%. WS13.3 In Europe approximately 88% of the patients will be eligible for the Tobacco smoke exposure limits the benefit of Symdeko® in paediatric currently approved modulators or triple combo, in some countries this cystic fibrosis patients: Cystic Fibrosis Foundation Patient Registry percentage is below 50%. With the ECFSPR data, a realistic and useful analysis overview could be created to support the design of a study for patients that G. Oates1, E. Baker1,S.Rowe1, S. Rutland1, W. Harris1. 1University of Alabama are not eligible to the currently available modulator and triple combination at Birmingham, Birmingham, AL, United States therapies.

Objectives: Tobacco smoke exposure reduces CFTR functional expression in WS13.5 vitro and contributes to acquired CFTR dysfunction in animal models. We Access to treatments for people with cystic fibrosis across Europe: a 6- investigated whether smoke exposure inhibits the clinical benefit of CFTR country pilot survey ® modulators, focusing on tezacaftor/ivacaftor (SYMDEKO ), FDA-approved 1 1 1 1, 2 1 E. McClenaghan , T. Speight , K. Earlam , N. Medhurst , S.C. Charman , in February 2018 for F508del homozygous patients age 12 years and older. 2 2 1 2 H. de Keyser , S. Joris . Cystic Fibrosis Trust, London, United Kingdom; Cystic Methods: A retrospective analysis of data in the CF Foundation Patient Fibrosis Europe, Brussels, Belgium Registry (CFFPR, 2016–2018) compared change in lung function (GLI ® FEV1%) after SYMDEKO initiation in smoke-exposed vs unexposed Objectives: Improved outcomes and survival for people with CF is owed patients age 12–18 years. Smoke exposure was dichotomized based on largely to the success of therapeutic innovation and treatments available to annual self-report. Its impact was assessed with fixed-effects modelling, manage symptoms. However, there is anecdotal evidence that access to key which accounts for non-time-varying factors (sex, race, parent education) treatments varies greatly across countries and settings. and additionally controlled for time-varying covariates. We aim to conduct a novel Europe-wide survey to describe variation in Results: SYMDEKO® was prescribed to 1,429 patients: mean age 14.7 (SD perceived access to medications for people with CF. This pilot survey stage

0.07) years, 54.6% female, mean baseline FEV1% 83.3 (0.51), 27.6% smoke- aims to assess the acceptability and feasibility of a pan-European survey, − exposed. During the study period, FEV1% improved 0.25% (95% CI: 0.39, ensure questionnaire items identify variability between and within 0.89) in those on SYMDEKO® and declined −2.4% (−2.80, −2.05) in those countries, and generate a valid questionnaire that provides patient- and ® not on the drug. Among those on SYMDEKO , FEV1% improvement varied clinician-led perspectives on access to treatments. by smoke exposure (p < 0.001). In unexposed subjects, FEV1% increased Methods: The online pilot survey will be administered via SurveyMonkey 0.72% (0.03, 1.41), while in smoke-exposed it declined 1.03% (−2.5, 0.5). In to respondents from 6 CF Europe member countries - Belgium, France, fixed-effect models, FEV1% improvement remained significant in unex- Israel, Slovakia, UK and Poland. posed subjects (0.5%; 0.08, 0.9, p = 0.017), while in smoke-exposed subjects Survey responses will be subjected to descriptive analysis, with primary there was no improvement (−0.44%; −0.20, 0.4, p = 0.452). focus on assessing feedback on wording and structure of the questionnaire. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S23

This will inform the design of a final survey to be administered to 37 European countries. WS14 When the going gets tough: improving Results: The pilot survey has received positive expert feedback from the CF multidisciplinary team working Europe taskforce and a revised draft will be sent to patient organisations to be distributed in six pilot countries. Thus far, the pilot survey consists of 64 WS14.1 questions distributed across 7 distinct domains - demographics, CFTR Staff experiences of moral distress in a cystic fibrosis unit modulators, mucocilliary clearance, anti-infection, nutritional/gastro- 1,2 3 4 5 1 intestinal, general access, and pilot feedback. Results will be collated and K. MacDonald , J. Robertson , M. Bruce , G. Halliday . Queen Margaret 2 analysed after a three-month data collection window (February - April University, Nursing, Edinburgh, United Kingdom; NHS Lothian, CF Unit, Ward 3 2020), to be disseminated in June 2020. 54, Edinburgh, United Kingdom; Scottish Adult CF Service, CF Unit, Ward 54, 4 Conclusion: This pilot survey will facilitate the most appropriate, rigorous Edinburgh, United Kingdom; Scottish Adult CF Service, , 5 and effective survey design. The subsequent pan-European survey will Edinburgh, United Kingdom; NHS Lothian, Psychology, Pain Management, provide valuable insights into variability in access to treatments for people Edinburgh, United Kingdom with CF, laying a valid evidence base for targeted policy change and Objectives: To explore staff experiences of MD in a CF unit. interventions to address disparities. Moral distress (MD) has received increased attention in nursing, medical and AHP literature. Little research has investigated MD in relation to CF. WS13.6 Research questions: Epidemiology and factors influencing lung disease in cystic fibrosis • What is the prevalence of MD in our unit?. with residual function mutations (RFm) • How/when do staff experience MD?. D. Salvatore1, B. Giordani2, R. Padoan2, A. Amato2,3, G. Ferrari2,4,F.Majo5, • What coping strategies do staff use to manage MD?. C. Colangelo1, F. De Gregorio1. 1Cystic Fibrosis Center, AOR Ospedale San Carlo, • What is the professional and personal impact of MD on staff?. Potenza, Italy; 2Italian Cystic Fibrosis Registry, Rome, Italy; 3Lega Italiana • What would help alleviate MD?. Fibrosi Cistica ONLUS, Rome, Italy; 4Istituto Superiore di Sanità, Centro Methods: Mixed methods: Stage 1. Nazionale Malattie Rare, Rome, Italy; 5Ospedale Pediatrico Bambino Gesù, • Demographic questionnaire. Cystic Fibrosis Center, Rome, Italy • Moral Distress Scale-R Adapted. Objectives: Patients with CF and RFm have often delayed diagnosis, mild • Relationship Structures Questionnaire-Adapted (ECR-RS). lung disease and pancreatic sufficiency, compared with homozygous • Professional Quality of Life Scale (PROQOL 5). F508del (FF). We describe Italian patients with RFm and analyse the factors Stage 2. influencing the lung disease, comparing with patients FF. • 2 Focus groups with nursing, medical and Allied Health Professional Methods: Data are from the 2017 Italian CF Registry. Percent predicted (pp) staff to explore the results of the questionnaires in depth. FEV1 was analysed over a 2-year period (2015 to 2017). Results: 904 subjects (452 males) with RFm were identified over a total of Analysis: Descriptive statistics provided an overview of questionnaire 5563 (16.3%), median age was 25.5 yrs (IQR 11.4–42.4), median age at scores. Thematic analysis provided insight into focus group data. diagnosis was 5.9 (IQR 0.25–23.5). Mean BMI z-score was 0.3 (SD 1.1) in Results: 60 questionnaires (32 returned-53% response rate) were dis- 2 children and BMI 23.4 (SD 4.1) kg/m in adults. Mean ppFEV1 was 84.2 (SD tributed across registered and unregistered ward staff and the CF team in a 23.8). Prevalence of chronic Pseudomonas Aeruginosa (Pa) and 35 bedded CF/respiratory unit). Staphylococcus Aureus was 27.1%, and 49.7%, respectively. The most Mean total scores revealed: low MD, low compassion fatigue, average-high frequent complication was liver disease (14.4%). FF patients had lower compassion satisfaction (with some differences noted according to years of age at diagnosis, worse nutrition and lung function (LF), and higher experience), and highly supportive relationship structures. prevalence of complications. Qualitative analysis provided insight into: factors contributing to MD, The multivariate analysis on LF outcome showed: associated feelings, coping strategies, and factors that would help reduce 1. RFm subjects: significant (p < 0.001) association of worse LF with MD. Feeling valued and the nature of relationships (staff-patient and staff- adult age and with chronic PA (−16.9, 95% CI: −16.3 to −13.4). Weak staff) were seen as important in both contributing to and reducing MD. evidence of difference in LF was found between females and males Conclusion: MD is a complex issue. This group of CF clinicians appears to (-3.0, 95% CI: −6.1 to 0.0, p = 0.052). function in a very supportive environment. Study timing/low sample 2. FF subjects: LF was negatively associated to increasing age from numbers may limit generalisibility. adolescence and to the colonization by Pa. LF was not different between females and males. WS14.2 3. Patients with 3849+10kbC>T/F508del: reported significant worse LF Maintaining the motivation of staff who are maintaining the compared to all RF patients (-11.2, 95% CI: −16.9 to −5.4). motivation of patients to change: it’s a parallel process A. Pipeva1, C. Carolan1, F. Edenborough1, R. Curley1, M. Wildman1, The longitudinal analysis showed no change over the period 2015–2017 in 1 1 R. Attfield . Sheffield Teaching Hospitals, Sheffield, United Kingdom the ppFEV1% trend among RF and FF patients. Conclusion: Patients with RFm are numerous in Italy and have a milder Background: Treatment for CF can be complex and demanding. For phenotype than FF. Lung disease of RF subjects is evident since the adult patients to change, they need to see the necessity for it and feel capable of age and associated to the colonisation by Pa.RFbut not FF females might it. How clinicians communicate with patients is related to their level of report more severe lung disease. Patients 3849+10kbC!T/F508del showed adherence. Therefore, CF MDTs need to ensure that their perceived more severe lung disease. need and ability to work on communication styles (e.g. motivational S24 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 interviewing, MI) is sustained over time. A parallel process of behaviour WS14.4 change exists as patients and clinicians try to sustain change. We discuss Google’s Aristotle, psychological safety and the role of microsystems how to maintain motivation and skills of the CF MDT through tailored focus meeting skills to optimise multidisciplinary meetings during groups, despite original training being delivered five years before. implementation of the CFHealthHub digital learning Objectives: To keep supervision groups focused, tailored to the individual C. Carolan1, M. Lowther1, C. Girling2, C. Eadson1, F. Edenborough1, R. Curley1, and interactive. To develop and embed skills within the wider MDT and M. Wildman1. 1Sheffield Teaching Hospitals, Sheffield, United Kingdom; maintain over time. 2SCHARR University of Sheffield, Sheffield, United Kingdom Methods: A clinical psychologist and physiotherapist developed a 6-month programme for a supervision group focused upon developing practical Background: High quality CF care requires high quality multi-disciplinary skills, emphasising the individual clinician’s ability to make change. team (MDT) function. The Google Aristotle project highlighted psycho- Members of the group completed SWOTs, confidence ratings and logical safety as the crucial attribute characterising excellent teams. 60% of concluded with a reflective case study. CF centres in the UK are now using the Microsystems approach to system Results: The SWOT analysis revealed all participants to have gained optimisation and central to microsystems is the “meeting skills tool” which strengths of improved understanding of MI and its technical components. optimises MDT function using explicit tools to create efficient processes Opportunities were identified within practice but highlighted the need for and psychological safety. repetition to be able to consolidate their learning. Threats included: Objectives: To use plan do study act (PDSA) cycles to implement the • Falling into possible MI ‘traps’. microsystems meeting skills approach to optimise the inpatient MDT • Time. meeting. • Confidence. Methods: Meeting skills were used to structure each MDT meeting. PDSAs captured the changes made, including: agreeing structure and order, allocating more time to complex patients and ensuring digital notes and Understanding of the use 4.25 6.25 the CFHealthHub adherence platform were visible to all MDT members. of MI Spirit (0 low -10 Improvement was measured by qualitative staff feedback, meeting scoring high) and duration. This was used to iterate the subsequent meeting. Confidence in technical 3.75 6.25 Results: Meeting scores improved from a baseline of 4.5 to 9.5/10. Staff aspects of MI (0 low reported: -10 high) • ‘It feels calmer with a facilitator’ ‘ ’ [Mean ratings before and after the supervision groups (n = 6)] • On time • ‘Better structure- people have a chance to talk’ Understanding and Confidence of MI increased during the course of the Despite an increasing number of patients to discuss, meeting time programme. Mean confidence scores were higher immediately after the reduced but team satisfaction increased and information sharing improved groups. (table 1). Discussion: Sustaining behaviour change can be hard for teams and patients alike. In order for CF teams to continue to invest in, and practice, Table 1. behaviour change skills, those facilitating the supervision groups need to Time spent to discuss each patient invest in new ways of keeping topics ‘alive’. 03/04/19 10/04/19 17/04/19 15/05/19 22/05/19 28/05/19

WS14.3 Number of 5109111312 Improving knowledge and support within the specialist nurses patients network at a large paediatric specialist centre discussed Average time in 9 6.5 6.6 7.2 6.5 6.1 1 1 S. Moledina . The Royal Brompton Hospital, London, United Kingdom minutes per patient Objectives: The Cystic Fibrosis Nurses’ Network Group started 4 years ago with the aim to improve communication, networking, share best practice 17/07/19 14/08/19 21/08/19 28/08/19 18/08/19 27/09/19 and standardise care throughout the Network. The Royal Brompton Paediatric CF centre cares for 300 patients. 150 of those patients have Number of 9 111110127 shared Care with a local Multi-Disciplinary Team. The Brompton team patients works with 10 shared care centres. The nurses at the shared care centres discussed feedback to us they would value more educational opportunities. Average time in 6.8 6.5 4.8 8.2 4.2 6.4 minutes per Methods: We meet twice a year. The day is split into two parts with a patient morning of talks, to date we have covered Nutrition (dieticians), Cystic fibrosis Diabetes (endocrinologists), Nebuliser cleaning and cough swabs (physiotherapists), Compliance (psychologists), School CF talk (RBHT CF Conclusion: PDSA methodology ensured changes were capture and their nurses), genograms and the social situations of the extended family (RBHT impact was documented. Agreeing a structure and adopting the effective CFCNS), CFSPID, CFTR modulators, Safeguarding and difficult case reviews. meeting skills meant the meetings were efficient and timely. Having

In the afternoon we are supported by a Senior Nurse from the Nursing CFHealthHub visible ensured that the key metrics of FEV1, BMI and Quality and Development team for Peer feedback. The shared care nurses adherence were reviewed, informing clinical decision making. bring an issue from their local team they want to improve. Nurses take ownership of issues and feedback at the following meeting. This initially WS14.5 was met with some scepticism but the feedback has been really positive as Piloting a communication training program for cystic fibrosis care the nurses have been encouraged by the positive changes they have teams to enhance the co-production of care enabled. Over time this has developed into the groups bringing Quality 1 1 C. George . Cystic Fibrosis Foundation, Bethesda, United States Improvement success’s sharing them with the group and discussing learning opportunities amongst the group. The Cystic Fibrosis Foundation (CFF) with the Academy of Communication Results: The programme has strengthened our team working across the in Healthcare piloted the Partnership Enhancement Program (PEP), an network ensuring we are all working to the same high standards. The evidence-based relationship-centred communication training program feedback has demonstrated the shared care nurses now feel more customised for cystic fibrosis (CF) care team members. supported and included in the specialist team. Objectives: PEP aimed to help teams meet the evolving demands in Conclusion: The collaborative working and learning will continue to providing CF care by teaching skills not traditionally offered. Feasibility, improve the care delivered to our patients. acceptability, and impact of this program were evaluated. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S25

Methods: All U.S. CF care centres were invited to participate in PEP through WS15.2 a call for applications (21 programs applied; 20 participated). The pilot Association of serum vitamin K and osteocalcin with glucose consisted of an 8-hour workshop and follow-up session (3-months post) metabolism, pulmonary function and body composition in adult held at participating CF centres and led by certified CF clinician trainers. patients with cystic fibrosis Participants completed a series of surveys throughout their participation C. Bergeron1, 2, V. Boudreau1,2, A. Bonhoure1,3, M. Mailhot4, A. Lavoie4, (before and after the workshop and post follow-up). Patient/family impact J. Lacombe1, M. Ferron1,2,3, G. Ferland2,5, R. Rabasa-Lhoret1,2,4. 1Montreal was assessed by comparing the CF centre’s IntegRATE and CollaboRATE Clinical Research Institute, Montreal, Canada; 2Université de Montréal, scores from the CFF’s Patient and Family Experience of Care (PFEC) survey Montréal, Canada; 3McGill University, Montréal, Canada; 4Centre Hospitalier before and after participation. de l’Université de Montréal, Montreal, Canada; 5Institut de Cardiologie de Results: From November 2018 - January 2020, 217 participants (20 Montréal, Montreal, Canada programs) participated. All respondents (100%) reported that the work- shop was “good” or “excellent.” Nearly all (99%) indicated they would Objectives: Patients with cystic fibrosis (CF) are at risk of vitamin K (VK) recommend the workshop to colleagues. Respondents felt that PEP deficiencies. Beyond its well-known role in coagulation, research has provided a “common language” for teams and a roadmap for effective highlighted the role of VK in bone metabolism and regulation of blood communication in clinical interactions. Improvements were shown pilot- glucose levels. Osteocalcin (OCN), a VK-dependent protein secreted by wide in the PFEC scores. osteoblasts, could be involved in these mechanisms. The circulating Conclusion: Feedback was overwhelmingly positive about the ease and uncarboxylated form of OCN (ucOCN) could act as a marker of VK status wide applicability of the skills to facilitate co-production. Participants felt and action. Few studies in have measured both the total (tOCN) their use of PEP skills enabled patients/families to share their preferences and the uncarboxylated form of OCN and the validity of previous methods and challenges with more ease and increased the team’s ability to respond of analysis have been questioned. The aim of this study is to assess VK and to these needs. OCN (total and ucOCN) status in adult patients with CF and investigate the association with glucose metabolism and clinical status: pulmonary function and body composition with bioimpedance. Methods: This study is a cross-sectional analysis with data from 167 adult WS15 Cystic Fibrosis-Related Diabetes: improved patients from the Montreal CF cohort. Serum ucOCN was measured using a recently validated immunoassay. VK and tOCN (validated methods) were diagnosis and prevention of complications measured from serum samples. Results from the oral glucose tolerance test (OGTT: 2 h with plasma glucose & insulin every 30 min), C-terminal WS15.1 telopeptide Impaired beta cell insulin secretion increases risk of Cystic Fibrosis- (CTX-I), a bone resorption marker, and clinical status were collected on the Related Diabetes same day. K.J. Potter1, V. Boudreau1,2, F. Tremblay3, P.A. Senior4, R. Rabasa-Lhoret1,2,3. Results: Low levels of VK (< 0.28 nmol/L) are observed in 66% of patients. 1Montreal Clinical Research Institute, Montréal, Canada; 2Université de Patients with a low VK status have higher ucOCN levels than patients with a Montréal, Montréal, Canada; 3Centre Hospitalier de l’Université de Montréal, normal VK status (10.70 ± 11.06 vs 5.20 ± 5.55, p < 0.001). Serum ucOCN Cystic Fibrosis Clinic, Montréal, Canada; 4University of Alberta, Faculty of correlates negatively with age (r = −0.175, p = 0.025), fat mass Medicine and Dentistry, Edmonton, Canada (r = −0.261, p = 0.001), lung function (r = −0.208, p = 0.008) and serum VK (r = −0.199, p = 0.011) and positively with the CTX-I (r = 0.397, p < 0.001). No Objectives: Cystic Fibrosis-Related Diabetes (CFRD) is a state of insulin significant correlations were observed between ucOCN and data collected deficiency that worsens pulmonary pathology and increases early during OGTT. mortality. The objectives of this study were to determine whether Conclusion: VK deficiency is common in CF patients. We observed an clinically-derived measures of beta cell function might improve diabetes association of ucOCN with VK, lung function, body composition and a risk prediction. marker of bone metabolism. Methods: The Montreal CF cohort was established in 2004 for prospective observational yearly assessment of pulmonary function (FEV1%), oral WS15.3 glucose tolerance testing (OGTT), and . We performed HOMA indexes diagnosis performance for Cystic Fibrosis-Related analysis of CFRD risk according to the insulinogenic index (II; (I30-I0)/ Diabetes (G30-G0)), at the first screening visit in 281 subjects who had available data T. Toin1, Q. Reynaud2,3, A. Denis4, I. Durieu2,3, C. Mainguy1, S. Touzet3,4, for all calculations. P. Reix1,5. 1Hôpital Femme-Mere-Enfant̀ - Hospices Civils de Lyon, Cystic Results: At baseline, II was progressively lower in subjects who later Fibrosis Pediatric Center, Bron, France; 2Centre Hospitalier Lyon Sud - Hospices developed CFRD (5.1 ± 4.1) and those with CFRD at initial screening Civils de Lyon, Cystic Fibrosis Adult Center, Pierre-Bénite, France; 3Université de (2.5 ± 2.0) than those who never developed CFRD (7.8 ± 8.6; p < 0.0001). We Lyon, EA 7425 HESPER, Lyon, France; 4Pôle de Santé Publique - Hospices Civils subdivided 191 subjects who did not have CFRD at baseline and who had at de Lyon, Lyon, France; 5CNRS, Université de Lyon, UMR 5558 Biométrie et least 1 follow up visit according to quartiles of II. The proportion of subjects Biologie Évolutive, Villeurbanne, France who developed CFRD was: Quartile 1, 37.2%; Quartile 2, 31.3%; Quartile 3, 19.1%, and Quartile 4, 12.2% (p = 0.0214); the progression to diabetes was Objectives: To investigate homeostasis model assessment indexes (HOMA) significantly faster in the lowest quartiles by Kaplan-Meier analysis of beta-cell function (HOMA%B) and of insulin resistance (HOMA-IR) (p = 0.0207). BMI (p = 0.0002), % fat mass (p < 0.0001), and FEV1 (%; performance for the diagnosis of cystic fibrosis related diabetes (CFRD). p = 0.0251) were all significantly lower in Quartile 1 as compared to Methods: Data from 228 patients with cystic fibrosis (117 adults) of the Quartile 4. The number of pulmonary exacerbations tended to be greater in DIAMUCO cohort were analysed. This prospective cohort study was Quartile 1 (p = NS). Subjects in Quartile 1 had significantly higher designed to follow the annual variations of oral glucose tolerance test frequency of total (p = 0.0045) and pseudomonal (p = 0.0062) respiratory (OGTT) outcomes over three consecutive years [1]. At each encounter, infections. insulin and glucose fasting levels were measured to calculate HOMA%B Conclusion: The II is lower at baseline in subjects who later develop CFRD. (20xfasting plasma insulin)/(fasting plasma glucose-3,5)) and HOMA-IR Subjects with the lowest quartile of II had increased and earlier risk of CFRD ((fasting plasma insulin x fasting plasma glucose)/22,5). Recommended and tended to have poorer measures of clinical health. thresholds of 2hours OGTT were used to define CFRD (plasma glucose≥11,1 mmol/L). HOMA%B and HOMA-IR were assessed for CFRD diagnosis in term of sensitivity (Sen), specificity (Spe), positive and negative predictive values (PPV and NPV). They were analysed separately in children and adults for each year of follow up and then pooled over the study period. S26 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

Results: In the “pooled” analysis, HOMA%B values < 100 (ie.insulinopenia) study was to compare insulin use and outcomes between two large and HOMA-IR values > 1 (ie.insulinoresistance) had good diagnosis national datasets. performance. In children, HOMA%B Sen, Spe, NPV and PPV were Methods: Data from annual review visits were available from the UK CF respectively 88%, 45%, 98% and 11%, while it was 42%, 48%, 91% and 6% Registry (2008-17) and compared to results from the German CF Registry for HOMA-IR. In adults, HOMA%B Sen, Spe, NPV and PPV were respectively (2004-16). We restricted inclusion to individuals with at least one prior 83%, 18%, 90% and 10%, while it was 39%, 80%, 92% and 18% for HOMA-IR. visit and no history of transplant. Incident CFRD diagnoses were identified Conclusion: We found that HOMA%B < 100 had a good Sen and NPV for at each visit. We assessed insulin use from diagnosis up to 4 years and

CFRD diagnosis in both children and adults while HOMA-IR > 1 had a good estimated change in FEV1% and BMI in consistent users and non-users of NPV in children and adults. This implies that calculation of HOMA%B and insulin in unadjusted and adjusted analyses. HOMA-IR indexes could be used as a first line diagnosis approach to Results: Incident CFRD was identified in 1961 people in the UK and 624 in exclude CFRD and avoid unnecessary OGTT to patients. Germany. Insulin treatment was recorded as the initial treatment in 1234/ This work was granted by clinical research program of French ministry of 1961 (63.0%) in the UK and 237/624 (37.9%) in Germany. In Germany, those health (PHRC-I) and association ‘Vaincre la mucoviscidose’ initiated on insulin had similar clinical characteristics to non-insulin users, however in the UK, those initiating insulin had lower age, FEV % and BMI Reference 1 (p < 0.001). 4 years complete follow-up data were available for 894 and 149 [1] Reynaud et al., Journal of Cystic Fibrosis,2018. from the UK and Germany respectively. After 4 years, the mean change in FEV1% predicted for insulin users and non-users was − 1.1% and − 2.0% in WS15.4 Germany and − 7.8% and − 5.4% in the UK. The differences in UK outcomes Early experience of flash glucose monitoring using the Freestyle Libre persisted after adjustment for baseline age, sex, DF508, and diagnosis year System in adults with Cystic Fibrosis-Related Diabetes (CFRD) attending (p = 0.02). There was no evidence of difference in BMI change in the two a large regional UK centre groups in either country. D. Shimmin1, M. Mansfield1, K. Taylor1, L. Pearson1, Y.W. Lim1, Conclusion: In this initial data comparison we found insulin initiation in C. Etherington1, I. Clifton1, D. Peckham1. 1Leeds Teaching Hospitals NHS Trust, incident CFRD is higher in the UK than Germany but despite most Adult CF Unit, Leeds, United Kingdom guidelines recommending insulin, a significant proportion of patients in each country go untreated initially. Outcomes associated with insulin use Objectives: The Freestyle Libre (FSL) flash glucose monitoring system differ between countries and further work is underway to robustly explore comprises a sensor and reader to measure interstitial glucose without the and compare outcomes associated with insulin and non-insulin inconvenience of routine (sometimes painful) self-measured blood glucose management. (SMBG) tests. FSL use is associated with improved metabolic control, treatment satisfaction and HRQoL for type 1 diabetes compared with WS15.6 SMBG. NHS England agreed FSL on prescription (from May 2019) for Prevalence of diabetes and microangiopathic complications in non- diabetes management including people with CFRD on insulin who agree to transplanted and transplanted cystic fibrosis adults scan > 8/day and use the sensor >70% of the time. The aim of this study was E. Burnet1, 2, H. Mosnier-Pudar2,3, C. Martin1,2,4, R. Kanaan1, 2, N. Carlier1,2, to evaluate the impact of using the FSL on glycaemic control, nutritional I. Honoré1, 2, V. Boussaud1, 2, P.-R. Burgel1,2,4. 1Adult CF Centre, Cochin status and patient reported outcomes in people with CFRD. Hospital, Paris, France; 2Université de Paris, Paris, France; 3Diabetes and Methods: Patients who commenced FSL from May-December 2019 were Endocrine Centre, Hôpital Cochin, Paris, France; 4Insitut Cochin, Inserm U 1016, identified and data extracted retrospectively from our electronic patient Paris, France records (EMIS®) and Libreview® secure cloud-based database. Target glucose range was set at 4–10 mmol/l for all subjects. BMI, HbA1c, time in Objectives: Given the aging of the CF population and the high prevalence of target range (TIR, %), time in hypoglycaemia (TIH %) and sensor use (scans/ those living with a lung transplant, CF related comorbidities are expected day and sensor data capture %) were collected at baseline and 3 months to rise. This study’s objectives are to determine the prevalence Cystic (3M). A survey was used to assess treatment satisfaction and HRQoL was Fibrosis Related Diabetes (CFRD) and related microangiopathic complica- assessed (n = 46). tions among CF adults (≥18years) followed at Cochin hospital’s CF centre in Results: 78 subjects (40 male, median age 37 [18–69] years) were Paris, France. identified. BMI remained unchanged at 3M (22.5 kg/m2). HbA1c decreased Methods: A cross-sectional study was conducted at our CF centre, which from 58.5 to 55 mmol/mol at 3M (p = 0.014). There was a modest but not follows a population of 577 CF adults, including 120 lung transplant statistically significant increase in mean TIR from 57.3% at baseline to 60.6% recipients (21%). CFRD was defined as insulin dependent diabetes and at 3M (p = 0.1). Median TIH remained at 4% from baseline to 3M (p = 0.36). microangiopathic complications as diabetic retinopathy, nephropathy or Sensor use remained above minimum NHS England requirements. neuropathy, as evaluated by a physician and documented in the patient’s Treatment satisfaction was high. All subjects (n = 46, 20 male) recom- medical file in 2019. Data on clinical characteristics in 2019 were also mended and wished to continue using FSL, with responses suggestive of collected. improved HRQoL. Results: Overall, 133/577 CF adults (23%) were found to have CFRD; with a Conclusion: In adults with CFRD using the FSL system was associated with prevalence of 17% in non-transplanted patients (n = 79/457) and of 45% in significant improvements in Hba1c and patient reported outcomes at 3 transplant recipients (n = 54/120, p < 0.0001). Although only 60% of CFRD months. Further data at 6 months will be available at the time of adults had documented evidence of complications screening in 2019, 27 conference. (21%) were found to have one or more complications, 44% of which were transplant recipients. Diabetic nephropathy was documented in 16 WS15.5 patients (including 6 transplanted), retinopathy in 17 (3 transplanted), An international comparison of insulin use in incident Cystic Fibrosis- and neuropathy in 5 (3 transplanted). Three patients had two complica- Related Diabetes: data from the UK and German Cystic Fibrosis tions and two had all three. Data on patient characteristics and risk factors Registries remain to be analysed. F. Frost1, 2, R.H. Keogh3, M. Ballmann4. 1Liverpool Heart & Chest Hospital, Conclusions: Although the prevalence of CFRD-related microangiopathic Liverpool, United Kingdom; 2University of Liverpool, Institute of Infection & complications is generally considered low, and in spite of a high proportion , Liverpool, United Kingdom; 3London School of Hygiene and of missing documentation, our data suggest an increasing trend in Tropical Medicine, London, United Kingdom; 4Universitatsmedizin Rostock, prevalence. Because CFRD and its complications can impact morbidity, Pediatric Medicine, Rostock, Germany mortality and quality of life, annual screening for complications should become systematic as the population ages. Introduction: Prior work has demonstrated that in Germany, a significant proportion of people with CFRD are not treated with insulin. The aim of this Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S27

(SD ± 261 m) in women. Before the endpoint of the study, 18 patients died WS16 The role of physical exercise: impacts (19%) and 32 underwent LoTx (33%). In patients with a ventilatory on health limitation (FEV1< 70%), we categorised the walking distance by: A) ≤500 m; B) 501–1000 m; C) 1000–1500 m. The Hazard Ratio for the risk of dying for category A was: 5.98 (95%CI;HR:2.2–15.1; P < 0.000) and for WS16.1 category B: 2.56 (95%CI;0.9–6.6; P < 0.052) in comparison to category C. Biopsychological, physical activity and sedentary behaviour profile of Conclusion: In patients with an FEV < 70%, those who’ve walked less than adults with cystic fibrosis in Ireland 1 500 m are 6.0 times more likely to die/Lotx and those who walk 501– 1,2 1,2,3 4 4 4 M. Curran , A. Tierney , L. Collins , L. Kennedy , C. McDonnell , 1000 m. are 2.6 times more likely to die/LoTx, compared to patients who 1 1,2 5 4 1, 2 A. Jurascheck , A. Sheikhi , B. Button , B. Casserly , R. Cahalan . walk more than 1000 m. This supports the relevance of treatment focused 1 2 University of Limerick, Limerick, Ireland; Health Research Institute, Limerick, on maintaining or improving exercise capacity in this patient group. Ireland; 3La Trobe University, Melbourne, Australia; 4University Hosital 5 Limerick, Limerick, Ireland; Monash University, Melbourne, Australia WS16.3 Objective: Sleep, well-being and quality of life (QOL) are important Relationship between physical activity and long-term health outcomes considerations in Cystic Fibrosis (CF) management. Furthermore, physical in adults with cystic fibrosis 1,2 3 3 2,4 1, 5 1 activity (PA) should be monitored and encouraged as it can improve patient T. Dwyer , R. Dentice , J. Marouvo ,P.Bye , J. Alison . University of 2 health. The objective of this study was to establish a biopsychological Sydney, Discipline of Physiotherapy, Sydney, Australia; Royal Prince Alfred 3 profile of adults with CF and assess PA and sedentary behaviour levels. Hospital, Department of Respiratory Medicine, Sydney, Australia; Royal Prince 4 Methods: Observational study which assessed QOL, wellbeing, sleep and Alfred Hospital, Department of Physiotherapy, Sydney, Australia; University of 5 PA levels in adults with CF, at University Hospital Limerick. Participants Sydney, Sydney Medical School, Sydney, Australia; Sydney Local Health were included if they were medically stable, with no exacerbation in the District, Division of Allied Health, Sydney, Australia previous month. Wellbeing was assessed by the Alfred Wellness Score For adults with Cystic Fibrosis (CF), higher levels of physical activity are (AWE), sleep quality by the Pittburgh Sleep Quality Index (PSQI) and QOL associated with improved exercise capacity and quality of life, as well as using the CF Questionnaire-Revised (CFQ-R). PA and sedentary behaviour reduced decline in lung function and bone mineral density. To date, the were assessed using an ActivPAL accelerometer which was worn for seven relationship between physical activity and long-term health outcomes, days. Sedentary behaviour consisted of both lying and sitting postures, as including survival, hospitalisation and CF-related diabetes, is unknown. the ActivPAL cannot distinguish between these positions. Objectives: Analyse differences in 13-year health outcomes (survival, Results: Thirty-three participants (13M/20F; 26.2 ± 7.1 years) were hospitalisation, lung function, bone mineral density and glucose tolerance) recruited. Mean FEV1 was 72.9% (±26.2 SD). CFQ-R (respiratory domain) according to moderate-vigorous physical activity (MVPA) in adults with CF. was 76.3% (±14.9 SD) and mean AWE score was 69.5 (± 12.6 SD) indicating Methods: Between 2007–2008, 104 adults from the RPA CF clinic (mean very good levels of wellbeing and QOL. Mean step count was 7788 (± 3583 age 29 ± 10 years, 45 female, FEV 63 ± 24%predicted) reported their MVPA SD). Over 75% of participants did not reach recommended PA targets 1 in a research study on exercise behaviour. Participants were prospectively (>10,000 steps), with females being 25% less active than males. Mean classified as achieving or not achieving physical activity recommendations sedentary time was 18.6 (±2.1 SD) hours per day. The mean PSQI score was (defined as ≥150 minutes of MVPA/week). Health data were collected from 5.7 (± 3.9 SD). Sixteen (48.5%) participants scored >5, indicating poor sleep RPA hospital records until 31/12/2019. Participants were censored at the quality. Pearson correlation co-efficients indicated that poor sleep quality time of transplantation or death. The mean follow-up period was 8.4 ± 4.1 was significantly negatively correlated with low step counts (-0.713, years (range 0–12.6). p = 0.000) and positively correlated with higher sedentary time (0.681, Results: 48 adults were prospectively classified as achieving physical p = 0.000). activity recommendations (“high activity”) and 56 were not (“low Conclusion: The majority of participants did not meet PA guidelines. PA activity”). The demographic and clinical characteristics of the groups and sedentary behaviour levels correlate to self-reported sleep quality and were similar at baseline for age, sex, lung function, bone mineral density, this should be considered in PA interventions. glucose tolerance and hospitalisations in the previous year. There was reduced incidence of transplantation or death in the “high activity” WS16.2 compared to the “low activity” group (29% v 43%). There was also a longer Is measurement of exercise capacity valuable to predict survival in time to transplantation or death in the “high activity” compared to the “low cystic fibrosis? activity” group, taking 2.1 years longer until 25% of participants had lung 1 1 2 3 1 W. Doeleman , M. Burghard , J. Twisk , E. Hulzebos . University Medical transplantation or died. Data for other health outcomes will be presented at Center Utrecht, Rehabilitation, Physiotherapy Sciences and Sport, Utrecht, the 2020 European CF conference. 2 Netherlands; Amsterdam University Medical Centers, University of Conclusion: There is a trend for increased time to transplantation or death Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam, with higher levels of MVPA in adults with CF. Netherlands; 3University Medical Center Utrecht, Child Development and Exercise Center, Utrecht, Netherlands WS16.4 Objectives: Recent studies recognised that cardiorespiratory fitness (CRF) Differences in the ventilatory response to incremental exercise in carries additional prognostic information to established predictors of death people with cystic fibrosis according to age and sex 1,2 1, 2 2 2 1 in Cystic Fibrosis (CF). Patients with a low CRF may especially benefit from C.A. Williams , O.W. Tomlinson , N.J. Withers , P.J. Oades , A.R. Barker . 1 regular monitoring of exercise capacity and exercise counselling. The Children’s Health and Exercise Research Centre, Sport and Health Sciences, 2 purpose of this study was to investigate the association between exercise University of Exeter, Exeter, United Kingdom; Royal Devon and Exeter NHS capacity and mortality in adult patients with CF. Foundation Trust, Exeter, United Kingdom Methods: We executed a cross-sectional, retrospective analysis, using data Objectives: Maximal oxygen uptake (VO ) is predictive of mortality in collected between 2000 and 2010 in the CF Centre of Utrecht. Death or lung 2max CF, independently of lung function [i.e. FEV ] and is significantly different transplantation (LoTx) were identified as index measurements and the 1 between people with CF of differing disease severity. It is unclear whether distance accomplished in the Modified Shuttle Test (MST) as a marker of dynamic measures of ventilatory function, such as peak minute ventilation exercise capacity. Using Cox regression with time as a dependent covariate, (V ), differ with age (adult vs. paediatric) and sex groups, considering we explored the risk of dying or undergoing LoTx, in relation to the Epeak the importance of static lung measures in CF. This study determines absolute distance walked. differences in V , based upon age and sex in CF. Results: The study sample consisted of 96 patients with CF (49 male, 47 Epeak Methods: Data from 87 patients (<18 y = 31 [19 male]; ≥18 y = 56 [32 male]; female; mean age 29 years, range 19–53 and FEV : 71%, range 38%-113%). 1 dF508/dF508 = 31, dF508/other = 46, no dF508 = 10) were included. CPET Mean covered MST distance was 825 m (SD ± 417 m) in men and 820 m using a reliable and valid combined ramp-incremental and supramaximal S28 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

verification cycle ergometer test determined VO2max and VEpeak, which Inhalation therapy and physiotherapy are introduced at diagnosis. This were then scaled for body mass. One-way ANCOVA (controlling for FEV1 study aims to describe the current use of inhalation therapies, airway and VO2max) with Bonferroni post-hoc tests compared age and sex clearance therapy (ACT) and physical exercise in the Swedish CF differences in VEpeak. population. Results: Mean (±SD) VO2max for male and female < 18 y were 38.9 (6.3) and Methods: Data from annual check-ups 2018 was collected from the − − 28.6 (5.4) mL·kg 1·min 1 respectively and 28.4 (9.1) and 22.7 (5.0) Swedish CF registry. Criteria for inclusion was confirmed CF diagnosis. −1 −1 ≥ ≤ ≤ mL·kg ·min for male and females 18 y. Mean VEpeak for < 18 y males Patients were divided into four age groups (grp 1: 0 6 yrs; grp 2: 7 11 yrs; −1 −1 ≤ ≥ and females were 1.77 (0.46) and 1.39 (0.40) L·kg ·min respectively and grp 3: 12 17 yrs; grp 4: 18 yrs). Genotype, FEV1% predicted, frequency − − 1.39 (0.43) and 1.11 (0.31) L·kg 1·min 1 in male and females ≥18 y. ANCOVA of inhalation therapy and ACT sessions, number of ACT techniques used, controlling for FEV1 showed main effects of sex (p < 0.01) and age and frequency of physical exercise sessions were recorded. (p = 0.04), but no interaction (p = 0.60) upon VEpeak. Pairwise comparisons Results: In total, 544 patients were included. Results from collected data in were significant, with VEpeak in male adults being significantly greater than the four age groups are presented in table 1. females (p < 0.01) and male paediatrics being significantly greater than Table 1. females (p = 0.01). When ANCOVA controls for VO2peak, no effects of age or sex are observed upon VEpeak (p > 0.05). Conclusion: VEpeak differs between age and sex groups when controlling for Grp 1: Grp 2: Grp 3: Grp 4: ≤ ≤ ≤ ≥ FEV1, but not VO2max, suggesting dynamic ventilatory measures are explained 0 6 yrs 7 11 yrs 12 17 yrs 18 yrs by fitness and not static lung function. This highlights the importance of Number of patients 37(18) 91(47) 87(48) 329(177) routine exercise assessments in addition to spirometry in CF management. (male) Age** 5.5(4.6–7) 9.6(7–11.7) 14.6(12–17.9) 31.4(18.1–76.5) WS16.5 Homozygous F508del 20 45 39 144

Expansion of a leading cystic fibrosis exercise programme: FEV1% pred* 101(±16) 95(±15) 83(±17) 72(±23) collaborative partnership between the UK’s largest healthcare charity Inhalation therapy/day* 1.95(±0.23) 1.77(±0.5) 1.75(±0.48) 1.28(±0.75) and 12 UK cystic fibrosis centres ACT/day* 1.89(±0.39) 1.75(±0.5) 1.7(±0.55) 1.09(±0.82) Number of ACT 2.27(±0.68) 2.48(±0.73) 3.07(±1.03) 2.95(±1.36) A. Ahlquist1, A. Q. Innes1, H. Douglas2, S. Rand2. 1Nuffield Health, Epsom 2 techniques used* Gateway, Ashley Avenue, London, United Kingdom; UCL Great Ormond Street Physical exercise/week* 1.05(±1.27) 2.29(±1.01) 2.08(±1.22) 1.6(±1.38) Institute of Child Health, London, United Kingdom [(*Mean (SD), **Median (range))] Objectives: The Nuffield Health (NH) CF Programme, which was established in 2011 offering complementary weekly personal training Conclusion: Children perform inhalation and ACT more frequently than (PT) for 5–17 year olds, swimming for under 5’s and free gym membership, adults. Number of ACT techniques used increases with age. Physical has continued to develop and maintain successful partnerships with UK CF exercise is performed in the whole population studied but frequency centres. This study reports on the implementation of outcome measures decreases with age. Decreased performance of airway clearance and (OMs) to monitor the programmes impact (2017), the expansion to physical exercise with increased age is a problem that may need to be additional CF units and NH centres, and the introduction of a complemen- addressed with a different type of physiotherapeutic interventions. It may tary family membership (2019) which aims to support families from lower be beneficial with an increased use of interventions in the field of income groups. behavioural medicine and closer cooperation with the team psychologist to Methods: OMs included CPET (Bruce Modified Protocol), height and support the patient’s self-management. weight and a self-efficacy for physical activity questionnaire (CSAPPA). These measures are taken at session 1, 3 months, 6 months and 6 monthly thereafter. New partnerships between NH and CF centres were instigated. Data on family membership uptake, overall attendance and socioeconomic WS17 Beyond modulators: approaches involving status of participants were collected. gene editing or alternative channels Results: Over the period 2017–2019 participation has increased from 155 to 493 children and young people (CYP). OMs data completeness >85% WS17.1 where CYP have had an assessment. Participating NH centres has increased Enhancing site-specific gene integration efficiency for permanent CFTR from 36–91, >550 NH employees trained to deliver the programme, >340 gene correction families have taken up the membership, participants from families with 1,2 1, 2 2 2 2 1, 2 2 lower income has increased. Z.P. Zhou , Z.R. Chen , H. Cao , R. Duan ,J.Li , S. Cai , H. Grasemann , K. Philip3, J. Zabner3, M. Welsh3, J.P.Ianowski4,J.Hu1,2. 1University of Toronto, Conclusion: OMs were successfully integrated, data completeness was high 2 despite a time burden. The programme’s growth continues, with the Department of Laboratory Medicine and Pathobiology, Toronto, Canada; The support of further UK CF centres. The on-boarding process has enabled the Hospital for Sick Children, Program of Translational Medicine, Toronto, Canada; 3University of Iowa, Department of Internal Medicine, College of expansion whilst maintaining quality. Some NH centres are at full capacity 4 with waiting lists. Family memberships are popular but more focus is Medicine, Iowa City, United States; University of Saskatchewan, Department needed to target lower income families. Analysis of OMs will follow. Future of Physiology, College of Medicine, Saskatoon, Canada plans include a national review, identifying areas of weakness, further Objectives: Using helper-dependent adenoviral (HD-Ad) vectors, we analysis on the benefits to families, ensuring the proposition is fit for scale demonstrated that a human CFTR minigene can be precisely integrated forother providers to run and designing an efficient governance framework. into a specific chromosomal location through CRISPR/Cas9-mediated homology repair in both pig and human cells. One unique advantage of WS16.6 our system is that following gene integration, there is no residual Cas9 Decreased performance of airway clearance and physical exercise with expression, which eliminates the potential risk of the host immune attack age in the Swedish cystic fibrosis population - what’s the solution? on cells with gene integration. In this study, we aim at enhancing the C. Rodriguez Hortal1, S. Wilhelmsson1, A. Törnberg1, L. Lannefors2, L. Hoel2, efficiency of gene integration to provide better long-term therapeutic K. Ersson3, U. Dennersten-Kvist4, K. Wallin4, M. Mårtensson4, A. Hedborg1. benefits. 1Karolinska University Hospital, Stockholm, Sweden; 2Sahlgrenska University Methods: HD-Ad vectors containing CRISPR/Cas9 and donor template Hospital, Göteborg, Sweden; 3Akademiska University Hospital, Uppsala, (6 kb LacZ or 8.7 kb hCFTR cassette flanked by homology arms) were Sweden; 4Skåne University Hospital, Lund, Sweden delivered into pig or human cells. To increase integration efficiency, we co- transduced a vector expressing A protein factor. Pig GGTA1 or human AAVS1 Objectives: Airway clearance and physical exercise are important compo- locus was chosen as a safe harbour to receive transgene integration. nents and part of physiotherapy in the basic treatment in Swedish CF care. CRISPR/Cas9 cleavage and transgene integration frequencies were Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S29 quantified by digital PCR. The LacZ integration was also verified by X-gal profile. We hypothesise that historically, inhaled ENaC blockers have failed staining and β-galactosidase assays. The CFTR function was assessed by to demonstrate clinical efficacy due to under-dosing as a result of safety membrane potential sensitive dye-based (FLIPR) and Ussing chamber limitations. assays. Methods: ETD001 was examined for potency on ENaC in primary cultures Results: We confirmed the site of gene integration by junction PCR and of CF bronchial epithelial cells (CF-HBE) using a short-circuit current assay Sanger sequencing. We detected transgene mRNA and protein expression. format. In vivo potency and duration of action was examined in a sheep The LacZ/hCFTR integration efficiency was increased by 2–5 fold with model of mucociliary clearance (MCC) in vivo, using gamma-scintigraphy. − – protein factors. In CFTR / cells, the function of integrated hCFTR was Safety and pharmacokinetics (PK) of ETD001 were evaluated in rat and dog − – measurable. We also detected hCFTR channel response in pig CFTR / studies, which included toxicology following 35 days of repeat dosing primary airway cells by the Ussing chamber assay. Immunostaining also under GLP conditions. confirmed hCFTR expression. Results: ETD001 attenuated the ENaC-mediated short-circuit current in

Conclusion: These results validated the potential of our CFTR gene CF-HBE with an IC50 value of 40 nM. Inhaled doses of ETD001 as low as targeting strategy. We showed that Cas9 expression was eliminated 2.1 μg/kg enhanced the rate and magnitude of MCC in the conscious sheep following transgene integration, which is important for in vivo applications with a long duration of action. Lung PK studies confirmed the presence of since Cas9 is a foreign protein and elimination of its expression would avoid high levels of ETD001 in the airway lumen for at least 6 hours after dosing immune responses to gene-corrected cells. that would be consistent with the observed long duration of action. Safety and PK studies demonstrated the tolerability of ETD001. Predictions of the WS17.2 maximum tolerated clinical dose indicate a safety window of >10-fold over Rescue of the W1282X mutation by gene editing in human the estimated dose required for efficacy, assuming a good translation from bronchial cells sheep to man. L. Santos1, 2, K. Mention2, K. Cavusoglu-Doran2, P.T. Harrison2, C.M. Farinha1. Conclusions: The preclinical profile of ETD001 is consistent with a 1University of Lisboa, BioISI - BioSystems and Integrative Sciences Institute, candidate that can be tested for efficacy in CF patients. The wide safety Faculty of Sciences, Lisboa, Portugal; 2University College Cork, Department of margin observed with ETD001 is predicted to enable dosing up to a Physiology, Cork, Ireland threshold required to observe a long-lasting enhancement of MCC in CF patients. Background: W1282X (c.3846G>A) is the sixth most common CF-causing variant in the CFTR gene. This nonsense mutation generates a premature WS17.5 termination codon (PTC) making the transcript susceptible to nonsense- Furin inhibition as a mechanism to reduce aberrant ENaC-mediated mediated decay (NMD) - without detectable production of CFTR protein. As sodium transport and rehydrate the airways in cystic fibrosis lung there are no approved modulators for patients with nonsense mutations, disease CRISPR gene editing tools can be of great value to them by permanently 1 1 2 2 1 1 L.E.J. Douglas , J.A. Reihill , M.W.-Y. Ho , J.M. Axten , S.L. Martin . Queen’s correcting genetic defects. University Belfast, School of Pharmacy, Belfast, United Kingdom; Aim: We investigated the potential of homology-directed repair (HDR)- 2 GlaxoSmithKline Laboratories, Philadelphia, United States mediated gene editing to correct W1282X in human bronchial epithelial cells. Objectives: In cystic fibrosis (CF), dysregulation of ENaC, secondary to the Methods: We used Cas9/gRNA ribonucleoproteins (RNPs) and single strand loss of functional CFTR leads to increased Na+ absorption which contributes DNA (ssDNA) oligonucleotide donor to correct the mutation in the 16HBE to airways dehydration, thickened mucus and impaired mucociliary W1282X CFTR cell line (obtained from CFF). Success of the strategy was clearance (MCC). The pro-protein convertase, furin is implicated in the assessed at DNA, RNA and protein level. activation of a distinct pool of ENaC as it passes through the biosynthetic Results: Co-transfection with Cas9 RNP and ssODN donor yielded 17.5% of pathway and as such plays a key role in the regulation of ENaC-mediated HDR at DNA level (plus 24% of insertion and deletions), as measured by Na+ absorption. As a promising mutation-agnostic therapeutic target for CF Inference of CRISPR Editing. This level of HDR in the pool of edited cells lung disease, the aim of this first-in-kind study was to determine the effect increased the production of CFTR mRNA by 12% relatively to non-edited of two chemically different, highly selective furin inhibitors (BOS-981 and cells. CFTR protein expression was evaluated by western blot in 16HBE WT BOS-318) on ENaC signaling and airway surface liquid (ASL) height, using and W1282X cell lines, and in the pool of edited cells. As expected, no primary human CF bronchial epithelial cells (HBEs). mature CFTR protein was detected in the untreated mutant cell line, but in Methods: Fully differentiated HBEs homozygous for Phe508del, grown at the pool of edited cells mature CFTR protein expression was restored to 6% air-liquid interface, were used to determine ENaC activity via equivalent of WT. CFTR expression was also analysed in two homozygous clones current (Ieq) readings obtained using a 24-well Transepithelial Current isolated from the pool, showing CFTR mRNA and protein levels similar to Clamp (TECC-24) system. ASL height was measured using confocal WT. microscopy. Conclusions: Results show that gene editing can successfully correct Results: We report BOS-981 and BOS-318 to be potent inhibitors of furin. W1282X in this cell line, restoring full length CFTR protein expression. Both compounds, applied basolaterally, significantly reduced ENaC- Ongoing work includes assessment of CFTR function in edited cells and mediated Na+ absorption as measured by an acute reduction in amilor- comparison with read-through and NMD inhibition drugs. ide-sensitive Ieq after immediate treatment, which was sustained after Work supported by: UID/MULTI/04046/2019 grant and BioSys PhD longer (48 hr) exposure. The compounds also protected ENaC against cell fellowship (Ref. PD/BD/130969/2017 to LS) from FCT, Portugal (to BioISI) surface activation by neutrophil elastase and CF sputum supernatant. and CFF grant HARRIS17G0. Furthermore, the reduction in ENaC activity after a 48 hr treatment correlated with an increase in ASL height. WS17.4 Conclusions: These ground-breaking results demonstrate that highly ETD001: a long-acting and safely inhaled ENaC blocker to enhance selective inhibition of furin by the novel inhibitors BOS-981 and BOS-318 mucociliary clearance presents a promising mechanism for the reduction of aberrant ENaC- + H. Danahay1, P. Russell1, S. Collingwood1, J. Ford1, J. Sabater2, J. Charlwood1, mediated Na absorption. This strategy has the potential to rehydrate the C. McCarthy1, M. Gosling1. 1Enterprise Therapeutics, Brighton, airways, restore effective MCC and reduce the devastating pulmonary United Kingdom; 2Mount Sinai Medical Center, Miami, United States decline observed in CF. Objectives: To design an inhaled blocker of the epithelial sodium channel (ENaC) with a long duration of action in the lung and excellent safety S30 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

WS17.6 outcome, a diagnosis of NTM pulmonary disease, using autoregressive Delineating SLC26A9 function in vitro for therapeutic strategies in integrated moving average modelling and network analyses. cystic fibrosis Results: Subjects with and without NTM pulmonary disease were similar J.J. Salomon1, S. Spahn1, J. Füllekrug2, M.A. Mall3,4. 1University of Heidelberg, in clinical characteristics, including age and lung function. Features of Translational Pulmonology, Translational Lung Research Center (TLRC), airway microbiota positively associated with NTM disease were identified, German Center for Lung Research (DZL), Heidelberg, Germany; 2University of and predominantly included oral-associated microbiota (e.g., Rothia, Heidelberg, Molecular Cell Biology Laboratory, Internal Medicine IV, Fusobacterium, Veillonella, and Prevotella). Network analyses identified Heidelberg, Germany; 3Charité Universitätsmedizin Berlin, Department of differences in clustering of taxa between those with and without NTM Pediatric Pulomonology & Immunology and Cystic Fibrosis Center, Berlin, pulmonary disease. Subjects with NTM pulmonary disease had less Germany; 4Berlin Institute of Health (BIH), Berlin, Germany intraconnectedness of clusters (lower modularity score). − Conclusions: CF airway microbiota preceding NTM infection are associated Objectives: The SLC26A9 Cl channel has been increasingly recognised as with subsequent diagnosis of NTM pulmonary disease, suggesting that an attractive molecular target in cystic fibrosis (CF), being associated as a airway microbiota contribute to outcomes of NTM infection, and may genetic modifier to CF disease severity and therapeutic CFTR potentiator represent targets for predictive markers of NTM infection and future efficacy (Strug et al. 2016; Lam et al. 2019). Lately, it has been shown that therapies. expression levels of SLC26A9 were decreased in the presence of F508del- CFTR (a common mutation of CFTR) due to proteasomal degradation (Sato WS18.4 et al. 2019). We aim to further decipher the functional modulation of − Amikacin Liposome Inhalation Suspension in cystic fibrosis patients SLC26A9 and CFTR (including genetic variants of CFTR) Cl channels at the with Mycobacterium abcessus lung infection: results from the French airway epithelium. cohort Methods: We generated stable SLC26A9-overexpressing epithelial cell 1 2 1 1 1 1 R. Chiron , W. Hoefsloot , M. Drevait , D. Caimmi , J. Moreau , R. Chelabi , lines via retroviral transfection of wtCFTR-transfected airway epithelial 3 3 4 5 6 S. Godreuil , Y. Dumont , N. Terrail , J.L. Herrmann , L. Kremer , cells originally derived from a patient with cystic fibrosis (CFBE wtCFTR) 7, 8 9 10 11 1 − H. Marchandin , D. Grenet , H. Morisse Pradier , E. Catherinot . Centre using a HA-tagged version of the protein. Transepithelial Cl currents were Hospitalier Universitaire de Montpellier, CRCM, Montpellier, France; measured in Ussing chambers. 2 3 Pulmonology – Nijmegen, Netherlands; Centre Hospitalier Universitaire de Results: SLC26A9 was overexpressed in transduced CFBE wtCFTR (CFBE 4 Montpellier, Bacteriology Department, Montpellier, France; Centre wtCFTR-SLC26A9) cells by 100-fold, but not in parental/mock-transduced Hospitalier Universitaire de Montpellier, Pharmacy Department, Montpellier, cells. Bioelectric measurements demonstrated that basal short circuit 5 France; Hopital Cochin, Poincare, UMR1173 - Service de Microbiologie, current (I ) was significantly increased in CFBE wtCFTR-SLC26A9 6 7 sc Garches, France; CNRS UMR 9004, Montpellier, France; Centre Hospitalier (27.7 ± 2.8 μA/cm²) compared to CFBE wtCFTR (13.5 ± 1.1 μA/cm²) epithelial Universitaire de Nîmes, Département de Microbiologie, Nîmes, France; cells. In the presence of SLC26A9, the IBMX/FSK stimulated CFTR-mediated 8 − − Université de Montpellier, Hydrosciences Montpellier, CNRS, IRD, Montpellier, Cl current was significantly increased by 5-fold. The specific CFTR Cl 9 10 France; Centre Hospitalier de Foch, CRCM, Faris, France; Centre Hospitalier channel inhibitors CFTR -172 and GlyH-101 showed strongest effects. 11 inh Universitaire de Rouen, CRCM, Rouen, France; Centre Hospitalier de Foch, Conclusion: Taken together, we established a stable CF epithelial cell line − Pneumology Department, Suresnes, France for studies of SLC26A9 Cl channel function. Our results confirm a − constitutively active SLC26A9 Cl conductance in the presence of CFTR Mycobacterium abcessus (Mabs) lung infection is difficult to treat, especially − and a functional cooperativity of CFTR and SLC26A9 Cl channels. This in considering the absence of robust recommendations. As an add-on therapy vitro approach will be further applied to CFBE dF508del-CFTR epithelial to other antibiotics, Amikacin Liposome Inhalation Suspension (ALIS) may cells to pharmacologically modulate the F508delCFTR-SLC26A9 relation- be an interesting therapy. ship for future therapeutic approaches in CF. Objectives: To describe the clinical and microbiological evolution of CF patients treated with ALIS for a Mabs lung infection. Methods: ALIS is available in France for compassionate use since 2015. We retrospectively collected data from all consecutive CF patients treated with WS18 Nontuberculous mycobacterial infection: ALIS for a Mabs lung infection. ALIS’s data (time of start and end of outcomes, transmission and treatment treatment, delivery) were collected and compliance was indirectly calculated as the % of delivered drug declared by authorized pharmacies. Results: 11 CF patients (29 years) were treated with ALIS for a Mabs lung WS18.1 infection from 2015 to December 2019 in 3 CF centres (Montpellier, Paris- Cystic fibrosis airway microbiota associated with outcomes of Foch, Rouen). Associated pathogens mainly included P. aeruginosa (8/11), S. nontuberculous mycobacterial infection aureus (6/11), A. fumigatus (4/11). Clinical evolution was heterogeneous. 1 1 1 2 1 1 L. Caverly , M. Zimbric , M. Azar , K. Opron , J. Lipuma . University of ALIS was well tolerated, except in two patients who stopped ALIS due to 2 Michigan, Pediatrics, Ann Arbor, United States; University of Michigan, bronchospasm and hearing loss. Mabs was not found in 5 patients’ sputum Internal Medicine, Ann Arbor, United States after a delay of 3 months (min-max, 1 to 6). In 4 patients, Mabs was persistently detected. One patient deceased due to multi-organ failure Objectives: Pulmonary infections with nontuberculous mycobacteria without presenting clear Mabs infection. Microbiological data were not (NTM) are increasingly prevalent in people with cystic fibrosis (CF). available after ALIS treatment in one patient. Compliance was good in all 5 Clinical outcomes of NTM infection are highly variable, ranging from patients with conversion, and it was poor in 3/4 non-converters. significant morbidity to transient, self-resolving infection. Predictors of Conclusions: ALIS is associated with Mabs conversion in compliant NTM clinical outcomes to facilitate targeting of NTM treatment are lacking. patients, while clinical evolution may be heterogeneous being the results Studies in non-CF bronchiectasis have identified relationships between of different aspects of the disease and concomitant pathogens. We found a airway microbiota and NTM infection; however, these relationships in CF poor compliance to ALIS in non-converters patients, which may explain the are unclear. We sought to identify differences in airway microbiota lack of Mabs eradication. Even though larger data are needed and we associated with NTM clinical outcomes in CF. suggest that guidelines for Mabs lung infection in CF should include ALIS. Methods: Longitudinally collected sputum samples (n = 188) from 24 subjects with CF and NTM infection were selected from a sputum repository. Samples were collected between 3.5 years prior to, and up until the time of, the first NTM positive culture. Sputum DNA extractions underwent 16S rRNA gene sequencing and measurement of total bacterial load. Measures of airway microbiota were compared based on the primary Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S31

WS18.6 lung volume at lobar level, reduced significantly at inspiration (5.30 ± Preclinical evaluation of liposomes carrying bioactive lipids as an 2.36mL/L to 5.07 ± 2.23mL/L, p = 0.005). The CFQ-R respiratory domain immune therapeutic tool against in vivo infection with Mycobacterium increased with 9.3 ± 13 points (p = 0.09), which was correlated to the abscessus reduction in air-trapping (r = 0.72, p = 0.03) and in specific airway volume C. Riva1,2, N. Poerio2, M. Rossi1, F. De Santis2, E. Tortoli1, M. Fraziano2, (r = 0.72, p = 0.03). None of the spirometric parameters showed any D.M. Cirillo1. 1San Raffaele Scientific Institute, Milano, Italy, 2University of significant change. Rome ‘Tor Vergata’, Rome, Italy Conclusion: Orkambi significantly decreased lung hyperinflation in combination with a decrease in airway geometry. Both air-trapping and Objectives: MA abscessus (MA) in an emerging pathogen that affect the decrease in airway geometry were correlated with an improvement in individuals with lung pathologies such as chronic obstructive pulmonary quality of life. These results indicate that the FRI parameters, reflecting disease (COPD), bronchiectasis and, especially, cystic fibrosis (CF). regional and distal lung structures, are more sensitive to changes caused by Apoptotic-body like liposomes (ABLs) carrying bioactive lipids have been Orkambi than conventional spirometry. demonstrated to significantly enhance bactericidal response in macro- phages from CF patients and in bronchoalveolar lavage (BAL) cells from WS19.2 non-CF patients with pneumonia caused by different bacterial pathogens, Long-term safety of lumacaftor/ivacaftor therapy in persons with cystic irrespective of bacterial species and multidrug resistance. Our murine fibrosis aged 2–5 years homozygous for the F508del-CFTR mutation model of MA respiratory chronic infection was useful to assess the (F/F) therapeutic effect of different ABLs against this pathogen. 1 2 3 4 5 5 J. Hoppe , M. Chilvers , F. Ratjen , J.J. McNamara , C.A. Owen , S. Tian , Methods: We established a chronic pulmonary infection in immunocom- 5 5 6 1 R. Zahigian , A.G. Cornell , S.A. McColley . Children’s Hospital Colorado, petent C57Bl/6N mice up to 36 days with MA reference strain (ATCC 19977) 2 3 Aurora, United States; BC Children’s Hospital, Vancouver, Canada, The and at different time point mice were treated with 3 different ABLs (ABL/PA, 4 Hospital for Sick Children, Toronto, Canada; Children’s Hospitals Minnesota, ABL/PI3P and ABL/PI5P). Mice lungs were processed for microbiological 5 Minneapolis, United States; Vertex Pharmaceuticals Incorporated, Boston, and inflammatory analysis to establish the therapeutic effect of ABLs. 6 United States; Ann & Robert H. Lurie Children’s Hospital, Chicago, United States Results: After 30 days of treatment all the 3 ABLs induced a statistical reduction of bacterial count in the total lung when compared to the control Objectives: Assess long-term safety of LUM/IVA in a 96-week extension mice. The results also revealed that these 3 immunomodulatory com- (EXT) study (VX16-809-116) following a 24-wk open-label parent study in pounds induced a statistical reduction of the recruitment of total F/F persons with cystic fibrosis (pwCF) who began treatment at 2–5y. leukocytes, in particular of neutrophils and macrophages, into the Methods: pwCF received wt- and age-based doses of LUM/IVA. Primary bronchoalveolar lung spaces compared to the control mice. Despite the endpoint was safety. Secondary endpoints included SwCl, growth, lung absence of effect in granuloma reduction at parenchymal level, analysed by function, and pancreatic markers. histological lung sections, ABLs were also able to statistically decrease the Results: 57 pwCF enrolled; 56 (98.2%) had ≥1 AE, most mild (33.3%) or IFNy production during the course of treatment. moderate (50.9%). Conclusion: ABLs treatment statistically reduced both lung’s bacterial The most common AEs (>25%) were cough, nasal congestion, pyrexia, burden and inflammatory response during chronic MA infection. ABLs, rhinorrhea, and vomiting. Serious AEs, most consistent with underlying CF combined with an antibiotic therapy, could represent a novel immunother- or common childhood illnesses, occurred in 15 pwCF (26.3%). Respiratory apeutic strategy to treat pulmonary infection induced by drug- event AEs occurred in 5 pwCF (8.8%); none were serious or led to treatment resistant MA. discontinuation. Elevated transaminases, most mild or moderate, occurred in 10 pwCF (17.5%). 47 pwCF completed treatment; 2 discontinued due to transaminase elevations and 1 due to viral gastritis/metabolic acidosis. Improvements in secondary endpoints seen in the parent study were WS19 New insights into CFTR-modulating maintained in the EXT study (Table). All pwCF had baseline pancreatic therapies insufficiency (fecal elastase-1 [FE-1] < 200 μg/g). At Week 96 of EXT study, mean FE-1 increased and mean immunoreactive trypsinogen level decreased from baseline, consistent with improved pancreatic function. 6 WS19.1 pwCF had FE-1 values ≥200 μg/g at Week 96. The short-term effects of Orkambi (lumacaftor/ivacaftor) on regional and distal lung structures using Functional Respiratory Imaging E. Lauwers1,2, D. Belmans3, B. Mignot3, K. Ides1,2, K. Van Hoorenbeeck1,2, Baseline in Parent Study Absolute Change From C. Van Holsbeke3, G. Leemans3,J.DeBacker3, S. Verhulst1,2. 1University of Mean (SD) Parent Study Baseline at Week 96 in EXT study Antwerp, Faculty of Medicine and Health Sciences, Laboratory of Experimental Mean (95% CI) Medicine and Pediatrics, Wilrijk, Belgium; 2Antwerp University Hospital, Department of Pediatrics, Edegem, Belgium; 3Fluidda NV, Kontich, Belgium Sweat Chloride, 105.8 (7.3) −29.6 (−33.7 to − 25.5) mmol/L n=53 n=39 Objectives: The CFTR modulator Orkambi (lumacaftor-ivacaftor) has shown BMI z score 0.16 (0.82) 0.27 (0.05 to 0.48) modest benefits in previous research, but the exact effects in the CF lung n=57 n=47 − − remain unclear. Functional Respiratory Imaging (FRI), combining high- LCI2.5 8.81 (1.87) 0.20 ( 0.99 to 0.60) resolution CT imaging with computational fluid dynamics, provides n=22 n=17 a detailed information about the lung structure and function, allowing a FE-1, μg/g 11.3 (16.1) 132.6 (37.1) more in-depth understanding of treatment effects. The aim of this study was n=45 n=22 − a to provide insights intothe effects of Orkambi on lung functionality with the IRT, ng/mL 305.1 (351.3) 108.5 (47.9) n=52 n=41 change in specific airway volumes using FRI as the primary outcome. Methods: Orkambi-naïve patients aged ≥12 years homozygous for F508del IRT, immunoreactive trypsinogen; LCI, lung clearance index. were recruited in an open-label study. Before and after three months of aValues reported are mean (SE). treatment with Orkambi, FRI was used to look at regional information like [Selected Secondary Endpoints for PwCF in EXT Study 116] airway volume, lobar volume and air-trapping. Secondary outcomes included spirometry and the CFQ-R questionnaire for health-related Conclusion: LUM/IVA was generally safe and well tolerated, and treatment quality of life. effects were maintained for up to 120 weeks in pwCF aged 2–5 y, including Results: To date, ten subjects aged 23 ± 10 years completed all study visits. improvements in SwCl and growth. These data also suggest that pancreatic Concerning the FRI parameters, hyperinflation of the lung decreased, function improved for a small group of pwCF. indicated by a reduction in air-trapping and lobar volume at expiration Sponsor: Vertex Pharmaceuticals Incorporated (both p < 0.001). Specific airway volume, i.e. the airway volume corrected for S32 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

WS19.3 Conclusion: The inflammation expressed in the GI tract seems to decrease Bidirectional pharmacokinetic interactions between ivacaftor and after Orkambi®, while not accompanied by a change in GI symptom scores. lumacaftor Repeated sampling over time in a larger cohort is needed to draw P. Hanafin1, G. Rao1, E. Schneider-Futschik2. 1UNC Eshelman School of conclusions. Pharmacy, Chapel Hill, United States; 2The University of Melbourne, Parkville, Australia WS19.6 Impact of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) triple Introduction and aim: The pharmacokinetic (PK) data of ivacaftor- combination therapy on health-related quality of life (HRQoL) in lumacaftor, break-through cystic fibrosis transmembrane conductance people with cystic fibrosis (pwCF) homozygous for F508del (F/F): regulator (CFTR) modulator treatment, in cystic fibrosis (CF) patients is results from a Phase 3 clinical study limited. This study aimed at characterizing the PK of ivacaftor and 1 2 3 4 5 6 lumacaftor and their metabolites population PK and inter-individual C. Majoor , K. Van Brunt , C. Daines , I. Durieu ,I.Fajac , J. Goralski , H. Heijerman7, C. Knoop8, J. Booth2, S.M. Moskowitz2, J. Savage2, C. Wang2, variability (IIV) in 57 patients from 5 different CF centres undergoing 9 1 standard CFTR modulator therapy. A. Quittner . Amsterdam University Medical Centers, University of Methods: Secondary objectives were to identify patient characteristics Amsterdam, Department of Respiratory Medicine, Amsterdam, Netherlands; 2Vertex Pharmaceuticals Incorporated, Boston, United States; 3University of responsible for IIV and simulate ivacaftor and lumacaftor exposure for 4 different dosing regimens. In this retrospective observational study, clinical Arizona, Banner University Medical Center, Tucson, United States; Hospices Civils de Lyon, Adult Cystic Fibrosis Centre, Université de Lyon, Lyon, France, data and plasma ivacaftor, lumacaftor and metabolite levels were collected 5 6 from CF patients on standard ivacaftor-lumacaftor combination APHP - Centre - Université de Paris, Paris, France; Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, United States; (125 mg + 200 mg). 7 8 PK modelling, covariate analyses, and explorative Monte Carlo dosing University Medical Center Utrecht, Utrecht, Netherlands, Hôpital Erasme, 9 ’ simulations (MCS) were performed using nonlinear mixed-effects model- Department of Chest Medicine, Brussels, Belgium; Nicklaus Children s ’ ling. Bootstrap and visual predictive checks were used to determine model Research Institute, Nicklaus Children s Hospital, Miami, United States adequacy. Objectives: Efficacy and safety of ELX/TEZ/IVA, a novel CFTR modulator Results: In total, 98 measurements were obtained from 57 patients. In the therapy, were evaluated in a Phase 3, randomised, double-blind, active- final model, the estimated clearance (CL) and volume of distribution (V1) control study (NCT03525548) in pwCF ≥12 years old with F/F genotypes; were 25.1 L/h (ivacaftor) and 2.38L/h (lumacaftor) and 86 L (lumacaftor), pwCF were randomised 1:1 to receive ELX/TEZ/IVA or TEZ/IVA for 4 weeks, respectively, for an adult patient. Half-life was reported as 9 h for ivacaftor after a 4-week TEZ/IVA run-in. Primary and secondary outcomes, including and 26 h for lumacaftor, respectively. MCS revealed that a substantial marked improvement in clinical outcomes and CFQ-R respiratory domain number of patients may not achieve the PK/pharmacodynamic target (RD) scores, were reported previously. The aim of this analysis is to report trough level (12.7 μg/mL for lumacaftor and 0.10 μg/mL for ivacaftor) when effects of ELX/TEZ/IVA vs TEZ/IVA on 11 other CFQ-R domains. administering the label-recommended doses for ivacaftor-lumacaftor Methods: The CFQ-R, a validated HRQoL instrument, was administered at combination therapy. study visits in the Phase 3 trial. Absolute change from baseline in CFQ-R RD Conclusion: A large inter- and intra-variability was observed in PK among was a prespecified secondary endpoint; other domains were prespecified cystic fibrosis patients. Cytochrome, p-glycoprotein and plasma protein other endpoints. A mixed-effects model for repeated measures was used to binding could partially explain the variabilities, though a large part of the calculate the change from baseline in CFQ-R domain scores vs TEZ/IVA. variability remains unclear. Minimal clinically important differences have not been determined for non-RD domains; score increases signify improvement. WS19.5 Results: 107 pwCF were randomised and dosed in the treatment period. ® Decrease of faecal calprotectin in adults after initiation of Orkambi ,a Improvements with ELX/TEZ/IVA over TEZ/IVAwere seen in 7 of the 11 non- Registry-based study RD scores (Table), including vitality, physical functioning, and health M. Gilljam1, A. Hedborg2, I. de Monestrol2, U. Lindberg3, C. Krantz4, perceptions. L. Hjelte2, A. Lindblad5. 1Gothenburg CF Centre, Sahlgrenska University Hospital, Gothenburg, Sweden; 2Stockholm CF-Center, Karolinska University 3 Hospital, Huddinge, Sweden; Lund University Hospital, Dept Clinical Sciences, CFQ-R Domain Mean CFQ-R Domain Mean 4 Respiratory Medicine and Allergology, Lund, Sweden; Uppsala CF Centre, difference vs difference vs Uppsala University Hospital, Uppsala, Sweden; 5Gothenburg CF Centre, Dept of TEZ/IVA (95% TEZ/IVA (95% Paediatrics, Sahlgrenska University Hospital, Gothenburg, Sweden CI) at 4 weeks, CI) at 4 weeks, points points Objectives: Orkambi® is since 1st July 2018 available for restricted prescription in Sweden. Follow-up after 1, 3, 6, 9 and 12 months is Physical Functioning 11.8 (6.5, 17.0) Health Perceptions 9.5 (3.6, 15.4) mandatory and data is entered in the National CF Registry. F-calprotectin, a Vitality 12.5 (6.0, 19.0) Weight 12.5 (4.1, 20.9) Emotional Functioning 1.8 (−1.4, 5.1) Digestion 0.9 (−5.1, 6.9) marker of intestinal inflammation and reported elevated in many CF Body Image 2.4 (−1.7, 6.6) Role Functioning 6.0 (1.1, 10.9) patients, was recommended for analysis at start and after 3 and 12 months. Eating Problems 6.8 (1.3, 12.4) Social Functioning 5.4 (1.2, 9.6) Methods: All adults (>18 years) with f-Calprotectin obtained at start of Treatment Burden 3.4 (−2.0, 8.7) Orkambi® and at a follow-up visit ≥3 months later were included. If > 1 follow-up value was available then the latest result was used. The CFQR GI *Analyses with P values <0.05 are bolded; these P values are considered nominal symptom score and the CFQUEST GI score were included in the analysis. because analyses for CFQ-R non-respiratory domains were not controlled for Results: Forty-four adults (25 males) with a mean age of 31.9 (SD 10.1) multiplicity. years were included. The median f-Calprotectin decreased from 93.5 (8– [Absolute change from baseline in CFQ-R non-respiratory domain scores*: ELX/ TEZ/IVA vs TEZ/IVA] 6000) at start to 48.5 (5–249) (p < 0.001, Wilcoxon signed rank test) after a median follow-up time of 4 (3–15) months. The mean CFQR GI symptom Conclusion: ELX/TEZ/IVA improved multiple aspects of HRQoL in pwCF score at start and follow-up did not change and was 78.1 (SD 17.5) and 79.0 with F/F genotypes over TEZ/IVA, illustrating broad benefits of treatment (SD18.7) respectively. The CF-QUEST GI score was also unchanged and 83.9 beyond previously reported clinical improvements. (15.7) and 85.4 (SD 16) respectively. The Spearman correlation between f- SPONSOR: Vertex Pharmaceuticals Inc. Calprotectin and CFQR GI symptoms was weak at start (N = 39, r = 0.109, p = 0.51) and follow-up (N = 41, r = 0.111, p = 0.49) and also between f- calprotectin and CF-QUEST GI at start (N = 35, r = 0.04, p = 0.82) and follow- up (N = 30, r = 0.01, p = 0.95). Thirteen (30%) patients had increased f- calprotectin (>150 mg/kg) at start and 3 (7%) at follow-up. Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S33

factors have shown their fixations in intron 1, 11 and 21 enhancers of CFTR WS21 CFTR gene: from regulation to phenotype gene. This variant could affect the recruitment of regulatory elements. Conclusion: Some significantly variants are identified in CBAVD patients WS21.1 with incomplete genotype, notably one regulatory variant localised in the Modules of co-expressed genes in blood samples reveal potential intron 21 enhancer of CFTR gene. This region plays an important role in modifier genes of diabetes and lung function in cystic fibrosis regulation of CFTR locus in combining with 3 others intestinal specific 1 2 1 1 1 3 enhancers. F. Pineau , D. Caimmi , M. Magalhaes ,E.Fremy, A. Mohamed , L. Mely , S. Leroy4, M. Murris5, M. Claustres1, R. Chiron2, A. De Sario1. 1University of 2 WS21.3 Montpellier, Montpellier, France; CHRU Montpellier, Montpellier, France; 3 4 5 Overview of shared benefits from the 6-year long collaboration CHRU Lyon, Hyeres,̀ France; CHRU Nice, Nice, France; Larrey Hospital, between the French Cystic Fibrosis Registry and the CFTR-France Toulouse, France genetics database Objective: We aimed to identify genes and pathways that (i) contribute to S. Sasorith1, 2, C. Bareil1,2, L. Lemonnier3, C. Dehillotte3, A. Farge3, the pathogenesis of cystic fibrosis (CF) and (ii) modulate the associated M.-P. Audrezet4, C. Ferec4, E. Girodon5, T. Bienvenu5, P. Fanen6, C. Mekki6, comorbidities. E. Bieth7, V. Gaston7, P. Fergelot8, M.-P. Reboul8, F. Dufernez9, A. Pagin10, Methods: The study population included 51 CF patients and 24 controls G. Lalau10, M.-C. Malinge11, F. Cabet12, A. Bergougnoux1, 2, M. Claustres2, from the MethylCF cohort. CF patients carried the homozygous p.F508del C. Raynal1, 2. 1CHU Montpellier, Montpellier, France; 2Université de mutation. We generated the transcriptome of blood samples by RNA-seq Montpellier, EA7402, Montpellier, France; 3Vaincre la Mucoviscidose, Paris, and identified modules of co-expressed genes using Weighted Gene France; 4CHU Brest, Brest, France; 5AP-HP Hôpital Cochin, Paris, France; 6AP- Correlation Network Analysis (WGCNA). Then, we calculated the correlation HP Centre Hospitalier Henri Mondor, Créteil, France; 7CHU Toulouse, Toulouse, between gene modules (eigengene) and the clinical data of the cohort. France, 8CHU Bordeaux, Bordeaux, France; 9CHU Poitiers, Poitiers, France; Results: We identified 28 modules of co-expressed genes in the blood 10CHU Lille, Lille, France; 11CHU Angers, Angers, France; 12Hospices Civils de transcriptome of the cohort. Gene modules that correlated with clinical Lyon, Lyon, France features of interest were analysed in more detail. Lung function and BMI best correlated with the dark turquoise module and a gene ontology (GO) Objectives: The collaboration that started in 2013 between the French CF analysis highlighted terms related to cell-cell adhesion and cell adherence Registry and the CFTR-France database aims to compare and to complete junctions. FLNA, a hub gene of this module, encodes Filamin A, an actin- clinical and genetics data collected in both databases. binding protein that interacts with integrins to regulate the leukocyte Methods: Patients from the two databases were paired on their last name, trafficking. first name, date of birth, gender, and disease-causing variations. Diabetes and glycated hemoglobin levels correlated with the light yellow Results: After the first round of comparison, 2141 patients were paired module. The GO analysis of this module revealed terms related to vesicle including 1924 patients that fully matched. Clinical data provided by the transport and platelet activation. Among the hub genes of this network Registry for the 2011–2013 period enabled to fill-in the missing phenotypic were integrin genes (ITGB3, ITGA2B, ITGB5). data of patients in CFTR-France and consequently to re-classify several Finally, the presence of a chronic P. aeruginosa infection negatively patients in different phenotypic groups. On the other hand, this data correlated with the magenta module that is enriched with terms related sharing allowed to correct and/or complete 110 genotypes in the Registry. to heme metabolic process. In 2019, we started to update clinical data of the matched patients with the Conclusion: Inspection of gene modules that correlated with the presence 2014 to 2017 follow-ups in the Registry, that will enable to assess the of diabetes and lung function pointed to cell adhesion, leukocyte trafficking clinical course of those patients. We are currently sharing data from a new and production of reactive oxygen species as central mechanisms in cystic dataset that comprises 2781 individuals from CFTR-France with no Registry fibrosis-related diabetes and pulmonary function decline. Blood is an ID, including 135 children born after 2012 and 126 asymptomatic informative surrogate tissue to study lung disease and diabetes in CF compound heterozygotes (excluded from the first dataset). In parallel, we patients. WGCNA is much valuable to analyse -omic datasets in CF as are continuing correction and classification of the sequence variations patient cohorts are inevitably small. collected in the French Registry. Thus, 877 entries (corresponding to 819 different variants) were cleaned and, when possible, corrected and WS21.2 annotated as CF-causing, varying clinical consequence, CFTR-RD causing, Identification of CFTR cis-regulatory variants benign or variants of unknown significance. The annotation was based on 1 1, 2 1, 3 1,2 1,2 data from CFTR-France and from the CFTR1 and CFTR2 databases. M. Collobert , K. Rouault ,C.L’Hostis , M.-P. Audrézet , C. Férec , 1, 2 1 Conclusion: Overall, this valuable collaboration will allow to refine S. Moisan . UBO, Inserm, EFS, UMR 1078, GGB, Genetics, Brest, France; 2 3 genotype/phenotype relationships in both databases in the light of Molecular Genetics and Histocompatibility Laboratory, Brest, France; Gaétan patients’ clinical evolution over the years and to improve the quality of Saleün Association, Brest, France data collected retrospectively as well as prospectively. Objectives: Although, more than 2075 variants have been discovered in Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, respon- WS21.4 sible of Cystic Fibrosis (CF) or one of CFTR-related disorders, the congenital Different protective effects on pancreatic structure in mild CFTR gene bilateral absence of vas deferens (CBAVD), some patients have an variants in Russia incomplete genotype or present extremes phenotypes. Development of S. Krasovskiy1,2,3, I. Butyugina3, Y. Gorinova4. 1Federal Pulmonology Research chromatin conformation study techniques has identified several long- Institute, Federal Medical and Biological Agency of Russia, Moscow, Russian range regulatory elements of CFTR gene. Federation; 2Research Centre for Medical Genetics, Moscow, Russian Methods: 17 cis-regulatory regions of CFTR gene have been sequenced in Federation; 3Municipal Clinical Hospital named after D. Pletnev, Moscow, 63 CBAVD patients. Russian Federation; 4Federal State Autonomous Institution of Russian Results: European population, some variants display a frequency signifi- Federation Ministry of Health ‘National Medical Research Center for Children’s cantly different. In particular, one variant located in cis-regulatory region of Health’, Moscow, Russian Federation intron 21, is 40 times more frequent in this group. Activity tests in Caco-2 intestinal cells have shown strong cooperative effects of the intron 21 Objectives: The duration of the protective effect of mild CFTR variants on enhancer with several strong enhancers specific to intestinal cells (Intron 1, the pancreas structure is not fully understood. According to Russian CF 11 and at + 15.6 kb of the CFTR gene) on CFTR promoter activity. Insertion of Registry (2018), there is a high total frequency of mild mutations, among the interest variant into intron 21 shows a strong decrease of CFTR which the leading mutations are E92K- 3.04%, 3849+10kbC>T- 2.38%, promoter activity and the loss of enhancers cooperation. Chromatin L138ins − 1.35%, in adult patients: 4.55%, 5.99%, 1.79%, respectively. immunoprecipitation (ChIP) analyses of HNF1a and EP300 transcription Variants E92 K and L138ins are extremely rare in Europe and are more common in Russia. S34 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

Aim is to study the relationship between the presence of mild mutation and WS21.6 the structure of pancreas. Clinical consequences of W1282R variant in Russian cystic fibrosis Methods: The analysis included 72 adult patients: 30 patients with E92 K, patients 34- with 384 9 + 10kbC>T and 8 with L138ins. An abdominal CT scan was N. Petrova1, N. Kashirskaya1, T. Vasilyeva1, A. Voronkova1, E. Kondratyeva1, performed with intravenous contrast and size and structure of the pancreas V. Sherman1, S. Krasovskiy2, E. Amelina2, V. Galkina1, E. Ginter1, S. Kutsev1, were evaluated. The conclusion was set based on the results: complete R. Zinchenko1,3. 1Research Centre for Medical Genetics, Moscow, Russian atrophy, partial atrophy or no changes. Federation; 2Scientific Research Institute of Pulmonology of the Federal Results: Median age of patients was 27.5 (12.0) years, groups did not differ Medical and Biological Agency, Moscow, Russian Federation; 3N.A. Semashko in age. Among patients with E92K: 9 (30%) patients had atrophy, 3 (10%) National Research Institute of Public Health, Moscow, Russian Federation had partial atrophy, 18 (60%) had no changes, for 3849+10kbC>T: 2 (5.9%) had atrophy, 3 (8,8%) had partial atrophy, 34 (85.3%) had no changes, for Objectives: According to the 2017–2018 Russian CF Patients Registry the L138ins: 1 (12.5%) had atrophy, 2 (25%) had partial atrophy, 5 (62.5%) had spectrum of identified CFTR mutations exceeds 200 various CF causing no changes. Among patients younger than 30 years old, atrophy was variants. The frequency of W1282R (c.3844T>C) variant is about 0.55% (38 detected in 7 patients and among them 6 patients were carriers of E92 K. CF patients). The aim is to study clinical presentation in CF patients with Conclusion: Among the discussed mild mutations E92 K has the least W1282R variant. protection on the pancreas structure, meanwhile the largest protection was Methods: The age at CF diagnosis, pancreatic status, lung function, established for 3849+10kbC>T. microbial infection, nutritional status (BMI), the presence of meconium ileus (MI) or DIOS, diabetes and severe liver disease were evaluated in three WS21.5 groups: 1–28 patients carrying W1282R and severe variant in trans; 2–46 Response to ivacaftor of the rare CFTR variants W57G and A234D in 3849+10kbC>T/F508del patients; 3–90 F508del/F508del patients. Patients intestinal organoids and Fisher Rat Tyroid (FRT) cells from group 2 and 3 were matched for gender and age with group 1. 1 1 1 2 2 2 Results: Age at diagnosis was significantly lower in group 1 than in group 2 V. Lotti , K. Kleinfelder , A. Farinazzo , M. Bertini , F. Pauro , D. Treggiari , 1 1 1 2 3 3 (1.93 ± 0.63 yrs vs 8.82 ± 1,12 yrs; p < 0.001). Pancreatic insufficiency was J. Conti ,S.Preato, F. Quiri , E. Pintani , L. Rodella , A. Cerofolini , 3 3 2 4 1 2 more frequent in group 1 than in group 2 (85.7% vs 11.8%; p < 0.001). The F. Catalano , F. Tomba , M. Cipolli , H. DeJonge , C. Sorio , P. Melotti , 1 BMI of adult patients was higher in groups 1 (18.31 ± 1.15) and 3 CFF Theratyping Group*. University of Verona, CFTR Lab Daniele Lissandrini, 2 (18.54 ± 0.54) than in group 2 (16.32 ± 0.44; p < 0.05). The FEV (%) in Dept. Medicine, Verona, Italy; Azienda Ospedaliera Universitaria Integrata 1 3 group 1 was lower than in group 3 (58.91 ± 7,20 vs 91.05 ± 3.37; p < 0.02). Verona, Cystic Fibrosis Centre, Verona, Italy; Azienda Ospedaliera 4 The sweat chloride in group 1 (107.52 ± 4.68) was higher than in group 2 Universitaria Integrata Verona, Endoscopy Unit, Verona, Italy; Erasmus (81.61 ± 3.24; p < 0.0001) but did not differ from group 3 (105.82 ± 2.25). University Medical Center, Gastroenterology and Hepatology, Rotterdam, There were no differences in the respiratory tract pathogenic microflora Netherlands and the frequency of CF complications (MI, DIOS, diabetes, liver damage) Background: The effect of ivacaftor (VX770) on the rare CF causing variant between the three groups. W57G (c.169T>G), in trans with the A234D (c.701C>A) is unknown. W57G is Conclusion: W1282R variant is seemed to lead to severe disease unaffected by treatment with VX809 and/or VX770 in C[PT1] FBE cell phenotype with PI, similar to F508del. model (Han et al, JCI, 2018). We would like to thank Cystic Fibrosis Patient Registry of Russian Methods: Intestinal organoids (OG) were developed from rectal biopsies of Federation for providing access to patient data and thank the individual a 37 years old female of Italian origin carrying CFTR genotype W57G/ regional CF centres representatives for allowing the use of data (http:// A234D with abnormal sweat Cl (112 mmol/L), pancreatic sufficiency, lung mukoviscidoz.org/). infection (Pseudomonas aeruginosa), impaired lung function (FEV1:65% of The research was partially supported by grant RFFR 18-015-00090 and predicted value), bilateral bronchiectasis, kidney stones, recurrent sinusitis. within the state task of the Ministry of Education and Science of Russia. ICM, NPD and beta adrenergic optical sweat test were consistent with diagnosis. OG were tested by Forskolin (FSK) Induced Swelling assay. CFTR function was measured by 24 well TECC methodology in FRT cells expressing W57G or A234D CFTR in the presence and absence of ivacaftor. WS23 CF Disease is evolving: latest data from Results: Combination of FSK 0.8 μM and VX770 3 μM induced a significant Registries swelling (3.5 ± 1.7 fold of increase vs untreated, n = 3; p < 0.05) of organoids after 60 min. TECC measurements in FSK-treated FRT cells showed undetectable activity for W57G in presence or absence of VX770 but WS23.1 response for A234D to FSK 3 μM alone (17% of wild type) with an increased Time trends in the incidence of cystic fibrosis: review of the 40-year response in presence of VX770 (56% of wild type). experience of Brittany (France) and comparison with other regions Conclusions: W57G variant is disease causing and nonresponsive (FRT worldwide 1 1 1, 2 3 4 5 cells), while successful targeting of this CFTR genotype in intestinal V. Scotet ,C.L’Hostis , M.-P. Audrezet , S. Ramel , G. Rault , M. Dagorne , 6 7 8 1, 2 1 organoids and FRT cells by VX770 suggest this potentiator as therapeutic E. Deneuville , H. Journel , P. Farrell , C. Férec . Inserm UMR 1078, Brest, 2 candidate for patients carrying A234D variant. The overlapping results France; CHU Brest, Laboratoire de Génétique Moléculaire, Brest, France; 3 4 5 obtained in different CF cellular models might provide a strong rationale CRCM Mixte, Roscoff, France; LEPS, Paris, France; CRCM Pédiatrique Rennes/ 6 for treatment with CFTR targeted drugs in this and other similar cases. Saint Brieuc, Saint Brieuc, France; CRCM Pédiatrique Rennes/Saint Brieuc, 7 8 *CFF Theratyping Group: Millen, L; Musisi, I; Thakerar Patel, A; Raraigh, K; Rennes, France; CRCM Mixte, Vannes, France; University of Wisconsin School Oyem, P; Allaire, N; Benjamin, D; Bihler, H; Bridges, R; Cutting, G; Mense, of Medicine and Public Health, Madison, United States M; Sivachenko, A; Thomas, P. Objectives: Implementation of newborn screening (NBS) for CF has Supported by: LIFC Associazione Veneta-Onlus; Italian CF Research allowed a better monitoring of the incidence of CF and its evolution over Foundation: FFC#7,16,13/2018). time. This study aims: 1°) to analyse time trends in the incidence of CF over a long period (43 years) in an area where CF is frequent (Brittany, France) and where NBS is implemented since 30 years (1989); 2°) to compare the current incidence and time trends to those observed in other areas/ countries worldwide, considering the public health policies implemented on CF in those areas. Methods: This study enrolled the CF patients born in Brittany over the 1975–2017 period (n = 554). Time trends in incidence were analysed using Poisson regression and the average percent change (APC). They were Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36 S35

compared to those reported in Veneto-Trentino Alto Adige (Italy), Israel, of percent predicted FEV1 (ppFEV1) for adults attending UK CF centres, Victoria (Australia), and Wisconsin and Colorado (US). The current accounting for age, sex and pancreatic status. incidence was compared to that observed in the other European countries Methods: Data on ppFEV1 were obtained from the UK Cystic Fibrosis that recently reported their experience in NBS for CF. registry from 2015–2017. Patients post-lung transplant were excluded. Results: Over the 43-year period, the incidence of CF was estimated at Multilevel modelling was conducted to calculate the annual rate of change 1/2811 in Brittany. Poisson regression showed that the incidence decreased in lung function accounting for sex and age in pancreatic insufficient (PI) significantly over the study period (annual APC: − 1.8%, p < 0.0001). It and sufficient (PS) adults. dropped from 1/1983 over the 1975–79 period to 1/3992 over the 2015-17 Table 1. period, leading to a decline of 50.3% (p = 0.0019). Comparison with other Rate of Decline in ppFEV1 predicted in One Year in Adults with CF areas revealed that: 1°) most areas reported a decline in incidence, but not all; 2°) the most significant declines were observed in areas where a carrier Pancreatic Insufficient Pancreatic Sufficient screening program was implemented; 3°) although halved, the incidence of CF in Brittany remained among the highest reported in Europe. N Mean 95% N Mean 95% annual Confidence annual Confidence Conclusion: This study highlights how the incidence of CF has evolved in change intervals change intervals an area where CF is frequent. It reports a clear drop in incidence that results in in from a complex mixture of factors. Comparison with other areas help to ppFEV1 ppFEV1 better understand factors influencing the incidence, which depends notably on the health policies implemented on CF. 18–28 years Females 1124 −1.76 −2.06 to −1.46 171 −1.01 −1.84 to −0.19 Males 1287 −1.61 −1.91 to −1.31 119 −0.53 −1.39 to 0.33 WS23.2 29–39 years Females 608 −1.49 −1.85 to −1.13 133 −0.74 −1.47 to −0.02 Epidemiology of European adults with cystic fibrosis Males 851 −1.31 −1.60 to −1.02 125 −0.86 −1.96 to 0.23 1 2 3 4 1 5 40–50 years Females 217 −1.42 −1.98 to −0.87 94 −0.79 −1.60 to 0.01 A. Zolin , L. Naehrlich ,A.Fox , M. Krasynk , A. Orenti , J. van Rens , − − − − − 1 2 Males 301 1.15 1.59 to 0.71 109 0.13 1.01 to 0.75 on behalf of the ECFSPR. University of Milan, Milano, Italy; Justus-Liebig- 51+ years Females 81 −1.61 −2.64 to −0.58 92 −0.51 −1.45 to 0.43 3 University Giessen, Giessen, Germany; European Cystic Fibrosis Society Males 148 −1.06 −1.66 to −0.46 75 0.86 −0.23 to 1.95 Patient Registry, Verona, Italy; 4European Cystic Fibrosis Society Patient Registry, Lviv, Ukraine; 5University Hospital Leuven, Leuven, Belgium − − Results: Overall, ppFEV1 declined annually by 1.52% (95% CI: 1.66 to The European Cystic Fibrosis Society Patient Registry (ECFSPR) collects −1.38%) and −0.55% (95% CI: −0.86 to −0.23%) in those PI and PS anonymised demographic and clinical data from consenting people with respectively. In PI patients, females had a greater rate decline in ppFEV1. CF in Europe. The aim of this study is to describe the adult population with The fastest rate of decline was observed in PI individuals between the ages CF in Europe. of 18–28 years (Table 1). The pattern was more inconsistent between sexes We considered patients of 18 years or older in the 2017 data, the latest year and age categories in those PS (Table 1). The largest annual rate of decline in of follow-up available. Countries with a coverage below 80% were not ppFEV1 was seen in 18–28 years old females, with the effect reducing with considered when reporting figures by country. Percentages are computed age. In contrast, men aged 29–39 years had the largest decrease in ppFEV1 for categorical variables; quartiles for numerical variables. and by age 51+ years there was no statistically significant change. For the year 2017, the ECFSPR database contains data of 48,204 patients Conclusions: PI individuals had three times the average rate of decline of from 35 countries. 24,491 (51.3%) are adults. those PS. Younger adults, especially females tended to have a faster rate of The percentage of adults varies from 6.5% in Albania to 62.8% in Sweden. decline and need close monitoring. The proportion of adult females varies from 37.1% in North Macedonia to Funded by UK CF Trust (SRC 012) 59.6% in Slovenia. The highest percentage of patients living with lung transplant is 22.7% in Slovenia. WS23.4 Considering patients of 18–29 years, the lowest percentage of chronic Investigating associations between air and the severity of Pseudomonas Aeruginosa is 30.6% in France, the highest is 79.4% in Serbia. cystic fibrosis in Great Britain For chronic Burkholderia cepacia complex species the lowest percentage of M. Saleem Khan1, N.J. Simmonds2, M.B. Toledano1, 3, R. Cosgriff4, F.B. Piel1. infected patients is 2.5% in Italy, the highest 20.6% in Serbia. The lowest 1UK Small Area Health Statistics Unit, School of Public Health, Faculty of percentage of CF related diabetes is 7.3% in Slovak Republic, the highest Medicine, Imperial College London, London, United Kingdom; 2Adult Cystic 34.2% in the Czech Republic. Median of BMI changes from 18.8 in the Fibrosis Centre, Royal Brompton Hospital, London, United Kingdom; 3MRC 2 Russian Federation to 22.4 kg/m in Luxembourg. Considering patients not Centre for Environment and Health, School of Public Health, Faculty of transplanted, we observe a percentage of patients with FEV1% below 40% Medicine, Imperial College London, London, United Kingdom; 4Cystic Fibrosis that varies from 3.0% in Denmark to 28.5% in the Russian Federation. Trust, London, United Kingdom We considered only countries with a coverage of 80% or higher, for a realistic reflection of CF and observed variation among those countries. Objectives: Our aim was to estimate the effect of on disease Data show that the percentage of adult population is higher in North severity among patients with cystic fibrosis (CF) in Great Britain (GB). Europe, infections are more frequent in Eastern Europe and growth and Methods: We used a semi-ecological small-area study design. High- lung function are worse in Eastern Europe. Further investigation is required resolution (100 × 100 m) modelled surfaces of NO2 (2009) and PM2.5 (2010) to investigate differences in healthcare systems to plan an adequate concentrations in GB, based on land use regression models, were obtained development of CF care services for adult CF people. from the Small-Area Health Statistics Unit, Imperial College London. Exposures were assigned based on postcode of residence. CF data for 2016 WS23.3 were obtainedfromthe UKCFRegistry,acentraliseddatabasewhich,for 2016, The average rate of lung function decline in adults with cystic fibrosis in included records of 9,297 patients from all CF specialist centres across GB. We the United Kingdom: data from the UK Cystic Fibrosis Registry used two common proxies of disease severity: the percent predicted forced L. Caley1, L. Smith2, H. White3, D. Peckham4. 1University of Leeds, Leeds, expiratory volume in 1 second (ppFEV1%) and the annual number of days on United Kingdom; 2University of Leeds, Clinical and Population Science intravenous antibiotics for pulmonary exacerbation (#IVdays). Linear and Department, Leeds, United Kingdom; 3Leeds Beckett University, Nutrition and Poisson regressions, adjusted for age, gender and deprivation (2015 Index of Dietetic Group, Leeds, United Kingdom; 4Leeds Teaching Hospitals NHS Trust, Multiple Deprivation), were used to explore the association between Department of Respiratory Medicine, Leeds, United Kingdom exposures (NO2 and PM2.5) and outcomes (ppFEV1% and #IVdays). Results: Excluding CF patients < 6 years old (n = 1,493) and those with

Objectives: The annual rate of change in lung function is an important a missing postcode (n = 64), 7,740 patients were included. Mean ppFEV1% measure of disease progression. We sought to determine the rate of decline and #IVdays were 70.5% (standard deviation (SD): 24%) and 19 (SD: 31) days, respectively. Annual mean concentrations ranged between 2.6 and S36 Workshops / Journal of Cystic Fibrosis 19S2 (2020) S1–S36

3 3 3 66.8 μg/m for NO2 (WHO guideline: 40 μg/m ), and 3.1 and 18.3 μg/m for Conclusions: The annual prevalence of NTM infection in children and 3 3 PM2.5 (WHO guideline: 10 μg/m ). An increase of 10 μg/m in NO2 was young people with CF in the UK has increased between 2010 and 2018. associated with a 0.58% decrease in ppFEV1% (p = 0.058), while an increase Given the lack of high-quality evidence to guide the management of NTM 3 of 10 μg/m in PM2.5 was associated with 1.2 more #IVdays per year pulmonary disease in children with CF, this highlights the urgent need for (p<0.001). further research to establish the most effective strategies. Conclusion: This study of patients with CF in GB using 2016 UK CF Registry data provides novel preliminary evidence that higher exposure to PM2.5 is WS23.6 associated with an increase in the #IVdays. The findings also suggest that Impact of the French high emergency program in cystic fibrosis: NO2 concentrations might be associated with a small decrease in ppFEV1%. survival comparison between France and Canada Further analyses to confirm these results are ongoing. 1 1 2 3 3 A. Coriati , J. Sykes , S. Stanojevic , L. Lemonnier , C. Dehillotte , P.-R. Burgel4, A. Stephenson1. 1St Micheal’s Hospital, Toronto, Canada; WS23.5 2 SickKids Research Institute, Translational Medicine, Toronto, Canada; Epidemiology of nontuberculous mycobacteria infection in children 3 4 Vaincre la Mucoviscidose, Paris, France; Université de Paris, Institut Cochin, and young people with cystic fibrosis: analysis of UK Registry data Paris, France 2010–2018 N. Zainal Abidin1,2, A.I. Gardner1, I.J. Haq1, 2, M. Thomas2, M. Brodlie1, 2. Survival of the CF population has dramatically improved over the past 3 1Translational and Clinical Research Institute, Newcastle University, Faculty of decades in several countries with patients living well into adulthood. Medical Sciences, Newcastle upon Tyne, United Kingdom; 2Great North Transplantation is the one therapy that can dramatically change survival Children’s Hospital, Newcastle upon Tyne Hospitals National Health Service estimates within a short time-frame which may be contributing to Foundation Trust, Department of Paediatric Respiratory Medicine, Newcastle improved survival. France implemented a high emergency (HE) program upon Tyne, United Kingdom at a national level for lung transplant listingin 2007. Objectives: Our aims were to Objectives: Respiratory infection with nontuberculous mycobacteria 1. compare post-transplant survival between Canada and France and (NTM) is a growing concern in the paediatric cystic fibrosis (CF) population. 2. determine the impact of the HE program on deaths in France We aimed to study the prevalence and risk factors for NTM infection in compared to Canada. children and young people using data from the UK CF Registry. Methods: Annualised data from 2010–2018 were obtained from the UK CF Methods: This population-based cohort study utilised data from 1992– Registry on request. Annual trends in prevalence of NTM infection and 2016 from two longitudinal national CF Registries. A total of 6259 Canadian species in individuals aged 16 or less were determined. Univariate analysis (from 42 Canadian CF clinics) and 9082 French CF patients (from 47 French was performed comparing key clinical factors with NTM status. Significant CF centres) were analysed. The Kaplan-Meier method (and log rank test) factors identified at the univariate level were then used to generate a was used to estimate the median post-transplant survival. A Fine and Gray multivariate logistic regression model. cumulative incidence model was used to assess time to transplant with Results: Pooled analysis revealed 6373 unique individuals with CF aged 16 death as competing risk in the era before and after the HE program began. or less at some point during the 9-year study period of which 553 were Results: Overall, demographic and clinical characteristics were comparable aged 16 or less at first recorded NTM isolation (8.7%). The annual between the two countries. Median survival time post-transplant was prevalence of individuals with NTM positive respiratory samples increased higher for France (14.1 years; 95% CI: 11.8–16.8) compared to Canada (10.4 every year between 2010 (76 [2.0%]) and 2016 (144 [3.5%]) with highest years; 95% CI: 8.9–12.1). Between 2002–2006, patients were more likely to prevalence recorded in 2018 (147 [3.6%]). Using data made available from die than to receive a transplant with no difference between countries (HR: 2014 onwards amongst NTM positive patients, Mycobacterium abscessus 1.13, 95% CI: 0.91–1.40). However, between 2008–2012, patients in France was the most prevalent species followed by Mycobacterium avium complex were significantly more likely to receive a transplant than die compared to and Mycobacterium chelonae making up on average 56%, 23% and 5% of Canada (HR: 1.73, 95% CI: 1.45–2.07). cases each year respectively. The most significant clinical factors associated Conclusion: Our study found there was improved access to transplant and with NTM infection were allergic bronchopulmonary aspergillosis (odds reduced pre-transplant deaths after the implementation of the HE lung − ratio [OR], 2.97, p = 7.8 × 10 14) and Pseudomonas aeruginosa infection (OR, transplant program in France. Further research is needed to understand − 1.75, p = 8.8 × 10 7). differences in access to transplant between countries. Journal of Cystic Fibrosis 19S2 (2020) S37–S54

E-Posters

ePS1.02 ePoster Session 1: Multiple challenges in Use of non-invasive ventilation in cystic fibrosis in the UK: physiotherapy developments over a decade L. Warnock1, A. Gates1, W.G. Flight1. 1Oxford Adult Cystic Fibrosis Centre, ePS1.01 Oxford, United Kingdom Long-term outcomes of adult patients with cystic fibrosis requiring Introduction: There is limited evidence to guide the use of non-invasive non-invasive ventilation ventilation (NIV) in CF. A previous survey of UK CF centres in 2009 indicated L. Wadsworth1, D. Riley1, R.J. Bright-Thomas1,2. 1Manchester Adult CF Centre, varied practice in the use of NIV. Manchester, United Kingdom; 2University of Manchester, Manchester, United Methods: Links to an online survey were emailed to a named lead Kingdom physiotherapist at each UK centre listed on the CF trust website. Data were compared to our 2009 survey. Objectives: NIV is a recognised treatment option for cystic fibrosis patients Results: 20/29 (69%) of centres responded. CF physiotherapists most with acute or chronic respiratory failure. Previous retrospective data from commonly led CF NIV services (61%) compared to 46% in 2009, and most our centre has demonstrated that NIV can slow or reverse decline in lung commonly identified patients requiring NIV (60%). 60% of centres were function in CF adults. This study examines NIV practice and patient routinely using sleep studies (25% TOSCA studies, 35% overnight oximetry) outcome data at our centre over a 9-year period. compared to 46% in 2009. Outcome measures to monitor response to NIV Methods: Prospectively data was recorded for all CF patients who were included ABG/CBG (95%), subjective symptom relief (90%), overnight initiated on or received acute or domiciliary NIV between January 2011– oximetry (60%), and TOSCA result (45%). May 2019 at our centre. Patients using NIV for airway clearance were 78% of centres reported using maximum IPAP pressures >25 cmH O excluded. 2 compared to 62% in 2009. 30% of centres reported they were able to choose the type of ventilator for a n=86 n = 47 prior patient based on the desired characteristics of the machine. The remainder 2011–2019 to 2011 of centres were guided by service contracts (35%), local protocol (20%), or machine availability (15%). Male/female 35:51 30:17 20% of centres were not able to issue NIV machines for use with airway Age 29 29 clearance techniques (ACTs) alone with 85% of centres reporting they BMI 19.8 19.7 would consider use in this situation compared to 54% in 2009. Indications FEV1 0.80 FVC 1.69 for NIV as an ACT adjunct included fatigue during ACT (80%), difficulty PO2 8.7 7.6 clearing secretions with other techniques (75%), positive response to IPPB PCO2 7.5 6.7 (70%), end stage disease (60%), and desaturation during ACT (55%) in line with current CF Trust/ACPCF guidance. [Baseline demographics at NIV set up: presented as mean] Conclusions: From 2009 to 2019, CF NIV services in the UK have shown an increased role for CF physiotherapists, more use of formal sleep studies and Results: 80/86 patients tolerated NIV during acute initiation. 67 patients increased use of NIV as an ACT adjunct. Many centres reported constraints continued to use domiciliary NIV. 6 patients stopped NIV due to bloating, on NIV device selection although the impact of this on patient experience compliance and episode of pneumothorax. 20 patients went on to have a and clinical efficacy is not clear. double lung transplant, 44 died (14 on the active transplant list) and 22 patients remain alive. ePS1.03 Sleep disorders, exercise capacity and daily physical activity levels in children and adolescents with cystic fibrosis Year −3 Year −2 Year −1 NIV set Year +1 Year +2 Year +3 F.M. Vendrusculo1, N. Evangelista Campos1, R. Ribeiro Batista Barbosa2, up P. de Freitas Coelho2, P. dos Reis Vidal2, M.V. Fagundes Donadio1. 1Pontifícia BMI 21.3 21.4 20.9 19.8 21.1 22.2 22.7 Universidade Católica do Rio Grande do Sul, Centro Infant, Laboratory of 2 FEV1 1.35 1.23 1.08 0.8 0.99 1.07 1.16 Pediatric Physical Activity, Porto Alegre, Brazil; Escola Superior de Ciências da FVC 2.51 2.36 2.17 1.69 2.02 2.18 2.3 Santa Casa de Misericórdia de Vitória, Department of Physiotherapy, Vitória, pO2 9.4 8.8 9.4 8.7 9.6 9.9 10.1 Brazil pCO2 5.8 6.3 6.4 7.5 7.1 6.8 6.9 Hospital IV days 24.6. 27.3 42.6 - 73.3 63.6 55.8 Objectives: To evaluate the presence of sleep disorders and its association with exercise capacity and daily physical activity levels. [Clinical outcomes 3 years pre and post NIV initiation presented as mean] Methods: A cross-sectional study including children and adolescents aged between 6 and 18 years, with a diagnosis of cystic fibrosis (CF) was Conclusions: NIV use at our centre has increased significantly over the last performed. Information regarding sociodemographic profile, lung function decade. NIV use is associated with improvement in PO and attenuation of 2 and nutritional status were collected. Sleep disorders (polysomnography), PCO . NIV initiation appears to be associated with a reversal in lung 2 exercise capacity (Modified Shuttle Test - MST) and daily physical activity function decline and improvement in weight. Intravenous antibiotics levels (international physical activity questionnaire and 5-days requirement appears to drop in year 2–3 post NIV initiation. S38 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 accelerometer use) were evaluated. All parents signed the informed ePS1.05 consent form. Spearman test for correlations, Student’s t test and the The barriers to expectorating sputum in children with cystic fibrosis Mann-Whitney test for comparisons, and a multivariate linear regression E. White1, R. Fishwick1, Z. Rushton1, F.J. Gilchrist1,2. 1University Hospitals of model were used. North Midlands NHS Trust, North West Midlands CF Centre, Stoke on Trent, Results: Thirty-one patients (20 girls) with a median age of 9.6 years and United Kingdom; 2Keele University, Institute of Applied Clinical Science, Keele, FEV1 (%) of 68.1 ± 24.4 were included. Obstructive sleep apnea syndrome United Kingdom (OSAS) was present in 10 participants (32.3%) and nocturnal hypoxemia was identified in 9 (29%). The distance achieved in the MST correlated with Objectives: Sputum is the gold standard microbiology sample for the diagnosis of lower airway infection in cystic fibrosis (CF). Alternatives are the average SpO2 during sleep (r = 0.40) and the percent of total sleep time − less reliable (cough swabs), time consuming (induced sputum) or invasive with SpO2<90% (r = 0.49). In addition, the SpO2 at the end of the MST correlated with the occurrence of OSAS (r = −0.48) and mean nocturnal (bronchoscopy samples). Expectoration of sputum is also vital for effective airway clearance. Unfortunately, many children are unwilling or unable to SpO2 (r = 0.45). On the other hand, the levels of daily physical activity correlated with sleep architecture, including the percent of stage II expectorate sputum. We wanted to understand the barrier to sputum (r = 0.50) and REM stage sleep (r = −0.47). Patients with OSAS and expectoration and identify interventions to overcome them. nocturnal hypoxemia presented lower values (p < 0.05) of distance and Method: We created the 17-point Barriers Of Spitting Sputum (BOSS) questionnaire covering the educational, mechanical, psychological and final SpO2 in the MST when compared to individuals without these alterations. Nocturnal hypoxemia was the main variable to influence resource related barriers to sputum expectoration. Children >6 years exercise capacity (r2 = 0.521). attending the CF clinic at the North West Midlands CF Centre (UK) were Conclusion: Sleep disorders are distinctively related with exercise capacity asked to complete the questionnaire. A physiotherapist analysed each and daily physical activity levels, as nocturnal hypoxemia is associated with questionnaire and created a personalised plan to address the barriers exercise intolerance and sleep architecture disorders are associated with identified by each child. sedentary physical activity levels. Results: 43 children completed the questionnaire. 10 (23%) always expectorated sputum, 29 (68%) sometimes expectorated and sometimes ePS1.04 swallowed and 4 (9%) never expectorated. Children in all three groups Effects of exercise with neuromuscular electrical stimulation on reported single or multiple barriers to expectoration. The most commonly peripheral muscle strength, lung function and aerobic fitness in identified barriers were: embarrassment/worry about being seen expec- patients with cystic fibrosis: a randomised controlled trial torating, physical difficulty in expectorating thick sputum, nausea/vomit- 1 2 2 3 4 ing caused by expectoration and fear of sputum getting stuck. Emotional M.V.F. Donadio , V. Sanz , J.R. Villa , R.M. Giron Moreno , F. Cobo , 4 4 4 1 barriers were addressed by CF psychologist and the other issues by the CF I. Diez-Vega , S. López-López , M. Pérez Ruiz . Pontifícia Universidade physiotherapy team. Católica do Rio Grande do Sul (PUCRS), Laboratory of Pediatric Physical 2 Conclusion: The BOSS questionnaire has enabled us to identify the barrier Activity - Centro Infant, Porto Alegre, Brazil; Hospital Universitario Infantil 3 to sputum expectoration in children with CF which we have attempted to Niño Jesús, Servicio de Neumología Pediátrica, Madrid, Spain; Hospital 4 address. We now plan to repeat the questionnaire to see if this process has Universitario de la Princesa, Madrid, Spain; Universidad Europea de Madrid, increased the percentage of children who are willing to expectorate Facultad de Ciencias de la Actividad Física y Fisioterapia, Madrid, Spain sputum. Objectives: To investigate whether the addition of neuromuscular electrical stimulation (ES) to an exercise program results in improvements ePS1.06 in peripheral muscle strength, lung function and aerobic fitness. Ventilatory limitations to exercise in cystic fibrosis are dependent on Methods: A randomised controlled trial was performed on children aged lung function and equation selection between 6 and 18 years. Patients were randomised to one of the following T. Kent1, J. Trott2, C.A. Williams3, P.J. Oades2, N.J. Withers2, O.W. Tomlinson3. groups: Control (CON) - standard exercise recommendations from the 1Royal Devon and Exeter NHS Foundation Trust, Cystic Fibrosis, Exeter, United cystic fibrosis (CF) team (n = 11); Exercise (E) - supervised resistance Kingdom; 2Royal Devon and Exeter NHS Foundation Trust, Exeter, United exercise (n = 8); and Exercise+ES (EES) - supervised resistance exercise Kingdom; 3University of Exeter, Exeter, United Kingdom using ES (n = 6). Both exercise programs were performed 3 times a week (8 weeks). ES was used in lower limbs and posterior trunk muscles. Muscle Objectives: During cardiopulmonary exercise testing (CPET), maximal strength, lung function and aerobic fitness were evaluated before (T1) and minute ventilation (VEmax) is closely analysed to determine if a patient is after (T2) the interventions. Repeated measures ANOVA followed by the able to achieve maximal effort when ventilatory limited (VL). VL is Bonferroni post-test was used (significance at p ≤ 0.05). determined if the patient’s VEmax exceeds 85% of their predicted maximal Results: Twenty-five patients with CF (20 boys) were included in the study voluntary ventilation (MVV), with a number of equations used to predict − MVV based on lung function. The aim of this study was to identify how with a mean age of 12.7 ± 2.9 years and mean FEV1 was 1.5 ± 1.5 (z score). No significant difference in both body weight and lung function was found. patients of differing disease severity were deemed to have VL when performing a CPET, dependent on how MVV was calculated. However, a significant increase in VO2 (% of max) at anaerobic threshold (AT) was noted in the EES, while a decrease was seen in the CON. The mean Method: Eighty-seven patients (56 adults/31 paediatrics, 51 male/36 VO (% of max) was 59.6 ± 14.9 vs 68.9 ± 10.8 (p = 0.05) in the EES group and female) were categorised into severe (<40% FEV1%Pred, n = 5, 5 adults), 2 – 71.8 ± 12.3 vs 62.1 ± 11.6 (p = 0.01) in the CON group. A significant moderate (40 69% FEV1%Pred, n = 26, 22 adults) and mild (>70% FEV1% interaction between groups and time was found for leg press strength Pred, n = 56, 29 adults) disease severity. All performed a CPET using a (p = 0.003), bench press strength (p = 0.001) and seated row strength validated combined ramp and supra-maximal verification protocol. VL was (p = 0.001). Both E and EES groups, but not CON, increased leg and bench determined from three different equations to predict MVV: FEV1 × 35; press strength after the 8-week program. As for seated row strength, all FEV1 × 40; and a paediatric-specific equation (27.7 (FEV1) + 8.8 (PredFEV1)) groups showed an increase on T2, although the use of ES induced a higher from Stein et al (2003). improvement as compared to the CON. Results: Five (100%) of the adult patients in the severe category were Conclusions: The results of the study suggest that ES as an adjunct to a deemed VL using both the FEV1 × 35 (124.4 ± 12.2%) and FEV1 ×40 supervised and individualised exercise program may contribute to aerobic (108.8 ± 10.6%) equations. In the moderate category,17 (81%) adult patients, fitness and peripheral muscle strength in patients with CF. were VL using the FEV1 × 35 (109.0 ± 27.5%) compared with, 14 (69%) when using the FEV1 × 40 (95.3 ± 24.0%) equation. In the mild category, 16 (52%) adults were VL using FEV1 × 35 (90.6 ± 19.9%) compared with 10 (36%) when using FEV1 × 40 (79.3 ± 14.4%). For children using the paediatric (Stein) equation, 3 (75%) of the paediatric patients were VL in the moderate category (87.2 ± 2.7%), compared with 11 (41%) (83.4 ± 18.5%) in the mild category. E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S39

Conclusion: When using both equations within the adult population, it is Conclusion: The study results showed that adherence to the physiotherapy evident the results differ in determining which patients are VL during a routine with, the aid of the PlayPhysio device, remained consistent over a 6- CPET. This study shows there is a need for standardisation when predicting month period. Feedback from participants that completed the study MVV. indicated satisfaction with the device and an increased confidence from parents about adherence to effective physiotherapy with fewer arguments. ePS1.07 Future developments of the device should take into account feedback from Patient experience of virtual consultations: survey results those that withdrew and consider alternative games. H. Parrott1,2, L. Funnell2,L.O’Connor2, L. Bosaeus1, U. Bertello1, S. Madge2. 1NuvoAir AB, Stockholm, Sweden; 2Royal Brompton and Harefield NHS Trust, ePS1.09 Department of Adult Cystic Fibrosis, London, United Kingdom Urinary incontinence in women and men with end stage chronic lung disease before and after lung transplantation Introduction: Digital health tools have the potential to support the care of 1,2,3 1, 3 3 3 1,3 1 B. Button , M. Poulsen , R. Robinson , A. Burge , L. Fuller . The Alfred a growing adult CF population. In addition, virtual consultations paired 2 Hospital, Respiratory Medicine, Melbourne, Australia; Monash University, with home spirometry assessment could reduce the burden and cross- 3 Medicine, Nursing and Health Sciences, Melbourne, Australia; The Alfred infection risk associated with clinic visits. Hospital, Physiotherapy, Melbourne, Australia Aim: To evaluate patient-reported perceptions of healthcare utilisation and acceptability of NuvoAir technology in patients who have taken part in a Objectives: In a prospective study to investigate the prevalence of urinary virtual consultation service for more than 6 months (the service incontinence before and after lung transplantation (LTx) in men and commenced in 2017). The NuvoAir platform consists of a smartphone women. application and Bluetooth spirometer, with a healthcare practitioner portal Methods: Once patients were listed for LTx and after informed consent allowing patients to share data with their healthcare team. they were asked to complete three questionnaires (Qx): The Leicester Methods: A survey was emailed to eligible patients, including questions on Cough Qx (LCQ), The International Consultation on Incontinence Qx (ICIQ) patient-reported healthcare utilisation, use of the technology and under- and the ICIQ Quality of Life (QOL) Qx. Three months after LTx they again standing of their CF. All patients provided consent. completed the three Qx. All patients undertook three months of supervised Results: Response rate: 41/67 (61%); males 46.3%, mean age 37.3 years (SD exercise rehabilitation after LTx three times per week. – 10.2), mean FEV1 57.3% predicted (range 24.2 103.0). Length of time using Results: Of 93 recruited participants, 71 (76%) were transplanted (43% the virtual consultation service: mean 13.0 months (range 6.9–25.8). The male, mean age 62 [SD 9] years, females 52 [14] years). Prostate problems virtual service reduced the number of booked face-to-face consultations by were reported by 12% of males; 30% of females were nulliparous and 41% 30.9% (from mean 5.4 to 3.7 visits/year; p < 0.001) and the number of postmenopausal. There was a difference between females and males for urgent face-to-face consultations by 39.8% (from 2.2 to 1.3 visits/year; report of UI pre LTx (42/53 females, 14/40 males, p < 0.0001) which was not p < 0.01). A total of 18/41 (43.9%) patients felt that they understood their CF demonstrated post LTx (20/37 females, 13/34 males, p = 0.182). In females better since starting the virtual service (23 [56.1%] unchanged; 0 worse) scores for UI symptoms (pre: median 3[IQR 0.3 60 6], post 1 [0 to 4], and 7/41 (17.1%) said their medication adherence improved (34 [82.9%] p < 0.0001) and quality of life (QOL) (mean difference 5.8 [95%CI 1.3 to unchanged; 0 worse). Overall acceptance of virtual consultations was high 10.2]) significantly improved post LTx. Pre LTx UI symptoms scores were (mean 9.4/10 [range 7–10]). The numbers of antibiotic courses and lower in males (pre: median 1 [IQR 0 to 2] and no difference was hospitalisations were not significantly changed. demonstrated post LTx (1 [0 to 3], p = 0.650). No difference in scores for Conclusions: These self-reported data show the acceptability of virtual quality of life was demonstrated in males (mean difference −0.7 {95%CI consultations and the potential to substantially reduce overall healthcare −7.1 to 5.7]). For participants with UI pre LTx, no relationship was observed utilisation. These results will help plan the service’s further development post LTx with improvement in UI and improvement consistent with the in a larger population and with a longer follow-up period. minimal important difference for LCQ (females p = 0.621, males p = 0.757). Conclusion: Improvement in UI symptoms and QOL scores were observed ePS1.08 in females following LTx. Resolution of UI did not appear to be related to A pilot study investigating the PlayPhysio Device; a novel addition to change in cough post LTx. The lack of improvement in UI in some oscillatory PEP devices in children with cystic fibrosis participants following LTx indicates the need for further work to identify L. Lowndes1, C. Hamilton1, A. Russo2, N.B. Shoshan1, D. McShane1. and treat UI. Routine screening for UI pre and post LTx is recommended. 1Addenbrookes Hospital, Cambridge, United Kingdom; 2Universita degli Studi di Salerno, Fisciano SA, Italy ePS1.10 Prevalence of female urinary incontinence in the paediatric Cystic Objectives: Cystic Fibrosis (CF) management requires regular chest Fibrosis Centre of Milan clearance treatments but it is known that adherence to these treatments 1,2 1,2 1,2,3 1,2 1, 2 A. Mariani , F. Carta , S. Gambazza , A. Brivio , G. Bassotti , is poor. Mobile applications may hold the potential to motivate and 1, 2 1, 2 1,4 1 A. Gesuele , E. Caverni , C. Colombo . Fondazione IRCCS Cà Granda strengthen adherence. ® Ospedale Maggiore Policlinico Milano, Cystic Fibrosis Centre of Milan, Milano, PlayPhysio is a device, with an associated app, that can be attached to any 2 Italy; Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, oscillatory PEP device. The clinician uses the app to set the length and 3 U.O.C Direzione delle Professioni Sanitarie, Milano, Italy; University of Milan, depth of the blows required as well as the physiotherapy routine. The Department of Clinical Sciences and , Milano, Italy; patient’s breaths control actions in games which have been designed to 4 University of Milan, Department of Pathophysiology and Transplantation, encourage the child to engage with the routine. Data is collected and sent Milano, Italy electronically in order to monitor adherence. The aim of this study was to look into the safety and efficacy of the Objectives: The reported prevalence of urinary incontinence (UI) in female PlayPhysio device and to investigate the effect of the device on adherence. with Cystic Fibrosis (CF) ranges from 30% to 76%. Currently, the prevalence Methods: This was a 24-week study in which the CF patients (ages 8–16) of UI in Italian CF patients is unknown. Due to the considerable impact of UI use the PlayPhysio® device and associated app. Lung function, in app on lifestyle, we aimed to determine the prevalence of UI in our centre. questionnaires and compliance data were all analysed. Methods: Validated questionnaires (ICIQ-SF, ICIQ-CLUTS) were adminis-

Results: 30 patients (14 Female; Mean age 10.9; Mean FEV1 94.3%) were tered to the available population during routine assessments over 6 consented of which 17 patients completed the study. Interim analysis months. Scores were correlated with disease severity (mutations, lung shows that the mean (S.D) adherence is 59.56 (37.01). Data showed function, bacterial colonization), nutritional status (pancreatic function, minimal change in adherence during study period. There were no adverse BMI, artificial feeding, CFRD), risk factors (urinary tract infections, events. Mean FEV1 at the end of the 6-month trial was 98.5%. Those that constipation, hospitalization, gynaecological interventions, physical activ- withdrew from the study stated that the games were not of interest to them ity (PA), pregnancy) and with anthropometric measures. or because of technical difficulties with the device. A logistic model was then fitted to predict UI probability. S40 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54

Results: Questionnaires were completed by 142 patients (71.3% coverage), prevalence of CF-Related Diabetes mellitus (CFRD). In UK primary care, aged 18 (IQR 11) yrs old. 47 (33%) reported UI (95% CI: 25–41%): 36 (77%) cardiovascular (CV) risk is calculated for the general population over 40 women (≥18 yrs), 9 (19%) adolescents (9–18 yrs), 2 (4%) children. years of age using QRisk® scoring. QRisk®3 predicts the risk of sustaining a According to ICIQ-SF score, 64% of women described mild UI, 25% CV event within ten years (>10% used as the threshold for significance) and moderate, 8% severe and 3% very severe (score 19–21 at ICIQ-SF). Main forms the basis of primary CV prevention. Calculations of CV risk triggers of UI were cough (76%) and PA (24%). Females without UI expressed necessitates classifying CFRD as either type 1 or type 2 diabetes mellitus higher lung function (P < 0.001), and lower rate of Pseudomonas aeruginosa (T1DM, T2DM). We investigated whether this distinction would signifi- (P = 0.004) and hospitalization (P = 0.004). Rate of insulin therapy (P = 0.04) cantly alter patient scores. and enzymatic supplementation (P = 0.021) were higher in patients with Methods: Data were prospectively collected for 37 patients over 40 years of UI. Genotype differed between the two groups (P = 0.027). The fitted model age with a diagnosis of CFRD, including blood pressure (BP), cholesterol, showed that UI associated with age (OR = 1.114, P = 0.002), pancreatic HbA1c and QRisk®3 score. Three distinct groups were defined by age range exocrine function (OR = 0.317, P = 0.05) and constipation (OR = 3.811, ≥40 years (40–49; 50–59; ≥60), and comparisons made using one-way P = 0.08). ANOVA analysis. Conclusion: UI represents an underdiagnosed disturbance in our CF Results: Data demonstrated mean (SD) HbA1c 47.9 (±9.80) mmol/mol, cohort. These results reinforce the need of primary prevention in order to cholesterol 3.95 (±0.85) mmol/L and systolic BP 129 (±13.0) mmHg, with no reduce long-term consequences. A jointly effort to survey prevalence of UI significant difference between groups. Mean (SD) QRisk®3 scores calcu- in Italian CF Centres will follow, in order to share common interventions lated using T1DM and T2DM as equivalents for CFRD were 10.3 (±5.68) and and strategies. 6.92 (±4.24)% respectively. A significant difference was observed between the two QRisk®3 diabetic groups (p < 0.001) and all three age groups (p < 0.001). 17 patients scored >10% risk in the T1DM group compared with 10 in the T2DM group (p = 0.08). ePoster Session 2: Adult complications Conclusion: The prevalence of CFRD, hypertension and hypercholesterol- aemia may increase as CF patients age. Calculation of QRisk®3 may be an ePS2.01 important future predictor of CVD and could provide an opportunity to Prevalence of hypertension in cystic fibrosis establish primary CV prevention in the older CF population. Classification of CFRD in terms of T1DM or T2DM as part of QRisk®3 scoring will have a C. Logue1, C.M.T. Smith1,N.Nath1, J. Beynon1, K. Tofeec1, A.L. Brennan1. significant influence on risk stratification for patients. 1Manchester Adult Cystic Fibrosis Centre, Manchester Foundation Trust, Manchester, United Kingdom ePS2.03 Objectives: Life expectancy in those with cystic fibrosis (CF) has increased Prevalence of gastrointestinal symptoms in pancreatic insufficient significantly; the predicted median age of survival for an infant with CF in adults with cystic fibrosis: a UK cohort study some countries is over 50 years. Patients are developing previously L. Caley1, H. White2, A. Jaudszus3, J. Mainz3, D. Peckham1. 1University of unrecognised complications. Little data is available on the prevalence Leeds, School of Medicine, Leeds, United Kingdom; 2Leeds Beckett University, and risk factors for hypertension (HTN) in CF. However, the presence of HTN Nutrition and Dietetics, Leeds, United Kingdom; 3University of Jena, Thuringia, could impact the development of micro- and macro-vascular complica- Germany tions, particularly in patients with CF-related diabetes (CFRD). 82% of UK adult physicians have experience of people with CF (age 20–59) with Objectives: Gastrointestinal (GI) symptoms are common in patients with cardiovascular disease. Furthermore, over the last decade over-nutrition Cystic Fibrosis (CF) and can impact on quality of life. In this study we assess has been described in CF which is a risk factor for the development of HTN. the frequency of GI symptoms in a large cohort of adults attending the The prevalence of HTN is, therefore, of clinical relevance in CF. Leeds regional CF centre. Methods: We performed a retrospective audit of blood pressure monitor- Methods: Pancreatic insufficient (PI) adults with CF were recruited as part ing performed in the clinic setting in all patients in our adult CF clinic in of an ongoing UK multicentre cohort study (Igloo-CF Study). Lung – transplantation was an exclusion criterion. GI symptoms were assessed 2018 19, using WHO criteria for assessment of HTN. The prevalence of © clinic HTN was calculated. with the validated CF Abd-Score (v4.0) during a period of clinical stability. Results: WHO criteria for HTN was met on ≥3 clinic encounters by 9.8% Preliminary data are presented. (n = 399) of patients. Prevalence increased with age (3.2% ≤30 y, 11% 31– Results: A total of 74 adults were assessed of which 61% were male (mean 40 y, 16.4% 41–50 y, 31.6% 51–60 y, 55.6% >60 y). Prevalence of HTN was age 36 ± 9.7 yrs). The majority of participants had at least one F508del – mutation (n = 68, 92%). Median FEV1pp was 51.5 (range: 20 99). The mean highest in patients with CFRD 11.7% (17/145) vs 8.7% (22/254) in patients 2 without CFRD. 5% (21/399) of subjects were already taking anti- BMI was 24 ± 3.8 kg/m . Abdominal pain was present in >60% of individuals hypertensive treatment. Of people with HTN, 67.5% (27/40) were male, with only 27% reporting no bloating and 30% experienced these symptoms 42.5% CFRD and 32.5% on a CFTR modulator. 12.4% (18/145) patients with frequently to always. Almost one in four reported flatulence almost always/ CFRD had evidence of renal end-organ damage. always. Half the participants described reflux and over half heartburn. Conclusion: HTN is potentially an under-recognised complication in adults Constipation was reported as occasional in 27% and 7% almost always/ with CF, affecting nearly a third of those over 50 years old. Early diagnosis, always with 15% reporting type 1 stools. Symptoms indicative of assessment and treatment is important to reduce risk of microvascular and steatorrhea were common, with >70% and >80% of participants experien- macrovascular disease, particularly as life expectancy is increasing. cing some degree of fatty and foul-smelling stool respectively. 41% reported Repeatedly high clinic BP recordings should trigger further evaluation type 6/7 stools. GI symptoms caused some degree of embarrassment, including ambulatory monitoring and assessment of end-organ damage. frustration/restlessness/irritability and fatigue in half of study participants. It also impacted on physical activity in >40% of people. ePS2.02 Conclusion: Structured assessment of GI symptoms is helpful in Assessing cardiovascular risk in an older cystic fibrosis patient cohort: identifying GI symptomatology. GI symptoms are very common, bother- implications of Cystic Fibrosis-Related Diabetes classification some and impact significantly on emotional and physical wellbeing. Symptoms of steatorrhea prevail, despite good nutritional status. S.L. Paterson1, 2, R.J. Bright-Thomas1, 2, A.M. Jones1, 2, A.-M. Kelly1,2, Funded by UK CF Trust (SRC 012). A.L. Brennan1. 1Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom; 2University of Manchester, Manchester, United Kingdom

Objectives: Longevity in CF may influence the development of cardiovas- cular disease (CVD), particularly in an ageing cohort with an increasing E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S41 ePS2.04 malignancy was B cell Lymphoma (27%) and skin cancer (27%) in post- Gastrointestinal surgery in adult patients with cystic fibrosis: transplant patients. 1 patient had both lymphoma and gastric adenocar- observational French prospective study over 11 years cinoma. Of the 5 non-transplanted patients, 3 had gastrointestinal cancer,1 N. Desmazes-Dufeu1, B. Coltey1, D. Birnbaum2, M. Serrero3, C. Dehillotte4, had leukemia and 1 had breast cancer. Clinical presentations were variable, L. Lemonnier4. 1Hopital Nord, AP-HM, Aix-Marseille University, CRCM, often indolent and in some cases very atypical. Marseille, France; 2Hopital Nord, AP-HM, Aix-Marseille University, Digestive Conclusion: Patients with CF are presenting with a wide range of cancers, Surgery, Marseille, France; 3Hopital Nord, AP-HM, Aix-Marseille University, some of which may be related to underlying CFTR defect. Gastrointestinal Gastro-Enterology, Marseille, France; 4Vaincre la Mucoviscidose, Paris, France malignancy was the most common form of cancer in patients who had not received solid organ transplant. Objectives: Gastrointestinal diseases are frequent in cystic fibrosis (CF) adult patients but only few studies on gastrointestinal surgery are reported. ePS2.06 The aim of this study was to describe the frequency, the type of digestive Early experiences of a bowel cancer screening programme in an adult surgery and clinical characteristics of CF patients. cystic fibrosis centre Methods: Between 2007 and 2017, all patients who were 18 years or older 1 2 1 2 1 S. Whiteley , J. Dalton , N. Withers , T. Shirazi . Royal Devon and Exeter NHS were included prospectively into the French CF national database. The 2 Foundation Trust, Adult CF Centre, Exeter, United Kingdom; Royal Devon and database was searched for all patients who had undergone gastrointestinal Exeter NHS Foundation Trust, Gastroenterology, Exeter, United Kingdom surgery. Demographics and clinical characteristics, genetic mutations and surgical procedure were analyzed. Objectives: People with cystic fibrosis (pwcf) are at greater risk of Results: A total of 3,876 patients were included during this period. Among developing bowel cancer at a younger age than people without CF. them, 428 patients (11%) underwent 494 digestive surgery for gallbladder Hadjiliadis et al. (2018) published colorectal screening consensus recom- lithiasis (n = 95, 19%), surgery for denutrition (n = 94, 19%), anti-reflux mendations outlining that pwcf should be screened for bowel cancer at 40 surgery (n = 94, 19%), bowel occlusion (n = 81, 16%), appendicitis (n = 72, years old. We describe early experience of introduction of a bowel cancer 15%), wall hernia (n = 44, 9%), proctology (n = 14, 3%). Compare to CF screening (BCS) programme for pwcf in a UK adult centre. population, surgery for occlusion was more frequent in men (median age Methods: Patients aged 40 years and over were identified from the UK CF 27.8 yrs, sex ratio W/M 0.52). A past history of meconium ileus was a registry and sent a letter explaining why they were being invited for BCS. significant risk factor for requiring surgery for occlusion (p > 0.001). Screening was discussed at their next clinic appointment and patients were Patients who underwent cholecystectomy had a better clinical status then referred to gastroenterology for pre-assessment and colonoscopy.

(median age 30 yrs, sex ratio W/M 2.37, FEV1 70%, pancreatic insufficiency Pre-assessment was undertaken by one dedicated nurse and all colonos- 59%, BMI21.7). In contrast, gastro or jejunostomy was performed on copies were undertaken by a BCS accredited Gastroenterologist using patients with more severe comorbidity than CF population (median age standard BCS protocol.

23.5 yrs, FEV1 31.8%, BMI 17, diabetes mellitus 48%). Anti-reflux surgery Results: Out of a total of 121 adults at our centre, 27 (18 male, mean age 50 concerned lung transplanted patients in 86%. Appendectomy was more years) patients were identified for screening. Of these, 3 were excluded as frequent compared to non-CF population. they had had recent colonoscopies for bowel symptoms. An additional Conclusions: Gallbladder disease, gastroesophageal reflux, bowel occlu- patient under 40 with a strong family history of colorectal cancer was also sion and renutrition were the most causes of digestive surgery in patients invited. Of the 25 patients sent a letter 18 have been referred for screening. with CF. Meconium ileus at birth is a risk factor for requiring surgery for Reasons for non-referral included non-attendance at clinic (2), recent occlusion. Surgeons will increasingly need to be aware of the abdominal colonoscopy at different hospital (1) and haematological malignancy manifestations of CF in order to optimise patient outcomes. diagnoses (1). Three patients require discussion at their next clinic attendance. No patient has declined a referral when approached. To date ePS2.05 6/18 patients have undergone BCS, all with good visualisation and no Cancer risk in cystic fibrosis patients: a 13-year experience in a UK complications. Benign polyps were identified in 2/6 patients. regional centre Conclusion: Bowel Cancer Screening has been well received and well W.Y. Lim1, C. Etherington1, G. Spoletini1, I. Clifton1, D. Peckham1. 1Leeds tolerated by patients. In our small group no cancers have been identified, Teaching Hospitals NHS Trust, Leeds, United Kingdom with follow up planned as per the current BCS guidelines. The screening programme continues and in 2020 will be rolled out to include all patients Objectives: As life expectancy increases, malignancy has become more who have received solid organ transplants. prevalent in patients with Cystic Fibrosis (CF). We set out to review the incidence of diagnosed cancer over a 13-year period in adults attending the ePS2.07 Leeds Regional CF Centre. Are women with cystic fibrosis at the All Wales Adult Cystic Fibrosis Methods: A retrospective review of electronic records (EMIS) of all patients Centre attending for cervical screening? ≥ 1 1 1 1 1 1 1 aged 17 years followed-up in our Unit from 2008 to 2020 was undertaken C. Wilson , I. Ketchell , D. Lau , P. Goble , L. Speight , J. Duckers . University to identify those with a diagnosis of cancer. Hospital Llandough, All Wales Adult Cystic Fibrosis Centre, Cardiff, United Kingdom

Cancer Number of Post-transplant Background: Cervical screening aims to prevent cancer from developing in patients the cervix. In Wales, women aged 25–64 are invited for cervical screening every 3–5 years, with coverage reported at 73.2%. Previous studies have B cell lymphoma 3 Yes demonstrated that women with cystic fibrosis (CF) have had insufficient Skin 3 Yes gynaecological follow-up and cervical screening, there is also evidence Gastrointestinal 3; 1 No; Yes which states women with CF have a higher frequency of cervical Cervical 2 Yes Breast 1 No inflammation and abnormal screening results. Leukaemia (CNS) 1 No Objectives: To establish uptake of cervical screening amongst women with Lung 1 Yes CF in the All Wales Adult CF Centre (AWACFC) and patient characteristics Renal 1 Yes predictive of attendance. Thyroid 1 Yes Methods: We identified and sent out letters requesting ten-year screening history to the of all women aged between 25 and 64 [Cancers in CF patients] eligible for cervical screening in the AWACFC. The data was anonymised, inputted to SPSS and analysed using the chi-square and t-test for statistical Results: We reviewed a total of 703 patient records. A total of 16 patients significance in regards to age, FEV , marital, parental and transplant status were diagnosed with cancer. 11 patients (69%) developed cancer between 1 on attendance at most recent test and number of missed tests. 21 months and 24 years post solid organ transplant. The most common S42 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54

Results: We identified 75 eligible females; with a response rate of 84% (63/ Methods: Ultrasound (US) examination of the joints according to a 75). 73% (46/63) attended their most recent cervical screening test. 38% specially developed US score for CFA (US-CFA) has been performed. A (24/63) missed at least one test in the last ten years. 27% (17/63) missed ≥2 clinical assessment has been conducted, including a clinical status, a survey tests in the last 10 years. 9% (6/63) did not attend any tests. Patients with a on arthropathy, and rheumatological scores (DAS-28, HAQ). This informa- history of non-attendance were more likely to repeatedly not attend tion has been gathered and analyzed in order to define different stages

(p < 0.001). Age, FEV1, marital, parental and transplant status were not of CFA. predictive of uptake of screening (P > 0.05). Results: Based on the results we have defined a staging system for CFA: Conclusion: We expected attendance rates may have been reduced in comparison to the general population, as has previously been noted in regards to bone density screening. However, our patient cohort is in line Ultrasound Symptoms/ CFA Class Intensity (A: mild, with the national average. As a centre we should continue to promote clinical scores B: moderate, women’s health, in particular post-transplant as increased cervical cancer C: severe) risk is documented, and as CF life expectancy continues to improve. −− no CFA A/B/C − + I A/B/C ePS2.08 + − II A/B/C Risk factors for cystic fibrosis arthropathy: data from the National + + III A/B/C German Cystic Fibrosis Patient Registry 1 2 3 4 1 [Clinical staging of cystic fibrosis arthropathy] C. Grehn , A.-M. Dittrich , J. Wosniok , L. Nährlich , C. Schwarz , Registry Working Group of the German CF Registry. 1Charité - Conclusion: For the first time, different stages for the clinical manifestation Universitätsmedizin Berlin, Department of Pediatric Pneumology, Immunology of CFA could be described. Defining these stages may lead to a better and Intensive Care Medicine, CF Center, Berlin, Germany; 2Hannover Medical understanding of the clinical phenotype of the disease and subsequently School, Pediatric Pneumology, Allergology, and Neonatology, Hannover, optimize the process of diagnosis and therapy as well as research on CFA. Germany; 3Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Since the distribution patterns found in the retrospective study seem to be Interdisziplinäres Zentrum Klinische Studien (IZKS), Mainz, Germany; 4Justus- replicated in US examination and the US-CFA is able to detect disease Liebig-University Giessen, Department of Pediatrics, Giessen, Germany activity concordantly with the other clinical scores, it seems to be a suitable Objective: Cystic fibrosis arthropathy (CFA) is frequently observed in diagnostic tool for further CFA research. patients with cystic fibrosis. We studied the epidemiology of CFA in the large dataset of the German cystic fibrosis (CF) patient Registry. ePS2.10 Methods: Retrospective cohort study of CF patients included in the CF Peak glucose during an oral glucose tolerance test associated with Registry in 2016–2017. Transplanted patients or patients with missing data clinical status in adult patients with cystic fibrosis were excluded. The prevalence of CFA was calculated. For initial risk factor A. Bonhoure1,2, J. Colomba1,3, V. Boudreau1,3, C. Bergeron1,3, K. Potter4, analysis, binary logistic regression (SAS 9.4) was used and only patients >18 M. Carricart3,5, F. Tremblay1, 5, A. Lavoie1,5, R. Rabasa-Lhoret1,3,5. 1Montreal years and without chronic Pseudomonas aeruginosa infection (chronic: two Clinical Research Institute, Montreal, Canada; 2McGill University, Division of or more positive P. aeruginosa sputum cultures per year) were included, to Experimental Medicine, Montréal, Canada; 3University of Montréal, reduce possible P. aeruginosa dependent confounding. Department of Nutrition, Montréal, Canada; 4University of Alberta, Results: 6,069 CF patients aged from 0 to 78 years were in the study cohort. Department of Endocrinology, Edmonton, Canada; 5University of Montréal CFA was observed in 4.9% of the patients. Prevalence was significantly Hospital Center (CHUM), Cystic Fibrosis Clinic, Montréal, Canada higher in adult patients (8.4%) compared to patients <18 years (0.7%; p < 0.0001). Binary regression analytics in adult CF patients without Objectives: Cystic Fibrosis-Related Diabetes (CFRD) affects about 50% of chronic P. aeruginosa infection (n = 1396) showed that CFAwas significantly adults with cystic fibrosis (CF) and is preceded by a decline in clinical status associated with age (OR = 1.026; 95% CI = 1.003–1.050; p = 0.0249), anti- (weight and lung function). Thus, an annual screening for glucose mycotic treatment (OR = 2.247; 95% CI = 1.057–4.778; p = 0.0354), hospi- abnormalities is recommended using a 2-hr Oral Glucose Tolerance Test talisation (OR = 1.395; 95% CI = 1.179–1.650; p = 0.0001) and the (OGTT). Diagnostic criteria for fasting and 2-hr OGTT levels are based on comorbidities of pancreatic insufficiency (OR = 2.306; 95% CI = 1.021– Type 2 Diabetes criteria (risk of retinopathy). However, CFRD is distinct as 5.211; p = 0.0446), pansinusitis (OR = 2.010; 95% CI = 1.194–3.385; p = the most critical complications are pulmonary and nutritional. The aim is to 0.0086) and osteopenia (OR = 2.482; 95% CI = 1.319–4.670; p = 0.0048). investigate which OGTT parameters most strongly correlate to significant Conclusions: CFA is a frequent and clinically relevant co-morbidity clinical markers in CF: lung function and nutritional status. particularly in adult CF patients. Methods: Transversal analysis at baseline (n = 293) and observational prospective analysis (n = 187; follow-up of 7.5 ± 4.2 years) of data from the ePS2.09 Montreal cohort with an OGTTand clinical data collection every 18 months. Defining different stages of cystic fibrosis arthropathy using Glycemic: fasting, 2-hr, maximum, and area under the curve (G0;G120; ultrasound imaging and clinical scoring Gmax;GAUC) and insulinemic (I0;I120;Imax;IAUC) parameters were studied in relation to lung function (Forced expiratory volume in 1s: FEV ), body mass F. Holz1, E. Can2, T. Kallinich3, C. Schwarz1. 1Charité - Universitätsmedizin 1 index (BMI), and risk of developing CFRD. Berlin, Pediatric Pulmonlogy/Cystic Fibrosis, Berlin, Germany; 2Charité - Results: FEV is inversely correlated with G and I (r = −0.175, Universitätsmedizin Berlin, Radiology, Berlin, Germany; 3Charité - 1 max 0 s p = 0.003; r = 0.121, p = 0.045), but not G &G .I,I , and I are Universitätsmedizin Berlin, Pediatric Rheumatology, Berlin, Germany s 120 AUC 0 max AUC significantly positively correlated to BMI (rs = 0.184, p = 0.002; rs = 0.230, Objectives: With an increasing life expectancy in cystic fibrosis (CF) the p < 0.001; rs = 0.221, p < 0.001). Prospective analyses show a significant − importance of co-morbidities like arthropathy in CF (CFA) is rising. In our inverse correlation between baseline Gmax and FEV1 decline (rs = 0.178, retrospective study a prevalence of chronic CFA was reported in 29% p = 0.022). This is not observed for G120 nor insulinemic parameters. A Gmax (Roehmel et al. 2019). It may lead to a significant reduction in the quality of ≥8 mmol/L is associated with an increased risk of developing CFRD life and be a restrictive factor for daily activities and exercise. It remains (p = 0.024). difficult to state a clear definition of CFA since the causes seem to be multi- Conclusion: In adult patients with CF, Gmax is more strongly associated factorial and the pathogenesis is not fully understood yet (Pertuiset et al. with FEV1 evolution than the current diagnostic criteria G120. Furthermore, ≥ 1992, Clarke et al. 2019). aGmax 8 mmol/L is associated to lower FEV1 and increased risk of Therefore we aimed to define different stages of the clinical manifestation developing CFRD. of CFA and implement a staging for the assessment with this prospective study. E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S43

significant increase in EVs were released from CFBE41o- (p < 0.0001) and ePoster Session 3: Inflammation goes wild CuFi-5 (p = 0.0209) relative to control cell lines. A significant decrease in EVs were released from CFBE41o- (p < 0.001) and CuFi-5 (p = 0.0002) cell ePS3.01 lines treated with current CFTR modulators. A significant increase in EVs Immunotyping of clinically divergent F508del homozygous were detected in BALF of PWCF in three age groups relative to controls monozygous cystic fibrosis twins (p = 0.0002–0.0007) which included 2 paediatric and one adult group. 1,2 1 3 1, 2 1 Significant changes in the protein expression of 126 unique proteins in total B. Tümmler , S. Hedtfeld , L. Wiehlmann , F. Stanke . Medizinische was determined in BALF EVs from PWCF (p < 0.001–0.05) which included Hochschule Hannover, Klinik für Pädiatrische Pneumologie, Allergologie und 2 inflammatory and integrin signalling pathways. Of particular interest, we Neonatologie, Hannover, Germany; Biomedical Research in Endstage and discovered distinct protein signatures in EVs obtained from children of Obstructive Lung Disease Hannover, German Center for Lung Research, 3 different age groups compared to adults. Hannover, Germany; Medizinische Hochschule Hannover, Core Unit A significant increase in chemotaxis of neutrophils derived from blood of Genomics, Hannover, Germany PWCF was observed compared to controls in the presence of CFBE41o EVs Objectives: Monozygous twins are a unique opportunity to gain insight (p = 0.0024) and was mediated by the pro-inflammatory protein S100 A12. into the role of postzygotic events on context-depending features such as Discussion: Overall this study on CF EVs has provided exciting initial data the immune response. We examined the clinically most concordant and on EV released from CF airway cell lines and in BALF from PWCF compared most discordant F508del homozygous monozygous twin pairs of the to their relative controls in a novel and developing area in CF. We discovered European CF Twin and Sibling Study in the postzygotic attributes that EVs from PWCF have differential protein expression at different age groups. generate most diversity in human blood, i.e. the B cell and T cell receptor Additionally, we discovered that clinically used CFTR modulators can repertoire. regulate EV release providing additional insights into their mechanisms of Methods: High-throughput multiplex amplicon sequencing of the CDR3 actions. Our data has also indicated that CF EVs can regulate chemotaxis of variable chain of B cell and T cell receptors in peripheral blood was neutrophils, which can be regulated in part through S100 A12/RAGE performed with the ImmunoSEQ immune profiling system. signalling pathways. Results: Amplicon sequencing revealed 16,000 to 43,000 unique Conclusion: This study demonstrates increased EV release in CF airways sequences in each twin. Each CF twin was harboring his own repertoire compared to controls and connects CFTR to EV release in epithelial airway of sequences distinct from that of the other CF sibling. More than 90% of cells. Unique protein fingerprints in BALF EVs with progressive disease sequences were only detected once, twice or three times reflecting the high illustrating a potential for EVs as biomarkers. The study also provides α-diversity of the pool. Whereas unrelated pairs shared less than 10 information on how CF airway cells may contribute to neutrophil activation sequences with each other, twins shared a significantly higher, but still very through the release of EVs. We believe this small translational study low number of 13 to 35 sequences (≈0.1% of total) which can be attributed provides us with valuable and potentially very useful information in a to the persistence of fetal clonotypes from shared cord blood cells. novel and developing area in CF. Conclusion: The immune cells in peripheral blood of the examined F508del homozygous monozygous CF twins showed individual profiles of ePS3.03 their B and T cell receptor repertoire reflecting the plasticity of the immune Probing the central role of macrophages in cystic fibrosis inflammation system of genetically identical humans to cope with the environment. J.L. Gillan1, G.R. Hardisty1, N.J. Robinson1, R.D. Gray1. 1Universtiy of Edinburgh, Centre for Inflammation Research, Edinburgh, United Kingdom ePS3.02 Increased extracellular vesicles mediate inflammatory signalling in Objectives: Macrophages are the most plastic of all myeloid cells and their cystic fibrosis immense functional diversity permits a central role in the inflammatory response, from initiation, to resolution and repair. Recent studies suggest A. Trappe1, Z. Useckaite2, M. Ward3, H. Davage4, J. Lennon4, S. Carter5, that macrophage immune function is defective in CF and that these cells E. McKone6, S. Donnelly7, P. McNally8, J. Coppinger1. 1Royal College of may actually be net contributors to the disease. This, along with the Surgeons, School of Pharmacy and Biomolecular Sciences, Dublin, Ireland; observation that monocytes and macrophages express functional CFTR in 2Flinders University, Bedford Park, Australia; 3Trinity College Dublin, healthy individuals, begs an interesting question regarding the cause of Department of Pathology, Dublin, Ireland; 4National Children’s Research this dysfunction and whether it is intrinsically linked to loss of CFTR in Centre, Dublin, Ireland; 5Royal College of Surgeons, Dublin, Ireland; these cells, or simply secondary to the diseased state in CF. 6St. Vincent’s University Hospital, Cystic Fibrosis Unit, Dublin, Ireland; 7Trinity Methods: In order to better understand the mechanisms underlying College Dublin, Medicine, Dublin, Ireland; 8Royal College of Surgeons, Crumlin, macrophage immune dysfunction in CF, we used flow cytometry, gene Ireland expression and protein analysis to investigate the proinflammatory Background: The role of extracellular vesicles (EVs) as essential vehicles of phenotype of human CF monocytes and monocyte-derived macrophages pathological processes is an emerging field. A role for EVs in inflammatory (MDMs) at a basal level and in response to P. aeruginosa LPS. Analysis of cell recruitment has recently emerged in inflammatory airway disease. genome-wide transcriptomics profiling of CF MDMs in response to LPS Cystic fibrosis (CF) is a progressive genetic disease which affects epithelial activation using the cap analysis of gene expression (CAGE) technique is innate immune function and airway clearance in the lung, ultimately also underway. leading to respiratory failure. Epithelial dysfunction has been implicated in Results: Circulating monocytes from CF blood exist in a higher state of modulating chronic inflammation in CF airways, resulting in the initiation activation than healthy controls, with significantly higher surface expres- of a pro-inflammatory cascade that leads to the recruitment of leukocytes sion of CD64 and CD11b and that CF MDMs, cultured from these cells into the airway. There still remains an important knowledge gap in CF as to in vitro, exhibit a failure to effectively regulate TLR4 signalling in response how diminished CFTR activity leads to the dominant inflammatory to LPS activation. This was shown by significantly dampened SOCS response that causes tissue destruction and eventual challenges to organ expression at 6 hrs post-LPS, culminating in significantly increased function. In this translational multi-collaborative study we examined the production of proinflammatory mediators IL-8, IL-1β, and TNF-α at inflammatory role of EVs in CF using EVs generated from both cell lines and 24 hrs. CAGE analysis is ongoing at time of submission. bronchial lavage fluid (BALF) from children and adults with CF. Conclusion: Macrophages are dysfunctional in CF due to dysregulation of Result: EVs were isolated from F508-del CFTR cell lines and BALF from 30 the inflammatory response to stimuli such as LPS. CAGE analysis is now persons with CF (PWCF) and analysed by NTA and mass spectrometry (MS) underway to probe the relevant pathways and how these are regulated in compared to controls. Neutrophils were isolated from the blood of PWCF to the absence of CFTR function. examine neutrophil migration in the presence of CFBE41o- EVs. A S44 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 ePS3.04 patients with CF. There was a significant difference in the levels of cSLPI NCR+ Type 3 Innate lymphoid cells are increased in lung tissue, present in sputum from stable CF patients and CF patients with bronchial lymph nodes and peripheral blood of cystic fibrosis patients exacerbation. O. Halle1, A. Melanie2, M. Schumacher1, K. Lobjanidze1, A.C. Jirmo1, Conclusion: Using Randox biochip technology, we will utilise the J. Rödiger1, J.-N. Falke1, S. Gaedcke3, D. de Luca3, P. Braubach4, D. Jonigk4, antibodies against cleaved SLPI as part of a near-patient immunodiagnostic G. Warnecke5, G. Hansen1, A.-M. Dittrich1. 1Hannover Medical School (MHH), test. Sputum and BAL samples from patients with cystic fibrosis, will be Pediatric Pneumology, Allergology and Neonatology, Hannover, Germany; tested on these biochips and correlated to clinical parameters including 2Paul-Ehrlich-Institute, Langen, Germany; 3Hannover Medical School (MHH), microbiological and inflammatory data. BREATH, DZL Consortium, Hannover, Germany; 4Hannover Medical School (MHH), Institute for Pathology, Hannover, Germany; 5Hannover Medical ePS3.06 School (MHH), Department for Cardiothoracic and Vascular Surgery, Dysregulation in expression of STATs and SOCS genes of cytokine Hannover, Germany signaling pathway favors Th2/Th17 mediated inflammation in cystic fibrosis Objectives: Innate lymphoid cells (ILCs) mediate cellular immune defense 1 2 1 S. Sagwal , M. Singh . All India Institute of Medical Sciences, Biochemistry, and tissue homeostasis at mucosal surfaces including the lung. Changes in 2 Bathinda, India; Postgraduate Institute of Medical Education and Research, composition of the ILC subsets ILC1, ILC2 and ILC3 have been reported in Pediatrics, Chandigarh, India various chronic inflammatory diseases, indicating that imbalance between ILC subsets may perpetuate chronic inflammatory disorders of the human Objectives: Bacterial infections are associated with Th17/Th2 skewed lung. CF lung disease has been associated with an IL-17A signature. We cytokine profile in Cystic Fibrosis individuals. In CF, the altered immune therefore hypothesized that that composition of ILCs might be skewed response might be the result of altered expression of immunoregulatory towards ILC3 s in CF. genes (STATs and SOCS) of cytokine signaling pathway. This might result in Methods: Using flow cytometry, immunofluorescence microscopy and cell defective cytokine signaling regulation and hence immune response which culture, we characterised the ILC composition and cytokine secretion in is difficult to control. The objective of the study was to assess the expression human lung and lung-draining lymph node tissues from patients with end profile of STATs and SOCS genes in CF. stage cystic fibrosis lung disease, in comparison to patients with end stage Methods: The mRNAwas isolated from peripheral blood mononuclear cells emphysema or idiopathic pulmonary fibrosis. Flow cytometric analyses of CF patients in exacerbation, colonization and post exacerbation phases of were also performed in peripheral blood. For flow cytometry, we addressed the disease. The relative gene expression level for SOCS 1, -3, -5 and STAT 1, − live CD45+CD127+Lin (CD3/CD4/CD14/CD19/CD11c/CD34/CD94) cells as -3,-4,-6 genes was quantified by quantitative Real-time PCR. The levels of − − − pan-ILCs and subdivided them into CD117 CRTH2 ILC1, CD117 CRTH2+ Th2 cytokine, IL-6 were also measured in the serum by ELISA. − ILC2, CD117+CRTH2 NKp44+ natural cytotoxicity receptor (NCR)+ ILC3 and Results: The expression of the Th1 pathway associated genes (SOCS1, − − − CD117+CRTH2 NKp44 NCR ILC3 subpopulations. SOCS5, STAT4 and STAT1) was downregulated while the expression of Th2/ Results: Our analyses confirm a strong IL-17A signature of lymphocytes Th17 pathway genes (SOCS3, STAT3, STAT6) was upregulated in both from CF lung tissue compared to other end stage lung diseases. Cluster exacerbation and colonisation phases as compared to healthy controls. The analyses additionally revealed high secretion of IL-17A associated serum levels of IL-6 were also elevated in both the disease groups. After mediators in CF samples compared to samples from other end stage lung antibiotic treatment, the expression of SOCS5 and STAT4 was increased diseases. Across all three compartments analyzed, lung tissue, bronchial while the expression of rest of the genes showed downregulation which lymph nodes and peripheral blood, we observed a higher proportion of shows a shift in immune response from Th2/Th17 to Th1. NCR+ILC3 s in samples from CF patients compared to samples from Conclusion: Our results suggest that infection alters the cytokine signaling patients with other end stage lung diseases. In lung tissue and bronchial pathway through modulation of STATs and SOCS genes and the alteration in lymph nodes these ILC3 s reside in specific spatial distributions. expression of SOCS genes is not able to regulate the overstimulation of Conclusion: Our results suggest ILC3 s to play a particular role in CF lung cytokine signaling. Thus, excessive cytokine signaling results in dysregu- disease, poised to provide early anti-infectious responses in the CF lung. lated immune response further leading to chronic inflammation in CF. ePS3.05 ePS3.07 A neutrophilic inflammation-derived marker of disease Pseudomonas aeruginosa influences the susceptibility and changes the B. Murray1, 2, M. Twigg1, 2, S. Brockbank2,P.Lowry2, P. Fitzgerald2, inflammatory response of primary bronchial epithelial cells (pBECS) to S. Weldon1, C. Taggart1. 1Queen’s University Belfast, Belfast, United Kingdom; rhinovirus infection 2Randox Laboratories Ltd., Crumlin, United Kingdom A. Endres1, C. Bellinghausen1, M. Hogardt2, R. Schubert3, P. Braubach4,5, D. Jonigk4,5, G. Rohde1. 1University Hospital Frankfurt, Medical Clinic I, Objectives: Individuals with cystic fibrosis (CF) experience chronic lung Department of Respiratory Medicine and Allergology, Frankfurt am Main, inflammation. This is due, in part, to abnormally high levels of neutrophils 2 Germany; University Hospital Frankfurt, Institute of Medical Microbiology present in their lungs, releasing neutrophil elastase (NE), which damages 3 and Infection Control, Frankfurt am Main, Germany; University Hospital lung tissue. Higher levels of NE in CF patients is associated with Frankfurt, Department for Children and Adolescents - Division for Allergy, exacerbation, increased disease severity and increased likelihood of 4 Pneumology and Cystic Fibrosis, Frankfurt am Main, Germany; Hannover developing bronchiectasis. Excess levels of NE in the lung results in the 5 Medical School, Institute of Pathology, Hanover, Germany; Hannover Medical cleavage of Secretory Leukocyte Protease Inhibitor (SLPI). SLPI is an anti- School, The German Center for Lung Research (Deutsches Zentrum für protease with host defense properties that inhibits NE activity. Cleavage of Lungenforschung, DZL), Hanover, Germany SLPI by NE results in the formation of a C-terminus derived polypeptide fragment. Due to the issues associated with reliably measuring NE activity, Objectives: Pseudomonas aeruginosa (Pa) is dominating the microbiome of this cleaved SLPI fragment may be used as a more reliable indicator of NE many cystic fibrosis (CF) lungs. We therefore investigated whether a co- activity in the airways. We predict, that cleaved SLPI (cSLPI) may therefore infection with Pa influences the susceptibility and changes the inflamma- act as a biomarker for inflammation and/or bronchiectasis in CF. tory response of primary bronchial epithelial cells (pBECS) to rhinovirus Methods: In silico modelling and BLAST analysis was used to design an infection. immunogen to raise antibodies to NE-cleaved SLPI. Monoclonal antibodies Methods: We isolated pBECS from explanted lung tissue of CF and lung specific to the cSLPI fragment were isolated and purified from hybridoma emphysema patients (n = 6) and cultured them in Air-liquid-Interface cell supernatant. culture until a mucociliary differentiated epithelial cell layer was achieved. Results: The antibodies were determined to be specific for cSLPI via ELISA, A chronic Pa infection was emulated by repeated addition of different detecting as little as 2.7 ng/ml and up to 2000 ng/ml of the recombinant clinical Pa-strains every four days for a total period of 20 days. For arresting protein, and showing negligible cross-reactivity with full length SLPI. The bacterial overgrowth tobramycin (25 μg/ml) was added to the apical side of monoclonal antibodies were used to detect cSLPI in sputum samples from E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S45 the cell cultures. Subsequently, cells were infected with Human Rhinovirus ePS3.09 (HRV)-16 or -1B. Neutrophil elastase inhibitor BI 1323495 restores epithelial barrier Concentrations of interleukin-6 (IL-6) and IL-8 were measured by ELISA. IL- integrity and ciliary beat frequency in cystic fibrosis bronchial 6, IL-8 mRNA expression and viral RNA was quantified using qPCR. Strain- epithelial cells and protects neutrophil-mediated Pseudomonas killing specific Pa elastase LasB activity was assessed through elastin-congo red M. Webster1, J. Garnett1,2, E. Mavin2, P. Nickolaus1, V. Schroeder1, C. Ward2, assay, the effect of other proteases was evaluated through addition of H. Koegler3, S. Kreideweiss1. 1Boehringer Ingelheim Pharma GmbH & Co. KG, inhibitors. Biberach, Germany; 2Translational and Clinical Research Institute, Newcastle Results: IL-6 and IL-8 levels were increased in cells infected with HRV-16 as University, Newcastle upon Tyne, United Kingdom; 3Boehringer Ingelheim well as HRV-1B. International GmbH, Ingelheim am Rhein, Germany Concentrations of both cytokines were comparable in cells co-infected with a mucoid Pa isolate. Infection with a non-mucoid Pa isolate however, Background: Bacterial infections in cystic fibrosis (CF) cause exaggerated abrogated IL-6 but not IL-8 levels. Differences in IL-6 were neither due to neutrophil recruitment to the airways, increasing free neutrophil elastase reduced expression of IL-6 mRNA, nor could we show a degradation (NE) concentration. NE causes epithelial barrier breakdown, alters ion through bacterial proteases. channel activity and induces MUC5AC expression, factors known to impact Viral load was unaltered, but we noticed an increased cytopathic effect ciliary beat frequency (CBF). Excess NE disables neutrophil bacterial killing visible in the co-infection with a non-mucoid Pa strain. ability. Conclusion: We showed that co-infection with Pa alters the inflammatory Objectives: To assess the ability of the NE inhibitor BI 1323495 to inhibit response of pBECS to RV-infection. As IL-6 is crucial for orchestrating anti- NE-induced epithelial barrier breakdown and to restore CBF and viral immunity and promoting lung repair after viral-induced lung injury neutrophil-mediated Pseudomonas aeruginosa (Pa) killing. this change could be a cause of the aggravated response to HRV infection in Methods: Human bronchial epithelial cells (HBECs) were cultured under Pa-colonised airways. air-liquid interface conditions to a fully differentiated tight epithelium (transepithelial electrical resistance [TEER] >400 Ω.cm2). Cells were ePS3.08 exposed to 0.75 μM NE ± BI 1323495 basolaterally for 48 hrs. Cell barrier Azithromycin potentiates avian IgY effects on pulmonary integrity was measured by TEER and apical-basal flux of 10 KDa FITC- inflammation in a murine lung infection model dextran. CBF was assessed by imaging. To assess neutrophil-mediated Pa 1 1 1 2 3 killing, neutrophils from healthy donors were exposed to 1 μMNE±BI K. Thomsen , L. Christophersen , C.J. Lerche , D.B. Holmgaard , H. Calum , 1,4 1 1 1323495 1 hr prior to Pa addition. Colony-forming units (CFUs) were N. Høiby , C. Moser . Rigshospitalet, Copenhagen University Hospital, 2 counted after 2 hrs. Department of Clinical Microbiology, Copenhagen, Denmark; Slagelse 3 Results: NE reduced epithelial barrier integrity in both normal and CF Hospital, Department of Clinical Microbiology, Slagelse, Denmark; Hvidovre HBECs, demonstrated by reduced TEER and increased barrier permeability. Hospital, Department of Clinical Microbiology, Hvidovre, Denmark; 4 Using 1–3 μM BI 1323495, barrier integrity was restored to similar levels as University of Copenhagen, Institute of Immunology and Microbiology, under control conditions, consistent with inhibition of NE-mediated Costerton Biofilm Center, Faculty of Health and Medical Sciences, Copenhagen, protease activity. BI 1323495 (3–10 μM) restored CF CBF to rates within Denmark the range of normal HBEC CBF measured under control conditions. Pa CFUs Objectives: Moderation of polymorphonuclear neutrophils (PMNs) as were reduced with neutrophils present; however, pre-exposure of critical defense against pathogens may pose a promising approach to delay neutrophils to NE prevented bacterial killing. Neutrophils exposed to NE the chronic settlement of Pseudomonas aeruginosa (Pa) lung infection in in the presence of BI 1323495 showed restored ability to kill Pa. cystic fibrosis (CF) patients. Avian IgYantibodies boost the innate immunity Conclusion: The NE inhibitor BI 1323495 restores epithelial barrier in the CF setting by facilitating a prompt bacterial clearance by PMNs*. integrity and CBF in NE-exposed CF HBECs and may protect against NE- Azithromycin (AZT) comprises immunomodulatory actions and the induced suppression of neutrophil Pa killing. present study evaluated possible adjunctive effects of AZT to IgY immunization on pulmonary inflammation in a murine lung infection ePS3.10 model. Patient demographics and baseline disease characteristics in a Methods: In vitro exposure of azithromycin pre-treated human poly- multicentre, randomised, double-blind, placebo-controlled phase 2b morphonuclear neutrophils (PMNs) to IgY opsonized P. aeruginosa PAO3 study of lenabasum, a selective cannabinoid receptor type 2 agonist, in was employed to evaluate phagocytosis mediated ROS production by cystic fibrosis luminol-chemiluminescense and bacterial killing by plating diluted R. Chiron1, J.S. Elborn2, P. Flume3, D. VanDevanter4, N. West5,I.Fajac6, samples overnight followed by colony counting. N. Dgetluck7, Q. Dinh7, B. White7, J.F. Chmiel8, M. Konstan4, Lung infection model: Bacterial suspension ±IgYand ±AZT was inoculated JBT101-CF-002 Investigators. 1Hôpital Arnaud de Villeneuve, CRCM, intranasally in Balb/c mice. 24 h post-infection, homogenized lungs were Montpellier, France; 2Dentistry and Biomedical Sciences, Queen’s University serially diluted and cultured for estimation of bacterial load. Inflammatory Belfast, and Belfast City Hospital, Belfast, United Kingdom; 3Medical University cytokines were quantified by luminex multiplex bead assay. of South Carolina, Departments of Medicine and Pediatrics, Charleston, United Results: The PMN-mediated bacterial killing of Pa was significantly States; 4Case Western Reserve University School of Medicine, Department of increased by IgY compared to non-IgY controls (p < 0.005). The bactericidal Pediatrics, Cleveland, United States; 5Johns Hopkins University, Department of capacity of PMNs was enhanced by AZT (+IgY) compared to non-AZT (+IgY) Medicine, Baltimore, United States; 6AP-HP.Centre - Université de Paris, Paris, control (p < 0.05). The pulmonary bacterial load of IgY treated mice was France; 7Corbus Pharmaceuticals, Inc., Norwood, United States; 8Riley Hospital reduced 2-log 24 h post-infection compared to non-IgY controls (p < 0.02) for Children IU Health and Indiana University School of Medicine, Indianapolis, and was further reduced by AZT treatment (p < 0.05). All cytokines United States paralleled the bacterial elimination from the lungs. Thus combining azithromycin and IgY significantly reduced the pulmonary cytokine Objectives: We report the baseline characteristics of a large cohort of Cystic concentrations of G-CSF (p < 0.05), IL-1b (p < 0.05) and MIP-2 (p < 0.02). Fibrosis (CF) participants enrolled in a Phase 2b trial of lenabasum, a Conclusion: Azithromycin treatment potentiates IgY immunisation and selective cannabinoid receptor type 2 agonist. Treatment with lenabasum facilitates prompt bacterial clearance of Pa and reduces inflammation in a was safe and well-tolerated in a prior Phase 2a study in adults with CF and murine lung infection model. was associated with fewer pulmonary exacerbations (PEx). Methods: This study was designed with input from study investigators, CF experts and regulatory authorities. An important intent of the design was * Thomsen K et al. J Cyst Fibros.2016. to have eligibility criteria that enriched for subjects at increased risk of PEx in the next 6 months. The study is ongoing and remains blinded. S46 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54

Results: Primary efficacy outcome is the rate of PEx (expanded Fuchs Table 1. criteria) at 28 weeks, comparing lenabasum 20 mg BID to placebo. Key Median BMI and FEV1% predicted from annual assessment, best and worst weight and inclusion criteria are subjects with new PEx treated with antibiotics within pulmonary function of the adult population in a year the past 12 months (2–3 with IV only OR 1 with IV and ≥1 with oral BMI (kg/m2) FEV % antibiotics), ≥12 years of age with CF who are on stable standard of care 1 ≥ , FEV1% predicted 40%. CFTR modulators are allowed. The study Annual assessment (n = 174) 21.63 60 enrolled 426 subjects over 19 months who received ≥1 dose of study drug BMI best weight in a year (n = 168) 22.39 67 in 21 countries with 105 sites (34 in North America and 71 in Europe), with BMI worst weight in a year (n = 168) 20.86 59 last subject first visit on NOV 14, 2019. Baseline characteristics are shown in BMI best FEV1 in a year (n = 167) 21.48 69 BMI worst FEV in a year (n = 167) 24.61 54 Table 1. 1

Table 1. Baseline Demographics and Disease Characteristics (Blinded) The most significant positive correlation with FEV1% was BMI, taken at annual assessment (r = 0.2, p = < 0.05) and serum creatinine (r = 0.159, 2–3 PEx past 1 PEx past 12 mo Overall p = 0.049). Percentage of weight loss correlated significantly with percent- 12 mo Requiring Requiring IV age of FEV1 loss (r = 0.3, p = 0.035). Also, number of exacerbations and days IV antibiotics antibiotics under medication in a year had a significant negative correlation with − Mean ± SD or % N = 220 (51.6%) N = 198 (46.5%) N = 426 FEV1%(r= 0.41, p = < 0.001, both). Years of age 28.1 ± 10.10 25.9 ± 10.50 27.0 ± 10.29 Conclusion: Cystic fibrosis clinical outcomes are complexly affected by Female 57.7% 49.0% 53.5% multiple variables. BMI, percentage of weight loss and number of

CFTR modulators 29.5% 22.2% 25.8% exacerbations influence lung function as measured by FEV1%. Further FEV1% Predicted 55.9 ± 16.25 64.7 ± 18.15 60.4 ± 17.81 analysis of these variables is needed but this questions the validity of BMI CFQ-R Respiratory 83.3 ± 6.80 76.0 ± 6.95 78.5 ± 7.50 taken alongside the best FEV1 in a year as a good marker of nutritional (Children 12 & 13) status. Whereas weight loss may be a more sensitive marker of longer term CFQ-R Respiratory 62.8 ± 18.9 65.5 ± 18.6 63.9 ± 18.64 health as measured by FEV . It may also be valuable to assess the (Teen/Adult) 1 underlying body composition of weight loss (fat vs. fat free mass).

Conclusion: This is the first Phase 2b study to use rate of PEx as the primary ePS4.02 efficacy outcome in a patient population with any CF mutation, bacterial The weight of the problem: obesity in people with cystic fibrosis profile, who maintained their current standard of care and who are at F. Kutubudin1, S. Pandya1, D. Nazareth1, M. Walshaw1. 1Liverpool Heart and higher risk of PEx in the next 6 months. Chest Hospital, Liverpool, United Kingdom

Objectives: Traditional care for people with CF (pwCF) has focussed not only on lung disease but also on improving nutritional status, and a high- ePoster Session 4: Highs and lows of nutritional fat, high-energy diet is part of standard management. However, mindful of status evaluation the worldwide epidemic of obesity and the major challenge it presents to health, we wished to determine the prevalence of and factors associated with overweight and obesity in pwCF in our large adult unit. ePS4.01 Methods: We looked at the BMI recorded at annual review in all 337 pwCF Highs and lows of nutritional status: an evaluation of nutritional status attending our unit between 2018 and 9 and identified those with a BMI in cystic fibrosis patients over the course of a year >25 kg/m2. The prevalence of CFRD, CFLD, osteoporosis/osteopenia, D. Sills1, J.A. Candanedo Carpinteiro2,J.Dewar1, H. Barr1. 1Nottingham obstructive sleep apnoea (OSA), Vitamin D deficiency (<75 nmol/L) and University Hospitals Trust, Nottingham, United Kingdom; 2University of insufficiency (26–75 nmol/L), hypercholesterolaemia (cholesterol Nottingham, Division of Nutritional Sciences, Nottingham, United Kingdom >5 mmol/L) and pancreatic insufficiency (defined as those requiring replacement enzymes) within this group were recorded. Data are Objectives: To evaluate of nutritional variables and pulmonary function of presented as mean ± SD. patients with cystic fibrosis. Results: See Table 1. There were 91 (27%) pwCF with a BMI >25 kg/m2:59 Methods: A retrospective observational study of adolescents and adult (18%), overweight (age 37 ± 11 yrs, 40 male) and 32 (10%) obese (BMI range: patient attending the Wolfson CF Centre, UK. Data were collected from 25–39.9 kg/m2, age 36 ± 13 yrs, 15 male). They were less likely to be DF508 medical records including height, weight, serum creatinine, number of homozygous (chi2 = 10.9, P < 0.05), and 58 (64%) were colonised with exacerbations in a year and days under medication as independent Pseudomonas aeruginosa. variables and lung function measured as FEV % as the dependent variable 1 Conclusion: The prevalence of overweight and obesity pwCF is high. With for the correlation analysis. improvements in life expectancy in CF, clinicians should be aware of Results: A total of 193 patients were selected as the main study group. The implications and potential risks associated with obesity in the CF mean age of the group was 30.0 ± 10.25 years with a mean BMI of 2 condition. 22.1 ± 3.94 kg/m and a mean FEV1% predicted of 62.5 ± 23.85. The median BMI of the patients was 22.39 kg/m2.

Table 1. (abstract: ePS4.02) Prevalence of overweight and obesity and associated nutritional problems

Pancreatic CFRD CFLD OSA Osteoporosis Osteopenia Vit D Vit D Raised insufficiency (n = 35) (n = 17) (n = 2) (n = 8) (n = 4) Insufficiency deficiency cholesterol (n = 61) (n = 58) (n = 3) (n = 24)

Overweight (n = 59) 44 (75%) 26 (44%) 14 (24%) 1 (1.7%) 6 (10%) 3 (5.1%) 38 (64%) 2 (3%) 11 (19%) Obese (n = 32) 17 (53%) 9 (28%) 3 (9.4%) 1 (3.1%) 2 (6.3%) 1 (3.1%) 20 (63%) 1 (3.1%) 13 (41%) E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S47 ePS4.03 Methods: We analysed 9147 datasets obtained between 1995 and 2019 Association of body composition and lung function in adult patients from 174 CF patients (86 girls and 88 boys) below 18 years of age. Weight, with cystic fibrosis - data from Croatia length, BMI, triceps skinfold, subscapular skinfold and percentage of body A. Vukic Dugac1, 2, A. Ladic3, L. Tanackovic2, L.T. Dobric2, I.K. Crnogorac2, fat (the latter only for children aged 8.0 to 17.9 yrs.) were compared to A. Dobric2, I. Bambir4, T. Jalusic-Gluncic1, T. Odobasic Palkovic1, recent German reference data [A] by calculating the respective z-scores. D. Tjesic-Drinkovic2,4, D. Tjesic-Drinkovic2,4. 1University Hospital Centre Results: Compared to healthy children, the patient cohort as a whole Zagreb, Clinic for Respiratory Disorders ‘Jordanovac’, Zagreb, Croatia; displayed poorer nutritional status (Table 1), with girls even worse than 2University of Zagreb, School of Medicine, Zagreb, Croatia; 3University Hospital boys. Triceps skinfolds were more frequently reduced than BMI values. 4 Centre Zagreb, Department of Gastroenterology, Zagreb, Croatia; University Patients with normal lung function (FEV1 in the upper quartile above 0.04 Hospital Centre Zagreb, Department of Pediatrics, Zagreb, Croatia z-scores) had significantly better nutritional status than those with the − poorest lung function (FEV1 in the lower quartile below 2.4 z-scores). Objectives: Pulmonary dysfunction is the main cause of mortality in cystic Conclusion: Triceps skinfold measurements were more often abnormal fibrosis and has a close relationship with . Therefore, early than weight, height or BMI z-scores. The potential to detect malnutrition detection of malnutrition is essential to starting nutritional interventions earlier by measuring skinfolds will be assessed in additional longitudinal as soon as possible. Routinely BMI is used as a marker of malnutrition but analyses. Bio-electrical Impedance Analysis (BIA) is now widely used method in body composition assessment. Our aim was to evaluate relationship Reference: between BMI, pulmonary function tests and BIA variables - fat free mass [A] Body measurements of children and adolescents in Germany- (FFM), sarcopenic index (SI), phase angle (PA) and fat free mass index KiGGS. Stolzenberg H et al. 2007. (FFMI). Methods: 30 adult CF patients treated in adult CF centre in Croatia were ePS4.05 included. After obtaining basic demographic, anthropometric and clinical Resting energy expenditure in patients with cystic fibrosis during a data, each patient had pulmonary function tests and BIA performed. pulmonary exacerbation Results: 30 CF patients (17F, 13M) entered the study. Mean age, FEV , BMI 1 2 2 2 1 1 J.A. Finocchiaro , A. Fernández , P. Barcellandi , N. Etcheverry , N. Irigoyen , and FFMI were 24.7 years (range 17–34), 2.03 L (range 0.53–4.38), 13.1 kg/ 1 1 2 2 F. Rentería . Sor Ludovica Children Hospital, Pediatric Pulmonology, La Plata, m (range 13.1–28.7) and 16.9 kg/m (range 12.9–21.5), respectively. We 2 Argentina; Sor Ludovica Children Hospital, Nutrition and Growth, La Plata, found positive correlations between FEV and BMI, FFMI, PA and SI (r = 0.31, 1 Argentina p = 0.09; r = 0.52, p = 0.0002; r = 0.45, p = 0.01; r = 0.65, p = 0.0001, respect- ively). Multiple linear regression showed statistically significant influence Introduction: Patients with CF may present an augmented resting energy of sarcopenia on pulmonary function (p = 0.04). There was a 0.4 increase in expenditure (REE). During a pulmonary exacerbation inflammation

SI for each extra litre in FEV1. increases and pulmonary function is reduced, causing further alteration Conclusion: We have presented the first evaluation of nutritional status on of REE. national level regarding adult CF population in Croatia. Sarcopenic index Objective: To evaluate REE, nutritional status and pulmonary function in a may be a better prognostic indicator of severe pulmonary dysfunction in group of patients with Cystic fibrosis admitted to hospital for intravenous adult CF patients than BMI, and the early recognition of malnutrition by BIA antibiotic treatment of a respiratory exacerbation. may improve clinical outcomes. These preliminary results point towards Methods: Prospective study in patients older than 6 years of age requiring the importance of an interdisciplinary approach and obligatory body treatment of a moderate pulmonary exacerbation. REE through indirect composition studies while assessing CF patients. calorimetry (IC), anthropometrics, pulmonary function and blood para- meters were measured upon admittance and previous to discharge. The ePS4.04 following variables were registered: REE (absolute value and percent of Skinfold measurements for nutritional assessment: a longitudinal calculated through Schofield); height, weight and BMI (Zscore); VEF1 single centre analysis (absolute and percent predicted); White blood count (WBC), platelet H. Ellemunter1, C. Hindinger2, M. Dumke2, G. Steinkamp3. 1Medicial count, hemoglobin (HB), C reactive protein (CRP) and erythrocyte University of Innsbruck Cystic Fibrosis Centre, Innsbruck, Austria; 2STAT-UP - sedimentation rate (ESR). Means were compared with t test for paired Statistical Consulting & Data Science GmbH, Munich, Germany, Munich, samples. Germany; 3Clinical Research and Medical Scientific Writing, Schwerin, Results: 19 patients were enrolled,17 completed the protocol and 2 IC were Schwerin, Germany discarded due to technical difficulties. All patients were pancreatic insufficient. Mean age was 11,5 years (6,1–18,3) and 47% were female. We Objectives: The nutritional status of people with CF has improved over the found a significative increase in Z score weight (−1,1/−0,6 p0, 013), Z score last decades. However, a substantial proportion of European patients BMI (−0,75/−0,37 p0, 008) and VEF1%predicted (57,89/72,94 p < 0,001) and remain malnourished, assessed by weight, height or body mass index absolute values (1,3/1,6 p < 0,001). There was a significant decrease in (BMI). At Innsbruck University CF centre skinfold measurements have been platelet count (p0, 03) and a non-significant decrease in ESR, CRP and WBC. performed at each outpatient encounter since 1995. We aimed to assess REE absolute value (1375,36/1374,14 p0, 98) and % predicted by Schofield whether skinfolds were more often abnormal than weight or BMI.

Table 1. (abstract: ePS4.04)

Median z-score Decreased z-score Median z-score in patients grouped

<-2 (% of data) by FEV1 z-score

Parameter Girls Boys Girls Boys Lower Upper quartile quartile

Length −0.41 −0.10*** 8.1%. 6.0%* −0.78 −0.20*** Weight −0.66 −0.35*** 11.8% 6.5%*** −1.20 −0.12*** Body mass index −0.66 −0.39*** 8.0% 6.2%* −1.13 −0.05*** Triceps skinfold −1.00 −0.68*** 14.6% 13.4% −1.13 −0.70*** Subscapular skinfold −0.50 −0.47 8.3% 8.6% −0.80 −0.19*** Percent body fat −0.79 −0.32*** 10.9% 3.6%*** −0.78 −0.32***

*: p < 0.01, ***: p < 0.0001, Fisher’s exact test and t-tests. S48 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54

(116,43/113,93 p0, 6) remained unchanged, as well as Z score height (p0, 68). Na:CrUr Na:CrUr *P value Conclusion: We found an augmented REE that persisted elevated after ratio ≤17 ratio >17 exacerbation treatment, despite an increase in pulmonary function, Age/yr (Mean ± S.D.) 10 ± 4.36 9 ± 4.21 NS improved nutritional status and a probable decrease in inflammation. Gender (Mean ± S.D.) 33/52 (63%) 12/38 (32%) 0.003 Data analysis of a bigger sample may be required to reach definitive BMI centile (Mean ± S.D.) 52 ± 26.29 51 ± 28.24 NS conclusions. FEV1 Z score (Mean ± S.D.) 90 ± 17.98 93 ± 16.67 NS Pancreatic status (Mean ± S.D.) 5/52 (10%) 4/38 (11%) NS ePS4.07 Abdominal symptoms 4/52 (8%) 6/38 (16%) NS The effects of solar insolation and dietary factors on the level of 25(ОН) (N, % with symptoms) D in patients with cystic fibrosis in 3 regions of the Russian Federation Under 10 Gender (N, %male) 16/26 (62%) 8/34 (24%) 0.003 1,2 1, 2 1,2,3 1 E. Kondratyeva , E. Zhekaite , T. Maksimycheva , A. Zodbinova , [Indices depending on Na status] 4 4 1,2 5 1 L. Klimov , S. Dolbnya , V. Sherman , N. Ilyenkova . FSBSI «Research Centre *Unpaired t-test was used for continuous variables and χ2 for categorical 2 for Medical Genetics», Moscow, Russian Federation; Children’s Clinical variables. Multidisciplinary Center of the Moscow Region, Mytishchi, Russian Federation; 3FSBEI FPE RMACPE MON Russia, Moscow, Russian Federation; 4Stavropol It appears sodium replete status is not related to nutritional status, age, 5 State Medical University, Stavropol, Russian Federation; Voino-Yasenetsky FEV1, pancreatic status or abdominal pain. This data suggest that CF males Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation are more often sodium depleted and this finding is not confined to post- pubertal subjects. Objectives: To study the effects of solar insolation and dietary factors on Conclusion: Young male CF patients appear more commonly sodium the level of 25(ОН)D in cystic fibrosis (CF) patients throughout the 4 depleted but this does not affect clinical status. This sex difference is likely seasons of 2018 in 3 CF centres in the Russian Federation (Moscow region multifactorial but differential sweating, oral intake, or physical activity may centre (M), Krasnoyarsk-Siberia(N), Stavropol-South (S)). play a part. Routine assessment of sodium status is not necessary beyond Methods: 1024 samples of serum 25(ОН)D (578 - from CF patients, 446 - infancy and we will adjust our practice accordingly. Future work will from healthy group) were assessed. Solar insolation level was evaluated investigate the observed sex difference. using the duration of sun exposure (DSE). Serum vit.D level was evaluated using ELISA. Vit.D intake was estimated using a survey (3 days). ePS4.09 Results: 25(ОН)D levels: Ме-28,6 ng/ml (CF), Ме-29,6 ng/ml (healthy) Spot urine sodium/creatinine ratio in cystic fibrosis patients and its (р≥0,05). DSE in region M was -2099, 4 hours; in region N-1978,7 h; in relation to nutritional status region S- 2347,0 h/year. 1 1 1 1 1, 2 ОН I. Bambir , A. Ladic , L. Omerza , I. Markelic , A. Vukic Dugac , The proportion of children with normal 25( )D levels in the CF group 1,2 1,2 1 throughout the 4 seasons was higher in regions M (51.9%) and N (41.8%) D. Tjesic - Drinkovic , D. Tjesic - Drinkovic . Cystic Fibrosis Centre р Pediatrics and Adults - University Hospital Centre Zagreb, Zagreb, Croatia; compared to region S (37.5%) ( < 0,05). The proportion of children with 2 normal 25(ОН)D levels in the healthy group was higher in region S(56.3%) University of Zagreb School of Medicine, Zagreb, Croatia compared to other regions (50.3% and 37.2%) (р < 0,05), which could be Objectives: Infants and toddlers with CF are likely to develop sodium explained by the longer DSE in region S. Low levels of 25(ОН)D in the CF depletion, but data on sodium homeostasis in older age groups is scarce. group could be due to the low prophylactic doses of vit.D in CF patients in Sodium creatinine ratio in spot urine (UNa/Cr) correlates well with region S, and the ineffective follow-up programs, unlike other regions. The fractional excretion of Na and can serve as a simple marker of low dependence of 25(ОН)D level on DSE was established in the CF group normonatremic sodium depletion (NNaD). We investigated the UNa/Cr in (r = 0,2,p = 0,02) and in patients over 3 years old receiving vit.D≤500 IU children and adults in our CF centre to determine the frequency of Na (r = 0,2, p = 0,03). When receiving a dose of more than 500 IU, no depletion and its possible association with nutritional status. dependence was revealed. Dietary factors’ impact on the level of 25(OH) Methods: We collected basic demographic, anthropometric and laboratory D not revealed. data: plasma Na, spot urine Na and Cr from 55 paediatric and adult patients Conclusion: The effect of DSE on serum 25(ОН)D level is noticed only in treated in 2019 in our CF centre. We defined optimal nutritional status as the absence of prophylactic vit.D and doses less than ≤500 IU. Intake of BMI ≥22 kg/m2 for women, ≥23 kg/m2 for men and ≥0 BMI-z-score in doses above 500 IU has a protective effect and could provide sufficient vit.D children. UNa/Cr ratio was considered pathological if <17 mmol/mmol. levels regardless of the region of residence and the child’s nutrition. This Descriptive statistics and Chi square test were performed using statistical study is carried out within the framework of the governmental mission package “R”. ААА-А18-118081390036-6. Results: 30 children (19F, 11M aged 1.3–17.4 yrs, median 9.2 yrs) and 25 adults (14F, 12M aged 18.4–35.1 yrs, median 22.8 yrs) entered the study. ePS4.08 Suboptimal nutritional status was noted in 22/30 (73%) of children and 17/ Sodium supplementation in cystic fibrosis: is it worth it? 25 (68%) of adults. All subjects had plasma Na within the normal range and C. Walker1, A. Hall1, G. Virdee1, C.S. Pao1,S.Brown1, C. Nwokoro1. 1The Royal 2 had UNa <20 mmol/L, suggesting an attempt to conserve Na. However, London Children’s Hospital, London, United Kingdom low UNa/Cr was found in a substantially high proportion of both children and adults (15/25 and 14/30, resp.; p = 0.32). There was no significant Objectives: CF patients risk sodium deficiency due to defective CFTR difference in the proportion of low UNa/Cr ratio in subgroups divided function. Our Regional Children’s CF Centre policy supports dietary and according to nutritional status, neither in paediatric (p = 0.29) nor adult medicinal salt supplementation for most patients. We queried the cohort (p = 0.60). appropriateness of routine supplementation beyond infancy and hypothe- Conclusion: Almost half of subjects of all ages have low UNa/Cr, supporting sised that cessation would be safe in our population, while mitigating long- the hypothesis that CF patients beyond toddlers’ age also suffer from term health sequelae associated with high salt diets, which are more sodium deprivation. The clinical significance of this finding is unclear. relevant as CF patient longevity improves. Sodium deprivation was described to contribute to poor weight gain, Method: We measured urine sodium:creatinine (Na:Cr ) ratio between Ur however, in this set of patients, no association of NNaD defined by UNa/Cr July 2018 and September 2019. Laboratory normal range was 17–52. Key and suboptimal nutritional status was established. markers of clinical status were recorded at the same encounter. Results: Urine samples were obtained from 81% (90/111) of patients (the remainder did not urinate or used incorrect specimen containers). Results were as follows: E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S49 ePS4.10 Results: n = 231 respondents from 33 different countries included a cross- The principles of the Toyota Production System (TPS) applied to an section of clinical specialists, people with CF, their carers and allied health inpatient food service model can improve nutritional outcomes for professionals. 59% of respondents did not routinely use PROMs during children with cystic fibrosis clinical practice. A wide variety of different PROMs/symptom report and T. Katz1,R.Oh2, A. Thomson1, J. Widger1. 1Sydney Children’s Hospital QoL tools were employed across surveyed sites. Barriers to use included Randwick, Sydney, Australia; 2TSSC Australia, Melbourne, Australia lack of time during clinic assessments, lack of staff resources, a lack of translations into multiple European languages and a lack of up to date, Objectives: Satisfaction with the current food service provided at Sydney standardised, disease-specific tools. Children’s Hospital has been poor with high plate waste of 65% across 160 Conclusion: There is a lack of sensitive, standardised patient reported plates (financial loss of $6.99 per meal). Average weight gain per patient is outcome measures in the current context of new generation modulator 0.36% per day of admission (n = 15) and in theory could be higher given the therapies in CF. This survey has been utilised to inform the ECFS CTN and CF poor consumption of hospital food. The CF team partnered with Toyota to Europe Patient Advisory Group in the development of a new disease- apply the principles of TPS in order to improve nutrition outcomes. The specific PROM and patient satisfaction questionnaire and this ongoing primary aim was to increase patient weight gain during a hospital project will enhance patient-clinician informed care in CF. admission. The secondary aim was to increase patient and carer meal satisfaction scores. ePS5.02 Methods: Patient and carer satisfaction was self- reported using a happy Development of quality outcome measures in the face (overall satisfaction with the meal and consumption of 50% or more) or Swedish Cystic Fibrosis Registry - pitfalls and possibilities a sad face (overall dissatisfaction with the meal and consumption of 50% or 1,2 1 1,3 4 L. Backström Eriksson , C. Laine , I. de Monestrol , A. Lindblad , less). Where a sad face was recorded, the patient or carer was asked to 4 5 1 E. Bergenmar-Ivarsson , S. Järvholm . Karolinska University Hospital, nominate a reason why from a list of set domains. Each sad face generated a 2 Stockholm CF-Center, Stockholm, Sweden; Karolinska Institutet, Department problem-solving report, the ‘5why’ methodology was used to determine a of Clinical Neuroscience/Division of Psychology, Stockholm, Sweden; root cause and a countermeasure designed so the problem didn’t recur. 3 Karolinska Institutet, Department of Clinical Science, Intervention and Results: There were a total of 60 sad faces out of 99 meals (60%) with 9 4 Technology/Division of Paediatrics, Stockholm, Sweden; Queen Silvia’s identified reasons, the two most common being ‘there were no suitable Children’s Hospital, CF Centre/Paediatric Clinic, Gothenburg, Sweden; options’ and ‘the meal did not taste good’. After conducting root cause 5 Sahlgrenska University Hospital, CF Centre/Adult Clinic, Gothenburg, Sweden analysis on both, the team determined that a more in-depth review of the statewide menu was necessary, but would extend beyond the scope and Objectives: In Sweden a CF Registry is used since 1994, and an active span of control for this project. Therefore, a temporary, but more national CF Registry since 2012. In recent years, the need of also including immediate solution was developed to provide CF patients with a selection measures addressing mental health has been highlighted. In 2015 the of alternate room service meals. At the conclusion of the project the board of the Swedish CF Registry assigned the psychologists at the CF number of sad faces reduced to 0% of 198 of the new meals served and Centres to develop 2–4 quality measures. Herein the scope is to describe average weight gain per patient per day increased to 0.42%. this process. Conclusion: The concepts and principles of TPS as applied to improving the Methods: The work was initiated with discussing quality indicators of nutritional status of children with CF admitted to SCH proved successful. addressing mental health in CF care. This resulted in four broad themes; “depression,”“anxiety,”“psychological interventions,”“contact with mental health care.” The operational possibilities of the themes were further discussed with the registry trustee; the measures were directed to ePoster Session 5: Measuring what people with be clearly defined, searchable and not dependent on interpretation. cystic fibrosis think Results: Three measures were created: “attending screening for anxiety and depression,”“self-reported level of anxiety and/or depression” and “contact with psychologist within CF care/elsewhere.” The first version of the mental ePS5.01 health registry module was launched in 2016, in 2017 a revised version was Patient reported outcome measures used in clinical practice: an ECFS finalised. Routines for collecting data were implemented according to local CTN and CF Europe survey conditions at the CF Centres, and 2017 was the first full year three (out of 1 2,3 2 4 5 1 K. Hayes , E. Lammertyn , H. de Keyser , P. de Carli , I. Sermet . The four) CF Centres consequently reported data in the registry module. In 2018 Wellcome Wolfson Centre for Experimental Medicine, Northern Ireland Clinical psychological data were reported with a 48% coverage (3/4 centres) of the Research Facility, The Queen’s University of Belfast, Belfast, United Kingdom; entire Swedish CF population (n = 716). 2 3 4 CF Europe, Brussels, Belgium; Muco Vereniging, Brussels, Belgium; Vaincre Conclusion: The process from wheat to bread requires a long-term time 5 la Mucoviscidose, Paris, France; Service de Pneumologie et Allergologie horizon, continuity, organisational and logistic competence, and increased Pédiatriques, Centre de Resources et de Compétence de la Mucoviscidose, personnel resources. The benefits are a more standardised way to address Hôpital Necker Enfants Malades, INSERM U1151, Institut Necker Enfants mental health minimising risks of leaving patients out, and possibilities to Malades, Université Paris Sorbonne, Paris, France conduct research on a national level in the mental health area. Taking this work to the next level international coordination will be required in Objectives: The European Cystic Fibrosis Society-Clinical Trial Network deciding on robust measurers making it possible to register and use shared (ECFS-CTN) and Cystic Fibrosis Europe (CF Europe), the federation of data across countries in Europe and worldwide. national CF patient associations in Europe, undertook an online survey from February to November 2019 to assess use of Patient Reported ePS5.03 Outcome Measures (PROMs)/symptom report and quality of life (QoL) tools Results of 2017–2019 screening of self-concept among children 6–12 used during routine cystic fibrosis clinic assessment visits. The objective years old at the 3 largest cystic fibrosis centres in Sweden was to establish the type and frequency of use of PROMs/symptom report 1 2 3 1 1 and QoL tools in clinical practice and elicit potential barriers to use. E. Bergenmar Ivarsson , C. Laine , P. Larsson , I. de Monestrol , A. Lindblad . 1 2 Methods: The survey was sent to all CTN clinical sites in 2019 (43 CF Queen Silvia’s Children’s Hospital, Gothenburg, Sweden; Karolinska 3 centres, located in 15 different countries throughout Europe), ECFS University Hospital, Stockholm, Sweden; Lund University Hospital, Lund, members both within Europe and beyond and CF Europe Patient Sweden Organisation members, to capture a representative sample of patients, Objectives: International mental health guidelines highlight the import- ’ clinicians and allied health professionals use of these measures. The survey ance of annual psychological screening of CF patients from the age of 12. In was distributed using a popular qualitative research software platform, Swedish CF care, systematic clinical screening regarding self-concept in email link and social media outreach. children 6–12 yrs with the use of the “I think I am” questionnaire (ITIA) (Birgerstam, 2013) was implemented in 2016. Data was routinely collected S50 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 in the Swedish national CF registry. Psychological registry data from the ePS5.05 three largest Swedish CF centres will be presented. Development and preliminary validation of a self-report measure of Methods: From year 2017 to 2019, patients 6–12 years attending three CF cystic fibrosis-specific distress centres in Sweden were asked to complete the ITIA-questionnaire at the C. Snell1, 2, I. Bailey1, 3, D. Sandage1, A. Alpern4, K. Regan1, A. Uluer1,2,3. time of their annual review. Depending on the CF centre the screening was 1Boston Children’s Hospital, Boston, United States; 2Harvard Medical School, made with an interval of one to three years. The results were listed in the Boston, United States; 3Brigham and Women’s Hospital, Boston, United States; national CF registry. After review, a clinical action plan was made for 4Children’s Hospital of Orange County, Orange, United States patients with low scores. Results: Out of the eligible 68 patients who met a psychologist at their Objectives: Despite benefits of mental health screening for patients with annual review 2017–2019, 53 (78%, age 5.6–12.8 of which 51% were girls) CF, research in other chronic illnesses has shown that illness-specific completed the ITIA with minimum interference from their parents. For distress- e.g., distress with managing complex treatments, or feeling those with multiple screening the latest data was chosen. The ITIA stanine powerless in the face of illness- is a stronger predictor of daily functioning scores ranged from 1 to 9 with a median of 5. No significant differences than depression alone. Developing a questionnaire to assess CF-related were found when comparing gender or age. 26 (49%) of the patients distress is critical to providing a more complete picture of distress and daily reported normal/good self-esteem (stanine 4–6). 12 (23%) reported high functioning in CF and enhancing future efforts for screening and self-esteem (stanine 7–9) and 15 (28%) of the patients reported low self- intervention. In this study, we conducted a preliminary validation of a esteem (stanine 1–3). self-report measure of illness-specific distress for adults with CF. Conclusion: Although international guidelines recommend mental health Methods: Thirty patients with CF ages 18 to 60 were administered the CF screening from the age of 12, screening of self-concept is here shown to be a Distress Scale (CFDS), which we adapted in a prior pilot study from an useful method to identity early need of support for patients from the age of established measure in diabetes. Patients in the current study also 6. The clinical experience is that screening of young children boosts their completed the PHQ9 and GAD7, and they completed the Positive and self-awareness and highlights multiple aspects of identity and psycho- Negative Affect Scale (PANAS) before and after the CFDS, to evaluate the logical development. Mental health screening of younger children has impact of the new measure on mood. become a useful part of routine care in three out of four CF centres. Results: With one exception, all CFDS subscales met the internal consistency cut-off of >0.7. The CFDS and its subscales were moderately ePS5.04 to highly correlated with the PHQ9 and the GAD7; correlations were Results of 2017–2019 mental health screening of adolescents at the 3 statistically significant. Using paired-samples t-tests, the increase in largest cystic fibrosis centres in Sweden negative affect and decrease in positive affect on the PANAS, post-CFDS, 1 2 3 2 1 were both statistically significant. Results of a McNemar test of the relative C. Laine , E. Bergenmar Ivarsson , P. Larsson , A. Lindblad , I. de Monestrol . 1 2 sensitivity of the CFDS vs. PHQ9 and GAD7 were highly statistically Karolinska University Hospital, Stockholm, Sweden; Queen Silvia’s Children’s 3 significant. Qualitative responses on the CFDS indicated that patients found Hospital, Gothenburg, Sweden; Lund University Hospital, Lund, Sweden the CFDS to be comprehensive (n = 20). Objectives: International mental health guidelines recommend annual Conclusion: Results suggest that the CFDS has good internal consistency, mental health screening of CF patients from the age of 12. Beck Youth and strong convergent validity with other measures of mental health. The Inventory (BYI-II) has been used systematically in Swedish CF care and CFDS was also found to be more sensitive than existing screening measures, national CF Registry since 2016. The objective of this study was to assess and patients reported they found the measure reflected their experiences. levels of anxiety and depression in adolescents 12–18 yrs in the Swedish CF Future directions include multisite validation of the CFDS. population. The aim was also to compare these screenings with the recommend PHQ-9 and GAD-7. ePS5.06 Methods: From 2017 to 2019 adolescents attending 3/4 CF centres in Assessment of patient satisfaction as a means of quality development Sweden were asked to complete the BYI-II anxiety and depression and patient participation in German cystic fibrosis centres subscales and from 16 yrs, BYI-II, GAD-7 and PHQ-9, at the time of their A.-L. Strehlow1, W. Bremer2, N. Fronia3, A. Goldbeck4, H. Ellemunter5, annual review. Depending on the centre the screening was made with an C. Schwarz6, C. Smaczny7, B. Stähle2, M. Schlangen1. 1Mukoviszidose e.V., interval of 1–3 years. The results were listed in the national CF Registry. German CF Association, Bonn, Germany; 2Working Group for CF Support After review, a clinical action plan was made for patients with high scores. Groups (AGSH), Mukoviszidose e.V., German CF Association, Bonn, Germany; Results: During the 3-year period a total of 94 screenings were completed 3BQS - Institute for Quality and , Hamburg, Germany; 4Working from 70 patients 9.5–18.1 yrs (51% girls). For those with multiple screening Group for Adults with CF (AGECF), Mukoviszidose e.V., German CF Association, latest data was chosen. 56 (80%) patients reported no symptoms of anxiety Bonn, Germany, Bonn, Germany; 5Medical University of Innsbruck, Cystic or depression in the BYI-II. 9 patients (12%) reported elevated range of Fibrosis Centre, Innsbruck, Austria; 6Charité University Hospital Berlin, Berlin, anxiety and 8 patients (11%) elevated range of depression. 5 (7%) of those Germany; 7University Hospital Frankfurt, Frankfurt, Germany with reported symptoms had elevated range of both anxiety and depression. No significant differences were found when comparing Objectives: The nation-wide assessment of patient satisfaction is part of gender, age or with the general Swedish population. 17 (24%) patients the quality management (QM) in cystic fibrosis (CF) care provided by the also completed GAD-7 and PHQ-9, 15 (88%) of these matched the BYI-II German CF Association. It was conducted for the second time in 2018/19 report. (first in 2011) and is an outstanding QM tool in rare disease care in Conclusion: The use of BYI-II has shown to be a good instrument for Germany. A group of patients, parents and physicians is continuously mental health screening to identify symptoms of depression and anxiety involved in the process. although more time-consuming. The comparison of BYI-II with PHQ-9 and Methods: All CF patients and parents of affected children treated in GAD-7 indicates that both instruments are relevant for the screening of German CF centres were invited to participate anonymously in the online anxiety and depression in youth CF population. In clinical use our survey conducted by an institute specialised on health care assessments. experience is that BYI-II is more detailed about the domains in life where The proven disease-specific questionnaire was accessible for six months adolescents experiences symptoms than GAD-7 and PHQ-9. and contained 120 items. The frequency of all chosen problematic response options resulted in a “problem score” (PS) for each item. All CF centres subsequently received their specific results and a benchmark for further analysis and discussion. Results: 46 of the 91 German CF centres cooperated, and 2.051 persons (1.138 CF patients; 913 parents) participated in the survey (2011: 56 centres, 2.475 participants). That corresponds to approximately one-third of the patients/parents potentially reachable in Germany. The results include ten factors with 5–11 items each. In the aggregated report, merging E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S51 all responses independent from individual centres, the factors “doctor- treatment ‘burden’. Using a qualitative approach, semi-structured inter- patient interaction” and “physiotherapy” had a low PS [highly satisfied], views were conducted to assess patient-perspective of the Cystic Fibrosis whereas “equipment/cleanliness” had a high PS in both, out- and inpatient Questionnaire (French) and identify areas that patients felt were not fully units. addressed by the current tool. Conclusion: By providing centre-specific data, the assessment enables CF Methods: Semi-structured interviews were conducted at 4 Paris CF centres to unravel problematic issues and to identify potential for Centres, with an age-stratified sample of patients with cystic fibrosis. improvement involving the whole CF team. The participation of patients Results: 125 patients: stratified by 6–11 yrs (n = 31); 12–19 (n = 38); >19 and local patient representatives leads to mutual exchange and patient (n = 30); parents/carers (n = 26); identified 15 common themes for further empowerment. To facilitate the process, the CF Association provides development. Themes recurring in all groups included burden of disease/ information material and training modules. Next step will be an evaluation treatments; stress/morale; growth and diet. Parental focused themes of process quality and overall effect. included concerns for their child’s future and treatment options, sport and a whilst paediatric focus was upon body image and the impact ePS5.07 of CF upon their social interactions with friends. The Q-Life app: an innovative patient-reported-outcome measure to Conclusion: This study assessed the experiential knowledge of the assess individual quality of life based on a 360 degrees evaluation participants to elicit patient understanding of their condition and their 1 1 2 1 perceptions of the impact of CF upon their everyday experience. Semi- D. Muilwijk , D.C. van der Heijden , V.A.M. Gulmans , C.K. van der Ent . 1 2 structured interviews can inform content and assessment of the impact of UMC Utrecht, Pediatric Pulmonology, Utrecht, Netherlands; Dutch Cystic new therapies beyond the remit of traditional efficacy and safety Fibrosis Foundation (NCFS), Baarn, Netherlands measurements. Wider benefits of the use of PROMs include facilitating Objectives: improved patient involvement in regulatory activities and increased • To identify which outcomes on quality of life (QoL) are relevant for participation in scientific advisory groups and protocol review. The ECFS individual patients with CF and their important relatives. CTN and CF Europe utilise patient experts in a wide variety of collaborative • To compare those individualised outcomes with CFQ-R outcomes. projects and protocol review processes to enhance the exchange of • To assess the feasibility of measuring individual QoL with the Q-Life information and improve patient-clinician informed research. app. ePS5.09 Methods: The Q-Life app was developed in collaboration with patients and CLInical Monitoring and Biomarkers to stratify severity and predict parents of patients with CF. outcomes in children with cystic fibrosis (CLIMB-CF): usability results In the Q-Life app, patients can define personal QoL indicators that are from our feasibility study relevant for their personal situation. These self-defined indicators are C. Edmondson1, 2, N. Westrupp1, 2, P. Seddon3, C. Olden3, C. Wallis4, labelled with an appropriate category and ranked according to importance. C. Dawson4, M. Brodlie5,6, F. Baxter6, J. McCormick7, M. Connon8, L. Blaikie9, For each indicator, patients score to what extent they are compromised by R. Thursfield10,L.Brown10, A. Price11, E. Fleischer11, D. Hughes12, P.Barrett12, CF on a 5-point Likert scale. Patients can invite important relatives to define D. Mak13, J. Wallenburg13, K. Brownlee14, E.W.F.W. Alton1, 2, A. Bush1, 2, and score additional indicators for the patient (360 degrees assessment). In J.C. Davies1,2, CLIMB-CF Study Group. 1Imperial College London, London, this pilot study, 25 clinically stable CF patients of ≥14 years were recruited United Kingdom; 2Royal Brompton Hospital, London, United Kingdom; 3Royal from our outpatient clinic. Patients were instructed to define their personal Alexandra Children’s Hospital, Brighton, United Kingdom; 4Great Ormond QoL indicators in the Q-Life app and to include at least 2 relatives. Street Hospital for Children NHS Trust, London, United Kingdom; Indicators were scored at baseline and after 14 days together with a CFQ. 5Translational and Clinical Research Institute, Newcastle University, Newcastle After study completion, a semi-structured interview was performed to upon Tyne, United Kingdom; 6Great North Children’s Hospital, Newcastle upon collect information about the feasibility and value of the Q-Life app. Tyne Hospitals National Health Service Foundation Trust, Newcastle upon Results: Most patients (56%) defined ≥4 personal QoL indicators. 68% of Tyne, United Kingdom; 7Ninewells Hospital, Dundee, United Kingdom; 8Royal patients labelled at least one indicator with category physical activity and Aberdeen Children’s Hospital, Aberdeen, United Kingdom; 9Raigmore Hospital, sport (68%), followed by social activities (64%), work and education (52%), Inverness, United Kingdom; 10Alder Hey Children’s NHS Foundation Trust, pulmonary symptoms (32%) and daily activities (32%). Almost all self- Liverpool, United Kingdom; 11Department of Pediatrics, London Health defined indicators in the Q-Life app were completely (49%) or partially Sciences Centre, London, Canada; 12IWK Health Centre, Halifax, Canada; (35%) different from any question in the CFQ. According to all interviewed 13Cystic Fibrosis Canada, Toronto, Canada; 14Cystic Fibrosis Trust, London, patients, the Q-Life app provides a better or at least complementary insight United Kingdom in their quality of life and is easier to use compared to the CFQ. Conclusion: Individual QoL outcomes can be identified and measured with Objectives: The clinical status of CF children is conventionally assessed at the Q-Life app, providing an important additional value to the CFQ. hospital visits irrespective of clinical severity; home monitoring could be useful but is not routine. It is unclear how much monitoring CF children and families would be willing to undertake, the minimum amount of data ePS5.08 required and whether any additional focus on health could adversely affect “Il faut continuer à poser des questions/We must continue to ask well-being. We sought to assess the feasibility of data collection with a questions.” Patient-reported outcomes in cystic fibrosis: a qualitative home monitoring app. study of patients with cystic fibrosis and their caregivers 1 2 3 4 4 Methods: We designed an app paired with Bluetooth devices (with advice K. Hayes , I. Sermet , V. Bontemps , P. de Carli , A. Chansard , – 5 5 2 1 from the CF Trust Youth Advisory Group) on which 2 17 year-olds (yo) E. Lammertyn , H. de Keyser , R. Coucke . Wellcome Wolfson Centre for from 8 sites in 2 countries were asked to collect objective and subjective Experimental Medicine, Northern Ireland Clinical Research Facility, The data for 6 months. Here, we report usage data for requested daily measures ’ 2 Queen s University of Belfast, Belfast, United Kingdom; Centre de Resources et (wellness, cough severity, appetite, sputum volume, breathlessness, de Compétence de la Mucoviscidose, Hôpital Necker Enfants Malades, INSERM tiredness; heart rate; O2 saturations; temperature; respiratory rate and U 1151, Institut Necker Enfants Malades, Université Paris Sorbonne, Service de 3 sleep disturbance) and twice weekly measures (weight and lung function Pneumologie et Allergologie Pédiatriques, Paris, France; Campus Condorcet, [only participants >5 yo]). Bâtiment Recherche Sud, Aubervilliers, Paris, France; 4Vaincre la 5 Results: We recruited 148 of a planned 160. 2 withdrew prior to starting Mucoviscidose, Paris, France; CF Europe, Brussels, Belgium (social issues), 2 failed to achieve clinical stability and 10 withdrew during Objectives: There has been a growing interest in the integration of patients’ the study. Median (IQR) completion rate of the cohort for daily measures perspective of their illness and treatment options into the wider healthcare was 38.6% (13.5–70.9%). For weight, twice weekly median completion rate scene. Patient reported outcome measures (PROMs) can prove beneficial as was 44.2% (20.6%–73.1%). 103 participants had spirometers at home; a means of capturing patient perspective of the impact of treatment upon completion rate was 51.9% (25%–76.9%) but was confounded by a daily functioning and well-being including often under-reported connectivity issue with Canadian spirometers which may have reduced S52 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 usage as participants had to enter data manually. However, in the 13–17 yo ePS6.02 15.7% (10.4–35.7%) of daily measures were completed compared to 21.2% Detection of exhaled bacteria in cystic fibrosis lung using novel (10.5–33.7%) for weight and 20.2% (11.5–49.5%) for lung function. facemask sampling system: a feasibility study Conclusion: Data collection at home was incomplete and variable but is R. Nair1, 2, A. Wisniewska1, N. Dayman3, O. Wardle3, D. Modha4, M. Barer1, 4, feasible. Percentage completion tended to be greater for twice weekly than E. Gaillard1,2. 1University of Leicester, Department of Respiratory Sciences, daily measures. Lung function was most often completed despite it being Leicester, United Kingdom; 2University Hospitals of Leicester NHS Trust, time-consuming; this may reflect participant engagement in the results. Paediatrics Respiratory Medicine, Leicester, United Kingdom; 3University Hospitals of Leicester NHS Trust, Department of Physiotherapy, Leicester, United Kingdom; 4University Hospitals of Leicester NHS Trust, Department of Microbiology, Leicester, United Kingdom ePoster Session 6: Cystic fibrosis airway infection: Microbiology samples are central aspects of selecting targeted antibiotic novel methods for detection and treatment therapy to treat pulmonary exacerbations in CF. We evaluated a novel non- invasive approach using face-mask-sampling (FMS). The clinical utility of ePS6.01 FMS in pulmonary tuberculosis has been demonstrated (1) and we Targeted analysis of volatile organic compounds for detection of hypothesized that this approach would detect lower respiratory tract Pseudomonas aeruginosa in cystic fibrosis patients by exhaled breath pathogens at similar rates to sputum or broncho-alveolar lavage (BAL). analysis Objectives: 1. To assess feasibility of FMS in children. 2. To evaluate R. Kos1, P. Brinkman1, A.H. Neerincx1,T.Paff2, M.G. Gerritsen1, A. Lammers1, diagnostic capabilities and processes to maximise yield. 3. To compare with A.D. Kraneveld3,4, H.G.M. Heijerman5, J.C. Davies6,7, H.M. Janssens8, conventional sampling. C.J. Majoor1, E.J. Weersink1, P.J. Sterk1, E.G. Haarman2, L.D. Bos1,9, Methods: Prospective study of participants with stable disease (single A.H. Maitland-van der Zee1,2, sample) or with pulmonary exacerbations (samples at initiation, midway on behalf of the Amsterdam Mucociliary Clearance Disease Research Group and end of IV therapy) wore duck-bill surgical masks fitted with a 3D and the Amsterdam UMC Breath Research Group. 1Amsterdam UMC - printed sampling matrix (SM) for 15–30 minutes. Exposed SM was Location AMC, University of Amsterdam, Respiratory Medicine, Amsterdam, dissolved, cells pelleted and DNA extracted then subjected to PCR to Netherlands; 2Emma Children’s Hospital, Amsterdam University Medical determine bacterial load (16SrDNA) and specific non-tuberculous myco- Centres, Paediatric Respiratory Medicine and Allergy, Amsterdam, bacterium (NTM) pathogen content. Wherever possible, cough swabs, Netherlands; 3Utrecht University, Div. of Pharmacology, Utrecht Institute for sputum and BAL were also obtained. Pharmaceutical Sciences, Utrecht, Netherlands; 4Utrecht University, Inst. for Results: 92 masks were obtained from 39 CF children (aged 4–17 years), 66 Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht, during exacerbations and 26 during stable state. Bacterial pathogens were Netherlands; 5University Medical Centre, Respiratory Medicine, Utrecht, detected in 5/91cough swabs, 16/55 sputum samples and 1/2 BAL samples. Netherlands; 6Imperial College London, National Heart and Lung Institute, The masks revealed bacterial burdens from 102 to 105 16S copies per London, United Kingdom; 7Royal Brompton Hospital, Paediatric Respiratory sample. Lower yield noted during delayed processing method was rectified Medicine, London, United Kingdom; 8ErasmusMC-Sophia Children’s Hospital, with immediate processing. DNAse activation in dissolved SM may explain University Hospital Rotterdam, Paediatrics, Div. of Respiratory Medicine and this. Four sputa were positive for NTM. NTM was detected in one paired Allergology, Rotterdam, Netherlands; 9Amsterdam UMC - Location AMC, mask. University of Amsterdam, Intensive Care, Amsterdam, Netherlands Conclusions: FMS is feasible in children with CF. Clinical utility will require extended studies relating FMS results to clinical outcomes, preferably in Objectives: In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa)isan patients with a higher frequency of samples positive by conventional important respiratory pathogen. Routine microbiology surveillance is analyses. Further testing to optimise bacterial yield and to investigate time-consuming, expensive, and requires expectorated sputum in CF isolation of other CF pathogens from FMS is planned. patients. Volatile organic compounds (VOCs) in exhaled breath may be indicative of Pa colonisation, but suffer from high within-patient variability Reference and lack validation.[van der Schee, Chest, 2015] We aimed to evaluate what [1] (Williams et al. 2014). VOCs have been associated with Pa in literature and performed a targeted analysis of the exhaled breath of CF patients in order to recognize ePS6.03 colonisation non-invasively. Alkyl-Quinolones derivatives could predict Pseudomonas infection Methods: This study consisted of 1) a literature review for a priori VOC chronicity in cystic fibrosis targeting, and 2) a cross-sectional analysis of a prospective CF-cohort study. S. Michalet1, P.-M. Allard2, C. Commun3, V.-T. Nguyen Ngoc1, K. Nouwade1, Pa positive was defined as A) Pa culture at visit and/or chronic Pa infection; B. Gioia4, M.-G. Dijoux-Franca1, J.-L. Wolfender2, A. Doléans-Jordheim3,5. Pa free defined as B) no Pa culture in the past year. VOCs from exhaled 1UMR CNRS-UCBL-VetAgroSup 5557 Ecologie Microbienne, Multi-résistance breath were identified via electron ionization quadrupole MS and the NIST- Environnementale et Efflux Bactérien - Lyon, France; 2Institute of library. The primary endpoint was the area under the receiver operating Pharmaceutical Sciences of Western Switzerland, University of Geneva, characteristics curve (AUROCC) of individual VOCs as well as VOCs Geneva, Switzerland; 3UMR CNRS-UCBL-VetAgroSup 5557 Ecologie combined in a multi-variate logistic regression model. Microbienne, Equipe Bactéries Pathogenes̀ Opportunistes et Environnement, Results: 241 VOCs were identified in literature of which 56 were further Lyon, France; 4Equipe EA 4446 - Molécules Bioactives et Chimie Médicinale evaluated and 13 could be detected in exhaled breath. Exhaled breath of 25 (B2MC), Lyon, France; 5Institut des Agents Infectieux, Lyon, France paediatric and 28 adult CF patients, Pa positive (n = 16) and free (n = 28) was available. 3 VOCs were significantly different (p < 0.05) between Pa Background: Pseudomonas aeruginosa (Pa) chronic infections in Cystic positive (n = 6) and free children (n = 15); 0 were for adults. A logistic Fibrosis (CF) are generally defined with Leed’s criteria. According to this regression model based on 5 or 1 VOC(s) showed a AUROCC of 0.86 (CI definition, one year is needed before chronic infections could be 0.71–1.0) and 0.87 (CI 0.72–1.0) for adults and children, respectively. characterized, limiting therapeutic follow-up of CF patients. A rapid and Conclusion: Targeted VOC analysis based on published data can discrim- standardized definition of chronic infection would allow a better inate children with and without Pa culture, composite VOC fingerprints can management of Pa infections, as well as a quick grouping of patients discriminate adults. These data merit further validation of breath analysis during clinical trials and comparisons between studies. as alternative for pathogen detection. Objective: This study compares the metabolic profiles of Pa strains isolated This work is supported by the Institut Mérieux and the UK CF Trust. from CF patients at different stages of infection in order to identify metabolites differentially produced according to these stages. Material and methods: 44 CF Pa strains were grouped in first and chronic colonization isolates using Leed’s criteria. Metabolites produced by each Pa E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 S53 in the supernatant of a liquid culture were extracted with dichloromethane ePS6.05 and with ethyl acetate. Metabolomics studies (UHPLC-DAD-ESI/QTOF, UV Performance of a new diagnostic tool for the selection of optimal and UPLC-Orbitrap, MS) were performed. antibiotics for patients with cystic fibrosis (clinical efficacy data) Results: Multivariate Analyses of the LC-MS data showed that first C. Kardava1, G. Tetz1, M. Vecherkovskaya1, T. Gembitskaya2,V.Tetz1. 1Pavlov colonization Pa strains could be differentiated from chronic colonization First Saint Petersburg State Medical University, Microbiology and Virology, ones. These Pa strains produced notably more Alkyl- Quinolones (AQ) Saint Petersburg, Russian Federation; 2Pavlov First Saint Petersburg State derivatives, especially five AQs that were discriminant: HQC5, HQNOC7, Medical University, Pulmonology Research Institute, Saint Petersburg, Russian HQNOC7:1, Db-PQS C9 and HQNOC9:1. However, the production of HHQ Federation was equivalent between strain types. The HHQ/HQNOC9:1 ratio was then observed to be significantly different between chronic and primo- Objectives: AntibioticSelection is a novel culture-based test system colonizing strains by using both UV ( p value = 0.003) and HRMS data ( p employing new microbiological algorithms and enabling the selection of value = 1.5E-5). effective antibiotics (Abx) even for polymicrobial drug-resistant infections Conclusions: Some of the AQ derivatives can be used as biomarkers for an in patients with cystic fibrosis (CF). AntibioticSelection is a multi-well plate improve management of CF patients as well as a better definition of the filled with nutrient medium (NM) enabling rapid simultaneous growth of clinical stages of Pa infection. Detection of AQs directly in biological fluids bacteria in mixed biofilms. Clinical specimen is directly plated to the as well as development of AQ biosensors could facilitate the implemen- medium. Each well contains NM supplemented with Abx (1 Abx or 1 Abx tation of such diagnostic tools. mix per well; control wells are Abx free). Antibiotics in the NM are at concentrations clinically achievable at the site of infection. Abx are ePS6.04 categorized as effective if they completely prevent the growth of all 2-Alkyl-4-quinolone quorum sensing signal molecules are potential bacteria present in the biospecimen. biomarkers in cystic fibrosis pseudomonal infection Methods: 6-y longitudinal data for the efficacy of the use of Antibiotic 1 2 3 4 5 Selection (10 patients) vs. conventional antimicrobial susceptibility testing N.M.M. Zain , K. Webb , N. Halliday , D.A. Barrett , E.F. Nash , 5 5 6 7 8 (AST) for antibiotic selection for CF patents. J.L. Whitehouse , D. Honeybourne , A.R. Smyth , D.L. Forrester ,J.Dewar , 9 3 2 10 1 3 Results: When ABXs were selected with conventional AST, the median A.J. Knox , P. Williams , A. Fogarty , M. Cámara , K.D. Bruce , H.L. Barr . 1 number of hospitalisations due to pulmonary exacerbations in 3 years was Kings College London, Institute of Pharmaceutical Science, London, United 2 around 6. Inflammation markers were elevated in all patients within 7 days Kingdom; University of Nottingham, Division of Epidemiology and Public 3 of hospitalisation. After the treatment selected with conventional AST,WBC Health, Nottingham, United Kingdom; Nottingham University Hospitals NHS was normalised in 30% of patients and CRP only in 10%. In turn, once Trust, Wolfson Cystic Fibrosis Centre, Department of Respiratory Medicine, 4 switched to AntibioticSelection, both WBC and CRP were normalised in Nottingham, United Kingdom; University of Nottingham, Centre for 100% patients. On year 2 and 3 of AntibioticSelection usage the levels of Analytical Bioscience, Division of Advanced Materials and Healthcare 5 these pro-inflammatory markers were not elevated. These patients had no Technologies, School of Pharmacy, Nottingham, United Kingdom; University signs of acute inflammation (p< 0.001%) and required no hospitalisations Hospitals Birmingham NHS Foundation Trust, West Midlands Adult CF Centre, 6 with the exception of a prophylactic one. We found that FEV, following the Birmingham, United Kingdom; University of Nottingham, Division of Child 7 use of AntibioticSelection, had increased by 18% and 27% after the 2nd and Health, Obstetrics and Gynaecology, Nottingham, United Kingdom; The 3rd years (p< 0.001%). Body Mass Index increased by 19% as well (p< 0.05%). Prince Charles Hospital, Thoracic Programme, Brisbane, Australia; 8 Conclusion: AntibioticSelection utilizing a novel principle of antibiotic Nottingham University Hospitals NHS Trust, Department of Respiratory 9 selection based on lung microbiota population response to the antibiotics Medicine, Nottingham, United Kingdom; University of Nottingham, Division 10 enables the selection of significantly more effective antibiotics for CF of Respiratory Medicine, Nottingham, United Kingdom; University of patients. Nottingham, National Biofilms Innovation Centre, Centre for Biomolecular Sciences, School of Life Sciences, Nottingham, United Kingdom ePS6.06 Objectives: Pseudomonas aeruginosa (P.aeruginosa) is an important Isolating and characterising phages against Pseudomonas aeruginosa respiratory pathogen in cystic fibrosis (CF) and is associated with increased and Staphylococcus aureus in children with cystic fibrosis mortality and lung function decline. J. Singh1, D. Subedi2, F. Gordillo-Altamirano2,R.Patwa2, H. Selvadurai1, P. aeruginosa produces intercellular signalling molecules including 2-alkyl- J. J Barr2, A. Khatami3,4. 1The Children’s Hospital at Westmead, Respiratory 4-quinolones (AQs), which regulate virulence factor production and Department, Westmead, Australia; 2Monash University, School of Biological biofilm formation in the CF airways. As AQs are detectable in sputum, Sciences, Clayton, Australia; 3The Children’s Hospital at Westmead, Infectious plasma and urine of adults with CF and chronic pulmonary infection of P. Disease and Microbiology Department, Westmead, Australia; 4University of aeruginosa, they are potential biomarkers of infection. Using culture- Sydney, Discipline of Child and Adolescent Health, Westmead, Australia independent methods, we explored the correlation of AQs measured in sputum, plasma and urine with live P. aeruginosa load in CF adults. Introduction and objective: Phage therapy to treat chronic lung infections Methods: Using a live/dead cell separation technique, we analysed 75 in patients with Cystic Fibrosis (CF) is attractive due to its safety, specificity, sputum samples at clinical stability and 49 paired sputum samples at the natural occurrence and ability to potentially be utilised as a targeted beginning and end of antibiotic treatment following pulmonary exacerba- inhaled aerosol therapy. In vitro studies have also shown the ability of tion in CF adults. P. aeruginosa load obtained from quantitative Polymerase phages to penetrate bacterial biofilms and thus help eradicate them. Chain Reaction (qPCR) was compared with the presence and concentration This study was designed to evaluate the feasibility of isolating, propagating of AQs measured previously in sputum, plasma and urine. and purifying phages against bacterial isolates commonly seen in children Results: At clinical stability, the AQs which showed correlation consistently with CF. in all sample types (sputum, plasma and urine) with live P. aeruginosa load Methods: Nine clinical bacterial isolates of Staphylococcus aureus (n = 6), were HHQ, NHQ and HQNO. During infective exacerbations, positive non-mucoid Pseudomonas aeruginosa (n = 2) and mucoid Pseudomonas correlations were observed with NHQ and HHQ pre-antibiotics in all aeruginosa (n = 1) were obtained from sputa of patients followed up in The sample types and a reduction of live P. aeruginosa load was associated with Children’s Hospital at Westmead CF clinic. Phages for each strain were changes in plasma and urine NHQ levels (Spearman rank correlation, isolated from cocktails of environmental water samples. The lysates plasma: r = 0.473, p = 0.005, urine: r = 0.445, p = 0.009). produced were extracted and subjected to phage propagation and Conclusion: AQ levels measured in adult CF samples are associated with purification using the Phage on Tap (PoT) protocol to produce high-titre culture-independent live P. aeruginosa load in the lungs and have potential homogenous phages. as biomarkers of microbial burden of infection during pulmonary Results: Fourteen morphologically distinct plaques were observed on the exacerbations. respective bacterial culture plates (S. aureus n=8,P. aeruginosa n = 6). Five phages (S. aureus n = 3 and P. aeruginosa n = 2) were selected and amplified to high titres (107 to 108 plaque-forming units [pfu]/mL). The 3 S. aureus S54 E-Posters / Journal of Cystic Fibrosis 19S2 (2020) S37–S54 phages showed highly isolate-specific lytic activity. Both P. aeruginosa & modifies lung architecture. Screened from a collection of 50 CF patients phages that were isolated exhibited a wider host range against all of the P. expectorations, 3 Lactobacillus (L. paracasei Lp, L. salivarius Ls & L. brevis Lb) aeruginosa clinical isolates tested, which included both mucoid and non- respiratory strains were identified for its anti-Pa properties in vitro. mucoid strains. The bactericidal activity was further demonstrated on a Methods: Selected strains IA & OA were tested, alone or cocktail (Lpsb, Lsb) time-kill curve. for preventive effect in a murine model of acute Pa pneumonia. Conclusion: We were able to successfully isolate and purify phages with Lactobacillus GG was used as a control. IA & OA of Lactobacillus strains lytic activity against both mucoid and non-mucoid P. aeruginosa as well as (106CFU/mice) 18 h prior to PaO1 infection (106CFU/mice) was evaluated in S. aureus clinical isolates. This pilot study demonstrates the feasibility of 12 groups of C57BL/6 mice (Lpsb, Lsb, Lp, Ls, Lb, Pa, Lpsb+Pa, Lp+Pa, Ls+Pa, isolating phages that may potentially be useful in the treatment of CF Lb+Pa, Lsb+Pa, LGG+Pa) & 3 groups (Lsb, Lsb+Pa, LGG+Pa) respectively. At patients with chronic respiratory infections. 24 h PA post-infection (pi), lung & serum were collected for bacterial counts & cytokines analysis. ePS6.07 Results: The Lpsb cocktail increased the survival rate to 7 days (100% Evaluation of the activity of lytic bacteriophages on a representative p < 0.001) compared to Pa group (11.7%). Lactobacillus treatment decreased collection of Pseudomonas aeruginosa clinical isolates collected from the Pa lung load 24 h pi compared to Pa group with a higher effect for adult patients with cystic fibrosis Lpsb, Lsb, Ls & Lb group (reduction >1log10 p < 0.05). Interestingly, our J. Save1, A. Sauty2, M. Prella3, A. Koutsokera3, G. Resch1. 1University of Lactobacillus strains had better anti-Pa properties than the LGG strain & its IA Lausanne, Fundamental Microbiology, Lausanne, Switzerland; 2Neuchâtel led to a better reduction of Pa lung load 24 h pi than OA. Preventive Hospital, Neuchâtel, Switzerland; 3University Hospital, Lausanne, Switzerland Lactobacillus treatment decreased proinflammatory cytokines (preliminary results). Objectives: Multi-resistant and pan-resistant P. aeruginosa are increasingly Conclusion: This study demonstrated the better protective efficacy of live found in cystic fibrosis (CF). Bacteriophages (phages) are viruses Lactobacillus IA vs OA against murine Pa pneumonia. Mechanistic specifically killing bacteria without affecting human cells and the approaches are under progress. L. salivarius & L. brevis are promising commensal flora. From this perspective, phage therapy could bring a beneficial strains in the context of lung infection in CF. significant benefit in the treatment of CF. In this study, we evaluated the susceptibility of P. aeruginosa clinical isolates from CF patients to an ePS6.10 extensive collection of lytic phages. Glatiramer acetate improves the killing ability of tobramycin in Methods: A representative collection of 51 P. aeruginosa isolates collected Pseudomonas aeruginosa cultured from cystic fibrosis clinical samples from 51 patients in 2016 at the CHUV was gathered according to their R.A. Murphy1, S. Thrane2, J. Harrisson3, S. Schelenz4, T. Vorup-Jensen2, different antibiogram profiles. 104 phages maintained in our laboratory J.C. Davies1,5. 1Imperial College London, National Heart and Lung Institute, were tested in this study. Phagograms were performed by spotting drops of London, United Kingdom; 2Aarhus University, Department of Biomedicine, serial dilutions of each phage stock on top of soft-agar plates containing the Aarhus, Denmark; 3Cycle Pharmaceuticals Ltd, Cambridge, United Kingdom; isolates. After overnight incubation at 37°C, phagograms were determined 4Kings College Hospital NHS Foundation Trust, London, United Kingdom; by checking for lysis zones. 5Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom Results: P.aeruginosa phages were able to infect 84,3% of the isolates. Phage 4073_0118 had the broadest host range with 45,1% coverage. 72,5% of the Objectives: Glatiramer acetate (GA), is a drug licensed for treatment of strains were susceptible to at least two phages and 70,6% to three phages or multiple sclerosis, with which we have previously reported modest more. Only eight strains (15,7%) were fully resistant to all phages. antimicrobial activity against Pseudomonas aeruginosa (Pa). Peptide in Conclusion: This study highlighted that our current phage collection has a structure, GA is similar to antimicrobial peptides, some of which have been high coverage of representative P. aeruginosa isolates collected from local shown to increase antibiotic efficacy. We investigated GA as an antibiotic patients suffering from CF. As at least two phages are necessary to design a resistance breaker of clinical cystic fibrosis Pa against the common cocktail often avoiding the selection of phage-resistant clones, such antibiotic, tobramycin. cocktails could be produced for ca. 70% of the patients with our current Methods: Ten clinical Pa from CF patients, with a range of antibiograms, phage collection. Next steps will be to. were incubated in Mueller-Hinton broth at varying tobramycin (TOB) i. assemble cocktails and study their in vitro antibacterial activities,. concentrations, with/without 50 mg/L GA. After overnight incubation, ii. isolate phages for the non-properly covered strains, and. colonies were counted (n = 3 experiments). Inhibition Curves of CFU/mL for iii. test the best cocktails in a relevant in vivo model. TOB and TOB+GA were generated by Nonlinear Fit, as a percentage of untreated bacteria (GraphPad Prism). Minimum inhibitory concentrations ePS6.08 of 50% (MIC50) and 90% (MIC90)ofPa cells were interpolated from the Intranasal or oral Lactobacilli administration: which one is best for curves. fighting against Pseudomonas aeruginosa respiratory tract infections? Results: Across 10 Pa strains tested, values of TOB MIC50 and MIC90 were 1 2,3 2 2 4 significantly reduced by addition of GA (p = 0.004 and 0.002, respectively), R. Lagrafeuille , M.-S. Fangous , C.-A. Guilloux , S. Gouriou , P. Gosset , 2,3 2,3 2,5 1 indicating the same inhibition of growth by lower TOB concentrations. S. Vallet , G. Héry-Arnaud , R. Le Berre . Inserm, Univ Brest, EFS, UMR 2 Mean TOB MIC reduced from 26.4 to 12.0 mg/L and mean MIC dropped 1078, GGB, Brest, France; Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, 50 90 3 from 67.6 to 44.8 mg/L by co-administration of GA. Presence of GA was France; Département de Bactériologie-Virologie-Hygienè Hospitalierè et 4 effective at lowering MICs in both TOB-sensitive (n = 5) and -resistant Pa; Parasitologie Mycologie, CHRU La Cavale Blanche, Brest, France; Opinfield, MIC dropped from 0.420 to 0.259 mg/L and from 52.4 to 23.8 mg/L, Center for Infection and Immunity of Lille, INSERM U 1019 - CNRS UMR 9017, 50 5 respectively. Institut Pasteur de Lille, Lille, France; Département de Médecine Interne et Conclusion: Both TOB-sensitive and TOB-resistant Pa strains demonstrate Pneumologie, CHRU La Cavale Blanche, Brest, France increased susceptibility to TOB in the presence of GA, in vitro.Co- Objectives: In CF patients, Pseudomonas aeruginosa (Pa) chronic lung administration of GA could enhance efficacy of TOB in cystic fibrosis, as infections combined with acquisition of antibiotics resistance leads to an antibiotic resistance breaker. With a good safety profile in a chronic therapeutic deadlock. Among non-antibiotic alternative, the use of condition, glatiramer acetate is a strong candidate for repurposing as an Lactobacilli is promising since its oral administration (OA) stimulates antibiotic adjunct. Work is ongoing onactivity of GA in the presence of immune system, decreases nosocomial pneumonia & CF exacerbations sputum for confirmation of potential clinical utility. incidence. IntranasaI administration (IA) stimulates respiratory immunity Supported by the NIHR Imperial Biomedical Research Centre. Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Posters

bidirectional Sanger sequencing of the entire 27 CFTR exons together Genetics with their exon/intron junctions, or by targeted PCR followed by Sanger sequencing or by real-time PCR. P001 Results: Mean age 10.4+_4.73. Thirty-two (71.1%) were Qatari. Seven Thirteen novel and rare mutations causing cystic fibrosis not included different mutations were identified: Homozygous c.3700 A > G (p. in CFTR 2 database Ile1234Val) in 30 (66.67%) Qatari CF children, homozygous F508del in 7 1 1 2 (15.56%) children that includes 2 Qatari from different family tribes which K. Zybert , L. Wozniacki , A. Sobczyńska-Tomaszewska , 3 2 4 1 has not previously reported; 1 Syrian with meconium ileus; 2 Pakistani and K. Wertheim-Tysarowska , K. Czerska ,M.Ołtarzewski , D. Sands . 1 2 Bangladeshi, homozygous c.1705T->G (Tyr569Asp) in 2 (4.44%) Pakistani Institute of Mother and Child, Department of Cystic Fibrosis, Warsaw, Poland; 2 3 siblings, homozygous 3120+1G>A (c.2988+1G>A) in 1 (2.22%) Pakistani, MedGen Medical Centre, Warsaw, Poland; Institute of Mother and Child, 4 homozygous deletion40 KB Exon4-9 in 1 (2.22%) Iranian, compound Department of Medical Genetics, Warsaw, Poland; Institute of Mother and heterozygous c.2805-2810 del TCAGA,c.2290C>T (p.Leu941Ter,Arg764Ter) Child, Department of Screening and Metabolic Diagnostics, Warsaw, Poland in 1 (2.22%) Bangladeshi, compound heterozygous c.254G>A,c.3196C>T (p. Introduction: Currently (January 2020) there are 2075 mutations listed in Gly85Glu,p.Arg1066Cys) in 1 (2.22%) Jordan, homozygous c.2997- CFTR1 database. However, the clinical consequences of the mutations 3000delAATT (p.Ile1000) in 1 (2.22%) Egyptian, and homozygous should be sought in CFTR2 database which contains only 346 mutations 2043delG (c.1911delG) in 1 (2.22%) Syrian CF child. classified as CF-causing. Due to the increasing number of mutations and Conclusions: F508del-CFTR mutation does exist in Qatar and another insufficient knowledge about correlation between the genotype and ethnicity. Recognition of the most frequent CFTR mutations in different phenotype, there is an urgent need to determine which mutations are populations will help in early CF genetic diagnosis and counseling. pathogenic, non-pathogenic or lead to variable clinical consequences. Aims: The aim of this study is to characterise the clinical outcome of CF P003 patients with 13 novel or rare mutations not included in CFTR2 database. The diffusion processes of the CFTR mutations in Brittany (France) Materials and methods: The study group included 13 patients born N. Pellen1, G. Bellis2, G. Rault3, L. Gueganton1, C. Belleguic4, E. Deneuville4, between September 2006 and May 2019, who had positive sweat tests H. Journel5, S. Ramel6, V. Scotet7, C. Ferec7. 1Ildys Foundation, Roscoff, France; (>60 mml/l) and clinical symptoms of cystic fibrosis or at least positive 2French Institute for Demographic Studies (Ined), Paris, France; 3LEPS, Paris, result of CF NBS (Newborn Screening). All patients had two CFTR mutations France; 4Rennes University Hospital, CF Center, Rennes, France; 5Bretagne- identified, including at least one mutation not listed in CFTR 2 database. Atlantique Hospital, CF Center, Vannes, France; 6Ildys Foundation, CF Center, Results: We identified 13 CF-causing mutations H199R, R289NfsX17, Roscoff, France; 7Inserm UMR 1078 ‘Génétique, Génomique Fonctionnelle et I618Rfs2, L468P, A1217E, Q359R, T682Kfs40, S1347PfsX13, T1036I, W356X, Biotechnologies’, Brest, France E33X, dup.16,17A and W1282R. The diagnosed patients presented with a wide spectrum of clinical symptoms. In one patient sweat tests values were Objectives: The purpose of this study is to understand the historical initially borderline, but in subsequent tests they become positive. Thus, spreading process of CFTR mutations in Brittany. sweat tests were positive in all patients. During our follow-up, most of Methods: Brittany is the French region where the prevalence of cystic children presented respiratory symptoms. The most common were cough fibrosis (CF) is the highest (French CF Registry-Annual Data Report 2017). and exacerbation of bronchopulmonary disease. One patient was treated The population at the root of this study was composed of 1037 CF carriers, for atelectasis of the upper right lobe before the age of three months, parents of 705 individuals clinically diagnosed with CF and having lived in despite the early start of physiotherapy. We reported positive pharyngeal Brittany. Their ancestry was traced back, by a genealogical reconstitution, swab for P. aeruginosa in 4 patients. and brought together more than 630 000 kinspeople combined in a Conclusions: Based on the clinical phenotype we concluded that all database. Then, thanks to the Granite-Muco software, specially created for described 13 CFTR mutations are CF-causing. This observation points that the needs of the study, calculations (couples common to healthy carriers, each patient with a mutation of unknown clinical consequences in one inbreeding rate, path taken by the gene, etc.) and maps made it possible to CFTR allele requires attentive follow-up. trace the path taken by the different mutations. Results: The analysis of couples common to the carriers of the same P002 mutation showed a differential territorial distribution for the 11 most Spectrum of CFTR mutations in children with cystic fibrosis in Qatar frequent mutations. An over-representation in the west of Brittany 1,2,3 1,2,3 1 2 encourages to put these results in relation with the phenomena of A. Abdulwahab , A. Alnaimi . Sidra Medicine, Doha, Qatar; Hamad 3 immigration from the British Isles between the 3rd and the 7th centuries. Medical Corporation, Doha, Qatar; Weill Cornell Medicine, Doha, Qatar Conclusion: The different origins of the populations (Ireland, Wales, Objectives: Cystic fibrosis (CF) is not a rare disease and found in all ethnic Brittany Cornwall) could explain the CF frequency of occurrence and its groups, with an evaluated prevalence of 1 in 10,000 births among Arabs. Breton distribution today. Identification of both mutated cystic fibrosis transmembrane regulator Limited in very specific areas, reconstructed family genealogies feed the (CFTR) allele in CF children is an important for genetic counseling and chronicle of genetic reproduction, particularly through the forms of probably patient specific treatment. alliance in an endogamous environment. This local rooting has the effect Methods: Total 45 children confirmed CF diagnosis by elevated concen- of reducing genetic diversity by external inputs. tration of sweat chloride (> 60 mmol/l) on two different occasions underwent CF genetic study. Molecular diagnosis was done by S56 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P004 months and a clinical visit every year or when requested by the family Association of MMP3 polymorphism with the formation of pulmonary pediatrician. and hepatobilic complications in children with cystic fibrosis A. Goryainova1, S. Semykin1. 1Russian National Research University named by P006 N.N.Y. Pirogov, Russian Children’s Clinical Hospital, Moscow, Russian Is Phoenician the origin N1303K CFTR mutation? Federation R. Farhat1, A. El Seedy1, 2, S. Corbani3, A. Megarbane4, A. Kitzis1, V. Ladevezè 1. 1Université de Poitiers, Poitiers, France; 2University of Alexandria, Department Objectives: To establish the cause of variability the formation of 3 of Genetics, Alexandria, Egypt; University St Joseph, Unité de Génétique pulmonary complications and liver cirrhosis in patients with CF. 4 Médicale Lebanon, Beyrouth, Lebanon; Institut Jérôme Lejeune, Paris, France Methods: Examined 186 children with CF from the age of 1 to 17 years old (99 girls, 89 boys). He carried out genetic analysis (the panel included The history of Lebanon characterised by flows of different ethnic groups has genes and polymorphisms of connective tissue- (COL3A1, LAMC1, IL10, IL8, enabled the introduction of new genes and a wide variety of genetic IL1B, VEGFA, ESR1, MMP2, MMP3, MMP9, TIMP2). diseases. CF figures among the 184 reported genetic diseases of the Results: Out of 186, in 47 children (25%) on the basis of a clinical and Lebanese population. laboratory examination, liver cirrhosis with portal hypertension was The N1303K mutation is very common in the Mediterranean countries and diagnosed, in 113 (61%) children, severe bronchopulmonary lesions- seems to have the highest frequency in the Lebanese population. multiple be (61%),interstitial pneumofibrosis (56%), CF- lung dysplasia Interestingly, the countries and geographic locations that have a high (21%), pneumothorax (1,6%). The remaining 28 children in the study were N1303K frequency were old Phoenician settled colonies or trading posts. without severe pulmonary/hepatobiliary pathology. From the entire panel Phoenician migration flows from current Lebanon, during the first of the studied genes, only MMP3-1171 insA polymorphism was identified: millennium BCE, may have introduced new genes in these coastal heterozygous (genotype- 6A/6A)- 87ch (47%),homozygous-37 (20%),52ch Mediterranean cities. Genetic Phoenician markers could be typed in (33,3%)- without polymorphism. In hetero- and homozygotes, liver worldwide CF-alleles carrying N1303K to support this hypothesis. cirrhosis and pulmonary complications in the form of pneumofibrosis, Moreover, for tracing the origin of the most common CFTR mutations atelectasis and bronchiectasis were statistically more often detected. (F508del, G542X and N1303K), several CFTR genetic markers have been (p < 0,001,OR = 6,005; CI = 6,0–11,5). used. The haplotype at CFTR markers IVS1CA-IVS6aGATT-T854-TUB20 was Conclusion: MMP3 polymorphism-1171insA (5A/6A) is possibly associated always 21-6-1-2 with the N1303K mutation as well for the F508del and with manifestations of pulmonary fibrosis and development of liver G542X mutations. In our study in Egyptian and Lebanese patients, the cirrhosis in children with CF. haplotype N1303K is always detected with 6GATT except in one Egyptian patient with 7GATT. Moreover, the c.869 + 11C is always detected in the WT P005 haplotype whereas N1303K is only associated with c.869 + 11T. Lessons from 5T;TG12 This haplotype is only present in 1.4% of normal chromosome in actual 1 2 2 2 1 1 European suggesting that these mutations arose from a none-European N. Cirilli , R. Munaretto , F. Perticaroli , A. Bruni , N. Baiocco , B. Fabrizzi . 1 population. Moreover, no population has presented this haplotype in a high Cystic Fibrosis Centre, Mother-Child, United Hospitals, Torrette di Ancona, 2 enough frequency to be considered at the origin of the three most common Italy; Biomedical Engineer, Ancona, Italy mutations. It is important to note here, that the highest frequency, even not Background: 5T;TG12 variant in association with a CF-causing mutation is sufficient, was detected in the Druze population of Palestine (other small defined as having varying clinical consequences (www.cftr2.org). People Druze community is also settled in Lebanon). Thus, the origin of the carrying the 5T;TG12 variant in association with a CF-causing mutation N1303K mutation could be Phoenician, but no previous studies have been should have periodic check-ups with their doctor even if they have no done in Lebanon (recent Phoenicia) to determine the frequency of the clinical signs or symptoms of CF at the present time. associated haplotype in normal CFTR. Case description: CF newborn screening program (IRT/DNA/IRT) in our Region (Marche, Italy) detected a baby, naturally conceived, carrying P007 N1303K (1° IRT = 50ng/ml). Sweat test resulted positive in 2 different Functional characterisation of c.1584+18672bpA>G/2183AA>G CFTR occasions (110 and 62 mmol/L) and a 2nd level genetic analysis revealed a variant in rectal organoids 5T;TG12 variant. The nutritional status of this child is normal (WHO J. Conti1, K. Kleinfelder1, V. Lotti1,S.Preato1, A. Farinazzo1, F. Quiri1, weight/height centile = 40), no other comorbidities. E. Pintani2, D. Treggiari2, L. Rodella3, A. Cerofolini3, F. Catalano3, F. Tomba3, His parents showed this genotype: the father N1303K/5T;TG12; the mother H. DeJonge4, M. Cipolli2, C. Sorio1, P. Melotti2. 1University of Verona, CFTR Lab 5T;TG12/-. Due to the genotype results and despite apparent good health Daniele Lissandrini, Department of Medicine, General Pathology Division, status the father performed 2 sweat tests in different occasions that Verona, Italy; 2Azienda Ospedaliera Universitaria Integrata, CF Center, Verona, resulted positive: 78 and 95 mmol/L. The father was also NPD tested (NPD Italy; 3Azienda Ospedaliera Universitaria Integrata, Endoscopy Unit, Verona, th test performed according to the ECFS NPD SOP (528.01, 6 May 2014)) and Italy; 4Erasmus University Medical Center, Department of Gastroenterology he showed these results:. and Hepatology, Rotterdam, Netherlands Sermét score (SS) (normal cut-off >0,27): Objectives: We developed rectal organoids (OG) from a CF patient carrying • right nostril 1 = −0,838 left nostril 1 = 0,242. the deep-intronic CFTR variant c.1584 + 18672bpA > G, expressing both • right nostril 2 = −0,024 left nostril 2 = 0,626. correctly and aberrant spliced transcripts, in trans with the frameshift 2183AA > G mutation, presenting with a mild defect of pulmonary function Wischanski index (WI) (normal cut-off <0,7):. (FEV1 around 83% of predicted value)and abnormal sweat chloride (106 mmol/L)while his younger sister affected by CF with abnormal • right nostril 1 = 0,983 left nostril 1 = 0,508. sweat chloride (93 mmol/L)is on waiting list for lung transplantation • right nostril 2 = 0,683 left nostril 2 = 0,390. with severe impact on lung function (FEV1 around 35% of predicted value). To our knowledge there is no information about the effect of VX770 or other modulators on these variants. We aimed to assess the CFTR Discussion: This is a challenging case in which we have the unique functional defect and determining responsiveness to VX770, a CFTR opportunity to investigate the father who have the same genotype of his modulator approved for different CFTR variants. child to predict the clinical picture of the child. Methods: OGs were developed and tested by Forskolin (FSK) Induced The NPD results are not conclusive: both SS and WI are not in the normal Swelling (FIS) assay (FSK ranging from 0,02 to 5 μM) +/− VX770 (3 μM). range, even if this 41 years old man, has no signs or symptoms suggestive of Area under the curve (AUC) (t = 180 min; baseline, 100%) and statistical CF. analysis were calculated using GraphPad. OG were also cultured in 1,12 Conclusions: The diagnostic designation for this child is suspended. The cm2snapwell inserts, mounted in the Ussing chamber using chloride-rich follow-up program will consist in a sweat test and a throat swab every 6 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S57 solution to determine the magnitude of FSK-induced short-circuit current database by Professor Milan Macek et al. in mid 2019 without a description

(Isc) change and its response to 0.3 μM VX770. of the clinical picture of CF manifestations. Results: AUC was significantly improved: 3 ± 1,3 fold following treatment Methods: Data of the 2017 CF Register, outpatient records and case with 0,128 μM FSK + 3 μM VX770for 180 minutes comparing to vehicle of 2 unrelated patients carrying a rare variant c.1083G > A and in

(FSK + DMSO) (n = 4, p < 0.01). The Iscresponse to 10 μM FSK was 19,78 with variant c.1521_1523delCTT (p.F508del) in trans were analysed. To reference WT values of 114,5 (n = 2), and VX770 addition increased the characterise the function of CFTR were used ICM and Forskolin-induced value to 27,11 μA/cm2. swelling in intestinal organoids (FISIO). Conclusions: Rectal organoids carrying c.1584 + 18672bpA > G and Results: Variant c.1083G > A was found in two patients from unrelated 2183AA > G CFTR variants present with a residual CFTR function as families from different regions of the Russian Federation (RF). The measured by both FIS and Iscassays and VX770 treatment improved it, frequency according to the Register of CF Patients in the RF in 2017 was suggesting a potential clinical benefit for patients with this CFTR genotype. 0.04%. Analysis of the clinical manifestations of the disease in children 6 Supported by: Lega Italiana Fibrosi Cistica Associazione Veneta-Onlus, and 9 years of age revealed the presence of chronic pancreatic insufficiency. Italian CF Research Foundation (FFCgrant#13/2018, Delegazione FFC di A child of 6 years old had a history of distal intestinal obstruction syndrome Tradate Gallarate). and a high demand for pancreatic enzymes (10.000 U/kg of weight) was noted. The clinical picture of the second 9-year-old patient was P008 characterised by the development of transient hyperbilirubinemia, Spectrum and frequency of CFTR gene mutations in cystic fibrosis Pseudo-Bartter syndrome at an early age, and subsequently repeated patients from the southern Russian and North Caucasus regions episodes of bronchial obstruction and the development of polypous N. Petrova1, N. Kashirskaya1, T. Vasilyeva1, A. Voronkova1, E. Kondratyeva1, rhinosinusitis. Both patients have chronic Staphylococc infection. ICM and V. Sherman1, V. Galkina1, A. Marakhonov1, E. Ginter1, S. Kutsev1, FISIO showed that the genetic variant c.1083G>A leads to loss of CFTR R. Zinchenko1, 2. 1Research Centre for Medical Genetics, Moscow, Russian protein function. Federation; 2N.A. Semashko National Research Institute of Public Health, Conclusion: The pathogenic variant c.1083G>A is severe, both in the Moscow, Russian Federation presence of pancreatic insufficiency, in the clinical manifestations of CF, and in the results of evaluating the function of the CFTR protein obtained by Objectives: The spectra and frequencies of CFTR pathogenic variants in CF the ICM and FISIO. Patients continue to be under the control in Russian CF patients from the southern Russia and North Caucasus regions were centers. “The study was carried out with partial funding of the RSF №17-15- compared. 01051 and the state assignment of the Ministry of Science and Higher Methods: 299 unrelated CF patients from the southern Russia and 115 from Education”. North Caucasus regions were tested. Results: Russians account for about 80% of CF patients in the southern P010 region. F508del (58%), CFTRdele2, 3 (6%) were prevalent in southern Russia The first described pathogenic variant of D579Y (c. 1735G> T) which is typical for all Russian patients. The maximum frequency of 1 1 1 1 1 Y. Melyanovskaya , E. Kondratyeva , N. Petrova , M. Starinova . FSBSI, F508del (65%) was in the Krasnodar region, the minimum in the Rostov Research Centre for Medical Genetics, Moscow, Russian Federation region (57%), the frequency of CFTRdele2,3 was 8.7% in the Rostov and 6% in the Krasnodar region. The North Caucasus region is a multi-ethnic region The pathogenic variant c.1735G > T, is the replacement of guanine with with more than 100 ethnic groups. The most frequent variants were thymine at position 1735 in exon 13. Variant with unclear clinical F508del (24%), 1677delTA (23%), W1282X (15%). The most common significance, class not known. The pathogenic variant is described in the variants in Russians from the Stavropol Kray were F508del (49%), CFTR1 and ClinVar databases. CFTR2 does not describe this option. CFTRdele2,3 (4.6%), 2184insA (3.6%), and 2143delT (2.7%); W1282X (89%) - Methods: Data of the 2017 CF Register, outpatient records and case in Karachay CF patients; 1677delTA (67%) and E92K (9%) - in Chechen CF histories of patients carrying a rare variant c.1735G > T and in variant patients. In Ingush (a people close to the Chechens) only 1677delTAvariant F508del in trans were analysed. To characterize the function of CFTR used was found. In CF Ossetian patients the variants W1282X, F508del and ICM. We used data from two patients 16 and 24 years old from the register 1677delTAwere recurrent. A high diversity of the spectrum of CFTR variants with the same genotype for each. (11/13 patients) and a high proportion of homozygous genotypes for Results: The frequency of the 2017 CF Register option is 0.1%. 9-year-old different variants (61.5%) was revealed in patients from Dagestan. This is patient (girl) with positive neonatal screening (IRT1 - 275 ng/ml, IRT2 - probably due to marriage ethnic assortativeness. 223 ng/ml) in the anamnesis, sweat test on the apparatus Nanodact - Conclusion: The differences of spectrum and frequency of CFTR variants in 122 mmol/l, stool-1 elastase - less than 15 μg/g feces. At 8 years of age, CF patients between southern Russia and North Caucasus regions is due to multiple bronchiectases and PNS polyposis were observed on CT. both geographical factors and a multi-ethnic composition of the Intermittent plating of P. aeruginosa, a history of Burkodeia gladioli population. (November 2018). The change in ΔISC in response to the addition of We would like to thank Cystic Fibrosis Patient Registry of Russian forskolin was 2.17 ± 0.2 μA/cm2, which corresponded to the absence of the Federation and thank the individual regional CF centres representatives function of the chlorine channel. for allowing the use of data (http://mukoviscidoz.org/). In two adult patients, the characteristic of the disease was as follows: sweat The research was partially supported by grant RFFR 20-015-0061A and test 105 and 95 mmol/l (according to Gibson Cook), chronic pancreatic within the state task of the Ministry of education and science of Russia. insufficiency, chronic pseudomonas infection, nasal polyps, bronchiectasis,

FEV1 was above 80%. P009 Conclusion: For the first time, an analysis of case histories of 3 patients and Clinical and genetic characteristics of cystic fibrosis patients carrying the functional state of the chlorine channel (CFTR) in one patient with the pathogenic variant c.1083G> A (p.Trp361*) genotype F508del/с.1735G > T was performed using ICM. The relation E. Kondratyeva1, Y. Melyanovskaya1, A. Efremova1, N. Bulatenko1, severe manifestations of the disease with absence of the chlorine channel T. Bukharova1, N. Petrova1, A. Zodbinova1, V. Sherman1, N. Kashirskaya1, functions as according sweat test, and by the lack of response to forskolin in V. Ledneva2,3, L. Ulyanova2,3, R. Zinchenko1, 4, D. Goldshtein1, S. Kutsev1. conducting the method of ICM. This genetic option is “heavy”. 1FSBSI, Research Centre for Medical Genetics, Moscow, Russian Federation; “The study was carried out as part of the state assignment of the Ministry of 2FSBEIHE, Voronezh State Medical University named after N.N. Burdenko, Science and Higher Education”. Voronezh, Russian Federation; 3BIHCVR, Regional Children’s Clinical Hospital No. 2, Regional Center for Cystic Fibrosis, Voronezh, Russian Federation; 4Moscow Regional Research and Clinical Institute, Moscow, Russian Federation The pathogenic genetic variant c.1083G > A (p.Trp361*) of the CFTR gene belongs to nonsense mutations (class I) and at first was listed in the CFTR1 S58 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P011 Results: The patients age range is 1–12 years, 3 male and 1 female. 3 were The diversity of large genomic rearrangements of the CFTR gene in diagnosed on NBS and the girl was investigated when sibling was Russian patients with cystic fibrosis diagnosed CFSPID on NBS. 2 patients are heterozygous for p.F508del/p. N. Petrova1, E. Kondratyeva1, S. Krasovskiy1, 2, T. Adyan1, A. Polyakov1, Arg117H and 7Tand 2 are heterozygous for p.F508del/p.Arg117H and 9T. All A. Zodbinova1, Y. Melyanovskaya1, N. Kashirskaya1, E. Amelina2, patients have a negative sweat test with normal sweat chloride and are M. Starinova1, A. Voronkova1, V. Sherman1, A. Chernyak2, M. Chepurnaya3, pancreatic sufficient. T. Filimonova3, V. Smirnova3, E. Stezhkina3, E. Vasilieva3, V. Yakovleva3, In agreement with the current literature all 4 patients show no A. Borisov3, E. Boychenko3, A. Kozlov3, O. Odinokova3, T. Gembitskaya3, manifestations of CF disease and require minimal input or treatment. V. Kovalev3, I. Alimova3,G.Baykova3, L. Kozyreva3, N. Ochirova3, Patient 1 has been confirmed to have absent vas deference while having his L. Mankieva3, E. Lakhova3, E. Ivakhnenko3, S. Trishina3, N. Komlev3, hydrocele repaired in 1st year of life. He has also needed to start mucolytics A. Dyachkova3, O. Pyaterkina3, G. Shakirova3, O. Togochakova3, due to worsening Northern score on CXR. E. Yagubyants3, R. Zinchenko1, S. Kutsev1. 1FSBSI, Research Centre for Medical Conclusion: Despite remaining asymptomatic, we continue to regularly Genetics, Moscow, Russian Federation; 2Pulmonology Scientific Research review our patients given the uncertain nature of the outcome of infants Institute, Moscow, Russian Federation; 3Regional CF Center, Russian CF Patient with R117H gene. Long term follow-up of CFSPID patients are needed to Registry, Moscow, Russian Federation clarify the risk of developing CF symptoms within this group. Further clarity is also required regarding the recommended frequency of monitor- Objectives: To describe and analyse large genomic rearrangements in the ing and input for these patients. CFTR gene in CF patients in the Russian Federation (RF). Methods: Data of 2017 CF Register of RF were used. The aim was to evaluate P013 the clinical characteristics of patients, carrying large genetic rearrange- Analysis of CFTR gene mutations in cystic fibrosis patients in the ments (group 1-21 patients), we compared them with 2 other groups. Krasnoyarsk region Group 2 (171 patients) with the CFTRdele2,3/F508del genotype, and group N. Ilenkova1, V. Chikunov1, E. Kondratyeva2. 1Krasnoyarsk State Medical 3 (846 patients) homozygous for F508del. University, Krasnoyarsk, Russian Federation; 2Research Center for Medical Results: According to the Russian CF Registry 2017, large rearrangements Genetic, Moscow, Russian Federation composed 7.5% out of the total pathogenic genetic variants, and they were equally detected both in children and adults. Genetic variants of the class 1 More than 1500 registered mutations in cystic fibrosis transmembrane were found in 24.5% of the cases according to the Registry data. regulator (CFTR) gene are responsible for dysfunction of an ion channel A total of 11 genetic variants of large rearrangements were revealed: protein and a wide spectrum of clinical manifestations in patients with CFTRdup7-11(6b-10*), CFTRdup7-8(6b,7*), CFTRdele4-11(4-10*), cystic fibrosis (CF). This study was performed to investigate the frequency CFTRdele1-11 (1-10*), CFTRdele2(2*), CFTRdele12,13del18, CFTRdele18- of a number of CFTR mutations in CF patients in Krasnoyarsk region. 20(16-17в*), CFTRdele19-22(17а-19), CFTRdele8(7*), CFTRdel4-8(4-7*); Objectives and methods: A total number of 88 documented CF patients del10-11(9-10*), CFTRdele2-8(2-7*). 4 types of rearrangements in CFTR participated in this study. Peripheral blood was obtained and DNA gene haven’t been mentioned before in the international data bases: extraction was done by the use of routine methods. CFTRdele1-11 (1-10*), CFTRdele12,13del16^, CFTRdele19-22(17а-19), Results: Among 176 alleles, 20 different mutations in the CFTR gene were CFTRdele8(7*), CFTRdele2-8(2-7*). The most frequent 2 large rearrange- identified: F508del (59,66%), CFTRdel2,3 (del21kb) (3,98%), not identified ments were - CFTRdup7-11(6b-10*) (4 patients), and CFTRdup7-8(6b,7*) (4 (17,61%), N1303K (2,27%), 394delTT (1,70%), R1162X (1,70%), c.(?_274)_ patients). (1584_?)del (1,7%), 2143delT (1,70%), 2184insA (1,70%), R1158X (1,14%), The clinical characteristics of patients with large rearrangements didn’t R334W (1,14%), R117C (0,57%), 2184delA (0,57%), 3944delGT (0,57%), differ from the control groups by the basic features used in the European 4040delA (0,57%), 1898+1G>A (0,57%), E92K (0,57%), L138ins (0,57%) Registry. However, due to having patients combining in their genotypes R553X (0,57%). both a large rearrangement and the Е92К variant, intact pancreatic Conclusions: Data obtained allow us to select patients in Krasnoyarsk function was noted more frequently in group 1 (p = 0.03, p = 0.01). region for targeted therapy of CF, to perform prenatal diagnostics and Accordingly, patients from the 1 group used pancreatic enzymes less genetic counseling. frequently. Conclusion: The clinical characteristics of patients with large rearrange- ment of CFTR gene didn’t differ from the two comparison groups carrying severe genotype in terms of basic disease features. Diagnosis/Screening

P012 P014 Clinical profile of 4 children with variant R117H in our cystic fibrosis Improvement in cystic fibrosis outcomes since newborn screening clinic implementation in the United States 1 1 1 1 1 1 N. Rao , J. Watkinson , L. Russell , K. Barker , L. Warburton . Manchester 1, 2 3 4 5 6,7 S.L. Martiniano , A. Elbert , P.M. Farrell , N. Fisher , C.L. Ren , University Foundtion Trust (Wythenshawe), Paediatrics, Manchester, United 8,9 3 5,10 1 M. Sontag ,R.Wu , S.A. McColley . University of Colorado, Aurora, Kingdom 2 3 United States; Children’s Hospital Colorado, Aurora, United States; Cystic 4 Objectives: Newborn screening (NBS) for Cystic Fibrosis (CF) has resulted Fibrosis Foundation, Bethesda, United States; University of Wisconsin- 5 in infants with positive results but inconclusive diagnosis and are labelled Madison School of Medicine and Public Health, Madison, United States; Ann 6 as CF screen positive, inconclusive diagnosis (CFSPID). There is uncertainty & Robert H. Lurie Children’s Hospital, Chicago, United States; Indiana 7 for healthcare professionals and families regarding diagnosis and University School of Medicine, Indianapolis, United States; Riley Hospital for 8 management. Children, Indianapolis, United States; NewSTEPs, Littleton, United States; 9 10 Our CF clinic has 4 patients who are heterozygous for p.F508del/p.Arg117H. Center for Public Health Innovation, Littleton, United States; Northwestern By itself p.Arg117H (R117H) is not a disease-causing variant. Whether University, Chicago, United States R117H causes disease is based on another region of the CFTR gene called Objectives: Newborn screening (NBS) for CF was implemented in all US the poly-T tract which occurs in 3 forms 5T, 7T, 9T. CFTR 2 identifies that states by 2010. Quality improvement efforts supported by the Cystic R117H/5T may act as a disease causing variant, whereas 7T/9T are unlikely Fibrosis Foundation (CFF) and other stakeholders have aimed to improve to cause CF disease. processes. We hypothesised that outcomes have improved over time as a Methods: By retrospective case notes review we aim to review the clinical result of these efforts. course of 4 children with CFSPID who are heterozygous for p.F508del/p. Methods: We included participants in the CFF patient registry born 2010– Arg117H. 2018 and diagnosed between at age 0–365 days of age. We assessed timeliness of evaluation (age at first event, AFE), age of centre-reported Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S59 diagnosis and key outcomes in 2010–2012 (cohort 1, C1), 2013–2015 (C2) P016 and 2016–2018 (C3). First results from national newborn screening program for cystic Results: Among 6354 infants, there were 2299 in C1, 2172 in C2 and 1883 in fibrosis in the Republic of North Macedonia C3. Reported age at diagnosis was earlier than AFE. Across time periods, S. Fustikj1, V. Anastasovska2, D. Plaseska Karanfilska3, L. Spirevska1, AFE decreased. Weight for age (WFA) and height for age (HFA) Z-scores at M. Pesevska2, M. Terzikj3, A. Stamatova1. 1University Children’s Clinic, age 1 were close to 0 and not different between the cohorts. HFA Z-score at Department for Cystic Fibrosis, Skopje, North Macedonia, the Republic of; age 5 was better in C2 than C1. Pseudomonas aeruginosa (PA) infection rates 2University Children’s Clinic, Laboratory for Neonatal Screening, Skopje, North decreased over time. Results are summarized in the table. Macedonia, the Republic of; 3Research Centre for Genetic Engineering and Biotechnology ‘Georgi D. Efremov’, MANU, Skopje, North Macedonia, the Republic of Patient C1 2010–2012 C2 2013–2015 C3 2016–2018 P-value (test) Characteristics Objectives: After a pilot study in 2018, newborn screening (NBS) for cystic fibrosis (CF) was introduced as a national program on all newborn – – – Age at diagnosis, 15 (0 3149) 14 (0 1630) 14 (0 945) 0.439 population in R.N. Macedonia in April, 2019. R.N. Macedonia is a median (range) (Kruskal-Wallis) Age at first event, 40 (0–365) 38 (0–365) 33 (0–33) <0.001 multiethnic country with approximately 2 million inhabitants, and total median (range) (Kruskal-Wallis) neonatal population of approximately 22,000 births per year. Macedonians WHO WFA Z-score, 0.05 (0.95) 0.08 (0.96) 0.015 (0.98) 0.15 (ANOVA) of Slavic origin are the majority (about 55%), then ethnic Albanians (about age 1 mean (SD) 30%) and others. WHO HFA Z-score, −0.59 (1.1) −0.58 (1.1) −0.66 (1.1) 0.10 (ANOVA) Methods: Two steps IRT-IRT algorithm were performed, and then a sweat age 1 mean (SD) test for confirmation/exclusion of the CF diagnosis when IRT values were CDC WFA Z-score, −0.04 (0.94) −0.04 (1.0) NA 0.06 (ANOVA) age 5 mean (SD) both over the cut off (70 ng/ml and 40 ng/ml, respectively). In cases of CDC HFA Z-score, −0.19 (1.0) −0.06 (0.99) NA 0.003 (ANOVA) positive or borderline sweat tests, mutation analysis of CFTR gene was age 5 mean (SD performed (snapshot reaction for 11 most common regional CFTR PA, age 0–1 (%) 25 23 18 <0.001 (Chi-square) mutations or extended gene analysis). If the baby was under 3 kg, a – PA, age 1 2 (%) 37 37 21 <0.001 (Chi-square) genetic diagnosis was made as first. PA, age 3–6 (%) 37 23 NA <0.001 (Chi-square) Results: During the period from April to December 2019, 15.033 newborns [Patient Outcomes] were screened for CF. Recall rate was 0.38% (No = 57). Out of 22 screening positive cases, the diagnosis of CF was confirmed in 8. Sweat test results Conclusion: Over the first 9 years of universal NBS in the US, median AFE were: 108, 112, 102, 90, 108, 104, 52 and 70 mmol/L). 6 were ethnic and PA infection rates decreased and HFA at age 5 increased. While Albanians and 2 were ethnic Macedonians. The majority of diagnosed cases causality cannot be inferred, these data suggest that earlier AFE may be (No = 6) at the end of the first month of life, already had symptoms associated with improved CF outcomes. consistent with the diagnosis of CF and 2 were asymptomatic. The patient’s genotypes were: F508del/F508del (4), F508del/G542X, G542X/N1303K, P015 N1303K/G126D and 457TAT > G/CFTRdupexon22. In the last case, a new Twelve years of newborn screening - the East London Experience CFTR mutation/variant (duplication of exon 22) was found with unknown J. Cowlard1,C.Pao1, C. Nwokoro1. 1Barts Health NHS Trust, London, United significance. This case has two positive sweat test results (70 mmol/L), and Kingdom so far no symptoms of CF disease. Conclusion: The NBS for CF showed a high incidence of the disease in our ’ Objectives: The Royal London Children s Hospital is a regional CF centre region (1:1880), especially among Albanian population. following the national newborn screen pathway (IRT & CFTR) since 2007, with automatic notification of positive results. We describe our experience P017 from inception to present day. Improving the efficiency of cystic fibrosis newborn screening (CF NBS) “ ” Methods: Day 5 positive CF suspected bloodspot results are notified to in the Khanty-Mansi region (Russia) using immunoreactive st nd the CNS - a raised 1 IRT+ genes or if no genes a 2 raised IRT. All notified trypsinogen (IRT) floating cut-off approach positive cases (not in neonatal care) receive a CNS home visit & sweat test. M. Donnikov1,2, V. Mescheryakov1, N. Satsuk3, L. Kolbasin2, I. Urvantseva2, Confirmed cases receive genetic counselling & MDT review (including L. Kovalenko1. 1Surgut State University, Medical Institute, Surgut, Russian home visits) 1–2 weekly according to need. We reviewed hospital records Federation; 2Diagnostics and Cardiovascular Surgery Center (Cardiology of all babies referred since the onset of screening. Clinic) of KHMAO-Ugra, Medical Genetics Counseling Service, Surgut, Russian Results: 143 babies were referred between July 2007–Jan 2020. Of these,15 Federation; 3Regional Children Clinical Hospital, Nizhnevartovsk, Russian babies (9%) were diagnosed clinically before screening results known (MI 9, Federation family history CF 6). 80 (58%) had CF confirmed by sweat test +/− mutational analysis. 4 babies were not within region so were referred to Objectives: Generally used in Russia CF NBS protocol IRT/IRT has some other CF centres. Sweat tests were arranged & successful in 47/80 (58%) of disadvantages, among them high numbers of IRT-1 false positives (FP) and screen positive babies.9/47 (19%) were designated as CFSPID. 6 screen absence of obligatory DNA testing. Thus we tried to improve NBS efficiency positive babies died of non-CF causes without completion of investigations. at regional level by increasing its specificity within regular NBS protocol. 2 children with CFSPID have since been diagnosed as CF with clinical Methods: Descriptive survey covered period 2006–2019 ys and included features. All parents gave written consent to the national CF registry. We all relevant data accumulated since NBS inception (IRT values, number of have a local database to monitor our population with CFSPID. 63 babies FP, false negatives (FN), positive/negative predictive values (PPV/NPV), who had CF excluded had the following ethnic distribution - White British confirmed CF cases, specificity (Sp), sensitivity (Se). CF regional incidence 24%, White Other 6%, Mixed 11%, Asian 16%, Black 25%, Chinese 1%,17% had and prevalence were evaluated as median (Me) with 1st (Q1) and 3rd no ethnic code recorded at screening. This was compared to 80 babies quartiles (Q3). Floating cut-off IRT-1 levels were calculated using newly diagnosed with CF or CFSPID who were 71% White British, 10% White developed proprietary software flIRT®. Other; 5% Mixed, 14% Asian. Our service consistently meets national Results: Retrospective analysis was conducted for decade-long (2006– standards but following a positive CF screening result 40% of babies had CF 2016) CF regional NBS performed as IRT/IRT protocol using fixed cut-off IRT excluded compared to 16% nationally. levels (57,8 ng/mL) for 260,602 newborns (∼99.0% coverage). Mean FP rate Conclusion: East London is ethnically diverse, this data calls into question was 1.97%, Se-100%, Sp-98.1%, PPV-0.64%, NPV-100%, CF was confirmed in the appropriateness of the standard screening algorithm/mutation panel in 29 newborns. Several validating simulations showed that using floating IRT our region. cut-off with most appropriate 99.5 percentile instead of fixed values decreased FP rate while maintaining FN rate low. This approach was applied during 2017–2019 ys in prospective study of NBS efficiency: 65,813 S60 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 newborns were screened with 99.0% coverage, mean FP rate was 0.44%, Se- less severe disease and 2 patients with inconclusive genetic results. The 100%, Sp-99.56%, PPV-3.57%, NPV-100%, CF confirmed in 11 newborns. diagnosed children presented a wide spectrum of clinical symptoms. The Number of IRT retests decreased by 74% (down to 305). Long-run (2006– most frequent were recurrent respiratory infections, malnutrition and 2019) annual CF regional fluctuating incidence was 1:8,440 newborns, Me diarrhea. There were 2 cases of late diagnosis in children diagnosed based (Q1-Q3) = 8,298 (7,497–9,154); increasing prevalence - 1:43,146 (36,708– on the examination of siblings with positive CF NBS. 59,280) ppl. Conclusion: In the presence of clinical symptoms, additional diagnostics Conclusion: Comprehensive analysis of regional NBS for CF found large have to be implemented, despite of normal concentration of IRT. At first, the number of FP samples as inherent disadvantage of IRT/IRT protocol using sweat test should be conducted, subsequently DNA analysis. The diagnostic fixed cut-off values. Changing to floating cut-off alternative allowed us to process requires consideration of occurrence of mutations with low sweat significantly decrease FP rate and improve overall regional NBS efficiency. concentration. Repetition of sweat tests enabled the diagnosis in a child whose initial chloride values in sweat were borderline and no CF-causing P018 mutations was detected. CF diagnosis should be considered in siblings of Symptoms at diagnosis and genotype of false negatives (FNs) in children diagnosed previously. newborn screening (NBS) in Tuscany: experience over 26 years M. Botti1, E. Camera1, S. Campana1, D. Dolce1, G. Mergni1, T. Orioli1, P020 N. Ravenni1, M.C. Cavicchi1, M. Francalanci1, V. Galici1, A.S. Neri1, V. Terlizzi1, False-negative results of the cystic fibrosis newborn screening in Russia L. Zavataro1, F. Festini2, G. Taccetti1. 1Cystic Fibrosis Centre, Meyer Children’s V. Sherman1, E. Kondratyeva1, S. Kutsev2, M. Starinova1, R. Budzinskiy3, Hospital, Florence, Italy, Florence, Italy; 2University of Florence, Department of J. Kondakova4, A. Orlov4, I. Asherova4, O. Golubtsova4, N. Ilyenkova4, Health Sciences, Florence, Italy V. Chikunov4, D. Moskvina4, M. Erzutova4, V. Shadrina4, T. Simanova4, V. Seroklinov4, O. Pyaterkina4, T. Vasilyeva4, T. Stashkevich4, E. Vasilyeva4, Background: An NBS protocol with immunoreactive trypsin and meco- 4 4 1 V. Ledneva , E. Yagubyants . Research Centre for Medical Genetics, nium lactase dosage (IRT1/IRT2+LACT) started in Tuscany in 1992. Since 2 Department of Cystic Fibrosis, Moscow, Russian Federation; Research Centre 2011 this protocol has been integrated with DNA mutation analysis. 3 for Medical Genetics, Moscow, Russian Federation; Research Center for Aims: To detect FNs and to identify their symptoms at diagnosis over a 26- Medical Genetic, Department of Cystic Fibrosis, Moscow, Russian Federation; year time period. To compare the FN genotype with true positives (TP) at 4 Regional CF Center, Russian CF Patient Registry, Moscow, Russian Federation NBS. Methods: In Tuscany all patients with symptoms suggestive of CF are Objectives: The newborn screening (NBS) for cystic fibrosis (CF) has been referred to the Centre in Florence. We reviewed the NBS database from performed in RF since 2006–2007, the protocol includes the IRT/IRT/Sweat 1992 to 2018. We evaluated clinical symptoms, age at diagnosis and CFTR test. The study of the cases of false-negative results of the NBS (FN NBS) of genotype of FNs (surveillance until December 2019). Russian patients has not been conducted before. Results: 746,686 neonates were screened: 180 (162 TP and 18 FN) had CF Methods: The data have been analysed of the CF Registry of 2017 year and (incidence 1: 4,148). The sensitivity of NBS was 87.5% in the period 1992– medical records of the patients with FN NBS. 2010 and 96.1% in 2011–2018. Median age at diagnosis of 18 FN was 0.9 Results: The 2017 national register contains 3096 CF patients, out of which years (range: 0.3–22 years). The symptoms at diagnosis were: respiratory 1,483 were subjected to the NBS in the period from June 2006 to December infections (44.4%), salt loss syndrome (38.8%, always within the first year of 2017, and 72 children (4.9%) had FN NBS. life), failure to thrive (33.3%), diarrhoea (22%) and nasal polyposis (16.6%). All these patients were diagnosed with clinical symptoms at different age. The 5 CFTR mutations (F508del, G542X, L1065P, N1303K, E585X) more The median age of the CF diagnosis in the FN NBS group was 1.5 years, in frequently detected in Tuscany were found respectively in 41.7% of alleles in the group of positive NBS results - 0.39 years. The oldest FN NBS patient was FNs and in 60.4% of alleles in TPs (p = 0.047). FNs also had a statistically 11.6 years old at the time of the study, and the youngest was 0.5 years old. significant prevalence ( p = 0.013) of unknown mutations (detection rate The number of girls and boys in the study group was comparable. The 98%). average IRT in 45 patients from the FN NBS group (for which the IRT data Conclusions: To maintain a careful surveillance for CF is mandatory in a was available) was 43.4 ± 18.4 ng/ml, with a min IRT level of 7.8 ng/ml and a region with an NBS programme. Salt loss syndrome is a frequent onset max of 69 ng/ml. Almost all indicators did not exceed the cut-off level of event in Tuscany. When compared with TPs, FNs frequently have rarer or IRT. The IRT levels of six patients were within the range of 60–70 ng/ml. unknown mutations. Sweat test is still the gold standard in CF. Two patients had positive results at the first stage of neonatal screening (IRT levels of 75 and 81.9 ng/ml), positive IRT retest results, but they had P019 negative results of a sweat test. In half of the genotyped patients, the CFTR Late diagnosis of cystic fibrosis as a consequence of normal IRT mutations of the classes 1–3 were identified on both alleles. In the FN NBS concentration in Newborn Screening for Cystic Fibrosis - false negative group 9.6% had meconium ileus (8.1% in the entire 3096 patient cohort). K. Zybert1,2, U. Borawska-Kowalczyk1,2, M. Dawidziuk2, M. Mielus1, 2, Conclusion: The main cause of FN NBS was a low level of neonatal IRT. In M. Ołtarzewski3, D. Sands1,2. 1Institute of Mother and Child, Cystic Fibrosis the studied group several patients could be diagnosed by regulating the Department, Warsaw, Poland; 2Childrens Hospital in Dziekanow Lesny, Cystic cut-off level (in 3 patients the IRT level exceeded 66 ng/ml). All patients Fibrosis Center, Warsaw, Poland; 3Institute of Mother and Child, Department of were identified based on the characteristic clinical presentation, and at the Screening and Metabolic Diagnostic, Warsaw, Poland time of diagnosis most had chronic lung damage.

Objectives: Early detection of cystic fibrosis (CF) enables therapeutic and P021 preventive interventions. Newborn Screening for Cystic Fibrosis (CF NBS) is Positive and borderline sweat test results for patients not referred via an efficient instrument to achieve this goal. Determination of immunor- the newborn screening pathway: a review of patient outcomes eactive trypsin (IRT) is the first step of all CF NBS protocols. 1 1,2,3 1, 2 1 1 1 A. Robson , A. Maitra , J. Edgar , B. Hird , L. Tetlow . Manchester The aim of the study was to present a complicated diagnostic pathway as a 2 University NHS Foundation Trust, Manchester, United Kingdom; Royal consequence of normal IRT concentration in CF patients who underwent CF 3 Manchester Children’s Hospital, Manchester, United Kingdom; University of NBS (false negative). Manchester, Manchester, United Kingdom Methods: The group of 1.869.246 newborns were screened in the Institute of Mother and Child in Warsaw in the period 01.01.1999 – 31.05.2019. Objectives: Sweat chloride is the gold standard diagnostic marker for cystic Screening protocols have changed starting from IRT/IRT, next IRT/IRT/DNA fibrosis (CF), providing a direct functional measurement of the cystic till IRTDNA/EGA. For IRT, the cut-off is currently established as 99.4 fibrosis transmembrane regulator (CFTR) in the skin. The introduction of percentile. During this time 267 children were diagnosed. newborn screening (NBS) for CF in 2009 has enabled early identification Results: Ten cases of CF have been detected late in patients from 2 months and diagnosis of many patients, for whom outcomes are followed up via to 15 years of age. There were 5 children with mutations associated with the NBS laboratories. Sweat test guidelines recommend that outcomes of severe disease, 3 cases with at least 1 mutation class IV – V combined with positive and intermediate results should be audited for all sweat tests on a Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S61 regular basis. This work reviews the outcomes of positive and borderline P023 results for patients at the Royal Manchester Childrens Hospital (RMCH) New delayed diagnosed cases of cystic fibrosis in Cystic Fibrosis Centre who were not referred through the NBS pathway. at the Institute for Respiratory Diseases in Children in Skopje, Republic Methods: Sweat chloride data were gathered for all sweat collections from of Macedonia April 2015 to March 2018. Patient outcome data was then reviewed for E. Gjinovska-Tasevska1, T. Jakjovska1, I. Arnaudova-Danevska1, sweat chloride results ≥40 mmol/L (≥30 mmol/L for patients <6 months) S. Momcilovikj1. 1Institute for Respiratory Diseases in Children, CF Center, and for insufficient sweat collections. Skopje, North Macedonia, the Republic of Results: Excluding NBS referrals, 566 individual sweat tests were performed on 440 patients. 50 (8.8%) of the tests performed were Objectives: Our institute is the largest of its kind in our country and it insufficient (26 patients (5.9%)). Sufficient sweat was subsequently specialises in paediatric pulmonology. During the last year at the institute, achieved for 17 of these patients leaving 9 for which a result could not 33 763 children were examined at the institute, out of which 3344 were be obtained. 35 patients were found to have either borderline or elevated hospitalised. The majority of patients with CF are diagnosed in the first levels of sweat chloride. 21 of these were newly referred RMCH patients, all decade of life, but it is difficult when you do not have newborn screening of whom underwent confirmatory genetic testing with the following for CF. In our country screening started at April 2019. We want to describe outcomes: 7 CF positive, 9 CF negative/unlikely, 2 CF carriers,1 CFTR related the clinical presentation and delays in diagnosis of patients with cystic disorder and 2 with an inconclusive diagnosis (deceased/lost to follow up). fibrosis (CF) with the goal of raising physicians’ awareness of CF. The average sweat chloride concentration for CF positive patients was Methods: We diagnosed 5 paediatric cases of CF, based first on the clinical 74 mmol/L (43–116 mmol/L) compared to 42 mmol/L (23–74 mmol/L) for picture, then on a sweat test, faecal elastase, sputum isolates and finally all unaffected patients. The average age at referral for these patients was 6 confirmed by genetic analysis. Period of examination was one year. years (3 months to 15 years). Results: Mean age at diagnosis of children with CF was 6.5 years (range 30 Conclusion: This review demonstrates the effectiveness of sweat testing in days to 5 years). Three children with CF remained undiagnosed at 1 year the referral pathway for CF diagnosis at RMCH. old. All respiratory and gastrointestinal symptoms were present before diagnosis. All 5 children were with Weight ≤5th percentile and height or P022 length ≤5th percentile. Also all of them have vitamin D levels <8 mmol/L. Earlier contact with a cystic fibrosis centre is associated with better Sputum cultures were positive for Pseudomonas aeruginosa in two child. nutritional outcomes in infants with cystic fibrosis Two patients had positive family histories of CF. But only 1 case was 1,2 3 4 5 6,7 diagnosed on the basis of family history; the patient had no symptoms at S.L. Martiniano , A. Elbert , P.M. Farrell , N. Fisher , C.L. Ren , 8,9 3 5,10 1 diagnosis. Average amount for Cl in sweat were 110 mmol/L. Faecal elastase M. Sontag ,R.Wu , S.A. McColley . University of Colorado, Aurora, 2 3 was 42 μg/ml. United States; Children’s Hospital Colorado, Aurora, United States; Cystic 4 Two of this patients were homozygotis for F508del/F508del, two were Fibrosis Foundation, Bethesda, United States; University of Wisconsin- 5 F508del/S466(TAG) and one was with F508del/G542X. Madison School of Medicine and Public Health, Madison, United States; Ann 6 Conclusion: Our only one year research has documented considerable & Robert H. Lurie Children’s Hospital, Chicago, United States; Indiana 7 morbidity and delay in diagnosis of CF when identification of the disease University School of Medicine, Indianapolis, United States; Riley Hospital for 8 was based on clinical suspicion. By time of diagnosis, some patients were Children, Indianapolis, United States; NewSTEPs, Littleton, United States; 9 10 already seriously ill. So we must always make sweat test and think of CF Center for Public Health Innovation, Littleton, United States; Northwestern when the respiratory and malnutrition persist. University, Chicago, United States

Objectives: Newborn screening (NBS) for CF was fully implemented in the P024 US in 2010, but process variations may affect timeliness of evaluation for Minority infants with cystic fibrosis are initially evaluated at a later age infants with positive NBS tests. We hypothesised that earlier age at first CF than non-Hispanic white infants Centre contact is associated with better nutritional outcomes at age 1 year N. Fisher1, A. Elbert2, P.M. Farrell3, S.L. Martiniano4,5, C.L. Ren6,7, in infants with CF. M. Sontag8,9,R.Wu2, S.A. McColley1,10. 1Ann & Robert H. Lurie Children’s Methods: We studied infants born during 2010–2018 enrolled in the CF Hospital, Chicago, United States; 2Cystic Fibrosis Foundation, Bethesda, United Foundation Patient Registry. We defined CF Center contact as age at first States; 3University of Wisconsin-Madison School of Medicine and Public event (AFE: sweat test, encounter, or care episode). Exclusions were Health, Madison, United States; 4University of Colorado, Aurora, United States; meconium ileus, prematurity, missing gestational age, sweat chloride 5Children’s Hospital Colorado, Aurora, United States; 6Indiana University <30 mEq/L, CFTR modulator use before age 1, missing zip code, diagnosis School of Medicine, Indianapolis, United States; 7Riley Hospital for Children, before birth, and age at first event >365 d. We compared outcomes of Indianapolis, United States; 8NewSTEPs, Littleton, United States; 9Center for infants from the lowest quartile (early, E) to the highest quartile (late, L) Public Health Innovation, Littleton, United States; 10Northwestern University, AFE, matching for sex, median income by zip code, race, ethnicity, genotype Chicago, United States (McKone class) and pancreatic status. Results: Among 6879 infants, 3607 met inclusion criteria. After quartile Objectives: Most US states perform newborn screening (NBS) for cystic assignment and matching, 579 infants were in each group. Median AFE was fibrosis (CF) using IRT and DNA panels. DNA panels may miss more CFTR 11d in the E quartile and 47d in the L quartile (p < 0.001). At age 1y, E had mutations in ethnic and racial minorities (M). We hypothesized that M higher median WFA Z-score (0.09 vs −0.07, p = 0.024) and HFA Z-score infants would be evaluated for CF at an older age and have a different (−0.45 vs −0.6, p = 0.004) than L. At 3 years, WFA Z-score was similar, but E distribution of CFTR mutations than non-Hispanic White (NHW) infants. (n = 358) had higher HFA Z-score (median −0.104 vs 0.24, p = 0.007) than L Methods: We compared median age at first event (AFE: sweat test, (n = 420). This persisted at 5 years (media −0.075 vs −0.26, p = 011; E encounter or care episode) of M to NHW infants born in 2010–2018 in the n = 226, L n = 283). There was no difference in Pseudomonas aeruginosa CF Foundation patient registry. M infants had race entered as African- infection rates at 1y (22 vs. 20%, p = 0.33) or 3–6 y (29 vs. 30%, p = 0.60). L American or other, and/or ethnicity entered as Hispanic, consistent with US were older than E at the end of 2018 (mean 5.2 ± 2.5 vs. 4.3 ± 2.6, p < 0.001). census categories. We compared rates of prematurity, clinical symptoms at Conclusion: Earlier evaluation at a CF Centre is associated with improved presentation, CFTR mutation class and lowest quartile (LQ) of cohort WFA and HFA at age 1 year, and improved HFA at age 3 and 5 years. The median income by zip code (MIZ). infants diagnosed later were older at the end of the study period, and a Results: We identified 1335 M and 5019 NHW infants. M had later AFE than cohort effect cannot be excluded. Further evaluation is underway. NHW infants (median, 31d vs 22d (range, 0–365 d), p < 0.001). More M (CFF MCCOLQ01). infants had CFTR mutations characterized as “other” (table, p < 0.001). Fewer M infants had a positive NBS or prenatal test. The prematurity rate was similar and M infants had lower mean birth weight Z-scores (−0.34 ± 1.17 vs −0.11 ± 1.12 p < 0.001). M infants were more likely to have S62 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

MIZ in the cohort LQ (34% vs 23%, P < 0.001). Symptoms were rare, but more The evaluation was based on a specific questionnaire and a visual analogic frequent in M infants. scale completed before training and after the first diagnosis announcement post- training. Results: Before participating in the training, physicians were mainly CFTR All minority Non-Hispanic concerned with the fear of not knowing how to react to parents’emotions, mutation infants (M) White infants the fear of not being up to the task, and not knowing how to answer class (NHW) parents’ questions. Physicians were not concerned by reacting parents’ emotion. During the scenarios, the main difficulty found among the I-III 53% 72% physicians was to make room for moments of silence during the interview. IV, V 14% 14% Other 33% 14% Interestingly the accompanying staff was concerned by the same topics but less frequently. All of these points were improved by the doctors. The skill [CFTR mutation distributions] mainly improved by more than 2/3 doctors were the capacity to leave room for active listening and silence during the consultation. Conclusion: Compared to NHW, M infants have later AFE and a different Conclusion: Simulation-based learning improved skills and comfort-level distribution of CFTR mutations. Thus, later AFE may be related to decreased in making the diagnostic announcement of CF after neonatal screening. mutation detection. M infants have lower birth weight Z-score and are Implementing announcement training should have a positive impact on more likely to have LQ MIZ, increasing their vulnerability to poorer health care givers and their relationship with the parents. The first results outcomes. We speculate that earlier diagnosis of M infants may reduce obtained encourage us to continue training. disparities in CF outcomes. (CFF MCCOLL19QI10). P027 P025 Diagnosis of cystic fibrosis in adulthood Possibility and reality of prenatal diagnosis of cystic fibrosis in Bulgaria E. Bourgani1, C. Kosti1, E. Stagaki1, F. Diamantea1. 1Sismanoglio General V. Nedkova1, N. Kolarova-Yaneva2, N. Yanev3. 1Medical University of Pleven, Hospital, Adult Cystic Fibrosis Unit, Athens, Greece Pediatric Department, Pleven, Bulgaria; 2Medical University of Sofia, Pediatric Objectives: Although the majority of Cystic Fibrosis (CF) patients are Department, Sofia, Bulgaria; 3Medical University of Sofia, Department of diagnosed in the first decade of life, there is a group that has delayed Pulmonary Diseases, Sofia, Bulgaria diagnosis during their adulthood. Therefore, we sought to record the Objectives: Prenatal screening for cystic fibrosis is available in Bulgaria and number of patients diagnosed with CF in adulthood in our Adult CF Unit. recommended especially among population in risk, because over 35 The clinical characteristics and symptoms at the time of diagnosis were also different mutations are detected until now and even in 10% of the clinically recorded. manifested forms there are still unproven mutations. Our aim is to analyse Methods: We recorded retrospectively the number of patients diagnosed the rate of prenatal testing performed in families with previously born with CF over the age of 17.5 and their lung function (FEV1), nutritional children with cystic fibrosis, during the subsequent pregnancies. status (BMI), clinical and microbiological characteristics at the diagnosis. Methods: 82 children with cystic fibrosis were genotyped for DNA Results: From 270 patients followed-up at our unit, 29(10.7%) were mutation and observed for an over 25-year period in Pleven, Bulgaria. identified with an adult diagnosis, 20 males. The median age at diagnosis Results: From all 82 observed families - 68% abstained from subsequent was 28.1 years (range 17.5–53 years). All of them had two CF related pregnancies. Although there is recommendation for prenatal screening in mutations and positive sweat test. 8 patients had two alleles of class I-II – all cases, only in 26% it was performed, as a result 17 children were born - mutations. At diagnosis they presented with an average ppFEV1:75.6%(31 healthy heterozygotes according to the pathological gene and 4 children 140%), while 16(55%) had normal lung function. 13(45%) presented with 2 2 homozygotes according to F508del, because the parents refused medical pancreatic insufficiency and BMI was on average 23.4 kg/m (15–34 kg/m ) 2 abortion.In6%parentsrefused prenatal diagnosis ofa secondpregnancy - in2 with only one underweight patient (BMI <18.5 kg/m ). The main clinical cases it results in giving birth to a second F508del homozygote in the family. characteristics were the frequent lower respiratory tract infections (45%) Conclusion: Despite the presence of prenatal screening test, most of the and gastrointestinal disorders with steatorrhea/constipation alternation families with previously born children with cystic fibrosis in Bulgaria (27%). Acute/chronic pancreatitis, chronic sinusitis, episodes of dehydra- abstained from subsequent pregnancies. That is why It is necessary to tion, azoospermia in men/reduced fertility in women were present in a increase the awareness about the advantage of this method. percentage of 7% for each. On chest imaging bronchiectasis were present at 35%. At the time of diagnosis Pseudomonas aeruginosa and Staphylococcus P026 aureus were isolated in sputum in 35% and 31% respectively. Health simulation to improve diagnostic announcement of cystic Conclusion: Diagnosis of CF in adulthood remains a challenge, as it usually fibrosis after neonatal screening presents atypically. The clinical manifestations are extremely diverse and involve many specialties. In this direction increased awareness is needed A. Ladaurade1, A. Munck2, A. Hadchouel-Duverge3, N. Remus4, not only in pulmonologists but also in other specialties, especially in the I. Sermet-Gaudelus3. 1Cystis Fibrosis Centre, Besançon University Hospital, light of new treatments with CFTR modulators. Pediatric Department, Besancon, France; 2Hôpital Robert Debré, Paris, France; 3Necker Enfants Malades University Hospital, Pediatric Pneumology and P028 Allergology, Paris, France; 4Cystis Fibrosis Centre, Intercommunal Hospital, Do fertility clinics use the current recommendations to exclude cystic Pediatric Pneumology, Créteil, France fibrosis in CBAVD men? A pilot study Introduction: Announcing a critical illness is a complex communication M. Destoop1, L. Peeters2, S. Daelemans2, E. de Wachter1, 2. 1Vrije Universiteit exercise that requires multiple skills. Nursing staffs were trained to improve Brussel, Brussels, Belgium; 2UZ Brussel, CFclinic, Brussels, Belgium their skills in delivering the diagnosis of Cystic Fibrosis (CF) through simulation sessions with standardized patients. The objective of the study Objectives: In order to exclude underlying CF in CBAVDmen, international was to evaluate skills improvement. recommendations were designed by Bombieri et al. (JCF 2011) These Methods: 10 pediatricians and 9 accompanying nursing staff members recommendations have been mainly published in respiratory scientific participated in the study. The simulated diagnosis announcement journals. As a result, the target group of physicians required to apply these scenarios were carried out by a team of advertisers. guidelines, as fertility physicians and geneticists, may be missed. To date, The sessions included: no studies have been carried out to determine whether these recommen- dations are known and applied in practice by the target group of doctors. The aim of this study is to describe and compare the knowledge and i. a telephone call to ask to the parents to come to hospital for sweat test, current practice between CF specialists, fertility physicians and geneticists ii. the diagnosis announcement consultation (broadcast live), regarding the international recommendations to exclude CF in CBAVDmen. iii. debrief of the simulation session. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S63

Methods: This survey compares knowledge and current practice in 3 Introduction: Sweat chloride is the cornerstone of cystic fibrosis diagnosis. groups of physicians (fertility doctors, geneticists and CF doctors) on The ion ratio obtained by the skin-wipe sweat sampling and analysed by CBAVD and its link with CF through an online questionnaire. Physicians capillary electrophoresis is a promising and cheap alternative screening from Belgium and The Netherlands are invited to participate. Each method. participant gets a score for knowledge and a score for current practice. Objectives: To verify sensitivity and specificity of ion ratios from skin-wipe Scores are compared between 3 groups of physician-specialists using sweat samples in patients with cystic fibrosis (CF) and healthy individuals univariate regression. (Healthy) during 10-week periods. Results: We do not have preliminary data yet but are convinced to present Methods: Comparison of longitudinal ion ratio data from 10 CF and 10 final data at the time of the ECFS2020. We hypothesise CF specialists score Healthy with cut-off values. All CF had 2 causing mutations and sweat better in terms of knowledge and current practice compared to fertility chloride >60 mmol/L. All Healthy had sweat chloride <30mmol/L and no doctors and geneticists. We expect geneticists score better in both areas signs of cystic fibrosis. Ion ratio cut-off values were established in previous − than fertility doctors. studies: for Cl /K+ cystic fibrosis >3.8 (sensitivity 93.9%, specificity 97.8%) − Conclusion: The recommendations for excluding CF in CBAVD men are of and for (Cl +Na+)/K+ cystic fibrosis >5.0 (sensitivity 99.1%, specificity 94%). great importance, as missing the diagnosis of CF in adult men has major All subjects underwent weekly skin-wipe sampling in 10 sessions. implications for their health status and . It is therefore Sampling consists of wiping a defined skin area with a precleaned cotton important to determine whether these recommendations have effectively swab moistened with 100 μL deionized water, then extracted for 3 min in reached the target group of doctors and take measures if necessary. 400 μL deionized water. The extract is analysed by capillary electrophoresis with contactless conductometric detection. P029 Results: 195 samples were obtained from 10 CF (age 9.8 ± 4.7, sweat Cl Validation of new sweat test control materials 95.8 ± 19.7 mmol/L), and 10 Healthy (age 9.9 ± 3.0, sweat Cl 14.4 ± 5.5 − + N. Cirilli1, T. Maggi2, B. Fabrizzi1, N. Baiocco1, G. Sbaragli2, L. Bianchi2. 1Cystic mmol/L). The mean Cl /K ratio was 7.6 ± 2.1 in CF. − + − + + Fibrosis Centre, Mother-Child, United Hospitals, Torrette di Ancona, Italy; The mean Cl /K ratio was 1.3 ± 0.3 in Healthy. The mean (Cl +Na )/K ratio 2 was 12.5 ± 3.0 in CF. Sclavo Diagnostics International srl, Siena, Italy − The mean (Cl +Na+)/K+ ratio was 2.6 ± 0.7 in Healthy. Background: Sweat test remains a gold standard for the diagnosis of Cystic Conclusions: Both ion ratio cut-off levels retained high sensitivity (100%), Fibrosis (CF). Existing guidelines include Internal and External Quality as no value dropped below the cut-off level in CF group. The specificity of − Assessments. Recent EU Sweat Test survey showed that 68% of participating Cl /K+ ratio was surprisingly high (100%). − centres/labs use internal quality control as recommended, while 52% The specificity of (Cl +Na+)/K+ ion ratio was similar to previously published − participate in an external quality assurance scheme. Cost and insufficient (95%) as five values in Healthy were above cut-off level. Cl /K+ outperforms − reimbursement were repeatedly reported as factors influencing choice of (Cl +Na+)/K+ in this longitudinal setting with no borderline cases. equipment and operating procedures Supported by MUNI/A/1566/2018 and NV18-08-00189. Objectives: To produce sweat test control materials in 3 clinically relevant levels P031 Methods: Blinded 3 levels aqueous simulated human sweat matrix, What is the role of sweat ions ratio in the diagnosis of cystic fibrosis? produced following good laboratory manufacturing protocols, were 1 1 1 1 1 1 D. Treggiari , G. Tridello , L. Menin , E. Pintani , A. Borruso , P. Iansa , assayed for chloride using coulometry (Jenway, PCLM3). All tests have 1 1 1 M. Cipolli , P. Melotti . Azienda Ospedaliera Universitaria Integrata Verona, been performed in the same laboratory, with the same instrument and by Cystic Fibrosis Centre, Verona, Italy the same technician Results: Blinded 3 level set of liquid control materials were assayed Objectives: Sweat chloride concentration [Cl] is the gold standard to (coulometry) for chloride for 3 months for a total of 60 batch sessions (2 confirm the diagnosis of CF but shows high intra-individual variability and replicates/level). Table 1 shows the results borderline values (Cl:30–59 mmol/L). Previous studies reported predictiv- ity of Cl/Na for diagnosis of CF but less is known about Cl/K and (Cl+Na)/K Table 1. ratios recently investigated in young subjects. The aim of this study was to Results of the assays define retrospectively the most appropriate outcome of sweat test. Level 1 Level 2 Level 3 Methods: Sweat [Cl], [Na] and [K] were quantified (Gibson&Cooke) in 2084 (mmol/L) (mmol/L) (mmol/L) subjects:1283 CF (age:0–5.9, n = 845;age:6–11.9, n = 175;age:12–17.9; age: n = 102;age:≥18, n = 161) and 801 non-CF (age:0–5.9, n = 417;age:6–11.9, Average 103,63 79,53 24,65 n = 202;age:12–17.9, n = 68;age:≥18, n = 114) based on clinical diagnosis Median 101,50 78,00 24,00 CV% 8,34 8,08 8,35 and in185 borderline (8.88% of our study population) subjects (n = 185: age:0–5.9 n = 65, age:6–11.9 n = 31, age:12–17.9 n = 19, age ≥18 n = 70; 45 had CF,24%). Sensitivity to discriminate CF from non-CF of Cl/Na, Cl/K and Conclusion: These materials respond to the requirements of stability (3 (Cl+Na)/K ratios was calculated (ROC curves). – months opened vials at 2 8°C) and reproducibility for sweat chloride Results: In overall population all the ratios significantly discriminated CF analysis. Further steps of validation of these materials will consist in: Real from non-CF; Cl/Na ratio showed the highest diagnostic capability for time stability studies (ongoing); Validation for other sweat analites (e.g., distinguishing CF, according to ROC curve analysis (age:0–5.9, AUC = 0.85, sodium); Correlation with other analytical methods (colorimetry, ISE p < 0,0001; age:6–11.9,AUC = 0.90, p < 0,0001;age:12–17.9, AUC = 0.95, p < module). This initiative can help to improve the adherence of CF centres/ 0,0001; age:≥18, AUC = 0.96, p < 0,0001). In the borderline population labs to Internal and External Quality Assessments overcoming the cost instead Cl/K and (Cl+Na)/K ratios were unable to completely separate CF barrier from non-CF (p range 0.2–0.9) except (Cl+Na)/K ratio for age 0–5.9 (p = 0.04). Significantly Cl/Na ratio separated CF and non-CF subjects P030 regardless age (age 0–5.9 p = 0.002, 6–11.9 p = 0.001,12–17.9 p = 0.007, ≥18 Skin-wipe sweat ion ratios - sensitivity and specificity in time p < 0.0001). M. Malá1, 2, L. Homola1, 2, P. Durč3, E. Pokojová2,4, E. Furstová5, P. Kubáň3. Conclusion: (Cl+Na)/K ratio seems to be informative as diagnostic outcome 1University Hospital Brno, Dpt. of Child Infectious Diseases, Brno, Czech that could support diagnosis in borderline neonatal screening while it Republic; 2Masaryk University, Brno, Czech Republic; 3CEITEC Masaryk seems unuseful for discriminating CF at age≥6years. Our results highlight University, Dpt. of Bioanalytical Instrumentation, Brno, Czech Republic; the capability of Cl/Na ratio as a valid and useful biomarker for diagnosis CF 4University Hospital Brno, Dpt. of Respiratory Diseases and TB, Brno, Czech in the overall population. Republic; 5Motol University Hospital, Cystic Fibrosis Centre and Dpt. of Supported by: Lega Italiana Fibrosi Cistica Associazione Veneta Onlus Paediatrics, Prague, Czech Republic S64 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

(1.1%), among adults - 7th place (1.6%).The AF of the L138ins in the regions Epidemiology/Registry of RF was different: in the Perm Region - 5.4%, in the Chelyabinsk Region - 4.1%, in the Sverdlovsk Region - 3.3%. The highest AF of the L138ins was in P032 the Republic of Mordovia, however, L138ins was found there in only two The dynamics of DNA diagnosis availability for cystic fibrosis patients in patients. Also, a high frequency was in Kurgan (6.3%) and in Kirov (5.6%) the Russian Federation, and genetic variation analysed using the regions - but one patient in each region. In the remaining regions, the National Disease Registry between 2013–2018 L138ins was found in isolated cases or was absent. 1 1,2 1 1 1 Conclusion: The L138ins is a rare variant CFTR in the world, but it is often E. Kondratyeva , S. Krasovskiy , N. Petrova , T. Adyan , A. Polyakov , 1 1 1 2 found in CF patients in the RF, to a greater extent in adult patients. The A. Zodbinova , Y. Melyanovskaya , N. Kashirskaya , E. Amelina , 1 1 3 3 3 widespread introduction of DNA diagnostics, the inclusion of the L138ins in M. Starinova , A. Voronkova , A. Chepurnaya , T. Filimonova , V. Smirnova , 3 3 3 3 3 the panel of common variants in the CFTR, the detection of CF among adults E. Stezhkina , E. Vasilieva , V. Yakovleva , A. Borisov , E. Boychenko , 3 3 3 3 3 has significantly increased the diagnosis of this variant in Russia. The A. Kozlov , O. Odinokova , T. Gembitskaya , V. Kovalev , I. Alimova , 3 1 1 1 L138ins was more common in CF patients living in the Middle Urals. We A. Lyamin , R. Zinchenko , S. Kutsev . FSBSI, Research Centre for Medical 2 would like to thank CF Patient Registry of the RF for providing access to Genetics, Moscow, Russian Federation; Pulmonology Scientific Research 3 patient data and thank the individual regional CF centres’ representatives Institute, Moscow, Russian Federation; Regional CF Center, Russian CF Patient for allowing use of data (http://mukoviscidoz.org/). Registry, Moscow, Russian Federation

Objectives: To analyse the dynamics of detecting genetic variants of CFTR P034 gene based on data from the Registry between 2013 and 2018 in the Prevalence of cystic fibrosis paediatric patients with p.Arg1162X Russian Federation (RF). mutation in southern Brazil: a migration flow outcome Methods: Registry for 2013 year contained data of 1968 patients from 74 P.B. Sanseverino1, M. Farias1, M. Michels2, M.T. Sanseverino3, P.J. Marostica4. different regions, for 2018 year - 3142 patients from 81 RF regions. 1Universidade Federal do Rio Grande do Sul, PPG Saúde da Criança e do Results: 94.3% out of all CF patients underwent genetic testing in 2018 Adolescente, Porto Alegre, Brazil; 2Universidade Federal do Rio Grande do Sul, compared to 87.5% in 2013. Children who underwent the testing composed Departamento de Genética, Porto Alegre, Brazil; 3Hospital de Clínicas de Porto 94.6%, adults −93.6% of the cases in 2018 (compared to 87.5% for children Alegre, Serviço de Genética, Porto Alegre, Brazil; 4Hospital de Clínicas de Porto and 91.0% for adults in 2013). The overall frequency of allele identification Alegre, Serviço de Pneumologia Pediatrica, Porto Alegre, Brazil made up to 89.3% (79.1% in 2013). Out of the entire group of patients who underwent genetic testing, 82.4% had 2 variants of DNA sequence of the There are more than 2000 mutations reported in CF. Brazilian population is CFTR gene (66.1% in 2013),14% had only one variant, and in 3.7% none of the a mix of African, European and Indigenous populations forming a genetic variants was identified (in 2013, 25.9% had one, 8% had none). A particular genetic background. One of the top 5 CF pathogenic variants in total of 212 genetic variants were revealed (112 in 2013). The most common Brazil is the stop codon mutation p.Arg1162X or R1162X. genetic variants are F508del - 53.05%, CFTRdele2,3 - 6.09%, E92K - 3.04%, Methods and objectives: Here we present data of CF paediatric patients 3849+10kbC->T - 2.38%, 2143delT - 2.11%, 2184insA - 1.84%, 1677delTA - from a referral center in the South of Brazil with at least 1 allele of p. 1.77%, W1282X - 1.75%, N1303K - 1.55%, G542X - 1.48%. «Mild» genotypes Arg1162X. The objective of this study was to report the prevalence of this were observed in 23% of the patients. «Severe» genotypes were predom- variant in Brazil and relate it to migration flows. inant among children and adults, 82.4% and 62.5%, respectively. Results: In our database of 87 CF paediatric patients, p.Arg1162X is the Clinical characteristics and functional evaluation of the chloride channel second most common (4.4%) mutation, a higher prevalence than that in the first described in patients with pathogenic variants: c.831G>A, c.1083G>A, whole country database (1.8%, p = 0.01). Seven of the patients have at least 3272-16T>A, D579Y and с.1585-94124A>G. 1 allele and 1 of them is homozygous for this mutation. The mean current Conclusion: The number of CFTR gene variants in RF has increased by 101 age of patients is 10y. The majority of diagnosis was made after newborn variants throughout the last 5 years due to the introduction of sequencing screening (58%). In the latest Brazilian CF Registry report, approximately and increased genetic testing. Also 49 rare mutations were observed and 70% of CF patients live in the south and southeast regions, where the the number of patients with one or two undetected mutations accordingly majority of European immigrants were settled in the past. The heterogen- decreased. The use of functional tests (Intestinal current measurement) eity of Brazilian genetic background is principally influenced by immigra- allows for a better understanding of the pathologic manifestation of the tion flows. Italian immigration to our region peaked in the 1880s and more different genetic variants. than half of immigrants were from the Veneto region. Italian studies show that the pathogenic variant p.Arg1162X is very common in Veneto and P033 Trentino regions (close to 10%). Epidemiological features “Middle - Ural” variant L138ins in the CFTR Conclusion: Our higher prevalence of the p.Arg1162X mutation is probably gene at cystic fibrosis in Russia due to a greater immigration of Veneto people to southern Brazil. V. Shadrina1, S. Krasovsky2, E. Kondratyeva3, E. Furman1. 1E.A. Vagner Perm 2 P035 State Medical University, Perm, Russian Federation; Scientific Research Comparison of clinical findings of the patients with cystic fibrosis in Institute of Pulmonology of the Federal Medical and Biological Agency, 3 terms of diagnosed with and without neonatal screening Moscow, Russian Federation; Federal State Scientific Budgetary Institution, 1 1 1 1 Research Centre for Medical Genetics, Moscow, Russian Federation T. Ramasli Gursoy , Z. Reyhan Onay , A. Tana Aslan , T. Sismanlar Eyuboglu , E. Cakir2, N. Cobanoglu3, S. Pekcan4, G. Cinel5, D. Dogru6, U. Ozcelik6, The allele frequency (AF) of the L138ins, according CFTR2, was only E. Yalcin6, V. Sen7, O. Ercan4, A.A. Kilinç8, H. Yazan2, D.U. Altintas9, D. Esen10, 0.00014% (https://cftr2.org). The L138ins in Russian CF patients was A. Bingol11, N. Sapan12, E. Celebi13, G.D. Tugcu5, A. Ozdemir14, describing since 2005 - with an AF of 0.2% (Kapranov N. et al., 2005). In K. Harmanci15, M. Kose16, N. Emiralioglu6, Z. Tamay17, H. Yuksel18, 2009, the AF of the L138ins in the European part of Russia determined to G. Ozcan3, E. Topal19, D. Can20, P. Korkmaz21, G. Caltepe22, M. Kiliç23, 0.004%, in the Siberian Federal District - 0.01% (Petrova N., 2009). Since S. Ozdogan24. 1Gazi University Faculty of Medicine, Pediatric Pulmonology, 2009, the L138ins has been included in the routine CFTR gene analysis in Ankara, Turkey; 2Bezmialem University Faculty of Medicine, Pediatric Russia. Pulmonology, Istanbul, Turkey; 3Ankara University Faculty of Medicine, Objectives: To study the epidemiological characteristics of L138ins in CF Pediatric Pulmonology, Ankara, Turkey; 4Necmettin Erbakan University, patients in Russia. Meram Medicine Faculty, Pediatric Pulmonology, Konya, Turkey; 5Ankara City Methods: The National Register of CF Patients in the Russian Federation Training and Research Hospital, Pediatric Pulmonology, Ankara, Turkey; (RF) for 2017 was analysed. 6Hacettepe University Faculty of Medicine, Pediatric Pulmonology, Ankara, Results: In the National Register were 196 different variants in the CFTR Turkey; 7Dicle University Faculty of Medicine, Pediatric Pulmonology, th gene. The L138ins was found in 70 patients and took 11 place in the AF of Diyarbakır, Turkey; 8Istanbul University Cerrahpasa̧ Medicine Faculty, th the CFTR gene variants in Russia (1.2%). Among children - in 10 place Pediatric Pulmonology, Istanbul, Turkey; 9Cukurova University Faculty of Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S65

Medicine, Pediatric Allergy and Immunology, Adana, Turkey; 10Ege University Methods: Data were retrospectively collected for patients ≥40 years of age Faculty of Medicine, Pediatric Pulmonology, Izmir, Turkey; 11Akdeniz University at a large adult CF centre in the UK, including age at diagnosis, genotype,

Faculty of Medicine, Pediatric Allergy and Immunology, Antalya, Turkey; pancreatic status, BMI and %predicted FEV1. In addition, prospective sweat 12Bursa Uludag University Faculty of Medicine, Pediatric Allergy and testing, using pilocarpine iontophoresis (Wescor Macroduct), was per- Immunology, Bursa, Turkey; 13Hacettepe University Faculty of Medicine, Chest formed to examine the relationship between sweat chloride and other Diseases, Ankara, Turkey; 14Mersin City Training and Research Hospital, demographics within this older CF patient cohort. Pediatric Pulmonology, Mersin, Turkey; 15Eskisehir Osmangazi University Results: Data were collated for 91 patients, with 58 of these patients Faculty of Medicine, Pediatric Allergy and Immunology, Eskisehir, Turkey; undergoing sweat test analysis. Patient data were analysed in three age 16Erciyes University Faculty of Medicine, Pediatric Pulmonology, Kayseri, groups (40–49; 50–59; ≥60 years) using one-way ANOVA, revealing Turkey; 17Istanbul University Faculty of Medicine, Pediatric Allergy, İstanbul, differences in sweat chloride (p = 0.025) and age of diagnosis (p < 0.001) Turkey; 18Celal Bayar University Faculty of Medicine, Pediatric Allergy and between groups. Lower sweat chloride, later age of diagnosis and higher Immunology, Manisa, Turkey; 19Inonu University Faculty of Medicine, Pediatric prevalence of pancreatic sufficiency was seen with advancing age. There 20 Allergy, Malatya, Turkey; Balikesir University Faculty of Medicine, Pediatric was no significant difference in BMI and baseline %FEV1 between age Pulmonology, Balikesir, Turkey; 21Ege University Faculty of Medicine, Chest groups. Genotype analysis reveals a difference in the prevalence of less Diseases, Izmir, Turkey; 22Ondokuz Mayıs University Faculty of Medicine, severe CFTR mutations (defined as ≥1 class IV-V mutation) between age Pediatric Gastroenterology, Hepatology and Nutrition, Samsun, Turkey; 23Firat groups 40–59 years and ≥60 years (p = 0.002). University Faculty of Medicine, Pediatric Allergy and Immunology, Elazig, Conclusion: CF patients over 40 years of age have a heterogeneous Turkey; 24Sisli Hamidiye Etfal Research and Training Hospital, Pediatric phenotype. Those greater than 60 years are more likely to have been Pulmonology, Istanbul, Turkey diagnosed in later life, be pancreatic sufficient, have lower sweat chloride and a less severe genotype. Within the older CF patient cohort there exists a Objectives: Newborn screening (NBS) for cystic fibrosis (CF) was distinct group with sufficient CFTR function to delay clinical presentation implemented on January 2015 in Turkey. The aim of this study was to for several decades. compare the clinical findings of CF patients diagnosed by NBS and patients who were diagnosed without or negative NBS in CF Registry of Turkey P037 (CFRT). Cystic fibrosis in Cyprus: results from the national patients’ Registry Methods: The total number of patients in the CFRT was 1488 in 2018. Three 1 1, 2 1 3 4 hundred and fifty-nine of these patients were included into the study who A. Matthaiou , P. Anagnostopoulou , P. Kouis , V. Neocleous , T. Adamidi , 5 3 3 4 3 1, 5 were born after NBS implementation. Age at diagnosis, gender, history of P. Ioannou , P. Fanis , C. Costi , A. Georgiou , L.A. Phylactou , P. Yiallouros . 1 meconium ileus (MI), results of sweat chloride test, and faecal elastase, University of Cyprus Medical School, Respiratory Physiology Laboratory, 2 colonisation status were compared in patients diagnosed with NBS and Nicosia, Cyprus; University of Bern, Institute of Anatomy, Bern, Switzerland; 3 4 patients without or negative NBS. NBS positive patients were classified as Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Nicosia General 5 group 1, NBS negative patients as group 2, and patients without NBS as Hospital, Department of Pulmonology, Nicosia, Cyprus; Archbishop Makarios group 3. III Hospital, Pediatric Pulmonology Unit, Nicosia, Cyprus Results: There were 299 (83.3%) patients in group 1, 40 (11.1%) patients in Objectives: Since the early 1990s, systematic recording of cystic fibrosis group 2 and 20 (5.6%) patients in group 3. The mean age at diagnosis was (CF) patients’ data has been implemented in Cyprus. Recently, we have 0.2 ± 0.4 in group 1, 0.9 ± 2.0 in group 2, and 0.5 ± 0.6 months in group established and maintained a national patients’ registry. We aim to present 3. The mean age at diagnosis was significantly higher in group 2 and 3 than a wide spectrum of genotypic and phenotypic features of CF patients in group 1 (p:0.001). Seventeen (5.6%) patients in group 1, two (5%) patients Cyprus from the most recent data collection in 2019. in group 2 and five (25%) patients in group 3 had MI. MI was more common Methods: Patients’ core data (demographics, diagnosis, genotype) and in group 3 than the others (p: 0.018). Two hundred and sixty-six patients in annual report data (growth, lung function, microbiology, complications, group 1, 26 patients in group 2 and 18 patients in group 3 had pancreatic treatment) were systematically collected, recorded, and analysed following insufficiency and it was more common in group 2 and group 3 than group 1 the specifications of the European patients’ registry online software system. (p:0.001). Chronic S. aureus infection was present in 16% patients in group Results: Overall, data from 50 CF cases are presented, 5 of whom have 1, 7% patients in group 2, 40% patients in group 3 and there were significant deceased and 13 have been lost to follow-up in last years. Μean ± SD age at difference between the group 3 and the others (p:0.004). Sweat chloride diagnosis was 6.2 ± 10.8 years, and mean ± SD age by the end of 2019 was tests results were higher (p:0.009) and faecal elastase results were lower 21.5 ± 14.3 years. Most commonly, patients presented at diagnosis with (p:0.033) in group 1 than the others. acute or persistent respiratory symptoms (46%), failure to thrive or Conclusions: NBS provides early diagnosis and patients could be malnutrition (42%), and dehydration or electrolyte imbalance (34%). In all diagnosed before the occurrence of pancreatic insufficiency findings and cases, diagnosis was confirmed by genotyping. p.F508del was the most pulmonary complications such as S. aureus colonisation. common mutation (45.2%), followed by p.Leu346Pro (6.7%), a mutation detected solely in individuals of Cypriot descent. According to the 2019 P036 annual report, mean ± SD BMI-for-age z-score was 0.07 ± 1.3, whereas Relationship between phenotype and genotype in an older cystic mean ± SD best FEV % predicted was 78 ± 19.9. Haemophilus influenzae was fibrosis cohort 1 1, 2 1,2 1, 2 1,2 the most common pathogen isolated in sputum cultures across all age S.L. Paterson , A.M. Jones , R.J. Bright-Thomas , P.J. Barry , groups (>60% of examined patients). Chronic colonisation with A.-M. Kelly1, 2. 1Manchester Adult Cystic Fibrosis Centre, Manchester, United 2 Pseudomonas aeruginosa and Staphylococcus aureus was confirmed in Kingdom; University of Manchester, Manchester, United Kingdom 37.5% and 50%, respectively, in patients who underwent a sufficient Objectives: The evolution of CF demography over time has seen an number of sputum cultures. exponential improvement in survival and an ageing CF population. The CF Conclusion: Systematic recording of patients’ data is necessary for the registry reported that 56.2% of patients in the UK in 2018 were adults and optimisation of healthcare for CF patients and for the overall improvement the number of older adults with CF continues to increase. It is therefore of disease prognosis. important to consider the specific demographics of the older CF population, in order to better understand this group and their potential complexities and trajectories. S66 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P039 Conclusion: This study found that transfer from a paediatric to an adult CF National Cystic Fibrosis Patients Registry of Russia (RCFPR) from 2011– centre was associated with worsening of the pulmonary function in males 2018 and females. No difference was shown for the nutritional status. E. Amelina1, S. Krasovskiy1, E. Kondratieva2, N. Kashirskaya2, A. Voronkova2, M. Starinova2, V. Seroklinov3, D. Petrova3, J. Dauletova3, D. Sergienko3, P041 T. Stashkevich3, V. Ledneva3, L. Ulyanova3, V. Ivleva3, I. Gaimolenko3, What are patients’ and parents’ expectations during transition process A. Petrova3, N. Potapova3, T. Bondarenko3, V. Shinkareva3, A. Mambetova3, in the French cystic fibrosis centres (SAFETIM Needs study) F. Maremshanova3, T. Protasova3, V. Brisin3, D. Ljagusha3, T. Golihina3, V. Vion Genovese1, M. Perceval2, L. Buscarlet Jardine3, N. Pinsault4, N. Ilenkova3, V. Chikunov3, V. Petrov3, E. Zhekaite2. 1Pulmonology Research A. Gauchet5, B. Allenet6, C. Llerena7. 1CHU Grenoble Alpes, Hôpital Couple Institute under FMBA of Russia, Moscow, Russian Federation; 2Federal State Enfant, CRCM Pédiatrique, Université Grenoble Alpes, ThEMAS TIMC-IMAG Scientific Budgetary Institution, Research Center for Medical Genetics, (UMR CNRS 5525), Grenoble Cedex, France; 2Filiere Muco CFTR_HCL, Lyon - Moscow, Russian Federation; 3Regional CF Center, Russian CF Patient Registry, Pierre Benite, France; 3Reseau EMERAA (Ensemble pour la Mucoviscidose en Moscow, Russian Federation Rhone Alpes Auvergne), Bron, France; 4Université Grenoble Alpes, ThEMAS TIMC-IMAG (UMR CNRS 5525), Grenoble, France; 5Université Grenoble Alpes, Aim: Is to present data collected in 2018 and to compare them with similar 6 LIP/PC2S, Saint Martin d’Heres, France; CHU Grenoble Alpes, Université data collected in 2011 when RCFPR was started. Grenoble Alpes, ThEMAS TIMC-IMAG (UMR CNRS 5525), Grenoble, France; Methods: In 2018 RCFPR included data of 3142 (1601 M) patients from 81 7 CHU Grenoble Alpes, Hôpital Couple Enfant, CRCM Pédiatrique, Grenoble, regions while in 2011 - 17 regions and 1015 (544 M) CF patients. France Results: The main data of 2018: average age was 12,8 ± 9,6 vs 11 ± 9 in 2011, the proportion of adult patients was the same - 25%. The age at diagnosis - Objectives: In 2017, there were 7114 CF (Cystic fibrosis) patients: 55.9% 3.1+5.8; diagnosed by the neonatal screening program - 48.2% (28.8% in adults, 44.1% children. Do the transition organisation, from paediatric to 2011). 82,4% of patients had both mutations identified vs 69,1% in 2011. adult centres, meet the patients and parents expectations? Chronic infection with P.aeruginosa, S.aureus, S.maltophilia din’t change, Methods: SAFETIM needs is a prospective multicentric observational study with B.cepacia complex decreased from 7.0% in 2011 to 5.8% in 2018. The carried out between 2017 and 2019. We interviewed each adolescent and treatment regimen was similar to 2011, except hypertonic saline 67% vs 9%, their parents, before transfer and after transfer. All interviews were intravenous antibiotics - 38% vs 71% and oral antibiotics - 74% vs 69%, transcribed and analysed by 2 different experts. Qualitative analysis based systemic steriods 3.7% vs 8.3%. CF complications: diabetes - 2.7% (2011- on content categorisation was performed in order to consolidate the data 3.2%), nasal polyps - 28,3% (2011 - 15%), electrolyte disorders - 2.9% (4.1%in interpretation. 2011), pneumothorax - 0.5% (1.5% in 2011). During 2018 51 patients died, Results: 43 adolescents & 41 parents were included in the pre-transfer mean age of death 22.6 ± 9,9, in 2011–15 patients, mean age 15,9 ± 12,7. period. So 145 interviews analysed. The mean of age was 17 year old, before Conclusion: The number of patients participating in RCFPR has tripled transfer and 20 years old after. since 2011. Increased role of neonatal screening program and improved Needs’ analysis highlights the importance of an optimal organisation by CFTR mutations identification should be noted. There is also a shift in the teams during transition: Announcing the transition process and the adult frequency of some medications used, especially hypertonic saline CF centre mode of organisation; Anticipating and involving patients and inhalations. parents in the transition organisation; Accompanying the adolescents in their individual consultations and in the progressive self-management P040 of their care; reinforcing their psycho-social skills; Helping the parents in Clinical effects of the transition from paediatric to adult care for their ambivalence when they transmit their own skills to their child and patients with cystic fibrosis have difficulties to let go. A. Denis1, S. Touzet1, S. Poupon-Bourdy1, C. Llerena2. 1Hospices Civils de Lyon, Conclusion: Caregivers are already aware of the impact of the transition Pôle de Santé Publique, Université de Lyon, EA HESPER 7425, Lyon, France; pathway. SAFETIM needs confirms that patients and their families wish an 2CHU Grenoble Alpes, Hôpital Couple Enfant, CRCM Pédiatrique, La Tronche, optimal organisation for transition and propose to include therapeutic France education programs in the process.

Objectives: Young adulthood is an important and vulnerable period for P042 patients with cystic fibrosis (CF). Our objective was to compare clinical A unique cystic fibrosis outpatient service model: a patient’s outcomes such as the pulmonary function and nutritional status during perspective adolescence and young adulthood to determine if transfer from paediatric 1 1 1 1 1 O. Bosher , R. Kular , N. MacDuff , K. Thickett . The Royal Wolverhampton to adult care made a difference. NHS Trust, Respiratory Medicine, Wolverhampton, United Kingdom Methods: Patients who transferred from paediatric to adult CF care in 2013 or 2014 were identified from the nationwide French cystic fibrosis Objectives: A unique service was developed for adult CF services at New database. Medical records were extracted for three years before and after Cross Hospital in Wolverhampton to provide a solution to capacity issues in transfer. Mixed-effects model with random slopes and intercepts was used existing centres in the West Midlands, a growing issue nationally. Existing to estimate the annual rate of change in FEV1 and BMI during adolescence centres were under increasing pressure and patients were travelling long and young adulthood. Analyses were gender stratified and adjusted for distances and sometimes experiencing delays to admission due to high patients’ characteristics. patient numbers. Patient choice was for local services provided by expert Results: The study enrolled 228 patients: 118 males and 110 females. The practitioners and we sought to provide a new model under the umbrella of mean age at transfer ±SD was 19 years ±0.8 (range: 17–22). Thirteen a specialist centre based an hour’s drive away. We set up a dedicated out- patients received a lung transplant. The transfer from paediatric to adult patient facility with key local MDT members (Consultant, nurse, dietician; − care was associated with a decline in FEV1 of 1.0% per year (/yr) (95% physiotherapist - all with the requisite expertise). We have bi-monthly Confidence Interval (CI): [−2.3; 0.3]) before and of −4.6%/yr (95% CI: [−5.6; clinics attended by the specialist centre wider MDT. All out-patient services − −3.6]) after in males (p < 10 3); and of −3.0%/yr (95% CI: [−4.3; −1.7]) and are provided close to home. If admission to hospital is required patients are of −1.6%/yr (95% CI: [−2.5; −0.7]) in females (p = 0.064). The BMI changed sent to the specialist centre at UHNM. from an increase of 0.34 kg/m2/yr (95% CI, 0.21–0.48) before to 0.20 kg/m2/ Methods: After 18 months the service was assessed using a patient yr (95% CI, 0.09–0.30) after (p = 0.0489) for males. For females, the BMI satisfaction survey. changed from an increase of 0.28 kg/m2/yr (95% CI, 0.13–0.43) before to a Results: Compared to the previous service, 100% rated this service as − decrease of 0.15 kg/m2/yr (95% CI, 0.06–0.26) after (p < 10 3). At the year of better: 87% rated it as “excellent” and 13% as “very good.” In particular,100% the transfer, no significant difference was shown. Changes over time in stated correspondence, ease of access to the CF team and continuity of care

FEV1 and BMI were not associated with the status of P. aeruginosa infection is better, 67% felt travelling to the appointment is better and 81% felt the and diabetes during adolescence. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S67 wait for review from different members of the multi-disciplinary team is PEx which could enable more prompt treatment and result in improved better. All would recommend this service to family and friends. outcomes. The primary aims of this study were to Conclusion: The results demonstrate increased satisfaction with the locally provided service at New Cross Hospital. This decentralisation of services 1. determine whether HM is effective compared with routine care (RC) in may help those with CF engage with the multi-disciplinary team to help reducing hospital inpatient bed days; and keep them as well as possible for as long as possible. We think this unique 2. assess whether this results in differences in health-related quality of outpatient satellite service could be replicated at other district general life. hospitals to improve overall patient experience and help reduce clinical burden from the specialist CF centres. Methods: We conducted a single-centre, non-blinded, randomised P043 controlled mixed-methods trial recruiting CF adults with at least 1 Explore patient experience of care and of life with cystic fibrosis in admission to hospital to receive intravenous antibiotics over the preceding order to determine measures that matter to patients and parents: the 24 months. Participants were randomised 1:1 to HM (twice-weekly FEV1 ExPaParM study and CFRSD-CRISS transmitted instantaneously) or RC for the 12-month D. Pougheon1, A. Fanchini1, P.Lombrail1, G. Rault1, C. Llerena2, Q. Reynaud3,4, study period. Quantitative outcomes (including health economic analysis) P. Michel4. 1Sorbonne Paris Nord, LEPS EA 3412, Bobigny, France; 2CHU were collected at baseline and 3-monthly study visits and semi-structured Grenoble, Pediatric CF Center, Grenoble, France; 3HCL, Adult CF Center, Lyon, qualitative interviews were performed at baseline and 12-month time France; 4Lyon1 University, HESPER EA 7425, Lyon, France points. Results: 88 participants were randomised (44 HM, 44 RC) with no Objectives: Identify and prioritise the patients’ care pathways and life significant differences in baseline characteristics. Participants in the HM situations in France to assess the quality of care based on the patients’ group that required admission were in hospital for (mean (S.D.) 23.2 (20.3) experience and their experiential knowledge days compared with 29.5 (24.8) for the RC group (p = 0.3), with no Methods: Collaborative study: Establishment of a research group including significant difference in other quantitative outcomes. The total societal 2 transplanted patients, 2 non transplanted patients and 2 parents, CF costs were approximately £1,650 more per patient for the RC group than clinicians and researchers. Patients and parents are trained to qualitative the HM group (p = 0.775). Qualitative interviews revealed that HM was research to collaborate at all steps of the study with researchers and generally well-received, with participants feeling empowered, with clinicians. The nominal group technique is used to identify and prioritise improved self-management and improved awareness of their own health patients’ health and life situations from diagnosis to life post status. transplantation. Conclusions: This data supports the outcomes of the eICE study in Qualitative study: Definition of patients’ profiles and associated CF centres demonstrating that HM is effective in detecting PEx with potential to to recruit patients representing the spectrum of health and life situations; reduce inpatient bed days. In addition, HOME-CF provides evidence for development of interview guides using open-ended questions to cover reduced costs and positive participant experience of receiving HM. domains of patient experience and experiential knowledge. Results: P045 1. Paediatric and Adult CF care pathways in France in 2020 taking into User experience of virtual consultations account the diversity of patients’ situations (co-morbidities, stages of L. Funnell1,L.O’Connor1, S. Madge1. 1Royal Brompton Hospital, Adult Cystic child development, social and family life of adults); Fibrosis Department, London, United Kingdom 2. Patients’ profiles for their recruitment in the associated CF centres Introduction: The use of technology in healthcare is no new concept. Most representing a cross-sectional view of the care pathway in 2020; CF adults CF are now staying in education, working and starting families. 3. Interview guides including open-ended questions to explore patients’ The disruption of routine clinic visits have time and financial cost to and parents’ experience and their experiential knowledge applied to individuals. At this adult CF service, we are introducing virtual consulta- quality of care and life with CF tions (VC) supported by video conferencing and Bluetooth spirometry. Conclusion: This first step aims to set up the conditions for this Objective: To review patient satisfaction with VC and evaluate the financial collaborative study and the methods and tools to investigate the different and time saving costs for patients. patients’ situations. Interviews with patients will then be carried out to Methods: After each consultation a survey was sent to the patient via email collect their 12-month retrospective experience. The verbatims will be to evaluate their experience. This included ten closed-ended or multiple- analysed using the grounded theory method to identify the quality of care choice questions and seven open-ended questions. This was analysed for and quality of life criteria from the point of view of patients and parents. positive and negative feedback, time and cost implications to the patient. Results: N = 42 survey responses over 18 months from 115 new patient P044 virtual consultations. A prospective randomised controlled mixed-methods pilot study of Number of virtual consultations replacing ‘usual care’ (n = ) home monitoring in adults with cystic fibrosis (HOME-CF) Routine clinic follow-up n = 23 (54%), Annual review follow-up n = 5 (11%), 1 1 1 1 2 2,3 Day case review n = 8 (19%), CFD review n = 3 (7%), Other n = 3 (7%) E.F. Nash , J. Choyce , V. Carrolan , E. Justice , K.L. Shaw , A. Sitch , 4 1 1 Survey responses: H. Mistry , J.L. Whitehouse . University Hospitals Birmingham NHS • Use of technology and conversation flow: excellent or good - 80% Foundation Trust, West Midlands Adult CF Centre, Birmingham, United 2 • VC rating: very satisfied - 71% Kingdom; University of Birmingham, Institute of Applied Health Research, 3 • Ability to express thoughts and feelings: excellent or good - 85% Birmingham, United Kingdom; NIHR Birmingham Biomedical Research 4 • 52% rated the VC as 5/5 Centre, Birmingham, United Kingdom; University of Warwick, Division of • 100% highly likely or likely to opt for VC again Health Sciences, Coventry, United Kingdom • Travel cost saving: median €35 (IQR 16.4–40.2) Objectives: Pulmonary exacerbations (PEx) are common in people with CF • Travel time saved: median 180 minutes (IQR 120–240) resulting in impaired quality of life and progressive lung function decline. • Time saved off work: whole day - 38%, half day - 21% Home monitoring (HM) has potential as an effective method of detecting • Arranging care for dependents: 21% S68 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Conclusion: This new service is well received with all respondents stating Methods: This project uses data from the Australian Cystic Fibrosis Data they would use it again. There were savings for patients’ financially, and Registry (ACFDR). The analysis included random effect mixed linear reduced travel time and time off work, in some instances quite regression. A two-way random intercept model (by Centre and patient) significantly. Further investigation of the health of this new along with a random slope for time from diagnosis for each patient was service is currently under review. Questions remain around the perception included. Potential predictors were sequentially evaluated in the model of the teams completing such consultations and the long-term engage- using the likelihood ratio test. Appropriate sub-group analyses were ment of the clinical team and CF patients. performed in the presence of interaction effects. Results: Participants included 2,670 patients (age <21 years) and 1991 P046 patients (age 21 and greater). For those aged less than 21 years, factors

Social deprivation as a marker for lung function decline in adult cystic found to be significantly and independently associated with FEV1PP fibrosis patients included years from diagnosis, BMI, age at diagnosis, mortality, pancreatic K. Worsdell1, N. Bell2, K. Bateman2. 1University of Bristol, Bristol, United insufficiency and lung transplantation. The predictors were similar for Kingdom; 2Bristol Royal Infirmary, Bristol, United Kingdom patients aged 21 years and greater, except for pancreatic insufficiency, which became insignificant. There was significant variation in FEV1PP Objectives: Poorer socioeconomic status has been demonstrated to be within sites and within patients. The FEV1PP trajectories were different associated with worse health outcomes in CF patients (1). We aimed to between patients who underwent lung transplantation and those who did investigate the association of social deprivation in Bristol, UK, with lung not, and between patients who died and those who did not. function in our CF patients. Conclusions: This study reports initial findings to develop a longitudinal Methods: We reviewed data from the Bristol Adult CF Centre (n = 244). model of lung function in people with CF, which will help identify potential Patients were excluded if they had previous lung transplants, insufficient risk factors and also provide a baseline model of FEV1 with which to FEV1 measurements or unavailable deprivation scores; this gave 175 evaluate interventions. eligible patients. We measured social deprivation using the Index of Multiple Deprivation decile score for each patient’s postcode (1 = 10% P048 population most deprived, 10 = 10% population least deprived). We Pseudomonas aeruginosa lung infection in paediatric cystic fibrosis measured lung function using rate of change of min FEV1 level over the patients: risk factors and impact on lung function last 3 years, performing subgroup analysis for gender, BMI and confound- 1 1 1 2 1,3 1 J. Mesinele , M. Ruffin , L. Guillot , P.-Y. Boëlle , H. Corvol . Sorbonne ing factors (CF-related diabetes, gene-modifying medications (GMM), NTM Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France; and BCC infection). 2 ’ 2 Sorbonne Université, INSERM, Institut Pierre Louis d Epidémiologie et de Results: Correlation coefficients and R values were determined per group. 3 Santé Publique, IPLESP, APHP, Hôpital Saint-Antoine, Paris, France; Pediatric Only very weak positive linear relationships exist in regression models for: Pulmonology Department, AP-HP, Hôpital Trousseau, Paris, France all patients, male, CFRD, GMM and NTM subgroups. A weak negative correlation exists for the female subgroup. Objectives: Lung disease is the primary cause of morbi-mortality in All patients n = 175 (0.067, R2 0.003), male n = 100 (0.237, R2 0.03), female Cystic Fibrosis (CF) patients. Airways infections, particularly by n = 75 (−0.119, R2 0.009), CFDiabetes n = 64 (0.137, R2 0.011), NTM n = 35 Pseudomonas aeruginosa, are among the most pejorative factors associated (0.27, R2 0.04). Only 12 patients had BCC colonisation. A moderate positive with lung function decline. Infectious pulmonary exacerbations occur in 2 correlation was shown between BMI and change in FEV1 (0.366, R 0.079), about 40% of the patients and lead to chronic colonisation in 50%. with no significant relationship between BMI and IMD score (0.005, R2 Moreover, age of initial infection by P. aeruginosa varies considerably inter- 0.00001). individually. This study aims to investigate risk factors associated with Conclusion: No significant relationship was found between lung earlier onset infection and chronic colonisation and to evaluate their function and social deprivation in BACFC patients, although a weak link impact on lung function decline. was noted in female patients. Future studies of a larger cohort are Methods: We analysed paediatric patients with pancreatic insufficiency, warranted to support further evidence of a relationship between these born after 2000, and recruited into the French CF Modifier Gene Study factors. Other confounding factors (e.g. ) may not have been since 2004. We evaluated demographic and clinical risk factors such as sex, accounted for. CFTR genotype, history of meconium ileus and nutritional status; and hospital environmental risk factors such as CF centre sizes, P. aeruginosa Reference prevalence per centre, and annual rate of visits per patient. We studied the [1] David Taylor-Robinson et al. (2013). Lancet Respiratory Medicine, impact of infection on the respiratory function by modelling jointly the – Vol. 1:121 128. decline of FEV1pp and age at P. aeruginosa first acquisition and chronic colonisation. P047 Results: Among the 1,395 paediatric patients analysed, 975 (69.9%) had an Lung function over the life course of people with cystic fibrosis initial P. aeruginosa infection at a median age of 4.7 yrs [4.1–5.3]; 299 of S. Ahern1, F. Salimi1, R. Raseckaite1, T. Ranger1, A. Earnest1. 1Monash those (27.2%) progressed to chronic colonisation. The principal risk factor University, Melbourne, Australia for a younger age at onset infection was the high number (>3) of annual visits (HR = 3.68, p < 0.0001). The annual rate of FEV1pp decline before Objectives: In people with cystic fibrosis (CF), Forced Expiratory Volume onset P. aeruginosa infection was −0.47% per yr, which accelerated by 0.94% (FEV pp) generally increases up to approximately 20 years of age, and then − 1 after infection, leading to an annual rate of FEV1pp decline of 1.42% progressively decreases. Existing statistical models of this trajectory, FEV1pp per yr. however, have several limitations, including assumptions that that Conclusion: Identification of these risk factors is a challenge that should decline in FEV1 is linear over time, and lack of censoring techniques, offer a way to distinguish the patients at risk of developing earlier and/or potentially leading to selection bias. We aim to establish and validate a chronic P. aeruginosa infection and to help to better understand its multivariable longitudinal model of FEV1 over the life span of people with physiopathological mechanisms. CF, addressing current statistical methodological limitations. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S69

P049 Results: Two MAC clusters revealed multiple episodes of patient overlap in The epidemiology of bacterial pathogens in cystic fibrosis patients from clinical care areas. Three patients in cluster 1 revealed overlaps in multiple the Russian Federation clinic areas, followed by first NTM+ culture of the previously negative N. Kashirskaya1, A. Voronkova1, E. Kondratyeva1, S. Krasovskiy1, 2, patient in 12 and 25 months. Two patients in cluster 2 shared a 5-day E. Amelina2, M. Starinova1, N. Petrova1, V. Sherman1, Y. Gorinova3, hospital overlap and PFTs on the same day, followed by first NTM+ culture O. Simonova3, A. Goryainova4, S. Semykin4, M. Mukhina4,A.Lavrova4, of the previously negative patient in 21 months. One M. abscessus cluster M. Erzutova4, Y. Kondakova4, N. Romanenko4, Y. Pinegina4, S. Goncharova4, revealed first NTM+ cultures over a 4-day period in two patients during a T. Korneeva4, T. Safonova4, A. Shevlyakova4, E. Pavlinova4, M. Rybalkina4, 15-day hospital overlap one room apart. Three clusters did not reveal any M. Skachkova4, E. Furman4, V. Shadrina4, T. Vasileva4, S. Voronin4, subject overlap. Environmental and clinical isolate relatedness compar- M. Kinyaikin4, O. Kondratenko4, S. Polikarpova4, M. Chernukha4, isons are ongoing. L. Avetisyan4, O. Voronina4, N. Kapranov1, E. Ginter1, S. Kutsev1, Conclusion: Our findings suggest overlapping periods of care in two MAC A. Marakhonov1, R. Zinchenko1, 5. 1Federal State Budgetary Scientific clusters suggesting patient-to-patient transmission. In these cases, NTM+ Institution, Research Centre for Medical Genetics, Moscow, Russian Federation; cultures occurred within 25 months of exposure to a known NTM+ patient. 2Scientific Research Institute of Pulmonology of the Federal Medical and Suspicion of an environmental healthcare-associated infection is highest in Biological Agency, Moscow, Russian Federation; 3FSAI, Scientific Research the two patients who became NTM+ within a 15-day hospital overlap in the Center for Children’s Health, of the Russian Federation Ministry of Health, absence of exposure to another known NTM+ patient. This study will reveal Moscow, Russian Federation; 4Regional CF Center, Russian CF Patient Registry, risk factors contributing to transmission of NTM within CF centres. Moscow, Russian Federation; 5N.A. Semashko National Research Institute of Public Health, Moscow, Russian Federation P051 Urban life as risk factor for aspergillosis Objectives: Pulmonary damage caused by chronic colonisation of the cystic 1 1 1 2 3 C. Grehn , P. Eschenhagen , S. Temming , U. Düesberg , K. Neumann , fibrosis (CF) lung by microbial communities is the proximal cause of 1 1 C. Schwarz , ART4FUN. Charité - Universitätsmedizin Berlin, Department of respiratory failure. Registries allow examining data for trends and clinical Pediatric Pneumology, Immunology and Intensive Care Medicine, CF Center, outcomes within patients and practice sites for quality improvement 2 3 Berlin, Germany; Mukoviszidose Institut, Bonn, Germany; Charité - efforts. The aim was to study the epidemiology of bacterial pathogens in CF Universitätsmedizin Berlin, Institute of Biometry and Clinical Epidemiology, patients using the data from the CF Patient Registry of the Russian Berlin, Germany Federation (CFPR-RF). Methods: The data of 3142 CF patients [776 adults (24.7%), 2366 children] Objective: Aspergillus fumigatus frequentlycolonises the airways of patients from the 2018 annual CFPR-RF was analysed. with Cystic Fibrosis (CF) and can cause serious complications, such as Results: The number of patients with chronic P. aeruginosa (33.0%), S. allergic bronchopulmonary aspergillosis (ABPA). The prevalence of ABPA in aureus (58.4%), MRSA (4.1%), B. cepacian complex (5.8%) and St. maltophilia patients with CF ranges between 12–25% [1]. An association between ABPA (4.3%) did not change since 2011, but we observe an increase in and pet owner ship has already been described in a smaller population [2]. Achromobacter spp. up to 5.8%. In general, the frequency of gram-negative The aim of the study was to investigate whether urban or rural life as well as flora increases with an increase in the age of patients. The highest infection pet owner ship could affect the appearance of an aspergillosis. rate of S. aureus was revealed in the age groups of 4–8 years old and 8–12 Methods: The prospective questionnaire survey was carried out in 31 years old patients (63.3% and 69.3%, respectively), P. aeruginosa - in patients German CF centres in 2018. Only completed surveys, including a clearly over 32 years old (58.7%), B. cepacia complex -in24–28 years old (18.0%), S. assigned settlement-structural district type [3] were included. Statistical maltophilia -in12–16 years old and in over 32 years old patients (6.5% and analysis was performed by chi-squared test (α = 0.05). 6.0%, respectively). The frequency of Achromobacter spp. was maximum in Results: A total of 1016 questionnaires were analysed (age: 23 ± 13; 0–88 patients over 32 years old (12.4%), MRSA - in the 28–32 year old (8.4%). The years; female gender: n = 492; 48%). Prevalence of 30.2% was found for A. frequency of gram-negative flora differs across the country. For example, fumigatus, with at least one positive proof within the 12 months of the frequency of B. cepacia complex was the lowest (1%) in the South Federal investigation period. ABPA was documented in 16.2% of the CF patients. A. District and the highest (9,8%) in the Volga Federal District of RF. fumigatus documentation was significantly associated with urban life Conclusion: A better understanding of the microbial epidemiology of CF (p = 0.004). ABPA was pronounced in large cities, but without statistical should provide further opportunities to improve treatment strategies and significance (p = 0.054). Pet owner ship (n = 500; 49.2%) was significantly refine infection control measures. associated with the documentation of ABPA (p = 0.029), confirming We would like to thank CFPR-RF for providing access to patient data and previous examinations [2]. The prevalence of 19.1% was found for ABPA thank the regional CF centres representatives for allowing the use of data within the pet owner population. (http://mukoviscidoz.org/). Conclusions: With regard to aspergillosis: Urban life and pet ownership should be included in patient guidance and preventive measures. P050 References Healthcare-associated links in transmission of nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (HALT NTM) [1] Schwarz C., et al. Mycopathologia (2018) 183:7–19. J.E. Gross1, N. Hasan2, M. Strong2, J.A. Nick3. 1National Jewish Health, [2] Thronicke A., et al. Pediatr. Allergy Immunol. (2016) 27(6):597–603. Department of Pediatrics and Medicine, Denver, United States; 2National [3] https://www.bbsr.bund.de Jewish Health, Center for Genes, Environment & Health, Denver, United States; 3National Jewish Health, Department of Medicine, Denver, United States P052 Сharacteristic of chronic rhinosinusitis with nasal polyps in children of Objectives: Healthcare-associated transmission of NTM among CF patients the Russian Federation with cystic fibrosis is concerning. Clusters of highly similar strains of NTM in CF patients cared A. Petrov1, D. Polyakov2,3, E. Kondratyeva4, A. Chernyak5, A. Voronkova4, for at the same centre may arise from healthcare sources including patient- V. Sherman4, M. Starinova4, N. Kashirskaya4, N. Odinaeva1,6, Y. Boytsova7, to-patient transmission and/or acquisition from water sources within D. Moskvina7, T. Stepanenko8, T. Filippova8, L. Konovalova9, healthcare settings. V. Makhmutova8, A. Orlov10, A. Pashkevich10, M. Nikitina10, M. Ignatyeva10, Methods: We have identified clusters of NTM isolates (<20 SNP difference O. Ushatskaya10, T. Borisenko10, L. Antipova10, N. Ponomareva11, I. Shulyak12, via WGS) between two or more patients, among 10 US CF centres. This O. Novikova13, E. Vodovozova14, L. Ledeneva14, Y. Yenina15, study standardizes traditional epidemiologic investigation by which T. Ponomaryova14. 1State Budgetary Healthcare Institution Ministry of Health centres may perform data abstraction on affected patients and determines of the Moscow Region, Children’s Clinical Multidisciplinary Center of the if clustered NTM strains are related to strains isolated from healthcare Moscow Region, Moscow, Russian Federation; 2Federal State Budgetary setting water biofilm sources. We investigated six groups of patients with Institution, Scientific and Clinical Center of Otorhinolaryngology of the Federal NTM isolates in clusters and receiving care in one centre. S70 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Medico - Biological Agency of the Russian Federation, Moscow, Russian Methods: Data from the Dutch CF Registry were used from people with at Federation; 3Pirogov Russian National Research Medical University, Moscow, least one gating mutation three years before start (T-3) with Ivacaftor, year Russian Federation; 4Federal State Budgetary Scientific Institution Research of start and three years during follow-up (T3). People with CF with data of Centre for Medical Genetics, Moscow, Russian Federation; 5Research Institute all seven years were included for analyses of each variable: lung function of Pulmonology, Federal Medical and Biological Agency of Russia, Moscow, (FEV1%pred, FVC%pred), nutritional status, treatment (inhaled antibiotics, Russian Federation; 6Moscow Regional Clinical Research Institute M.F. mucolytics, bronchodilators, enzymes), chronic infection with Vladimirsky, Moscow, Russian Federation; 7Pavlov First Saint Petersburg State Pseudomonas, comorbidities ABPA and CFRD. Analyses were performed Medical University, Saint Petersburg, Russian Federation; 8Сity per year before and during treatment, with paired t-tests and Wilcoxon Multidisciplinary Hospital №2, Saint Petersburg, Russian Federation; Signed-Rank Tests, using SPSS Statistics 25. Significance level was set at 9Leningrad Regional State Budgetary Institution of Health, Children’s Clinical 0.05. Hospital, Saint Petersburg, Russian Federation; 10St. Olga Children’sCity Results: Twenty-six patients were included (79% with S1251N mutation) Hospital, Saint Petersburg, Russian Federation; 11Sverdlovsk Regional Clinical with data from all seven years. Median age at start with ivacaftor was 25 Hospital №1, Ekaterinburg, Russian Federation; 12Regional Children Clinical years. Median FEV1%pred increased significantly from 58% three years Hospital №1, Ekaterinburg, Russian Federation; 13Smolensk State Medical before start (T-3) to 72% three years after start (T3). FVC%pred showed the University, Smolensk, Russian Federation; 14Stavropol State Medical same pattern: from 80 to 91%. BMI increased significantly from 21.6 to 23.4. University, Stavropol, Russian Federation; 15Regional Children’s Clinical Use of supplemental feeding decreased significantly from 58% to 29%. Hospital, Stavropol, Russian Federation Chronic Pseudomonas infection decreased significantly from 59% to 31% and inhaled antibiotics (chronic) decreased significantly from 60 to 36%. Objectives: Studies in adults with CF show high incidence of chronic Use of bronchodilators decreased from 73% to 54% and dornase-alpha from rhinosinusitis with nasal polyps (CRSwNP). Almost all patients have 64% to 52%, which did not reach statistical significance. Use of pancreatic sinonasal symptoms. The aim of our study was to characterise different enzymes, inhaled hypertonic saline, and inhaled corticosteroids did not aspects of CRSwNP in paediatric CF population. change over time. The proportion of patients with CFRD increased in the Methods: Multifactorial correlation analysis of data on 2366 children with years before start from 11% to 23, and remained stable during treatment at CF of Russian National CF Registry. 20%. No significant changes were observed for the low occurrence of ABPA Results: Mean prevalence of verified CRSwNP in paediatric (0–18 yrs) CF (4%). population was 27.03%. According to the age it was 13.77,19.87, 36.19, 45.5% Conclusion: The (relatively small) group of Dutch people with a gating in 3, 6, 7,18 years of old respectively. It is a rare condition in age under 3 yrs mutation using ivacaftor show substantial long-term clinical improvement (1.98–3.01%). There is no difference in prevalence of homozygotes F508del with a lesser need of medication. and soft genotypes in groups with and without CRSwNP. We also did not find any reliable correlation between lung function and nutritional status P054 with presence of CRSwNP.We estimated the following differences between Partial report of the monitoring program of patients with cystic fibrosis the groups with and without CRSwNP: concomitant P. aeruginous infection in treatment with lucaftor therapy (lumacaftor-ivacaftor) 36.18% vs 22.89% (p = 0.001); intermittent P. aeruginous infection 20.14% vs A.C. Mendez1, M.G. Garcia Darderes1,M.C.Brown1, M. Dziubecki1, 15.97% (p = 0.001); MSSA infection 68.47% vs 56.78% (p = 0,02322); MRSA 1 1 1 infection 5.28% vs % (p = 0.001); need for i.v. antibiotics 39.26% vs 28.21% C. Damnotti , C. Incardona . Gador S.A., Villa Crespo, Argentina (p = 0.001); need for inhaled antibiotics 55.89% vs 38.36% (p = 0.001); Objectives: Ensure patient care in a safe manner, strengthening knowledge prevalence of CF-associated diabetes 3.19% vs 0.8% (p = 0.001); osteopor- about and promoting the notification of adverse events osis 5.32% vs 2.21% (p = 0,0137); liver damage 28,64% vs 16,05% (p = 0.001). among health professionals. Conclusion: CRSwNP was verified in 27% in paediatric CF population in Methods: All patients signed an Informed Consent Form and 2 model Russia with increasing trend due to the age. Lesion of paranasal sinuses was forms were used. Form # 1: Follow-up of Patients per visit, Form # 2: associated with more severe disease characteristics such as P. aeruginous, Notification of Adverse Events. Form # 1 was adapted from the form of the MSSA and MRSA infection, need for systemic treatment and inhalations; Argentine Society of Pediatrics, National Consensus of Cystic Fibrosis and CF-associated diabetes; liver damage and osteoporosis. Thereby necessary approved by ANMAT including multiple-choice questions and others to active diagnostic tactic regarding CRSwNP in children with CF using nasal complete, while form # 2 gathered the main adverse events identified and endoscopy and CT. We commend CF Patient Registry of Russia for providing potential present in the Risk Management Plan. access to patient data and thank the regional CF centres representatives Results: 50 physicians from 40 centres in the country participated with the (http://mukoviscidoz.org/). following distribution: 50% CABA; 37.1% Prov. Bs. As.; 4.8% Mendoza; 1.6% Formosa, 1.6% Sta Fe, 4.8% Cordoba, 1.6% Other. The program included 88 P053 patients, 47 of them female (53%) and 41 male (47%), who experienced a Long-term clinical effects of ivacaftor (Kalydeco): real-life data from total of 70 adverse reactions including: 21 reports of “Preexisting Disease the Dutch cystic fibrosis Registry Improvement”, 36 reports of “Respiratory, thoracic disorders and medias- D. Zomer1, V. Gulmans1, H. Heijerman2, H. Hendriks3, H. Janssens4, tinics”, 3 notifications of “Cardiac disorders”, 1 notification of “Cataracts”,5 G. Koppelman5, C. Majoor6, R. van der Meer7, P. Merkus8, M. Nuijsink9, notifications of “Tumor lesions”, 1 notification of “Death”, 3 notifications of S. Terheggen10, H. Van der Vaart11, K. de Winter12, J. Noordhoek1, “Weight Loss”. All adverse reactions processed during the program are Dutch CF Registry Steering Group. 1Dutch CF Foundation, Research, Baarn, contemplated for the underlying disease, described in the current leaflet, Netherlands; 2University Medical Centre Utrecht, Lung Diseases, Utrecht, and detailed in VigiAccessTM. Netherlands; 3Maastricht UMC, Pediatric Lung Diseases, Maastricht, Conclusion: The follow-up program of patients under treatment with Netherlands; 4ErasmusMC/Sophia Children’s Hospital, Pediatric Lung Diseases, lumacaftor-ivacaftor provided information on native patients in real life, Rotterdam, Netherlands; 5UMC Groningen, Pediatric Lung Diseases, allowing a deeper understanding of this new therapy with modulators of Groningen, Netherlands; 6Amsterdam UMC - Location AMC, University of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), the Amsterdam, Lung Diseases, Amsterdam, Netherlands; 7HagaZiekenhuis, Lung underlying cause of the disease. Diseases, The Hague, Netherlands; 8Radboud UMC, Pediatric Lung Diseases, Nijmegen, Netherlands; 9HagaZiekenhuis, Pediatric Lung Diseases, The Hague, P055 Netherlands; 10Amsterdam UMC - Location AMC, University of Amsterdam, Real-world trends in long-term clinical outcomes of lumacaftor/ Pediatric Lung Diseases, Amsterdam, Netherlands; 11UMC Groningen, Lung ivacaftor 12 Diseases, Groningen, Netherlands; University Medical Centre Utrecht, D. Muilwijk1, D.D. Zomer2, V.A.M. Gulmans2, C.K. van der Ent1, Pediatric Lung Diseases, Utrecht, Netherlands on behalf of the Dutch CF Registry Steering Committee. 1UMC Utrecht, 2 Objectives: To study the long-term clinical effects of ivacaftor after Pediatric Pulmonology, Utrecht, Netherlands; Dutch Cystic Fibrosis reimbursement in 2015, for Dutch people with CF aged 12 years or older. Foundation (NCFS), Baarn, Netherlands Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S71

Objective: To describe the long-term clinical changes in CF patients using P057 lumacaftor/ivacaftor. Assessing the timing and clinical characteristics of patients with cystic Methods: Annual clinical data of all Dutch CF patients using lumacaftor/ fibrosis referred for a lung transplant: an observational single centre ivacaftor before it was reimbursed at the end of 2017 were collected from study 1,2 1 1 2 1 1 the Dutch CF Registry. Data of lung function (FEV1%pred), pulmonary K. Dave , R. Dunk , S. Madge ,A.Reed , N.J. Simmonds . Royal Brompton & exacerbations (days of IV antibiotics) and nutritional status (BMI) in 5 years Harefield NHS Foundation Trust, Adult Cystic Fibrosis Centre, London, United before to 3 years after treatment initiation were used to compare long-term Kingdom; 2Royal Brompton & Harefield NHS Foundation Trust, Department of trends over time pre- and post lumacaftor/ivacaftor. Exploratory descrip- Cardiothoracic Transplantation, London, United Kingdom tive analysis was performed using paired t-tests. Additional longitudinal trend analysis with generalised linear mixed effect models is currently Objectives: The CF Foundation (CFF) lung transplant referral guidelines being performed and will be presented at the conference. 2019 provide recommendations to facilitate timely referral for patients Results: 70 Dutch CF patients (63% male) with mean age at baseline of 28 with CF. We examined the clinical characteristics of our transplanted years (10.6 SD) and mean treatment duration of 29 months (7.1 SD) were patients at time of referral to benchmark our practice against these guidelines. included in the analysis. In the 5 years before treatment, mean FEV1 significantly decreased from 60.2% (SE 2.4) to 50.0% (SE 2.3), with an Methods: Observational retrospective study using hospital records of patients transplanted 2010–2019 at our adult CF centre (n = 562). Clinical absolute mean difference of 10.2% (SE 1.6), p < 0.001. In contrast, FEV1 stabilised in the 3 years after treatment, with a mean FEV1 of 49.0% (SE 2.4) characteristics, including high-risk severity markers from the CFF guide- in year 3 post-treatment (mean difference 1.7% (SE 1.2, p = 0.157) between lines (e.g. NIV, significant haemoptysis, and pneumothorax (PTX)) were assessed at time of referral. baseline and year 3 post-treatment). Average rate of FEV1 decline was 1.8% per year in the pre-treatment period and 0.8% per year in the post- Results: 58 patients underwent lung transplantation. Of these, median treatment period. A non-significant decrease in IV antibiotic use was (range) age at referral was 33 (17–50) years. 59% (n = 34) were male, 57% observed after treatment initiation: average of 28.0 days (SE 6.2) at baseline (n = 33) homozygous F508del, and 55% (n = 32) had CF diabetes. 79% compared to 20.6 days (SE 4.1) in year 3 post-treatment. BMI significantly (n = 46) were chronically infected with P. aeruginosa, 12% (n = 7) S. increased in both pre- and post-treatment period (mean BMI 19.5–20.3 (SE maltophilia, 0.3, p < 0.001) vs. 20.2–20.7 (SE 0.3, p = 0.013), respectively). 7% (n = 4) B. cepacia complex (no cenocepacia) and 5% (n = 3) A. xylosidans. Conclusion: Long-term benefits of lumacaftor/ivacaftor can be established 7% (n = 4) had previous successful treatment for M. abscessus,2%(n=1) as indicated by observed improvement on several important clinical were on treatment at referral (negative for >12 months). outcomes. At referral, median (range) %predicted FEV1 (ppFEV1) was 27 (12–43)% and BMI 20.5 (17.1–29.2)kg/m2. 60% (n = 35) were on NIV for respiratory failure; P056 7% (n = 4) had significant haemoptysis, 7% (n = 4) had a PTX, and 2% (n = 1) A review of anaesthesia and perioperative care for patients with cystic had both within a year prior to referral. There was no difference in ppFEV1 fibrosis at Cardiff and Vale University Health Board (a national cystic at referral in those with or without NIV, significant haemoptysis or PTX. fibrosis Centre) Median (range) time on waiting list was 167 (2–1554) days. At time of 1 1 2 2 1 1 transplant, 29% (n = 17) were inpatients and 9% (n = 5) required intubation C. Francis , C. Dunstan , J. Duckers , L. Speight , K. Simpson . Cardiff & Vale 2 or ECMO. 12% (n = 7) died in the peri-operative period. 85% were alive at 1 University Health Board, Anaesthesia, Cardiff, United Kingdom; Cardiff & Vale year. University Health Board, All Wales Adult Cystic Fibrosis Centre, Cardiff, United Conclusion: There was a broad range of clinical characteristics at lung Kingdom transplant referral, but a high proportion had high risk features. CFF Objectives: Quantify the numbers of cystic fibrosis patients having surgery guidelines suggest earlier referral in this situation. In light of these findings at a national CF centre (Cardiff and Vale University Health Board) over a 5 we are reviewing our local and national guidelines to enhance the referral year period (2014–2018); Quantify the surgical procedures being per- process. formed; Identify how many of these patients required higher level care (Post anaesthesia care unit [PACU], High Dependency Unit [HDU], or P058 Critical Care admission) post operatively. Then to perform a pilot review of Follow-up before and after lung transplantation for cystic fibrosis: state anaesthetic practice in this patient group. The aim being to utilise; this of the French practices between 2011 and 2017 based on the French information; multidisciplinary discussion and consensus; and published Registry literature to produce a guideline of best practice for use at Cardiff and Vale S. De Miranda1, A. Fanton2, D. Grenet1, L. Lemonnier3. 1Hopital Foch, CRCM et UHB for the perioperative and anaesthetic care of the CF patient presenting Centre de Transplantation Pulmonaire, Suresnes, France; 2CHU Bocage, Service for surgery. de Pneumologie, Dijon, France; 3Association Vaincre La Mucoviscidose, Paris, Methods: Data collection using Cardiff CF Centre registry notes, paper and France electronic patient notes, and anaesthetic records. Literature review and multidisciplinary discussion to inform best practice Objectives: In France in 2017, CF represents 22% of indications for lung guidance. transplantation (86 patients) and 811 patients live with a pulmonary graft. Results: 315 surgical procedures were carried out between 2014–2018 in LT for CF is performed in 9 LT centres, most of them (8) sharing staff with a Cardiff, 33 (10.45%) required higher care post operatively. Most common CF centre (Mixed centre). post-operative destination was back to the CF ward, although day surgery The growing number of lung transplanted patients has encouraged the has been successfully performed. The most common surgical procedures organisation of a shared follow-up between LTand CF centres. This is made were for; Vascular access; Urology or Renal surgery; PEG (percutaneous necessary by practical reasons (distance, overcrowding of LTcentre) and is a endoscopic gastrostomy or Jejunostomy placement for feeding; ENT request from patients and teams for management of CF-related disease. surgery particularly nasal sinus surgery and polypectomy. The majority Shared follow up care is initiated by the LT centre, with well-defined of patients presenting for surgery were in the higher risk groups for medical objectives, for selected patients once stabilised after transplant- perioperative morbidity and mortality using ASA as an anaesthetic risk ation. The management of transplant issues remains the expertise of the LT stratification tool (ie. ASA 3 and 4). centre. The CF centre’s follow-up during stable periods consists of a control Conclusion: Local multi-disciplinary consensus is that a best practice visit at a frequency defined with the LT centre. It also allows treatment in guidance pathway will help standardise the perioperative care provided to acute situations before, if necessary, transfer to the LT centre. patients with cystic fibrosis presenting for surgery. Planning and pre- The objective of this work is to describe the follow up of French CF patients optimisation of patients should begin at the time for decision for surgery after LT using data from the French CF Registry. and requires input from the whole multidisciplinary team. Methods: Review of follow-up data from The French CF Registry for patients who underwent lung transplantation between 01.01.2011 and 31.12.2015 S72 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Results: 335 patients underwent a first LT. Two years before LT, 33% have Pediatric Allergy and Pulmonology, Bursa, Turkey; 13Hacettepe University already been seen in a LT or Mixed centre. Faculty of Medicine, Department of Chest Diseases, Ankara, Turkey; 14Mersin Two years after LT, 75% of patients have a follow-up including specific City Training and Research Hospital, Division of Pediatric Pulmonology, management of CF: 14% via shared care with a CF centre, 63% via follow-up Mersin, Turkey; 15Eskisehir Osmangazi University, Division of Pediatric Allergy in a Mixed centre. The other follow-up data were provided either by a LT and Pulmonology, Eskisehir, Turkey; 16Erciyes University Faculty of Medicine, centre (2%) or by a CF centre (17%). Division of Pediatric Pulmonology, Kayseri, Turkey; 17Istanbul University Conclusion: Thanks to this care organisation, the French CF Registry Faculty of Medicine, Pediatric Allergy, Istanbul, Turkey; 18Celal Bayar University collects data for all recipients. Unsurprisingly, most LT recipients are Faculty of Medicine, Division of Pediatric Allergy and Pulmonology, Manisa, followed by a LT centre that provide data to the Registry, either directly or Turkey; 19Inonu University Faculty of Medicine, Pediatric Allergy, Malatya, through a CF centre. Work is still needed to increase implication of CF and Turkey; 20Balikesir University Faculty of Medicine, Division of Pediatric LT centres in the follow-up of these patients. Pulmonology, Balıkesir, Turkey; 21Ege University Faculty of Medicine, Department of Chest Diseases, Izmir, Turkey; 22Ondokuz Mayıs University P059 Faculty of Medicine, Division of Pediatric Gastroenterology, Hepatology and Factors associated with post lung transplantation mortality in a cystic Nutrition, Samsun, Turkey; 23Firat University Faculty of Medicine, Division of fibrosis centre in Lisbon - a retrospective review Pediatric Allergy and Pulmonology, Elazig, Turkey; 24Sisli Hamidiye Etfal T. Rodrigues1,F.Ferro1, C. Lopes1, P. Azevedo1. 1Hospital de Santa Maria, Research and Training Hospital, Division of Pediatric Pulmonology, Istanbul, CHULN, Serviço de Pneumologia, Lisboa, Portugal Turkey

Despite therapeutic advances, for many patients with CF there comes a Objectives: Lung transplantation (LT) is a treatment option for cystic time when lung transplantation (LT) is the only option. A recent systematic fibrosis (CF) due to prolong life and confers a survival benefit. We aim to review showed the only pre-LT factors associated with post-LT mortality investigate number of patients, indications and contraindications for LT of were Burkolderia cepaciae colonisation and older year of LT. The aim of this all CF patients in CF Registry of Turkey (CFRT). study is to identify the factors associated with post-LT mortality in a CF Methods: All CF patients in CFRT were evaluated in terms of LT indications Centre in Lisbon. We did a retrospective review of the files of transplanted and contraindications according to the current guideline for LT (Lung patients from 2005 to 2019 comparing the group of survivors (G1) with the transplant referral for individuals with cystic fibrosis: Cystic Fibrosis group of deceased (G2). Foundation consensus guidelines). Patients who are older than 6 year-old Eighteen patients were transplanted, of which 4 (22%) died. The mortality and who could perform pulmonary function tests were included to study. rate in women was 33% vs 11% in men. The average age at the time of LT was Patients who need LT classified as Group 1 and who do not need LT similar for G1 and G2 (30 vs 29 years, respectively). G1 patients were classified as Group 2. transplanted between 2005 and 2019 and those from G2 between 2007 Results: Totally 1,488 patients were recorded in the registry in 2018 and 659 patients were included the study. There were 51 (7.7%) patients in and 2015. Mean FEV1 was lower in G2 (25 vs 31% pred), as well as BMI (17 vs 18.8 Kg/m2). In G2 75% had pancreatic insufficiency vs 79% in G1 and 50% Group 1 and 608 (92.3%) patients in Group 2 and 30 patients in Group 1 had diabetes vs 14% in G1. In G2 100% were under long-term oxygen were <18 years and 21 patients were >18 year-old. Mean age of diagnosis therapy vs 57% in G1 and 50% were under non invasive ventilation vs 7% in was 5.3 ± 8.9 years in Group 1 and 3.3 ± 4.9 years in Group 2 and 43.1% G1. No patient in either groups were colonised by B. cepaciae.InG2100% patients of Group 1 and 55.3% of Group 2 were male (p > 0.05). Mean FEV1 had colonisation by P. aeruginosa (vs 79% in G1) and 25% by MRSA (vs 14% in percentage of Group 1 was 31.4 ± 8.2 and 87.5 ± 23.9 in Group 2 (p < 0.05). G1). Treatment with inhaled hypertonic salin, mannitol, antibiotic, broncho- This study showed that, on average, patients who died after LT had worse dilator, oxygen support, non-invasive ventilation, azithromycin were respiratory and pancreatic function, lower BMI and higher rates of significantly higher in Group 1 (p < 0.05). colonisation before LT. It also showed that the mortality rate among Chronic colonisation of P.aeruginosa, H.influenzae and Achromobacter were women was higher than in men. Although these differences are not significantly higher in Group 1 (p < 0.05). B.cepacia was detected in 2 statistically significant they show a trend we think is important. This study patients and in Group 1 and 5 patients in Group 2 and nontuberculosis reinforces the importance of analysing criteria of referral to LTand keeping mycobacteria was present in 1 patient in Group 1 and 3 patients in Group patients in the best possible status in order to assure longer survivals post- 2. These were accepted as contraindication for LT. No other contra- LT in patients with CF. indications were detected. Conclusion: Totally 51 patients had need for LT. Patients who need more P060 pulmonary medications and colonisation with P.aeruginosa, H.influenzae Indications and contraindications for lung transplantation of cystic and Achromobacter could be carefully follow up in terms of LT need. fibrosis patients in Turkey 1 1 1 1 2 P061 Z.R. Onay , T. Ramasli Gursoy , A.T. Aslan , T. Sismanlar Eyuboglu , E. Cakir , 3 4 5 6 6 6 Malnutrition, oxygen use and diagnosis before 6 months are risk N. Cobanoglu , S. Pekcan , G. Cinel , D. Dogru , U. Ozcelik , E. Yalcin , 7 4 8 2 9 10 11 factors for death in children and adolescents diagnosed with cystic V. Sen , O. Ercan , A.A. Kilinc , H. Yazan , D. Altintas , E. Demir , A. Bingol , 12 13 5 14 15 16 fibrosis in a western region of Mexico N. Sapan , E. Celebi , G.D. Tugcu , A. Ozdemir , K. Harmanci , M. Kose , 1 1 1 N. Emiralioglu6, Z. Tamay17, H. Yuksel18, G. Ozcan3, E. Topal19, D. Can20, R. Hernández-Raygoza , O.M. Medina-Mendoza , A. Aguilar-Aranda , 1 1 P. Korkmaz21, G. Caltepe22, M. Kilic23, S. Ozdogan24. 1Gazi University Faculty H.H. Ruíz-Gutierrez . Instituto Mexicano del Seguro Social, Neumologia of Medicine, Division of Pediatric Pulmonology, Ankara, Turkey; 2Bezmialem Hospital de Pediatria Centro Medico Occidente, Guadalajara, Mexico University Faculty of Medicine, Division of Pediatric Pulmonology, Istanbul, 3 Objectives: To Identify the risk factors associated with survival in children Turkey; Ankara University Faculty of Medicine, Division of Pediatric and adolescents diagnosed cystic fibrosis in western region of Mexico. Pulmonology, Ankara, Turkey; 4Necmettin Erbakan University, Meram 5 Methods: The study design is a retrospective cohort analysis using Centro Medicine Faculty, Division of Pediatric Pulmonology, Konya, Turkey; Ankara Medico de Occidente Hospital de Pediatria IMSS patient registry data from City Training and Research Hospital, Division of Pediatric Pulmonology, 6 2008 to 2018, of children and adolescents-diagnosed cystic fibrosis treated Ankara, Turkey; Hacettepe University Faculty of Medicine, Division of in the pulmonology department. The data were obtained from the patients Pediatric Pulmonology, Ankara, Turkey; 7Dicle University Faculty of Medicine, 8 electronic clinical record: age of death, cause of death, gender, age of Division of Pediatric Pulmonology, Diyarbakir, Turkey; Istanbul University diagnosis, genotype, pancreatic functional status, use of supplementary Cerrahpasa̧ Medicine Faculty, Division of Pediatric Allergy and Pulmonology, 9 oxygen, bacterial cultures, nutrition state, CF-related diabetes mellitus and Istanbul, Turkey; Cukurova University Faculty of Medicine, Division of pulmonary hypertension. To be included in the analysis, patients needed at Pediatric Allergy and Pulmonology, Adana, Turkey; 10Ege University Faculty of 11 least 2 visit annually. Kaplan Meier test was used to estimate the median Medicine, Division of Pediatric Pulmonology, Izmir, Turkey; Akdeniz age of survival. Hazard ratios (HR) and 95% confidence intervals (CI) were University Faculty of Medicine, Division of Pediatric Allergy and Pulmonology, generated for univariable analyses. Multivariable cox proportional hazards Antalya, Turkey; 12Bursa Uludag University Faculty of Medicine, Division of Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S73 regression was used to model the simultaneous effects of risk factors 4407 (26.2%) “Moderate risk” and 592/4407 (13.4%) “High risk”. Death or associated with death. transplantation occurred in 2.1% of “Low risk” individuals, 7.0% “Moderate Results: A total of 106 children and adolescents between newborn to 16 Risk” and 30.2% “High Risk”. “Low Risk” and “Moderate Risk” outcomes years old were included who met the inclusion criteria. Median survival were similar to those in the French and Canadian studies, but the UK “High age was 15 years (95% CI 13.8–16.1 years). Multivariable Cox proportional Risk” population were significantly less likely to die or be transplanted than hazards regression was used to model the simultaneous effects of risk in the French and Canadian population (p < 0.0001). Overall, the factors associated with death revealed that Malnourished patients discriminatory power of the French score was less (AUC 0.82) than (p = 0.02 HR 2.3 95% CI 1.0–5.1), use of supplemental oxygen (p = 0.000, previously reported in other CF populations. HR 4.6 95% CI 2.4–8.9) and diagnosis of CF <6 months (p = 0.003 HR 2.6 95% Discussion: The French prognostic score does not perform as well in the UK CI 1.3–5.0) were at increased risk of death. The rest of variables were not as reported elsewhere internationally. Differences may relate to poorer statistically significative. access to transplant in the UK. Bespoke scores or recalibration of existing Conclusion: Life expectancy in Children and adolescents diagnosed with scores are needed in the UK to aid prognostication and inform transplant CF in western region of México is 15 years. Risk factors such malnutrition, decision making. use of supplemental oxygen and diagnosed < 6 months are associated with an increased risk of death. The newborn screening for CF was established in P064 Mexico since 2018. Evaluation of a 5-year predicted survival model for cystic fibrosis in later time periods P062 T.G. Liou1, C. Kartsonaki2, R.H. Keogh3, F.R. Adler4. 1University of Utah, Mortality trends related to cystic fibrosis in Brazil from 1999 to 2017: a Internal Medicine, Adult CF Center and Center for Quantitative Biology, Salt multiple cause of death study Lake City, Utah, United States; 2University of Oxford, Nuffield Department of A. Hasiak Santo1, L.V. Silva Filho2,3. 1Faculdade de Saúde Pública, University of , Clinical Trial Service Unit and Epidemiological Studies Unit, São Paulo, São Paulo, Brazil; 2Instituto da Criança HCFMUSP, Pediatric Oxford, United Kingdom; 3London School of Hygiene and Tropical Medicine, Pulmonology Unit, São Paulo, Brazil; 3Hospital Israelita Albert Einstein, Medical Statistics, London, United Kingdom; 4University of Utah, Mathematics, Instituto de Ensino e Pesquisa, São Paulo, Brazil College of Science and College of Biological Sciences and Center for Quantitative Biology, Salt Lake City, United States Background: Despite recent advances in the knowledge of cystic fibrosis (CF) in Brazil, comprehensive data about CF mortality are lacking. Objectives: We evaluated a multivariable logistic regression model Objectives: This study aims to describe causes of death related to CF with predicting 5-year survival derived from a 1993–1997 cohort from the the use of multiple-cause-of-death methodology. United States Cystic Fibrosis (CF) Foundation Patient Registry to assess Methods: Annual mortality data from the calendar-years 1999 to 2017 whether therapies introduced since 1993 have altered applicability in were extracted from the public database of the Mortality Information cohorts, non-overlapping in time, from 1993–1998, 1999–2004, 2005– System (Brazilian Ministry of Health). All death certificates where CF (ICD- 2010 and 2011–2016. 10 code E84) was cited as underlying or associated (non-underlying) cause Methods: We applied Kaplan-Meier statistics to assess unadjusted of death were selected. Epidemiological and clinical data were described, survival. We tested logistic regression model discrimination using the C- and mortality rates calculated by year and for the entire period. A join point index and calibration using Hosmer-Lemeshow tests to examine original regression analysis was performed to detect changes in mortality rates model performance and guide updating as needed. during the studied period. Results: Kaplan-Meier age-adjusted 5-year probability of death in the CF Results: A total of 2,854 overall deaths related to CF were identified from population decreased substantially during 1993–2016. Patients in succes- 1999 to 2017, ranging from 68 in 1999 to 289 in 2017. CF was the underlying sive cohorts were generally healthier at entry, with higher average age, cause of death in 83.5% certificates. A continuous upward trend of death weight and lung function and fewer pulmonary exacerbations annually. CF- rate was observed, with a significant annual percent change of 6.84% (±5.3– Related Diabetes prevalence, however, steadily increased. Addition of new 8.4%) among males and 7.50% (±6.6–8.4%) among females. However, variables substantially increased missingness making further refinements median age at death increased during the study period, from 7.5 years in of logistic survival models challenging and subject to bias. Newly derived 1999, to 56.5 years in 2017. multivariable logistic regression models for 5-year survival in new cohorts Conclusions: A significant and continuous increase in death rate due to CF had similar estimated coefficients to the originals. was observed in Brazil in the last years, associated with an increase in Conclusion: The original model exhibited excellent calibration and median age at death. discrimination when applied to later cohorts despite improved survival and remains useful for predicting 5-year survival. Stability of coefficients P063 suggests that extended longitudinal follow up data may be used to evaluate Assessing the validity and applicability of the French 3-year prognostic survival effects for less well reported variables or rare disease occurrences score in the UK cystic fibrosis population with high potential for death such as massive hemoptysis. All models may F. Frost1, 2, D. Nazareth1,2, M. Al-Aloul3. 1Liverpool Heart & Chest Hospital, be used to stratify patients for new studies, and the original variables and Liverpool, United Kingdom; 2University of Liverpool, Institute of Infection & coefficients may be useful as a baseline to search for additional but rare Global Health, Liverpool, United Kingdom; 3Manchester University NHS events that affect survival in CF. Foundation Trust, Manchester, United Kingdom P065 Objectives: There has been much interest globally in developing models Perspectives on personalised life expectancy information and how it which can predict outcomes, aid prognostication and inform the should be presented: a qualitative study assessment of urgency of need for lung transplantation (LT) in cystic 1 2 3 3 3 2 1 F. Malik , K. Tanner , T. Smith , R. Cosgriff , N. Medhurst , R. Keogh . King’s fibrosis (CF). A prognostic score derived from the French adult CF registry 2 College London, Medical School, London, United Kingdom; London School of data to predict death or LT over a 3-year follow up period was described in 3 Hygiene and Tropical Medicine, London, United Kingdom; Cystic Fibrosis 2017 and subsequently validated in a North American setting using the Trust, London, United Kingdom Canadian CF Registry. We assessed its performance in the UK CF population. Methods: We applied the French prognostic score to un-transplanted Previous work by Keogh et al. (PLoS ONE 2019) suggested that many people adults with CF in the UK CF Registry. The index year was 2014 and with CF (PWCF) want access to more personalised information on life subsequent outcomes (Death or Lung Transplantation) were evaluated to expectancy. Building on this, we studied what resources are currently 2017. Receiver operator characteristics plots were drawn and area under available on this topic and developed different graphical options for curve (AUC) was computed. improved communication. Results: In 2014, 4407 adults with CF met the inclusion criteria. Using the We conducted semi-structured interviews with PWCF (n = 7) and CF French prognostic score 2656/4407 (60.7%) were deemed “Low risk,” 1159/ healthcare professionals [HCPs] (n = 13). Interviews assessed the desire for S74 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 and potential impact of access to life expectancy data with different Objectives: The Manchester Adult CF centre was an outlier with respect to degrees of personal tailoring and discussed comprehension of different FEV1 and BMI in the UK CF Registry 2016 Annual Data Report. Using communication tools. Participants were recruited via convenience and Registry data, we examined the longitudinal outcomes of patients between respondent-driven sampling. Interviews were recorded, transcribed and 2010 and 2016 in an attempt to explore these findings. thematically analysed. Methods: Pseudonymised data was extracted from the UK CF Registry PWCF had an idea of summary survival statistics from internet searches but 2010–2016 verified datasets and analysed by the UK CF registry team. Adult none were aware of the current estimated UK CF Registry median predicted centres with at least 200 annual reviews in 2016 were included. For each survival of 47. Both HCPs and PWCF said discussions on this topic in clinic centre, patients with 2010 annual reviews were followed through were rare except when considering transplant. However, all participants subsequent annual entries to describe their longitudinal outcomes until said they do want to have such conversations and that having information death, transplant, or their 2016 annual review. We examined FEV1% based on specific patient characteristics would be beneficial. HCPs saw the predicted, BMI, number of deaths and transplants. possibility of using the data to motivate adherence. PWCF emphasised how Results: There were 333 patients at Manchester and 2314 at comparator it could help them plan. One PWCF said, “Yeah it would help me plan…like adult centres with data in the 2010 Registry. 13.2% of patients at right now do I get a mortgage and if so, how long do I get the loan for?” Manchester and 23.2% from other centres were excluded from analyses “ Another said, The more [info] we can get around [survival] the more of FEV1 and BMI change as they did not have data input at the same centre empowered I can be in terms of accessing care, making life plans and self- in one or more subsequent year. Death (11.7% vs 10.8%) and lung or liver managing well”. HCPs cautioned about providing data that is too transplant rates (3.9 v 4.7%) between 2010 and 2016 were similar. personalised outside of clinic where they can answer questions and give Downward trends in FEV1% predicted were observed in both Manchester support. Although PWCF agreed this information could be emotive, many and comparator centres. An absolute decrease in FEV1% predicted of 7.6 was felt it would remove some of the uncertainty they face. observed in Manchester, compared to a reduction of 5.1 in comparator

In summary, both PWCF and HCPs expressed an interest in improved centres from 2010 to 2016. Mean FEV1% in Manchester and comparator communication on life expectancy and both groups saw value in centres was similar up to 2013, but from 2014 it was consistently lower in information based on specific patient characteristics. Manchester; this corresponded with the implementation of different spirometry equipment. BMI in Manchester was lower than that of P066 comparators sites. Between 2010–2016, an increase in BMI of 0.35 kg/m2 Development of an online tool to provide accessible and personalised was observed in Manchester, compared to an increase of 0.78 k/m2 in information on life expectancy in cystic fibrosis comparator sites. K. Tanner1, F. Malik1, T. Smith2, R. Cosgriff3, N. Medhurst3, R. Keogh1. 1London Conclusion: Registry data can generate longitudinal data which may be School of Hygiene and Tropical Medicine, London, United Kingdom; more informative than cross-sectional annual data at describing outcomes 2ProPatient, Newcastle upon Tyne, United Kingdom; 3Cystic Fibrosis Trust, for individual centres. London, United Kingdom P068 Objectives: People with cystic fibrosis (PWCF) are living longer lives and Treatment follow-up with a patient support system for pro-active, facing complex planning decisions about their future for which life patient-driven care at Lund Cystic Fibrosis Centre, Sweden expectancy is a critical input. In clinic, predictions assist in care planning 1 1 1 2 2 1 S. Diemer , M. Mårtensson , C. Hansen , A. Hager , M. Montan . Skånes and patient conversations. We studied how best to present life expectancy 2 University Hospital, Lund, Sweden; Genia, Upstream Dream, Stockholm, information to clinicians and PWCF and developed a corresponding online Sweden tool, making use of UK CF Registry data. Methods: Semi-structured interviews (n = 20) were used to assess need for Objectives: As new life-changing therapies for Cystic Fibrosis (CF) become survival estimates and to test presentation styles. Because people want available, Sweden’s CF stakeholders strive to build a system for structured different degrees of personalisation depending on their sex, age, and follow-up and evaluation of new treatments for optimal care, best use of clinical measurements, we created a layered presentation where partici- resources and patient participation. A national follow-up system, including pants first receive general population-level data. They choose whether to the National CF Quality Registry and an integrated mobile patient support continue through increasingly more tailored predictions. system (PSS) was developed for use when the decision for national Results: PWCF found existing life expectancy data too general. When asked reimbursement for lumacaftor/ivacaftor was made July 2018. about the impact of having personalised information, one person explained Methods: Lund paediatric CF Centre has been working with the PSS since that it would help them focus on how to live their life. Another described 2015 to support patient self-management, pre-visit planning and shared the difficulty of not knowing what to expect in terms of survival. Clinicians decision-making. Systems and processes for working with the PSS were saw value in data based on individual patient characteristics in addition to already well established and institutionalised with the multi-disciplinary the national median. Respondents all favoured a pictogram to illustrate team at the paediatric program when a feature for lumacaftor/ivacaftor survival and many felt including uncertainty of estimates was important as self-management and adherence support was developed within the it provided “hope” for outliving the prediction. These interviews led to the existing PSS. This feature includes weekly treatment check-in reports and creation of an app for life expectancy of PWCF in the UK, currently hosted at question on antibiotic use that can be shared with healthcare teams. https://tannerk.shinyapps.io/life_expectancy/ and work is underway to Results: Lund paediatric CF Centre results as of December 2019: embed it on the CF Trust website. • Conclusion: We found PWCF are lacking information about their expected Of the patients on the new treatment, 84% (26) have the mobile patient survival and want access to this data to help plan. Clinicians agreed it would support system (PSS) with treatment support. • ≥ be useful but some raised concerns about providing it outside the clinic Of the PSS users with the treatment support feature, 58% (15) sent 2 where support and explanation could be provided. To help meet this need check-in reports in December and 88% (23) were active in the PSS in a sensitive way, we developed an app that provides survival information during the last 3 months. • conditional on age and sex. Since the treatment was made available in July 2018, a total of 491 lumacaftor/ivacaftor check-in reports have been sent to the Lund P067 paediatric CF Centre. Using a national cystic fibrosis Registry to explore longitudinal Conclusion: After over a year, the Lund paediatric CF Centre has shown outcome measures at an adult cystic fibrosis centre in comparison with significant success with the implementation of the mobile patient support other centres system (PSS) for the follow-up of lumacaftor/ivacaftor. It has contributed to P. Barry1,A.Lee2, S. Charman2, R. Cosgriff2, A. Jones1. 1Manchester University patient participation, adherence support and patient education. The use of NHS Foundation Trust, Manchester Adult Cystic Fibrosis Centre, Manchester, PSS can allow patients to gather and share real world data with healthcare United Kingdom; 2Cystic Fibrosis Trust, Registry Team, London, United to support pro-active, patient-driven optimal care. Kingdom Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S75

P069 Patient reported outcome measures are collected to identify outcomes that A retrospective evaluation of healthcare utilisation and clinical charges matter most to those living with CF. Desired health outcomes are measured in children and adults with cystic fibrosis throughout this study from the patient perspective as we move into an era R. Perkins1,2, M. Shah3, P. Marchetti1, M. Dimalaluan3, G. Sawicki1. 1Boston of innovative precision therapy in CF. Children’s Hospital, Pulmonary Diseases, Boston, United States; 2Brigham and Comparative analysis Women’s Hospital, Pulmonary and Critical Care Medicine, Boston, United Process maps from all sites are compared so that knowledge is gained from States; 3Harvard Business School, Institute for Strategy and Competitiveness, any differences that may exist in how patients receive care. Areas of highest Boston, United States cost are analysed. Value Stream Mapping is applied to identify non-value areas of care across all sites. Objectives: Prior studies have examined components of the cost of CF care Results: This is an ongoing study. with estimates from $8,000–$131,000 annually; however, these studies Conclusion: This study provides real-time data from the true patient/ likely underestimate current costs. This study aims to assess current parent perspective. Knowledge is gained through comparative analysis patterns of utilisation and cost of CF care in a single centre in the United between leading CF centres in Ireland and Boston. This is a timely States. opportunity in an emerging era of high cost CFTR modulator therapy, to Methods: A retrospective review was performed of care utilisation patterns evaluate and improve the care pathway in order to remove ineffective and and costs for children and adults with CF at a large paediatric-adult CF unnecessary care and to maximize health outcomes for our patients. centre from November 2017–November 2018. Subjects were stratified into subgroups by age. Descriptive statistics were performed. The cost of care P071 was calculated based upon hospital-derived charges for utilisation. All The new gene-modifiers therapy: obstacles to availability for Bulgarian reported charges are annual means. patients Results: 166 patients were reviewed (mean age 11.4 years, 52% males, 1 2 3 1 G. Petrova , M. Baycheva , S. Zelenski . Medical University of Sofia, Pediatric mean BMI 19.1 kg/m2 and mean ppFEV 95.1). 28% had at least one 1 Department, Pediatric Clinic,University Hospital ‘Alexandrovska’, Sofia, hospitalisation during the year. The mean clinical charges were $28,755 2 Bulgaria; Medical University of Sofia, Pediatric Department, Gastroenterology (range $66–$492,094) and were highest in those ≥18 years (mean $57,264). 3 Clinic, SBALDB ‘Prof. Ivan Mitov’, Sofia, Bulgaria; Sofia University ‘St. Kliment The mean ambulatory charges were $5,313. Lab testing (25%), pulmonary Ohridski’, Sofia, Bulgaria clinic (22%) and inpatient admissions (18%) were the largest contributors of components of total charges. Lower lung function ($23,032 ppFEV1 >80, Objective: Gene-modifiers are not currently available for Bulgaria. For the – $62,293 ppFEV1 40 80, $186,786 ppFEV1 <40; p = 0.0001), hospitalizations last 4 years more than 20 patients and their families have immigrated with ($85,452 yes, $6,362 no; p = 0.0001), Pseudomonas positive respiratory the hope for getting better treatment for cystic fibrosis (CF). culture ($48,660 positive, $22,013 negative, p = 0.02), and CF-Related Therefore we have asked ourselves why multinational companies for Diabetes ($161,892 CFRD, $22,153 no CFRD, p = 0.0001) were associated orphan drugs have problems to emerge on Bulgarian market. with an increased total charge. Patients utilising ivacaftor had lower Method: We evaluated the paths for approved in Bulgaria orphan drugs for charges than the cohort mean (mean $6,634). other rare diseases - outlining all the obstacles and know-how strategies Conclusion: Our study characterised the utilisation and charges for clinical for success. Very detailed review of the Bulgarian legislation and accepted care among a US-based cohort with CF. Lower lung function, hospitalisa- procedures was also evaluated. Special attention was noted to the tions, and CFRD were associated with increased total charges. Future companies with EMA approved orphan drugs for cystic fibrosis. prospective studies are needed to assess the relationship between cost, Results: There are two main obstacles for the orphan drugs in Bulgaria. One clinical, and patient reported outcomes as well as to capture hidden is the capability of the market and the other are the health authorities in administrative, ancillary and pharmacy costs. Bulgaria. Our country is a small market, especially for rare or ultra-rare diseases. There is one very lazy and time-consuming procedure for P070 reimbursement of the medication - roughly 500 days (compared to 100 Determining the cost of treating cystic fibrosis using Time Driven days in UK or Sweden for example). Our national pricing and reimburse- Activity Based Costing (TDABC) in an era of CFTR modulator therapy, a ment commission follows up strictly IRP (international reference pricing) collaborative paediatric study by taking the lowest price for 17 countries, thus it can reflect also to other E. O’ Grady1, 2, C. Landers2, G. Doyle2. 1Children’s Health Ireland, Pharmacy/ small countries taking us as reference. The HTA (health technology Cystic Fibrosis, Dublin 1, Ireland; 2University College Dublin, Smurfit School of assessment) procedure is relatively new with still scarce number of Business, Dublin, Ireland experts and therefore it takes too long for evaluation report. For example, it took almost 4 years for the first patient in Bulgaria to receive ivacaftor on Objectives: 30th of December 2019, and this procedure is only for this patient. The • To map the process of care received by children with CF. other patients are still “fighting with the dragons” towards the brighter • To apply TDABC to determine the true cost of CF. future. • To measure health outcomes from the patient and caregiver Conclusion: Even though Bulgarian is part of EU for more than a decade perspective. there is still huge gap in policy and availability of orphan drugs for CF and • To conduct comparative analysis between CF centres in Ireland and we still can foresee the stable tendency for health immigrants to prevail. USA. Methods: This is a prospective study. P072 Process mapping Using Registry data to investigate differences in casemix and health Participants are stratified by age (0–1 year; >1–<7 years; 7–<12 years; 12 indicators at an adult centre versus national peers years+). The patient journey is documented by direct observation of care. 1 2 2 2 1 1 A. Jones , R. Cosgriff ,A.Lee , S. Charman , P. Barry . Manchester University All steps are recorded to include activities, interventions and resources ® NHS Foundation Trust, Manchester Adult CF Centre, Manchester, United expended. The care process is mapped using Visio software. 2 Kingdom; Cystic Fibrosis Trust, Registry Team, London, United Kingdom TDABC The costs of healthcare resources are determined as the patient moves Objectives: The Manchester CF Centre was identified as an outlier with along the process map. A per minute cost for each resource is generated respect to FEV1 in the 2016 UK CF Registry Annual Data. Here we describe (capacity cost rate) and multiplied by its time requirement. The total cost the casemix and key health indicators at Manchester compared to other over a full cycle of care is obtained. In addition, costs incurred by families as large adult CF centres, in an effort to better understand the differences that a result of living with CF as well as societal costs are included. exist. Health Outcomes S76 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Methods: Pseudonymised data were extracted from the UK CF Registry 2016 verified dataset. Adult patients at the Manchester centre (n = 404) and Microbiology/Antibiotics those (n = 3429) from other large (>200 patients) centres were included. Results: Manchester and comparator centres were similar in age (mean P075 30.6 vs. 31.0 yrs, p = 0.31), pancreatic insufficiency (83.2% vs 80.8%, Live anaerobic bacteria in the sputum microbiota are associated with p = 0.24), males (56.2% vs 54.8%, p = 0.58) and homozygous F508del long-term clinical outcomes in cystic fibrosis (51.5% vs 47.5%; p = 0.13). Manchester had a lower proportion of 1 2 3 1 4 4 K. Webb , N.M. Zain , I. Stewart , A. Fogarty , E.F. Nash , J.L. Whitehouse , Caucasians (94.3 vs 97.7%; p < 0.001), higher rate of CFRD (41.8% vs 33.4%, 5 2 3 6 6 2 A.R. Smyth , A. Lilley , A. Knox , P. Williams , M. Cámara , K. Bruce , p = 0.001) and higher social deprivation scores (p < 0.001). A greater 7 1 H. Barr . University of Nottingham, Division of Epidemiology and Public proportion of patients transferring to Manchester adult centre had lung 2 Health, Nottingham, United Kingdom; Kings College London, Institute of function in the lowest quartile for 2 consecutive years between 2009–2015. 3 Pharmaceutical Science, London, United Kingdom; University of Nottingham, Rates of chronic Pseudomonas (64.1% v. 45.9% p < 0.001), Burkholderia (9.2% 4 Division of Respiratory Medicine, Nottingham, United Kingdom; University vs 5.5%, p = 0.004), and Aspergillus (18.8% v. 14.5%, p = 0.02) were higher in Hospitals Birmingham NHS Foundation Trust, West Midlands Adult CF Centre, Manchester, and NTM lower (5.2% vs 7.6%, p = 0.08). Mean BMI in 5 Birmingham, United Kingdom; University of Nottingham, Division of Child Manchester (22.3 vs 23.1 kg/m2, p < 0.001) was lower. Manchester had a Health, Obstetrics and Gynaecology, Nottingham, United Kingdom; lower proportion of patients receiving mucolytics (59.2% v. 72.6%; p < 6 University of Nottingham, National Biofilms Innovation Centre, Centre for 0.001). There was no difference in proportion of patients receiving inhaled Biomolecular Sciences, School of Life Sciences, Nottingham, United Kingdom; antibiotics (68.6% vs 70.0%, p = 0.55), but it was lower in patients with 7 Nottingham University Hospitals NHS Trust,, Wolfson Cystic Fibrosis Centre, chronic PsA (83.0% vs 90.2%, p < 0.001). Rates of supplemental feeding Department of Respiratory Medicine, Nottingham, United Kingdom (34.4% v. 31.7%, p = 0.264) and mean IV antibiotics days (20.0 days vs 20.1, p = 0.96) were not different to peers. Objectives: Microbiome studies have shown that anaerobic bacteria are Conclusion: Registry data can be used to investigate differences at an adult present in abundance in cystic fibrosis (CF) airways but their role in disease centre versus national peers. Understanding the processes driving these are not fully understood. differences may be informative for quality improvement projects within CF Using a novel live-dead cell separation technique where only bacterial cells centres. with intact cell membranes were amplified for microbiome analysis, we hypothesised that the presence and relative abundance of live anaerobic P073 bacteria in sputum of adults with CF were associated with adverse clinical The Cystic Fibrosis Atlas approach to community-based discovery and outcomes. explanation of improvement needs and inequalities of care Methods: We analysed clinical data over an 8-year period for 75 people Å. Silfverplatz1, A. Jarblad1, C. Fältström2, A. Sixhöj2, A. Hager3, with cystic fibrosis who had previously provided sputum samples at M. Grimhusen4, L. Hjelte2, I. de Monestrol2. 1Swedish Cystic Fibrosis clinical stability. The most abundant anaerobic bacteria present in sputum 2 Association, Uppsala, Sweden; Stockholm CF-Center, Karolinska University were studied to explore associations with mean annual rate of FEV1 decline Hospital, Stockholm, Sweden; 3Sweden Coalition CF, Bromma, Sweden; and all-cause mortality using two-way t-tests, linear and cox regression 4Sweden Coalition CF, Stockholm, Sweden models. Results: The annual rate of FEV1 decline if genus Porphyromonas was Objectives: Swedish Cystic Fibrosis Association (RfCF) is a patient present was 75.1 mL/yr (95% Confidence Intervals CI: 41.3 to 108.8) organisation working for equal and high quality care. In 2019, RfCF compared with 36.8 mL/yr (95% CI: 21.2 to 51.4) when absent (t-test started CF Atlas together with a digital patient support system and a p = 0.02). The relative abundance of genus Porphyromonas was associated learning network formed around the National Swedish Registry. β with rate of FEV1 decline; coef : 2.9 (95% CI: 0.86 to 4.93, p = 0.005). This CFAtlas explores how the patient community can contribute to discovery of finding was also confirmed on species level presence and relative care inequality and healthcare improvement through stories, patient abundance of Porphyromonas pasteri and Porphyromonas species. The reported data and visualisation. The goal is also to enrich Registry where presence and relative abundance of Prevotella nanceiensis was associated there are data shortcomings. – with annual rate of FEV1 decline; 99.9 mL/yr (95%CI: 22.6 177.4) when CF Atlas first addressed access to hypertonic saline. Due to unintended present compared to 42.1 mL/yr (95%CI: 28.1–56.1, p = 0.01) when absent, β effects of changes in the national reimbursement system, some patients 4.7 (95% CI: 1.65–7.8), respectively. Increments in the relative abundance of were abruptly excluded from reimbursement. Porphyromonas species was associated with increased risk of mortality; CF Atlas collaborated with Stockholm CF Centre to map patient demo- Hazards ratio: 1.1 (95% CI: 1.02–1.24, p = 0.018). graphics and patient scenarios in a way that supported actions to assess Conclusion: Live anaerobic species present in the sputum of people with and improve lacking and non-equal access to hypertonic saline free of cost. CF were associated with an increased rate of lung function decline and Methods: The hospital invoicing system was used to extract geographical mortality in a longitudinal dataset. These findings should be confirmed data on the patient population and a patient survey investigated patient with further prospective studies. perspectives. An interactive map gave visual support for RfCF assessment of the situation and decision-making on course of action. P076 Results: Of 116 paediatric and 155 adult patients at Stockholm CF Centre, Pulmonary anaerobes as guardians of respiratory function in patients 36 and 33 percent respectively live outside commuting distance and with cystic fibrosis (ANA-MUCO study) belong to local “shared-care” clinics with an average of 4 CF patients each. 1 1 1 1 1 C.-A. Guilloux , C. Lamoureux , A. François , R. Le Berre , S. Gouriou , Location of local sites and distance to the CF Centre was mapped. Survey 2 1, 3 1,3 1 S. Ramel , C. Beauruelle , G. Héry-Arnaud . Univ Brest, Inserm, EFS, UMR responses from patients revealed important variations in local solutions for 2 1078, GGB, Brest, France; CRCM Mixte de Perharidy, Fondation Ildys, Roscoff, cost-free access to hypertonic saline. 3 France; Unité de Bactériologie, Pôle de Biologie-Pathologie, Centre Hospitalier Conclusion: Mapping techniques support gap analysis and can enrich the Régional et Universitaire de Brest, Hôpital de la Cavale Blanche, Brest, France Registry. Visualisation helped RfCF assess the situation and facilitated the decision-making process. The CF Atlas approach is generalisable and will Objectives: Recent data show the importance of anaerobes in cystic fibrosis this year be used in a national real-world data program to enrich the (CF). However, their impact on lung function is not clearly established. The Registry with patient reported data on antibiotics use in support of follow- objectives of the ANA-MUCO study were to provide a comprehensive up and introduction of new therapies. description of bronchopulmonary anaerobiome in CF patients, with an emphasis on Porphyromonas (POR), which could be of interest in CF (Keravec et al., 2019). Methods: ANA-MUCO is a prospective, monocentric, descriptive, non- interventional study. In 2018, 101 CF patients from Roscoff CRCM (France) were included. Sputum was collected via an anaerobic sputum collector, Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S77 specially designed for the study. Identification and quantification of strict laboratories. Cystic fibrosis (CF) patient follow-ups rely on traditional anaerobic bacteria were performed by culturomics and qPCR. culture methods to identify bacteria involved in lung disease. However, not Antimicrobial susceptibility testing was conducted according to the only pathogen-like microorganisms but also the composition of their lung EUCAST 2019. Clinical and biological data were collected. microbiome play important roles in disease development. Their accurate Results: 866 anaerobic isolates were recovered (35 genera, 73 species). detection and characterisation is critical to provide appropriate treatments. 96.7% of samples were positive in culture to at least 1 species of anaerobes Yet, downstream processing of 16S rRNA sequencing needs to be (median: 7 species). Main genera were Prevotella (PR), Veillonella (VE), standardised for clinical purposes. Atopobium and Fusobacterium. 13 were identified as POR (8 P. pasteri [PP], 2 Methods: Here we describe an improved bioinformatic pipeline for 16S P. catoniae [PC], 2 P. uenonis [PU] and 1 P. gingivalis [PG]). All POR were rRNA gene processing to analyse the CF lung microbiome with special sensible to EUCAST antibiotics except PC, resistant to vancomycin, and PU emphasis on the selection of gene regions and denoising procedures for resistant to clindamycin. 17 anaerobic genera were firstly described in this better taxonomic assignments. We further compare results with current clinical context. PR and VE were significantly positively correlated with diagnostic protocols. improved lung function (VEMS≥70%). Results: Our analysis shows that different sub-regions show bias in the Conclusion: The ANA-MUCO study is the largest descriptive study of bacterial taxa they were able to identify at the genus level. Best resolution pulmonary anaerobes conducted in a French CF cohort. POR were was obtained with denoised longer reads not forced to merge. Amplicon successfully recovered. The main species is PP, phylogenetically close to sequencing provided more sensitive and accurate pathogen detection in all PC (unpigmented), and not PG (pigmented) as in the oral microbiota. These CF patients with the added value of describing non-pathogens and results raise the relevance of discriminating to species level, as the impact potentially beneficial microbiome counterparts. on lung health may vary totally from one species to another. This may Conclusions: With an appropriately curated reference database for explain the contradictory results of targeted-metagenomics studies on clinically relevant bacteria, a 16S rRNA gene amplicon sequencing anaerobes. workflow could be implemented to provide a plug and play output showing an overall picture of the microbial community and accurately P077 identifying relevant bacterial species. This approach combined with The role of PCR testing for Pseudomonas aeruginosa in the airways of optimised oligonucleotide arrays for detecting key pathogen genes (ex. children with cystic fibrosis antibiotic resistance) could very well be a game-changer for infection F. Hernon1,S.O’Donnell2, R. Saleh2, P.N.McNally2, S. Javadpour2,R.O’Reilly2, diagnosis in CF patients. A. Habington1,N.O’Sullivan1, D.W. Cox2. 1Children’s Health at Crumlin, Microbiology Department, Dublin, Ireland; 2Children’s Health at Crumlin, P079 Respiratory Department, Dublin, Ireland Optimisation of an approach for characterisation of the cystic fibrosis lung microbiome using whole-genome metagenomics Objectives: The aim of the study is to examine the impact of Pa L.L. Wright1, S. Nicholls2, J. Quick2,F.Frost3, D. Nazareth3, N. Loman2, (Pseudomonas aeruginosa) PCR testing on prevalence rate of chronic Pa C. Winstanley1, J.L. Fothergill1. 1University of Liverpool, Liverpool, United infection in children with CF. Kingdom; 2University of Birmingham, Birmingham, United Kingdom; Methods: A retrospective review was done on children with CF from 2011 3Liverpool Heart & Chest Hospital, Liverpool, United Kingdom to 2017 attending Children’s Health Ireland at Crumlin, Dublin, Ireland. Data on cultures and real-time PCR from sputa, throat swabs and BAL Objectives: Metagenomics studies have uncovered complex bacterial samples were collected. Demographic and clinical data was also collected communities in the cystic fibrosis (CF) lung, including well-known from patient’s notes. pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus,as Results: During the period studied, 211 patients were included in the study. well as many other genera. However, we still know little about how these In 2011, 424 samples from 139 patients were tested and 43% were Pa species might interact with each other and the effect on clinical status. We positive on airway samples. Of the Pa positive group, 83% were positive by aimed to develop a whole-genome metagenomic sequencing method to both PCR and culture testing, 14% were detected by PCR and negative by study the CF lung microbiome. culture, 3% were detected by culture methods and negative by PCR. In 2017, Methods: We collected multiple matched sputum and nasal swab samples 1093 samples from 151 patients were tested and 28% were Pa positive. In from 24 adults with CF at the Liverpool Heart and Chest Hospital over a 20- this group, 76% were positive by both PCR and culture testing, 24% were month period. Clinical data including antimicrobial treatments and clinical detected by PCR and negative by culture, 0.1% were detected by culture microbiology results were collected. We trialled a variety of methods for methods and negative by PCR. Over the study period, there was a human DNA depletion and DNA extraction to assess the best approach to significant decrease in the Pa detection rate from 43% to 28%. recover as much of the bacterial microbiome as possible. A total of 66 Conclusion: Our data suggests that real-time PCR testing may detect Pa sputum samples and 61 nasal swabs were extracted and subjected to earlier than standard culture methods. Routine PCR testing could provide Illumina whole-genome metagenomics. Resistance determinants were an opportunity for early Pa eradication prior to the establishment of identified with the CARD database. chronic infection. Results: Clinical data indicated that 14 participants had a chronic P. aeruginosa infection while S. aureus and yeast infections were most P078 common in the remaining participants. Human DNA depletion of sputum An improved bioinformatic pipeline for cystic fibrosis lung microbiome samples, using a saponin method before DNA extraction, significantly characterisation reduced the proportion of human reads in the metagenomics data (mean 85% v 18%) while increasing the proportion of reads for common genera L. Velo-Suarez1, 2, S. Schutz1, S. Gouriou1, R. Le Berre1,3, G. Héry-Arnaud1, 4. found in the CF lung including Pseudomonas (4% v 17%) Staphylococcus (2% v 1Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France; 2Association Gaétan 10%) and Streptococcus (2% v 17%). Many resistance determinants could be Saleün, Brest, France; 3Département de Médecine Interne et Pneumologie, identified from sputum, expected to be from different species present CHRU La Cavale Blanche, Brest, France; 4Unité de Bactériologie, Pôle de within the CF lung. Biologie-Pathologie, Centre Hospitalier Régional et Universitaire de Brest, Conclusion: Metagenomics has potential for use in the CF clinic to identify Hôpital de la Cavale Blanche, Blvd Tanguy Prigent, Brest, France pathogens and resistance determinants. DNA extraction methodologies for Objectives: Molecular techniques, such as next-generation sequencing metagenomics studies must be optimised in order to understand and have become increasingly fast, sensitive and cost-efficient. Due to the reduce the potential biases that may be introduced with different increase in DNA sequencing platforms, 16S rRNA gene sequencing is not approaches. limited to research purposes but may soon be available to clinical S78 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P080 HV-OPR samples. Alpha-diversity showed significantly lower richness, − − Variability of respiratory tract microbiota in patients with cystic Shannon-Wiener diversity and evenness (p = 8.76*10 11, p = 3.21*10 10 and − fibrosis p = 0.02, respectively) and higher dominance (p = 1.54*10 8) in CF-SPU L. Avetisyan1, M. Chernukha1, I. Shaginyan1, V. Zhuhovitsky1, O. Medvedeva1, compared to CF-ORP, HV-SPU and HV-OPR. For beta-diversity, we observed E. Burmistrov1, E. Siyanova1, A. Soloviev1, D. Grumov1, E. Rusakova1, significant difference between CF-SPU and CF-OPR (ADONIS; Bray-Curtis; 2 S. Krasovsky2, M. Afanasieva2, A. Voronkova3, E. Zhekayte3, A. Ginzburg1. R = 0.241; p = 0.001; 999 permutations). In addition, there was a 1National Research Center for Epidemiology and Microbiology named after the significant difference in community structure between the PWCF and HV 2 Honorary Academician N.F. Gamaleya, Moscow, Russian Federation; 2Federal (ADONIS; Bray-Curtis; R = 0.321; p = 0.001; 999 permutations). No Pulmonology Research Institute», Federal Medical and Biological Agency of difference was detected between communities of the “lower” airways Russia, Moscow, Russian Federation; 3Research Centre of Medical Genetics of and oropharynx in HV (p > 0.05). the Russian Academy of Medical Sciences, Moscow, Russian Federation Conclusion: CF-SPU samples differ considerably in their microbial community composition and structure when compared to CF-OPR. The aim is to study the composition of associations of bacteria in mixed Furthermore, composition of CF-OPR was significantly different compared pulmonary infection and the variability of the microflora of the respiratory to HV, indicating an independent acquisition of community structures in tract in patients with cystic fibrosis. PWCF. Methods: Since 2008 to 2018 2300 samples of sputum and throat swabs from CF patients (300 children and 94 adults) were examined. MALDI-TOF, P082 PCR, MLST, WGS were used. Patterns of acquisition and loss in the cystic fibrosis airway Results: Chronic lung infection (CLI) was caused in 70% of cases by microbiome: competition among bacteria contrasts with associations of microorganisms. These associations included from 2 to 6 reinforcement among fungi and mycobacteria species of bacteria. Mixed infections caused by S. aureus in combination 1 2 3 1 F. Asfour , F.R. Adler , T.G. Liou . University of Utah, Pediatrics, Primary with non-fermenting microorganisms (NFMO) prevailed. The most 2 Children’s CF Center, Salt Lake City, Utah, United States; University of Utah, common combination was P. aeruginosa with S. aureus (18.2%). Mathematics, College of Science and College of Biological Sciences and Center Longitudinal studies have identified that respiratory microbiota (RM) in 3 for Quantitative Biology, Salt Lake City, United States; University of Utah, children with CF was characterized by great diversity and variability. For Internal Medicine, Adult CF Center and Center for Quantitative Biology, Salt example, over a year of monitoring we observed 5 different combinations of Lake City, Utah, United States bacteria in a child: P. aeruginosa-E. coli, A. pittii-C. gilenii, C. indologenes-E. coli, S. aureus-Elizabethkingia miricola, K. pneumonia-E. cloacae. Transient Objectives: Airway microbes have been shown to intensely compete microbiological changes with the dominance of the core taxa were also within the airway in CF. More recent data would facilitate exploration of observed. interactions with new pathogens and confirm prior findings. Unlike children in adult patients with CF, the composition of associations is Methods: We obtained culture data from the 2010–2015 US CF Foundation less diverse. From adult patients we identified about 40 species of bacteria Patient Registry for seven bacteria, three fungi and two mycobacteria. We (NFMO predominated), while from children more than 90 species. Our applied logistic regression and generalised estimating equations to studies have demonstrated less variability and remarkable stability among estimate the association of each of these organisms in one year with adult CF RM. For example, during a 3-year monitoring, we saw that the acquisition, loss or presence of the other organisms in the following year. combination of 4 pathogens B. cenocepacia - S. aureus - S. epidermidis - We adjusted models for concurrent infections, clinical characteristics and Candida albicans was the cause of CLI in an adult. treatments. Conclusion: In childhood, the respiratory microflora in patients with CF is Results: The Registry reports over 70,000 cultures for over 21,000 patients more diverse and dynamic, and over individuals’ lifetimes community in each year of the study. Using a significance cut-off of p < 0.00001, we diversity decreased and traditional CF pathogens and individual taxa evaluated 132 cross-species interactions between each organism present begins to dominate. This indicates the need for continuous monitoring of one year and all other organisms in the next year: 28 interactions were lung microflora in CF patients. associated with acquisition (21 that increase probability of acquisition), 24 with loss (21 that increase probability of loss) and 55 with presence (32 P081 that increase probability of presence). Negative effects on presence are The airway microbiome dynamics: relationships with disease and concentrated among bacteria; positive effects among fungi and mycobac- health teria. There were few interactions between these two broad groups with G.G. Einarsson1, R.W. Lord2, A.J. Lee1, J.A. Smith3, J.S. Elborn1, A.M. Jones2, the exception of Stenotrophomonas maltophilia which competes with other M.M. Tunney4. 1Halo Research Group, School of Medicine, Dentistry and bacteria and promotes fungi and mycobacteria. Results persist with Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom; inclusion of clinical characteristics and treatments including antibiotics. 2Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom; Conclusions: Organisms without clear direct clinical effects may influence 3University of Manchester, Manchester, United Kingdom; 4Halo Research outcomes through complex networks of interactions. Treatments targeting Group, School of Pharmacy, Queen’s University Belfast, Belfast, United organisms directly associated with clinical outcomes may have unexpected Kingdom consequences due to the indirect effects of interacting organisms.

Objective: To determine if the microbiota in the “lower” airways differs P083 from the microbiota of the oropharynx in people with CF (PWCF) and Importance of preventing “healthy” part of lung microbiome healthy volunteers (HV). 1 1 1 1 1 O. Voronina , N. Ryzhova , M. Kunda , E. Aksenova , N. Zigangirova , Methods: Matched sputum (SPU; induced for HV) and oropharyngeal rinse 1 1 1 2 3 L. Kapotina , S. Saidakova , G. Danilina , A. Lasareva , E. Amelina , (OPR) samples were collected from PWCF (n = 41) and HV (n = 9). Microbial 2 2,4 5 6 V. Chernevich , O. Simonova , E. Kondratyeva , A. Chuchalin , community profiles were determined by Illumina MiSeq sequencing and 1 1 A. Gintsburg . N.F. Gamaleya National Research Center for Epidemiology and changes in alpha- and beta-diversity compared between groups. 2 Microbiology, Moscow, Russian Federation; National Medical Research Center Results: At the phyla level, in CF-SPU, there was significant enrichment in ’ 3 −16 for Children s Health, Moscow, Russian Federation; Pulmonology Research the mean relative abundance (RA) of Proteobacteria (p = 1.00*10 ). 4 Institute under FMBA of Russia, Moscow, Russian Federation; I.M. Sechenov Conversely, CF-OPR, HV-OPR and HV-SPU samples contained significantly 5 −14 −5 First Moscow State Medical University, Moscow, Russian Federation; Research higher levels of Firmicutes (p = 2.15*10 ), Bacteroidetes (p = 2.50*10 ) 6 − Centre for Medical Genetics, Moscow, Russian Federation; Pirogov Russian and Fusobacteria (p = 2.55*10 13) compared to CF-SPU. At the genus level, National Research Medical University, Moscow, Russian Federation Pseudomonas spp. RA was significantly higher in CF-SPU samples (p = − − 1.10*10 9). Conversely, Streptococcus spp. (p = 3.80*10 6) and a number of Objectives: The airways of cystic fibrosis (CF) patients harbour diverse, common anaerobic taxa such as Prevotella spp. (p = 0.005) and Veillonella polymicrobial communities. The interaction between representatives of spp. (p = 0.001) showed a significantly higher RA in CF-OPR, HV-SPU and community plays a key role in the CF. The aim of our work was to study Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S79 association between lung microorganisms, their cytotoxicity, and patient CF microbiome that could guide therapeutic decision-making and severity. ultimately improve the outcome of the disease and the quality of life of Methods: Sputum and tracheal aspirate of 751 patients several months - 68 CF patients. years of age were used. The microbes were identified by sequencing of taxa specific targets, and massively parallel sequencing of 16S rDNA gene. P085 MALDI-TOF mass spectrometry, cytotoxicity tests, MLST and ExoU/ExoS The effect of gastro-oesophageal reflux on the respiratory tract genotyping of P. aeruginosa isolates were performed. Statistical hypothesis microbiome testing and correlation analysis was done. R.W. Lord1, 2, G.G. Einarsson3, A.J. Lee3, J.S. Elborn3, J.A. Smith2, Results: In analysed cohort 45% of patients were infected by P. aeruginosa. M.M. Tunney3, A.M. Jones1. 1Manchester Adult CF Centre, Manchester, United 55 isolates were tested in detail. 84% of isolates belonging to ExoS lineage Kingdom; 2University of Manchester, Manchester, United Kingdom; 3Queen’s related to 21 genotypes (ST), characterizing the multiplicity and inde- University Belfast, Belfast, United Kingdom pendence of the sources of infection. 7 isolates were ExoU. 5 of them (ST235 and ST313) had high cytotoxicity, that confirmed risk of infection of Objectives: It has been proposed that the increased amounts of gastro- CF patients with nosocomial strains. oesophageal reflux seen in CF patients can lead to reflux aspiration, which Analysis of the lung microbiome showed exhaustion of the “healthy” part in turn influences composition of the respiratory tract microbiome. of biocenosis (Actinobacteria, Bacteroidetes, Firmicutes) with age, accom- The aim of this study was to assess microbial community composition and panied by the dominance of proteotobacteria, primarily P. aeruginosa.At structure in the upper and lower respiratory tracts, and their relationship to the same time, presence of P. aeruginosa positively correlated with fungi. intra-oesophageal measures of gastro-oesophageal reflux. Analysis of interrelation of clinical parameters of patients and microbiome Methods: CF subjects (n = 17) provided spontaneous sputum and mouth composition revealed that the most informative spirometry indicator was swill samples, then immediately underwent pH-impedance reflux mon- itoring. Genomic DNA was extracted and microbial community profiles MEF50. Decreasing of MEF50 (<35%) and frequent exacerbations associated with depletion of the Firmicutes and Prevotella fractions, and with determined by sequencing the V4 region of the 16S rRNA marker-gene dominance of Staphylococcus and Proteobacteria. Absence of using the Illumina MiSeq platform. Measures subsequently analysed Actinobacteria also correlated with respiratory function decline. included alpha-diversity (taxonomic richness, Shannon-Wiener diversity, Conclusion: So, the elaboration of the drug with selective action against evenness and dominance) and beta-diversity (PERMANOVA and mean pathogenic microorganisms and prevention of the “healthy” part of distance to group centroid). Reflux measures of interest were selected (total microbiome is the most urgent task. events, proximal events and oesophageal acid exposure), and based on these the subjects were divided into tertiles for analysis. Results: Sputum samples showed no difference in alpha-diversity for any P084 reflux measure. However, in oral rinse samples, subjects with the greatest Quick full-range determination of the composition of the cystic fibrosis total number of reflux events (upper tertile) had less alpha-diversity than lung microbiome from sputum by phylopeptidomics 1 1 2,3 2,4 1 those with the least number (lower two tertiles): richness (p = 0.016); P. Hardouin , O. Pible , H. Marchandin , R. Chiron , J. Armengaud , Shannon-Wiener diversity (p = 0.007); and dominance (p = 0.007). No 1 1 ‘ L. Grenga . Laboratory Innovative Technologies for Detection and significant difference was noted for proximal events or oesophageal acid ’ ̀ 2 Diagnostics , Bagnos-sur-Ceze, France; University of Montpellier, PHySE, exposure. There were no significant differences (p > 0.05) observed in beta HydroSciences, CNRS, IRD, Montpellier, France; 3Centre Hospitalier 4 diversity for any reflux measure for mouth rinses or sputum samples. Universitaire de Nîmes, Microbiology, Nîmes, France; Centre Hospitalier Conclusions: Our data suggests that reflux does not affect the lower Universitaire de Montpellier, Centre de Ressources et de Compétences de la respiratory tract microbiome, but may influence the upper respiratory tract Mucoviscidose, Montpellier, France microbiome. This could relate to the requirement for reflux to overcome Objectives: Our view of cystic fibrosis (CF) microbiology has drastically upper airway defences in order to reach the lower respiratory tract, but not changed over the last years but additional efforts are still required to the upper respiratory tract. understand the CF pathobiome. Here, we present the characterisation of the CF microbiome composition by Phylopeptidomics. P086 Methods: This revolutionising methodology allows quick identification Fungi in the airways of people with cystic fibrosis: traditional and and relative quantification of the microorganisms present in a complex sequence-based detection sample, even those uncultivable or poorly characterised. Phylopeptidomics N. Alghamdi1, R.C. Barton2, M. Wilcox1, S. Mitra1, D.G. Peckham1. 1University is based on peptide information acquired by high-throughput tandem of Leeds, Leeds Institute of Medical Research, Leeds, United Kingdom; 2Leeds mass spectrometry. In particular, we applied the methodology: Teaching Hospitals NHS Trust, Microbiology, Leeds, United Kingdom 1. to evaluate the impact of different mucolytic solutions on the total Objectives: Fungal pulmonary disease is increasingly being recognised as microbial signal and alpha diversity of sputum samples. Samples an important cause of morbidity and mortality in patients with cystic supplemented with RhDnase, NaCl 0.9% or DTT as well as the plain fibrosis (CF). Traditionally, routine mycology cultures are used to identify sputum collected from four different patients were analysed. In fungal isolates in CF sputum. Isolates commonly identifies, with variable addition, since some patients do not spontaneously produce sputum,. prevalence, include Aspergillus fumigatus, other Aspergillus sp., 2. we assessed the impact of the sputum sampling method on the Scedosporium apiospermum, Rasamsonia argillacea and Exophiala dermati- composition of the CF microbiome by comparing paired spontaneous tidis. The aim of this study was to compare differences between culture and and induced sputum obtained from three different patients. sequence-based methods in detecting fungi in respiratory samples taken from adult with CF. Results: Our results suggest that: Methods: We examined sputum samples from 125 people with CF by 1. the addition of mucolytic agents has an important impact on the culture and mycobiome analysis (DNA extraction, rRNA intervening microbial diversity detection of the sample. Consequently, we transcribed sequence (ITS) PCR and next generation DNA sequencing). recommend that untreated mucus should be analysed in order to Results: Culture results were dominated by yeasts including Candida sp, obtain an unbiased and comprehensive characterisation of CF Exophiala moulds, Aspergillus fumigatus, Scedoporium and Penicillium sp. respiratory tract microbes. Preliminary results suggest mycobiome analysis is significantly more 2. The effect of the sampling method should be considered when sensitive at detecting fungi in CF sputum and results in a wider range of analysing the lung microbiota and its dynamics. fungal species being detected. Conclusion: Mycobiome analysis provides a sensitive and comprehensive Conclusion: Overall, our results demonstrate that the Phylopeptidomics method for detecting fungi present in the airways of people with CF. The approach we used can provide additional valuable information to those method may also help identify viable and non-viable fungi, not isolated on obtained by classical bacteriology i.e. changes in community composition. conventional culture, which may be driving infection and allergic disease. This could open the door for systematic full-range characterisation of the S80 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P087 is given as % positive samples compared to all positive samples. Postal Inhaled and intravenous treatment strategies exert different effects on samples detected all Burkholderia spp. and 89% of P. aeruginosa (versus 93% the lung microbiome during acute pulmonary exacerbations of cystic for the clinic sample). All other organisms were detected in postal samples fibrosis: results from the AZTEC-CF study at the same or higher rate as clinic samples. F. Frost1, 2, D. Nazareth1,2, M. Walshaw1, G. Young3, C. Winstanley2, J. Fothergill2. 1Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; 2University of Liverpool, Institute of Infection & Global Health, Liverpool, Organism P. S. aureus Burkholderia Achromobacter Aspergillus Exophiala United Kingdom; 3NU-OMICS, Northumbria University, Newcastle, United aeruginosa complex sp. sp. Kingdom Overall 46 (70%) 23 (33%) 13 (19%) 11 (16%) 24 (34%) 8 (11%) prevalence, Objectives: To compare the effects of inhaled and intravenous antibiotic n (% of all treatments for acute pulmonary exacerbations on the lung microbiome of samples) adults with cystic fibrosis. Clinic sample 43 (93%) 22 (96%) 13 (100%) 9 (82%) 16 (67%) 7 (88%) Methods: AZTEC-CF was an open-label randomised crossover study prevalence, conducted at a regional adult cystic fibrosis centre in the UK n(%of positive (ClinicalTrials.gov: NCT02894684). Inclusion criteria included age >16 samples) years, Pseudomonas aeruginosa infection and no prior use of inhaled Postal sample 41 (89%) 22 (96%) 13 (100%) 10 (91%) 18 (75%) 7 (88%) aztreonam lysine (AZLI). During consecutive exacerbations, subjects prevalence, received 14 days AZLI plus intravenous colistimethate (AZLI + IV) or n(%of standard dual intravenous antibiotics (IV + IV). Sputum samples were positive collected before and after each treatment. Sequencing of the V4 region of samples) the 16S rRNA gene was undertaken on the Illumina MiSeq System for study [Overall prevalence of all organisms present in >10% of clinic and posted samples, negative and positive controls. QIIME2 was used for quality samples] control and amplicon sequence variant (ASV) inference. Greengenes database was used for taxonomical assignment. Conclusions: Despite being in the post for a median of 5 days, there was Results: Sequencing of 56 samples from 16 participants confirmed little difference in the culture-based microbiology results. Posting sputum Pseudomonas was the dominant ASV, representing >75% relative abun- samples therefore does not appear to reduce the identification of key CF dance in over two-thirds of subjects. Subjects known to culture the microorganisms, which remain viable for several days after collection. PCR- Liverpool Epidemic Strain had reduced Shannon Diversity (p = 0.001). based analyses of these same samples is ongoing. Alpha diversity was stable across the study with no observed treatment effect for either treatment. Unweighted Bray-Curtis analyses showed P089 IV + IV (r2 = 0.18, p = 0.001), but not AZLI + IV (r2 = 0.03, p = 0.64) was Microbiological and genetical characteristics of multidrug-resistant associated with significant changes in beta-diversity. We found no Pseudomonas aeruginosa isolated from cystic fibrosis patients in Qatar consistent effect on Pseudomonas abundance for either treatment. M. Sid Ahmed1,2, A. AbdulWahab1,3, K. Zahreldin1, H. A. Hadi1,A.L.AlKhal1, However, reductions in total and relative abundance of Pseudomonas M. Allangawi1, A. A. Sultan4, E. Ibrahim1, 4, A. Omrani1, J. Jass2. 1Hamad were associated with improved CFQ-R respiratory domain outcomes Medical Corporation, Doha, Qatar; 2Orebro University, Orebro, Sweden; 3Sidra − (r = 0.62, p = 0.0042). Medicine, Doha, Qatar; 4Weill Cornell Medicine, Doha, Qatar Conclusion: IV + IV exerted different effects to AZLI + IV on the compos- itional make-up of the lung microbiome. Neither treatment consistently Objectives: The emergence of multidrug-resistant Pseudomonas aerugi- reduced Pseudomonas abundance but where reductions did occur they nosa (MDR-Pa) is a therapeutic challenge in patients with cystic fibrosis were associated with improved quality of life. (CF). Colonization with P. aeruginosa can rapidly progress to a persistent infection that can ultimately develop into MDR-Pa and in CF patients this is P088 associated with significant morbidity and mortality. This study is aimed at Determining the effect of postage on the recovery of cystic fibrosis comparing the microbial and molecular characteristics of subsequent pathogens from respiratory samples MDRA-Pa infections in patients with CF. 1 2 1 3 1 2 Methods: A prospective study was conducted between 2014–2017 L. Hatfield , B. Bianco , H. Gavillet , P. Burns , D. Rivett , A. Jones , TM C. van der Gast1, A. Horsley2,4. 1Manchester Metropolitan University, for all lower respiratory tract specimen. The BD Phoenix was used fi Manchester, United Kingdom; 2Manchester Adult CF Centre, Manchester, for identi cation and antimicrobial susceptibility testing, while the fi ® fi United Kingdom; 3Hull University Teaching Hospitals NHS Trust, Hull, United Lio lchem MIC Test Strips were used as con rmation tests and the Kingdom; 4University of Manchester, Manchester, United Kingdom Illumina HiSeq 2000 system for whole genome sequencing (WGS). Results: Of the 246 MDR-Pa isolates from respiratory tract infections, 18 Objectives: Regular microbiological surveillance of sputum to detect (7.32%) were isolated from five CF patients with moderate-to-very severe pathogens is a cornerstone of CF care. In many CF centres, patients may be obstructive lung disease (4 CF patients with homozygous I1234V mutation required to post samples to the clinic, due to difficulty producing sputum and 1 with homozygous Y569D mutation). All MDR-Pa isolates were on demand or for enhanced surveillance outside of routine clinics. These resistant to cefepime, amikacin and gentamycin, while 83.3% (15/18) were samples may experience fluctuations in temperature before processing. resistant to ciprofloxacin, 27.8% (5/18) to ceftazidime/avibactam and 50% Here we report the impact of posting on the detection of common CF (9/18) to ceftolozane/tazobactam. WGS showed that the majority of MDR- pathogens, and hence reliability of the culture reports. Pa isolates belong to sequence type (ST)-389 (n = 6), and 1 isolate of each; Methods: Sputum samples were collected from 70 adults with CF. Samples ST-17, ST-235, ST-308, ST-310, ST-446, ST-823 and ST-1284, whereas 5 were weighed, mixed and split. One part was sent immediately to the isolates had an unknown ST. Analysis for drug resistance determinants microbiology lab and another was posted back to the lab through the post. revealed that the strains carried the following resistance genes: aminogly- Postal samples were returned and processed after a median of 5 (max 8) cosides; AAC(3), aadA12, APH(3′), APH(3″), ANT(2″) and APH(6), b- − days. Aliquots at each stage were stored at 80°C for subsequent PCR-based lactamases; blaVIM-2, blaVEB-9, blaPDC1,3,7,8, blaOXA-10,50.114a, blaSHV-11 and analysis. In this study, we compared clinical microbiology reporting for the blaTEM-87,116,126, and fluoroquinolones; P. aeruginosa gyrA mutation. paired-sputum samples. Conclusion: CF patients colonised with MDR-Pa have a high variability in Results: Overall prevalence for all organisms present in >10% of samples is both ST and their resistance genes suggesting that many of the infections shown in the Table. Sensitivity of the different sample types to each species are caused by newly acquired strains. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S81

P090 cystic fibrosis with livestock-associated methicillin-sensitive S. aureus Molecular epidemiology of methicillin-resistant Staphylococcus aureus ST398, in absence of symptomatology. in cystic fibrosis: eleven years in the life of a French cystic fibrosis centre A. Boudet1,2, B. Lemaire1, C. Domenjod1, F. Aujoulat3, R. Chiron3,4, P092 J.-P. Lavigne1, 2, C. Remy Dunyach1,2, H. Marchandin1, 3. 1Centre Hospitalier Heterogeneity of the population of Burkholderia cepacia complex Universitaire Nîmes, Département de Microbiologie, Nîmes, France; 2INSERM strains isolated from patients with cystic fibrosis in 2019 in the Russian U 1047, Université Montpellier-Nîmes, Nîmes, France; 3Université de Federation Montpellier, Equipe PHySE, HydroSciences Montpellier, CNRS, IRD, O. Kondratenko1, A. Lyamin1, A. Kozlov1, A. Zhestkov1, D. Ismatullin1. Montpellier, France; 4Centre Hospitalier Universitaire de Montpellier, Centre 1Samara State Medical University, Samara, Russian Federation de Ressources et de Compétences de la Mucoviscidose (CRCM), Montpellier, Objectives: Burkholderia cepacia complex (BCC) bacteria are one of the France most prognostically unfavourable microorganisms in cystic fibrosis (CF). Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) colonisa- During long-term colonisation, strains change their properties, which tion has been associated with a deterioration of CF lung disease and despite leads to the appearance of a heterogeneous population, within which there MRSA eradication is recommended, MRSA can persistently colonise the CF are morphotypes with different antibiotic resistance, cultural differences, airways. Distinct MRSA prevalence and epidemiology between countries growth rate, etc. support the need for national studies in CF. Molecular epidemiology studies Methods: The analysis of the population of BCC strains isolated from of MRSA in French and more largely in European CF patients remain scarce. respiratory samples of patients with CF for 2019 was carried out. Our aim was to characterise MRSA strains isolated in patients in the CF Identification of the isolated strains was carried out using MALFI-ToF centre of Montpellier, France. Microflex. The sensitivity of strains to antibiotics was determined by the Methods: Out of the 250 patients attending the centre, we included those disco-diffusion method (CLSI recommendations). with at least a MRSA identification between 2006 and 2016 (n = 35): 87 of Results: 123 respiratory samples were examined in which BCC strains were the 485 isolated strains were selected (1–13/patient) and subjected to isolated. Of these, strains of B. cenocepacia were isolated in 98 samples. In Multi Locus Sequence Typing, of which 20 (6 patients) were analysed by a 55 samples as a morphologically homogeneous culture, and in 43 samples microarray detecting 336 alleles of 181 genes (DNA S. aureus genotyping as a heterogeneous population of 2 morphotypes, in 8 samples with kit 2.0, Alere®). identical antibiotic resistance, and in 35 samples - with different. In 4 Results: The 87 strains belonged to 11 sequence types (STs), of which 5 samples, growth of B.contaminans was obtained. In 2 samples in the form of were undescribed. ST5 (17 patients, 45%), ST8 (11, 29%) and ST30 (2, 5%) a homogeneous population and 2 samples in the form of a heterogeneous were the more frequent and the 3 STs identified in more than one patient. 3 population with 3 different morphotypes with different antibiotic patients harboured strains of distinct STs isolated from a sputum sample resistance. In 12 samples, the growth of B.stabilis was obtained, while in and/or from successive samples in a patient; in each case, a strain of known 9 samples as a homogeneous population, and in 3 samples as a mixture of 2 ST was associated to one of new ST differing from the co-colonising strain morphotypes (with identical antibiotic resistance with 1 sample, and by 1–5 mutations in 1 of the 7 loci. None MRSA harboured the Panton- different in 2 other samples). In 4 samples, the growth of B.multivorans was Valentine leukocidin-encoding gene while 8 patients were colonised by obtained, in 3 samples as a homogeneous population, and in 1 sample as a toxic shock syndrome toxin-positive MRSA. Microarray analysis revealed heterogeneous population of 2 morphotypes with different antibiotic variability in gene content (antibiotic resistance, virulence, adhesion and sensitivity. In addition, growth of B. gladioli was obtained in 5 samples and miscellaneous genes) both among strains of a same ST and between strains growth of B.vietnamensis in 1 sample. All strains were morphologically of related STs within a sample and in successive samples in a patient. homogeneous. Conclusion: Despite monocentric, our study brought new insights into a Conclusion: Heterogeneity of strains should be considered by both still underestimated diversity and a high adaptive capacity of MRSA in CF, bacteriologists and pulmonologists when prescribing therapy. with unknown genotypes and gene content variability highlighted both at the intrasample and the intrapatient level. P093 The epidemiology of cystic fibrosis-associated infections with the P091 Burkholderia cepacia complex has evolved over the 2003–2015 period in Detection of methicillin-susceptible Staphylococcus aureus ST398 France: B. cepacia and cystic fibrosis Registry data analysis livestock-associated in children under 1 year H. Guet-Revillet1, 2, C. Dehillotte3, L. Lemonnier-Videau3, C. Segonds1, C. Saralegui1, E. Pérez2, P. Caro2, J.D.D. Caballero1, M.I. Morosini1, French CF care network. 1Centre Hospitalier Universitaire de Toulouse/Vaincre A. Halperin1, R. del Campo1. 1Hospital Universitario Ramón y Cajal, la Mucoviscidose, Observatoire Burkholderia cepacia, Toulouse, France; Microbiology, Madrid, Spain; 2Hospital Universitario de Málaga, Pneumology, 2Centre Hospitalier Universitaire de Toulouse, Service de Bactériologie- Málaga, Spain Hygiene,̀ Toulouse, France; 3Vaincre la Mucoviscidose, Paris, France Objectives: To screen the colonisation of Staphylococcus aureus in the Objectives: Burkholderia cepacia complex (Bcc) infections in CF are intestinal and respiratory niches of infants diagnosed with cystic fibrosis associated with decline in lung function, cepacia syndromes and poor and study their genetic profile and phenotypic resistance to antibiotics. transplantation outcomes. In France, the 90s were marked by large Methods: Stool and nasopharyngeal washes were collected from infants outbreaks, due to 3 B. cenocepacia and 2 B. multivorans strains. Our aim diagnosed with cystic fibrosis on consultations every two months, was to describe the 2015 Bcc-positive population and assess 2003–2015 approximately. Samples were re-suspended in 0.1% NaCl solution epidemiologic trends. and sewed on selected agar media for bacteria isolation. After incubation at Methods: The Observatoire B. cepacia, the French CF Registry and the CF 37°C 24 h, species identification of single colonies was obtained by MALDI- Care Centres participated in the study. All patients with at least 1 positive TOF. Pulsed-field gel electrophoresis (PFGE) was performed for using SmaI sputum were included. Isolates were characterized using recA sequencing or Cfr9i for enzymatic digestion. Representatives of each pulsotype were and genotyping. The following data were recorded: CF centre, gender, age, submitted for MLST analysis and clonal complexes were determined. year at first Bcc isolation, co-colonisations, clinical outcome and trans- Antibiotic susceptibility was obtained by Microscan Walkaway. plantation data. The Bcc population was compared to the whole CF Results: A total of 20 S. aureus isolates were recovered from 9 patients. population included in the Registry. Eight pulsotypes were obtained after PFGE analysis, corresponding to 8 Results: In 2015, Bcc was detected in 101 patients (sex ratio 1.4), including different MLST profiles. One patient presented ST398 in three consecutive 11 new cases and 35 long-term colonisations (>10 y), in 38 Centres. The samples, both in nasopharyngeal and intestinal niches (n = 6 isolates). frequency of other CF pathogens was similar to that in the whole CF Microscan reported susceptibility to methicillin in all cases. population. From 2003 to 2015, Bcc prevalence and incidence decreased Conclusion: Zoonotic bacteria can develop mechanisms for adaptation to from 2.4% to 1.5% and 0.30% to 0.17%, respectively. Mean age at first recovery human niches. This is the first documented colonisation of an infant with (y) increased from 14.9 to 17.4, and that of the Bcc population from 19.5 to S82 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

25.2. The B. multivorans/B. cenocepacia ratio rose from 1.0 to 2.2. The since 2013 was high (16–17.9%), but stable. This high prevalence is mainly proportion of historic epidemic strains dropped from 54% to 29%, despite due to a high rate of intermittent colonisation. Only 2.8% of CF patients 30 new acquisitions. Clustered cases due to another B. multivorans strain showed chronic colonisation, with significantly more frequent co- were detected in 2010–2012. From 2003 to 2015, 5 bloodstream infections colonisation by methicillin-susceptible Staphylococcus aureus (p < 0.0001) (BSI) occurred in untransplanted patients, and among the 48 patients who and Pseudomonas aeruginosa (p < 0,05). During chronic colonisation, S. underwent lung transplantation, the number of early BSI and of deaths maltophilia acquired resistance to cotrimoxazole and β-lactams. within 6 mo was higher in the B. cenocepacia than in the B. multivorans Interestingly, there were cases of spontaneous decolonisation. group (p < 0.05). Conclusion: We present an epidemiological report of S. maltophilia in a Conclusion: Though incidence and epidemic spread decreased during the high prevalent CF region in Europe (Roscoff, Western France). Prevalence last decade, Bcc remains of concern due to frequent persistence and was stable but above the national average. This high prevalence is mainly challenging transplantation outcomes. due to a high rate of intermittent colonisation. Chronic colonisation was rare and significantly correlated to acquired resistance. The epidemio- P094 logical investigation did not find any arguments for cross-transmission. S. Prevalence of Stenotrophomonas maltophilia in a paediatric centre: maltophilia WGS would allow us to ensure that there is no common source infection and nutritional outcomes explaining the high prevalence in this CF centre. V. D’Alessandro1, M. Bettiol2, L. Guzzetti2, M.F. Gil2, F. Rentería1. 1Children’s Hospital ‘Sor María Ludovica’, Pulmonary, La Plata, Argentina; 2Children’s P096 Hospital ‘Sor María Ludovica’, Microbiology, La Plata, Argentina Colonisation prevalence and antibiotic susceptibility of Haemophilus influenzae recovered in cystic fibrosis patients in Madrid, Spain Introduction: Stenotrophomonas maltophilia (Sm) is a non-fermenting V. Cerrudo1, R. Del Campo1, M. Velázquez1, R. Cantón1, J.D.D. Caballero1. Gram-negative bacillus considered an emerging microorganism in CF in 1Hospital Universitario Ramón y Cajal, Microbiology, Madrid, Spain recent years. It has high resistance to a broad spectrum of antimicrobials and therefore its therapeutic alternatives are scarce. The clinical implica- Objectives: To study the prevalence and antibiotic susceptibility of tion of its finding is still to be defined. Haemophilus influenzae isolated from respiratory samples of cystic fibrosis Objective: To present Sm prevalence in 2018 in our centre and to assess (CF) patients who attended to a national reference centre during a 1-year nutritional outcomes. period (2019). Materials and methods: A total of 141 patients who were 0–15 years old Methods: Patients’ culture results and demographical data were retro- and followed in our centre during 2018 was studied. Respiratory samples spectively reviewed over the study period. Respiratory samples were were cultured and sensitivity tests were performed according to CLSI 2018. seeded in chocolate agar plates supplemented with bacitracin Body mass index (BMI) z score was assessed as a clinical parameter. (Thermofisher, United Kingdom) and incubated at 37°C in 5% CO2 Results: Sm was isolated in 22 of 141 patients (15.7%). Of these,14 (64%) had atmosphere for H. influenzae isolation, being suspicious colonies identified their first and only isolation and only 8 (36%) had isolates in previous years by MALDI-TOF (Bruker Daltonics, Germany) mass spectrometry. Antibiotic or more than one during the year. Regarding coinfections, 12/22 isolated susceptibility of the isolates was performed by disk-diffusion following methicillin-sensitive Staphylococcus aureus, 4/12 Sm as the only flora, 2/22 EUCAST recommendations. methicillin-resistant Staphylococcus aureus, 2/22 Enterobacteriaceae, 2/22 Results: A total of 186 patients (58% males) attended to our CF-Unit over Achromobacter sp., 2/22 Haemphilus sp, 1/22 Pseudomonas aeruginosa and the study period. Patients median (IQR) age was 12.5 (28–4) years, being 1/22 Pseudomonas aeruginosa mucosa. In respect of sensitivity, 100% was 45% (n = 83) older than 18. Patients contributed with a median (range) sensitive to minocyclines and levofloxacin and 3/22 (13.6%) were resistant number of 3 (1–11) respiratory samples. The prevalence of H. influenzae to TMS. In 10 patients, BMI z score was evaluated before and after the was 33%, having 62 patients at least one positive culture over the study isolation, finding a decrease in 7 (70%). period. Colonised patients had a median (IQR) age of 5 (8–3) years. Conclusions: The prevalence of Sm in CF has increased in recent years. Sm Antibiotic susceptibility of 131 H. influenzae strains was studied and results was found mostly associated with methicillin-sensitive Staphylococcus are showed in the table below. aureus. Resistance to TMS was 13.6%, one of the most used antibiotics for its AMP: 75% S empirical treatment. We found a decrease in BMI z score in the evaluated AMC: 100% S patients. CTX: 100% S SXT: 61% S P095 CIP: 99% S Investigation of Stenotrophomonas maltophilia epidemiology in a AMP: ampicillin; AMC: amoxicillin-clavulanate; CTX: cefotaxime; SXT: French cystic fibrosis centre trimethoprim/sulfamethoxazole; CIP: ciprofloxacin. C. Capaldo1, C. Beauruelle1,2, P. Saliou3, G. Rault4, S. Ramel4, Conclusion: The prevalence of H. influenzae is high in our CF-Unit when G. Héry-Arnaud1, 2. 1CHRU de Brest, Département de Bactériologie-Virologie, compared with previously published data for Spain, especially among Hygienè et Parasitologie-Mycologie, Brest, France; 2Univ Brest, Inserm, EFS, children. Antibiotic resistance to ampicillin and trimethoprim/sulfameth- β UMR 1078, GGB, Brest, France; 3CHRU de Brest, Equipe Opérationnelle oxazole was also significant, whereas other -lactams and quinolones d’Hygiene,̀ Brest, France; 4Centre de Ressources et de Compétences de la remained almost completely active against H. influenzae. Mucoviscidose (CRCM), Roscoff, France P097 Objectives: Stenotrophomonas maltophilia is an emerging opportunistic Review of nontuberculous mycobacterium growths and clinical pathogen. The increasing incidence is of particular concern in patients with outcomes in a Leeds paediatric cystic fibrosis unit 2017–2019 cystic fibrosis (CF). Since 2012, the Western France has witnessed high E. Guy1, H. Afridi1, C. Sowerby1, M. Denton1. 1Leeds Children’s Hospital, Leeds annual prevalence of S. maltophilia colonization/infection. This retrospect- Paediatric Cystic Fibrosis Unit, Leeds, United Kingdom ive observational cohort study investigated the epidemiology of S. Objectives: Non-tuberculous mycobacterium (NTM) is now an established maltophilia emergence in a reference CF center in Western France pathogen in cystic fibrosis (CF) patients. We reviewed our microbiological (Roscoff center), a region of high prevalence of CF in Europe. data to report numbers of CF patients under 16 who have grown a NTM in Methods: All CF patients with S. maltophilia isolated in respiratory samples sputum samples over 2 years and analyse their treatment, eradication rates between December 2013 and February 2017 were included. For each and clinical progress. patient the colonisation status with S. maltophilia was determined. The Methods: Using our electronic patient records with cross reference to the epidemiological and microbiological characteristics collected were com- microbiological samples we identified all patients growing a NTM in the set pared between colonisation statuses. time period. Results: S. maltophilia was isolated in 90 patients (42 males, 48 females). Clinical records were correlated to look at treatment regime (including Mean age at first colonization was 24.4 ± 13.5 years. Annual prevalence medication type, number and duration), and whether the organism Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S83 isolated was eradicated or regrown in the 2 year timescale. Clinical difficulties might influence detection/treatment/outcome of NTM infec- indicators FEV1 and BMI were reviewed in this patient cohort over the 2 tion. Slovenia (2 million inhabitants), faces additional challenge. We years. namely have less than 50 CF-adult patients and two CF-adult centres Results: Sixteen paediatric CF patients had positive growths of despite that small number. Thus the aim was to present the Slovenian Mycobacterium abscessus between 2017 and 2019 on respiratory sampling. surveillance of NTM infections from our adult CF centre, where almost all Age range 7–15 years, male to female ratio 6:10. CF adults with advanced disease are treated. 100% of patients received treatment, and of this group 75% followed our Methods: We conducted a retrospective cohort analysis of all CF Leeds NTM treatment protocol (Appendix 1). Any issues with the treatment adults since establishment of our centre in 2000 with focus on NTM regime were also reported. 25% of patients were free of NTM at the end of infection. the review period and 56% had regrown the organism. 19% were negative Results: Since 2000 36 CF-adults have been referred to us. One (moved on sampling, but were still either on treatment or just had completed it. abroad after first visit) was excluded from cohort. 35 CF-adults (22 women,

FEV1 showed persistent decline in 3 patients and BMI was only significantly 13 men) aged 22.5 (16 to 52) at first presentation were included. 21 reduced in 1 patient. underwent lung transplantation (LuTX) just prior (4) or during observation Conclusion: Of the 16 paediatric patients who acquired Mycobacterium time (17). No-one died prior to LuTX except one, who died due to heroin abscessus, 100% received treatment (with 75% getting triple oral antibiotic overdose. Three CF-adults died in the first year and one 8 years after LuTX. plus nebulised therapy for 12 months) and 25% eradicated the organism. We had diagnosed and successfully treated NTM infection in 2 women. There is a group of patients whose clinical parameters seem unaffected by Both were in early phase of infection with Mycobacterium abscessus subsp.

NTM and a group that seem more seriously clinically effected. More abscessus, sensitive to macrolide antibiotics. First one (27 years, FEV1 75% at research in this group of patients is needed to find out if we can find co- the time of NTM diagnosis) is stable since then for 77 months after founding factors and minimise the risk of clinical decline after acquisition treatment. Second one was diagnosed while she has been already on LuTX of NTM. list (37 years, FEV1 22%). 5 months after initiation of iv antibiotics she had successful LuTX and iv antibiotics were discontinued 4 months thereafter.

P098 She is now stable (FEV1 60%), without signs of NTM 14 months after Analysis of differences in protein profiles of Mycobacterium abscessus discontinuation of antibiotics. strains isolated from a patient with mycobacteriosis Conclusion: Results showed good detection (prevalence 2/35, 5,7%) and D. Ismatullin1, A. Lyamin1, A. Kozlov1, O. Kondratenko1, A. Zhestkov1. treatment of NTM infection despite low number of CF-adults, financial and 1Samara State Medical University, Samara, Russian Federation organisational problems in our adult CF centre.

Objectives: Non-tuberculous mycobacteria (NTM) are of great clinical P100 importance in patients with CF. Every year, new data appear on the Mycobacterium abscessus in paediatric cystic fibrosis patients in a detection of NTM in patients with CF around the world. reference centre in Argentina Methods: In total, from 2017 to 2019, 568 patients with CF were allocated 1 2 2 2 3 G. Manonelles , S. Zaragoza , S. Lubovich , V. Rodriguez , L. Ibarra , 45 strains of M.abscessus in 15 patients. One strain was isolated from a 2 2 1 E. Rodriguez , A. Teper . Hospital de Niños Ricardo Gutierrez, Infectious watering can in a patient’s house. To isolate NTM, a selective medium was 2 Disease, Ciudad de Buenos Aires, Argentina; Hospital de Niños Ricardo used BCC. Identification using the MALDI Biotyper system (Bruker Daltonik 3 Gutierrez, Respiratory Center, Ciudad de Buenos Aires, Argentina; Hospital de GmbH). The cultivation time of crops is 21 days. After the extraction Niños Ricardo Gutierrez, Microbiology, Ciudad de Buenos Aires, Argentina procedure according to the standard protocol of the manufacturer, the analysis was carried out using the ClinProTools 3.0 program. We analysed 8 Background: Incidence of Mycobacterium abscessus (MA) infection is being protein profiles of M.abscessus strains isolated at different times in one increasing in cystic fibrosis (CF) patients in the last years. patient with a confirmed diagnosis of mycobacteriosis according to ATS Objective: To describe the incidence of MA, demographic data, clinical criteria. impact, and treatment response in a paediatric CF centre in Buenos Aires, Results: In the study of protein profiles, changes occurred in 6 different Argentina. proteins. 2 strains isolated in 2017 were stable in all protein profiles until Methods: Descriptive study. Medical records obtained between June 2014 2018. In 2018, there was no protein with a mass of 5770 Da in these two and December 2019 were reviewed. Diagnosis of MA infection was made strains. In the 2nd half of 2018, no protein with a mass of 5498 was released. using 2 positive sputum cultures and clinical symptoms. Age at diagnosis of At the same time, it was customary to sow water from the shower, as a MA infection, nutritional status, genetic mutation, bacterial coinfection, result, the protein profile of the isolated strain was identical to the strains lung function and treatment response were analysed. seeded from sputum. Until 2019, the patient did not receive therapy due to Results: MA was diagnosed in 7/160 (4.4%): 5 females, 1 F508del a stable condition. Since 2019, the following changes have occurred in homozygous, 2 F508del heterozygous and 4 with other mutations, 6 had strains, there has been a loss of proteins with masses of 2042, 4033, 5498 pancreatic insufficiency. Median age at first MA isolation was 11 years (3– and 7193 Da, but proteins with masses of 5770 and 7200 Da have been 22). BMI median Z-score was −1.43. Four patients had Pseudomonas ’ identified. Since that time, the patient s condition according to CT data coinfection. Median FEV1 (n = 6) was 65% in MA patients. 7 MA were began to deteriorate and a decision was made to prescribe therapy. susceptible to cefoxitín, 4 to linezolide, 3 to clarithromycin,1 to amikacin, 3 Conclusion: The study showed the correspondence of changes in the intermediate resistance to amikacin and all were resistant to ciprofloxacin protein profiles of M.abscessus strains to changes in the process in patients and doxycycline. All patients received an intensive phase treatment at least according to CT data. The identity of the strains isolated from the 28 days including amikacin, clarithromycin or azithromycin and one or environment and sputum of the patient was noted. more additional IV antibiotic (cefoxitin, tigecycline, imipenem/merope- nem, linezolide) followed by a maintenance phase with macrolide, inhaled P099 amikacin and two or three oral drugs of moxifloxacin, ciprofloxacin, Nontuberculous mycobacteria (NTM) infection in adults with cystic minocycline, linezolid and clofazimine) during 6 months. Microbiological fibrosis: a surveillance from Slovenian adult cystic fibrosis centre cure was achieved in 4 patients. B. Salobir1, 2, M. Badovinac1,M.Žolnir3, D. Lestan1, M. Harlander1,2, M. Turel1 Conclusions: MA infection occurs in later ages than other infections in CF . 1University Medical Center Ljubljana, Department of Pulmonology and patients. More than a half of them had already Pseudomonas chronic Allergic Diseases, Ljubljana, Slovenia; 2University of Ljubljana, Medical Faculty, infection. In spite of an adequate treatment there was a high level of Ljubljana, Slovenia; 3University Clinic of Respiratory and Allergic Diseases treatment failure. MA showed a high resistance profile. Golnik, Laboratory for Mycobacteria, Golnik, Slovenia

Objectives: NTM infection is emerging as a significant threat to adults with CF. However, there are limited data on diagnosis, treatment and prognosis, especially from Eastern countries, where lower income/organisational S84 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P101 were stable in 43% (n = 3), one patient showed progressive disease on HRCT Diagnostics and surveillance of nontuberculous mycobacteria in cystic and one patient showed improvement in cavitary disease. The most fibrosis patients common reported were nausea, sensorineural hearing loss, and O. Voronina1, N. Ryzhova1, M. Kunda1, E. Aksenova1, E. Amelina2, peripheral neuropathy. O. Simonova3,4, A. Chuchalin5, A. Gintsburg1. 1N.F. Gamaleya National Conclusion: Management and treatment of MABS is difficult although Research Center for Epidemiology and Microbiology, Moscow, Russian eradication can be successful. The main challenges are treatment toxicity Federation; 2Pulmonology Research Institute under FMBA of Russia, Moscow, and lengthy duration of therapy. Russian Federation; 3National Medical Research Center for Children’s Health, Moscow, Russian Federation; 4I.M. Sechenov First Moscow State Medical P103 University, Moscow, Russian Federation; 5Pirogov Russian National Research Lymphocyte responses to Mycobacterium tuberculosis and Medical University, Moscow, Russian Federation Mycobacterium bovis are similar between BCG-vaccinated patients with cystic fibrosis and healthy controls Objectives: Nontuberculous mycobacteria (NTM) are widely spread in the 1 1 2 1 1 3 R. Mauch , P.C. Alves , C.E. Levy , J.D. Ribeiro , A.F. Ribeiro , N. Høiby , environment (water and soil), persist for a long time on the surface of 1 1 M.T. Nolasco da Silva . University of Campinas, Center for Investigation in fomites and can cause chronic infections in CF airways, complicating the 2 Pediatrics, Campinas, Brazil; University of Campinas, School of Medical course of the disease. Refinement of the approach for NTM express 3 Sciences, Department of Clinical Pathology, Campinas, Brazil; Rigshospitalet, identification and comparison was the goal of our investigation. Department of Clinical Microbiology, Copenhagen, Denmark Methods: Amplification and sequencing of groEL2 gene was used for NTM taxonomic identification, 6 loci panel of unique genes and VNTR (variable Objectives: The low rate of nontuberculous mycobacteria (NTM) among number tandem repeat) regions was elaborated for Micobacteroides Brazilian patients with cystic fibrosis (CF) may be due to a cross-reactive abscessus epidemiological control. Microbiome sequencing by Illumina Bacille Calmette-Guérin (BCG) . In the present pilot study, we platform was used for estimating the percentage of NTM in the lung aimed to compare the lymphocyte responses against Mycobacterium biocenosis. 332 CF patients from several months to 68 years of age were in tuberculosis and M. bovis (BCG) in Brazilian BCG-vaccinated CF patients our cohort. Sputum and tracheal aspirate were used for analysis. and healthy controls. Results: 21 (6%) of patients had at least 1 sample positive for NTM. 70% of Methods: The lymphocyte response of CF patients (n = 10; mean age = 16.8 revealed NTM were M. abscessus. Slow-growing Mycobacterium lentiflavum years) and healthy controls (n = 10; mean age = 29.3 years) was assessed in and fast-growing Mycolicibacterium aubagnense were detected in sputum terms of lymphocyte proliferation index (LPI), using flow cytometry. of adult patients after long-term therapy against Bukholderia. M. gordonae Median rates of each cell subtype (CD4, CD8, CD19 and gamma-delta) were and M. simiae were revealed in samples of young and adult patients with also determined. Staphylococcus and Achromobacter infections. M. abscessus was found in Results: Median LPIs (CF vs. controls) were 22.9% vs. 13.0% (p = 0.481) and samples of 10–39 years old patients with and without proteobacteria 23.1% vs. 17.6% (p = 0.481), upon stimulation with M. tuberculosis and BCG, infections. The lung microbiome of one adult patient was represented only respectively. Both groups had a predominant CD4 response to M. by M. abscessus. Comparison of M. abscessus demonstrated that bacteria tuberculosis (median rate = 82.5% vs. 79.7%; p = 0.796) and BCG from 3 patients were from one clone according to 6 loci testing. All these (LPI = 84.3% vs. 83.0%; p = 0.853), which were significantly higher than patients were from geographically distant regions and had no contact with the CD8, CD19 and gamma-delta responses within both groups. We did not each other. found significant correlations between time of vaccination and LPI against Conclusion: So we could conclude that dangerous for CF patients M. either M. tuberculosis or BCG in any of the groups. CF patients tended to abscessus clone is spread globally. Elaborated approach was effective in have a higher CD8 response upon stimulation with the phytohemagglu- monitoring of NTM. tinin mitogen than healthy controls (median rate = 42.8% vs. 31.7%, p = 0.075). P102 Conclusion: The responses of BCG-vaccinated CF patients to Mtb and BCG Mycobacterium abscessus treatment complexity in adult patients with are at least similar to those of healthy individuals. These are probably cystic fibrosis: case series and review memory responses elicited by the BCG vaccination, that can cross-react A. Alameeri1, A. Sahadevan2, A. Connolly2, C. Gallagher2, E. Mckone2. with nontuberculous mycobacteria (NTM) and may explain the low 1National Referral Center for Adult Cystic Fibrosis, St Vincent University frequency of NTM lung infection in our CF centre. Also, an elevated CD8 Hospital, Respiratory Department, Dublin, Ireland; 2National Referral Center T cell production may protect CF patients against Mtb. for Adult Cystic Fibrosis, St Vincent University Hospital, Dublin, Ireland P104 Objectives: This report describes a case series of 8 CF patients who Epidemiology of fungal airway colonisation in patients with cystic underwent eradication treatment for MABS between 2011–2018 in our fibrosis - a single centre 11-year observational study adult CF centre. 1 1 2 1 2 J. Patzer , V. Strenger , W. Buzina , M. Egger , L. Masoud-Landgraf , Methods: Case series of 8 patients treated for MABS infection was 1 1 1 1 1 E. Haber , A. Pfleger , M. Modl , E. Eber . Medical University of Graz, Dep. of performed by using the medical charts of treated CF patients attending 2 Paediatrics and Adolescent Medicine, Graz, Austria; Medical University of our CF centre between 2011–2018. The diagnosis was based on microbio- Graz, Institute of Hygiene, Microbiology and Environmental Medicine, Graz, logical criteria by the consensus guidelines from the United States CF Austria Foundation and European CF Society. The primary outcome was microbio- logical eradication of Mycobacteria abscessus measured by conversion to Objectives: Data on fungal airway colonisation in patients with cystic negative sputum cultures. Secondary outcomes were sputum conversion to fibrosis (CF) are heterogeneous with Candida albicans and Aspergillus smear negative MABS, radiographic improvements on HRCT, and tolerabil- fumigatus as the most common species with reported colonisation rates of ity of the treatment. 38–78% and 4–42%, respectively. Their impact is under discussion. Results: For the 8 patients with positive MABS culture the baseline forced Methods: We analysed results of sputum cultures obtained from 2009 to expiratory volume in 1 second (FEV1) ranged between moderate to severe 2019 from paediatric and adult CF patients treated in our centre. Modified – disease (FEV1 Range 45% 70% predicted). The average time to initiate culture methods were used for fungal cultures. treatment from the first MABS culture was 24 months. The average Results: 8,941 sputum specimens obtained from 148 CF patients were intensive phase of IV treatment period was 8.5 weeks. The main antibiotics analysed. From 39,868 cultures, 8,919 (22.4%) grew fungi, cultured from used were: Amikacin, Imipenem, Tigecycline and Azithromycin. The 5,070/8,941 specimens (56.7%). 144/148 (97.3%) of patients showed fungal average continuation phase period was 13.4 months. The most commonly colonisation at least once (see table for details on the most prevalent fungal used therapies in the continuation phase were Meropenem nebulized, species). Rate of patients with detection of fungal colonisation did not Azithromycin, Minocycline, Linezolid and Clofazimine. Of the 8 patients, change significantly from 2009 (76/91, 83.5%) to 2019 (94/108, 87.0%). 50% of patients are smear and culture negative to date. The HRCT changes Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S85

Conclusion: Nearly all CF patients showed fungal colonisation, with high Conclusion: The prevalence of fungi in the respiratory tract of our CF rates of 1st colonisation before adulthood and long-time colonisation for patients is high, being isolated in almost half of them during the study several years. Besides C. albicans and A. fumigatus, other less common period. Among moulds, Aspergillus fumigatus complex species were the reported species were detected in relevant numbers of patients, mostly most prevalent. Together, these results may reflect an older CF patient exceeding colonisation rates reported so far. The observed differences population with more intensive treatment and more advanced lung might be explained by culture methods and the long observation period disease. rather than by actual differences in analysed cohorts. To further study the impact of fungal colonisation in CF patients, adequate laboratory methods P106 are crucial. Structure and prevalence of micromycetes among patients with cystic fibrosis in the Russian Federation O. Kondratenko1, A. Kozlov1, A. Lyamin1, Y. Borzova2, T. Bogomolova2, Species Patients Age (yrs) at 1st Interval Number of N. Vasilyeva2. 1Samara State Medical University, Samara, Russian Federation; colonised/ isolation during (yrs) pat. (% of 2North-Western State Medical University named after I.I. Mechnikov, Kashkin tested (%) observation between 1st pos.) with Research Institute of Medical Mycology, Saint Petersburg, Russian Federation period, min-max, and last isolation median (number repeated until end of Objectives: Cystic fibrosis (CF) is one of the most common hereditary and % of pat isolation observation diseases. It incidence in Russia is approx. 1:10.000 newborns. <18a at 1st during period Micromycetes tend to get evident clinical significance in CF patients over isolation) observation the last decade. The rate of micromycetes occurrence in the respiratory period, substrates of CF patients varies from 6 to 57%. min-max, median Methods: We analyzed the material from the respiratory tract of CF patients from 55 regions across Russia in 2019. Fungi were cultured on the C. albicans 127/148 (85.8) 0.1–54.5, 15.6 (76, 59.8%) 0.1–10.8, 6.5 36 (28.3%) Sabouraud’s medium at a temperature of 27° and 37°C; they were A. fumigatus 119/148 (80.4) 0.4–54.5, 16.6 (71, 59.7%) 0.1–10.8, 6.4 23 (19.3%) identified based on the morphological and biochemical properties and – – C. parapsilosis 47/148 (31.8) 1.1 60.7, 15.4 (27, 57.4%) 0.2 9.9, 3.3 17 (36.1%) using MALDI-ToF mass-spectrometry method. C. dubliniensis 36/148 (24.3) 2.4–56.7, 20.3 (15, 41.7%) 0.1–9.5, 5.7 9 (25%) Results: In total, in 2019 we investigated 2,099 cultures from 750 CF A. niger 35/148 (23.6) 1.2–60.2, 18.6 (16, 45.7%) 0.2–8.8, 2.4 6 (17.1%) C. glabrata 26/148 (17.6) 2.8–35.4, 20.9 (11, 42.3%) 0.1–11.6, 2.5 10 (38.5%) patients and picked 5,832 microorganism strains; the percentage of Exophiala 25/148 (16.9) 2.7–37.0, 18.7 (10, 40%) 0.4–9.9, 5.2 14 (56%) micromycetes was 11.4% (663 strains). Fungi of Candida species dominated: dermatitidis 88.2% of all picked fungi (585 strains) including: C.albicans - 91.4%, C. A. flavus 23/148 (15.5) 3.9–39.8, 16.9 (12, 52.2%) 0.1–5.3, 1.3 3 (13%) dubliniensis - 4.3%, C.parapsilosis - 1.7%, C. tropicalis - 1%, C.lusitaniae - 0.7%; C. guilliermondii 23/148 (15.5) 0.4–57.9, 14.4 (13, 56.5%) 0.1–7.9, 0.6 2 (8.7%) C.inconspicua - 0.2%, C.glabrata 0.2%, C. blankii 0.2%, C. metapsilosis - 0.2%, C. kefyr - 0.2%. Fungi of Aspergillus genus are the most clinically significant in [Details on the most prevalent fungal species] patients with cystic fibrosis. In our study we picked out 43 strains of Aspergillus spp. (6.5% of the total number of fungi) including: A.fumigatis - P105 55.8%, A.flavus - 16.3%, A.niger - 14.0%, A.terreus - 9.3%, A.versicolor - 4.6%. Fungal epidemiology of cystic fibrosis patients from a Spanish referral The percentage of fungi of Penicillium genus was 2% of all obtained fungi (12 centre over a 7-month period strains): P.chryseogenum - 75.0%, P.expansum - 16.7%, P.citrinum - 8.3%. 1 1 1 J. Sánchez-López , A.V. Halperin , M. Velázquez , Among rare micromycetes, we picked out Scopulariopsis brevicaulis, 1 1 1 1 E. Gómez García de la Pedrosa , R. Cantón , J.D.D. Caballero . Hospital Fusarium oxysporum, Mucor ramosissimus, Exophiala dermatitidis, Universitario Ramón y Cajal, Microbiology Department, Madrid, Spain Alternaria alternata, Acremonium strictum. Objectives: Pulmonary disease is the most severe manifestation of cystic Conclusion: The micromycetes picked out from respiratory biosubstrates fibrosis (CF) and it is caused by a polymicrobial colonisation of the lungs, of CF patients are diverse. Mycological examination is indicated to all CF being Pseudomonas aeruginosa and Staphylococcus aureus the most patients for the purpose of epidemiologic control and selection of adequate prevalent and clinically important bacterial pathogens. Epidemiology and and up-to-date therapy of mycoses in CF patients. clinical impact of fungi in CF patients is much less understood. Here we provide epidemiological data of fungal colonisation in a CF patients cohort P107 from a Spanish referral centre. ECFS/CFF global survey on diagnosis and treatment of Aspergillus Methods: Fungal culture results and clinical data from CF patients fumigatus-related conditions 1 2 3 4 5 5,6 attending to our centre over a 7-month period (April to October 2019) G. Hong , R.B. Moss , B. Marshall , B. Quon , P.Eschenhagen , C. Schwarz , 1 were collected. Sputum samples were homogenised with N-acetylcysteine, ECFS Fungal Pathogens Working Group. University of Pennsylvania cultured in Sabouraud dextrose agar with chloramphenicol (Becton Perelman School of Medicine Pulmonary, Allergy and Critical Care Division, 2 Dickinson, NJ) and incubated up to 28 days at 30°C. Fungal isolates were Philadelphia, United States; Stanford University, Center for Excellence in 3 identified by MALDI-TOF (using the MSI online application) and micros- Pulmonary Biology, Stanford, United States; Cystic Fibrosis Foundation, 4 copy using lactophenol blue staining. Bethesda, United States; University of British Columbia, Vancouver, Canada; 5 6 Results: A total of 163 CF patients attended to our unit during the study Charité - Universitätsmedizin Berlin, Berlin, Germany; ECFS Fungal period, with a median (Q1-Q3) age of 12 (5–27) years and 49% were males. Pathogens Working Group, Karup, Denmark A total of 398 sputa were collected, with a mean (range) of 2.4 (1–8) per Objectives: We performed a global survey to investigate the practice patient. Seventy-eight (48%) patients had at least one positive fungal variability of cystic fibrosis (CF) clinicians in the diagnosis and manage- culture, being 142 the total number of fungi isolated. The prevalence of the ment of Aspergillus fumigatus (Af) related conditions in CF. different fungal species was: Methods: A 28 question electronic survey was created by the ECFS Fungal A.fumigatus complex: 45/142 (31.7%) Pathogens Working Group and members of the CFF and was distributed to Aspergillus spp: 10/142 (7.0%) CF clinical providers of the ECFS, CFF, and CF Canada networks. The sections Scedosporium spp: 9/142 (6.3%) of the survey included: Exophiala spp: 10/142 (7.0%) 1. screening for Af related conditions, Yeasts: 42/142 (29.6%) 2. diagnosis of Af related conditions, Other filamentous fungi: 25/142 (17.6%) 3. treatment for allergic bronchopulmonary aspergillosis (ABPA), Of note, 3 unusual species were identified among the isolates of the 4. ABPA monitoring, and fumigati section: 2 Neosartorya udagawae and 1 N. pseudofischeri. 5. treatment for non-ABPA Af conditions. S86 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Results: A total of 369 respondents completed the survey (317 were 5Regional CF Center, Stavropol, Russian Federation; 6Regional CF Center, analysed). Thirty-four countries were represented and grouped as North Tomsk, Russian Federation; 7Regional CF Center, Yaroslavl, Russian Federation; American (NA) 114 (36.0%) and non-North American (non-NA) 203 (64.0%). 8Regional CF Center, Tyumen, Russian Federation; 9Regional CF Center, Izhevsk, The survey revealed that fungus cultures are checked less frequently in NA Russian Federation; 10Regional CF Center, Ulyanovsk, Russian Federation vs. non-NA (38% vs. 66%, p < 0.001) and screening methods differ between Objectives: The diagnosis of allergic bronchopulmonary aspergillosis regions, including fungal culture, Af specific IgE/IgG, recombinant Asp (ABLA) in cystic fibrosis is complex and often late, since many diagnostic based antibody tests. ABPA diagnostic criteria are similar between regions criteria intersect with typical manifestations of the underlying disease. It is (NA: 53% vs. non-NA: 56%), but ABPA first-line treatment differs between necessary to conduct a comprehensive specialised examination for the regions (prednisone/prednisolone alone use was greater in NA, 37% vs. diagnosis of ABLA. The aim is to study the characteristics of ABLA in adult non-NA 15%). Significant differences were found between Af bronchitis patients according to Russian CF Registry (2018). diagnostic criteria between regions (37.7% in NA responded “don’t know Methods: The analysis of Russian CF Registry (2018) was performed. The how to define Af bronchitis” vs. 18.2% in non-NA, p < 0.001). Treatment for study included data of 3142 patients amid which there were 776 adult Af bronchitis differs between regions (Itraconazole is used more in non-NA patients. with 45% vs. NA 25%, p < 0.001). Results: ABLA in adult was found in 24 cases (12 men), which amounted to Conclusion: Clear differences exist between countries by region in current 3.09%. The group of patients with and without ABLA does not differ in main clinical management of Af related conditions. Therefore, new guidelines for indicators of the Registry. However for patients with ABLA diabetes defining and treating Af related conditions are needed. As a consequence, a mellitus was more common: 29.2% vs 10.1%, p = 0.003, nontuberculous ECFS and CFF task force is aiming to implement a new consensus guideline mycobacteriosis was found more often: 13.0% vs 2.0%, p = 0.0006, non- in 2020. fermentable gram-negative flora was determined: 70.8% vs 36.0%, p = 0.0005, inhaled antibiotics were prescribed more often: 91.7% vs 52.1%, P108 p = 0.0001. Chronic co-infection with Pseudomonas aeruginosa and Aspergillus Conclusion: ABLA is more likely to be found among CF patients with fumigatus in cystic fibrosis is associated with accelerated decline in diabetes mellitus, nontuberculous mycobacteriosis and those who were lung function 1, 2 2 3 4,5 1 prescribed active inhalation antibiotics. K. Keown ,A.Reid , J. McCaughan , J.E. Moore , C.C. Taggart , We would like to thank the Cystic Fibrosis Patient Registry of Russian 1, 5 1 ’ D.G. Downey . Queen s University Belfast, Wellcome Wolfson Institute for Federation for providing access to patient data and thank the individual Experimental Medicine, Belfast, United Kingdom; 2Royal Belfast Hospital for 3 regional CF centres representatives for allowing the use of data (http:// Sick Children, Belfast, United Kingdom; Royal Group of Hospitals, Department mukoviscidoz.org/). of Medical Microbiology, Belfast, United Kingdom; 4Northern Ireland , Department of Bacteriology, Belfast City Hostpital, Belfast, 5 P110 United Kingdom; Belfast City Hospital, Adult Cystic Fibrosis Unit, Belfast, Characteristics of allergic bronchopulmonary aspergillosis in children United Kingdom of the Russian Federation Objectives: Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Asp) E. Kondratyeva1, R. Budzinskiy1, Y. Borzova2, A. Chernyak3, A. Voronkova1, are the most common pathogenic bacterial and fungal species present in V. Sherman1, S. Krasovskiy1, 3, N. Klimko2, M. Starinova1, N. Kashirskaya1, Cystic Fibrosis (CF) airways respectively. Recent cross-sectional observa- N. Odinaeva4, E. Kozlova5, N. Sikora5, O. Molchanova5, N. Saczuk5, tional studies have shown that chronic co-infection with Pa and Asp is N. Revel’-Muroz5, I. Karimova5, O. Golubczova5,P.Pavlov5, I. Asherova5, ’ 5 1 associated with lower FEV1, more frequent pulmonary exacerbations (PEx), I. Zil ber . Federal State Budgetary Scientific Institution «Research Centre for increased antimicrobial usage and lower BMI. However, longitudinal Medical Genetics», Moscow, Russian Federation; 2Mechnikov North-West State effects on progression of lung disease have not yet been assessed. Medical University, St. Petersburg, Russian Federation; 3Scientific Research Methods: Patients chronically isolating both Pa and Asp, and chronic Pa Institute of Pulmonology of the Federal Medical and Biological Agency, without Asp were identified using the Northern Ireland regional Moscow, Russian Federation; 4State Budgetary Institution of the Moscow microbiological CF database. Lung function records and the electronic Region ‘Children’s Clinical Multidisciplinary Center of the Moscow Region’, care records (ECR) for 22 of these patients were reviewed from 2009–2019. Moscow, Russian Federation; 5Regional CF Center, Moscow, Russian Federation Results: Patients co-colonised with Pa and Asp (n = 11) had a more rapid Objectives: to study the characteristics of ABPA in Russian children annual decline in FEV mean % (SD) 3.54 (4.2) as compared to patients 1 Methods: analysed data of the CF Registry of the Russian Federation in colonised with Pa without Asp (n = 11) 1.96 (1.15); p = 0.01. Patients co- 2018. The study included data of 2366 children. colonised had a lower FEV (highest value in 2019) % (SD) 64.6 (18) vs 66.9 1 Results: ABPA frequency in children was 1.55%. ABPA is not common up to 2 (23.6), p = 0.0001; and were younger than those with chronic Pa mean age years, from 2 to 10 years was 0.2% to 2%, in 18 years was 6.3%. Children years (SD) 32.8 (8.9) vs 38.5 (8.0); p = 0.0001. differed in age 12.72 (10.7–15.1) in patient with ABPA and 7.8 (4.1–11.8) in Conclusion: We report lower and more rapid decline in lung function in the group without ABPA (p < 0.001) and the age of diagnosis 0.83 (0, 3–1.7) patients co-colonised with Pa and Asp. This study adds to the growing body and 0.26 (0.11–1.0), p < 0.001. Significant differences obtain in BMI Z-score of evidence indicating that Asp is a contributory pathogen in the −0.9 (−1.9 −0.1) and −0.5 (−1.2 –0,3), p = 0.029. ABPA patients had lower progression of CF lung disease. Pathogenicity may be consequential to FEV1 80.11 (58–88)% and 87 (75–102)%, p = 0.0018 and FVC 86.0 (64–94)% interspecies interactions, however further study is needed to understand and 90 (75–102)% p = 0.0299. Chronic P. aeruginosa (75% and 25%, mechanisms and characterise the clinical, microbiological and inflamma- p < 0,001) is typical for ABPA, as well as St. maltophilia (p = 0,042), NTM tory implications of this co-infection. (p < 0.001), MRSA infection (p < 0.001). ABPA patients often receive all kinds of antibacterial therapy, the intravenous antibiotic therapy was in P109 75% and 31.4% in the group without ABPA (p < 0.001), and more often Frequency and characteristics of allergic bronchopulmonary hospitalized— 29 (16–48) days per year (p < 0.001). children with ABPA aspergillosis in adult cystic fibrosis patients in the Russian Federation received Inhaled and tableting glucocorticosteroids more frequently than S. Krasovskiy1,2,3, E. Amelina1, E. Kondratyeva2, R. Budzinskiy2, Y. Borzova4, 1 5 5 6 7 in the control group (41.7% and11.2% and 33.3% and23% respectively), as A. Chernyak , I. Oganesyan , N. Kanukova , E. Ravzhaeva , I. Zilber , well as bronchodilators, azithromycin and proton pump inhibitor (38,9% I. Bulatova8, E. Osipova9, O. Starodubtceva9, N. Muraleva9, T. Kochergina9, 9 10 1 and 17,1%). It is noted combination ABPA with CF-associated diabetes E. Gogoleva , T. Gubareva . Federal Pulmonology Research Institute, Federal mellitus (8.2% and 0.7%), and with the development of cirrhosis (111% and Medical and Biological Agency of Russia, Moscow, Russian Federation; р 2 3.8%), < 0,00. Children with ABPA had a liver transplant in history more Research Centre for Medical Genetics, Moscow, Russian Federation; frequently (p = 0.026). 3Municipal Clinical Hospital named after D. Pletnev, Moscow, Russian 4 Conclusion: ABPA usually develops after the age of 10 years with chronic P. Federation; Regional CF Center, Saint Petersburg, Russian Federation; aeruginosa, St. maltophilia, NTM and MRSA, which is accompanied by more Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S87 frequent antibiotic therapy. ABPA results in a reduction in lung function level and are considered as novel bacterial species. The predominant and is combined with CF-associated diabetes mellitus, hepatic cirrhosis number of β-amyloid-producing bacteria were represented by with portal hypertension and low nutritional status. Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, We would like to thank CFPR-RF (http://mukoviscidoz.org/). Stenotrophomonas maltophilia and Proteus mirabilis. Of the selected strains 80% produced large amount of β-amyloid. The high β-amyloid P111 producers facilitate biofilm formation in the lungs of CF patients promoting Diversity of Bordetella strains isolated from the respiratory tract and persistence and are characterized with higher toxicity to the cells. We the domestic environment of cystic fibrosis patients have previously shown that the amount of secreted β-amyloid in Gram- Q. Menetrey1, E. Jumas-Bilak1, 2, R. Chiron1, 3, H. Marchandin1,4, C. Dupont1, 2. negative bacteria can be modulated by tempered bacteriophages. 1Université de Montpellier, Equipe PHySE, UMR HSM, Montpellier, France; Conclusion: The obtained data supports the idea that the effects of 2CHU Montpellier, Laboratoire d’Ecologie Microbienne Hospitaliere,̀ bacterial β-amyloid on the course of CF can be viewed as an example of Montpellier, France; 3CHU Montpellier, Centre de Ressources et de bacteriophages involvement as a previously overlooked human pathogens. Compétences de la Mucoviscidose, Montpellier, France; 4CHU Nîmes, Laboratoire de Microbiologie, Nîmes, France P113 The role of sporobiota in cystic fibrosis Objectives: Airway colonisation by diverse bacteria of environmental 1 1 1 1 2 M. Vecherkovskaya , G. Tetz , C. Kardava , T. Lazareva , T. Gembitskaya , origin is frequent in CF patients. To date, the Bordetella genus, closely 1 1 V. Tetz . Pavlov First Saint Petersburg State Medical University, Microbiology related to the emerging Achromobacter genus, has been little studied in CF. 2 and Virology, Saint Petersburg, Russian Federation; Pavlov First Saint Main objective of our study was to report and compare the diversity of Petersburg State Medical University, Pulmonology Research Institute, Saint Bordetella strains isolated from the respiratory tract and the domestic Petersburg, Russian Federation environment of CF patients. Methods: A total of 71 Bordetella strains were studied including 61 strains Objectives: The aim of this study was to identify spore-forming bacteria in isolated from 32 sputum samples of 6 patients of the Montpellier CF centre lung microbiota of cystic fibrosis (CF) patients and evaluate their possible over a 7-year period (1–34 strains per patient) and 10 strains from the association with disease progression. domestic environment of 2 CF patients. Identification was performed by Methods: A unique workflow designed in our laboratory, combining 16S rRNA gene sequencing. Pulsed-Field Gel Electrophoresis (PFGE) was microbiological (spore-forming bacteria selective cultivation, identifica- used to compare clinical and environmental strains belonging to a same tion, biofilm studies), and genomic (genome sequencing, genome analysis, species, and successive strains isolated from a patient. protein and signaling pathway investigation) was used. Results: Three species colonised the 6 patients: Bordetella bronchiseptica Results: We have identified a number of spore-forming bacteria, (n = 3), Bordetella hinzii (n = 1), and Bordetella genomospecies 2 (n = 2). representatives of Bacillales order including several previously uncultur- None of the strains displayed identical or related PFGE profiles, suggesting able species in the lungs of patients with CF. These were Bacillus sporadic acquisitions from different sources. Two patients were chronically thuringiensis, Bacillus sonorensis, Bacillus licheniformis, Bacillus cereus/ colonised by B. bronchiseptica and Bordetella genomospecies 2, respect- thuringiensis/mycoides, Bacillus subtilis, Paenibacillus glucanolyticus, ively. PFGE revealed genomic evolutionary events in the latest isolates of B. Paenibacillus borealis, Paenibacillus pabuli. The newly isolated species are bronchiseptica. Environmental strains belonged to 3 undescribed species Paenibacillus VT-16-210 sp. nov., Paenibacillus VT-16-200 sp. nov., Bacillus related to the 3 recently described environmental Bordetella species B. VT-16-40 sp. nov. and Bacillus VT-16-28 sp. nov. We identified a number of muralis, B. tumbae and B. tumulicola. virulence genetic determinants responsible for the persistence of the Conclusion: No cross transmission between patients was observed in our infection, including hemolysin secretion protein D, enterotoxin, proteases, centre. Bordetella genomospecies 2 is reported for the first time in CF. peptidases, phospholipases, and exonucleases, as well as capsular, flagellar, Bordetella genomospecies 2 and B. bronchiseptica have the ability to persist and sporulation proteins. In addition, we identified superoxide dismutase, in CF airways and genomic modifications observed probably reflect which is considered to possess cancer-inducing properties in some adaptive potential of Bordetella to the lung microenvironment. An bacteria. We also identified the presence of multidrug resistance important diversity of new species exists in the domestic environment, transporters of the ABC, multidrug and toxic compound extrusion these species being different from those isolated from the patients’ airways. (MATE), and major facilitator superfamily (MFS) families, and genes conferring resistance to antibiotics, including aminoglycosides, dauno- P112 rubicin, fosfomycin, oxetanocin, betalactam antibiotics, tetracycline, and A New role of bacterial amyloid in cystic fibrosis hydroperoxides. T. Lazareva1, G. Tetz1, M. Vecherkovskaya1, C. Kardava1, N. Artemenko1, Conclusion: The members of sporobiota are actively engaged in CF by T. Gembitskaya2, V. Tetz1. 1Pavlov First Saint Petersburg State Medical causing irreversible lung damage and chronic inflammation and by University, Microbiology and Virology, Saint Petersburg, Russian Federation; maintaining resistome within lung microbiota of patients with CF. 2Pavlov First Saint Petersburg State Medical University, Pulmonology Research Institute, Saint Petersburg, Russian Federation P114 The analysis of bacterial pathogens in cystic fibrosis patients of the Objectives: Bacterial amyloids were recently identified as a novel bacterial Russian Federation in 2018–2019 with evaluation of antibiotic virulence factor. Their β-sheet structure is known to play an important role resistance in biofilm organization and is characterized by protease and heat resistance 1 1 2 2 2 A. Voronkova , E. Kondratyeva , M. Chernukha , L. Avetisyan , I. Shaginyan , as well as toxic effect on eukaryotic cells. The aim of this study was to 1 3 1 V. Sherman , N. Portnov . Federal State Budgetary Scientific Institution identify β-amyloid in biofilms formed by bacteria isolated from bronch- Research Centre for Medical Genetics, Department of Cystic Fibrosis, Moscow, oalveolar lavage fluid (BAL) samples of patients with adult pulmonary 2 Russian Federation; N.F. Gamaleya National Research Centre of Epidemiology cystic fibrosis (CF). and Microbiology, Laboratory of Molecular Epidemiology of Nosocomial Methods: Pure bacterial cultures isolated from 20 BAL samples of patients 3 Infections, Moscow, Russian Federation; Captain Computing Agency LLC, with CF were studied. Bacterial strains that can form β-amyloid fibers were Moscow, Russian Federation identified by cultivation on LB agar supplemented with Congo red (CR) stain for 48 hours. Bacterial identification was performed by MALDI- Objectives: The evaluation of bacterial pathogens and of antibiotic TOF MS. resistance of CF patients of Russian Federation (RF). Results: We have obtained multiple pure β-amyloid-producing bacterial Methods: The data of 78533 microbial strains of 1110 CF patients in 2018– cultures. Among them 25 bacterial strains with the ability to produce 2019 was analysed with a help of the «Program of control of bacterial β-amyloid were selected from which seven bacterial strains, belonging pathogens in respiratory tract of CF patients in RF and of sensitivity to to the genera Lactobacillus, Acinetobacter, Chryseobacterium, Paenibacillus, antibacterial medication» Stenotrophomonas, Proteus, Streptococcus were not identified to the species S88 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Results: The primary causative agents in 2018/2019 were S.aureus (62/ P116 64%), P. aeruginosa 23,0/23,2%), S. maltophilia (5,7/5,7%), A. xylosoxidans Identification difficulties of non-fermenting microorganisms from the (5.6/3,9%), Bсс (2,6/2,17%). There was registered the reduction of MRSA 7,5/ respiratory tract of patients with cystic fibrosis 5,4%. The growth of resistance of P. aeruginosa to colistin (1,2/7,1%) and M. Chernukha1, L. Avetisyan1, I. Shaginyan1, V. Zhuhovitsky1, E. Burmistrov1, carbapenems (17/25,3%) was registered. The number of mucoid pheno- O. Medvedeva1, E. Siyanova1, N. Polyakov1, D. Grumov1, E. Kondratyeva2, types (P. aeruginosa muc) which are resistant to carbapenems 40/45%, V. Sherman2, N. Kashirskaya2, E. Rusakova1, A. Ginzburg1. 1National Research ceftazidime 26,3/30,2% has increased. High resistance of Achromobacter spp Center for Epidemiology and Microbiology named after the Honorary to carbapenems 15,4/29,1% was registered. Bcc is characterized by high Academician N.F. Gamaleya, Moscow, Russian Federation; 2Research Centre of frequency and by increase in resistance to 42,8/55,5%. There was registered Medical Genetics of the Russian Academy of Medical Sciences, Moscow, a big number of P. aeruginosa strains resistant to ceftazidime 33.3% among Russian Federation children from 0 to 3. The number of strains P. aeruginosa grow with age: P. aeruginosa resistant to carbapenems from 8.3% in age from 0 to 3 and to The aim: Assessment of identification difficulties of non-fermenting 45% between 12 and 18 years. The resistance of P. aeruginosa to microorganisms (NFMO) from the respiratory tract of patients with CF. ciprofloxacin is 16% among children from 12 to 18 years while it is only Methods: 2300 throat swabs and sputum samples were examined since 4,3% in a group from 7 to 12 years. During the analysis of sensitivity of P. 2008 to 2018. MALDI-TOF, PCR, MLST, WGS were used. aeruginosa to ceftazidime among children from 12 to 18 the number of Results: From the respiratory tract of patients with CF 90 different species resistant strains amount to 50% and only 9% in the age group from 3 to 7 were isolated. Among them 50 species were NFMO. Bacteria of the genus years. Achromobacter, Burkholderia cepacia complex (Bcc) and some rare NFMO Conclusion: The growth of resistance of P. aeruginosa to colistin (1,2/7,1%) (Pandoraea spp., Ralstonia spp., Brevundimonas diminuta, Delftia acid- and carbapenems was noticed. There is an increase of S. maltophilia, A. ovorans, Elizabethkingia miricola, Sphingobacterium multivorum, xylosoxidans, Bсс. It is necessary to underline the growth of Achromobacter Acinetobacter tjerbergiae, Aeromonas caviae, Wautersiella falsenii, spp in comparison with Bcc. There is an increase of resistant strains of Comamonas testosteronii, Sphingomonas parapaucimobilis and others) microorganisms connected with age. The rise of resistant flora over time were difficult to identify by phenotypic methods. A. ruhlandii, was noticed. A. xylosoxidans, A. insolitus, A. piechaudii, A. insuavis, A. spanius were identified by MALDI-TOF, of which 76% belonged to A. ruhlandii and 7.2% to P115 A. xylosoxidans. Repeated studies of genetically identical strains of Prevalence of bacterial pathogens in respiratory secretions of cystic Achromobacter spp. from one patient gave different results by MALDI- fibrosis patients in Argentina TOF. MLST showed that some strains were mistakenly identified. Five 1 1 2 2 2 species of Bcc were identified by MALDI-TOF: B. cenocepacia, B. cepacia, B. L. Ibarra , L. Galanternik , S. Lubovich , S. Zaragoza , V. Rodriguez , 3 4 1 2 1 contaminans, B. multivorans, B.vietnamensis. 83.3% of isolates were B. G. Manonelles , F. Bournissen , M. Vazquez , A. Teper . Hospital de Niños 2 cenocepacia. MALDI-TOF allowed to identify Bcc to the genus, as well as Ricardo Gutierrez, Microbiology, Ciudad de Buenos Aires, Argentina; Hospital some species of Bcc (B. cenocepacia and B. multivorans), but, as our studies de Niños Ricardo Gutierrez, Respiratory Center, Ciudad de Buenos Aires, 3 have shown, it makes errors in the identification of B. contaminans. 3 strains Argentina; Hospital de Niños Ricardo Gutierrez, Infectious Disease, Ciudad de 4 of Bcc, which WGS identified as B. cepacia, MALDI-TOF mistakenly Buenos Aires, Argentina; Schulich School of Medicine Western University, identified as B. contaminans. Paediatric Clinical Pharmacology, Ontario, Canada Conclusion: MALDI-TOF revealed a variety of NFMO that colonise the Background: Respiratory tract infections are the main cause of morbidity respiratory tract of patients with CF. Reliable identification of and mortality in Cystic Fibrosis (CF) patients. Prevalence of CF pathogens Achromobacter spp. and Bcc to a species by MALDI-TOF, despite the isolated from respiratory secretions change over time, but this has not been presence in its database of 6905 species of reference microorganisms was thoroughly studied in Latin American patients. difficult. Thus, identification of these bacteria requires confirmation by Objective: To analyse microbiological changes in respiratory specimens of molecular genetic methods. CF patients attending a paediatric hospital in Buenos Aires city, Argentina, between 2009 and 2019. P117 Material and methods: Respiratory samples (sputum, oropharyngeal Association between Pseudomonas aeruginosa (Pa) strain genotype and swab and BAL) taken every 2 years from 2009 to 2019 were analysed. viable bacterial community profiles in sputum Samples were plated on 5% blood agar, chocolate agar, CLED agar, Mannitol D. Allen1, 2, L.J. Sherrard1, G.G. Einarsson3, D.F. Gilpin1, J.P. McKenna4, salt agar, BCSA and Cetrimide Agar. D.J. Fairley4, J.S. Elborn3, M.M. Tunney1. 1Queen’s University, Belfast, School of Results were analysed using logistic regression for analysis of year-to-year Pharmacy, Belfast, United Kingdom; 2Queen’s University Belfast, School of trends. Chemistry and Chemical Engineering, Belfast, United Kingdom; 3Queen’s Results: See Table University, Belfast, Centre for Experimental Medicine, Belfast, United Kingdom; Conclusions: During the last 10 years the prevalence of S. aureus increased, 4Belfast Health and Social Care Trust, Department of Microbiology, Belfast, MRSA persisted high, P.aeruginosa remained stable and B. cepacia complex United Kingdom declined significantly. In the last 5 years there was an increasing trend in the isolation of S. maltophilia, SaSCV and M. abscessus. Knowledge of these Objectives: To determine if people with CF (PWCF) infected with a shared findings is important to improve therapeutic approaches in CF patients. or unique Pseudomonas aeruginosa (Pa) strain have different viable bacterial airway community profiles.

Table 1. (abstract: P115)

2009 2011 2013 2015 2017 2019 p

Patients/Samples (median per pt.) 115/445 (4) 124/505 (4) 136/561 (4) 162/751 (5) 169/709 (5) 164/689 (4) S. aureus (%) 76.5 71.8 65.4 80.9 87.6 87.2 <0.001 MRSA (%) 23.5 33.1 30.1 35.2 29.6 27.4 NS S.aureus SCV (%) (small colony variant) ND ND ND 8.6 9.5 14.6 NS P.aeruginosa (%) 41.7 44.4 39.0 40.1 44.4 35.4 NS B.cepacia complex (%) 11.3 6.5 7.3 3.7 4.1 4.9 <0.05 Achromobacter spp (%) 9.6 4.8 4.4 6.2 10.1 5.5 NS S. maltophilia (%) 9.6 8.9 8.1 8.0 13.6 14.6 NS M. abscessus (%) 0 0 0 1.9 0.6 3.0 NS

[CF Pathogens Prevalence] Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S89

Methods: Multiple Pa isolates (n = 254) from sputum, collected from 38 Reference PWCF, were discriminated using a 5-loci Multi-Locus VNTR Analysis [1] Allen et al., J Cyst Fibros. 2019; 18 (June 2019): S107–108 (MLVA) strain genotyping scheme developed by the BHSCT and compared to MLVA-profiles of 25 isolates previously identified as the Liverpool P119 Epidemic Strain (LES). PWCF were classed as having a shared (highly Does pyocyanin production negatively correlate with clinical similar MLVA-profiles from multiple people; ≥1 isolate identified as a parameters in people with cystic fibrosis (PWCF) who have infection shared strain) or unique strain infection. Sputa were analysed by extended- with Pseudomonas aeruginosa (Pa)? quantitative culture and bacterial community density and ecological 1, 2 1 3 1 3 indexes were compared between groups. D. Allen , L.J. Sherrard , G.G. Einarsson , D.F. Gilpin , J.S. Elborn , 2 1 1 ’ Results: The most commonly identified 5-loci MLVA profiles detected (6, 3, S.E.J. Bell , M.M. Tunney . Queen s University, Belfast, School of Pharmacy, 2 ’ 7–10, 4, 4) were characteristic of LES in this study. One third of PWCF Belfast, United Kingdom; Queen s University Belfast, School of Chemistry and 3 ’ (34.2%) were classed as having a LES infection; the remaining PWCF had Chemical Engineering, Belfast, United Kingdom; Queen s University, Belfast, infection with a unique strain. There was no difference in lung function Centre for Experimental Medicine, Belfast, United Kingdom between PWCF with or without a LES infection (58 vs 65% predicted; Objectives: Pyocyanin (PCN) producing Pseudomonas aeruginosa (Pa) 7 7 p = 0.2). Both groups had similar mean total (3.5 × 10 vs 7.7 × 10 CFU/mL; isolates have been associated with worse outcomes in people with cystic 7 7 p = 0.2), aerobe (3.4 × 10 vs 7.3 × 10 CFU/mL; p = 0.3) and obligate fibrosis (PWCF). Surface enhanced Raman Spectroscopy (SERS) has the 4 5 anaerobe (2.4 × 10 vs 1.0 × 10 CFU/mL; p = 0.2) viable counts. PWCF potential to detect PCN produced by Pa isolates after short periods of 6 5 with a LES infection had a higher Pa viable count (3.5 × 10 vs 2.2 × 10 culture. The objective of this study was to compare clinical parameters, Pa CFU/mL; p = 0.04). Comparison of the ecological indexes showed no phenotypes and viable bacterial community profiles in patients colonised statistically significant differences between groups: richness (6.3 vs 6.6; with PCN and non-PCN producing PA isolates. p = 0.6), dominance (0.6 vs 0.6; p = 0.6), diversity (Shannon-Wiener index, Methods: Pa isolates (n = 122) were collected from sputum from 42 PWCF. 0.8 vs 1.1; p = 0.3) and evenness (0.4 vs 0.5; p = 0.06). Permutation-based Isolates were cultured after 6 hours and spectra were recorded. PWCF were statistical testing to compare community structures based on LES or unique categorised as being colonised with either PCN producing (≥1 isolate strain status showed no significant difference (ADONIS; Bray-Curtis; identified) or non-PCN producing isolates based on peaks present at 1350, − R2 = 0.04; p = 0.09; 999 permutations). 1492, 1598 and 1615cm 1. Sputa were analysed by extended-quantitative Conclusion: The sputum bacterial community composition and structure culture. Clinical and PA isolate characteristics, bacterial community density did not differ based on infection with a LES or unique strain. and ecological indexes were compared. Results: One quarter of isolates (n = 32/122, 26%) from 14 PWCF were PCN P118 producing. There was no association between PCN production and age Is variation in Pseudomonas aeruginosa Surface-enhanced Raman (p = 0.3), BMI (p = 0.2), gender (p = 0.7), CFTR genotype (p = 0.6), chronic spectroscopy spectra related to genotype? inhaled (p = 0.6) and oral therapies (p = 0.4), multi-drug resistance D. Allen1,2, L.J. Sherrard1, G.G. Einarsson3, D.F. Gilpin1, J.S. Elborn3, (p = 0.5) and morphology (p = 0.3). Both groups had a similar mean total J.P. McKenna4, D.J. Fairley4, S.E.J. Bell2, M.M. Tunney1. 1Queen’s University, (5.40 × 107 vs 6.89 × 107 CFU/mL; p = 0.8), aerobe (5.20 × 107 vs 6.51 × 107 Belfast, School of Pharmacy, Belfast, United Kingdom; 2Queen’s University CFU/mL; p = 0.8), obligate anaerobe (3.66 × 104 vs 3.78 × 104 CFU/mL; Belfast, School of Chemistry and Chemical Engineering, Belfast, United p = 0.5) and Pa (1.12 × 105 vs 7.30 × 105 CFU/mL; p = 0.6) viable count. No Kingdom; 3Queen’s University, Belfast, Centre for Experimental Medicine, statistically significant differences were observed in the mean ecological Belfast, United Kingdom; 4Belfast Health and Social Care Trust, Department of indexes: richness (5.8 vs 6.8; p = 0.2), dominance (0.6 vs 0.5; p = 0.5), Microbiology, Belfast, United Kingdom diversity (0.9 vs 1.1; p = 0.4) and evenness (0.5 vs 0.5; p = 0.9). Lower lung function (FEV ) was associated with infection with non-PCN producing Objectives: Surface-enhanced Raman spectroscopy (SERS) is a novel 1 isolates compared to PCN producing isolates (55% vs 70% predicted; technique that produces a whole-organism spectroscopic fingerprint at p = 0.02). high speed. Reproducible spectra of Pseudomonas aeruginosa (Pa) were Conclusion: In this preliminary study, detection of non-PCN producing Pa previously obtained.1 However, variation in the spectra of Pa isolates within isolates was associated with lower lung function. Sputum bacterial and between patients was noted.1 The objective of this study was to community composition and structure did not differ between groups. determine if the variation observed in the spectra was related to the Pa strain genotype. P120 Methods: Raman spectra of Pa clinical isolates (n = 143) were obtained by Detection of ceftazidime-avibactam resistance in Pseudomonas adjusting the inoculum to 1 × 108–109 CFU/mL with the resulting bacterial aeruginosa isolates pellet mixed with citrate reduced silver colloid (CRSC) and dried; the 1, 2 1 3 1 4 Raman spectra were recorded (4 × 10 seconds at 785 nm). Pa isolates were D. Allen , L.J. Sherrard , G.G. Einarsson , D.F. Gilpin , J.P. McKenna , 4 3 1 1 ’ discriminated using a 5-loci Multi-Locus VNTR Analysis (MLVA) strain D.J. Fairley , J.S. Elborn , M.M. Tunney . Queen s University, Belfast, School of 2 ’ genotyping scheme developed by the BHSCT. Hierarchical cluster analysis Pharmacy, Belfast, United Kingdom; Queen s University Belfast, School of 3 ’ was performed using R. Chemistry and Chemical Engineering, Belfast, United Kingdom; Queen s University, Belfast, Centre for Experimental Medicine, Belfast, United Kingdom; Results: 59 different MLVA profiles were observed; the most commonly 4 identified MLVA profile (6, 3, 7–10, 4, 4) was found in 14 people with CF and Belfast Health and Social Care Trust, Department of Microbiology, Belfast, was similar to that of the Liverpool Epidemic Strain (LES) in this study. With United Kingdom SERS, two distinct clusters were observed; one was dominated by the Objectives: In CF, multi-drug resistance (MDR) in Pseudomonas aeruginosa pigment pyocyanin (n = 49). The remaining spectra (n = 94) had peaks (Pa) isolates is increasing; ceftazidime-avibactam (CZA) is a combination −1 present at 661, 735 and 800 cm , corresponding to guanine, adenine and antibiotic that may be a treatment option for Pa including MDR-strains. The uracil, respectively. Variation was evident in the intensity and position of objectives of this study were to determine the prevalence of MDR and CZA these peaks and a hierarchical cluster dendrogram sub-divided the Pa resistance in a biobank of Pa isolates. spectra into 5 main clusters. 15 different spectra were obtained for the LES Methods: Pa isolates (n = 399) from a range of sources were tested; CF lung isolates (n = 60) and these were found throughout the 5 main clusters in the infection (n = 278), urinary tract infection (UTI; n = 14), non-CF lung dendrogram. No correlation was found between the MLVA profiles and the infection (n = 105) and the environment (n = 2). Susceptibility of Pa to 12 corresponding Pa spectra. antibiotics including CZA was tested by disk diffusion (CLSI guidelines) and Conclusion: The variation in the Pa spectra could not be attributed to isolates were categorised as MDR based on a previous definition.1 Pa differences in strain genotype observed using MLVA. Thus, SERS may not be isolates were discriminated using a 5-loci Multi-Locus VNTR Analysis a suitable method for typing Pa. Future work will investigate if variation in (MLVA) strain genotyping scheme developed by the BHSCT. the Pa spectra is due to phenotypic biochemical differences. Results: MDR was only detected in Pa isolates from CF lung infection (118/ 278; 42%). Resistance to CZA was found in 10/399 (2.5%) Pa isolates, which S90 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 were all from CF lung infection. CZA resistant (CZAres) isolates were MDR Methods: We implemented in a single centre Bcc eradication protocol that and non-mucoid. Percentage resistant/intermediate (R/I) amongst these included an intensive combination of inhaled and oral antibiotic therapies. isolates were: ceftazidime 100%, meropenem 100%, piperacillin/tazobac- We conducted a retrospective cohort analysis of clinical outcomes. We tam 100%, temocillin 100%, imipenem 90%, aztreonam 90%, amikacin 90%, analysed sputum samples of patients with CF between June 2017 and levofloxacin 60%, ciprofloxacin 40%, colistin 30%, tobramycin 30%. 6/10 November 2018. The samples were pre-treated with sodium hydroxide, CZAres isolates had a 5-loci MLVA profile (6, 3, 7–10, 4, 4) characteristic of sodium citrate and N-acetylcysteine, followed by extraction of the genetic the Liverpool epidemic strain. material by column method. We analysed 18 compatible strains for Bcc. Conclusion: Despite only ceftazidime being used clinically at the time of Pa Nucleic acids extracted from the samples and strains were amplified by isolation, resistance to the antibiotic combination, CZA, was detected in CF real-time PCR in the StepOne thermal cycler. Patients included in the isolates, albeit at a low rate. Colistin and tobramycin demonstrated the eradication group start during six months with ceftazidime 500 mg daily most activity in vitro against these isolates. Further work will include nebulized and minocycline 100 mg per 12 hours oral during 3 weeks. investigating mechanisms of CZA resistance. Results: 18 patients were identified as having a newly rec A Bcc and 13 started on the eradication protocol. Sequential sputum samples after Reference completion of the protocol demonstrated sustained clearance of Bcc in all [1] Magiorakos et al. Clin Microbiol Infect 2012; 18:268–81. patients, except one. Five patients had isolation when they were children and median umbral cycle was lower 22 ± 7 instead of an umbral cycle of P121 33 ± 2.71 of the adult group. In vitro susceptibility of Achromobacter species isolated from cystic Conclusion: Clearance of Bcc from sputum cultures using a standardised fibrosis patients protocol was successful at one year and was associated with clinical T. Demuyser1, F. Echahidi1, I. Wybo1, A. Verroken2, E. André3, C. Peeters4, stability. Lung function and nutritional status remained stable in the year E. De Canck4, P. Vandamme4, D. Piérard1. 1UZ Brussel, Microbiology, Jette, following eradication except patients who had an isolation of Bcc when Belgium; 2Cliniques Universitaires Saint-Luc, Microbiology, Brussels, Belgium; they were children. 3UZ Leuven, Clinical Bacteriology and Mycology, Leuven, Belgium; 4Ghent University, Biochemistry and Microbiology, Gent, Belgium P123 Management of Pseudomonas aeruginosa infections in cystic fibrosis Objectives: Achromobacter spp are emerging human pathogens causing patients in France opportunistic infections. These non-fermenting Gram-negative bacilli are S. Leroy1,2, C. Marguet3, M. Murris-Espin4, S. Bui5,6. 1Université Côte d’Azur, frequently isolated from respiratory samples of CF patients. In this study, CHU de Nice, FHU OncoAge, Department of Pulmonary Medicine and we evaluated the in vitro antimicrobial susceptibility of 222 Achromobacter Allergology, Nice, France; 2Université Côte d’Azur, CNRS UMR 7275, Institut de spp to 13 antimicrobial agents by microdilution, with the Sensititre Testing Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, France; 3CHU System (Thermofischer). Charles-Nicolle, Département de Pédiatrie Médicale, Centre de Ressources et Methods: Samples were isolated from three Belgian CF centers. A. de Compétences de la Mucoviscidose Pédiatrique, Rouen, France; 4CHU de xylosoxidans represented 67% of the population. From a subset of 83 of Toulouse, Service de Pneumologie-allergologie, Centre de Ressources et de these isolates, susceptibility testing was repeated with E-test (Biomérieux). Compétences de la Mucoviscidose Adulte, Hôpital Larrey, Toulouse, France; Since there are no species-specific EUCAST breakpoints available for 5Université CHU Pellegrin, Pediatric CF Center, Pediatric Pulmonology, Achromobacter spp, the EUCAST PK/PD (non-species related) breakpoints Bordeaux, France; 6University CHU Pellegrin, CIC 1401, Bordeaux, France were applied for most antibiotics. Results: The tested Achromobacter strains were rather resistant to beta- Background: Therapeutic management of Pseudomonas aeruginosa (Pa) lactam antibiotics. However, approximately 50% of the isolates were infections is essential to limit the pulmonary degradation of cystic fibrosis susceptible to piperacillin. The addition of tazobactam improved the (CF) patients. Different therapeutic strategies can be used in order to susceptibility rate to 64%. Seventy percent of our isolates had a MIC ≥8 mg/ eradicate primo-colonisation with Pa or to avoid exacerbations in chronical L for ceftazidim. All quinolone and aminoglycoside antibiotics showed low infections. Indeed, in accordance to recommendations, different types of antimicrobial activity (0–5% susceptibility). The combination of trimetho- molecules, forms (dry powder or nebulisation), administration regimens prim and sulfamethoxazole had a good in vitro activity, with 66% (continuous, continuous-alternate, discontinuous), different dosages and susceptibility. Only 52% susceptibility was noted for meropenem, indicat- dose-regimen per day are feasible for patients. ing carbapenemase activity. Finally, colistin, an antibiotic often used in Objective: The objective of this study is to establish an overview of the cystic fibrosis patients, depicted a susceptibility of 31%. therapeutic practices used in France for the management of Pa infections in Conclusion: We observed a good correlation between the Sensititre and E- cystic fibrosis patients. test results, with maximum one dilution difference in the obtained MIC50 Methods: We prospectively conducted an anonymous survey of all values. Furthermore, we observed that a subset of 20 A. xylosoxidans practitioners working in the 45 French CF centres, between November isolates of sequence type ST-137 showed a higher overall resistance 2019 and February 2020. Clinical cases of infants, children, adolescents or susceptibility profile. In general, we can conclude that trimethoprim with adults were submitted. The topics covered were primo-colonisation and sulfamethoxazole, piperacillin (with or without tazobactam) and merope- chronic infection with Pa, in toddlers, children and adults. nem are in vitro the most effective antibiotic agents (susceptibility >50%). Results: The preliminary results of this study allowed the analysis of several points: P122 1. the diagnostic criteria selected by the teams for each case; Implementation of a successful eradication protocol for sputum 2. the variability in the choice of therapeutics; samples of gen Rec A Burkholderia cepacia complex 3. the rationale and E. Baran1,F.Perez1, M.E. Benencia1, A. Godoy1, M.D.l.A. Baridon1, 4. the decisive criteria that determine the therapeutic strategy. V. D’Ascenzo1, V. Negrone1, E. Zattera1, S. Gastal1, F. Dominguez1, If the teams agree on the definitions of Pa infections, we observed that the M. Rose Cash1, M.E. Iribarne1, P. Ruscitti1, M.F. Butti1, L. Volta1, L. Menna1. therapeutic strategy was heterogeneous and adapted in particular 1HIGA R Rossi, La Plata, Argentina according to the microbiological profile (co-colonisation), the clinical Objectives: To evaluate a protocol for eradication of Burkholderia cepacia state, and the patient’s known compliance. complex (Bcc) from a PCR kit in real time from sputum samples of gen Rec Conclusions: International recommendations and guidelines are not A. Infection with Bcc results in a heterogeneous clinical course ranging homogeneous on therapeutic strategies, in paediatric and adults CF from asymptomatic colonisation of the airways to fulminant respiratory centres in France. Within the same country, it is relevant to analyse the failure in patients with cystic fibrosis (CF). Early eradication of Bcc improves differences in strategic practices around Pa, a major pathogen in cystic clinical outcomes. The efficacy and clinical outcomes following imple- fibrosis. mentation of an eradication protocol for Bcc are less well understood. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S91

P124 (41.1%) were in the category of resistant to tobramycin. According to the The use of 2 beta-lactam antibiotics in treatment of adult patients with MENSURA criteria:113 (89%) strains were interpreted as sensitive, and14 cystic fibrosis infected with B. cepacia complex (11%) as resistant I. Butyugina1, S. Krasovskiy1,2,3, M. Afanaseva2, E. Amelina2. 1Municipal Conclusions: Clinical Hospital named after D. Pletnev, Moscow, Russian Federation; 2Federal 1. When determining indications for the use of inhaled tobramycin in Pulmonology Research Institute, Federal Medical and Biological Agency of patients with CF, along with determining the degree of sensitivity of P. Russia, Moscow, Russian Federation; 3Research Centre for Medical Genetics, aeruginosa (S/R), it is recommended to determine the value of MIC. Moscow, Russian Federation 2. P. aeruginosa strains resistant to tobramycin according to the EUCAST Objectives: EUCAST does not recommend determining the sensitivity of B. criteria must be interpreted based on the criteria proposed by cepacia complex to antibiotics (ab), which complicates the appointment of MENSURA. ab therapy. The aim is to compare the effectiveness of ab therapy in a hospital with the use of ceftazidime (C) and meropenem (M) regimens compared with the use of C or M. P126 Methods: 37 CF patients (pts) received 143 courses of ab therapy (January Synergy testing of antibiotic combinations used to treat chronic 2015–December 2019 period). Group 1 (85 pts) was prescribed C or M, Pseudomonas aeruginosa lung infections in cystic fibrosis patients С group 2 (58 pts) was prescribed both C and M. o-trimoxazole and/or 1 1 1 2 1 levofloxacin were also prescribed. Most pts were included in both groups. A. Schmidt ,T.Preis, S. Schwarz , A. Hector . University Hospital Tübingen, Institute for medical Microbiology and Hygiene, Tübingen, Germany; Treatment efficacy was assessed by spirometry data and C-reactive protein 2 (CPR) levels at the beginning and end of treatment. Exclusion criteria: B. Universitäts-Kinderspital Zürich, Pneumologie, Zürich, Switzerland cepacia syndrome. Objectives: Although eradication of early-life Pseudomonas aeruginosa (Pa) Results: Age of pts was 25 (7) years, the duration of treatment was 14 (3) infections is often successful, it remains the main pathogen in later life days, FEV1/FVC is 61.3 (20.8)%. The groups were comparable in age, affecting 60–70% of adult patients with CF. Its high intrinsic resistance to duration of therapy, FEV1/FVC and baseline CRP- group 1: 9.1 (21.6), group many antibiotic classes, the growth in biofilms and its adaption to the CF – 2 12.2 (12.6) mg/L. The initial differences between the groups were in FEV1 lung influence the antibiotic susceptibility. To reduce the amount of Pa (p = 0.006): 1.76 (1.2) L or (51 (37)%) vs 1.4 (0.95) L or (36 (32)%), FVC during chronic infection, combinations of antibiotics are used. However, (p = 0.03): 2.92 (2.13) L or 72 (46)%) vs 2.54 (1.08) L or 53 (28.5)%) and BMI until now there are not enough studies to prove the efficiency of these 2 2 (p = 0.024): 18.8 (5.2) kg/m vs 18.4 (4.0) kg/m for groups 1 and 2, combinations. In our study we aimed to identify effective combinations of respectively. antibiotics under conditions that mimic the CF lung. Against the background of treatment, in the vast majority of cases, an Methods: We used different growth media in broth microdilution and in a increase in spirometry and a decrease in inflammation were noted and biofilm model to test the susceptibility to antibiotics and antibiotic Δ amounted (all data p > 0,05): FEV1- group 1: 0.08 (0.27) l or 2.5 (8.0)%, combinations most used in CF therapy and compared it to the routine group 2: 0.09 (0.28) l or 3.5 (8.8)%. ΔFVC-group 1: 0.1 (0.42) L or 2.9 (10.9)%, measurement in our diagnostic department. In these experiments we used Δ group 2: 0.28 (0.38) L or 7.0 (11.5)%. FEV1/FVC-group 1: 1.50 (5.73)%, group different laboratory Pa strains as well as an early and a chronic CF isolate 2: 1.5 (7.95)%. ΔCRP- group 1: decrease by 5.6 (19.5) mg/l, group 2: decrease and a multidrug resistant clinical isolate. by 13.6 (21.3) mg/l. Results: We found that the chronic CF isolate shows different MIC values in Conclusion: The use of 2 beta-lactam ab does not improve the results of the standard measurement compared to the broth microdilution method. spirometry and does not reduce systemic inflammation more significantly These differences were not detected for all other strains. Comparing than the use of beta-lactam alone. However, this requires further study. minimal medium, mimicking the CF sputum environment, with standard medium the MIC for both CF isolates did not change. All other Pa isolates P125 showed higher MICs. These MIC changes lead for tobramycin to MICs above Determination of MIC of tobramycin for inhalation use against strains the breakpoint for resistance. As expected even a twofold MIC was not able of Pseudomonas aeruginosa in patients with cystic fibrosis to eradicate the bacteria grown as biofilms. Interestingly, colistin was not V. Gazina1, S. Polikarpova1, O. Timofeeva1, N. Pivkina1, N. Bondarenko1, able to reduce the biofilm for all used strains, despite they all show very low V. Vechorko1. 1Municipal Clinical Hospital No.15 named after O. M. Filatov, colitstin MICs in planktonic growth. Moscow, Russian Federation Conclusion: The combination of tobramycin/ceftazidime showed a high synergistic effect for all strains grown planctonically or as biofilms. In Introduction: Patients with cystic fibrosis (CF) supposed to the develop- further experiments we want to use additional sequential CF patients’ ment of a infection of the respiratory tract. P. aeruginosa is the most isolates to validate our findings. common pathogen, increased mortality. The inhalation antibiotics of administration allows to create high concentrations and overcome the resistance of microorganisms with a low risk of systemic side effects. When P127 determining the clinical sensitivity/resistance (S/R) of P. aeruginosa to Zebrafish embryo as a suitable animal model to screen new molecules tobramycin, the criteria are the boundary values of the MIC focused on against Pseudomonas aeruginosa in normal or cystic fibrosis context 1 1 1 1 parenteral or oral administration in accordance - EUCAST: strain is P. Nogaret , M. Moussouni , A. Blanc-Potard . LPHI, CNRS UMR 5235, considered sensitive if its MIC is less than or equal to4mg/l; resistant-if Montpellier, France its MIC is more than4mg/l. These criteria do not take into account the high Objectives: Pseudomonas aeruginosa is a major cause of lung infections and concentrations achieved during inhalation. The Spanish Council mortality in cystic fibrosis patients. Due to increasing resistance to (MENSURA, 2005) set higher cut-off points for inhaled tobramycin in currently available antibiotics, P. aeruginosa has been listed by WHO determining the S/R of P. aeruginosa: a strain is considered sensitive if its among the most critical group of pathogens for which new therapeutic MIC is less than or equal to64mg/l, resistant-if its MIC is more than or equal strategies are urgently needed. To allow the screening of novel molecules to128 mg/l. against P.aeruginosa, it is important to have simple animal models, possibly Objectives: To determine the categoryS/Raccording to theEUCASTcriteria where CFTR can be genetically inactivated in the context of cystic fibrosis. and compare the data with the MENSURA criteria. We propose to use the zebrafish (Danio rerio) embryo, a vertebrate model Methods: The study included127 P. aeruginosa strains of various morpho- that is increasingly used to study host-pathogen interactions. types. The determination of MIC of tobramycin was carried out by the Methods: We used the zebrafish embryo model to concentration gradient method (< 0.064–>1024 μg/ml) E-test (bioMerieu, i. develop a simple assay to monitor P. aeruginosa infection, France). ii. test in vivo known and novel molecules against P. aeruginosa, Results: According to the results of the study:of127 strains according to the iii. evaluate P. aeruginosa infection in embryos carrying an inactivated cftr EUCAST criteria,74 (58.9%) strains were evaluated as sensitive, and 53 gene. S92 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Results: We have validated a simple and reproducible assay based on Methods: For 9 CF patients, a pair of Pa strains isolated from the same infection by immersion of zebrafish embryos to monitor P. aeruginosa sample but presenting the two interaction states with Sa was identified virulence. This new approach is currently used to test in vivo the efficiency thanks to competition tests. Genome sequencing and comparisons of these against P. aeruginosa of compounds targeting bacterial NADK, type three competition and coexistence strains within a pair were performed. In secretion system (T3SS), quorum sensing (QS) and MgtC virulence factor. parallel, one pair of Pa strains was experimentally evolved in vitro in Moreover, we have shown that embryos deficient for the CFTR channel are presence or in absence of Sa. Interaction state with Sa was monitored more susceptible to P. aeruginosa infection. through experiment and genomes of evolved Pa strains were sequenced. Conclusions: We propose zebrafish embryos as first intention vertebrate Results: Genomic comparisons show that the two Pa co-infecting strains model to screen for anti-Pseudomonas molecules. The availability of belong to the same clone, indicating that the coexistence strain derives cftr−/− embryos allows to carry out experiments in a CF context. from the competition one. In comparison to competition isolates, the operon yecS-fliY of unknown function was identified as mutated in 7 P128 coexistence strains out of the 9 sequenced. Experimentally, competition Trophic cooperation promotes Pseudomonas aeruginosa and strains evolved towards coexistence in more than half of the cases. This Staphylococcus aureus survival in cystic fibrosis patients interaction change was concomitant with the production of new pigments 1 1 1 1,2 3 and independent of Sa presence. L. Camus , P. Briaud , S. Bastien , A. Doléans-Jordheim , S. Elsen , 1, 2 1 1 Conclusion: Our results confirm that the establishment of coexistence F. Vandenesch , K. Moreau . Centre International de Recherche en 2 with Sa is linked to Pa genetic adaptation, which may involve the operon Infectiologie, Lyon, France; Institut des Agents Infectieux, Lyon, France; 3 yecS-fliY. The transition competition-coexistence can be reproduced in vitro Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France and does not require Sa presence. Objectives: Lungs of cystic fibrosis (CF) patients are colonized by numerous microorganisms including Pseudomonas aeruginosa (PA) and P130 Staphylococcus aureus (SA). These bacteria can co-infect up to 40% of Competition between Achromobacter xylosoxidans and Pseudomonas patients according to the age class. Different interaction patterns between aeruginosa in cystic fibrosis PA and SA can be observed throughout infection: PA strains can either Q. Menetrey1, S. Brandt2, L. Grenga3, C. Escobar1,2, R. Chiron1, 4, inhibit SA growth through well-described mechanisms or coexist with SA. E. Jumas-Bilak1,5, V. Molle2, C. Dupont1, 5, J. Armangaud3, H. Marchandin1, 6. We aim to better understand the coexistence interaction state with SA by 1HydroSciences Montpellier, CNRS, IRD, Université de Montpellier, Montpellier, characterizing its impacts on PA physiology. France; 2DIMNP, CNRS, Université de Montpellier, Montpellier, France; Methods: 22 PA/SA strain pairs in coexistence were isolated from CF 3Laboratory ‘Innovative Technologies for Detection and Diagnostics’ CEA- patient expectorations and cultivated in monoculture or co-culture. PA Marcoule, Bagnols-sur-Ceze,̀ France; 4Centre de Ressources et de Compétences genic expression was assessed by RNAseq (2 pairs) and confirmed by de la Mucoviscidose (CRCM), Centre Hospitalier Universitaire de Montpellier, RT-qPCR (22 pairs). Deletion mutants of the aco system were produced in Montpellier, France; 5Laboratoire d’Écologie Microbienne Hospitaliere,̀ a clinical PA isolate and cultivated in regular or long-term co-culture with Centre Hospitalier Universitaire de Montpellier, Montpellier, France; 6Centre SA, during which acetoin concentration and bacterial survival were Hospitalier Universitaire de Nîmes, Département de Microbiologie, Nîmes, monitored. France Results: Transcriptomic analyses show that co-culture with SA significantly affects the expression of numerous genes involved in nutrient metabolism Objectives: Lower airway infections in Cystic Fibrosis (CF) are considered in PA. In presence of SA, 70% of PA strains presented an important polymicrobial with competitive strategies observed between microorgan- overexpression of the aco system, involved in acetoin catabolism. Acetoin, isms. Current studies are mainly focused on the characterization of the produced by SA strains and detected in CF sputa, was shown to be interactions between the major CF pathogens Pseudomonas aeruginosa (Pa) responsible for aco system induction in PA. Clinical PA strains actually and Staphylococcus aureus. The aim of the study was to characterise catabolized acetoin, especially during coexistence interaction. This catab- competition observed during agar screening assays between strains of Pa olism promoted the survival of both pathogens in nutrient-depleted and Achromobacter xylosoxidans (Ax) isolated from a CF patient chronically conditions. colonised by Ax and sporadically by Pa. Conclusions: We show that coexistence with SA induces the up-regulation Methods: Pairs of Ax (n = 3 variants with different morphotypes and of the aco system and acetoin catabolism in PA. Due to its beneficial effects identical genotype) and Pa (n = 4, 3 distinct genotypes) were studied for on both bacteria, acetoin catabolism could testify to the establishment of growth in liquid medium, biofilm formation, and production of side- trophic cooperation between SA and PA in the CF lung environment, rophores. For the most highly competitive Ax/Pa couple, virulence was promoting their persistence. assessed in zebrafish embryos and the molecular components of their exoproteomes were characterised by label-free shotgun proteomics. P129 Results: We observed a significant inhibition of Pa growth by Ax, a Pseudomonas aeruginosa evolution in cystic fibrosis patients promotes significant decrease in biofilm formation for Ax/Pa co-cultures, and coexistence interaction with Staphylococcus aureus siderophore production by Ax. Competition heterogeneity was observed among variants of Ax in presence of Pa. Regarding virulence, a significant L. Camus1, S. Bastien1, P. Briaud1, A. Doléans-Jordheim1,2, F. Vandenesch1,2, decrease in the mortality of zebrafish embryos was observed for Ax/Pa co- K. Moreau1. 1Centre International de Recherche en Infectiologie, Lyon, France; cultures. In agreement with these results, the shotgun proteomic analysis 2Institut des Agents Infectieux, Lyon, France showed a decreased abundance of the proteins of the Pa type III secretion Objectives: The opportunistic pathogen Pseudomonas aeruginosa (Pa) can system and a derivate of pyocyanin. colonise various environments thanks to its adaptability. In the case of Conclusion: This is the first study evaluating the competitive ability of the cystic fibrosis (CF) lung infections, Pa evolves in vivo towards a low- emerging opportunistic pathogen Ax in CF. Multiple interactions between virulence but high-resistance state. This genetic adaptation of Pa also Ax and Pa were observed that affect negatively growth, biofilm formation seems to affect its interactions with co-infecting microorganisms such as and virulence of Pa. Ax siderophore production, reported herein for the first the highly prevalent Staphylococcus aureus (Sa). Acute infection Pa strains time, likely represents a competitive trait of Ax. Related to the patient are thus in competition with Sa, whereas chronic infection strains are able colonisation history, our results questioned on the importance of bacterial to coexist. We aim to characterise the genetic factors that drive PA strains competitiveness in shaping the colonisation pattern of CF airways. towards this coexistence state. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S93

P131 Results: Results of cBRT distinctly showed an adhesion induction for the Most of Staphylococcus aureus and Pseudomonas aeruginosa co- spontaneous non-adherent strains by β-lactam molecules. The microscopic infecting isolates coexist, a condition that may impact clinical study specified the formation of connected bacterial clusters linked by outcomes in cystic fibrosis patients polysaccharidic fibres and for various conditions, the induction of a P. Briaud1, S. Bastien1, L. Camus1, M. Boyadjian2,P.Reix2, C. Mainguy2, filamentous phenotype. F. Vandenesch1, A. Doléans-Jordheim3, K. Moreau1. 1Université Lyon1 - CIRI, Conclusion: To conclude, the cBRTand more broadly the Antibiofilmogram Staphylococcal Pathogenesis, Lyon, France; 2Hôpital Femme-Mere-Enfant-̀ assay, allowed to highlight in few hours the inducing property of antibiotics Hospices Civils de Lyon, Pediatric Pulmonology Department, Lyon, France; on bacterial adhesion and their ability to modify the bacteria morphology. 3Hospices Civils de Lyon, Institut des Agents Infectieux, Lyon, France This new diagnostic tool appears to be pertinent for the antimicrobial selection in CF and its clinical use must be verified in clinical trials. Staphylococcus aureus (SA) is the major lung coloniser of cystic fibrosis (CF) patients during childhood. As patient aged, Pseudomonas aeruginosa (PA) P133 becomes the main pathogen infecting adult lungs. Nevertheless, SA In vivo demonstration of Pseudomonas aeruginosa biofilms as remains significant and coinfection with SA and PA are frequent. In vitro independent pharmacological compartments studies deciphered the relationships between SA and PA in a context of co- L. Christophersen1, F.A. Schwartz1, C.J. Lerche1, T. Svanekær2, K. Thomsen1, infection. PA early-colonising isolates show a strong antagonism towards 2 1, 3 1 1 SAwhile PA late isolates succeed to coexist durably with SA. The aim of this T. Sams , N. Høiby , C. Moser . Copenhagen University Hospital, study was to analyse if co-infection and coexistence between SA and PA Rigshospitalet, Department of Clinical Microbiology, Copenhagen, Denmark; 2Technical University of Denmark, Department of Health Technology, Kgs. could lead to worse clinical outcomes. 3 The clinical and bacteriological data of Lyon CF patients were collected, and Lyngby, Denmark; Faculty of Health and Medical Sciences, University of patients were ranked into three groups: SA, PA or SA + PA. Interaction Copenhagen, Institute for Immunology and Microbiology and the Costerton profile of SA and PA isolates from co-infecting patients was defined to Biofilm Center, Copenhagen, Denmark create two groups: coexistence and competition. Univariate and multi- Objectives: To study the biofilm pharmacokinetic (PK) compartment and variate analysis were used to compare the 4 groups of patients. pharmacodynamic (PD) relationship of tobramycin in an in vivo biofilm SA patients are younger than co-infected patients, themselves younger model. than PA patients. SA group is distinguished by a lower number and duration Methods: To resemble a biofilm infection we installed three freshly of hospitalisations, a number of exacerbations and a higher FEV1.Co- produced seaweed alginate beads (D0) and beads incubated for 5 days infected and PA groups were not statistically different. (D5), both embedded with Pseudomonas aeruginosa PA01 (tobramycin MIC Among co-colonised patients, 65.38% of strain pairs were in coexistence. No 1.5 mg/L), s.c in BALB/c mice (n = 64). All mice received tobramycin 40 mg/ statistical difference was found between PA and SA + PA in either kg s.c. to resemble human PKs and were sacrificed at 0.5, 3, 6, 8, 16 or 24 h coexistence or competition. However, only competitive group is signifi- after treatment. Untreated controls (n = 14) were sacrificed, correspond- cantly different from SA group with higher BMI, number and duration of ingly. Tobramycin concentrations were determined in serum, muscle tissue, hospitalisations. lungs and beads. Quantitative bacteriology was determined in the beads. In conclusion, coinfection does not cause excess morbidity compared to the Results: The tobramycin peak concentration in serum was 58.3 (±9.2) mg/L, presence of PA alone. No significant difference between patients with in lungs 7.1 mg/L (±2.3), muscle tissue 2.8 mg/L (±0.5), all after 0.5 h and in coexisting and competitive pairs was observed. Nevertheless, compared to D0 beads 19.8 mg/L (±3.5) and in D5 beads 24.8 mg/L (±4.1) (both 3 h). SA group, competitive pairs presented more severe clinical outcome than Tobramycin bead accumulation remained above the serum values between coexisting pairs. However, since co-existence seems to be the predominant 3 h and 8 h for D0 beads and from 3 h to 24 h for the D5 beads. Tobramycin state of interaction, it can be an important stage in pulmonary bacterial concentration inside the beads showed a delayed build up over 3 h, but colonisation. remained above the MIC throughout 8 h and 16 h (D0 and D5beads, respectively). P132 The D0 beads, had a 1-log reduced bacterial survival after 6 h, 8 h and 16 h Role of β-lactams in the induction of early adhesion and phenotype (p < 0.0001), but the reduction in numbers of bacteria in the treated group variation in cystic fibrosis Pseudomonas aeruginosa isolates from the starting levels to 24 h was not statistically significant (p = 0.20). highlighted by clinical BioFilm Ring Test For the D5 alginate beads the bacterial levels were 1-log higher as E. Olivares1, 2, S. Badel-Berchoux3,C.Provot1,3, G. Prévost2, T. Bernardi1, 3, compared to D0 alginate beads and remained higher including the 16 h F. Jehl2. 1Biofilm Pharma, Saint Beauzire, France; 2EA 7290 Virulence (p < 0.05). However, at 24 h there was no longer a significant difference Bactérienne Précoce, Strasbourg, France; 3Biofilm Control, Saint Beauzire, between bacterial levels of D0 and D5 alginate beads. France Conclusion: The present in vivo study based on tobramycin exposure supports that biofilm behave as an independent pharmacokinetic micro- Objectives: P. aeruginosa biofilms are recognized as being responsible of compartment. The study indicates, reducing the biofilm matrix would the chronic lung colonization in cystic fibrosis (CF) patients. Adherent increase free tobramycin concentrations and improve therapeutic effects. bacteria frequently lead to treatment failures as they are inherently recalcitrant to antibiotic therapies. Despite this basic knowledge, anti- biograms are still performed on planktonic cells. Furthermore, it is now P134 well-recognized that low doses of antibiotics can stimulate biofilm Pseudomonas aeruginosa produces 4-hydroxyquinoline derivatives formation and currently, no diagnostic tools are available to detect this involved into antagonist interactions with Staphylococcus aureus in phenomenon. cystic fibrosis patients 1 2,3 1 2 4 Effects of low concentrations of β-lactams on biofilm establishment by P. B. Gioia , A. Doléans-Jordheim , A. Arnaud , C. Commun , S. Michalet , 1 4 1 1 1 aeruginosa strains were analysed through a new device, allowing the study S. Radix , M.-G. Dijoux-Franca , N. Walchshofer , L. Rocheblave . Equipe EA 2 of antibiotic effects on sessile bacteria. The aim was to highlight the 4446 - Molécules Bioactives et Chimie Médicinale (B2MC), Lyon, France; UMR potential deleterious impact of antimicrobials in CF lung infections, as CNRS-UCBL-VetAgroSup 5557 Ecologie Microbienne, Equipe Bactéries ̀ 3 patients are regularly subject to fluctuating treatments. Pathogenes Opportunistes et Environnement, Lyon, France; Institut des 4 Methods: We performed clinical BioFilm Ring Test (cBRT) assay on Agents Infectieux, Lyon, France; UMR CNRS-UCBL-VetAgroSup 5557 Ecologie bacterial isolates to test the effect of low concentrations of β-lactams on Microbienne, Multi-résistance Environnementale et Efflux Bactérien-, Lyon, their biofilm behavior. This assay, derived from the Antibiofilmogram, France measures cell propensity to adhere in contact with antibiotics. To confirm Background: In Cystic Fibrosis (CF), Staphylococcus aureus (Sa) is the major data, complementary microscopy analyses were carried out. pathogen in young patients, but over the time, Sa decreases in favor of S94 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Pseudomonas aeruginosa (Pa). This succession could be explained by P136 antagonist interactions between the two bacteria which could be mediated Pseudomonas aeruginosa mechanisms of virulence in bronchial by the production of molecules secreted by Pa, belonging to the Alkyl- epithelial cells infection cases: the role of ExoY exotoxin Quinolones (AQ) family. These molecules have been identified by using L. Marti1, 2, U. Mechold3, L. Touqui1, 2. 1Institut Pasteur, Equipe Mucoviscidose both a bio-guided fractionation approach and a metabolic profiling et Bronchopathies Chroniques, Département Santé Globale, Paris, France; approach by LCUV/HRMS of supernatants of clinical Pa strains. 2Sorbonne Université, UPMC Paris 6, Centre de Recherche Saint-Antoine, Paris, Objective: Our goal is to synthesise the previously identified AQs to France; 3Institut Pasteur, Unité de Biochimie des Interactions confirm their structure and their activity against Sa. Macromoléculaires, Département de Biologie Structurale et Chimie, Paris, Materials and methods: Three classes of molecules have been synthesised. France The first class was obtained by the Suzuki coupling reaction. The resulting compounds were used as starting products for the synthesis of the two Objectives: Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative other classes by catalytic hydrogenation of the side chain or by N-oxidation opportunistic bacterium responsible for chronic respiratory infections. The of quinolone system. The synthesised molecules were tested to determin- proliferation of this bacterium can cause inflammation and cellular ate their inhibitory activity on Sa growth, spotting 5 μl of each compound damages in the bronchial epithelium. This pathogen has several factors on solid media inoculated with various CF Sa strains. essential to its virulence, as the Type 3 Secretion System (T3SS), which Results: We managed to synthesise 27 compounds. Nine derivatives had synthesises and injects four exotoxins into the cytoplasm of cells. ExoY is inhibitory effects on Sa growth: 3 compounds showed a very weak known to exhibit a nucleotidyl cyclase activity. This toxin function inhibitory effect (inhibition +/−), four compounds showed a weak increases vascular permeability but also induces apoptosis through the inhibitory effect (inhibition +) and two other compounds showed complete important production of cyclic GMP and protein kinase G (PKG). In this inhibitory effect (inhibition +++). One of the latter derivatives was a study, we determine the involvement of the virulence factor ExoY into the mixture of two regioisomers. phenomenon of cellular apoptosis. Conclusions: The AQs production by Pa could partially explain the Pa-Sa Methods: Bronchial epithelial cells line (NCI-H292) were infected with interactions in the CF lungs and then promote Pa implantation. PAO1 P. aeruginosa bacterial strain; wild-type (PAO1-WT) or deleted for Understanding these interactions could lead to a better understanding of ExoY (PAO1- ΔexoY). Apoptosis was examined first by revealing the cleaved how Pa interacts with Sa which might allow to prevent lung infections Caspase-3 protein by Western blot and then by an AnnexinV-PI staining by blocking Pa-Sa interactions. This project will also allow the identifica- analysed by flow cytometry. tion of new antimicrobial molecules and new therapeutic targets in Pa Results: S and T exotoxins have been shown in previous studies to induce and Sa. cell apoptosis. Our results support this finding because our results from both analytical techniques show that apoptosis is greater in epithelial cells P135 infected with the mutant PAO1- ΔexoY compared to PAO1-WT strain. Testing the predatory spectrum of Bdellovibrio bacteriovorus on Meaning that in the absence of ExoY the apoptosis rate in cells is increased. Pseudomonas aeruginosa isolates Therefore, it is likely that ExoY attenuates the virulence of P. aeruginosa, 1 1 1 1 notably by decreasing the apoptosis case. C. Saralegui , C. Herencias , J.D.D. Caballero , P.M. Ponce-Alonso , 1 2 1 1 Conclusions: We have shown that the PAO1 bacterium is more virulent in Á. San Millán , A. Prieto , R. del Campo . Hospital Universitario Ramón y 2 the absence of one of its exotoxins, Exo Y, in the phenomenon of cell Cajal, Microbiology, Madrid, Spain; Centro de Investigaciones Biológicas, apoptosis. We will determine the metabolic pathways involved in the Madrid, Spain regulation of these cellular functions by P. aeruginosa. With a particular Objectives: To evaluate the predatory activity of Bdellovibrio bacteriovorus focus on PKG and MAP-kinases activities. on Pseudomonas aeruginosa isolates from cystic fibrosis patients and from bacteremias. P137 Methods: The predatory capability of B. bacteriovorus has been tradition- Further exploring phenotype and virulence differences between ally evaluated by double-layer method, which is time-consuming and chronic Pseudomonas aeruginosa isolates from patients with cystic laborious to perform. During this work, we implemented a new multiwell- fibrosis and non-cystic fibrosis bronchiectasis (Bx) based system to speed up the assessment of predatory capability. This W.D. Smith1,2, F.J. Terpstra1,3, O.L. Fletcher1, R.A. Murphy1, A. Simbo1, methodology is based on the monitorization of the optical density at C. Hogg1,2, A.A.M. Filloux4, A. Bush1, 2, J.C. Davies1, 2. 1Imperial College London, 600 nm of the co-cultures during 72 h. Two independent well-character- National Heart and Lung Institute, London, United Kingdom; 2Royal Brompton ized P. aeruginosa collections were tested as preys, including 50 invasive Hospital, Paediatric Respiratory Medicine, London, United Kingdom; isolates causing bacteraemia, and 60 isolates obtained from the respiratory 3University of Groningen, Medicine, Groningen, Netherlands; 4Imperial College airway of cystic fibrosis patients. The collections included recognized high- London, Department of Life Sciences, London, United Kingdom risk clones as ST175, ST111, ST646 or ST532 and other uncommon lineages, as well as antibiotic susceptible, multiresistant and extremely resistant Objectives: Pseudomonas aeruginosa (Pa) airway infection is seen in all isolates. chronic suppurative lung disease. We previously demonstrated greater Pa Results: Fifty-eight percent of the cystic fibrosis isolates and 35% of the biofilm biomass in samples from CF patients in comparison to Bx patients invasive isolates were susceptible to predation by our B. bacteriovorus (Smith WD et al, J Cyst Fibros. 2017). Here, we expand upon this study, strain. Predation was not influenced by neither the genetic background nor comparing in vitro virulence features in the same group of Pa strains. the microbial features of each strain (morphotype, or antibiotic resistance). Hypothesis: Virulence differs between CF and Bx strains when assessing The analysis of the clinical data of the patients was also inconclusive with motility and enzymatic production. predation profile. Methods: Pa from chronically infected patients (CF n = 70, Bx n = 69) were Conclusion: Despite P. aeruginosa is the main prey of B. bacteriovorus, inoculated at controlled optical density into twitching, swimming, clinical isolates are not completely susceptible to predation, and this protease, elastase and lipase agar plate-based assays. For motility, distance feature are not mediated by the genetic background or the microbiological of travel in agar was measured. Enzymatic assays were measured as a characteristics of the strains. Anyway, the use of predators could represent a zone of clearance (protease and elastase) or zone of salt crystallization new ecological alternative to fight against the global health problem of the (lipase). antibiotic resistance in human infections. Results: A greater proportion of CF strains demonstrated twitching motility than Bx (CF 70%; Bx 54%, X2 p = 0.05); median twitching diameter was 1mm Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S95 greater for the CF strains (p = 0.001). Twitching motility was weakly Methods: 34 Achromobacter spp. clinical isolates were longitudinally correlated with biofilm biomass (Spearman r 0.35, p < 0.0001). Swimming collected over 3 years from 10 patients (CF Center of Verona, Italy) and motility showed no difference between groups. Bx strains produced more underwent whole genome sequencing. Phylogenetic and variant analyses lipase than CF strains, corresponding to a median 2mm greater diameter were performed. Presence of high impact mutations in mismatch repair crystallization (p = 0.01). This reflects a greater proportion of strains in the (MMR) system genes, transition/transversion (ts/tv) ratio >3 and variant upper tertile from the Bx group (CF 23%; Bx 43%, X2 p = 0.03). No inter- rate >3 were arbitrarily defined as criteria for hypermutation. group difference was seen in protease and elastase production. Results: According to sequencing and phylogenetic analyses, 3 species of Conclusion: A detailed assessment of phenotype and virulence factors Achromobacter spp. were identified: A. xylosoxidans (25 isolates, 7 patients), reveals differences between chronic Pa from CF and Bx airway cultures This A. rhulandii (4 isolates, 1 patient) and A. insuavis (5 isolates, 2 patients). may reflect adaptive differences within the airways or phenotypes MMR genes analysis showed that all A. rhulandii and A. insuavis genomes enabling persistence at acquisition of Pa. Understanding Pa persistence presented 2 copies of mutS gene while a single copy was detected in A. phenotypes could lead to identification of disease specific severity xylosoxidans genomes. Regardless of the species and number of mutS gene biomarkers or new treatment approaches. copies, 21 isolates (7 patients) overall were identified as hypermutators: Supported by the British Lung Foundation. Affiliated to the UK CF Trust- they presented high impact mutations in either mutS, mutL,ormutT, high funded Strategic Research Centre for Pseudomonas infection. ts/tv ratio and increased mean yearly variant rate. Conclusions: Most of the enrolled patients (70%) with chronic infection P138 presented hypermutators strains. Such a high prevalence confirms the Staphylococcus aureus pathogenicity in cystic fibrosis patients - occurrence and importance of hypermutation as an adaptive mechanism in virulence genes, phylogeny and horizontal gene transfer Achromobacter spp. infection. Hypermutation could potentially influence J. Lange1, D. Görlich2, K. Heidenreich1, K. Higelin1,K.Dyck1, V. Marx1, the clinical outcomes and the efficacy of treatments, highlighting the need C. Reichelt1, B. Kahl1. 1University Hospital Münster, Medical Microbiology, to clarify its impact in order to develop appropriate therapeutic regimens. Münster, Germany; 2University Hospital Münster, Institute of Biometrie and Acknowledgments: This study was supported by the Italian CF Research Clinical Research, Münster, Germany Foundation (project FFC#18/2019).

Objectives: There is a lack of information about the impact of P140 Staphylococcus aureus on lung function and disease progression in patients Normobaric oxygen enhances the effect of quinolones against with CF. We aimed to identify bacterial factors associated to clinical Pseudomonas aeruginosa biofilms deterioration in CF patients. 1 2 3 3 M. Kolpen , C. Thyssen , L. Katrine Drasbæk Philipsen , D. Faurholt-Jepsen , Methods: During an observational prospective multicentre study, respira- 2 2 1,4,5 1 K.-Å. Henneberg , T. Sams , P. Østrup Jensen . Rigshospitalet, tory specimens from 195 CF-patients (16 centres in Germany, 1 center in 2 Department of Clinical Microbiology, Copenhagen, Denmark; Technical Austria) were processed at a central laboratory. All S. aureus isolates University of Denmark, Biomedical Engineering, Department of Health (n = 3963) were analyzed for the presence of virulence genes by single and 3 Technology, Lyngby, Denmark; Rigshospitalet, Copenhagen University multiplex PCR (adhesins: cap, clfA/B, cna, eap, emp, fnbA/B, sasG/H, sdrC/D/E; Hospital, CF Center, Department of Infectious Diseases, Copenhagen, Denmark; toxins: eta/etb, hlg, pvl, seA/B/C/D/E/G/H/I/J, tst; immune escape: chip. 4 University of Copenhagen, Costerton Biofilm Center, Department of Molecular typing was performed by spa-typing. Clinical data related to Immunology and Microbiology, Faculty of Health and Medical Sciences, lung disease exacerbation were reported in case report forms. 5 Copenhagen, Denmark; Rigshospitalet, Copenhagen University Hospital, Results: The average follow-up time was 80 weeks with a mean of 7 visits. Institute for Inflammation Research, Center for Rheumatology and Spine Neither the quantity of virulence genes, nor the presence of specific Diseases, Copenhagen, Denmark virulence genes characteristic for S. aureus were associated to a clinical deterioration. However, for the agr -types 1 and 4 a link to the subject’s Background: In cystic fibrosis (CF) patients, Pseudomonas aeruginosa clinical status became evident. Moreover, agr -types showed a clear biofilms cause severe recalcitrant chronic infection in the lower respiratory association to the clonal background of S. aureus. The analyses revealed a tract with zones of oxygen (O2) depletion. Quinolones can perturb aerobic significant longitudinal decrease regarding the number of virulence genes metabolism in bacteria leading to formation of lethal reactive O2 species during persistence. There were significantly increased plasticity rates for which contribute significantly to the bactericidal effect. Thus, susceptibility virulence genes in the presence of environmental stress. to quinolones in anaerobic P. aeruginosa biofilms may be restored by

Conclusions: These results provide evidence for the concept that rather the normobaric O2 treatment (NBOT) (100% O2, 1 bar). phylogenetic background than the presence of specific virulence genes Objective: Our aim is to evaluate the possibility to oxygenate fresh CF accounts for differences in S. aureus pathogenicity. The significantly sputum and sensitize anoxic biofilms of P. aeruginosa to quinolones by increased gene plasticity rates in the presence of environmental stress oxygenation using NBOT. suggests host and iatrogenic influence on S. aureus genome plasticity. The Materials and methods: Freshly expectorated CF sputum samples were loss of virulence genes during persistence most likely reflects the treated with NBOT for 360 min. In addition, we estimated the effect of adaptation process directed towards a persistent and colonizing rather NBOT on the treatment of O2-depleted P. aeruginosa (PAO1) agarose than an infecting lifestyle. embedded biofilms with two-fold concentration of ciprofloxacin (0.25– − − 2 μgmL 1) and levofloxacin (2–16 μgmL 1) for 90, 180 and 360 min. The P139 results are compared to a reaction diffusion model. Hypermutation as an evolutionary mechanism for Achromobacter spp. Results: NBOT was able to oxygenate PAO1 biofilms and fresh CF sputum. in cystic fibrosis lung infection NBOT expanded the oxygenated zone from 1.3 mm to 4 mm in sputum. L. Veschetti1, A. Sandri2, R. Passarelli Mantovani2, P. Melotti3, G. Malerba1, NBOT enhanced the bactericidal activity of ciprofloxacin during 180 and M.M. Lleo2. 1University of Verona, Laboratory of Computational Genomics, 360 min of NBOT (P < 0.0001) and levofloxacin during 180 min of NBOT Department of Neurosciences, Biomedicine and Movement Sciences, Verona, (p < 0.0001) in PAO1 biofilm. The maximum enhancement of killing by −1 Italy; 2University of Verona, Department of Diagnostics and Public Health, NBOT exceeded 1 log using 0.25–2 μgmL of ciprofloxacin. The expanded Microbiology Section, Verona, Italy; 3Azienda Ospedaliera Universitaria killing zone is in qualitative agreement with the mathematical model. Integrata Verona, Cystic Fibrosis Center, Verona, Italy Discussion and conclusion: This study demonstrates the potential of NBOT as an adjuvant to expand and enhance antibiotic susceptibility in Objectives: Achromobacter spp. can cause chronic infections in the lungs of chronic P. aeruginosa lung infections in CF patients by enhancing the supply CF patients. One of the main mechanisms favouring the persistence of CF of O2 for bacterial aerobic respiration. We suggest considering NBOT as a pathogens is hypermutation, in which defects in DNA repair processes save adjuvant for improving antibiotic treatment of CF patients where the promote an increased DNA mutation rate. In this study, longitudinal lung infection has not yet advanced into creating exacerbation and zones of isolates were screened to verify the occurrence of hypermutators. trapped air. S96 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P141 promising lead compound for the development of colistin adjuvants for the Investigating an ajoene derivative as a new combination therapy with treatment of multidrug resistant bacterial infections. antibiotics against Pseudomonas aeruginosa infections E. Ashworth1, L. Sykes2, J. Fothergill1, A. Kadioglu1. 1University of Liverpool, P143 Liverpool, United Kingdom; 2Neem Biotech, Abertillery, United Kingdom Clinical observation leads to the synthesis of BG185, a new anti- staphylococcal compound Objectives: Chronic lung infections in patients with cystic fibrosis (CF) 1 2 1 3 1 B. Gioia , C. Commun , A. Arnaud , S. Michalet , S. Radix , cause progressive and extensive lung damage and can lead to patient death. 3 2 1 1 M.-G. Dijoux-Franca , D. Blaha , N. Walchshofer , L. Rocheblave , By adulthood up to 80% of CF patients are infected with opportunistic 2,4 1 A. Doléans-Jordheim . Equipe EA 4446 - Molécules Bioactives et Chimie pathogen Pseudomonas aeruginosa (Pa). The World Health Organisation has 2 Médicinale (B2MC), Lyon, France; UMR CNRS-UCBL-VetAgroSup 5557 declared that Pa is a key human pathogen that is in urgent need for new Ecologie Microbienne, Equipe Bactéries Pathogenes̀ Opportunistes et antibiotics. This need is driving the development of new anti-virulence 3 Environnement, Lyon, France; UMR CNRS-UCBL-VetAgroSup 5557 Ecologie strategies, such as antibiotic stewardship. Neem Biotech have developed a Microbienne, Multi-résistance Environnementale et Efflux Bactérien-, Lyon, novel synthesis method of a therapeutic compound called ajoene, which is 4 France; Institut des Agents Infectieux-Hospices Civils de Lyon, Lyon, France derived from garlic. It has been hypothesised that ajoene and related analogues can inhibit biofilm formation in Pa and could be used in Background: In Cystic Fibrosis (CF), Staphylococcus aureus (Sa) is the major combination with antibiotics to treat CF patients. The aim of this project is pathogen in children, but over the time, this bacterium is gradually to determine the synergistic effect of potential anti-virulence ajoene with replaced by Pseudomonas aeruginosa (Pa). This succession could be antibiotics; tobramycin and colistin. explained by antagonist Pa-Sa interactions, mediated, among others, by Methods: The synergistic effects of ajoene and antibiotics tobramycin and anti-Sa molecules secreted by Pa. Based on this observation, we identified colistin were assessed in Artificial Sputum Medium in a checkerboard assay Alkyl-Quinolones (AQ) that could be responsible for this anti-Sa activity. to determine the effects ajoene has on bacterial growth on adapted clinical Because of the difficult access to pure compounds, we synthesised de novo a Pa strain NP162. The effect of bacterial growth was determined using a carbonate derivative (BG185) as a mixture of regioisomers, belonging to the metabolic assay and the percentage inhibition of metabolic activity was D2-AQNO-C12 series, which has demonstrated an antimicrobial activity calculated. The synergistic effect was determined using Zero Interaction against Sa. Potency (ZIP) reference model. Objective: Our goal was to biologically characterise the activity of BG185 Results: It was found that ajoene is synergistic with both colistin & against Sa. tobramycin against clinical isolate NP162. Materials and methods: The antimicrobial activity was evaluated by Conclusion: Ajoene could be a potential combination therapy with inhaled determining the Minimum Inhibitory Concentration (MIC) of BG185 on 9 colistin or tobramycin to treat infected CF patients. Sa strains (2 Sa ATCC strains and 7 CF Sa strains methicillin sensible-SASM and resistant-SARM) as well as performing killing-curves. Ciprofloxacin P142 was used as a reference. MICs were also evaluated on 4 Staphylococcus non A novel colistin adjuvant identified by virtual screening for ArnT aureus strains and on 3 non-Staphylococcus strains (P. aeruginosa, inhibitors Escherichia coli, Enterococcus faecalis). L. Cavinato1, F. Ghirga2, R. Stefanelli1, A. Lo Sciuto3, S. Corradi4, D. Quaglio4, Results: BG185 MIC ranged from 0,25 to 4 mg/L on SASM strains and from 1 A. Calcaterra4, B. Casciaro2, M.R. Loffredo5, F. Cappiello5, P. Morelli6, to 4 mg/L on SARM strains. The killing curves demonstrated a bacteriostatic M. Mangoni5, C. Mancone7, B. Botta4, M. Mori8, F. Ascenzioni1, F. Imperi3. activity of BG185, but not a bactericidal one. This antimicrobial activity was 1Sapienza University of Rome, Department of Biology and Biotechnology also observed for the 3 Staphylococcus non-aureus (with MIC ranging from Charles Darwin, Rome, Italy; 2Italian Institute of Technology, Sapienza, Rome, 0.25 mg/L to 4 mg/L). No activity was observed against the other bacteria. Italy, Center for Life Nano Science, Rome, Italy; 3Roma Tre University, Conclusions: Observing a clinical situation led us to synthesise BG185 Department of Sciences, Rome, Italy; 4Sapienza University of Rome, which could represent an original chemical hit to elaborate new molecules Department of Chemistry and Technology of Drugs, Rome, Italy; 5Sapienza acting against Staphylococcus isolates (SARM and non-aureus strains University of Rome, Department of Biochemical Sciences, Rome, Italy; included), that could be used to prevent and cure CF lungs infections but 6Giannina Gaslini Institute, Microbiology Laboratory, Genoa, Italy; 7Sapienza also various other staphylococcal infections (skin disease, catheter University of Rome, Department of Molecular Medicine, Rome, Italy; mediated infections…). 8University of Siena, Department of Biotechnology, Chemistry and Pharmacy, Siena, Italy P144 Short and long-term effect of cinnamaldehyde on Pseudomonas Objectives: This study aimed to identify, by in silico screening of a chemical aeruginosa antibiotic resistance library, potential inhibitors of ArnT, which catalyses the last committed step 1 1 1 1 A. Tetard , S. Galliot , C. Llanes . UBFC, Besançon, France of lipid A aminoarabinosylation, and to validate them in vitro as colistin adjuvants. Objectives: Pseudomonas aeruginosa is the key bacterial agent of cystic Methods: The available ArnTcrystal structure was used for a docking-based fibrosis lung infections, and the most important pathogen in this virtual screening of an in-house library of natural products. The resulting progressive and severe lung disease. Because of bacterial persistence, putative ArnT inhibitors were tested in growth inhibition assays using a patients are looking for alternatives to treat these infections, including the reference colistin-resistant P. aeruginosa strain. The most promising use of essential oils (EOs). However, if some of them exhibit a high compound was further characterized for range of activity, specificity and bactericidal activity, little is known about their activity when used in cytotoxicity. Additionally, the effect of the compound on lipid A combination with antibiotics. Through the example of cinnamaldehyde aminoarabinosylation was verified by mass spectrometry analyses of (CNA), the main compound of cinnamon EO, we explored the impact of this lipid A. molecule on efflux-mediated antibiotic resistance after a short- or an Results: A putative ArnT inhibitor (BBN149) was discovered by molecular iterative-exposition. docking and demonstrated to specifically potentiate colistin activity in Methods: P. aeruginosa susceptible strain PA14 was used in this study. colistin-resistant P. aeruginosa isolates, without relevant effect on colistin- Expression of efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN and susceptible strains. BBN149 showed adjuvant activity also against colistin- MexXY/OprM) coding genes was quantified over-time by RT-qPCR after resistant Klebsiella pneumoniae, and low toxicity to bronchial epithelial CNA exposure. Minimal Inhibitory Concentrations (MICs) of antibiotics cells. Lipid A aminoarabinosylation was reduced in BBN149-treated cells, were determined with CNA 0, 256 or 512 μg/mL. Metabolization of CNAwas although only partially. visualized by TLC and HPLC on culture supernatants. Mutants resistant to Conclusion: This study demonstrates that in silico screening targeting ArnT CNA were obtained after 5 to 10 days of contact and their genome was fully can successfully identify inhibitors of colistin resistance and provides a sequenced by the Illumina technology. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S97

Results: Thirty minutes post-exposure, CNA simultaneously induced the Results: 1. In vitro screening of compounds against Mab is in progress. So overexpression of four efflux systems (especially MexAB-OprM), leading to far, out of 658 compounds tested, only one belonging to pyridine class was an increased resistance to ß-lactams, aminoglycosides and fluoroquino- active against Mab. It is very active against both Mab wild-type (MIC = 1 ug/ lones. This overexpression was transient because of CNA metabolization ml) and MDR isolates. Moreover, other NTM as well as Mycobacterium into the less toxic cinnamic alcohol, reverting PA14 to a susceptible avium wild-type and MDR isolates are sensitive to this compound. Its phenotype. In contrast, long-term exposure to CNAwas able to select stable activity seems to be specific against mycobacterial species. The character- mutations (especially in MexAB-OprM regulatory gene nalC) modifying the ization of its mechanism of action is in progress using the following resistance profile of the bacterium. approaches: RNA-Seq; drug combinations; possible activity against Mab Conclusion: Overproduction of efflux pumps allows PA14 to resist to CNA; biofilm; study of its possible bactericidal activity. but, the emergence of cross-resistances points out that the combination of 2. In silico virtual screening by means of pharmacophore modelling and EOs and antibiotics should be antagonistic in the case of P. aeruginosa. docking simulations on compound libraries (in total 276.000 molecules) were performed against Mab MmpL3 structure. MmpL3 is recently P145 emerged as a drug target against Mab. 48 candidate MmpL3 inhibitors Bactericidal effects of antimicrobial peptides in the presence of human were selected and assayed by REMA. Three inhibitors were found to be lung epithelial cells active against Mab growth, thus their characterization is in progress. L. Touqui1. 1Institut Pasteur, Paris, France Conclusion: In the future, the most active compound(s) will be tested in vivo to find more effective weapons against Mab. Objectives: Antimicrobial peptides (AMPs) are promising alternatives to combat antibiotic resistance. Publications in this field reported bactericidal P147 activity of AMPs only in absence of host cells. We evaluated the effects of Longitudinal effects of ivacaftor on Aspergillus fumigatus serology and bronchial epithelial cell line IB3 from CF patients on the bactericidal culture in eligible adults with cystic fibrosis activity of two AMPs (LL-37 and CAMA) against Pseudomonas aeruginosa 1, 2 1,2 1,2 1, 2 1,2 N.C. Fritsch , A.M. Jones , A.R. Horsley , H.D. Green , P.J. Barry . (PA). 1 2 Manchester Adult CF Centre, Manchester, United Kingdom; University of Methods: The killing effects of LL-37 and CAMA were examined using the Manchester, Division of Infection, Immunity & Respiratory Medicine, Faculty of PA laboratory strain PAK. This was performed as we previously established Biology, Medicine and Health, Manchester, United Kingdom (Geitani et al., Microbiol. 2019) in absence or in presence of IB3 cells. Results: Our results showed that treatment of IB3 cells by AMPs exerted Objectives: The development of ‘highly effective’ CFTR modulation has the different effects against PA survival depending on the timing of AMPs potential to revolutionise CF care. To fully predict their impact it is administration. The highest bactericidal effects of AMPs were observed necessary to understand the effects they will have on common CF-related when IB3 cells were pretreated by CAMPs prior infection: when added to complications. Little is known regarding the effects of CFTR modulation on IB3 cells 30 min pre-infection, subminimum bactericidal concentrations Aspergillus related lung disease, information that is essential due to drug- (sub-MBCs) of LL-37 and CAMA killed 99% and 83.5% of PA respectively, drug interactions between CFTR modulators and common anti-fungals. whereas in absence of IB3 cells, AMPs killed only 53% and 60.5% of PA, Methods: We conducted a retrospective cohort study examining patients respectively. However, no bactericidal effects were observed when supra- who commenced ivacaftor. Over a period of 5 years we monitored the MBCs of AMPs were added to IB3 cells simultaneously to or 30 min post- isolation of Aspergillus in sputum samples and patients’ serological infection. AMPs had no toxic effects on cells (LDH release) and only weak response to Aspergillus fumigatus. pro-inflammatory effects (cytokines release). Results: In 40 patients, ivacaftor therapy resulted in a significant decrease Conclusion: These findings suggest a prophylactic effect of AMPs on PA and in sweat chloride (from 112 [102.75–119.25] to 45 [37–61], p < 0.001), and that the presence of IB3 cells impact this effect. A possible inactivation an increase in FEV1 from 53.2% to 63.1% predicted. One patient was treated (likely by proteases or AMP inhibitors produced by IB3 cells) post-infection with concomitant itraconazole for ABPA. There was no difference in the play a role in the alteration of LL-37 action. Further studies are crucial to proportion of Aspergillus positive sputum cultures over time. There was an identify the mechanisms by which IB3 cells inactivate LL-37 and the role of early decrease (at 6 months) in total IgE levels from 35.6 [15.9–202.5] to PA in this process. We will also examine strategies to prevent this 26.7 [9.5–108.25] (p = 0.02) but these were not sustained beyond the initial inactivation which will allow to valorize AMP usage as prevention and/or 6 months of initiation of Ivacaftor and at 5 years were 51.1 [15.4–121 ku/L]. therapeutic agents in CF. There were no significant changes in Aspergillus specific IgE or IgG over the study time. P146 Conclusions: Effective CFTR modulation does not appear to alter patient New weapons are necessary to fight Mycobacterium abscessus susceptibility or immunological response to Aspergillus fumigatus in G. Degiacomi1, J.C. Sammartino1, A. Urbani1, O. Riabova2, L. Muñoz Muñoz3, clinical settings. These findings suggest that Aspergillus will remain a L.R. Chiarelli1, F. Manetti4, S. Ramon-Garcia3,5, V. Makarov2, M.R. Pasca1. significant pathogen in a new era of CF when most patients will receive 1University of Pavia, Department of Biology and Biotechnology ‘Lazzaro CFTR modulator therapy. This will potentially result in clinical challenges Spallanzani’, Pavia, Italy; 2Research Center of Biotechnology of the Russian due to difficult drug-drug interactions between -azole medications and Academy of Sciences, Moscow, Russian Federation; 3University of Zaragoza, CFTR modulators. Department of Microbiology, Preventive Medicine and Public Health, Faculty of Medicine, Zaragoza, Spain; 4University of Siena, Department of Biotechnology, P148 5 Chemistry and Pharmacy, Siena, Italy; Research & Development Agency of Inhaled levofloxacin: impact of susceptibility testing results on FEV1 Aragon (ARAID) Foundation, Zaragoza, Spain and exacerbation rate P.Eschenhagen1, H. Schäfer2, C. Grehn1, S. Temming1,A.Lewin2, C. Schwarz1. Objectives: Nontuberculous mycobacteria (NTM) are recently emerging as 1 Charité - Universitätsmedizin Berlin, Department of Pediatric Pneumology, important pathogens among cystic fibrosis (CF) patients worldwide. The Immunology and Intensive Care, Division of Cystic Fibrosis, Berlin, Germany; NTM incidence in CF is approximately from 3.3 to 22.6%. At the same time 2 Robert Koch Institute, Division 16, Mycotic and Parasitic Agents and for other CF pathogens such as Pseudomonas aeruginosa and Burkholderia Mycobacteria, Berlin, Germany cepacia, the incidence decreased. Among NTM subspecies, Mycobacterium abscessus (Mab) is becoming the most worrisome pathogen in CF centres Objectives: Cystic fibrosis is a life-shortening, multisystem disorder with worldwide. Mab drug therapy is long up to 2 years and its failure causes an the major cause of mortality and morbidity being a progressive chronic accelerated lung function decline. In fact, it is intrinsically resistant to many obstructive lung disease. Acute and chronic infections due to bacterial drugs, due to its physiology and its acquisition of new mechanisms of drug colonisation with Pseudomonas aeruginosa are the most common clinical resistance. Consequently, there is an urgent need of new drugs against Mab. indications for antibiotic treatment in cystic fibrosis. Therapeutic strategies Methods: Both in silico and in vitro strategies were pursued to this aim. are divided into acute intervention and chronic suppression therapy in chronic Pseudomonas aeruginosa colonised patients. Inhaled antibiotics S98 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 play an important role in treating chronic Pseudomonas aeruginosa Methods: AZTEC-CF was an open-label randomised crossover study colonisation and infection. Currently with levofloxacin four inhaled designed and conducted at a regional adult cystic fibrosis centre in the antibiotics are available for CF. UK (ClinicalTrials.gov: NCT02894684). Inclusion criteria included age > 16 Methods: Patients with CF starting new treatment with inhaled levoflox- years, P. aeruginosa infection and no prior use of AZLI. Exclusion criteria acin were included into this study. Data were prospectively collected in the included Burkholderia cepacia complex infection and solid-organ trans- German patients’ registry Muko.web. In addition, detailed data were plant. During two consecutive exacerbations requiring hospitalisation for collected from the patient’s data file. intravenous antibiotics, subjects received 14 days AZLI plus intravenous Results: 86 patients (54 were female) were included into the study that colistimethate (AZLI + IV) or standard dual intravenous antibiotics (IV + IV). was conducted from 4/2016 and 5/2018. Median age was 34.3 years (range Primary outcome was recovery of % predicted FEV1 (ppFEV1) at 14 days. Key – 18 73 years). Mean FEV1 was 42.1 percent predicted before study start. secondary outcomes included health-related quality of life outcomes, Mean BMI was 20 kg/m2 (range 16–28). In 12 patients susceptibility testing sputum bacterial load, systemic inflammatory markers, aztreonam revealed a change from chinolone sensitive to resistant and in 11 patients resistance and safety outcomes. from chinolone resistant to sensitive. In 63 patients no changes in Results: Sixteen adults with CF were consented and randomised, and by susceptibility to chinolones were found. Regardless of the resistant status March 2019 (censorship date) 28/32 (87.5%) exacerbations were com-

FEV1 (p = 0.011 after 4 weeks) and exacerbations rate (p < 0.05 after 12 pleted. At 14 days, improvement in ppFEV1 was greater for AZLI +IV month) improved after initiating inhaled levofloxacin. compared to IV+IV (mean +13.5% versus +8.3%; paired differences [95% CI] Conclusion: Resistant status of patients with chronic Pseudomonas +4.6% [2.1 to 7.2], p = 0.002). The minimum clinically important difference aeruginosa infection has no clinically significant impact on treatment in CFQ-R Respiratory Domain was achieved more frequently in exacerba- success. On the contrary, FEV1 and exacerbation rate improve despite tions treated with AZLI + IV (83.3% vs. 43.8%, p = 0.03). No significant resistant Pseudomonas aeruginosa strains. differences were found between treatments for changes in sputum bacterial load, systemic inflammation or adverse events. P149 Conclusion: AZLI is effective, safe and well tolerated in the treatment of A review of the clinical trajectory of adults with cystic fibrosis acute pulmonary exacerbations of CF. Superior improvements in lung prescribed nebulised Aztreonam Lysine (Cayston™) function and quality of life suggest AZLI may represent a new treatment C. Bradley1, C. McKeown2, C. Rutherford1, D.G. Downey1,3, C. Addy1,4, approach for acute pulmonary exacerbations and further work is required S. Caskey1. 1Belfast Health and Social Care Trust, Adult CF Centre, Belfast, to understand how its use in the acute setting can be optimised. United Kingdom; 2Belfast Health and Social Care Trust, Pharmacy Department Belfast City Hospital, Belfast, United Kingdom; 3Queens University Belfast, P151 Centre for Experimental Medicine, Belfast, United Kingdom; 4Queens Monitoring clinical and microbiological changes in people with cystic University Belfast, Centre for Medical Education, Belfast, United Kingdom fibrosis during the early stages of modulator therapy in an adult centre in the UK Objectives: Currently in the UK, nebulised Aztreonam Lysine (AZLI) is T.S. FitzMaurice1,2, L. Wright3,F.Frost1, 3, E. Scott1, C. Winstanley3, prescribed third line for chronic Pseudomonas aeruginosa suppression. M. Walshaw1, 3, D. Nazareth1,3, J.L. Fothergill3. 1Liverpool Heart & Chest There is limited data on real-world outcomes with long-term AZLI usage. Hospital, Adult CF Unit, Liverpool, United Kingdom; 2University of Liverpool, This study reports the clinical trajectory of adults with CF prescribed AZLI. Institute of Translational Medicine, Liverpool, United Kingdom; 3University of Methods: Electronic care records for all adults with CF currently prescribed Liverpool, Institute of Infection and Global Health, Liverpool, United Kingdom AZLI (n = 21) at the NI Regional Adult CF Centre were assessed (n = 21). Lung function [ ppFEV1] and IV days pre and post AZLI initiation were reviewed. Objectives: The introduction of modulator therapy has triggered a new era Results: Of those prescribed AZLI, 71% were female, with mean (SD) age of in the management of people with CF. This has unlocked many questions in

38 (11.1) years and mean (SD) ppFEV1 of 43 (9.1)%. Most (91%) were relation to clinical management and the continued need for certain prescribed an alternate month regime with a second inhaled antibiotic, therapeutics in the post-modulator period. In this study we sought to with 9% (n = 2) on continuous AZLI. In the 12 months following initiation, IV closely monitor the microbiology of adult people with CF during this days were significantly reduced, compared to 12 months prior to initiation transition period at our large adult CF unit. [36.14 (32.8) vs 25.3 (32.6)] days [ p = 0.03]). Prior to the initiation of AZLI Methods: Adults with CF (n = 33) were recruited prior to starting – there was a significant drop in mean ppFEV1 between the time periods 6 modulator therapy (Symkevi [n = 30] or Ivacaftor [n = 3], Vertex ® 12 months, and 0–6 months pre commencement [42.8 (13.3) vs 39.05 Pharmaceuticals ). Clinical measures including age, sex, FEV1, BMI, long

(12.30] % [ p = 0.016]. Mean ppFEV1 in the 6 months pre and post AZLI term medication use, microbiological status and antibiotic usage were initiation was not significantly different [39.05 (12.3 vs 39.24 (13.0) %] recorded during outpatient and inpatient periods. Detailed microbiological [ p = 0.78]. There was also a significant reduction in IV days when those changes prior to, and once commenced on, modulator therapy are being with a ppFEV1 >40% (n = 11) [36.9 (36.3) vs 21.5 (32.4)] [ p =0.17]were monitored using both standard culture techniques and next generation considered. sequencing of the 16S rRNA V4 region using Illumina sequencing and Conclusion: Here we report a reduced rate of hospitalisation and slowing previously optimised protocols. of lung function decline following AZLI initiation, even in those people with Results: The average age was 29 years (range 18–51 years), 55% female, 2 CF with relatively higher lung function, suggesting there is a role for early baseline mean ppFEV1 59%, BMI 23kg/m . 88% of those recruited were AZLI use to prevent further decline. chronically infected with P. aeruginosa and of these, 30% were identified as carrying the Liverpool Epidemic Strain of P. aeruginosa. Other microbes P150 identified through standard culture were Staphylococcus aureus (42%), Aztreonam lysine recovers lung function and improves quality of life in Aspergillus sp. (15%), Achromobacter xylosoxidans (9%), Stenotrophomonas the treatment of acute exacerbations of cystic fibrosis: results from an maltophilia (9%), Serratia sp. (3%), Mycobacterium abscessus (3%) and open-label randomised crossover study (AZTEC-CF) Exophiala sp. (6%). Conclusion: Monitoring these early changes in both clinical parameters F. Frost1, 2, J. Fothergill2, C. Winstanley2, M. Walshaw1, 2, D. Nazareth1,2. and detailed microbiology, including whole bacterial population changes, 1Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; 2University of will provide an insight into the impact of CFTR modulators on our CF Liverpool, Institute of Infection & Global Health, Liverpool, United Kingdom population. Understanding these changes will potentially enable informed Objectives: The AZTEC-CF study aimed to evaluate the use of aztreonam decisions on future patient management, monitoring of antibiotic lysine (AZLI) for the treatment of acute pulmonary exacerbations of cystic resistance and the use of therapeutics such as antibiotics. fibrosis. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S99

P152 goodness-of-fit and predictive performance. PK/PD simulation with the Practical challenges to daily intravenous tobramycin dosing in patients final model was performed by computing steady-state concentrations of with cystic fibrosis TOB in 1000 virtual patients, for various TOB dosage regimens and 1 2 1 2 1 ≥ L. Barry , P. Drennan , S. Sivam , S. Van Hal . Royal Prince Alfred Hospital, covariates values. The target values of PK/PD indices were AUC24/MIC 100 Department of Respiratory Medicine, Sydney, Australia; 2Royal Prince Alfred and Cmax/MIC ≥10. Maximal MIC was set at 2 mg/L, the EUCAST Hospital, Department of Microbiology and Infectious Diseases, Sydney, epidemiological cut-off of Pseudomonas aeruginosa.PTA≥90% was Australia considered as acceptable. Results: We analysed data from 195 patients who received a total of 754 Objectives: Intravenous (IV) tobramycin is commonly used in the courses of TOB, from 2010 to 2018. The mean ± SD of age, weight (WT) and management of infective exacerbations of cystic fibrosis (CF) due to creatinine clearance (CLcr) were of 11.4 ± 5 yr, 35.3 ± 15 kg and 82.6 ± 30 Pseudomonas aeruginosa. Once daily IV tobramycin requires therapeutic mL/min, respectively. The final model was a two-compartment model drug monitoring (TDM) to ensure patients receive therapeutic exposures as including WT, body surface area and CLcr as covariates. Only the 20 mg/kg/ assessed by the area under the concentration time curve over 24 hours day dosage was associated with acceptable PTA for Cmax/MIC in patients – (AUC24, target = 80 120 mg.h/L). Supratherapeutic exposures may result in with low renal function. None of the tested regimens could achieve renal dysfunction, ototoxicity or vestibular toxicity. Due to concerns acceptable PTA for the AUC24/MIC target. regarding cumulative toxicity, local practice has been to cap doses at Conclusion: Our results question the dosing and PK/PD targets for TOB 560mg. The aim of this study was to identify factors which may influence therapy in CF children, as well as MIC breakpoints. attainment of therapeutic targets in a single tertiary CF centre. Methods: We conducted a retrospective audit of patients admitted with an Reference infective exacerbation of CF between January and December 2018. [1] Neely MN, van Guilder MG, Yamada WM, Schumitzky A, Jelliffe Demographic and TDM data were collected from the electronic medical RW. Ther Drug Monit. Août 2012;34(4):467–76. record. Results: 53 patients had infective exacerbations requiring 97 admissions. P154 28 patients (52%) were admitted once in the study period (range 1–6). Population pharmacokinetic (POP-PK) model is useful to optimise There were 256 TDM episodes (mean 2.6 per admission) with 24 (25%) tobramycin dosage in cystic fibrosis patients achieving the target AUC on their first TDM episode. 26 (37%) were below 1 2 3 4 1 1 24 L. Darnaud , M. Mittaine , M. Murris , H. Guet-Revillet , P. Gandia . CHU target AUC for the entire admission, largely due to dose capping. 24 Toulouse, Laboratoire de Pharmacocinétique et Toxicologie, Toulouse, France; Examining workflow suggested potential difficulties in both pre and post 2 3 CHU Toulouse, CRCM Pédiatrique, Toulouse, France; CHU Toulouse, CRCM analytical practices: in 33% of readmissions during the study period, the 4 Adulte, Toulouse, France; CHU Toulouse, Laboratoire de Bactériologie, initial prescribed dose was lower than the optimised dose from the Toulouse, France previous admission, while post analytical difficulties delayed dose modification in 97 episodes (46%). Objectives: For aminoglycosides, the optimum pharmacokinetic-pharma-

Conclusion: The target AUC24 was not achieved for a large proportion of codynamic (PK-PD) endpoint for bacteriological and clinical efficacy is an patients. In many cases, this occurred due to dose capping, however pre AUC/MIC ratio (i.e. area under concentration-time curve over minimum and post analytical issues were important contributors. From January 2019, inhibitory concentration), with a threshold value of 70 (EUCAST). The ratio – higher doses (>560 mg) were used to achieve target AUC24. An electronic of maximal concentration (Cmax) to MIC (Cmax/MIC) with a threshold >8 10, method for TDM requests may facilitate transfer of information in a more may be used as alternative. In clinical practice AUC is difficult to determine timely, accurate and reliable manner. and the MIC is generally not known at the start of treatment. The Cmax value, with a threshold between 30 and 40 mg/L derived from the P153 Pseudomonas aeruginosa breakpoint (4 mg/L), is therefore often used

Population PK analysis and dosing simulation of tobramycin in instead. Our objective was to determine whether both the Cmax/MIC and paediatric patients with cystic fibrosis AUC/MIC ratios in 8 paediatric and 12 adult CF patients lead to the same 1,2,3 4 4 2,3,5 A. Praet , F. Vételé , V. Bréant , O. Dumitrescu , interpretation as using the Cmax value alone. A. Doléans-Jordheim2,3,6,P.Reix1, 7, L. Bourguignon1,2,8, S. Goutelle1,2,8. Methods: The tobramycin AUC was estimated for each patient, using 2 1LBBE - Laboratoire de Biologie et Biométrie Evolutive, CNRS UMR 5558, Equipe concentrations and the Touw’s population pharmacokinetic (POP-PK). EMET, Université Claude Bernard Lyon 1, Université Lyon, Lyon, France; 2ISPB - Pseudomonas aeruginosa MIC was determined and PK/PD criteria were Faculté de Pharmacie de Lyon, Université Claude Bernard Lyon 1, Université calculated. 3 Lyon, Lyon, France; IAI - Institut des Agents Infectieux, Groupement Results: Cmax/MIC and AUC/MIC led to different interpretations compared 4 Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Service de Pharmacie, to using Cmax alone (table 1). Differences between adult and paediatric Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; 5CIRI - patients can be explained by MIC and dosage differences (adults 10 mg/kg Centre International de Recherche en Infectiologie, CNRS UMR 5308, INSERM and children 15mg/kg). 6 U1111, Université Claude Bernard Lyon 1, Université Lyon, Lyon, France; LEM - Table 1. Laboratoire d’Ecologie Microbienne, CNRS UMR 5557, INRA UMR 1418, Comparison of the three PK-PD criteria Université Claude Bernard Lyon 1, Université Lyon, Villeurbanne, France; 7CRCM pédiatrique Lyon, Hôpital Femme Merè Enfant, Hospices Civils de Lyon, Adult Median [Min - Pediatric Median [Min Bron, France; 8Service de Pharmacie, Groupement Hospitalier Nord, Hospices Max] Percentage of - Max] Percentage of Civils de Lyon, Lyon, France patients reaching cut patients reaching cut off off Objectives: Children with cystic fibrosis (CF) may benefit from tobramycin MIC 3 [1–32] 1.25 [0.25–6] (TOB) therapeutic drug monitoring and pharmacokinetic-based dosage Cmax (mg/L) Cut off 30–40 mg/L 18.7 [16.6–25.6] 0% 27.6 [18–39.2] 37.5% adjustment. Two pharmacokinetic/pharmacodynamic (PK/PD) indices Cmax/MIC Cut off >10 7.3 [0.5–21.4] 42% 25.8 [3.9–156.8] 87.5% have been associated with response to aminoglycoside therapy: the ratio AUC/MIC Cut off >70 28.4 [2.3–83] 8% 86.8 [10.9–515.6] 62.5% of the 24 h-area under the concentration-time curve to the MIC (AUC24/ MIC) and the ratio of maximum concentration to the MIC (Cmax/MIC). The aims of this study were to analyse the population pharmacokinetics of TOB In 2020, new clinical breakpoint was recommended (2 mg/L, EUCAST). This in CF children and the probability of target attainment (PTA) of those two raises questions about implementation of new Cmax clinical cut off values – PK/PD indices. (16 20 mg/L) and advantages of using tobramycin in CF patients with MICs Methods: Population PK analysis was conducted with the Non-parametric greater than 2 mg/L. Adaptive Grid (NPAG) algorithm, implemented in the R package Pmetrics (1). The final model was selected based on classical criteria including S100 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Conclusion: Estimating AUC using a POP-PK approach associated to MIC are expressed as median (quartiles 25–75). The accepted PD target for total might improve the clinical management of CF patients as a threshold value unbound colistin is 2 mg/L. has now been recommended by EUCAST. Results: We included 24 patients [14 F, median age (min-max) 34.5 yrs (20–57), body weight 57 kg (40–69), serum creatinine 0.7 mg/dL (0.47– P155 1.1)]. PK data are at present available from 17 patients. Cmax for CMS was Pharmacokinetic of aminoglycosides in children with cystic fibrosis 10.4 (8.4–12.4) mg/L, for total colistin A+B 1.97 (1.31–2.55) mg/L and for P. Gallet1, S. Bouchet2, J.-B. Woillard3,4,M.Fayon1, 5, S. Bui1. 1CHU de unbound colistin A+B 0.55 (0.37–0.69) mg/L. At trough level, all total Bordeaux, Hôpital Pellegrin-Enfants, CRCM Pédiatrique, Centre d’Investigation colistin results (0.48 [0.25–0.67] mg/L) and unbound colistin (0.05 [0.03– Clinique (CIC 1401), Bordeaux, France; 2CHU Bordeaux, Pharmacologie, 0.09] mg/L) were inferior to the MIC of isolated strains and protein binding Bordeaux, France; 3CHU Limoges,, Department of Pharmacology and of colistin was high 87.5 (83.7–90.1) %. No serious adverse events were Toxicology, Limoges, France; 4INSERM, IPPRITT, U1248, Limoges, France; observed. 5University of Bordeaux, INSERM, Centre de Recherche Cardio-thoracique de Conclusions: Standard dose regimens of iv colistin in CF patients did not Bordeaux (U1045), Centre d’Investigation Clinique (CIC1401), Bordeaux, reach therapeutic plasma target levels in any patient. Higher dose regimens France plus nebulized administration may be required in severe clinical presentations. Objectives: The vital and functional respiratory prognosis of cystic fibrosis This work was funded by the Belgian CF association. is essentially related to pulmonary colonization by bacteria such as Pseudomonas aeruginosa (Pa). Aminoglycoside dosages currently recom- P157 mended in paediatrics have been inferred from studies in adults or very Comparison of Medicine Possession Ratio for nebulised aztreonam small cohorts. The objective was to describe the pharmacokinetic lysine before and after introduction of homecare provision parameters in children with cystic fibrosis. 1 1 1 1 1 M. Lea-Davies , J. Duckers , D. Lau , R.I. Ketchell . Cardiff & Vale University Methods: In this retrospective single-centre observational study, we noted Health Board, All Wales Adult Cystic Fibrosis Centre, Llandough, United all intravenous antibiotic courses including an aminoglycoside, carried out Kingdom between 2013 and 2018. Peak and residual plasma assays were performed on the first day of the treatment, pharmacokinetic data were obtained Objectives: To compare the Medicine Possession Ratio (MPR) for nebulised using PK-Just software, and the dosage was individually adapted by aztreonam lysine (Cayston®) prior to and after the introduction of Bayesian method. Respiratory function was assessed by FEV1, and bacterial homecare provision, and identify whether moving from hospital supply load by cytobacteriological examination of sputum before and after to home delivery had an effect on the MPR. treatment. Methods: All people with Cystic Fibrosis (PWCF) under the care of the All Results: 493 courses were analysed in 90 patients aged between 1 and 19 Wales Adult Cystic Fibrosis Centre (AWACFC) prescribed Cayston® and years. Amikacin was used for 259 (52.5%) courses, tobramycin for 174 registered to receive supplies via a homecare provider were identified. (35.3%) courses and gentamicin for 60 (12.2%) courses. We observed an Those registered for homecare for less than six months or who had been on increase in clearance, area under the curve and a decrease in half-life treatment for less than a year were excluded. The pharmacy computer compared to a healthy population, with significant differences by age and system identified the dates and quantities of Cayston® supplied from 1/1/ sex. After adjustment by Bayesian method, the dosage used for amikacin 18 to 31/12/19. The MPR was calculated for supplies made via the hospital was 32 [11–61] mg/kg/d, allowing a Cmax of 104.3 [53.8–126, 0] mg/L; for pharmacy from 1/1/18 until the point of registration with the homecare tobramycin 13 [7–23] mg/kg/day, allowing a Cmax of 54.4 [46.7–107.0] mg/ provider. The MPR was calculated for supplies made by home delivery from L; for gentamicin 15 [9–20] mg/kg/day, allowing a Cmax of 51.4 [31.7–57.1] registration with the homecare provider until 31/12/19. mg/L. Results: 29 PWCF (9.7% of our total cohort) prescribed aztreonam lysine Conclusion: The particular pharmacokinetics in cystic fibrosis requires the and registered to receive supplies via homecare were identified. 11 were use of high doses of aminoglycosides, making monitoring of plasma excluded either due to duration of homecare registration or lack of dosages essential. This study allowed us to define an initial dosage of comparable data. MPR was calculated for the remaining 18. The mean (SD) amikacin of 35 mg/kg/day for children under 12 years and 30 mg/kg/day duration of hospital prescribed days was 462.6 (53.0), with a range of 365– after 12 years; and 15 mg/kg/day for tobramycin and gentamicin. 561. The mean (SD) duration of homecare prescribed days was 250.5 (47.4), with a range of 169–334. The MPR for hospital supply ranged from 15 to P156 100%, with a mean of 63.8% (SD 29.2). The MPR for homecare supply ranged Standard doses of intravenous colistin do not achieve therapeutic from 61 to 100%, with a mean of 85.3% (SD 15.0). The MPR for homecare plasma target levels in adult cystic fibrosis patients: preliminary results supply was statistically significantly higher than that for hospital supply from a multicentre, prospective pharmacokinetic study (p = 0.007). D. Fage1, I. Etienne2, J. Pirson3, M. Hites4, F. Jacobs4, F. Cotton1, C. Knoop2, Conclusion: Moving from hospital-based supply to homecare-based S. Vincken5. 1LHUB-ULB, Chemistry, Brussels, Belgium; 2CHU Erasme, Chest supply resulted in a higher MPR within this cohort of adults with CF. A Medicine, Brussels, Belgium; 3CHR Citadelle, Pulmonology, Liege,̀ Belgium; higher MPR may be associated with increased adherence to prescribed 4CHU Erasme, Infectious Diseases, Brussels, Belgium; 5UZ Brussel, treatment. Pulmonology, Brussels, Belgium P158 Objectives: The polymyxin colistin, commercialized as a prodrug (colis- Is sputum induction of benefit following completion of Pseudomonas timethate-CMS), is considered a last-resort drug for Pseudomonas eradication regimes in children with cystic fibrosis? aeruginosa (Pa), as it shows no cross-resistance with more conventional 1 1 1 1 E. Edwards , C. Blackburn , T. Lee . Leeds Childrens Hospital, Regional antibiotics. Its use is however limited by its neurological and renal Paediatric Cystic Fibrosis Unit, Leeds, United Kingdom toxicities. Optimal dosing for CF patients is still unknown. We, prospect- ively, evaluated the pharmacokinetic (PK) profile of intra-venous (iv) Objectives: Current practice in our unit is to perform sputum induction colistin as well as its safety in adult CF patients presenting an acute following completion of Pseudomonas aeruginosa (Pa) eradication. exacerbation and colonized with Pa. Although not invasive sputum induction can be uncomfortable, cause Methods: Patients were treated with a conventional dose of CMS bronchoconstriction, and increases the duration of clinic visit so we wanted (Colistineb®) of 2 MIU tid and a broad spectrum beta-lactam for 10–14 to assess the benefit of this practice. days. Serum trough drug concentrations were measured at day 1–3 and a Methods: Children who had sputum induction following Pa eradication full PK profile was obtained at steady state between day 3–5. Serum treatment between January 2018 and December 2019 were identified and creatinine was assessed before and during treatment. Neurotoxicity was clinical notes reviewed. evaluated clinically. CMS, total and unbound colistin A+B concentrations Results: 45 sputum inductions were performed between 2 weeks to three were determined by mass spectrometry (LC-MS/MS method). PK results months following Pa eradication treatment being finished. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S101

Sputum samples were successfully obtained in 29 (64%) subjects. Methods: Study subjects are children under six years of age with CF In 3 (7%) subjects Pa was isolated on the induced sputum sample but not on attending for routine surveillance flexible bronchoscopy (FB). Cases have pre induction cough swab samples. six lobe BAL performed during FB and controls have traditional two lobe 2 (4%) subjects isolated Pa on pre induction cough swab but not on the BAL (RML and lingula) performed. Safety is compared between case and induced sputum sample. control groups using 13 intra/post-procedural parameters and intraproce- 3 subjects (7%) isolated clinically significant pathogens other than Pa on the dural pulse oximetry. Marginal efficacy was determined by comparing the induced sputum sample that were not isolated in pre induction cough microbiological semi-quantitative culture and PCR yield from pooled swabs. lavages between the case and control cohorts. Safety outcomes were 4 (9%) subjects had positive isolates of Pa in routine samples within 6 compared using Chi-squared test, students t-test for oximetry data and months of the sputum induction being performed. descriptive statistics used for microbiological outcomes. Sputum induction was tolerated by all patients with no adverse effects Results: Seventeen cases and nine controls have been enrolled to date documented. (mean age 3.9 vs 3, range 0.8–6.2 yrs). No significant differences in any Conclusion: Routine sputum induction following Pa eradication regimes predefined safety outcomes are demonstrated between cohorts (P values led to changes in patient management in 13% of subjects This included ns). No differences in mean and median SpO2, 4% desaturation indices and demonstrating failure of the eradication regime in 7% of subjects when percent time spent with SpO2 <90% were seen (P values ns) between cases routine sampling were falsely reassuring, allowing for further anti- (N = 15) and controls (N = 7). Although numbers are still small, no Pseudomonal therapy to be promptly initiated. The significance of negative significant difference was seen in BAL microbiological yield between sputum induction in the context of positive cough swabs is unclear but may groups. be worthy of further study. Conclusion: In this interim analysis, six lobe BAL (6 × 2 ml/kg) in children with CF demonstrated a similar safety profile and microbiological yield P159 compared to standard two lobe BAL. Recruitment and data analysis is Value of sputum induction for children with cystic fibrosis who have a ongoing. rise in serum Pseudomonas antibodies not associated with positive routine airway culture P161 E. Edwards1, C. Blackburn1,T.Lee1. 1Leeds Children’s Hospital, Regional Antibiotics adherence monitoring and use of technologies in children Paediatric Cystic Fibrosis Unit, Leeds, United Kingdom with cystic fibrosis: a systematic review E. Flynn1, S. George1. 1Royal College of Surgeons in Ireland, Dublin, Ireland Objectives: Performing sputum induction in response to an unexplained rise in serum Pseudomonas antibodies is current practice in our unit. We Children with Cystic Fibrosis (CF) are susceptible to recurrent infections reviewed how many were undertaken, the success rate and tolerance of and antibiotics are regularly used to prevent, treat or eradicate these sputum induction, and if the results help inform further management. infections. The repeated use of antibiotics with poor adherence may lead to Methods: Children with CF who had sputum induction in response to antibiotic resistance. In Ireland, children with CF have a multi-centre and raised serum Pseudomonas antibodies between January 2018 and multidisciplinary management approach which may cause inadequate December 2019 were identified and clinical notes were reviewed. monitoring of antibiotic use. The aim of this systematic review was to Results: 12 subjects were identified. Sputum samples were successfully provide an understanding of antibiotics adherence and monitoring obtained in 11 patients, 10 of which were unable to expectorate when a techniques for children with CF and insight into available technologies routine clinic sample was taken pre induction. and their applicability. Post induction samples in 2 patients were positive for Pseudomonas We searched Cochrane, Medline, PubMed and Embase databases using the aeruginosa (Pa). For 1 of these subjects Pa was not identified on pre following key words: antibiotics monitoring, children, cystic fibrosis, induction cough swab. medication adherence, Medication therapy management, Apps, eHealth, 5 of the subjects who did not isolate Pa with sputum induction and mHealth. Selected articles were reviewed in their entirety. The quality subsequently had Pa isolated from routine samples taken within 18 of included studies was assessed using an EBL checklist. months. 1 study matching the inclusion criteria used a nebulised (iNEB) device to All patients tolerated the procedure with no adverse effects documented. monitor doses of colistin. (EBL score 78%) For 8/28 patients antibiotic Conclusion: In the setting of an unexplained rise in Pseudomonas management plans were changed by their clinician in response to antibodies, sputum induction resulted in earlier diagnosis of new Pa in adherence data collected by the device. 2 further studies on Medication 8% of our subjects compared to routine sampling. A further 42% of subjects event monitoring systems/drug exposure monitors used in children are had a positive airway culture for Pseudomonas within 18 months, shown to be useful tools and facilitate clinician intervention. A further 2 suggesting sputum induction is not fully sensitive. Given the importance studies describe improved outcomes with use of reminder/education of early identification of new Pa, and the good tolerability, we plan to functions alone and gamification strategies for treatment adherence but continue this practice. larger trials were needed. There is a significant lack of research on antibiotic adherence monitoring in P160 children with CF. Development of systems for accurate measurement of Study to Evaluate the Additional Gains of Upper and Lower Lobe adherence to antibiotics in children with CF is an important measure. This Sampling in children with Cystic Fibrosis (SEAGULLS): safety and review demonstrates the availability of technology that could be applied to microbiological yield antibiotic adherence monitoring in children with CF and may have use in D. Butler1, 2, T. Montegue3,N.O’Sullivan4,D.Cox5, P. McNally1,5. 1Royal improving medication adherence rates but further research is needed on College of Surgeons in Ireland, Paediatrics, Dublin, Ireland; 2Children’s Health their applicability. at Crumlin, Dublin, Ireland; 3Children’s Health at Crumlin, Anaesthetics, Dublin, Ireland; 4Children’s Health at Crumlin, Microbiology, Dublin, Ireland; P162 5Children’s Health at Crumlin, Respiratory, Dublin, Ireland Aseptic centralised versus home extemporaneous preparation for cystic fibrosis outpatients’ parenteral antibiotic therapy: a survey on patients’ Objectives: To assess if standardised six-lobe BAL safe and leads to a greater satisfaction yield in terms of detection of infection as compared to two-lobe BAL in 1 2 3 3 3 3 J. Wdowik ,V.Nave , M. Perceval , I. Duperray , Q. Reynaud , I. Durieu , stable pre-school children with CF. Over 12 months this prospective single 2 1 2 I. Carpentier . Hospices Civils de Lyon, France, France; Hospices Civils de centre case-control study of pre-school children with CF compared 3 Lyon, Saint Genis Laval, France; Hospices Civils de Lyon, Adult Cystic Fibrosis standardised six lobe (cases) against controls undergoing traditional two Centre, Université de Lyon, Pierre Bénite, France lobe BAL using 2 × 1 ml/kg/lobe (max 20 ml/aliquot) aliquots in each lobe. Data from year 1 of SEAGULLS is presented. Objectives: Since 1995, the hospital pharmacy associated to the CF centre of Lyon has been preparing sterile treatments in the form of ready to use S102 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 portable elastomeric pumps (rPP) for CF patients with intravenous chronic infection with MRSA. However, there have been no studies on antibiotic treatment at home. Treatment is delivered for 7 days at home MRSA in adult pwCF in the UK. We looked for any association between and stored at 4°C before administration. For some antibiotics, stability in chronic infection and deprivation at our large adult UK CF centre in the rPP was not evaluated. Preparation of those antibiotics is done extempor- north of England. aneously at patient home (ePP). The objective is to compare patients’ Methods: We used the 2019 English Indices of Multiple Deprivation (IMD) satisfaction with rPP, as opposed to ePP. to calculate the deprivation index of all English adult pwCF attending our Methods: We selected patients who had received at least one course of rPP clinic (n = 291, mean age 32.5 years [SD 10.9], 59% male) by home postcode, and one course of ePP in the past five years, in order to allow a comparison and looked for any association with chronic infection with PsA (n = 222), between the two. NTM (n = 46), MRSA (n = 28) or Burkholderia spp (n = 23) using logistic A questionnaire was constructed to assess patients’ satisfaction. regression. IMD includes separate measures such as education and skills, The questionnaire was tested by 5 treated patients for opinion and a final crime and employment, and each of these was assessed. We then looked at version was obtained after slight modifications. deprivation by comparing the most deprived IMD decile with all other Results: Evaluated items are security, quality of life and general deciles. Odds ratios were adjusted for age, gender and number of hospital organization in the two courses. The results will provide patients’ overall admissions. levels of satisfaction and identify which aspects have to be improved. One Results: There was no significant association between MRSA infection and open question will allow patients’ suggestions and guide amelioration overall IMD score (adjusted OR 1.900 [95% CI 0.835, 4.322], p = 0.13), practice. The collection process is currently taking place. In our cohort, 110 however a significant association with MRSA infection was found in two patients meet inclusion criteria (83.6% adults). component measures: income deprivation affecting children (adjusted OR Conclusion: This study is being carried out as part of the ongoing research 2.478 [95% CI 1.097, 5.596], p = 0.029) and education and skills (adjusted OR on the levels of satisfaction of nurses with rPP. The study will enable a 4.779 [95% CI 2.001, 11.414], p < 0.001). There was no association with critical evaluation of our practices and is part of a process to improve the deprivation and chronic infection with PsA, NTM or Burkholderia spp. quality of our practices. Conclusions: Our data show that the most deprived pwCF are more likely to be chronically infected with MRSA, but not other common CF pathogens, P163 suggesting that deprivation may be an important consideration in UV-C decontamination reduces cystic fibrosis clinic room bacterial strategies to reduce MRSA rates. These interesting results merit further counts over existing infection control measures exploration in larger national registry data studies. M. Allenby1, G. Jones2, L. Jadkauskaite3. 1University Hospital Southampton NHS Foundation Trust, Cystic Fibrosis, Southampton, United Kingdom; 2University Hospital Southampton NHS Foundation Trust, Microbiology, Southampton, United Kingdom; 3Inivos, King’s Lynn, United Kingdom Pulmonology/Inflammation/Immunology Objectives: Cross infection between patients remains a risk in CF centres. P165 Infection control measures such as adequate air exchange and surface Correlation of clinical profile and respiratory bacteriology of adult decontamination may be variably achievable in a clinical setting with patients in a cystic fibrosis unit in Argentina limitations on time and clinical space. Decontamination with UV-C has 1 1 1 been shown to reduce surface contamination but its effect on airborne L.M. Tamburri , L.M. Cano . Universidad de Buenos Aires, Hospital del Tórax bacterial counts is unknown. We aimed to evaluate the effects of UV-C on Dr. Antonia A. Cetrángolo, Vicente Lopez, Argentina surface and air bacterial counts in clinic rooms. Objective: To assess the relationship between forced expiratory volume in Methods: Bacterial counts were performed on samples taken from air first second (FEV1), body mass index (BMI) and sputum cultures positive for (Coriolis air sampler) and surfaces (contact plates used on key sites) within Pseudomona aeruginosa, Methicillin resistant Staphylococcus aureus recently vacated clinic rooms after standard decontamination (6 samples (MRSA) and Burkholderia cepacia complex (BCC) from adult patients with from 4 clinic rooms over 2 separate clinics, surface cleaning with Clinell cystic fibrosis (CF). wipes and air filtration) and after additional UV-C decontamination (7 Materials and methods: Retrospective, descriptive and comparative samples from 4 rooms over 2 clinic dates, Ultra-V Hygiene Solutions). analysis of 64 adult CF patients assisted from February 2018 to February Results were expressed as total viable colonies (TVC) for surface samples 2019. and colony forming units per cubic metre (CFU/cu m) for air samples. Results: The average follow-up time in the adult unit is 41 months (range: Results: The addition of UV-C produced a significant reduction in all 1.6–98.6 months); median age 23 years (range: 18–73); 50% male gender; surface contamination (2.98 vs 22.27 TVC), the largest benefits being seen 86% diagnosed in childhood and 14% after 18 years old; 74% had at least one on surfaces that were not routinely wiped between patients (phone F508del mutation (31% homozygous and 43% heterozygous); median FEV1 receiver, door handle, light switch, basin and basin tap). There was no 56.5% (range: 21–107); mean BMI was 20.53 ± 2.78 SD kg/m2;no additional benefit on airborne counts (0.47 vs. 1.05 CFU/cu m, P = 0.34), statistically significant association between the decline in BMI and the though overall levels of airborne contamination seem to be low with deterioration of FEV1 (p = 0.494). The annual death rate was 7.25%; the current infection control measures. Existing surface decontamination median age of death was 23 years (range: 21–30). The predominant lung methods were effective where used (patient chair, desk, and examination pathogens were Pseudomona aeruginosa in 61% of patients; S. aureus in couch) but there was a small additional benefit from UV-C. – 54.6% (MRSA 17%) and BCC in 17%. P. aeruginosa median FEV1 52% (21 98); Conclusion: UV-C decontamination provides a significant reduction in mean BMI was 20.45 ± 2.83 SD kg/m2 with greater nutritional deterioration surface bacterial counts in a manner which is not effort dependent. There – (p = 0.018). MRSA median FEV1 51% (21 96); mean BMI was 19.7 ± 3.2 SD was a non-significant reduction in airborne bacteria compared to current kg/m2. BCC genotypes: B. cepacia, B. cenocepacia, B. vietnamiensis and air filtration system. UV-C may provide a useful adjunct to standard B. contaminans; predominance in the female gender (p = 0.003); median measures of infection control. – 2 FEV1 53% (21 106); mean BMI was 21.2 ± 2.07 SD kg/m . Conclusions: Greater nutritional deterioration is observed in patients with P164 P. aeruginosa and predominance of BCC in the female gender. Association between chronic microbial infection and deprivation in a north-west cystic fibrosis centre T.S. FitzMaurice1, M. Shaw2, D. Nazareth1, M. Walshaw1. 1Liverpool Heart & Chest Hospital, Adult CF Unit, Liverpool, United Kingdom; 2Liverpool Heart & Chest Hospital, Research Department, Liverpool, United Kingdom Objectives: Socioeconomic deprivation is associated with worse outcomes in people with CF (pwCF), and in children with CF it has also been linked to Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S103

P166 activity in sputum, L-arginine solution was incubated with heat-activated Urinary biomarkers of kidney injury in children with cystic fibrosis sputum lysates and urea production was determined by spectrophotom- S. Boardman1, M. Coffey1, 2, K. Taylor3, J. Erlich3,4, A. Jaffe2,3,5, Z. Endre3,4, etry. We investigated chemical and mechanical means to overcome C. Ooi1,2,6, S. Kennedy1,7. 1School of Women’s and Children’s Health, University heterogeneity of samples. We also tested protease inhibitors to overcome of New South Wales, Discipline of Paediatrics, Sydney, Australia; 2Molecular loss of arginase activity due to high proteolytic activity. A protease cocktail and Integrative Cystic Fibrosis (miCF) Research Centre, Randwick, Australia; with high amounts of serine and cysteine proteases was shown to improve 3Prince of Wales Clinical School, University of New South Wales, Australian sample stability. Interference from urease activity was overcome by Kidney Biomarker Reference Laboratory, Sydney, Australia; 4Prince of Wales increasing sample dilution from 2- to 8-fold. Dose-dependent inhibition Hospital, Department of Nephrology, Randwick, Australia; 5Sydney Children’s by nor-NOHA, a specific arginase inhibitor, confirmed specificity. 6 Hospital, Department of Respiratory, Randwick, Australia; Sydney Children’s 2) NO3/NO2 Airway inflammation increases NOS activity, yet resultant NO Hospital, Department of Gastroenterology, Randwick, Australia; 7Sydney may not diffuse into airways in CF but rather remain in sputum in oxidized Children’s Hospital, Department of Nephrology, Randwick, Australia form. Hence, sputum NO3/NO2 levels may better mirror NOS activation than exhaled NO. Therefore, we developed a method for assessment of total Objectives: Children with cystic fibrosis (CF) are at risk of acute kidney NO3/NO2 in sputum. In 2 steps, NO3 is converted to NO2 using NO2 injury (AKI) due to use of nephrotoxic antibiotics. Repeated episodes of AKI reductase, and NO2 to azo compound by adding Greiss reagent. may lead to chronic kidney disease which can be detected subclinically by Results: 1) A serine and cysteine protease cocktail was shown to improve urine biomarkers. We evaluated levels of known urinary biomarkers of sample stability. Interference from urease activity was overcome by kidney injury in children with CF and healthy controls (HC). increasing sample dilution from 2- to 8-fold. Dose-dependent inhibition Methods: A single-centre, cross-sectional study of children with CF and age of urea formation by nor-NOHA, a specific arginase inhibitor confirmed and sex matched HC. Urine was assayed for known urine biomarkers of specificity. kidney injury using commercially available ELISAs or immunobead-based 2) Antioxidant (e.g. DTT) interference was minimized using a correction assays. Differences in biomarker levels between (i) CF and HC and (ii) − factor (based on comparison of standard curves +/ DTT) to calculate NO3/ nephrotoxic drug use in CF, were assessed. Results expressed as median NO2 levels. [IQR]. Conclusion: The 2 cases illustrate that a “fit-for-purpose” approach to Results: 25 CF and 25 HC subjects were included (52% male, age 9.5 years method development and investigation helps overcome challenges for [5.9–12.3] and 9.4 years [5.2–12.8] respectively). 22 (88%) CF subjects were bioanalysis of sputum biomarkers. pancreatic insufficient and their median estimated glomerular filtration 2 rate was 131.6 mL/min/1.73m [115.9–146.8]. All patients were clinically P168 stable. Compared to HC, CF subjects had significantly lower levels of the The sputum proteome in cystic fibrosis lung disease and healthy biomarkers listed in Table 1. Urinary calbindin and TFF3 levels were volunteers significantly elevated in subjects prescribed nephrotoxic antibiotics 1, 2 3 3 3 2 R.W. Lord , R.E. Maher , V.M. Harman , P.S. McNamara , J.A. Smith , (Table 2). 3 1 1 R.J. Beynon , A.M. Jones . Manchester Adult CF Centre, Manchester, United Kingdom; 2The University of Manchester, Manchester, United Kingdom; 3University of Liverpool, Liverpool, United Kingdom Biomarker Units Healthy Controls (n = 25) Cystic Fibrosis (n = 25) p value Objectives: Mass spectrometry techniques can generate comprehensive protein profiles (proteomes) from biological samples. Investigating the CF – – Clusterin ng/mL 7.93 (2.58 25.07) 2.49 (1.00 8.09) 0.011 sputum proteome may provide insights into pathological processes, such IL-18 pg/mL 40.00 (10.00–50.00) 10.00 (10.00–30.00) 0.014 as those during exacerbations. This may lead to new treatments, or Albumin μg/mL 11.95 (8.28–20.62) 6.45 (5.29–12.68) 0.011 Cystatin C ng/mL 58.70 (27.59–90.75) 25.71 (12.31–49.35) 0.003 development of protein-based biomarkers. The aim of the study was to Osteopontin ng/mL 1324.69 (821.03–1548.85) 735.82 (551.96–953.25) 0.002 assess factors influencing the CF proteome. Methods: Spontaneous sputum samples were collected from CF (n = 37) [Urinary biomarker levels in HC and CF patients. IGFBP7, TIMP-2, GST-p, KIM-1, and induced from healthy volunteers (n = 33). Bottom-up shotgun MCP-1, B2M, NGAL, OPN and TFF3 were not significant.] proteomic analysis of samples was undertaken using liquid chromatog- raphy-mass spectrometry. Spirometry was measured at baseline and longitudinally, and exacerbation events recorded. For comparison of Biomarker Units No nephrotoxins Tobramycin (n = 6) Tobramycin and p relative protein abundance between cohorts, principal component analysis (n = 15) colistin (n = 4) value (PCA) and ANOVA with adjustment for false discovery rate were Calbindin ng/mL 21.8 (14.9–36.1) 305.3 (145.2–363.7) 58.6 (31.4–150.8) 0.032 undertaken. TFF3 ng/mL 573.8 (433.4–880.2) 523.2 (463.8–776.3) 1327.4 (829.4–1997.7) 0.035 Results: PCA demonstrated obvious differences in sputum proteome of healthy volunteers and CF patients, and between CF patients with varying [Urinary biomarker levels and associations with nephrotoxin exposure in CF severities of lung disease based on FEV % predicted. ANOVA found relative subjects] 1 abundance of 91 proteins significantly different (p < 0.05) between these Conclusion: Overall, children with CF have similar or lower levels of kidney groups. There were no differences noted for change in lung function and injury biomarkers compared to matched HC, with no evidence of exacerbation frequency over the preceding 12 months, or time to next subclinical CKD in this cohort. A subset of CF children with nephrotoxic exacerbation. antibiotic exposure have elevations in kidney injury biomarkers. Discussion: There were clear differences between the CF sputum proteome and that of healthy subjects, and also differences in the sputum proteome relating to baseline severity of CF lung disease. However, the sputum P167 proteome did not appear to relate to longitudinal changes in lung function Challenges and solutions in bioanalysis of sputum to support cystic and exacerbation frequency. This may reflect that severity of lung disease fibrosis clinical studies influences the proteome sufficiently, so that it masks the influence of other A.D. van Haarst1, M. Marzuki2,S.Kar2, R. Islam2. 1Celerion Belfast, Scientific 2 factors. This will need to be considered when developing biomarkers, for Affairs, Belfast, United Kingdom; Celerion Lincoln, Bioanalytical Services, example for early detection of pulmonary exacerbations. Further work is Lincoln, United States ongoing to assess the clinical significance of longitudinal changes in the Objectives: Unlike BAL, sputum sampling is not invasive and allows repeat sputum proteome in CF. sampling, yet bioanalysis has its challenges. We present 2 cases with unique challenges and solutions. Methods: 1) Arginase Activity Arginase is present in bronchial/alveolar cells and plays a key role in the pathogenesis of CF. To assess arginase S104 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P169 RV was −27,4%pred., RV/TLC was −5,6% and VTG was −7,8%pred.) and Implementing nitrogen Multiple Breath Washout - a feasibility study clinical symptoms (the change in dyspnea score was −1, cough score was C. Constant1,2,3, A. Descalço1, A.M. Silva1, L. Pereira2,3,4, C. Barreto3,4, −2,5), but not in LCI (the change in LCI was −0,5 (−9%)). Significant T. Bandeira1,2,3. 1Hospital de Santa Maria, CHULN, Department of Pediatrics, correlations between the changes in LCI and air trapping during treatment 2 Paediatric Lung Function Laboratory, Lisbon, Portugal; Hospital de Santa were found (RRV = 0,63 and RRV/TLC = 0,54). Maria, CHULN, Department of Pediatrics, Paediatric Respiratory Unit, Lisbon, Conclusions: An increased LCI indicates ventilation inhomogeneity and Portugal; 3Lisbon Academic Medical Centre, Lisbon, Portugal; 4Hospital de changes in peripheral airways (air trapping). Nevertheless, further Santa Maria, CHULN, Cystic Fibrosis Reference Centre, Lisbon, Portugal investigation is needed to define clinically significant changes in LCI.

The Lung Clearance Index (LCI), derived from Multiple Breath Washout P171 (MBW) tests, detects early changes associated to obstructive pulmonary Spirometry quality improvement exercise across a paediatric cystic disease. The availability of commercial devices has allowed its inclusion in fibrosis network the routine assessment of cystic fibrosis (CF) patients and as outcome 1 1 2 1 1 P. Lawrence , S. Mayell , K. Southern , R. Thursfield . Alder Hey Children’s measures in clinical trials. 2 Hospital, Respiratory, Liverpool, United Kingdom; University of Liverpool, Aim: to assess the feasibility of nitrogen MBW (N MBW) in a paediatric 2 Liverpool, United Kingdom lung function (LF) laboratory in children with CF, primary ciliary dyskinesia (PCD) and healthy controls. Objectives: Spirometry is a key indicator in monitoring respiratory status Methods: Throughout one year (Dec17–Nov-18), children with CF and PCD, in patients with Cystic Fibrosis (CF). Spirometry requires skilled technicians and healthy controls were recruited. On the same testing session, N2MBW to communicate with children and understand infection control issues. We (Exhalyzer D, EcoMedics AG), plethysmography and spirometry (Jaeger conducted a quality improvement exercise across a regional CF network, MasterScreen) were performed. Patients were recruited from the Paediatric whilst providing support for staff performing spirometry. Pulmonology outpatient clinic and healthy children from the local Methods: The Senior Respiratory Physiologist attended 10 network clinics community. Descriptive [median (min; max)] and comparative analysis to observe practice. Local spirometers were checked ensuring correct was done. A local ethics committee gave approval. settings and reference values. Support and training were offered to the Results: We assessed 34 children, five were excluded due to invalid MBW technicians. readings and the test was successfully repeated in two. We analysed LF data Results: 10 network clinics were visited between May 2019 and Dec 2019. 9 from 29 children: 10 CF, 6 PCD and 13 healthy controls. Patients’ group: 6 clinics used members of the CF team (mainly physiotherapists) to perform − − boys, age 13.7 (7.7;19.2) years, LCI 10.8 (7.6; 15.3), z-score FEV1 0.8 ( 2.8; spirometry, 1 clinic used the adult laboratory. The majority of technicians − − 0.4), FEV1/FVC 0.82 (0.74; 0.95), z-score MMEF 1.0 ( 2.6; 0.3). Healthy had not received formal training in spirometry. A range of spirometers were group: 10 boys, age 12.2 (8; 17.3) years, LCI 6.9 (6.5; 7.5), z-score FEV1 0.7 used. 3 clinics did not service the spirometer annually. Calibration was − − ( 0.9; 1.8), FEV1/FVC 0.88 (0.83; 0.98), z-score MMEF 0.02 ( 0.5; 1.6). LCI performed prior to use in 9 clinics. Only one clinic was using correct was higher in the patients’ group (p < 0.001). The MBW execution took 28 reference values. Technique between clinics varied: 60% had good (16; 76) minutes, with a maximum of 15 trials. The duration of the test was technique; 30% adequate and 10% poor. Only half of clinics ensured influenced by pathology, cooperation and equipment. patients washed their hands prior to spirometry. 20% did not clean Conclusions: We had a high success rate (>75%) on the first attempt at equipment in between patients and 40% of centres did not disinfect

N2MBW and throughout the first year of implementation of the technique. equipment appropriately after clinic. LCI was higher in the diseased group. The time to perform N2MBW and its Conclusion: Observation of spirometry in network clinics identified inclusion in research and daily practice must have this pragmatic significant differences in equipment and quality of technique across a experience in consideration. paediatric network. This finding is likely to be replicated in other paediatric networks. Equipment issues and incorrect reference values were easily P170 corrected. In contrast to the regional centre, there were no standards for Lung Clearance Index in the assessment of airways disease in adults cleaning and disinfection of equipment which is a vital part of infection with cystic fibrosis control. Spirometry Standards are being designed to ensure spirometry is A. Cherniak1,2, S. Krasovsky2,3, E. Amelina3, Z. Naumenko1, G. Nekludova1, performed to a high standard across our network. Networks need to K. Mikhailichenko1. 1Pulmonology Research Institute under FMBA of Russia, establish training programmes to ensure spirometry is consistent with Functional Diagnostics Department, Moscow, Russian Federation; 2State international standards. Budgetary Institution of Healthcare of Moscow “City Clinical Hospital named after D.D. Pletnev of the Moscow Health Department’, Moscow, Russian P172 Federation; 3Pulmonology Research Institute under FMBA of Russia, Cystic Different spirometry equipment produces clinically important Fibrosis Department, Moscow, Russian Federation differences in lung function measurements in adults with cystic fibrosis Objectives: The aim of this study was to determine the association 1 2 1 1,3 1,3 1, 3 I. Waller , G. Nolan , J. Mitchell , P.J. Barry , A.K. Webb , A.M. Jones . between LCI and traditional pulmonary function tests (PFTs) (spirometry, 1 Manchester Foundation Trust, Manchester Adult Cystic Fibrosis Centre, body plethysmography) in CF adults during exacerbation at the beginning 2 Manchester, United Kingdom; Manchester Foundation Trust, North West Lung and in the end of treatment. 3 Centre, Manchester, United Kingdom; University of Manchester, Division of Methods: PFTs were performed in 15 adults with CF aged 19–37 years Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine (mean 26 years) upon admission to the hospital with exacerbation (first and Health, Manchester, United Kingdom point) and after 8–14 days of treatment (second point). LCI was measured by performing multi-breath nitrogen washout test (MBNW) after PFTs. Objectives: Lung function measurement is the gold standard for assessing MBNW measurements were performed using the Easy-One Pro, MBW disease severity in CF, however there are no guidelines for which Module (ndd Medical Technologies). Dyspnea and cough were evaluated technology to use to monitor this key outcome measure. Treatment with Borg scale. decisions are often based on lung function measurements including the

Results: At the first point the median FEV1 was 42,4%pred., FVC was 66,9% recently described FIES (FEV1 Indicated Exacerbation Signal). Systematic ’ pred., FEV1/FVC was 55,1%, TLC was 121,8%pred., RV was 248,4%pred., RV/ differences in measurements may influence a Centre s standing on national TLC was 57,0% and VTG was 153,1%pred. The median LCI was 17,6 (or 298% registry reports. We sought to assess whether there was a systematic pred.). The median dyspnea score was 3, cough score was 4. There difference in results achieved in CF patients using two different spirometers. were significant correlations between LCI and PFT values (RRV = 0,87; Methods: A convenience sample of adults with CF were recruited to − − RRV/TLC = 0,83; RFEV1 = 0,81; RFVC = 0,72; RVTG = 0,66), but not with perform spirometry on the same day using heated wire (HW) and dyspnea or cough. After the treatment there were significant improve- ultrasonic (US) spirometers. All systems were calibrated daily and prior ments in PFT values (the change in FEV1 was 6,2%pred., FVC was 9,9%pred., to testing. Testing was performed by a single clinician according to ATS/ERS Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S105 guidance. Measures were also repeatedly conducted in a healthy control Results: 28 patients had at least 1 positive ENT finding. Chronic subject without lung disease. rhinosinusitis (CRS) was found in 12 (in 42,8%), most of the affected Results: In 65 assessments in the healthy control subject coefficient of patients were males, equally in all age groups and the most frequent variation in both technologies was deemed acceptable at <3%, however associated mutation was F508del/F508del and heterozygote for F508del.

FEV1 was 30 ml higher using HW technology. 20 adults with CF completed 66,6% of the patients with CRS were receiving nasal steroids (NS). Nasal the study. HW examination was performed first in 11 subjects. Mean FEV1 polyps were found in 6 patients, 5 of them are males, equally in all age and FVC were significantly higher when utilising HW technology groups, 3 of all are heterozygote for F508del, 4 of them were receiving NS, 2 (57.3 ± 22.6 vs 53.1 ± 23.3% predicted, p < 0.001 and 88.6 ± 19.3 vs patients were operated, but 1 presented recurrence. Allergic rhinitis was 79.4 ± 18.6% predicted, p < 0.001 respectively). This equated to a mean found in 7 patients (in 25%), 4 of them are males, mainly in children group,

105ml difference in FEV1 and 235 ml difference in FVC. In 9/20 subjects a 5 of them were receiving NS and the most frequent associated mutation relative difference of >10% in FEV1 was observed between the two was F508del/F508del and heterozygote for F508del. Other ENT findings: technologies. Kiesselbach’s plexus in 4 patients (in 14,2%), Nasal septum deviation in 3 Conclusion: The technology used to measure lung function may lead to patients (in 10,7%), Adenoid vegetation in 2 patients (in 7,1%). clinically important differences in CF patients. This is an important Conclusions: Chronic rhinosinusitis, allergic rhinitis and nasal polyps are consideration when comparing lung function in an individual when most frequently ENT findings in CF patients in our centre, most of them are differing equipment may have been used. CF centres should be aware of found in males and they are associated with F508del mutation. these differences when considering equipment changes and the potential for introduction of a systematic bias in their outcomes. P175 Asthma prevalence in Bulgarian cystic fibrosis patients P173 B. Gospodinova1, M. Nikolova2, D. Miteva3, K. Ketev4, E. Chachi3, Comparison of respiratory resistance measured with Forced Oscillation V. Nedkova5, N. Guenkova6, I. Hristov2, P. Perenovska3, G. Petrova3. 1Medical Technique and body plethysmography University of Sofia, Pediatric Department, Pediatric Clinic, University Hospital 2 R. Bekkema1, 2, E. Veldhoen2, B. Arets1, K. Ent van der1, J. Tersmette1. 1UMC ‘Alexandrovska’, Sofia, Bulgaria; Medical University of Varna, Pediatric Utrecht, Kinderlongziekten, Utrecht, Netherlands; 2UMC Utrecht, Pediatrische Department, Pediatric Clinic, University Hospital ‘St Marina’, Varna, Bulgaria; 3 Intensive Care, Utrecht, Netherlands Medical University of Sofia, Pediatric Department, Pediatric Clinic, University Hospital ‘Alexandrovska’, Sofia, Bulgaria; 4Medical University of Plovdiv, Objectives: Resistance of the respiratory system (Rrs) can be measured Pediatric Department, Pediatric Department, University Hospital ‘St George’, ® with Forced Oscillation Technique (FOT) (Resmond Pro ) and resistance of Plovdiv, Bulgaria; 5Medical University of Pleven, Pediatric Department, ® the airways (Raw) with bodyplethysmography (Geratherm ). In children Pediatric Clinic, University Hospital ‘G. Stranski’, Pleven, Bulgaria; 6Medical Raw might be more difficult to measure than Rrs, because they have to take University of Plovdiv, Pediatric Department, Pediatric Clinic, University place in a closed cabin, and have to breathe against a shutter. Hospital ‘St George’, Plovdiv, Bulgaria In this study we compared results of resistance measured with FOT and bodyplethysmography in children with Cystic Fibrosis (CF). Objectives: Many patients with cystic fibrosis (CF) wheeze, but it is difficult Methods: In this prospective, single-centre study we included children to determine which have concomitant asthma and which wheeze as a with CF above 6 years of age. All patients started with FOT measured at 5– result of their underlying CF lung disease. 11–19 Hz, followed by bodyplethysmography at a breathing frequency of We aimed to estimate the asthma prevalence in Bulgarian CF patients. 30/min. These measurements were performed less than 5 minutes apart. Methods: We evaluated all Bulgarian CF patient that have required A FOT measurement was considered successful when Rrs value was recurrent therapy with bronchodilator for the last 2 years. We also obtained from 10 tidal breathing curves. The bodyplethysmography was gathered the full family and medical history. We performed spirometry performed according to ERS criteria. testing with bronchodilation test, checked nasal, sputum and serum We compared both methods, using paired t-tests and evaluated inter- eosinophil counts. device measurement agreement using Bland-Altman plots. Results: A total of 108 patients out of 195 required bronchodilation therapy Results: We included 39 patients (median age of 17 years, IQR 6–20) in for the last 2 years, while 48 of them did so recurrently. From those patients which both tests were successful. We analyzed our data with a paired t-test 15 required additionally inhaled corticosteroids for maintaining overall and found a high correlation (0.834) with p = 0,000. stable condition. Positive bronchodilation test was confirmed in 8 of our Conclusion: Both the bodyplethysmograph and FOTare devices to measure patients, elevated eosinophils in sputum were found in 7 patients, while 10 respiratory resistance (Rrs). We show high agreement between both had elevated eosinophils in nasal smear. We found only one patient with measurements. elevated eosinophils in blood. All of these patients didn’t have Aspergillus or some parasitic infection. Based on the findings and history in each P174 patient we determined that 10 patients have asthma besides CF. Conclusion: Prevalence of asthma is around 6% (5.6%) in the Bulgarian CF Ear, nose and throat (ENT) disorders in cystic fibrosis patients in the Cystic Fibrosis Centre at the Institute for Respiratory Diseases in patients. Children in Skopje, Republic of North Macedonia P176 I. Arnaudova Danevska1, T. Jakjovska1, S. Momchilovikj1, 1 1 Genetics, complications and exacerbations in relation to atelectasis in E. Gjinovska-Tasevska . Institute for Respiratory Diseases in Children, CF cystic fibrosis Department, Skopje, North Macedonia, the Republic of M. Martínez Redondo1, C. Prados Sánchez1, M. Ruíz de Valbuena1, Objectives: CF patients have quite frequent ENT disorders and this study is M. Barrio Gómez de Agüero1, E. Quintana Gallego2, S. Castillo Corullón3, aimed to assess its structure and characteristics. R. Girón Moreno4, M. García Clemente5, M. Martínez Martínez6, Materials and methods: We reviewed histories of 30 CF patients (mean A. Solé Jover7, M. Blanco Aparicio8, D. Iturbe Fernández9, age 16,6 years),18 male (60%) and 12 female (40%); 12 children (0–12 years, A. Salcedo Posadas10, L. Máiz Carro11, C. Martín de Vicente12, mean age 6,66 years), adolescents (12–18 years, mean age 13,14 years) and J. Costa Colomer13, J.G. Mainz14, R. Cordovilla Pérez15. 1Hospital Universitario adults (over 18 years, mean age 32,60 years) who are followed in CF Centre La Paz, Madrid, Spain; 2Hospital Universitario Virgen del Rocío, Sevilla, Spain; at the Institute for Respiratory Diseases in Children in Skopje, Republic of 3Hospital Clínico Universitario de Valencia, Valencia, Spain; 4Hospital North Macedonia, over 12 month period from 1 January to 31 December Universitario La Princesa, Madrid, Spain; 5Hospital Universitario Central de 2019. We analysed ENT findings (evaluated by ENT examination, nasopha- Asturias, Oviedo, Spain; 6Hospital Universitario Doce de Octubre, Madrid, ryngeal endoscopy and paranasal sinuses CT scan), age, sex, treatment and Spain; 7Hospital Universitario La Fe, Valencia, Spain; 8Complejo Hospitalario associated mutation. S106 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Universitario La Coruña, La Coruña, Spain; 9Hospital Universitario de (ng*hour/ml) were obtained in girls. Significantly lower values AUC Valdecilla, Santander, Spain; 10Hospital Universitario Niño Jesús, Madrid, “nuclease activity-time” (ng*hour/ml) and peak levels of nuclease activity Spain; 11Hospital Universitario Ramón y Cajal, Madrid, Spain; 12Hospital were found in patients who received inhaled glucocorticosteroids (ICS) in Universitario Miguel Servet, Zaragoza, Spain; 13Hospital Universitario San therapy (p < 0.05). Juan de Dios, Barcelona, Spain; 14Jena University Hospital, Jena, Germany; Conclusion: The level of nuclease activity during inhalation of Dornase alfa 15Complejo Asistencial de Salamanca, Salamanca, Spain in patients with CF depends on gender, BMI and ICS therapy, which should be taken into account when prescribing this drug. The inhalation time can Objectives: Determine if the mutation and complications could be risk be selected according to the possibilities of the patient’s daily routine. factors for atelectasis and assessment of exacerbations. Further study of PK Dornase alpha will help in choosing the optimal dosage Methods: Retrospective study in 14 Spanish monographic units of CF and regimen taking into account the use of other inhaled drugs and in the Jena University Hospital. Including CF patients who have suffered development of more effective kinesitherapy regimens. Also, the data atelectasis (case group) and a control group. Variables: mutations, obtained will help determine the possibilities of using this drug from the comorbidities, pulmonary complications and exacerbations. point of view of other links in the pathogenesis of CF associated with free Results: 110 patients. 62.7% women. No demographic differences between DNA. groups: sex, weight, height and age. • Mutations: heterozygous F508del (60% cases, 52.7% controls). No P178 differences between groups. Lung transplantation and mortality in patients with cystic fibrosis • Comorbidities: No differences in pancreatic insufficiency and CFRD. under oxygen therapy • Pulmonary complications: No differences in hemoptysis, emboliza- 1,2 1 1 1 1 tion, pneumothorax and chronic bronchial infection in the last year. S. Gambazza , F. Ambrogi , A. Zolin , A. Orenti . Università degli Studi di • – Milano, Department of Clinical Sciences and Community Health, Milano, Italy; ABPA >more associated in the group with atelectasis (p = 0.001). 2 • Exacerbations: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, Cystic Fibrosis, Milano, Italy • Comparison mild-moderate and severe in the last year between Objectives: There are few studies about survival in patients with Cystic groups–> higher average number of severe exacerbations in cases Fibrosis (CF) under oxygen therapy (OT). Considering its clinical meaning (1.09 ± 1.43) versus controls (0.31 ± 0.77) (p = 0.001). and impact on patients’ lifestyle, we aimed to determine how OT is • Relationship between the number of exacerbations in the last year associated with known prognostic factors and with lung transplantation and in the year prior to atelectasis (p = 0.026,coefficient 0.309) and (LTx) and death (D). in the year after it (p = 0.001,coefficient 0.455), as well as between Methods: We considered patients ≤50 years registered in the ECFSPR from the number of exacerbations in the year before and after atelectasis 2008 to 2017. An illness-death multi-state model was fitted, denoting LTx (p < 0.001, coefficient 0.477). as intermediate state. Cox’s proportional hazard models were fitted using • No radiological improvement: greater average number of exacerba- age as time scale and left truncation corresponding to age at entry into tions in the year after atelectasis (4.67 ± 3.51) than those who ECFSPR. Models were used to estimate transition intensities and OT hazard improved (2.68 ± 2.32) (p = 0.037). ratio (HR), adjusted for known prognostic factors (age, sex, insulin, • No clinical improvement: higher average number of exacerbations in Pseudomonas aeruginosa (Pa), Burkholderia cepacia (BC), BMI and FEV % the following year (4.73 ± 3.39) than those who improved 1 predicted). (2.92 ± 2.76) (p = 0.035). Results: 58576 patients were included in the analysis and 7627 (13%) had Conclusions: - ABPA as a possible risk factor for the appearance of OT during the follow-up. 27587 (47.6%) were females, 35784 (61.1%) were atelectasis <18 yrs old, 5228 (10.6%) had FEV <40%predicted, 5185 (9.5%) were - Significant increase in exacerbations: 1 underweight (BMI z score <−2), 6386 (10.9%) used insulin, 14037 (26.9%) 1. severe in the last year between groups, had Pa, 1236 (2.4%) had BC. 2. between the year before and after the atelectasis with respect to During the follow-up, 2509 patients had LTx and 3091 patients died: 2338 the last year, before and 753 after LTx. 3. between the year before and after the atelectasis, From the multi-state model, patients in OT have higher probability of 4. no clinical-radiological improvement. having LTx (HR = 12.9, 95% CI: 11.6–14.4). The HR of death for patients in OT is 7.8 (95% CI: 6.9–8.7) before LTX, while it is 1.4 (95% CI: 1.2–1.7) after LTx. Conclusions: The need for oxygen therapy represents a turning point in P177 patients’ life, decreasing their chances of survival, with implications in the The pharmacokinetics of dornase alpha in children and adolescents post LTX period yet. Undoubtedly OT should be considered as a marker of CF with cystic fibrosis 1 2 2 2 2 disease severity, and patients with a supplemental oxygen requirement Y. Kondakova , E. Kondratyeva , S. Kostyuk , E. Ershova , A. Voronkova , should have prompt and fully clinical reassessment. Preventing respiratory 2 3 1 1 ’ V. Sherman , V. Shadrina , S. Zyryanov . Peoples Friendship University of failure with oxygen requirement remains one of the main goals of CF care. Russia, Moscow, Russian Federation; 2Research Center for Medical Genetic, 3 Moscow, Russian Federation; Perm State Medical University named after P179 Academician Ye. A. Wagner, Perm, Russian Federation A personalised internet-supported exercise and nutrition program Objective: Optimisation of Dornase alpha therapy for cystic fibrosis (CF) in increases Resolvin-D1 plasma levels paediatric practice. R.L. Knoll1, 2, B. Hillen3, S. Wirsching2, J. Klopp2, A. Kemper1, S. Gruca1, Material and methods: The level of nuclease activity was measured in 35 V. Bähner1, S. Gehring2, O. Nitsche2, K. Poplawska1. 1Childrens Hospital, patients after inhalation of Dornase alpha. University Medical Center of the Johannes-Gutenberg-University Mainz, Results: An increase in the level of nuclease activity of blood plasma after Pediatric Pulmonology, Allergology and Cystic Fibrosis, Mainz, Germany; inhalation of Dornase alpha by patients with CF was obtained. High 2Childrens Hospital, University Medical Center of the Johannes-Gutenberg- variability was observed in the dynamics of changes in the level of nuclease University Mainz, Pediatric Immunology and Infectiology, Mainz, Germany; activity during therapy with the inhaled drug Dornase alpha. Depending 3Johannes Gutenberg-University Mainz, Department of Sports Medicine, on the period of reaching the peak level of nuclease activity after inhalation Faculty of Social Science, Media and Sports, Mainz, Germany of the drug (Tmax), the patients were divided into 4 groups: Tmax 1.5 hours Objectives: There is established evidence that poor nutrition status and (1 group), Tmax 3.0 hours (2 group), Tmax 4.5 hours (3 group), Tmax 6.0 low activity levels are accompanied by high inflammation burden and rapid hours (4 group). The change in the area under the curve (AUC) “nuclease decline of lung function. Altered production of pro-resolving lipid activity-time” (ng*hour/ml) in 88.59% of cases and the PK parameter — mediators, as Resolvin-D1 (RvD1), play a key role in chronic inflammation peak nuclease activity (Cmax, ng/ml) in 89.17% is determined by the of CF pathogenesis. parameter - BMI (p < 0.0001). Higher AUC values nuclease activity-time Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S107

This study aimed to examine the hypothesis that a monitored physical P181 exercise program and an optimised nutrition status will reduce chronic Structure-function relationships in early cystic fibrosis lung disease; inflammation and improve physical fitness. impact of reducing radiation dose in computed tomography Methods: 17 patients aged 12–52 years were enrolled in the prospective K. Bayfield1, B. Kennedy1, C. Boyton1, R. Fitzpatrick1, A. Middleton1, longitudinal interventional study. Nutritional status and physical fitness O. Weinheimer2, N. Caplain1, M. Weilputz2,L.Yu3, C. Galban4, T. Robinson5, were assessed prior to study start (V1), after 3 (V2) and 9 months (V3). D. Fitzgerald1, C. Pandit1, S. Towns1, B. Bartholmai3, G. King6, Blood sampling was performed respectively. Nutritional status was H. Selvadurai1, 7, P. Robinson1,6,7. 1The Childrens Hospital at Westmead, estimated using a 3-day weight dietary protocol. Physical fitness was Respiratory, Sydney, Australia; 2University of Heidelberg, Germany, Heidelberg, assessed through cardiopulmonary exercise testing (CPET) and 6 minutes’ Germany; 3Mayo Clinic, Minnesota, United States; 4University of Michigan, walk test (6MWT). Throughout the study patients received a personalised Michegan, United States; 5Stanford University, , United States; strength and endurance training, monitored via an internet platform. 6Woolcock Institute of Medical Research, Respiratory, Sydney, Australia; 7The After 3 months food supplement with Lactobacillus rhamnosus was University of Sydney, Sydney, Australia introduced and patient received prebiotics and n-3 polyunsaturated fatty acids (fish oil capsules) if needed. Introduction: Efficient detection of progressive Cystic Fibrosis (CF) lung An ELISA Kit (Cayman Chemicals) was used to determine RvD1 plasma disease is critical for early intervention strategies. levels. Aims: 1. Define structure-function relationships between novel lung Results: Resolvin D1 levels increased significantly after only 3 months of function tests and computed tomography (CT), exercise intervention and raised further on after nutritional support. At V1 2. Assess impact of novel analysis indices on early structural disease mean plasma level was 38,6 pg/ml, at V2 60 pg/ml and at V3 mean level detection, and was 92,9 pg/ml (V1–V2 p = 0.009; V2–V3 p = 0.035). Improvement in 3. Assess impact of novel ultra-low radiation dose CT settings on these physical fitness was modest, only 3 patients extended their 6MWT during relationships. the study period. However most of the patients improved in least one CPET Methods: 50 CF subjects (≥5years) with mild/normal spirometry ≥ parameter. (FEV1 70%) will complete: Multiple breath washout (MBW), Forced Conclusion: Our data suggest that exercise and nutritional support impacts Oscillation Technique, Cardio-pulmonary exercise testing (≥8 years) and chronic inflammation in CF by promoting resolution of inflammation due spirometry directed CT (low dose and ultra-low dose (ULD); analysed using to increased Resolvin D1-levels. YACTA CT analysis platform). Results: Recruitment has completed and 31/50 (62%) subjects have P180 completed the study protocol (remaining 19 scheduled before April Characterisation of the extent of polypharmacy in adults with cystic 2020). Interim analysis (Table 1) has identified fibrosis 1. substantial structural and functional abnormality despite normal 1,2 2 2 1 spirometry, M.K. Dooney , N. Iqbal , K.J. Martin . Blackpool Teaching Hospitals NHS 2. greater sensitivity with novel MBW analysis indices and Foundation Trust, Blackpool Adult Cystic Fibrosis Service, Blackpool, United 2 3. comparable structural disease detection for ULD vs. low dose CT (data Kingdom; Manchester University NHS Foundation Trust, Manchester Adult not shown). Effective radiation dose was reduced by 78% in ULD Cystic Fibrosis Centre, Manchester, United Kingdom protocol. Objectives: People with cystic fibrosis (CF) face a heavy treatment burden which presents itself in various forms. One of which is a vast array of Table 1. medication that is to be taken daily in various formulations and routes of Interim Demographic results administration including oral, inhaled, nebulised and parenteral. Polypharmacy is well documented to reduce quality of life, increase the Parameter Result (31pax) (mean ± SD or median (range)) risk of drug interactions and adverse reactions and potentially compromise Age (years) & Gender 11.76 (6–17) & 18/31 (58.1%) adherence. We aimed to discover the extent of and characterise (Female n&%) polypharmacy in adults with CF. Height (cm & Zscore) 149.2 ± 18.7, 0.2 (−1.9–2.4) Methods: Hospital medication lists for 477 adults with CF were analysed. Weight (kg & Zscore) 43.5 ± 14.5, 0.4 (−1.0–1.5) − – All regular and when required medication was included for all routes of FEV1 (%pred & Z score) 99.4% ± 10.6, 0.1 ( 1.69 2.4) (1/31 (3%) <80%) administration as well as any oral and enteral tube supplements. Diluents FEV1/FVC (%) 84.3% ± 5.5 (0/31 <70%) – for nebulised treatments were excluded if they were not active drugs. Each Lung Clearance Index 8.68 ± 1.86, 5.3 (0.1 13.9). (22/31 (71%) LCI>7.5) (LCI & Zscore) medication was counted as one data point regardless of how many were to Clinical CT report 27/31 (87%) had structural disease; of those, be taken in a day of that specific drug. 73% gas trapping, 40% Bronchiectasis, 40% Results: Average age of population = 31.7 years. The average number of Bronchial wall thickening. medication prescribed = 14 (range 0–48) and the mode = 14. 91.8% of individuals (n = 438) prescribed ≥5 medications, 76.2% (n = 364) ≥10, 19.7% Conclusions: In this cohort, novel lung function tests and CT detected (n = 94) ≥20 and 2.3% (n = 11) ≥30. When grouped by age the average abnormality that spirometry missed, and improved sensitivity was seen number of medication prescribed for individuals aged ≤20 years = 12.0, 21– with novel MBW indices. Completed analyses across the entire cohort will 25 = 13.9, 26–30 = 15.0, 31–35 = 12.8, 36–40 = 15.0, 41–45 = 14.9, 46– describe structure-function relationships, compare sensitivity of novel and 50 = 16.5 and >50 = 15.5. conventional indices, and utility of ULD scanning. Conclusion: Polypharmacy and hyperpolypharmacy are exceptionally common in CF. Hyperpolypharmacy is highly prevalent by the time P182 individuals reach adulthood but the number of medications taken does not Audit of parental and professional perceptions of exacerbations in seem to be significantly worse with increasing age. A study looking at cystic fibrosis polypharmacy trends at an individual level over time is needed to confirm V. Harrison1, C. Onyon2. 1Worcestershire Acute Hospitals NHS Trust, if this is correct to account for potential disease differences. It is vital that 2 work is done to help reduce this medication burden and unsurprising that Paediatrics, Worcester, United Kingdom; Worcestershire Acute Hospitals NHS ways to effectively reduce treatment burden in CF is the number 1 priority Trust, Paediatrics, Worcestershire, United Kingdom from the James Lind Alliance CF top 10. Objectives: Fuch’s criteria specifies that 4 out of 12 domains are met to diagnose an exacerbation in adults with CF. In clinical practice, diagnosing an exacerbation is less clear with differences in perceptions particularly regarding children. An audit comparing practice to the application of Fuch’s criteria was undertaken, examining parental and professional perceptions of the features constituting a CF exacerbation in a paediatric clinic. S108 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Methods: A questionnaire was designed to look at the symptoms parents P184 and professionals considered to indicate a chest exacerbation, preferred Evaluation of the inflammatory cytokine network in cystic fibrosis - treatments and when their CF team should be contacted. Questionnaires ultra-sensitive assessments in blood and sputum were given out to parents of children at a network clinic and professionals P. Brennecke1, P. Doytcheva1,J.O’Hagan2, F. McNeilly2, A. van Haarst2, at a regional CF meeting. The response rate from the parents 94% (34/36) P. Struwe1. 1Celerion Switzerland AG, Fehraltdorf, Switzerland; 2Celerion and from professionals was 89% (24/27). Belfast, Belfast, United Kingdom Results: A wide range of symptoms were reported by both parents and Inflammation related to Cystic Fibrosis (CF), leads to airway obstruction and professionals. In comparison to Fuch’s criteria the majority of parental and loss of lung function, ultimately followed by patient’s death. Over the past professional respondents reported that only 1 or 2 symptoms were decades research has focused on new anti-inflammatory drugs, since the necessary to diagnose an exacerbation (77% of parental and 62% of pivotal role of dysregulated immune responses by an increased leucocyte professional responses). The majority of parental and professional infiltrate and the related cytokine secretion was observed. Among the respondents reported that increased physiotherapy was the best treatment leucocytes a dominant neutrophil infiltration, secreting the pro-inflam- followed by antibiotics for a chest exacerbation. There was variation in the matory mediators TNF-α, IL-1β IL-6 and IL-17 and responsiveness towards responses regarding when the CF team should be contacted. The majority the stimuli IL-33, GM-CSF, G-CSF and IL-8, was reported. Most recently IL- of professionals reported contact should be made after 2 days of a wet 17 was in the focus of CF research since the number of IL-17 producing cough or if unresponsive to treatment. Parent responses varied from the neutrophils inversely correlated with lung function (FEV ) in CF patients. In start of a cough to being unresponsive to treatment. 1 addition to neutrophils also macrophages haven been detected in Conclusion: There is a poor correlation between parental and professional substantial numbers showing increased secretion of TNF-α, IL1-β, IL-6, IL- opinions and Fuch’s criteria for diagnosing an exacerbation in a paediatric 8 and low amounts of IL-10, pointing towards a pro-inflammatory M1 network clinic population. This raises the question whether specific criteria phenotype, rather than an Arginase-I producing M2 phenotype. Last but are required to diagnose an exacerbation in the paediatric CF population. not least also prominent populations of TH2 and TH17 Tcells, secreting IL17 as well as IL-8 have been reported in CF patient lungs. P183 Objectives: This study aims at evaluating (dysregulation of) cytokines Increase of HLA-G in plasma of cystic fibrosis paediatric patients treated produced by various leucocytes as potential therapeutic targets/biomar- with Docosahexaenoic acid (DHA) kers for CF. Comparing CF patient sputum and blood using ultra-sensitive P. Melotti1, G. Tridello1, R. Rizzo2, S. Volpi1, M. Passiu1, I. Meneghelli1, 1 3 3 3 1 4 technologies will lead to the identification (confirmation) of key cytokines S. Cordioli , C. Sorio , G. Bergamini , E. Calcaterra , M. Boraso , M. Salmona , in sputum, not detectable so far. Furthermore, findings of this study may 4 5 1 6 ’ 1 1 L. Diomede , P. Rise , M. Cipolli , B.M. Assael ,C.DOrazio . Azienda facilitate CF patient stratification based on sputum only. Ospedaliera Universitaria Integrata Verona, Cystic Fibrosis Centre, Verona, 2 3 Methods: In the current study we explore the high sensitive technologies Italy; University of Ferrara, Ferrara, Italy; University of Verona, CFTR Lab ECLIA from MSD (Mesoscale Discovery) and SIMOA (Quanterix) in order to Daniele Lissandrini, Dept Medicine, Verona, Italy; 4Istituto di Ricerche 5 detect small but significant changes within the level of the inflammatory Farmacologiche Mario Negri IRCCS, Milano, Italy; University of Milano, Dept cytokine network in CF opposed to healthy individuals. 6 ’ Pharmaceutical Sciences, Milano, Italy; Fondazione IRCCS Ca Granda Results: To be presented. Ospedale Maggiore Policlinico, Dept Internal Medicine, Respiratory Unit and Conclusion: To be presented. Cystic Fibrosis Adult Center, Milano, Italy P185 Objectives: n-3 FA play an important role in the integrity of cellular Inflammatory systemic complications in adult cystic fibrosis patients in membranes, and exert an anti-inflammatory effect. Abnormal FA amounts a Lyon cystic fibrosis centre in plasma and cells membrane have been reported in CF patients. The 1 1 1 increase of the immune-modulator HLA-G might control an excessive M. Antoine , I. Durieu . Hospices Civils de Lyon, Adult Cystic Fibrosis Centre, activation of immune response in CF. We observed that DHA and DHA+5- Université de Lyon, Lyon, France methyltetrahydrofolate (MTHF)+B12 supplementation decreased the Objectives: We describe 21 adult CF patients out of our total cohort of 406 microviscosity of monocytes membrane suggesting a possible anti- patients diagnosed with inflammatory complications inflammatory effect. Clinical trials performed on CF patients have revealed Methods: Patients followed in our CF adult centre of Lyon (France), that n-3 PUFA supplementation modifies FA profiles in plasma and cell between January 2014 and January 2017. membranes, improves nutritional, clinical, and inflammatory parameters. Results: The majority of them were men (60%), 48% (10/21) were F508del In CF children, 5-MTHF and B12 supplementation might ameliorate cells homozygous, 48% (10/21) F508del heterozygous and 4% (1/21) had a membrane features. However, effectiveness of n-3 PUFA in CF remains mutation other than F508del. 24% (5/21) had lung transplantation. controversial. Inflammatory complications observed were episodic arthritis (13/21, This study aims to evaluate in CF children the effects of DHA supplemen- 61%), inflammatory bowel disease (3/21, 14%), rheumatoid purpura (1/21, tation and compare to those of DHA+5-MTHF+B12 supplementation, on FA 5%), pleuro-pericarditis (1/21, 5%), rheumatoid arthritis (1/20, 5%), femoral profile, inflammation, immunity, and clinical outcomes. osteonecrosis (1/21, 5%), and arthropathy related to inflammatory bowel Methods: 32 CF children received DHA, 5-MTHF and B12 or DHA for 6 disease (1/21, 5%). weeks. Before and after treatment and one month later the FA profile in 20% (2/10) of patients with episodic arthritis were tested positive for ACPA, blood, inflammatory markers in EBC and in plasma, HLA-G in plasma, and 20% (2/10) for rheumatoid factors, 33% (4/ 12) for ANA and 33% (1/3) for lung function were evaluated. cryoglobulinemia. No patients were positive for HLA B27. No patients with Results: A plasma DHA enrichment and an increase of DHA/AA ratio were inflammatory bowel disease were positive for ANCA or ANA. induced by DHA and DHA+5-MTHF+B12, without significant difference Conclusion: The relationship between autoimmunity antibodies and between the two groups. Levels of inflammatory cytokines were not episodic arthritis is probably not specific. Treatment is based on the significantly changed in plasma and in EBC after treatments in both groups. experience of doctors, as there are no well-conducted clinical trials in cystic Differently, the amount of plasmatic HLA-G increased in both groups after fibrosis related arthropathy (1). There are very few cases described in treatments. No between-group difference was observed in FEV1 at the end literature. The relationship between cystic fibrosis and the risk of of treatments. developing inflammatory bowel disease is currently unknown (2). Conclusion: Our results are consistent with previous studies showing no Recently, Lanitti and al showed a reduction of inflammation in CF mice but effects of increased plasma levels of DHA on inflammatory cytokines and also in human epithelial cells after treatment with anakinra (3). With lung function. Our findings of increased plasmatic HLA-G might suggest a similarities in pathophysiology to auto-inflammatory diseases, the ques- possible immune-modulatory effect of DHA that require further tion of anti IL-1 treatment in CF patients can be raised in order to reduce investigations. inflammatory complications. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S109

This study highlights the emergence of systemic. In our study, the uninfected. The reduction of lung function (%FEV1) after two year was prevalence of these complications remains low. Their management greater in NTHi colonised patients than in those uncolonised. remains a challenge is the specific context of CF. Results: In mice, we successfully induced long term NTHi infection with sustained bacterial load up to 14 days post challenge using both a reference P186 and a clinical strain. NTHi persistence was associated with lung chronic Macrorheology of cystic fibrosis and pulmonary inflammation inflammation, such as recruitment of neutrophils and cytokine release (KC, A. Lepissier1, C. Schmitt2, C. Straub3, H. Avril2, G. Prugnieres2, MIP-2 and IL-6) at 2 and 14 days post infection. We observed an increased D. Achimastos4, J. Patarin5, I. Sermet-Gaudelus1. 1Institut Necker Enfants burden of T cell mediated response (CD4+ and γδ cells) localised in Malades, Paris, France; 2CRCM Pédiatrie Hôpital Necker Enfants Malades, bronchus-associated lymphoid tissue (BALT)-like structures and associated Paris, France; 3CIC Necker Enfants Malades, Paris, France; 4Vaincre la with tissue remodeling marker (pro-MMP9) at 14 days post-infection. Mucoviscidose, Paris, France; 5Rhéonova, Grenoble, France Conclusion: Our results demonstrate that NTHi persistence has a pro- inflammatory activity in the human and murine lung and may contribute Objectives: Cystic fibrosis (CF) is an autosomal recessive disease causing, to fuel the exaggerated lung inflammatory burden in CF patients. among other deficiencies, chronic pulmonary disease which progressively evolves to respiratory insufficiency. Several studies suggest that the P188 abnormal viscoelasticity of respiratory secretions from CF patient could Cardiopulmonary exercise testing in cystic fibrosis: trained versus be linked to inflammation, but no study has explored this relationship in untrained vivo. This pilot study aims to establish the correlation between sputum’s V. D’Alessandro1, L. Erenchun1,G.D’Agostino2, F. Rentería1. 1Children’s viscoelastic properties and level of inflammation. Hospital ‘Sor María Ludovica’, Pulmonary, La Plata, Argentina; 2Children’s Methods: We studied sputa from 30 stable patients presenting a typical Hospital ‘Sor María Ludovica’, Respiratory Care, La Plata, Argentina form of CF. Inflammation biomarkers (IL1b, IL6, IL4, IL2, TNFa, IFNy) were quantified by electrochemiluminescence (MSD technology). Rheological Introduction: Cardiopulmonary exercise testing is a well-known, valuable characteristics of sputum were analysed by an oscillatory strain sweep test tool in the clinical evaluation of patients with different causes of exercise ® (Rhéomuco technology). limitation and unexplained dyspnea. There is very limited data on the Results: The 30 patients included in the study are from 6 to 20 years old effects of maximal exercise and exercise capacity in children with cystic (mean 13.2 years) and present a median FEV1 of 86% (29% to 121%). Among fibrosis. them 6 have chronic bronchial infection with P. aeruginosa, and 21 with S. Objectives: To assess ventilation parameters, work performed and aureus. Macro-rheology analyses show that the crossover yield stress is cardiovascular function during cardiopulmonary test in trained and between 2.66 and 207 (median 27.8); crossover yield strain between 314 untrained CF patients. and 8.27 (median 20.6), elastic force (EF) between 2.6 and 9540 Pa2 Material and methods: A cross-sectional study was made. Ventilation (median 110.81). Crossover yield stress, the critical stress that have to be parameters were assessed by minute ventilation (VE) and maximum overcome so that a fluid can flow, is significantly correlated with the voluntary ventilation (MVV), work performed (maximum VO2 in absolute concentration of IL6 (r = 0.563; p = 0.0018), IL2 (r = 0.450, p = 0.0161), IL4 values and percentage, respiratory exchange ratio (RER)) and cardiovascu- (r = 0.430; p = 0.0223). lar function (maximum Heart Rate, ECG) for interpreting maximum Conclusion: This is the first description of those rheological parameters in cardiopulmonary test. Two groups were compared: trained CF patients a paediatric CF population. These results show a significant correlation (defined as trained in a sport professionally or outside school hours) versus between sputum viscoelastic parameters and pro inflammatory cytokines untrained CF patients. The Modified Bruce protocol was used and the levels. This suggest a relationship between pulmonary inflammation and means were compared through t-test (software SPSS 24.0). mucus rheological properties. The study of sputum inflammation biomar- Results: Twenty-six patients were measured. The mean age was 13.15 ± 3 kers and rheological biomarkers is necessary for a better understanding of years and the BMI was 19.01 ± 3.47. Trained CF patients (n = 9) showed the pulmonary pathology genesis and its evolution. higher values of VO2 in absolute as percentage, VE, MVV, maximum heart rate, and RER compared to untrained patients (n = 17). Absolute values and P187 percentage of VO2 max and VE were statistically significant ( p0.01and p Unravelling the contribution to the pro-inflammatory burden caused 0.04, respectively). by the persistence of nontypeable haemophilus influenzae in cystic Conclusions: Regular physical activity should be a mainstay in cystic fibrosis fibrosis treatment. Exercise shows to be a tool for maintaining a better 1 1,2 3 4 4 1 F. Saliu , G. Rizzo , B. Sipione , S. Rizzetto , L. Cariani , D.M. Cirillo , physiological integration of the cardiovascular, respiratory, metabolic, 3 3 1, 2 1 A. Bragonzi , C. Cigana , N.I. Lore’ . San Raffaele Scientific Institute, musculoskeletal and neurosensory systems. Division of Immunology, Transplantation, and Infectious Diseases, Emerging 2 Bacterial Pathogens, Milan, Italy; Università Vita-Salute San Raffaele, Milan, P189 3 Italy; San Raffaele Scientific Institute, Division of Immunology, Structure-function relationships in early cystic fibrosis lung disease: do Transplantation, and Infectious Diseases, Infection and Cystic Fibrosis, Milan, measures of breathing mechanics during cardiopulmonary exercise 4 Italy; Fondazione IRCCS Ca’ Granda, Cystic Fibrosis Microbiology Laboratory, testing offer additional utility to oxygen uptake (VO2)? Milan, Italy A. Middleton1, K. Bayfield1, B. Kennedy1, C. Boyton1, R. Fitzpatrick1, Objectives: Nontypeable Haemophilus influenzae (NTHi) is a bacterium O. Weinheimer2, N. Caplin1, M. Wielputz2,L.Yu3, C. Galban4, T. Robinson5, commonly isolated in chronic respiratory diseases such as cystic fibrosis D. Fitzgerald1, C. Pandit1, S. Towns1, B. Bartholmai3, G. King6, H. *Selvadurai1, (CF). However, to what extent NTHi persistence contributes to the lung P. *Robinson1, *Joint Senior Authors. 1The Children’s Hospital at Westmead, inflammatory burden during CF chronic airway diseases is controversial. Westmead, Australia; 2University of Heidelberg, Heidelberg, Germany; 3The Here, we aimed at determining the pathogenic potential of NTHi Mayo Clinic, Rochester, United States; 4University of Michigan, Ann Arbor, persistence in a small cohort of CF patients and in a new mouse model. United States; 5Stanford University, Stanford, United States; 6Woolcock Methods: The pathogenic potential of NTHi persistence in CF patients in Institute of Medical Research, Sydney, Australia term of cytokines production and lung functionality has been assessed, Understanding of relationships between cardiopulmonary exercise testing respectively, by ELISA on respiratory samples and through a retrospective (CPET) indices and early structural lung disease, as detected by CT, are study in CF patients with NTHi colonisation or uncolonised by any limited to oxygen uptake (VO ) alone. pathogen. Using C57BL/6N mice, we evaluated NTHi persistence and the 2 Objectives: To describe relationships between CPET and structural lung associated pro-inflammatory profile (lung cellular infiltrates and cytokines disease on CT in mild CF lung disease. production) during the development of chronic infection at 2 and 14 days Methods: Subgroup analysis within a larger study (n = 50, age ≥5 yrs) post-infection. investigating structure-function relationships in mild CF lung disease In our study cohort, we found that CF patients chronically colonised by (FEV ≥70% predicted). CPET (treadmill, Bruce Protocol) performed in those NTHi had significantly higher levels of IL-8 and CXCL1 than those 1 S110 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

≥ 8years. CPET indices include VO2, breathing reserve (BR), ventilatory Conclusions: CF adults awaiting LUTX have minimal morphologic equivalents, dead space ventilation, % inspiratory time and tidal volume (% alteration of the right heart with slightly impaired RV systolic function, inspiratory capacity) measured at anaerobic threshold and peak exercise. without overt pulmonary hypertension. Echocardiography may be useful Structural disease quantified by YACTA CT analysis platform (in progress). as a screening tool in detecting patients with RVEF<40%. Formal statistics will include correlation and sensitivity analyses. Results: Overall recruitment completed - 18 of projected 25 with paired P191 – CPET and CT collected to date (finished by April 2020): age 9 16 yrs, FEV1 Patent foramen ovale and oxygenation in patients with cystic fibrosis 77–101% predicted. High, and comparable, rates of abnormality in BR E. Enakpene1, T.G. Liou2, J.L. Jensen3, A.P. Moe3, H. Carveth3, B.C. Cahill4, during CPET at peak exercise and structural disease (initial radiologist CT A. Tandar5. 1University of Utah, Internal Medicine, Division of Cardiovascular reporting: gas trapping 67%; bronchiectasis 40%) within this mild CF Medicine, Salt Lake City, United States; 2University of Utah, Internal Medicine, cohort. BR at peak exercise frequently abnormal (69% with BR <30%) Adult CF Center and Center for Quantitative Biology, Salt Lake City, Utah, – 3 despite preserved VO2 (77 151% predicted). United States; University of Utah, Internal Medicine, Adult CF Center, Salt Lake Conclusion: Significant, and comparable, rates of abnormality on CT were City, Utah, United States; 4University of Utah, Internal Medicine, Adult CF detected using novel CPET indices, missed by VO2. Future analyses will Center and Lung Transplantation Program, Salt Lake City, Utah, United States; formally compare sensitivity and correlation between breathing mechanics 5University of Utah, Internal Medicine, Division of Cardiovascular Medicine, during CPET and CT in this setting. Structural Cardiac Intervention Program, Salt Lake City, United States

P190 Objectives: The general population prevalence of patent foramen ovale Right ventricle dysfunction in adult cystic fibrosis patients enlisted for (PFO) is 25%, but in cystic fibrosis (CF) it is unknown. PFO may contribute to lung transplantation clinical disease and mortality in CF. This project assesses prevalence of PFO 1 1 1 2,3 1,4 in patients with CF and examines associations with hypoxemia, lung A. Guzzardella , S. Scansani , A. Grasso , M. Vicenzi , M. Nosotti , 1,5 1, 6 6 1 function and mortality. F. Blasi , A. Pesenti , V. Scaravilli . University of Milan, Department of 2 Methods: After IRB approval, we conducted a retrospective case-control Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca’ study among CF patients seen in our clinic during 2010–2017 who Granda - Ospedale Maggiore Policlinico, Cardiovascular Disease Unit, Milan, 3 underwent echocardiography with bubble study. We compared echocar- Italy; University of Milan, Department of Clinical Sciences and Community 4 diography results to those obtained from non-CF age-matched patients at Health, Milan, Italy; Fondazione IRCCS Ca’ Granda - Ospedale Maggiore the University of Utah. We performed logistic regression and proportional Policlinico, Thoracic Surgery and Lung Transplant Unit, Milan, Italy; 5 hazards modelling to understand the impact of a PFO in CF. Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Department of Results: Of 339 patients with CF, 28 had echocardiographic bubble studies; Internal Medicine, Respiratory Unit and Cystic Fibrosis Center, Milan, Italy; 6 17 (61%) had shunts: 15 had PFO and 2 pulmonary shunts; 19 (68%) had Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Department of hypoxemia. Three underwent percutaneous PFO closures. Among 81 non- Anesthesia, Critical Care and Emergency, Milan, Italy CF age- and sex-matched controls, 30 (37%) had a PFO. In age-adjusted Objective: Describe the right heart function of adult CF patients at lung logistic regression, patients with CF were more likely to have a PFO (OR transplant (LUTX) enlistment. 2.63, p = 0.03). Patients with CF with PFO more frequently had hypoxemia Methods: We retrospectively analysed and compared to standards the (OR 114, p = 0.016) and were more likely using supplemental oxygen (OR echocardiography of CF adults awaiting LUTX and assessed the relationship 11.6, p = 0.04), but percent predicted FEV1 was similar in patients with between echocardiography and invasive right heart catheterisation and and without PFO. Nineteen patients with CF (12 with PFO) died during radionuclide ventriculography (MUGA). follow up with mean time to death = 1.16 years. In proportional hazards Results: We included 49 patients (25 male, 29 ± 9 y.o.) with FEV1 31 ± 11% modelling, PFO was not significantly associated with increased CF predicted, LAS 36 ± 5; no cardiac dysfunction: invasive mean pulmonary mortality (hazard ratio 1.85, p value = 0.20). artery pressure (PAPm) 17 ± 5 mmHg, MUGA right ventricle ejection Conclusions: PFO is more frequent in CF and is associated with hypoxemia fraction (RVEF) 50 ± 9%. Compared to standards, patients had increased RV and use of supplemental oxygen. The results suggest that patients with PFO end-diastolic area and RV wall thickness, with subnormal systolic function may have oxygen requirements not reflective of the degree of lung disease. indexes (i.e., Tricuspid Annular Plane Systolic Excursion -TAPSE, tissue However, an increased hazard ratio for death associated with PFO did not Doppler positive peak systolic wave velocity -S’, Fraction Area Change-FAC) reach statistical significance. Further study with a larger number of patients and pulmonary artery acceleration time (Table 1). A good correlation may improve our understanding of PFO in CF and refine clinical between echocardiographic and invasively measured systolic PAP (PAPs) recommendations. was observed (R2 = 0.554, p < 0.001). Subnormal FAC (<49%), TAPSE (<23 mm) and S’ (<14 cm/sec) had high sensitivity and negative predictive P192 value, with low specificity and positive predictive value in predicting right Cardiovascular risk in patients with cystic fibrosis: a combined ventricle dysfunction (RVEF <40%). diagnostic approach to the detection of endothelial dysfunction in Table 1. children and adults Right heart echocardiographic analyses M. Kreslová1, A. Sýkorová1, P. Jehlička1, R. Bittenglová2, L. Trefil3, J. Sýkora1. 1Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Normal Measured Z test 2 p-value Department of Paediatrics, Pilsen, Czech Republic; Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Department of Right atrium area/BSA (cm2/m2) 8.3 ± 0.1 6.7 ± 1.8 <0.001 Pneumology, Pilsen, Czech Republic; 3Charles University in Prague, Faculty of Right Ventricle end-diastolic 8.4 ± 1.8 9.5 ± 1.8 0.001 Medicine in Pilsen, Faculty Hospital, Department of Institute of Clinical area/BSA (cm2/m2) Biochemistry and Hematology, Pilsen, Czech Republic Right Ventricle basal diameter 33.0 ± 4.5 32.4 ± 4.8 0.492 (mm) Objectives: Endothelial dysfunction (ED) is an early functional preclinical Right Ventricle wall thickness 3.0 ± 1.0 4.6 ± 1.1 <0.001 manifestation of atherosclerosis. ED patterns and the risk of cardiovascular (mm) disease in CF patients are largely unknown. Aim of the study was to Right Ventricle Fractional Area 49 ± 7 44.8 ± 9.8 0.002 evaluate cardiovascular risk by using a combined diagnostic approach by Change (%) Tricuspid Annular Plane Systolic 23.0 ± 3.5 19.9 ± 3.5 <0.001 measuring Reactive Hyperemia Index (RHI) and specific biomarkers in Excursion (mm) comparison by age and healthy controls (HC). Pulmonary Artery Acceleration 130 ± 20 96.7 ± 23.6 <0.001 Methods: A total of 22 CF subjects (17 CF children) and the same number of Time (ms) age-matched controls were enrolled. We evaluated RHI using a new S’ vel RV (cm/s) 15.0 ± 2.5 11.4 ± 2.0 <0.001 noninvasive plethysmographic method and measured plasma concentra- PAPs (mmHg) 29 (24–38) tions of four biomarkers related to ED: VCAM-1, ADMA, high-sensitive CRP Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S111

(hsCRP) and E-selectine. We sought mutual correlations RHI and modulators may alter the immune response in CF. In this context, we biomarkers within individual groups. evaluated six cases of unusually severe pneumonia under therapy with Results: No statistically significant difference in RHI between the test CFTR modulators. groups with CF children was found but we confirmed the decreasing trend Methods: Four patients’ clinical courses have been analysed due to severe of RHI since adolescence and significantly lower RHI values in CF adults pulmonary infections with focus on clinical data and radiological findings (p < 0,05), confirming the progressive development of atherogenesis and as well as microbiology. worsening of ED with age. Biochemical parameters showed significantly Results: In total, 4 patients have been included into the study. Three higher levels of hsCRP (p < 0,005), sVCAM-1 (p < 0,001) and E-selectin patients were female. Age was between 20 and 51 years. In one case, (p < 0,001) in CF patients. tezacaftor/ivacaftor and in three cases lumacaftor/ivacaftor was used. All Conclusion: The important outcome is the development of RHI with age in patients were homozygous for F508del. In all cases CT scans revealed new CF subjects. The results of our study suggest a possible occurrence of ED in acute infiltrates caused in two cases by bacteria and in two cases by fungi. CF patients, associated with a higher risk of premature manifestation of All patients responded to the anti-infective treatment. In all patients, atherosclerosis. Elevation of three established biomarkers in CF patients modulator therapy was continued. already in childhood with not yet proven RHI but with significantly Conclusion: CFTR modulator therapy may lead to changes in immuno- reduced RHI in adults and lipid changes (significantly lower levels of HDL logical mechanisms that may result in increased susceptibility to serious cholesterol) indicate the possible occurrence of ED with specific risk factors infections. Further research is required to understand the impact of CFTR in CF and gradual progression of endothelial changes with age. The modulator therapy on immunological processes in CF lung disease. conclusions show the possibility of using this method for the detection of ED and subsequent evaluation of cardiovascular risk of CF children and P195 adults in the long term. Real-life experience with CFTR modulators in Latin American cystic fibrosis patients homozygous p.F508 P193 1 1 1 1 1 A. Teper , V. Rodriguez , S. Lubovich , S. Zaragoza , F. García Bournisen . Impact of ivacaftor on polypharmacy in adults with cystic fibrosis 1 Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina M.K. Dooney1,2, N. Iqbal2, K.J. Martin2. 1Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool Adult Cystic Fibrosis Service, Blackpool, United Objective: To report our real life experience on the use of the lumacaftor/ Kingdom; 2Manchester University NHS Foundation Trust, Manchester Adult ivacaftor combination in patients with homozygous CF p.F508 in our centre. Cystic Fibrosis Centre, Manchester, United Kingdom Patients and methods: We conducted a prospective, single centre, cohort study of patients with a confirmed diagnosis for CF homozygous p.F508, Objectives: Since its introduction to the UK in 2013 ivacaftor (IVA) has treated with a CFTR modulator. Clinical records, lung function and revolutionised treatment in cystic fibrosis (CF). Those eligible for treatment laboratory tests of patients with at least 6 months of follow up were have benefitted from dramatic improvements in lung function and analysed. exacerbation rates as well as significantly lower rates of CF-Related Results: 16 patients were included in the analysis. Average follow-up: 263 Diabetes, liver disease and gastrointestinal complications. We aimed to days ± 159. Mean age: 12.1 years ± 4.7 (9/16 males). 9 patients received assess if the introduction of IVA has had any effect on polypharmacy that is MR lucaftor (lumacaftor 200 mg, ivacaftor 125 mg) and 7 patients highly prevalent in adults with CF. MR Orkambi (lumacaftor 150/100, Ivacaftor 188/125), according to age. Methods: Hospital medication lists for 477 adults with CF analysed. All Clinical, respiratory and nutritional indicators can be found in Table 1. Drug regular and when required medication was included for all routes of adverse events were relatively rare (4/16) and mild. administration as well as any oral and enteral tube supplements. Diluents for nebulised treatments were excluded if they were not active drugs. Each medication was counted as one data point regardless of how many were to N = 16 Pre Treatment Intra Treatment p be taken in a day of that specific drug. Data was then compared for individuals taking and not taking IVA. This data was collected prior to the Weight Z Score −0.62 ± 1.1 −0.35 ± 1 0.1 introduction of second generation CFTR modulators in the UK. IMC Z Score −0.30 ± 0.9 0.11 ± 0.7 <0.005 Results: Average age of population = 33.2 years (n = 37) IVA vs 31.6 years FEV1 86.8 ± 23.7 93.9 ± 22.1 <0.05 (n = 440) non-IVA. The average number of medications prescribed = 12.9 Severe exacerbations 10/16 4/16 <0.05 Moderate exacerbations 12/16 7/16 <0.05 (range 4–21) IVA vs 14.2 (range 0–48) non-IVA p = 0.12. Prescribed Less expectoration 9/16 <0.01 medication rates were lower for IVA vs non-IVA across almost all age Less dyspnea 6/16 <0.05 ranges: ≤20years = 10.3 vs 12.1, 21–25 = 11.5 vs 14.1, 26–30 = 13.9 vs 15.1, 31–35 = 10.0 vs 13.0, 36–40 = 13.6 vs 15.2, 41–45 unable to compare, 46– [Clinical, respiratory and nutritional indicators before and after treatment] 50 = 13.8 vs 17.0 and >50 = 19.5 vs 14.8. Conclusion: IVA reduces the extent of polypharmacy in adults with CF, Conclusions: The use of CFTR modulators in our patients with CF likely due to reduced rates of CF-related complications, but not to a homozygous p.F508 showed a statistically significant and clinically significant extent. This effect may be greater in the distant future as IVA has relevant improvement in lung function, nutritional status and respiratory been initiated in younger age groups and potentially preventing or delaying symptoms and a decrease in respiratory exacerbations. These results, the more CF-related complications than for those who started IVA as an adult. first reported to our knowledge in a Latin American cohort, mirror those But for the foreseeable future CFTR modulators will not significantly previously reported in other regions. decrease polypharmacy in adults with CF. P196 P194 Effects of lumacaftor/ivacaftor on physical activity and exercise Severe pneumonia under therapy with CFTR modulators - a study of tolerance in cystic fibrosis: an Italian multicentre study four cases and discussion of possible pathomechanisms A. Porcella1, A. Gramegna2, M. Di Paolo1, M. Vicenzi3, I. Rota3, C. Biglia4, P. Eschenhagen1, C. Schwarz2. 1Charité - Universitätsmedizin Berlin, B. Messore4, E. Leggieri1, F. Blasi2, P.Palange1, D. Savi1. 1Sapienza University of Department of Pediatric Pneumology, Immunology and Intensive Care Rome, Department of Public Health and Infectious Diseases, Rome, Italy; Medicine, Cystic Fibrosis Center, Berlin, Germany; 2Charité 2University of Milan, Department of Pathophysiology and Transplantation, Universitätsmedizin Berlin, Department of Pediatric Pneumology, Immunology Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult and Intensive Care Medicine, Cystic Fibrosis Center, Berlin, Germany Center, Milan, Italy; 3University of Milan, Department of Clinical Sciences and Communty Health, Milan, Italy; 4Azienda Ospedaliera Universitaria San Luigi Objectives: The introduction of CFTR modulators represents a milestone in Gonzaga, Adult Cystic Fibrosis Center, Orbassano, Italy the therapy of Cystic Fibrosis (CF). It is known that the immune response in CF is dysregulated, which is both dependent on the CFTR defect and on Objectives: The combination of lumacaftor and ivacaftor (LUM/IVA) has chronic inflammatory processes. Therefore, it can be assumed, that CFTR been approved for treatment of cystic fibrosis (CF) patients homozygous for S112 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 the Phe508del mutation. Only one report is available detailing the positive P198 effects of LUM/IVA on physical activity (PA) and exercise tolerance. The aim Diagnostic and therapeutic approach of atelectasis as a pulmonary of this study is to assess the long-term impact of this therapy on daily PA complication in cystic fibrosis and exercise tolerance. M. Martínez Redondo1, C. Prados Sánchez1, M. Ruiz de Valbuena1, Methods: In this 12 month-long multicentre study, lung function and M. Barrio Gómez de Agüero1, E. Quintana Gallego2, S. Castillo Corullón3, exercise tolerance will be prospectively evaluated through spirometry and R. Girón Moreno4, M. García Clemente5, M. Martínez Martínez6, cardiopulmonary exercise testing (CPET) in a cohort of CF patients A. Solé Jover7, M. Blanco Aparicio8, D. Iturbe Fernández9, candidate to treatment with LUM/IVA. CPET-related measurements will A. Salcedo Posadas10, L. Máiz Carro11, C. Martín de Vicente12, ’ 13 14 15 1 include: minute ventilation, oxygen uptake (V O2), indices of ventilatory J. Costa Colomer , J.G. Mainz , R. Cordovilla Pérez . Hospital Universitario efficiency, oxygen saturation, registered at peak exercise and throughout La Paz, Madrid, Spain; 2Hospital Universitario Virgen del Rocío, Sevilla, Spain; the test. Daily PA will be monitored using a multi-sensor armband 3Hospital Clínico Universitario de Valencia, Valencia, Spain; 4Hospital (SenseWear Pro3 Armband, SWA) that patients will wear at home for Universitario La Princesa, Madrid, Spain; 5Hospital Universitario Central de seven full consecutive typical days. Health-related quality of life will be Asturias, Oviedo, Spain; 6Hospital Universitario Doce de Octubre, Madrid, assessed by the adult version of the revised Italian CFQ-R questionnaire. All Spain; 7Hospital Universitario La Fe, Valencia, Spain; 8Complejo Hospitalario the procedures will be performed at baseline and at 6 and 12 months after Universitario La Coruña, La Coruña, Spain; 9Hospital Universitario de initiation of LUM/IVA therapy. Pulmonary exacerbations will be prospect- Valdecilla, Santander, Spain; 10Hospital Universitario Niño Jesús, Madrid, ively recorded throughout the whole study length. Spain; 11Hospital Universitario Ramón y Cajal, Madrid, Spain; 12Hospital Results: Five adults with CF (median age 30 years (range 28–43 years); Universitario Miguel Servet, Zaragoza, Spain; 13Hospital Universitario San – – 2 14 median FEV1 75 (68 113)% pred; median BMI 22.1 (17.1 24.2)kg/m ) were Juan de Dios, Barcelona, Spain; Jena University Hospital, Jena, Germany; ’ 15 recruited between June and October 2019. Baseline median V O2 peak value Complejo Asistencial de Salamanca, Salamanca, Spain was 27.0 (24.9–38.4)ml/min/kg, corresponding to 67.0 (59.7–110.1)% predicted. Objectives: Evaluate the radiological characteristics of atelectasis and its Conclusions: Preliminary data collected after 6 months on LUM/IVA treatment. therapy will be presented at the ECFC 2020 event. Methods: Retrospective and longitudinal study in 14 Spanish monographic units of CF, as well as the German Jena University Hospital. Inclusion of P197 patients with CF who have suffered atelectasis (case group) and a control The effect of ivacaftor on clinical trajectory of adults with cystic fibrosis group. Variables: atelectasis location, imaging study, treatment and clinical carrying a R117H mutation and radiological improvement. 1 1 2 1 1, 3 Results: 110 patients (55 cases and 55 controls). Prevalence of atelectasis C. Rutherford , C. Bradley , C. McKeown , S. Caskey , D.G. Downey , 4,5 1 3.91%. C. Addy . Belfast Health and Social Care Trust, Adult CF Centre, Belfast, 2 • Location: Lobar (58.2%) and in the right lung, mainly in middle lobe United Kingdom; Belfast Health and Social Care Trust, Pharmacy Department 3 (ML). Belfast City Hospital, Belfast, United Kingdom; Queens University Belfast, 4 • Imaging study: 5 chest x-rays for diagnosis and resolution (9.1%), 43 CT Centre for Experimental Medicine, Belfast, United Kingdom; Queens scans for diagnosis (78.2%), 2 CT scans for resolution (3.6%) and 5 CT University Belfast, Centre for Medical Education, Belfast, United Kingdom; 5 scans for diagnosis and resolution (9.1%). Belfast City Hospital, Adult CF Centre, Belfast, United Kingdom • CT at diagnosis: most frequent finding diffuse bronchiectasis with Objectives: Ivacaftor is licenced for people with CF (PWCF) and a R117H mucoid impaction (36.5%). mutation, with trial data suggesting modest improvements in ppFEV1 in • CT at resolution: more frequent finding cylindrical and varicose the short term. In Northern Ireland, the mutation is more prevalent bronchiectasis (7.3%). (approximately 20%), enabling comparison of clinical trajectory in PWCF • Medical treatment: with R117H mutations, on and not on IVA therapy. • – Methods: Electronic care records for PWCF attending the NI Regional Adult Comparison of the treatment of the last visit of both groups > CF Centre with R117H mutations were reviewed (n = 55). Baseline significance use of inhaled corticosteroids (p = 0.01). • demographics were recorded annually. Clinical trajectory through 2015– Comparison of pre-atelectasis treatment and last visit (case – 2019 was assessed by annual measurement of mean ppFEV , IV days and group) >significance use of DNAse (p = 0.002), hypertonic saline 1 (p = 0.006), colimycin (p = 0.007), LABA (p = 0.001) and SABA percentage ppFEV1 decline. Comparison between those prescribed and not prescribed IVA are reported at each time point. (p = 0.008). • Results: At baseline the R117H cohort had mean (SD) age 40 (12) years, Fibrobronchoscopy: Was performed in 22 patients (40.7%), with saline being the most used substance No significance between its mean weight 75.9 (18) kg and mean ppFEV1 85 (17) %. Eighteen percent were chronically colonised with Pseudomonas aeruginosa (Pa) (n = 10) and performance and clinical-radiological improvement (p = 1.00). • 24% were pancreatic insufficient (n = 13). Clinical-radiological improvement: Clinical improvement in 26 Twenty two percent received IVA, with most (n = 8) commencing in 2015, patients (48.1%), no radiological resolution in 32 patients (58.2%). and 4 in 2016. There were no significant differences in age, ppFEV1 or Conclusions: - The most frequent location was in the right lung, mainly in ≥ weight between the cohort receiving IVA and those not (p 0.05). ML. The most frequent radiological finding was bronchiectasis. – Between 2015 2019, ppFEV1 decreased significantly in those not pre- - Greater use of inhaled corticosteroids in the case group. Strengthening the scribed IVA [87 (18) vs 82 (21)] % [p = 0.02], while in those receiving IVA the use of mucolytics, colimycin and β2-agonist bronchodilators after the onset decline in ppFEV1 was not significant [78 (14) vs 75 (15)] % [p = 0.27]. There of atelectasis. was a trend towards a greater rate of lung function decline in the group not - No significance between the use of fibrobronchoscopy and subsequent − − on IVA compared to those on IVA [ 5.5 (9.3) vs 3.5 (5.55] % [p = 0.35]. IV clinical-radiological improvement. days were significantly higher in the IVA group compared to those not on IVA [13 (18) vs 11 (38)] [p = 0.02]. Conclusion: In R117H adults, IVA has positive effects on lung function over a 5 year period, with a trend towards a reduction in the rate of decline. With wider UK access to IVA, there is an opportunity for further research to understand the effects of IVA on clinical trajectory in PWCF with the R117H mutations. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S113

P199 with the potentiator VX770, in order to identify biomarkers related to the Cystic fibrosis plus systemic lupus: a relation of inflammatory diseases efficacy of the therapy. P. Sanseverino1, M. Farias1, M. Michels2, M.T. Sanseverino3, P.J. Marostica4. We used PBMCs and/or monocytes, isolated from CF patients carrying 1Universidade Federal do Rio Grande do Sul, PPG Saúde da Criança e do residual function mutations and eligible for Ivacaftor therapy, to perform Adolescente, Porto Alegre, Brazil; 2Universidade Federal do Rio Grande do Sul, both CFTR activity assay, by using HS-YFP method, and proteomic analyses Departamento de Genética, Porto Alegre, Brazil; 3Hospital de Clínicas de Porto through nano-LC chromatography and high-resolution mass spectrometry. Alegre, Serviço de Genética, Porto Alegre, Brazil; 4Hospital de Clínicas de Porto Our results show that this approach is able to identify specific leukocytes Alegre, Serviço de Pneumologia Pediatrica, Porto Alegre, Brazil proteomic profiles related to a restored CFTR activity following the ex vivo cells treatment. Particularly, the preliminary bioinformatic elaborations Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of evidenced that proteins involved in the leukocyte transendothelial unknown cause that affects almost every body system. CF is also an migration, focal adhesion and regulation of actin cytoskeleton are down- inflammatory disease and studies suggest the presence of inflammation in regulated by VX770 treatment. These results, following the comprehension CF airways is independent of a previous infection. of the molecular events involved in the pathways, allow us to identify those We present two cases of female CF patients with SLE diagnosis followed at a specific biological functions related to the CFTR activity restored following CF referral center in Southern Brazil. Studies showed increased mucus the cells treatment. clogging and lung injury in CF are associated with neutrophil cytotoxins, The identification of biochemical markers, associated with drug response extracellular DNA, and neutrophil extracellular traps (NETs). Dysregulated in a readily available source of primary cells, could be used for the NET formation or clearance has been associated with CF, chronic evaluation/prediction of the efficacy of new therapies targeting the defect inflammatory, and autoimmune disorders. The relationship between CF of Cl- transport in cystic fibrosis. and autoimmune disorders has been a matter of discussion in medical literature. P202 The first patient is a 18yo patient with two CF pathogenic variants: p. Sweat proteomics for cystic fibrosis diagnosis and personalised therapy F508del plus 1812–1G->A. Her CF diagnosis was on clinical grounds at the 1 2 1 1 1 2 B. Burat , A. Reynaerts , D. Baiwir , M. Fléron , G. Eppe , T. Leal , age of 3 months. She has severe lung disease, with a 35% of predicted FEV . 1 1 1 G. Mazzucchelli . University of Liege, Mass Spectrometry Laboratory, MolSys The Shwachman-Kulczycki score is 55. SLE diagnosis was when she was 11 2 Research Unit, Liege, Belgium; Université Catholique de Louvain, Louvain yo when she presented thrombocytopenia, ANA (antinuclear antibody) Center for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche 1:160 with speckled pattern, low C4 level, coombs +++ and intermittent Expérimentale et Clinique (IREC), Louvain, Belgium arthralgia. Our second CF patient had a positive neonatal screening and has two CF pathogenic variants identified: p.F508del and p.Gly551Asp. She also In clinical routine, the diagnosis of cystic fibrosis (CF) is still a challenge due has a severe lung disease and very recently had a lung transplant. Her to the limitations of the sweat test. Besides, the physiology of sweat previous FEV1 was 24% of predicted. The Shwachman-Kulczycki score is 40. remains partly unexplored in both normal & pathological (e.g. CF) Her SLE diagnosis was based on cutaneous rash, arthralgia and myalgia, conditions. Meanwhile, sweat composition has been already linked to with Groton skin lesions and heliotrope, ANA (antinuclear antibody) 1:320 disease-specific profiles of non-electrolytes (i.e. proteins, peptides & with nuclear pattern, low C4 level and coombs ++. Both patients are metabolites). chronically colonized by PA and pancreatic insufficient. Nowadays, the promise of sweat as a biofluid of interest for diagnosis & This inflammatory process may be partly responsible for severe disease in personalised therapy becomes a reality, thanks to the possibility of a both of these patients. Physicians should be aware of this to further standardised sample collection along with the access to sensitive analytical investigate other inflammatory diseases in female teen patients that show techniques. In the current study, the collection, sample preparation, LC-MS/ lung function loss. MS analysis & data processing were all optimised & applied to the proteomic profiling of sweat. Individual sweat secretion from 30 healthy volunteers (HV, 15 male, 15 female, no CF history, normal sweat test) was stimulated by pilocarpine iontophoresis (1.5 mA, 5 min) & collected for 30 min (Macroduct). First, Cell Biology/Physiology/Clinical Trials/New individual sample preparation consisted in the separation of proteins from Therapies metabolites & peptides by precipitation. Then, the protein fractions were reduced, alkylated & trypsin-digested before analysis by UPLC-MS/MS (M- Class, Waters, Q-Exactive +, Thermo). The proteins were identified & P201 quantified using MaxQuant (v.1.6.6.0, Uniprot Homo sapiens). Identification of new leukocytes biomarkers directly related to a Analysing the protein fractions, nearly 500 proteins were identified & restored CFTR activity by shotgun proteomic analysis quantified in each HV sample. These last results outperformed past studies 1 1 1 2 2 3 A. Franchi , M. Pedrazzi , R. De Tullio , C. Castellani , R. Casciaro ,F.Cresta , on pooled sweat, collected in a similar or less standardised, more 4 5,6 4 1 1 M. Patrone , M. Manfredi , E. Marengo , M. Averna . University of Genova, contamination-prone way, using similar LC-MS/MS platforms. Most 2 Department of Experimental Medicine, Genova, Italy; Hospital, Regional CF proteins were linked to catalytic activity & metabolism, cell adhesion & 3 Center IRCSS G.Gaslini, Genova, Italy; Hospital, Regional CF Center IRCSS G. cytoskeleton, or, immunity. 4 Gaslin, Genova, Italy; University of Piemonte Orientale, Department of In conclusion, standardised sample collection coupled to adapted shotgun 5 Sciences and Technological Innovation, Alessandria, Italy; University of proteomics significantly increased the sweat proteome coverage. Our Piemonte Orientale, Department of Translational Medicine, Novara, Italy; results prove the proteomic profiling of sweat is promising to highlight 6 ISALIT, Novara, Italy potential HV vs CF differences, discover candidate CF biomarkers. Leukocytes are recognised in the scientific literature not only as key P203 components of the pathogenetic events associated to cystic fibrosis but also Media impact on phenotype and function of an established airway as a valuable source of cellular biomarkers to be evaluated during the epithelial cell line progress of treatment response. Our previous studies suggest that, CFTR 1 2 2 2 2 activity can be assayed using leukocytes from healthy donor as well as from G. Livnat-Levanon , J. Moncivaiz , L. Strecker , A. Ostmann , J. Clancy , 2 1 2 CF patients in order to monitor the channel activity before and during J. Brewington . Technion, Carmel Medical Center, Haifa, Israel; Cincinnati therapy. Shotgun proteomic analysis is a powerful technique able to Childrens Medical Center, Cincinnati, United States identify and quantify thousands of proteins in a biological sample. Objectives: CF is caused by mutations in the gene coding for CFTR. Wild The goal of our study is to identify specific proteomic profiles, related to a type (WT) and F508del CFTR transduced CFBE41o- cells are a human restored CFTR activity in CF leukocytes before and after ex vivo treatment airway cell line frequently used in CF-related research. Cell behaviour may be influenced by growth conditions. S114 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Aim: To determine the impact of media on CFBE41o- growth, resistance, P205 ion transport, and expression of airway cell markers. Diminishing returns or sustained gains? A real-world long-term follow Methods: CFBE41o- cells stably transduced with CMV-promoter driven up of outcomes associated with ivacaftor use WT or F508del were expanded in DMEM/F12 with 10% FBS MEM (Base) A. Bull1,F.Frost1, D. Nazareth1, M. Walshaw1. 1Liverpool Heart and Chest media. Cells were passaged onto permeable inserts and exposed to 4 Hospital, Liverpool, United Kingdom different media (Base, USG, ALI, Pneumacult) for 7–10 days and VX-809 was applied for 72 hours to correct F508del CFTR. RNA levels were measured by Objectives: CFTR modulatory therapies are likely to prove “game- RT qPCR, protein expression assessed by immunoblotting and immuno- changers” for people with CF (pwCF), but they are expensive and their fluorescence. Ion transport was measured in Ussing chambers. long-term efficacy is unknown. One such modulator, ivacaftor (iva), Results: wtCFTR cells in Base media expressed >5x more CFTR than the effective in gating mutations, has been available in the UK for more than other media (all p < 0.001), Total F508del CFTR expression was slightly 5 years: we wished to study its long term clinical effect in our pwCF. increased in PC media (p < 0.01). F508del and wtCFTR maturation was not Methods: We looked at lung function, sweat chloride and pulmonary impacted by media selection. F508del CFTR function was minimally exacerbation rates in all 23 pwCF taking ivacaftor at our large adult CF impacted by media choice, In contrast wtCFTR function was greatly centre (n = 347). We used the Kruskal-Wallis test (significance at the 5% reduced in non-Base media (all p < 0.0001). VX-809 and genistein had level). similar corrective/potentiating effects on F508del CFTR in the different Results: Over a period of 7 years, there was a sustained reduction in sweat media conditions. Media choice had large effects on epithelial/mesenchy- chloride (p < 0.01), pulmonary exacerbations (p < 0.02), and IV antibiotic mal balance and the direction of these changes was dependent on WT use (p = 0.02), with maintenance of the immediate improvement in versus F508del CFTR expression. Media selection had minimal impact on spirometry following iva initiation. See table 1. gross morphology, mucus production or ciliation. Table 1. Conclusion: Different media alter key characteristics of airway epithelial cell line including epithelial/mesenchymal balance and CFTR expression/ function. These differences are dependent on wtCFTR and F508del CFTR Sweat Chloride %predicted Days of IV Number of expression. Our results indicate that media selection may critically impact [mmol/L] FEV1 Median antibiotics annual study results, particularly for comparisons between wt and F508del CFTR median (IQR) (IQR) per pwCF exacerbations (mean ± SD) per patient and cellular differentiation state. (mean ± SD)

P204 Pre-ivacaftor 99 (91.3–102.8) 72 (45.5–86.3) 13.1 ± 34 1.13 ± 2.5 A check of the organoid FIS assay reproducibility when performed in a Year 1 40.5 (32.5–46.5) 80.5 (52.5–102) 6.7 ± 13 0.85 ± 1.7 newly established local lab Year 2 39.5 (30–57.5) 84 (57.8–98) 9.0 ± 19 0.84 ± 1.7 – – 1 1 2 2,3 3 Year 3 42 (28.5 62.5) 87 (68.3 97) 9.9 ± 27 0.60 ± 1.5 E. Furstova , T. Dousova , I.A.L. Silva , R. Centeio , K. Kunzelmann , – – 2 1 1 Year 4 50.5 (40.3 62.0) 84.5 (65.6 99.3) 7.3 ± 16 0.61 ± 1.0 M.D. Amaral , P. Drevinek . Charles University, 2nd Faculty of Medicine, Year 5 48 (33–46.5) 89 (54–100) 12.0 ± 20 0.95 ± 1.8 Department of Paediatrics 2nd Faculty of Medicine and Motol University Year 6 38 (33–46.5) 80.5 (58.5–96.4) 12.9 ± 25 0.75 ± 1.2 2 Hospital, Prague, Czech Republic; University of Lisboa, Faculty of Sciences, Year 7 35 (34–55) 77 (49–100.3) 8.4 ± 16 0.5 ± 0.8 BioISI - Biosystems & Integrative Sciences Institute, Lisbon, Portugal; 3University of Regensburg, Department of Physiology, Regensburg, Germany Conclusion: The improvement in clinical parameters associated with the Intestinal organoids from individuals with CF were shown to help to introduction of ivacaftor has been maintained in our pwCF, suggesting that identify responders to CFTR modulator drugs. To be able to screen for the introduction of CFTR modulators will continue to have a profound responders locally, we strive to establish an organoid lab at the Prague CF effect on the CF condition. centre. Objectives: To perform lab-to-lab comparison of the Forskolin Induced P206 Swelling (FIS) assay between the newly established Prague lab and the Drug allergy to CFTR modulator therapy associated with lumacaftor- state-of-the-art organoid lab in Lisboa. specific CD4+ T lymphocytes Methods: We performed the FIS assay on organoids derived from 3 J. Roehmel1, M. Ogese2, E. Manuel2, J. Farell2, R. Alexander1, M. Mall1, 3, subjects (SJ) with CF (CFTR genotypes of SJ A: F508del/F508del; SJ B: 2789 D. Naisbitt2. 1Charite - Universitätsmedizin Berlin, Pediatric Pneumology, +5G>A/CFTRdele2,3; SJ C: W57G/3272–26A>G) using forskolin (fsk) alone Immunology and Critical Care Medicine, Berlin, Germany; 2University of or fsk with the CFTR modulators tezacaftor(teza) or ivacaftor(iva) Liverpool, Liverpool, UK, MRC Centre for Drug Safety Science, Department of individually and in combination. Rectal biopsies were taken in Prague, Molecular & Clinical Pharmacology, Liverpool, United Kingdom; 3Berlin transported to Regensburg to set organoid cultures and then to Lisboa to Institute of Health (BIH), Berlin, Germany perform FIS assays. Once the Prague lab opened, organoids were transported on dry ice back to Prague for re-culture and to redo FIS assays. Objectives: Although patients with CF have an increased risk to develop T Results: The responses to the tested compounds were reproducible cell mediated allergy against antibiotics, the risk of allergic reactions to between labs. SJ A’s organoids exhibited the area under curve (AUC) CFTR modulators remains unknown. We report a hypersensitivity reaction value for teza/iva at 0.8 μM fsk of 650 in Lisboa and 1046 in Prague. to lumacaftor in a 20a old patient with CF (F508del homozygous), Organoids of SJs B and C demonstrated residual function of the CFTR at advanced lung disease and known allergy to piperacillin. The patient 0.8 μM fsk with AUC of 470 and 1700, respectively, in Lisboa, and AUC of suffered from a severe generalised exanthema two weeks after the 1300 and 2800, respectively, in Prague. Data from both labs indicate that initiation of lumacaftor/ivacaftor, which led to a hospitalisation and a rescue of CFTR function was best by teza/iva at 0.8 μM fsk. discontinuation of treatment. Conclusion: This initial evaluation of the FIS assay performance at the Methods: The aims of this study were: (i) to diagnose allergy to CFTR newly established Prague lab showed satisfactory findings in terms of the modulator using in vitro assays and (ii) to characterise the phenotype/ assay reproducibility. These encouraging results indicate that the method is function of drug-specific Tcell clones (TCC) and characterise the pathway of well transferable to less experienced sites. Importantly, results showed the T cell activation. Lymphocyte transformation test and IFN-gamma assays same patterns of swelling response in both labs. Differences in AUC values using peripheral blood mononuclear cells (PBMC) were negative with between labs might be due to culture conditions, different microscopy lumacaftor, ivacaftor and tezacaftor; however, hypersensitivity diagnosis equipment or software analysis. was confirmed through T cell cloning. T cell lines were established by Work in MDA lab supported by UID/MULTI/04046/2013 center grant (to culturing PBMC with drugs for 14 days in IL-2-medium. Clones were BioISI). generated by serial dilution and repetitive mitogen stimulation. The proliferative response of the clones and cytokine release were measured using [3H]-thymidine uptake and ELIspot. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S115

Results: 33 lumacaftor-specific TCC were generated but no clones were index (BMI) and reduction in pulmonary exacerbations, it remains unclear generated from ivacaftor and tezacaftor lines. Lumacaftor-responsive whether these effects occurred in combination in individual patients. clones were proliferated in a dose-dependent manner and did not cross Methods: We used data from a real-life study, which included all patients react. All lumacaftor-responsive clones were CD4+ and HLA class II- aged ≥12 years who started LUMA-IVA in 2016 across all French CF centres restricted. Lumacaftor stimulation resulted in the secretion of IFN-gamma, (AJRCCM 2020; 201:188–197). After 1 year of treatment, we defined ≥ ≥ IL-10, IL-13, IL-22 and granzyme B. clinically significant improvement in ppFEV1 ( 5%) and BMI ( 0.5 kg/m2 in Conclusion: These data confirm a strong lymphocytic response to adults or ≥0.5 z-score in adolescents). For exacerbations (defined as lumacaftor in a patient with clinical signs of drug allergy to lumacaftor/ intravenous antibiotics), improvement was defined as being exacerbation ivacaftor. T cell cloning enabled the detection of lumacaftor as the cause of free or by a 50% reduction in the year of treatment as compared to the year allergy. This method may be important for future individualised treatment prior to treatment initiation. with respect to the triple therapy. Results: Among 589 patients (231 adolescents; 358 adults ≥18 years) treated continuously for 1 year with LUMA-IVA, 213 (36%) had response for

P207 ppFEV1, 286 (49%) had response for BMI and 420 (71%) had response for Start of lumacaftor/ivacaftor in adult cystic fibrosis patients with exacerbations. Combined response on ppFEV1, BMI and exacerbations homozygous F508del results in temporal and moderate changes in lung occurred in 89 (15%) patients, whereas no response on any criteria was microbiome and metabolome found in 68 (12%) patients. Response for only one or two criteria occurred 1 2 2 1 1 A.H. Neerincx , K. Whiteson , J.L. Phan , P. Brinkman , M.I. Abdel-Aziz , in 432 (73%): among these latter patients, 29% had response for ppFEV1, E.J.M. Weersink1, J. Altenburg1, C. Majoor1, A.H. Maitland-van der Zee1,3, 46% for BMI and 77% for exacerbations. Higher rates of response were found 1, 4 L.D.J. Bos , in adolescents vs. adults, in patients with higher ppFEV1 at baseline and in Amsterdam Mucociliary Clearance Disease Research Group, Amsterdam those with lower rates of P. aeruginosa colonisation and lower rates UMC Breath Research Group. 1Amsterdam UMC - Location AMC, University of exacerbations. Amsterdam, Department of Respiratory Medicine, Amsterdam, Netherlands; Conclusion: Although only 15% of patients derived combined benefit on 2 Whiteson Lab, University of California Irvine, Irvine, United States; ppFEV1, BMI and exacerbations, more than two thirds of patients had 3Amsterdam UMC - Location AMC, University of Amsterdam, Department of clinically significant benefit on some criteria, often in the absence of 4 Pediatric Respiratory Medicine, Amsterdam, Netherlands; Amsterdam UMC - ppFEV1 improvement. These data suggest the need for developing Location AMC, University of Amsterdam, Department of Intensive Care, multidimensional tools to assess response to CFTR modulators in clinical Amsterdam, Netherlands trials and in daily practice.

Objectives: Targeted cystic fibrosis therapy with lumacaftor/ivacaftor, P209 partly restores chloride channel function and improves epithelial fluid Correlation between structural changes of the lungs and airways on CT transport in the airways. Consequently, changes in the microbiome that is scan and recovery of pulmonary function after start of CFTR adapted to cystic fibrosis lungs may occur. The objective of this study is to modulators in cystic fibrosis patients investigate the effects of lumacaftor/ivacaftor on respiratory microbial 1 2 1 1 B. Aalbers , F. Mohammed Hoessein , R. Hofland , I. Bronsveld , composition and microbial metabolic activity by repeatedly sampling the 3 3 1 1 3 K. de Winter-de Groot , B. Arets , M. Kruijswijk , S. Schotman , C. de Kiviet , lower respiratory tract. 3 3 3 1 M. van Oirschot-van de Ven , S. Michel , K. van der Ent , H. Heijerman . Methods: This was a single-centre longitudinal observational cohort study 1 2 UMC Utrecht, Pulmonology, Utrecht, Netherlands; UMC Utrecht, Radiology, in adult cystic fibrosis patients with a homozygous F508del mutation. Lung 3 Utrecht, Netherlands; Wilhelmina Children’s Hospital, Pediatric Pulmonology, function measurements and microbial cultures of sputum were performed Utrecht, Netherlands as part of routine care. An oral and nasal , and an exhaled breath sample were collected before and every three months after starting Objective: The objective of this study is to verify if extensive structural lung therapy, up to one year. damage visible on CT scan is correlated to poor recovery of ppFEV1 after the Results: Twenty patients were included in this study. Amplicon 16S rRNA start of CFTR modulating therapy in CF patients. and metagenomics sequencing revealed that Pseudomonas aeruginosa was Methods: In our retrospective observational study, patients aged 6 years or most abundant in sputum and seemed to decrease after 6 months of older starting on ivacaftor or lumacaftor/ivacaftor in standard care were in treatment. Two types of untargeted metabolomics analyses in sputum strict follow up. For these patients, data were obtained about ppFEV1, BMI, showed a change in metabolic composition between 3 and 9 months after CFQ-R and sweat chloride before start and after 6 months of treatment, and treatment that almost returned to baseline levels after 12 months of data about ppFEV1 and BMI were recorded every 3 months. Exacerbations follow-up. The volatile metabolic composition of breath was significantly were recorded continuously. From the group of patients who have used different after 3 months of treatment and remained different from baseline, CFTR modulators for at least 6 months, patients were selected who until 12 months after treatment. underwent a CT thorax for any reason, within 18 months before or after Conclusions: After starting cystic fibrosis transmembrane conductance start of treatment. These CT scans were reviewed to determine Brody score. regulator (CFTR) modulating treatment in cystic fibrosis patients with a ppFEV1 data was retrieved. To assess correlation, Pearson R and Spearman R homozygous F508del mutation, a temporary and moderate change in the tests were applied. lung microbiome is observed, which is mainly characterized by a reduction Results: We identified 30 patients who met the inclusion criteria, with in the relative abundance of Pseudomonas aeruginosa. Brody scores between 1.0 and 143.5 (mean: 55) and ppFEV1 before treatment ranging from 19 to 113 (mean: 66). 24 patients had started

P208 lumacaftor/ivacaftor, 6 patients started ivacaftor. Change in ppFEV1 in 6 Multidimensional assessment of response to lumacaftor-ivacaftor in months of treatment ranged from −19 to +24 (mean change on lumacaftor/ cystic fibrosis patients homozygous for the F508del mutation ivacaftor: 2.4, mean change on ivacaftor: 12.7). For patients using P.-R. Burgel1, J. Da Silva2, J.-L. Paillasseur3, lumacaftor/ivacaftor, a correlation between Brody score (total or sub- 1 − the French Cystic Fibrosis Reference Network Study Group. Université de domains) and change in ppFEV1 was not significant: Pearson R = 0.057, Paris, Cochin Hospital, AP-HP, Respiratory Medicine and Adult CF Center, Paris (p = 0.398). For patients using ivacaftor, there was a significant correlation 2 Cedex, France; Cochin Hospital, Respiratory Medicine and Adult CF Center, between Brody score and ppFEV1 change, with a Pearson R = 0.822 Paris, France; 3EFFI-STAT, Paris, France (p = 0.012). Conclusion: Extensiveness of structural damage to the lungs of CF patients Objectives: Response to lumacaftor-ivacaftor (LUMA-IVA) has been is correlated with the response in ppFEV1 on ivacaftor, however this assessed at the population level but not at the patient level in clinical correlation was not demonstrable in patients on lumacaftor/ivacaftor. trials. Although studies have shown improvement in ppFEV1, body mass S116 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P210 reduction was also seen in the number of intravenous courses required in Safety and effectiveness of lumacaftor-ivacaftor in cystic fibrosis the subsequent year (−1.74, CI −2.33 to −1.14). ≥ − patients with ppFEV1 <40% or 90% FEV1 remained stable over one year (+1.43, CI 0.70 to +3.56) and no P.-R. Burgel1, J. Da Silva2, J.-L. Paillasseur3, significant change was observed in measures of body composition. the French Cystic Fibrosis Reference Network study group. 1Université de Conclusion: This real-world data in patients with severe CF, illustrates that Paris, Cochin Hospital, AP-HP, Respiratory Medicine and Adult CF Center, Paris, Orkambi may have significant benefits in reducing infective exacerbations 2 France; Cochin Hospital, Respiratory Medicine and Adult CF Center, Paris, and improving QOL in patients with FEV1 below 40% predicted, France; 3EFFI-STAT, Paris, France homozygous for the F508del CFTR mutation.

Objectives: Phase 3 trials of lumacaftor-ivacaftor (LUMA-IVA) have shown P212 safety and efficacy in patients with cystic fibrosis (CF) homozygous for the Real world Orkambi Long-term Leavers (ROLL) study - a prospective 6- Phe508del mutation and ppFEV [40–90%]. Marketing authorizations have 1 month descriptive analysis to understand factors influencing choice of been granted in patients at all ppFEV levels. 1 dual CFTR modulator therapy in patients with cystic fibrosis Methods: We used data from a real-life study, which included all patients 1,2 2 1 1 1 ≥ D. Morrissy , J.A. Eustace , C. Fleming , M. McCarthy , K. Cronin , aged 12 years who started LUMA-IVA in 2016 across all French CF centres 1 1 1 2 1, 2 (AJRCCM 2020; 201:188–197). Our goal was to evaluate safety (in the C. Howlett , E. Madden , C. Meade , Y. McCarthy , D.M. Murphy , B.J. Plant1,2. 1University College Cork, Cork Centre for Cystic Fibrosis, overall population) and effectiveness (in patients exposed for 1 year) of 2 ≥ Respiratory Department, Cork University Hospital, Cork, Ireland; University LUMA-IVA in patients with ppFEV1< 40% or 90% by comparison with those – College Cork, HRB Clinical Research Facility Cork, Cork, Ireland with ppFEV1 [40 90%]. Results: 827 patients were classified in 3 groups according to ppFEV1 at Objectives: Since the recent availability of Symkevi (T-I) as a second dual- treatment initiation (< 40% n = 121, [40–90%[ n = 609, ≥90% n = 97). CFTR modulator, preliminary data suggests that bronchospasm and Treatment discontinuation rate was higher in ppFEV1< 40% patients (29%) contraceptive preference are factors supportive of its use over Orkambi – ≥ than in those with ppFEV1[40 90% [(16%) or 90% (17.5%). Respiratory (L-I). adverse events (AEs) represented the main cause (74%) of treatment The objective of this study was to prospectively assess all patients in our discontinuation in ppFEV1<40% patients, but only 42% and 29% of causes in unit who have commenced T-I and therefore enhance our understanding as patients [40–90%[ or ≥90%, respectively. After 1 year of treatment, median to why patients change dual-CFTR modulator therapy in a real world – [IQR] increase in ppFEV1 was +2.9% in ppFEV1 [40 90%[ patients and was setting. ≥ significantly greater than in those with ppFEV1< 40% or 90% (+0.5% and Methods: We assessed all patients in our unit on dual-CFTR modulator +1.7%, p = 0.03 and p = 0.05; respectively). Compared with the year prior to therapy (n = 62) with an emphasis on those on T-I for over 6 months initiation, numbers of days of intravenous antibiotics were reduced by 17%, (n = 13). – ≥ 40% and 59% in ppFEV1<40%, [40 90%[ or 90% patients, respectively Changes in; (p < 0.05). Numbers of patients with IV antibiotics were significantly 1. clinical parameters, ppFEV , FVC, BMI, IV antibiotic usage, number of – ≥ 1 reduced in patients with ppFEV1 [40 90%[ or 90%, but not <40%. Mean hospital admissions; increase in body mass index occurred in all groups of patients and was 2. surrogate marker of CFTR modulation sweat chloride & 2 comparable among groups (+0.68 to +0.75 kg/m ). 3. quality of life-related symptoms questionnaires were assessed. In all Conclusion: Although patients benefited from LUMA-IVA at all levels of patients who discontinued L-I, a reason was sought by chart review. ppFEV1, characteristics and magnitude of response varied at different baseline ppFEV1. Heterogeneity of response to treatment was present in all Results: 11 of 13 patients receiving T-I previously stopped L-I. groups of patients. Bronchospasm/clinical deterioration (n = 6/11), contraceptive preference (n = 2/11) and GI upset (n = 3/11) were the reasons for discontinuation. P211 Group A (direct switch of CFTR therapy) and Group B (prior discontinuation Real-world experience of lumacaftor/ivacaftor combination in Welsh of L-I/CFTR therapy naïve) contain 6 and 3 patients respectively. cystic fibrosis patients homozygous for the F508del CFTR mutation Improvement in CFQR-R (4/6(patients),Δ+5.5 (median)), CFQR-D (3/6, with severe lung disease Δ0.0), Fatigue Score (3/6), IV antibiotics (2/6,25% reduction) and Hospital L. Tan1, L. Speight1, D. Lau1, M. Lea-Davies1, H. Jones2,D.Proud1, J. Duckers1. admissions (1/6, 25% reduction) were noted in group A. Interestingly 1 Δ− Δ− Δ− Cardiff & Vale University Health Board, All Wales Adult Cystic Fibrosis Centre, ppFEV1 (3/6, 2.0), FVC (6/6, 7.5), BMI (4/6, 0.8) and Sweat Chloride Cardiff, United Kingdom; 2Cardiff & Vale University Health Board, Division of (2/6,Δ+5.0) deteriorated. Δ Population Medicine, Cardiff University, Cardiff, United Kingdom As expected, improvements in all parameters including ppFEV1 (3/3, +1.0) were noted in group B. Objectives: CFTR modulator Orkambi (Lumacaftor/Ivacaftor) has been Conclusion: Fewer than expected patients changed dual-CFTR therapy recently agreed for renumeration in England, Scotland and Wales for cystic with clinical deterioration/bronchospasm being identified as the primary fibrosis (CF) patients homozygous for the F508del CFTR mutation. reason for switching. Contraceptive preference was found to be less However, there is currently a lack of real-world UK experience in patients influential. with severe CF. In addition, there is increasing interest in health-related Those who swap therapy directly showed mixed responses in clinical Quality of Life (QOL) measures, alongside traditional outcome measures of parameters despite a deterioration in ppFEV , BMI and Sweat chloride. lung function and body composition. 1 We present the outcome of a year of Orkambi therapy in adult CF patients with severe lung disease in Wales on a managed access program (MAP). P213 Methods: All adult patients at the All Wales Adult Cystic Fibrosis Centre Long-term effect of lumacaftor/ivacaftor on patients aged over 6 years receiving Orkambi via MAP were included. Patient lung function, body with cystic fibrosis homozygous for F508del-CFTR 1 1 1 1 1 composition (body mass index, fat free mass index and hand grip strength), E. Hatziagorou , S. Kyrvasili , E. Kouroukli , L. Nousia , J. Lialias , 1 1 1 pulmonary exacerbation frequency and QOL scores using the CFQ-R C. Mantsiou , J. Tsanakas . School Of Medicine, Aristotle University Of questionnaire were recorded prior to initiation and repeated at one year Thessaloniki, CF Unit, Hippokration Hospital, Thessaloniki, Greece post. Objectives: To examine the effect of lumacaftor/ivacaftor combination Results: 18 patients (4 female, mean age 31.8yrs) with mean FEV 28.8% 1 therapy on FEV %predicted, Lung Clearance Index (LCI), Pulmonary predicted (SD 8.6) on Orkambi MAP were followed up over 1 year. 1 Exacerbations and BMI among F508del homozygous CF patients aged 6 Improvements were observed in 11/12 QOL indicators with most marked years and older. improvements in patient-reported Physical Functioning (+22.4, CI +5.6 to Methods: This prospective observational real - life study assessed clinical +39.1), Vitality (+22.0, CI +8.7 to +35.3), Respiratory Symptoms (+16.2, CI outcomes including FEV % predicted, Lung Clearance Index (LCI), BMI, as +3.5 to +28.8) and Health Perception (+14.1, CI +2.1 to +26.2). A significant 1 well as, pulmonary exacerbations (PeX) before and one year after initiation Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S117 of lumacaftor-ivacaftor. Thirty- one CF patients (7–27 years, 38% colonised parameters, blood investigation and spirometry were performed at start with Pseudomonas aeruginosa) were evaluated; they performed N2 - MBW (T0), one month later and then every 3 months. Sweat test, lung clearance (Nitrogen Multiple Breath Washout), and spirometry before and one year index (LCI), chest CT scan or MNR were also performed at T0 and then once after treatment initiation. a year. Results: Baseline mean (SD) BMI was 19.06 kg/m2 (3.33), LCI: 14.1 (4.68), Results: At T0 their median age was 10,6 [10,6;10.8]. Median time of

FEV1% predicted: 81.36 (24.82). One year after treatment initiation, observation was 30 months (T30). In no case it was necessary to stop OR; no significant improvements from baseline were observed in BMI (+0.62; patient reported any drug-related adverse events. Slight improvement in 95% CI, 0.50 to 0.73; P < 0.0001), LCI (−1.16; 95% CI, −1.89 to −0.45; nutritional status (median BMI z-score at T0: −1,31[−1.85; −0.44]; at T30: − − − − P = 0.002) and PeX ( 7.2; P = 0.024). FEV1% predicted remained stable 0,65 [ 1.24; 0.42]) , no change in FEV1 (median value at T0: 91.4 %[78; (+2.18; 95% CI, 0.59 to 4.9; P = 0.122). 93.5]; at T30: 89.1% [75.3;100]) but a reduction in the number of Conclusions: Lumacaftor in combination with ivacaftor improved venti- respiratory exacerbation was observed. Sweat chloride concentrations lation inhomogeneity and reduced pulmonary exacerbations in patients decreased from T0:110 mEq/L [99.9; 120.2] to T30:100.4 mEq/l [97.6;101.1]. with cystic fibrosis homozygous for the F508del CFTR mutation. LCI showed a trend towards reduced variability, CT/MNR a limited lung involvement at T0 with no evidence of bronchiectasis progression. P214 Conclusions: These preliminary data confirm that OR was safe and well Real-life evaluation of the multi-organ effects of lumacaftor/ivacaftor tolerated in children aged 9–11 years. A positive trend in nutritional status (Orkambi) on F508del homozygous cystic fibrosis patients was documented. Pulmonary function remained stable for more than 2 K. Yaacoby-Bianu1, Z. Schnapp2, I. Koren3, A. Ilivitzki4, M. Shteinberg5,6, years associated with a remarkable reduction in the number of acute G. Livnat1, 6. 1Carmel Medical Center, Pediatric Pulmonology Unit & CF Center, exacerbation and sweat chloride concentrations. These data demonstrate Haifa, Israel; 2Carmel Medical Center, Pediatrics, Haifa, Israel; 3Carmel Medical that OR con be a valuable treatment with potential to slow the progression Center, Endocrinology Unit, Haifa, Israel; 4Ruth Rappaport Children’s Hospital, of the disease. Rambam Health Care Campus, Pediatric Radiology, Haifa, Israel; 5Carmel Medical Center, Pulmonology Institute and CF Center, Haifa, Israel; 6Technion- P216 Israel Institute of Technology, B. Rappaport Faculty of Medicine, Haifa, Israel Sweat chloride response to lumacaftor/ivacaftor treatment in cystic fibrosis: weight correlates with magnitude of response Objectives: Orkambi is one of the new modulators to treat F508del 1 1 1 2 2 B. Aalbers , R. Hofland , I. Bronsveld , K. de Winter-de Groot , B. Arets , homozygous CF patients. It improves pulmonary function tests (PFT) and 1 1 2 2 M. Kruijswijk , S. Schotman , C. de Kiviet , M. van Oirschot-van de Ven , reduce pulmonary exacerbations (PEx). However, CF is a multi-organ 2 2 1 1 S. Michel , K. van der Ent , H. Heijerman . UMC Utrecht, Pulmonology, disease and therefore there is a need for real-life research on the systemic 2 Utrecht, Netherlands; Wilhelmina Children’s Hospital, Pediatric Pulmonology, effects of CFTR modulators. Utrecht, Netherlands Aim: To evaluate pancreatic function, bone metabolism and respiratory changes through a year of Orkambi treatment. Objectives: To explore which patient-related factors influence sweat test Methods: A prospective one-year study on F508del homozygous adult CF response to CFTR modulators, as well as examining the correlation between patients, treated with Orkambi. At screening and at 12 months the patients the sweat chloride response and ppFEV1 or BMI response, using underwent sweat test, oral glucose tolerance test (OGTT), chest CT and systematically collected real-life clinical data. Dual-energy X-ray absorptiometry (DEXA). Visits were made at first day of Methods: CF patients of any age were identified who had used lumacaftor/ treatment and every 3 months evaluating: BMI, symptoms, treatments, PFT, ivacaftor for at least six months. Of these patients, age, sweat chloride laboratory tests and CF Questionnaire-Revised (CFQR). levels, ppFEV1 weight and BMI at the start of treatment and after 6 months Results: 12 patients were recruited, mean age 28.3 years, 8/12 males. All were collected retrospectively. Pearson and Spearman tests were per- pancreatic insufficient, with median BMI 20 which was stable throughout formed to assess correlation. the study. Sweat test decreased significantly after a year (107.7 to 86 meq/L, Results: A modest but significant correlation was found between patient p = 0.003). PFT improved in the first 3 months (FEV1% p = 0.019, FEF25–75% age and sweat chloride response to CFTR modulating therapy (Pearson p = 0.035). Less severe PEx needed I.V antibiotics (28.6% with Orkambi vs. R = 0.139, p = 0.040). Correlation between patient weight and chloride 56.7% 1 year before, p = 0.031). There was a significant decrease in average response was stronger (Pearson R = 0.244, p = 0.001). Sweat chloride − alkaline-phosphatase level with a trend towards increased albumin and response showed no correlation to ppFEV1 change (Pearson R = 0.008, calcium level and a minimal improvement in DEXA scores. Only 8 patients p = 0.460) or BMI change (Pearson R = −0.092, p = 0.123) at 6 months after (no CFRD) had OGTT, with no consistent change regarding glucose, insulin start of therapy. Females in this group had a larger response in BMI (+0.55 and c-peptide. No change was found in chest CT and in CFQR scores. versus +0.28, p = 0.046) and sweat chloride (−28.58 mmol/l versus Conclusion: This study suggests a positive trend towards improvement in −18.01 mmol/l, p = 0.000) compared to males. bone mineral density, with supportive evidence to known literature Conclusion: Age and sex correlate with the response in sweat chloride regarding improved PFT, sweat chloride and PEx, following a year of concentration after start of lumacaftor/ivacaftor, which may both be Orkambi treatment. Further larger studies should continue investigating explained by the correlation between patient weight and sweat chloride the effect of CFTR modulators on extra-pulmonary manifestations. response. Sweat chloride response does not correlate with ppFEV1 change of BMI change. This information may help the interpretation of sweat test P215 results acquired for the follow-up and evaluation of CFTR modulating Safety and efficacy of lumacaftor/ivacaftor treatment in cystic fibrosis treatments and could lead to a critical revaluation of the sweat test in this patients aged 9–11 years: preliminary data setting. E. Nazzari1, V. Daccò1, A. Bulfamante1, I. Borzani1, F. Corti1, C. Colombo1, 2. 1Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan, Italy; P217 2Università degli Studi di Milano, Milan, Italy Real-world outcomes of adult patients transitioning from Orkambi to Symkevi In 2018, the combination therapy of lumacaftor and ivacaftor (OR) was 1 1 1 1 P.C. Ridge , C.D. Campbell ,M.O’Mahony . Galway University Hospital, approved by the European Commission for F508del-homozygous children Respiratory Department, Galway, Ireland aged 6–11 years. Data regarding the safety and efficacy in this range of age are limited to the 24 weeks treatment (2017, Ratjen et al.) Objectives: Symkevi (Tezacaftor/Ivacaftor) is the next generation cystic Methods: Between March and July 2017, 5 CF male patients aged 9–11 fibrosis transmembrane conductance modulator that is used in the years with pancreatic insufficiency and F508del-homozygous, started OR treatment of individuals with cystic fibrosis who are homozygous for treatment (100 mg/125 mg twice a day) within the compassionate use F508del. Clinical trials have shown benefit for lung function and program. All of them had a history of recurrent respiratory exacerbations exacerbation reduction in this group of patients compared to placebo. and were colonised by multi-resistant bacteria. Anthropometric S118 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

We sought to document the “real world” impact of Symkevi in our cohort of Objectives: Study data suggest the CFTR modulator therapy tezacaftor/ patients who were already on Orkambi in Galway University Hospital. ivacaftor (Symkevi) has little effect on lung function but can reduce Methods: We performed a retrospective review of the clinical notes of pulmonary exacerbation rates by one third. It has been available in the UK individuals with Cystic Fibrosis attending our clinic who commenced on since 2018 for pwCF with a FEV1 < 40% through the Vertex Managed Access Symkevi from January 2019, most transitioned from Orkambi (Lumacaftor/ Program (MAP) and we wished to report our real-world experience in this Ivacaftor) to Symkevi. Up to eight months of data was available since ill cohort. commencing Symkevi. Data was last updated on the 24th October, 2019. Methods: We looked for any effect on lung and liver function, exacerbation Results: 18 patients commenced Symkevi in our cohort. One patient rates, and nutritional state, and any side-effects following initiation of stopped due to hair loss and fatigue attributed to their treatment. Of note 2 Symkevi therapy via the MAP in 22 pwCF for up to 15 months. The results patients who previously did not tolerate Orkambi, due to rash and chest are reported as mean ± SD. tightness respectively, tolerated Symkevi. FEV1 improved bya mean of 4.7%. Results: There was no effect on lung function (ppFEV1: 34 ± 3.9 to 34 ± 3.1, FEV1 increased in 9/18 (50%) patients, remained unchanged in 7/18 (39%) p = 0.78), nutritional state (BMI: 22.12 ± 2.97 to 22.24 ± 3.07, p = 0.63) or any and decreased in 2/18 (11%) in our cohort. There appears to be a trend hepatic toxicity based on serological tests. Time to exacerbation increased towards reduced exacerbation frequency in our Symkevi cohort. There was by 32% (53 ± 33.6 days to 78 ± 36.6, p = 0.018). There was one death a mean increase of 0.26 kg in weight amongst the cohort. The largest unrelated to Symkevi (initial ppFEV1 30%). Three pwCF (14%) suffered side weight gain documented was 5.7 kg. Sputum production reduced in 6/18 effects: one rash, one viral symptoms (both resolved without suspension of (33%), increased in 2/18 (11%) and remained unchanged in 10/18 (55%). treatment). Another suffered rash and blurred vision, and the drug was Conclusion: There is no published data on transition from Orkambi to suspended for one month after no ophthalmological problems were found Symkevi. In the published clinical trials the efficacy of Symkevi appears to and vision improved. be similar to Orkambi, but in our clinical practice we saw further Conclusion: Our real-world data of the use of Symkevi in ill pwCF show improvements in patient’s clinical status on Symkevi. Symkevi was also that it has a good safety profile and improves the exacerbation rate whilst better tolerated than Orkambi in our group. maintaining lung function, mirroring the results found in clinical trials.

P218 P220 CFTR modulators in the real world: an observational study of patient Starting Symkevi for all eligible patients within 30 days of NHS response to tezacaftor/ivacaftor therapy England’s funding announcement: dedicated Symkevi initiation clinic N.J. Robinson1,2, C. McMullan1, A. Berwick1, J. Robertson1, L. McIntosh1, J. Cunningham1, C. Orchard1, A. Higton2. 1Frimley Park Hospital, Cystic D. McCabe1, G.R. Hardisty2, R.D. Gray1,2. 1NHS Lothian, Scottish Adult Cystic Fibrosis Unit, Frimley, United Kingdom; 2Frimley Park Hospital, Cystic Fibrosis, Fibrosis Service, Edinburgh, United Kingdom; 2University of Edinburgh, Centre Frimley, United Kingdom for Inflammation Research, Edinburgh, United Kingdom Objectives: The objectives of these dedicated Symkevi clinics at Frimley Objective: To assess the efficacy of CFTR modulators in a clinical setting Park Hospital (FPH) were to safely and swiftly initiate this medication in following roll-out of tezacaftor/ivacaftor in Scotland, UK. eligible patients (71 of our 140 patients), giving them the relevant Background: CFTR modulator therapy is likely to change CF patient health information and support required. and clinical service provision. Scotland was the first nation in the United Methods: The eligible patients were contacted within 2 days of NHS Kingdom to approve tezacaftor/ivacaftor and lumacaftor/ivacaftor for England’s announcement and were then invited to attend a dedicated eligible patients and the Scottish National CF Service in Edinburgh have Symkevi assessment clinic. The majority of these patients were seen in established a modulator clinic to roll out therapy to patients and collect weekend clinics set up solely for Symkevi initiation which were run by real-world data. specialist CF consultants and nurses. A total of 3 separate clinics were held, Methods: Eligible patients were selected by genotype. Patients had enabling all 71 eligible patients to be seen within a month of NHS England’s baseline spirometry, blood testing and completed a CFQ-R questionnaire announcement, of which 89% (63 patients) decided to start Symkevi. FPH and pre-therapy counselling. Patients returned at 1 and 3 months following was the first CF unit in the UK to initiate Symkevi in all eligible patients. treatment and these measurements were repeated. 8 weeks later, in order to collect feedback on this process, an electronic Results: Collection of data is on-going. To date, 50 patients have survey was sent out to the patients who attended these clinics. commenced tezacaftor/ivacaftor (6 transferred from lumacaftor/ivacaftor). Results: Responses were received from 49% of attendees. From these CFTR modulator naïve subjects had a mean absolute change in ppFEV1 of results we found that 100% of patients felt their contact by the CF team, +1.9% at 1 month (n = 24), rising to +4.9% at 3 months (n = 12) following clinic time frames and that the dedicated clinics were useful. 96.8% of tezacaftor/ivacaftor therapy. Furthermore, they also had an absolute patients reported that they were fully supported by the CF team during this change in ppFVC by +3.4% at 1 month and +5.3% at 3 months. Switching process. Additionally, in the short timeframe of 4 to 8 weeks since the from lumacaftor/ivacaftor to tezacaftor/ivacaftor was not associated with initiation of Symkevi, 35.5% felt their health had already improved. At the any change in lung function. To date, CFQ-R analysis shows improvements time of the survey, 90% of patients plan on continuing Symkevi. The staff in every domain at both 1 month (n = 19) and 3 months (n = 5), with the involved found careful clinic preparation was essential, and that the most marked improvement in the Physical, Vitality, Health and Respiratory dedicated clinics were an efficient way to see all relevant patients. domains of over 20 points at 3 months. Adverse events occurred in 10% of Conclusion: Our patient survey and achieved timescales show that patients. 1 patient stopped due to deranged liver function. dedicated Symkevi clinics are an efficient and popular way to commence a Conclusions: Treatment with the CFTR modulator tezacaftor/ivacaftor was new therapy promptly. This approach to safely and efficiently starting new associated with improved outcomes in real-world data in line with therapies in CF patients is also applicable to future therapies, such as previous clinical trial data, underlining the importance of monitoring Trikafta, which will require a similarcoordinated approach from the CF MDT. therapy in a dedicated clinic. CFQ-R has improved in every domain, which has not been reported previously. Data collection is on-going at the time of P221 submission. Impact of elexacaftor/tezacaftor/ivacaftor triple combination therapy on health-related quality of life in people with cystic fibrosis P219 heterozygous for F508del and a minimal function mutation: results Symkevi: real-world experience in an ill cohort at an adult cystic from a Phase 3 clinical study fibrosis centre I. Fajac1, K. Van Brunt2, C. Daines3, I. Durieu4, J. Goralski5, H. Heijerman6, R. Robinson1, T. FitzMaurice1, M. Shaw1, S. Dawood1, D. Nazareth1, C. Knoop7, C. Majoor8, J. Booth2, S.M. Moskowitz2, J. Savage2, C. Wang2, M. Walshaw1. 1Liverpool Heart and Chest Hospital, Respiratory Medicine, A. Quittner9. 1APHP.Centre - Université de Paris, Paris, France; 2Vertex Liverpool, United Kingdom Pharmaceuticals Incorporated, Boston, United States; 3University of Arizona, Banner University Medical Center, Tucson, United States; 4Hospices Civils de Lyon, Adult Cystic Fibrosis Centre, Université de Lyon, Lyon, France; 5University Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S119 of North Carolina, Division of Pulmonary and Critical Care Medicine, Chapel Background: In CF, ENaC inhibition is a mutation-agnostic approach to Hill, United States; 6University Medical Center Utrecht, Utrecht, Netherlands; restore airway surface liquid and enhance mucociliary clearance. The 7Hôpital Erasme, Department of Chest Medicine, Brussels, Belgium; inhaled ENaC inhibitor BI 1265162 has demonstrated preclinical efficacy 8Amsterdam University Medical Centers, University of Amsterdam, and was well tolerated in Phase I studies up to doses of 1,200 μg/day. Department of Respiratory Medicine, Amsterdam, Netherlands; 9Nicklaus Methods: BALANCE-CF™ 1 (NCT04059094) is a multinational, rando- Children’s Research Institute, Nicklaus Children’s Hospital, Miami, United mised, double-blind, placebo-controlled, parallel-group, dose-ranging States Phase II trial in patients with CF aged ≥12 years to assess efficacy, safety and pharmacokinetics of 4 doses of BI 1265162 vs placebo, on top of Objectives: Efficacy and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/ standard treatment (2-week screening period, 4-week randomised IVA), a novel CFTR modulator therapy, were evaluated in a Phase 3, treatment, 1-week follow-up). Ninety-eight patients, including 21 adoles- randomised, double-blind, placebo (PBO)-controlled study (NCT03525 cents, will be randomised. Twenty-eight patients will be allocated to the 444) in people with cystic fibrosis (pwCF) ≥12 years old with minimal highest dose of BI 1265162 (200 μg BID) or placebo in a 1:1 ratio. A futility function mutation (F/MF) genotypes; pwCF were randomised 1:1 to receive analysis after the first 28 patients will assess the potential for biological ELX/TEZ/IVA or PBO for 24 weeks. Primary and secondary outcomes, activity. The remaining 70 patients will be allocated to one of five treatment including marked improvement in clinical outcomes and CFQ-R respiratory arms (200 μg,100 μg, 50 μg, 20 μg or placebo, BID) in equal ratio, leading to domain (RD) scores, were reported previously. The aim of this analysis is to a final distribution ratio of 2:1:1:1:2. Recruitment and randomisation will report the effects of ELX/TEZ/IVA on 11 other CFQ-R domains. begin with adult patients only. The design supports dose ranging and Methods: The CFQ-R, a validated health-related quality of life (HRQoL) unbalanced allocation minimises the number of patients required. The instrument, was administered at study visits in the Phase 3 trial. Absolute primary endpoint is change from baseline in trough FEV % predicted; change from baseline in CFQ-R RD score was a prespecified secondary 1 secondary endpoints include change from baseline Lung Clearance Index. endpoint; other domains were prespecified other endpoints. A mixed- An independent data monitoring committee will review safety data effects model for repeated measures was used to calculate the change from periodically to advise on trial continuation and when to include baseline in CFQ-R domain scores vs PBO. Although a minimal clinically adolescents. important difference has not been determined for non-RD domain scores, Results: Baseline characteristics from the first 28 randomised patients and score increases signify improvement. an update on the ongoing trial will be presented. Results: 403 pwCF were randomised and dosed in the study. Conclusion: BALANCE-CF™ 1 will increase understanding of efficacy, Improvements with ELX/TEZ/IVA over PBO were observed in all non-RD safety and optimal dosing of BI 1265162 in patients with CF aged ≥12 years. scores except digestion (Table), including vitality, physical functioning, and health perceptions. P223 Establishing the Dutch Cystic Fibrosis Trial Consortium: opportunities CFQ-R Domain Mean CFQ-R Domain Mean difference for better trial participation difference vs vs PBO (95% CI) S. Michel1, A. Geel2, N. Keijzers3, N. Adriaens4, M. Smink5, H. van der Vaart6, PBO (95% CI) through 24 7 5 8 1 ’ through 24 weeks, points E. Dompeling , R. van der Meer , D. Zomer . Wilhelmina s Childrens 2 weeks, points Hospital, Utrecht, Netherlands; Erasmus MC, Rotterdam, Rotterdam, Netherlands; 3Radboud UMC, Nijmegen, Netherlands; 4Amsterdam UMC - Physical Functioning 12.5 (9.9, 15.0) Health Perceptions 17.0 (14.1, 20.0) Location AMC, University of Amsterdam, Amsterdam, Netherlands; Vitality 13.1 (10.5, 15.8) Weight 13.1 (8.3, 17.9) 5HagaZiekenhuis, Den Haag, Netherlands; 6UMC Groningen, Groningen, − Emotional Functioning 3.4 (1.5, 5.2) Digestion 2.5 ( 0.1, 5.1) Netherlands; 7Maastricht UMC, Maastricht, Netherlands; 8Dutch CF Body Image 3.8 (1.2, 6.5) Role Functioning 6.8 (4.6, 9.1) Foundation, Baarn, Netherlands Eating Problems 4.9 (2.6, 7.1) Social Functioning 5.9 (3.7, 8.0) Treatment Burden 6.8 (4.5, 9.2) Objectives: With the increasing numbers of trials for people with CF, often *Analyses with P values <0.05 are bolded; these P values are considered nominal with very few patients per centre, it is hard for individual centres to set up a because analyses for CFQ-R non-respiratory domains were not controlled for lot of these concurrent trials. Patients might want to participate in trials not multiplicity. running in their own centre. Our aim was to set up a network with all CF [Absolute change from baseline in CFQ-R non-respiratory domain scores*: ELX/ centres in the Netherlands for cooperating in clinical studies by sharing TEZ/IVA vs PBO] facilities, expertise and professionals. Methods: A working group was established to explore the needs and Conclusion: ELX/TEZ/IVA improved multiple aspects of HRQoL in pwCF wishes for a collaboration between all CF centres in the Netherlands. A with F/MF genotypes, illustrating broad benefits of treatment beyond framework was written and tasks where divided. In addition, a consortium previously reported respiratory and other clinical improvements. agreement was set up to formalise all roles and responsibilities. Sponsor: Vertex Pharmaceuticals Inc. Results: All seven CF centres and the Dutch CF Foundation (NCFS) are members of the NCFTC and have signed a consortium agreement. The P222 NCFTC Steering group, with representatives from all parties, determines An update on BALANCE-CF™ 1: a Phase II trial of the inhaled ENaC the policy. The operational work is done by the Clinical Trial Facility (CTF). inhibitor BI 1265162 in adults and adolescents with cystic fibrosis The CTF is consisting of research coordinators of five CF centres, three I. Fajac1, M.A. Mall2,3, R. Jain4, W. Seibold5, A.-C. Picard6, M.-C. Hsu7, principal investigators of three different CF centres, the Dutch CF A. Gupta5, C.H. Goss8,9. 1AP-HP. Centre-Université de Paris, Paris, France; Foundation (NCFS) and the NCFTC coordinator. All external communication 2Charité Universitätsmedizin Berlin, Department of Pediatric Pulmonology, for companies, sponsors and investigators goes through the NCFTC Immunology and Intensive Care Medicine, Berlin, Germany; 3Berlin Institute of coordinator ([email protected]). Health (BIH), Berlin, Germany; 4University of Texas Southwestern Med Center, Conclusion: The Dutch CF Trial Consortium (NCFTC), a collaboration Dallas, United States; 5Boehringer Ingelheim, Biberach, Germany; 6Boehringer between the seven CF centres, was established and formalised in December Ingelheim, Reims, France; 7Boehringer Ingelheim, Shanghai, China; 8University 2019. of Washington, Department of Medicine, Department of Pediatrics, Seattle, United States; 9Seattle Children’s Hospital & Research Institute, Seattle, United P224 States The UK clinical trials accelerator platform R. Brendell1, L. Allen1, C. Round1, E. Cousins1, K. Brownlee1. 1Cystic Fibrosis Objectives: To provide an update on the ongoing Phase II BALANCE-CF™ 1 Trust, London, United Kingdom trial of a new epithelial sodium channel (ENaC) inhibitor for patients with cystic fibrosis (CF). The Clinical Trials Accelerator Platform (CTAP) is a national CF clinical trials network, funded by the US Cystic Fibrosis Foundation (CFF). The Cystic S120 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Fibrosis Trust set-up and manages the programme, working in synchrony P226 with the European Cystic Fibrosis Society’s Clinical Trials Network (ECFS- CFTR modulators therapy for cystic fibrosis: a nationwide survey among CTN) and collaborating with the CF clinical community to provide sponsors Italian clinicians with parallel access to trial participants. F. Majo1,M.Ros2, R. Casciato3, S. Costa4. 1Bambino Gesù Children’s Hospital, Through the following workstreams CTAP supports the CF community Rome, Italy; 2Ca’Foncello Hospital, Treviso, Italy; 3G. Gaslini Institute, Genova, access a breadth of clinical trials, whilst supporting sponsors with trial Italy; 4G. Martino Hospital, Messina, Italy delivery: 1. Network of centres: 29 CF centres form the CTAP network, providing Objectives: To evaluate CFTRm use and perception of efficacy by Italian CF coverage of 82% of the UK CF population. 20/29 centres are funded physicians in different patient types. with a CTAP Coordinator to oversee local trial delivery. Methods: Between May and October 2018 (national reimbursement for 2. CF Ambassadors: CF Ambassadors (pwcf and CF parents) represent lumacaftor/ivacaftor >12 years and ivacaftor >2 years) all Italian CF the therapeutic needs of the CF community and collaborate with physicians were contacted to participate in an online voluntary survey of sponsors to make recommendations on trial design and outcomes. 13 questions on CFTRm use and expectations for patients F508del 3. Sponsor Engagement: CTAP supports commercial and academic homozygous (F/F) < and >12 years of age and with residual function sponsors by offering a centralised feasibility service to support site mutations; monitoring parameters and treatment propensity by disease selection and facilitating engagement with CF Ambassadors. stage were evaluated. Likert scale in 4 points was used to categorize 4. CF Clinical Trials Hub: Hosted on the Cystic Fibrosis Trusts website, responses and descriptive analysis is presented below pooling great/ the hub has a suite of information about clinical trials, including the CF moderate and somewhat/very. Trials Tracker database. Results: Fifty-nine of 78 clinicians responded (76%). All clinicians expect CFTRm to modify exacerbations rate and slow down the annual decline of Since launch in autumn 2017, CTAP metrics show ∼5% of the UK CF FEV1 (95% and 86% of them to a great+moderate extent, respectively). population were screened for a trial within the CTAP network, ∼3.5% of Exacerbations appear the main parameter considered to initiate treatment whom went on to enrol. Awareness of clinical trials in people with CF (90–95%). Bacterial colonisation is of particular interest for F/F patients <12 increased from 60% in 2017 to 71% in 2019. for 68% of respondents while lung clearance index (LCI) is rated high in all Through the infrastructure created, guidance from CFF and alignment with categories (61–76%) the highest being in F/F < 12. the ECFS-CTN, CTAP has established a clear pathway for sponsors to invest Multiple outcomes are used to monitor treatment (FEV1, exacerbations, CF trials in the UK. This, alongside the information hub created for the CF BMI, bacterial colonisation, imaging, LCI) in similar proportions for all community has enabled CTAP to maximise a unique opportunity to lead a groups, with a preference for pulmonary exacerbations (90–97%). positive culture change in the UK, becoming a significant contributor to the Treatment propensity increases with severity with slight preference for global effort for CF drug development. case by case approach rather than treatment in all patients for subjects <12 vs those >12. “Case by case” approach is followed by 50% of respondents for P225 asymptomatic patients. Establishment of a paediatric CFTR modulator clinic Conclusion: Pulmonary exacerbations seem to be the most important M. Desai1, M. Tabberner1, L. Paskin1, W. Nixon1, S. Rao1, P. Nagakumar1. factor used to prioritise treatment initiation with CFTRm. CF physicians rely 1Birmingham Women’s and Children’s NHS Foundation Trust, Respiratory most on this parameter to monitor treatment and evaluate efficacy. Paediatrics, Birmingham, United Kingdom P227 Objectives: Following the NHS England announcement on 24th October A long-acting alternative DNase for the treatment of cystic fibrosis lung 2019 that CFTR modulator treatments would be prescribed as per their disease marketing authorisations, CF patients and families were keen to commence G. Mori1, D. Delfino1, A. Grigoletto2, G. Bizzotto2, G. Pasut2, R. Percudani1. treatment as soon as possible. The CF Team produced a pathway and 1Università di Parma, Dipartimento di Scienze Chimiche, della Vita e della documentation to ensure the safe delivery of the new medicines to the Sostenibilità Ambientale, Parma, Italy; 2Università di Padova, Dipartimento di right patients across the network. The pathway was evaluated over a period Scienze Farmaceutiche e Farmacologiche, Padova, Italy of one month. Methods: Patients were screened prior to attending the clinic the genotype Objectives: Lung disease is the major cause of morbidity and mortality in of all CF patients were validated and letters to opticians for formal testing CF. The airways are obstructed by thick and sticky mucus rich in DNA for Cataracts given to eligible patients, liver bloods were reviewed. The causing breathing failure and predisposition to infections. Recombinant patients were reviewed in a clinical setting by a CF nurse, consultant and a human DNase1 (Pulmozyme®) is the only mucolytic agent that has proven pharmacist prior to commencing treatment. This enabled counselling, efficacy in CF by decreasing mucus viscosity, and thus increasing airways review of possible drug interactions, set-up of homecare delivery. clearance. However, DNase1 has critical issues as evidenced by the Observations were recorded including blood pressure and a quality of life percentage of non-responders (30%). Our project aims at developing an questionnaire was completed. The patients who commenced on a alternative DNase with improved catalytic properties and prolonged modulator were appointed to a nurse-led telephone clinic on Day 1 and residence time in the lung to solve the limitations of DNase1 and overcome Day 8 with a structured proforma followed by a clinical review on Day 30. drug resistance. Results: 141 patients were identified as being eligible. Over a month a total Methods: Through bioinformatics analysis we explored the rich repertoire of 32 patients commenced either Symkevi or Orkambi. 32/32 Day 1 phone of DNases in the human genome. To acquire the candidate protein in calls were completed as per the pathway. 19/32 Day 8 phone calls were sufficient amount and active form, we established its recombinant competed at time of writing.4/32 Day 30 reviews were completed. On Day expression in the yeast Pichia pastoris and purified it by anion-exchange 32/32 had no side effects from the drugs by Day 8 many patients reported and size exclusion chromatography. To prevent in vivo proteolytic that any cough had dried up.2/32 reports of constipation resolved by day 8 degradation and enhancing retention time, we chemically modified the and 1/32 blood glucose level in a known CFTR patient falling resulting in protein by covalent attachment of polyethylene glycol (PEG) chains. We reducing insulin intake. assayed endonuclease activity in vitro by using supercoiled plasmid DNA as Conclusion: All patients were safely commenced on CFTR modulators and substrate both on agarose gel and artificial mucus. were successfully reviewed via the telephone. Ongoing review of outcomes Results: We identified a potential alternative to DNase1, namely DNase1L2, including lung function (where appropriate), discontinuation of treatment, which is specifically expressed in epidermis. DNase1L2 exhibits optimal prescription collection and quality of life measures will be collected for this activity under acidic conditions (pH 5–6) and is insensitive to G-Actin cohort. inhibition. Conjugated DNase1L2 with N-hydroxysuccinimide activated PEG (PEG-NHS) retains its endonuclease activity and mucus penetration ability. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S121

Conclusions: Our alternative therapeutic DNase has significant advan- solution, with/without manuka honey, daily for a total of 30 days (+/−7 tages: i) acidic optimum that could be preferable for CF therapy because of days), after which repeat measurements were completed for all tests. the increased acidity of the airway surface in CF patients; ii) insensitivity to Differences between day 0 and day 30, between control and test groups G-Actin inhibition that is one relevant limit of DNase1. In the obtained (without/with manuka honey, respectively) and correlations between PEGylated form, DNase1L2 is suitable for trials in a mouse model of CF. quality of life and bacterial load/composition will be analysed. Results: A total of 15 patients have been recruited thus far, with SNOT-22 P228 scores ranging from 7 to 79 (total score range 0–110). The study is on-going Repurposing old drugs: the thin end of the wedge? Reporting and remains blinded at present, however preliminary SNOT-22 scores have experiences of nebulised heparin for mucolysis in adults with cystic changed. Initial microbiological analysis shows Staphylococcus aureus and fibrosis Staphylococcus epidermidis as the prominent culturable colonisers of the E. Major1, H. Dunn1, T. Daniels1, M. Carroll1, L. Bundy1. 1University Hospital nasal cavity pre- and post-sinal rinse use, with Pseudomonas and Southampton NHS Foundation Trust, Adult Cystic Fibrosis, Southampton, Burkholderia species also being isolated. The isolates have a range of United Kingdom antibiotic sensitivities. Conclusion: It is hoped that manuka honey will reduce symptoms Objectives: Optimising mucolysis for people with CF (PWCF) is a key associated with nasal disorders through reduced bacterial load and/or a component of maintaining lung health. There are a limited range of change in community composition favouring less problematic species. approved medications for this purpose, including rhDNase, hypertonic saline (HTS), and dry powder mannitol. However, many PWCF will be P230 intolerant of these medications or receive sub-optimal treatment from The efficacy of a novel complex liposomal formulation of fat-soluble them. Real world data suggests that 1.4% of PWCF are intolerant of rhDNase vitamins: a randomised trial and 8.1% are intolerant of HTS at initial test dose. Nebulised heparin has 1 1 1, 2 J.K. Nowak , P. Krzyzanowska-Jankowska , S. Drzymala-Czyz , been shown to be effective in vitro as a mucolytic and has been shown to be 3 4 5 5 I. Wojsyk-Banaszak , E. Sapiejka , J. Gozdzik-Spychalska , A. Nowicka , safe during a short-term clinical trial. However, there are no reports of real- 6 1 1 1 W. Skorupa , A. Lisowska , J. Walkowiak . Poznan University of Medical world use. Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Methods: Drug reaction test doses were prepared by mixing 50,000 2 Poznan, Poland; Poznan University of Medical Sciences, Department of international units of unfractionated heparin with 0.9% sodium chloride 3 Bromatology, Poznan, Poland; Poznan University of Medical Sciences, solution. It was administered via nebulisation during hospital admissions Department of Pediatric Pneumonology, Allergology and Clinical Immunology, for pulmonary exacerbation in patients assessed as receiving sub-optimal 4 5 Poznan, Poland; Outpatient Clinic for CF Patients, Gdansk, Poland; Poznan mucolysis. Subsequent short- and long-term prescription was twice daily. University of Medical Sciences, Department of Pulmonology, Allergology and Exclusion criteria were: 1) haemoptysis during current admission; 2) 6 Respiratory Oncology, Poznan, Poland; Institute for Tuberculosis and Lung history of massive haemoptysis or bleeding diathesis; 3) history of Diseases, I Department of Lung Diseases, Warsaw, Poland intolerance to nebulised heparin. Data was collected by retrospective case notes review. Acute intolerance was defined as a drop in FEV1 of >10% Objectives: We aimed to assess the efficacy of a novel liposomal fat-soluble or symptoms of acute breathlessness. Delayed intolerance was defined vitamin formulation in CF as compared to standard treatment. subjectively. Methods: An open-label multi-centre trial with block randomisation was Results: Since 2008, 63 PWCF have received a test dose of nebulised performed. The liposomal formulation containing vitamin A as retinyl heparin. Of these, 1/63 (1.6%) experienced acute intolerance at test dose, 2/ palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E 63 (3.2%) reported delayed intolerance at up to 10 months and 17/63 (27%) (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 μg) was compared used nebulised heparin as a long term mucolytic following hospital with the standard vitamin supplements in the closest possible doses discharge. (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively) without Conclusions: Nebulised heparin was well tolerated in this group of sick vitamin K2. PWCF, many with intolerances to other muco-active agents. In our Results: One hundred pancreatic-insufficient CF patients were enrolled, of experience, it has been found to be a cheap and effective mucolytic, whom 6 withdrew from the liposomal group and 3 from the control group. representing a potentially useful and economic alternative or adjunct to In per protocol analysis 42 patients were in the liposomal and 49 in the currently licensed muco-active medications. control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m2, FEV1% 70% ± 30%). The main characteristics, supplementation P229 doses, and vitamin status at baseline did not differ. The results for the main A pilot study investigating the effects of a manuka honey sinus rinse on (status change) and the secondary (status after 3 months) outcome are sino-nasal disorders in cystic fibrosis patients presented in the table below (the Welch test, two-sided p). A. Roberts1, C. Hankins2, A. Hopkin2, J. Duckers2, E. Mahenthiralingham3, All-trans-retinol change, ng/mL liposomal 1.48 ± 95.9 vs. standard R. Jenkins1. 1Swansea University, Institute of Life Sciences, Swansea, United −43.1 ± 121.4, p = 0.054 Kingdom; 2University Hospital Llandough, All Wales Adult Cystic Fibrosis • after 3 mo. 370.0 ± 116.5 vs. 323.1 ± 100.6, p = 0.045 Centre, Penarth, United Kingdom; 3Cardiff University, School of Biosciences, 25-hydroxyvitamin D3 change, ng/mL 9.7 ± 13.4 vs. 2.0 ± 9.8, p = 0.004 Cardiff, United Kingdom • after 3 mo. 43.2 ± 16.6 vs. 32.7 ± 11.5, p < 0.001 α-tocopherol change, μg/mL 1.5 ± 2.5 vs. −0.2 ± 1.6, p < 0.001 Objectives: Patients with Cystic Fibrosis (CF) have reduced treatment • after 3 mo. 9.0 ± 3.1 vs. 7.7 ± 3.0, p = 0.037 options due to the increasing emergence of antimicrobial resistance (AMR). %undercarboxylated osteocalcin change −17.2 ± 24.8 vs. −8.3 ± 18.5, To aid the AMR crisis, natural products with antimicrobial activity are p = 0.061 making a resurgence, and manuka honey is one such product. With excellent antimicrobial activity against a broad spectrum of multi-drug • after 3 mo. 13.0 ± 11.2 vs. 22.7 ± 22.0, p = 0.008. resistant organisms. Here we aim to determine the efficacy of a manuka Conclusion: The liposomal fat-soluble vitamin supplement enriched with honey sinus rinse on patient wellbeing, infection symptoms, bacterial load, vitamin K2 was superior to standard in providing vitamin D3 and E to and bacterial community composition. pancreatic-insufficient patients with CF. It was also more efficacious in Methods: Eligible participants recruited onto the study completed quality enabling vitamin K-dependent carboxylation and could enhance vitamin A of life questionnaires and Sino-nasal Outcome Tests (SNOT-22) to ascertain status. the severity of current sino-nasal disorders. Nasal swab, sputum, and sinal (The study was funded from a regional EU grant awarded to Norsa Pharma. rinse samples are collected and subject to both conventional microbio- Reg.DRKS00018814-DRKS00014295). logical and bioinformatics analysis. Participants then use a sinal rinse S122 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Complete obstruction: 4/4 (100%) PI and previous bowel surgery/ Gastroenterology/Liver Disease/Endocrinology/ meconium ileus. Medical treatment attempted in 3/4 (75%) patients. All Metabolic Complications 4 required surgery and had a protracted hospital admission. Median length of hospital stay: 60.5 days. Conclusion: The majority of admissions for suspected DIOS in our centre P231 meet the ESPGHAN definition for CF related constipation. The number of Discontinuation of Pancreatic Enzyme Replacement Therapy (PERT) in admissions meeting the criteria for DIOS is small but with significant children on ivacaftor morbidity, often requiring surgery and a protracted hospital stay. I. Hutchinson1, P. McNally2. 1Children’s Health Ireland, Dublin, Ireland; 2Royal College of Surgeons in Ireland, Dublin, Ireland P234 Objectives: To examine faecal elastase (FE) measurements and PERT usage Aloe arborescens improves intestinal function and quality of life in 3 in children after the initiation of ivacaftor. children with cystic fibrosis 1 1 1 1 1 2 Methods: Retrospective review of case notes. Our centre measures faecal N. Laborde , M. Mittaine , G. Labouret , P. Maumus , C. Lannibois , C. Viard , 1, 3 1 elastase annually after ivacaftor initiation and commences a trial of E. Mas . CHU Toulouse, Centre de Ressources et de Compétences de la 2 ivacaftor discontinuation when FE levels are >200 mcg/g. Mucoviscidose Pédiatrique, Toulouse, France; CHU Toulouse, Service de 3 Results: Sixteen children at our CF centre with G551D CFTR mutations have Pharmacie, Toulouse, France; Université de Toulouse, INSERM, INRA, ENVT, started ivacaftor in the last 11 years at a mean age of 6.6 years (range 2– UPS, IRSD, Toulouse, France 11.4 yrs). FE levels have increased in all but one individual, with 10 Objectives: CFTR dysfunction can impair intestinal function leading to returning to the PS range (>200 mcg/g), 3 to the partially sufficient range constipation or intestinal obstruction syndrome (DIOS). These patients (100–200 mcg/g) and 2 becoming detectable. Children achieving suffi- often require long-use of laxatives and hospitalisation. Our aim is to report ciency were more likely to have had detectable FE at baseline (6/10 v 0/6, the efficacy of Aloe arborescens, which is a natural laxative containing p = 0.01), less likely to have a second ‘severe’ CF mutation (F508del or anthroquinone. minimum function, 3/10 v 5/6, p = 0.03) and more likely to be younger at Methods: Since January 2019, 3 children over 120 were treated with Aloe ivacaftor commencement (mean 4.89 yrs v 8.83 yrs, p < 0.001). All 10 arborescens, initiated for the first one by his parents. We report their sufficient children have discontinued PERT without incident despite close clinical characteristics at baseline and their evolution until 31/12/19. monitoring (median follow up 6 months [2–16 months]). PERT usage Quantitative variables are expressed as mean (min-max). reduced in all but one individual after starting Ivacaftor. In the 6 individuals Results: The 3 boys were 11.4 years old (10–13.75) at Aloe arborescens who have not discontinued Ivacaftor, PERT usage has significantly reduced initiation, their weight was 37 kgs (27.8–47.8). Two were diagnosed by (mean 5600 v 3636 units/kg, p = 0.03) without incident. neonatal screening and one underwent surgery for meconium ileus; 2 were Conclusion: Our data show that improvements in FE, even after several F508del homozygote, and one was compound heterozygote (c.2988+1G>A years, can reflect clinical pancreatic sufficiency and suggests that we should and c.1904delA). All of them are pancreatic insufficient and suffered from closely monitor FE levels, symptoms and enzyme use for many years after constipation with recurrent disabling abdominal pain, and two required modulator treatment begins. several hospitalizations (0–3 the previous year) because of DIOS, despite high-dose of osmotic laxatives (PEG4000, 40 to 60 g/d). P232 Aloe arborescens was used for 8 months (5–12), at a median dose of 5 mL Retrospective review of admissions to a tertiary paediatric hospital twice a day (max 20 mL/d), continuously. In all cases, PEG4000 could be with suspected DIOS over 5 years stopped and abdominal pain reduced, improving their quality of life. We S. Murphy1, L. Thomson2. 1Royal Hospital for Children, Glasgow, United observed a marked reduction of hospitalisation; one of them was Kingdom; 2Royal Hospital for Children, Paediatric Respiratory, Glasgow, United hospitalised for a mild DIOS and required a lower dose of PEG 4000 at Kingdom home. It was well tolerated without potassium abnormalities. Conclusion: These clinical observations revealed that Aloe arborescens Objectives: was effective and well tolerated at short and medium-term in CF - To establish the proportion of CFGI admissions with severe constipa- children. Anthroquinones are described as CFTR potentiators that tion requiring inpatient treatment vs. DIOS (Incomplete and Complete) stimulate colonic chloride and fluid secretions. It suggests that Aloe as defined by ESPGHAN working group. arborescens could be considered as an alternative treatment for chronic - To compare the management and complications of each group. constipation in CF children. A clinical trial should be performed to confirm - To obtain baseline data prior to more universal use of CFTR modulators. these data. Methods: All CF admissions June 2014–2019 coded as ‘Gastrointestinal P235 manifestation of cystic fibrosis’ were reviewed. Digestive endoscopy in adult cystic fibrosis patients Patients were classified as Constipation, DIOS (Incomplete) and DIOS 1 2 1 1 1 1 (Complete) as defined by the ESPHGAN working group. M.V. D’Ascenzo , E. Baran , C. Girotti , M.C. Calzona , M. Ferrario . HIGA R 2 Data was collected on patient demographics, pancreatic status, previous Rossi, Gastroenterology, La Plata, Argentina; HIGA R Rossi, Pulmonology, La meconium ileus/bowel surgery, treatment, length of stay. Plata, Argentina Results: 52% (42/81) of all CFGI admissions were managed as suspected Objectives: Upper gastroscopy and colonoscopy are techniques that play a DIOS. role key in improving diagnostic and therapeutic making decision in the 57% (24/42) male, 43% (18/42) female. follow up of adult patients with cystic fibrosis. 2 patients were on a CFTR modulator (ivacaftor), both had CF-related Methods: Retrospective, descriptive study of adults >16 years with constipation. diagnosis of cystic fibrosis (CF), period evaluated 2006–2019. Clinical, CF related constipation: 34/36 (94%) pancreatic insufficient(PI) and 18/36 mutations, body mass index (BMI), forced expiratory volume in the first (50%)previous bowel surgery/meconium ileus. All successfully medically second (FEV1) were analysed and reports of abdominal video endoscopic managed. findings were obtained. The results were expressed as mean 1 ± SD or 34/36 (94%) received gastrograffin, alone or with additional laxative. median and range. 10/36 (28%) required enemas (5 multiple). 6/36 (17%) received Kleanprep Results: 70 patients, 39 (55.8%) males, average age 29.5 ± 10.2 years. Range (all had >1 dose). 16–68 years. Mean age at diagnosis 27.5 months. Average BMI 21.2 ± 2.69 Median length of hospital stay: 2.5 days. m/kg2. Pancreatic insufficiency in 47 (67.1%), cirrhosis in 6 (8.5%), CF related Incomplete obstruction: 2/2 (100%) PI, 1/2 (50%) previous bowel surgery/ – diabetes in 21 (30%) patients. Median FEV1 45% (R = 11 107%). F508del in meconium ileus. Both initially medically managed. 1 required surgery and 56.1% of mutated alleles. Twenty endoscopic studies were performed: 12 1 resolved with combination of medical treatments. diagnoses (9 gastroscopies and 3 colonoscopies) and 8 therapeutic Median length of hospital stay: 10 days. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S123

(3 percutaneous endoscopic gastrostomies, 3 ligatures of oesophageal with the HRB Clinical Research Facility in Cork for project steerage, varices, 1 gastric polypectomy, 1 colonoscopic polypectomy). statistical support, and assistance with PPI. Our steering committee will Conclusion: Digestive endoscopy is a procedure that facilitates the include a patient representative as well as representation from Cystic diagnosis and allows to perform minimally invasive techniques to Fibrosis Ireland. various abdominal disorders that involve adult patients with cystic fibrosis. Results: The project has been granted ethical approval and patient Upper gastroscopy and colonoscopy are techniques that play a key role in recruitment has begun. improving diagnostic and therapeutic decision making in the follow-up of Conclusions: There is currently no data available on the oral health of adult patients with CF. adults with CF. If CF patients are found to have high levels of dental disease they will need to be categorised as high-risk individuals from the moment P236 of diagnosis. Considering the requirement for any transplant candidate to The level of faecal calprotectin in patients with cystic fibrosis in the be dentally fit, oral health must be part of the holistic management of CF. Krasnoyarsk region 1 1 2 1 P238 N. Ilenkova , V. Chikunov , E. Kondratyeva . Krasnoyarsk State Medical 2 Gastrointestinal problems in cystic fibrosis patients after lung University, Krasnoyarsk, Russian Federation; Research Center for Medical transplantation Genetic, Moscow, Russian Federation A. De Jaegere1, S. Van Meerbeeck1, J.G. Mainz2,R.Vos3, L. Dupont1,3. There is increasing evidence that intestinal inflammation plays a major role 1University Hospital Leuven, CF Center, Leuven, Belgium; 2Brandenburg in gastrointestinal symptoms in cystic fibrosis (CF). Calprotectin, a protein Medical School (MHB) University, Pediatric Pulmonology and Cystic Fibrosis, found mainly in neutrophils, but also in monocytes and macrophages, is Brandenburg an der Havel, Germany; 3University Hospital Leuven, Lung released during neutrophil activation or death. Faecal calprotectin (FC) is Transplant Team, Leuven, Belgium inflammatory marker and elevated in a variety of inflammatory intestinal diseases, but little is known about its value in CF. Background: With increasing survival due to better nutritional manage- The present study was performed to determine the frequency of FC in CF ment and medical therapy, more CF patients will experience GI problems. patients in Krasnoyarsk regional and to determine whether there are any In CF patients with end stage lung disease refractory to current therapies, associations with different characteristics such as pancreatic status, lung transplantation (LTx) remains a viable option and 10–15% of the CF gastrointestinal morbidities, pulmonary function tests? exacerbations population have currently been transplanted. In contrast to the improved and antibacterial therapy. respiratory disease morbidity, we hypothesize that LTx patients are more Methods: The study involved 32 patients. Faecal calprotectin was susceptible to abdominal complications, that may have a profound impact measured using the commercially available ELISA kits (PhiCal test). on morbidity and quality of life (QoL). Clinical data were collected from patients’ records and CF registry. Objectives: We evaluated the frequency and impact of GI problems in adult Results: A total of 32 patients participated in the study. The median patient CF patients that received a LTx by means of the CFAbd-score, a PROM for age was 11 years. The median FC level was 280 mcg/g (16,4–600 mcg/g). assessment of abdominal involvement and related QoL in CF. There was a statistical difference in regards to the use of antibiotics (inhaled Methods: 41 transplanted CF patients filled in the CFAbd-Score, the total & or/and oral): patients who did not take antibiotics had faecal calprotectin subdomain scores (reversely scored on a 0 to 100 scale) were calculated and levels above 50 mcg/g (average 480 mcg/g) (p = 0.01). related to demographics, medical history and different disease Conclusion: The causes of intestinal inflammation in patients with СFare characteristics. multifactorial. FC is used as a marker of inflammation, but may not be as an Results: GI problems were present in a majority of patients (CFLD 24%, accurate indicator of intestinal inflammation in CF. However, a larger cohort DIOS 37%, GERD 48%, Clostridium 59%, CFRD 81%). The median CFAbd- of patients is needed to confirm these findings. Score was 77, which was lower (meaning more symptoms) than previously reported scores in non-LTx CF patients. Female patients had a significantly lower score (70 vs 87; p = 0.01) and reported significantly more abdominal P237 pain, GI symptoms and related QoL. A history of abdominal surgery, Oral health in adults with cystic fibrosis meconium ileus or GERD was associated with significantly higher loads of 1 ’ 1 1 1 1 N. Coffey ,F.O Leary ,M.Hayes, F. Burke . University College Cork, symptoms. Restorative Dentistry, Cork, Ireland Conclusion: Receiving a LTx apparently leads to more GI symptoms and Objectives: To conduct a cross-sectional study to lower QoL. Our study suggests that the CFAbd-Score is a useful tool for 1. Measure Dental Caries (tooth decay) prevalence in adults with CF assessing morbidity related to GI problems in CF patients after LTx. 2. Measure Periodontal Disease (gum disease) prevalence in adults with CF P239 3. Generate data to secure grant funding to study the oral health of CF Liver damage in cystic fibrosis: visualisation versus serum markers in sufferers on a larger scale and in particular to sequence the oral paediatrics microbiome of adults with CF. Y.Gorinova1, A. Surkov1, I. Smirnov1, E. Kulebina1, O. Simonova1, A. Ignatova1. 1Federal State Autonomous Institution of Russian Federation Ministry of Methods: A cross-sectional study will be conducted. Adults (age ≥18) with Health ‘National Medical Research Center for Children’s Health’, Moscow, CF will be recruited from the Adult Cystic Fibrosis Unit in Cork University Russian Federation Hospital. Age and gender matched counterparts will be recruited through Objectives: To assess the severity of pathological changes in liver of cystic advertising. A sample size calculation was performed for one of the fibrosis (CF) patients. parameters of the study- namely decayed, missing, filled teeth (DMFT). Methods: 80 CF patients were enrolled. The degree of fibrosis was assessed Using the average reported DMFT in the Irish adult population (DMFT = 15), using transient elastography on Fibroscan R502 apparatus in accordance it was calculated that 63 in each group will have 80% power to detect a with the METAVIR scale (stages F0-F4). Additionally, hepatoscintigraphy difference in means of 2.0 assuming that the common standard deviation is was performed on a Millennium MG gamma camera using Technefit 4 when a two group t-test is used with a 0.05 two-sided significance level. Tc99m. The following indicators were studied: the coefficient of blood However, given the lack of baseline data, a target of 90 participants per retention (CBR), the index of hepatic uptake (IHU) and the rate of uptake of group will be set. Participants will be given a full dental examination the drug by cells (RDU). recording DMFT and periodontal pocketing depths. We will collaborate S124 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

To assess the severity of liver fibrosis matrix metalloproteinase-2,8,9 Methods: We evaluated all Bulgarian CF patient’s data regarding the results (MMP-2,8,9), tissue inhibitor of MMP (TIMP-1) and transforming growth for transaminase levels and echography images. We also gathered the full factor β (TGF β) were determined. family and medical history. Results: The absence of liver fibrosis was detected in 57 patients (71%), Results: A total of 53 patients out of 195 were receiving therapy for CFLD. mild-moderate fibrosis (F1–2) in 12 patients (15%), severe fibrosis-cirrhosis Echography changes in liver were found in 41, additionally 12 more had (F3-F4) in 11 patients (14%). There were no statistically significant constantly elevated transaminase levels. Two patient had complications differences between the concentrations of the studied biomarkers in such as portal hypertension and oesophageal varices. patients with fibrosis/cirrhosis (F1–4) and without it (F0). Conclusion: Prevalence of CFLD is around 27% in the Bulgarian CF patients. A correlation was revealed (Spearman test) between TIMP-1 with CBR: r=−0.462, p = 0.03, MMP-8 with CBR: r = −0.511, p = 0.015 and IHU: P242 r = 0.333, p = 0.043, TGF β with MMP-8 : r = 0.229, Therapy with lumacaftor/ivacaftor (LUM/IVA) in paediatric patients p = 0.04. with liver cirrhosis Conclusion: The concentrations of serum hepatic fibrosis markers do not I. Rudolf1, M. Stahl2, N. Junge1, E. Pfister1, O. Sommerburg3, D. Schöndorf3, reflect the severity of structural changes in liver of CF patients, but their A.-M. Dittrich1. 1Medizinische Hochschule Hannover, Hannover, Germany; correlation with hepatoscintigraphy data may indicate to participation of 2Charité Berlin, Berlin, Germany; 3Universitätsklinikum Heidelberg, these molecular compounds in liver fibrogenesis. Heidelberg, Germany

P240 Objectives: LUM/IVA is approved for the treatment of CF patients Non-invasive evaluation of liver fibrosis by transient elastography and homozygous for F508del ≥2 years in Germany. Elevation of LFTs biochemical markers in patients with cystic fibrosis culminating in liver failure is a known adverse reaction of LUM/IVAbut A. Stamatova1, S. Fustikj1, L. Spirevska1, M. Trajkovska2, A. Petlichkovski3. CFTR- modulator therapy might also stabilise CF liver disease where other 1University Children’s Clinic, Department for Cystic Fibrosis, Skopje, North treatment options are limited. We present two 8-year old boys with severe Macedonia, The Republic of; 2University Clinic for Gastroenterohepatology, CF hepatopathy (Child-Pugh class A) comprising cirrhosis and portosys- Skopje, North Macedonia, The Republic of; 3Institute for Immunobiology and temic collaterals initiated on LUM/IVA. Human Genetics, Skopje, North Macedonia, The Republic of Methods: Examination of LFTs, anthropometry, lung function testing, abdominal ultrasound, sweat testing, lung X-ray. Objectives: This study aims to show the diagnostic accuracy of transient Results: We initiated LUM/IVA in both patients at a reduced dosing scheme elastography (TE)-FibroScan and non-invasive serum markers tests in the (100/125 mg QD). After bi-weekly assessment of LFTs, we reached an assessment of liver fibrosis in patients with cystic fibrosis (CF). increased dose of 100/125 mg BID in both patients after two months. Methods: 14 patients with CF were involved in this study. The non-invasive In patient A LFTs declined (AST 91/62 U/l, ALT 67/44 U/l) during the initial 3 markers used were: hyaluronic acid (HA), N peptide of collagen type III months of LUM/IVA and parameters of liver synthesis showed improve- (PIIIN-P) and collagen type IV (C IV). Chemiluminescence immunoassay ments (CHE 4,38/5,5 kU/l, albumin 29/34 g/l). Similarly, LFTs in patient B (CLIA) analyzer MAGLUMI was used for quantitative determination of the allowed LUM/IVA increases to 100/125 mg QD after two months but didn’t markers in human serum. Transient shear wave elastography was show significant improvements yet. performed using Hitachi HI VISION Ascendus system and four fibrosis In patient A FEV1%pred. remained stable, LCI (16 vs. 8) and BMI (16,2 vs. stage were defined: Mild fibrosis (F0-F1), Significant fibrosis (F > 2), 18,3 kg/m2) improved during the first 18 months on LUM/IVA. Patient B has Advanced fibrosis (F > 3) and liver cirrhosis (F = 4). been on LUM/IVA for only two months now during which we observed an

Results: Mean age of the patients was 19,9 ± 5,1. Three patients (20%) were improvement in FEV1 (67 vs. 76%pred.), LCI (9 vs. 7.9) and in BMI (17.4 vs. evaluated to have ≥F3 hepatic fibrosis, eight had stage F2 hepatic fibrosis 18.1 kg/m2). In neither patient could we observe changes in liver (53,9%) and four had stage F0-F1 (26,6%). From the fibrosis markers the ultrasonography after initiation of LUM/IVA yet. most commonly elevated marker was PIIIN-P (75%) which showed higher Conclusion: Our cases illustrate successful initiation of LUM/IVA therapy levels in patients with fibrosis grade F2 and above (positive correlation, despite advanced CF hepatopathy. We observed no adverse effects of LUM/ r = 0,06). IVA treatment on LFTs. Our patients also benefited in the well described The other markers didn’t show elevation in patients with fibrosis grade F2 domains of lung function and BMI. We caution however, to extrapolate our and bellow. cases, as young age (and recent diagnosis in patient A) might have also Conclusion: Our study, even though limited in the number of patients, affected outcomes. More research on the effect of CFTR modulation on CF showed positive correlation between the fibrosis markers PIIIN-P and liver liver disease is therefore highly desirable. fibrosis, evaluated with transient elastography. Further studies with a bigger patient pool are necessary to establish the connection between the P243 other examined fibrosis markers and the extent of liver damage. Is there a need to set standardised HbA1c and continuous glucose monitoring targets for people with Cystic Fibrosis-Related Diabetes? P241 L. Jones1,H.Sunsoa1,E.F.Nash1, R. Rashid1,N.Patel1,A.Syed1, J. Whitehouse1. Cystic fibrosis-associated liver disease prevalence in Bulgarian cystic 1University Hospitals Birmingham, West Midlands Adult Cystic Fibrosis Centre, fibrosis patients Birmingham, United Kingdom M. Nikolova1, B. Gospodinova2, M. Baycheva3, K. Ketev4, N. Guenkova4, V. Nedkova5, I. Hristov1, M. Georgieva1, P. Perenovska2, G. Petrova2. 1Medical Objectives: At our large regional adult CF centre we routinely use both University of Varna, Pediatric Department, Pediatric Clinic, University Hospital HbA1C and Continuous Glucose Monitoring (CGM) to diagnose and ’ ‘St Marina’, Varna, Bulgaria; 2Medical University of Sofia, Pediatric monitor patients diabetes. There are clear guidelines regarding targets Department, Pediatric Clinic, University Hospital ‘Alexandrovska’, Sofia, for both Type 1 and Type 2 diabetes but there are no similar guidelines with Bulgaria; 3Medical University of Sofia, Pediatric Department, Gastroenterology regards to CFRD. We conducted a survey to identify HbA1C and CGM Clinic, SBALDB ‘Prof. Ivan Mitov’, Sofia, Bulgaria; 4Medical University of targets currently being used in CF centres in the UK. Plovdiv, Pediatric Department, Pediatric Clinic, University Hospital ‘St George’, Methods: An online survey monkey was distributed to CF clinical nurse Plovdiv, Bulgaria; 5Medical University of Pleven, Pediatric Department, specialists and dieticians across the UK. The survey included 10 questions Pediatric Clinic, University Hospital ‘G. Stranski’, Pleven, Bulgaria gathering information on the HbA1C and CGM targets that are currently being used and which guidelines being followed. Objectives: Published data so far claim that cystic fibrosis-associated liver Results: We had 56 completed surveys. 73% were unaware of any national disease (CFLD) affects around 30% of patients. or international guidelines that set targets for HbA1C in CFRD and 87% were We aimed to estimate the CFLD prevalence in Bulgarian CF patients. unaware of any guidelines for CGM in CFRD. 62% had set targets for HbA1C, however they varied. Only 38% had a set target for CGM, again with Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S125 variation (Table 1). Those who did not currently have set targets for CGM P245 were asked what targets they would like patients to aim for, again Screening and treatment of Cystic Fibrosis-Related Diabetes at a UK producing varied suggestions (Table 2) adult cystic fibrosis centre 1 1 1 Table 1. M. Mitchell-Whyte , D. Sills . Nottingham University Hospitals NHS Trust, CGM targets currently being used by individuals Wolfson Cystic Fibrosis Unit, Nottingham, United Kingdom

CGM Results % below % target range % above Objectives: To assess current practice in screening and treatment of cystic 3.9 mmol/L (4–8 mmol/L) 8 mmol/L fibrosis related diabetes (CFRD) at an adult centre. Methods: Retrospective observational study of adults at Wolfson Cystic – – – Range of individual 0 565100 0 30 Fibrosis Centre, UK. Data was collected from medical records including responses current diagnosis of CFRD, screening status for those without CFRD, method of screening and result. For those with CFRD, treatment and HbA1C Table 2. were checked. This audit was based on the National Diabetes Mellitus Proposed CGM targets by individuals audit1 CGM results % below % target range % above Results: 215 individuals were identified, 95 female and 120 male with a 3.9 mmol/L (4–8 mmol/L) 8 mmol/L mean age of 30.43 years ± 10.26. 78 people had prior CFRD (36%). 90 people (42%) without known CFRD were screened and 47 were not (22%). Only 66% Range of individual 0–20 60–100 0–25 of those eligible were screened. The majority of screening was done via responses OGTT.

Conclusion: It is common practice for HbA1C and CGM to be used in the management of CFRD, however this survey highlights wide differences in Method of screening N Percentage how CFRD is managed and the lack of guidelines available. Recent (%) guidelines were published with an international consensus for CGM targets for both type 1 and 2 diabetes. Our proposal would be to adapt OGTT 45 50 OGTT & Home glucose monitoring 7 8 these guidelines for the CF population with a modified target range ie: 70% – OGTT & Continuous Glucose monitoring 2 2 of readings to be within target range of 3.9 8 mmol/L, <4% to be below, Random glucose monitoring 31 34 <25% to be above but with <5% to be above 13.9 mmol. Development of Continuous Glucose monitoring 1 1 agreed targets will improve outcomes and reduce confusion amongst Home glucose monitoring 4 4 patients and practitioners. [Screening Methods] P244 Simplification of Cystic Fibrosis-Related Diabetes screening by the use Total number with CFRD at the centre was 87 (40%). Of those diagnosed of a home-based oral glucose tolerance test: a pilot study to evaluate with CFRD 79% were treated with insulin, with a small number being feasibility, validity and patient perception (AtHome) treated with DPP4 inhibitors or sulphonylureas (6%). Hbac1c was checked at least annually in 96% of those with CFRD, with a mean level of V. Boudreau1,2, A. Bonhoure1,3, C. Bergeron1,2, J. Colomba1,2, D. Mignault1, 54.6 mmol/mol ± 22.97. K. Desjardins1, F. Tremblay4, R. Rabasa-Lhoret1,2,4. 1Montreal Clinical Conclusion: Rate of screening was below national standards which Research Institute, Montréal, Canada; 2Université de Montréal, Montréal, recommends annual screening for all patients over 10 years2. The Canada; 3McGill University, Montréal, Canada; 4Centre Hospitalier de method of screening could also be improved. Majority of patients are l’Université de Montréal, Montréal, Canada treated with insulin, which is recommended, however its efficacy would be Objectives: We propose a pilot study (n = 40) to compare, in adult patients useful. This review provides a good baseline based on current practice for with CF, the standard hospital-based OGTT to alternative home-based comparison next year when screening guidelines are changed. OGTTs with measures of glucose using continuous glucose monitoring References system (CGMS) and capillary blood glucose (CBG) with 75 g of glucose using the standard glucose beverage or candies. [1] NHS Digital (2019) National Diabetes Audit,2017–18 Methods: We recruited 34 participants. After the standard hospital-OGTT [2] Cystic Fibrosis Trust (2016) Nutritional Management of Cystic (reference method), a CGMS (Abbott Flash Libre) was installed for a 2-week Fibrosis period. Participants had to perform two OGTTs at home in a randomised order, one with the glucose beverage and one with candies. Participants P246 had to measure CBG before each OGTT (fasting), at 1-h and 2-h. Participants A multidisciplinary approach to assessing whether the use of an oral also filled out a test appreciation form and reported side effects (nausea, glucose tolerance test alone in cystic fibrosis is an adequate test to headache and dizziness). capture cystic fibrosis diabetes in the early stages or does the use of the Results: At the standard OGTT,16 patients had a normal glucose tolerance, ‘Medtronic iPro2®’ continuous glucose monitoring device improve the 5 had undetermined glucose tolerance (>11.0 mmol/L at 1-h, but < rate of early diagnosis and treatment? 7.8 mmol/L at 2-h), 9 were glucose intolerant (IGT; 2-h value >7.7 mmol/ D. O’Neill1, O. Smith1, V. Lynch1, C. Gorman1, E. Moore1, M. Emma1, V. Mills1, L) and 4 had CFRD (2-h value >11.0 mmol/L). When comparing results from A. Nugent1, J. Rendall1. 1Belfast Health and Social Care Trust, CF Unit Level 8 the home-based OGTT using the glucose beverage with the standard OGTT, Belfast City Hospital, Belfast, United Kingdom there was a 50.0% concordance for CBG measures and a 66.7% concordance for CGMS time-points (fasting, 1 h and 2 h). When comparing results from Objectives: Cystic fibrosis diabetes (CFD) is known to be associated with the home-based OGTT using the candies with the standard OGTT, impaired pulmonary function, weight loss and a higher mortality rate. concordance was 50% for both the CBG measures and the CGMS results. Earlier detection and treatment with insulin improves outcomes including Only 12.5 to 33.5% of patients who were IGTat the standard OGTT remained mortality rates. To investigate if the introduction of continuous glucose classified into this glucose-tolerance category after the home-based tests monitoring (CGM) would yield positive diagnosis of CFD and prompt (sweet beverage or candies) with CGMS or CBG. Sixteen patients reported subsequent earlier treatment with insulin when oral glucose tolerance test having difficulties to eat all candies in 5 minutes. (OGTT) has been inconclusive i.e. impaired or indeterminate. Conclusion: Classification of glucose tolerance with home-based OGTTs Methods: Patients were offered annual OGTT. Patients with an impaired or are inconsistent with the standard OGTT regardless of the glucose source or indeterminate result with clinical decline or reactive hypoglycaemia at the measurement method (CGMS or CBG). OGTT were offered CGM and positive results discussed at a CFD MDT lead by the CF consultant and Diabetologist. S126 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Age range: males 18–42 years with median of 27 years and females 21–39 days. At day 14, sensors were removed, data was uploaded and participants years with median of 27.5 years. were requested to complete a user experience questionnaire. CGM was carried out on 35 patients 11% of CF population) in 12 months. Of Results: 18 Subjects provided a total of 1156 duplicate measurements with those, 22% (n = 8) were normal, 17% (n = 6) had impaired glucose tolerance a mean (95% CI) of 64 (55–74) duplicate readings per subject. Mean age, and 12% (n = 4) indeterminate on CGM. There were 49% (n = 17) in the CF- Weight and Body Mass Index were 36.4 years, 69.3 kgs and 24.1 kg/m2. The related diabetes range who were started on insulin. Of the patients mean HbA1c was 60.1 mmol/L. The mean (95% CI) absolute difference diagnosed with CFD on CGM, only 11% (n = 4) were in the diabetic range on (FreeStyle Libre versus CBG) was 0.27 mmol/L (−1.7, 2.5). The mean (95% CI) OGTT. relative difference (FreeStyle Libre/CBG) was 105% (82%, 130%). In 41.4% of Results: Data are presented for 35 patients (51% female); duplicates the relative difference was >10% (28.2% of duplicates were >110%, 13.2% of duplicates were < 90%). The sensitivity of the FreeStyle Libre for a Table 1. CBG reading of <4.0 mmol/L (n = 120) was 73% with a mean absolute Diabetes investigation results difference (FreeStyle Libre versus CBG) in this subgroup of 0.47 mmol/L. In HbA1c OGTT CGM 16/18 patients, the user experience questionnaire favoured the FreeStyle Libre device with 94% of patients recommending its use for other CF Normal 69% 10% 22% patients. There was a high sensor fall off rate with 5 participants (27%) Hypo N/A 20% N/A reporting this. Impaired 31% 42% 17% Indeterminate N/A 17% 12% Conclusion: Whilst user acceptability is very high in our cohort the level of CFRD 11% 11% 49% variability between CBG and FreeStyle Libre supports a cautioned use of this potentially liberating technology pending further data.

Conclusion: Following CGM 49% (n = 17) were identified as being in the P250 diabetic range and needing treatment despite having an OGTT result which The impact of FreeStyle Libre flash glucose monitoring system on would not have prompted diagnosis of CFD. HbA1c in patients with Cystic Fibrosis-Related Diabetes Our results suggest that CGM is superior to OGTT in diagnosing CFD thus M.O. Hagan1, J.A. McDermott1, L.N. Spillman2,3, C.A. Stackhouse1. 1Royal prompting earlier intervention to prevent deterioration. Papworth Hospital NHS Foundation Trust, Adult Cystic Fibrosis Centre, Cambridge Centre for Lung Infection, Cambridge, United Kingdom; 2MRC P247 Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom; Cystic Fibrosis Diabetes Mellitus (CFDM)? Can we predict who is at risk? 3 1 1 Cambridge University Hospitals NHS Foundation Trust, Cambridge, United J. Still . Aberdeen Royal Infirmary, Nutrition & Dietetics, Aberdeen, United Kingdom Kingdom Cystic Fibrosis-Related Diabetes (CFRD) is common in adults (CF Trust, Objectives: Clinical consequences of CFDM include, poor lung function, 2019). Raised HbA1c is associated with nutritional and lung function low weight, mental health issues and reduced life expectancy. It has been decline alongside microvascular complications (CF Trust, 2004). The shown however that early detection and treatment can delay clinical FreeStyle Libre flash glucose monitoring system (FSL) is funded for use in deterioration. The objective of this study was to investigate clinical risk CFRD (NICE, 2019). The use of FSL in patients with diabetes has been factors for the development of CFDM, allowing those at risk to be identified. studied (Al Hayek, 2017) but there is limited data in CFRD. Methods: This retrospective cohort study included 66 individuals in Objectives: Our aim was to investigate the effect of FSL on the HbA1c in Grampian with Cystic Fibrosis. Age, gender, genotype, weight, BMI, lung CFRD. function, liver disease status and pancreatic sufficiency status were all Methods: Twelve patients with CFRD on insulin commenced regular use of collected from the participants medical notes. Univariate associations the FSL between 1st June 2018 and 31st July 2019. HbA1c was recorded at between the development of diabetes and possible clinical risk factors baseline and between 3–9 months post FSL as part of routine care. To were analysed using Kaplan Meier plots with log-rank tests of statistical compare natural variance, HbA1c was recorded 6–12 months prior to significance. Patients were grouped for FEV1% predicted (<50%, > = 50%) and starting FSL (pre-baseline). Median results were compared using Wilcoxon for BMI (<=19, >19). signed-rank test. Results: This study did not find statistical significance for the presence of Results: There was no significant difference in median HbA1c (mmol/mol) DF508 gene or FEV1 as a risk factor for the development of CFDM. This at pre-baseline (52.5, IQR 37.8–76.0) compared with baseline recordings study did find that the presence of liver disease, low BMI and previous IGT (59, IQR 41–85.8), p = 0.20. There was a trend towards a reduction median were linked with an increased risk of CFDM. BMI was the only independent HbA1c (mmol/mol) post FSL (52, IQR 39.5–62.8), p = 0.05 compared with risk factor which had statistical significance ( p = <0.001). baseline (59, IQR 41.3–85.6). Conclusion: The data gained from this study could be used to identify Conclusion: We conclude regular use of FSL showed a reduction in median those at risk of CFDM allowing prompt diagnosis and treatment, which may HbA1c after 3–9 months. We propose further study with longer term ’ in turn improve individual s outcomes. evaluation to confirm the impact of FSL on HbA1c in patients with CFRD.

P249 References Clinical utility and effectiveness of the flash glucose monitor FreeStyle CF Trust (2019) UK Cystic Fibrosis Registry Annual Data Report 2018. Libre versus capillary blood glucose (CBG) measurements in adults with Published by Cystic Fibrosis Trust. London. – Cystic Fibrosis-Related Diabetes (CFRD) a pilot study CF Trust (2004) Management of Cystic Fibrosis related Diabetes. 1, 2 1, 2 1,3 1 1 C. Howlett , K. Cronin , D. Morrissy , M. Mc Carthy , C. Flemming , Published by CF Trust. London. 3 1, 3 1 J.A. Eustace , B.J. Plant . Cork University Hospital, Cork Centre for Cystic NICE (2019) Flash Glucose Monitoring: National arrangements for Fibrosis, Cork, Ireland; 2Cork University Hospital, Department of Nutrition and 3 funding of relevant diabetes patients. NICE. Dietetics, Cork, Ireland; University College Cork, HRB Clinical Research, Cork, Al Hayek A. et al. (2017) Evaluation of FreeStyle Libre flash glucose Ireland monitoring system on glycemic control, health-related quality of Objectives: To assess the relationship between simultaneous self-mon- life, and fear of hypoglycemic in patients with type 1 diabetes. itoring capillary blood glucose (CBG) readings and FreeStyle Libre readings Clinical Medicine Insights: Endocrinology and Diabetes, Vol. 10: 1–6. in a cohort of cystic fibrosis patients with CFRD and user acceptability/ safety of the FreeStyle Libre in a cohort of patients with CFRD. Methods: Participants were required to perform 6 CBG tests daily followed immediately by a FreeStyle Libre flash sensor reading for 14 consecutive Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S127

P251 median of 6% (0 to 28). After 3 months of using flash glucose monitoring, 3/ “It’s an absolute life-changing device”- adults with Cystic Fibrosis- 28 (11%) patients achieved good control (time in range >70%). Related Diabetes experiences of the Freestyle Libre (FSL) flash glucose Conclusions: Flash glucose monitoring was beneficial in the majority of monitoring system patients with CFRD who are administering insulin. After 3 months of flash D. Shimmin1, M. Mansfield2, K. Taylor2, L. Pearson2, Y.W. Lim2, glucose monitoring 58% of patients had improved their % time in range. C. Etherington2, I. Clifton2, D. Peckham2. 1Leeds Teaching Hospitals NHS Some patients saw a decrease in % time in range after 3 months, the reasons Trust, Adult CF Unit, Leeds, United Kingdom; 2Leeds Teaching Hospitals NHS for which require further investigation. Data collection is ongoing and we Trust, Adult CF Unit, Leeds, United Kingdom will continue to measure the impact of flash glucose monitoring on a number of relevant CFRD outcomes. Objectives: Self-measured blood glucose (SMBG) testing is important for diabetes management, with >8 tests/day being associated with improved P253 glycaemic control. Repeated daily SMBG can be painful, inconvenient and Continuous monitoring of diabetes mellitus (DM) parameters, difficult to maintain long-term. For people with CFRD this may add to their correlated with pulmonary function monitoring, leading to improving high treatment burden and impact on treatment satisfaction and health- general health in patients with cystic fibrosis related quality of life (HRQoL). 1 2 2 S. Momchilovikj , T. Jakjovska , I. Arnaudova-Danevska , The FSL system comprises a wearable sensor and reader to monitor glucose 2 2 1 E. Gjinovska-Tasevska , M. Atanasova-Nadjinska . Institute for Pulmonary levels at any time without need for routine SMBG tests. Use of FSL has 2 Diseases in Children, Skopje, North Macedonia, The Republic of; Institute for proven clinical and non-clinical benefits in types 1 and 2 diabetes. In the UK Pulmonary Diseases in Children, CF Department, Skopje, North Macedonia, FSL has become available for people with CFRD on insulin since May 2019. The Republic of This study aimed to explore early experience of FSL use by adults with CFRD attending a large regional CF unit. Background: Diabetes Mellitus is a very common disease in adult patients Methods: Adults with insulin-treated CFRD using the FSL system were with Cystic Fibrosis. Patients with uncontrolled diabetes may experience invited to respond to a short survey exploring previous SMBG practice, FSL more worsening of the main disease as well as prolonged hospital days and usability, treatment satisfaction and health related quality of life (HRQoL). intravenous therapy. Results: Responses from 48/50 (96%) surveys were received (20 male, Material and methods: We followed adult Cystic Fibrosis-Related Diabetes median age 37 [19–52] years). Prior to using FSL, 27% (n = 13) checked <1 (CFRD) patients that attended our department of Cystic Fibrosis in Skopje, SMBG/day; 21% (n = 10) checked > 8/day (recommended). More than 88% of North Macedonia during 2019 year. Collected data included age, gender, all subjects agreed/strongly agreed FSL system was easy and comfortable to weight, height, body mass index (BMI), forced vital capacity (FVC), forced wear, obtaining glucose was more discreet than routine SMBG testing and expiratory volume at 1 second (FEV1), glycated hemoglobin (HbA1c), that they engaged in more frequent glucose checks than before. SMBG fasting plasma glucose (FPG), days of hospitalisation, genotype, microbio- tests/day were reduced, with additional tests primarily to check a displayed logical finding in sputum. hypoglycaemia or confirm accuracy of the FSL system. Most subjects (n = 47, Results: From 26 patients, 12 are with DM (46,15%), 58,3% of them are 98%) recommended and wished to continue using FSL, with glucose trend homozygote for F508del , male 8 (66,66%), female 4 (33,33%), median age arrows and scanning function being the highest rated features. Additional 27,8 years (20–33 y), median HbA1c = 7,46% (ranged 6,3–12,6%), median responses (n = 28) received were suggestive of overall improved HRQoL and BMI = 19,16 kg/m2, 3 (24%) of them are with low weight under 18 kg/m2 treatment satisfaction. BMI. Median FPG = 6,0 mmol/l (ranged 5,2–8,2), glucose in urine = positive Conclusion: The FSL system is highly rated by adults with CFRD attending a in 6 (50%) patients (glu/u = +1+4). With peripheral neuropathy are 6 regional CF unit and may have an important role in improving diabetes self- patients (3 of them are women). For pulmonary function we obtained the management. following results: median FVC = 3,24 L (ranged 1,34–6,73 L), 71,63% (37,08– 123%), median FEV1 = 2,12 L (0,85–5,33 L), 50,17% (25–116%), with chronic P252 Pseudomonas aeruginosa are 66,66%, the others are with chronic Initial impact of flash glucose monitoring for patients with Cystic Staphylococcus aureus infection. Days of hospitalization with intravenous Fibrosis-Related Diabetes antibiotic therapy, for each individual patient median average is 27,25 days J. Snowball1, H. Corry1, A. Hart1, S. Chapman1,R.Rea2,3, A. Lumb2,3, per year, (1–4 hospitalisation for 14 days/year). W. Flight1. 1Oxford University Hospitals NHS Trust, Oxford Adult Cystic Fibrosis Conclusion: Uncontrolled diabetes in the patients with CF, is associated Centre, Oxford, United Kingdom; 2Oxford Biomedical Research Centre, Oxford, with worsening of the main disease which includes chronic pulmonary United Kingdom; 3Oxford Centre for Diabetes, Endocrinology and Metabolism, infection, prolonged hospital days, worse lung function, with lower or Oxford, United Kingdom normal weight. Continuous follow-up of patients and their blood glucose level are importance to reduce micro and macro vascular complications and Objectives: Flash glucose monitoring became widely available for people worsening of the main disease. with CFRD in the UK in March 2019. We assessed the initial impact of this technology on glucose control. P254 Methods: Patients with CFRD using flash glucose monitoring (FreeStyle Establishing face validity of the MAGIC programme for people with ® Libre ) at our centre were included. Data was collected retrospectively from cystic fibrosis diabetes (CFD) the Libreview web-based platform. Optimal flash glucose range was set as 1, 2 1 2 2 1 S. Collins , A. Jones , S. Woodward , J. Sturt . Royal Brompton & Harefield 3.9–7.8 mmol/l with >70% time in range considered good glucose control NHS Foundation Trust, Cystic Fibrosis Department, London, United Kingdom; (based on international consensus in type 1 diabetes). We compared % time 2 King’s College London, London, United Kingdom in range over 14 days at baseline and at 3 months. Results: 42 patients used flash glucose monitoring with 33 patients (17M/ Background: The Managing Abnormal Glucose In Cystic fibrosis (MAGIC) 16F) having complete data at baseline and 3 months. Baseline median % programme is an on-line, evidence-based, self-management education time in range was 23.5% (range 3–89%) compared with 41% (range 7–86%) programme for people with cystic fibrosis diabetes (CFD). It was developed, at 3 months, an overall increase in median % time in range of 17.5%. using the principles of co-design, by a stakeholder development group 5/33 (15%) patients were classed as having good glucose control at baseline consisting of people with CFD and healthcare professionals. The MAGIC (>70% time in range). 3 of these patients improved their % time in range at 3 programme is grounded in evidence generated from a qualitative months with a median of 5.5% (3–8%). The other 2 patients had a decrease systematic review, qualitative interviews and shared experiences of in % time in range at 3 months with a median of 9% (3–15%). people with CFD and healthcare professionals expert in the management 28/33 (85%) patients had a time in range of <70% at baseline. 16/28 (57%) of of CFD. It was designed as a patient focussed, staged approach to learning; these patients improved their % time in range by a median of 8% (range 1– with the aim to develop self-efficacy, knowledge and skills as the 26%). 12/28 (43%) patients had a decrease in their % time in range by a participants progress through the four modules. Objective: To determine the face validity of the MAGIC programme. S128 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Method: A range of cognitive interviewing techniques including: exposure control. Previous research has shown poor IIT in people with type 1 and to test material, think aloud, observation, probing and task completion type 2 diabetes but this has not previously been reported in CFRD. were used to verify understanding of content and instructions, identify Method: We conducted a survey-based cohort study including insulin- gaps and appraise the visual appeal of the MAGIC programme. Ten adults treated adults with CFRD as well as adults with type 1 and type 2 diabetes. participated in the interviews, these lasted between 71 and 134 minutes The survey included questions designed to assess patients’ current (median 107 minutes). knowledge of IIT. Six of the study participants had CFD, three did not have CFD and one had Results: We recruited 40 adults with CFRD, 20 adults with type 1 and 18 impaired glucose tolerance, for which they was not currently receiving adults with type 2 diabetes with survey results presented in Table 1. treatment. Each module was reviewed by at least two participants. Table 1. Results: The MAGIC programme was highly regarded by the review participants. The reviewers identified omissions, errors, technical issues, visual problems and comprehension difficulties within the programme. All CFRD Type 1 Type 2 of which were addressed before face validity was established. Conclusions: The MAGIC programme is a unique evidence-based self- Sex, % male 50 50 50 Median age, yrs 37 37.5 60.6 management education programme for people with CFD with established HbA1c, % 6.9 9.5 8.7 face validity. Further studies are however required, to demonstrate Aware to change needle for each injection, % 60 65 67 effectiveness, before the MAGIC programme can be used in routine clinical Correctly check that their insulin pen is working 50 40 28 practice. correctly at each injection, % Aware to insert the needle at 90 degree angle, % 68 50 39 P255 Aware to leave the needle in place for 10 seconds 45 45 33 Evaluation of a newly developed virtual cystic fibrosis diabetes clinic after dispensing insulin, % 1 1 1 1 1 1 Correctly rotating injection sites, % 98 60 67 S. Collins , I. Felton , L. Funnell , C. Fernandos ,A.Peres. Royal Brompton & Injection sites checked by healthcare professional 83 40 39 Harefield NHS Foundation Trust, Cystic Fibrosis Department, London, United in the last 12 months, % Kingdom

Background: CFD has a significant impact on nutritional status, respiratory Conclusions: The majority of adults with CFRD taking this survey had function, morbidity and mortality and is associated with an increased similar or superior knowledge of correct insulin injection technique burden of treatment. We developed a multidisciplinary, virtual CFD clinic compared with a cohort with type 1 and type 2 diabetes. This reflects the to offer support to people with CF in managing their diabetes. work of our full-time CF diabetes specialist nurse in providing diabetes Objective: To retrospectively review the virtual CFD service, including education, however Table 1 illustrates areas of IIT that still need patient’s experiences. improvement. Continuing diabetes education will aim to address these Method: Demographic data including: HbA1c, FEV1, BMI, CFD treatment gaps and we will reassess patient knowledge on a regular basis. and number of clinics attended were collected retrospectively. An online survey was sent out to patients who attended virtual CFD clinics between P257 10th July–20th November 2019. Assessing possible role of enterovirus infections in diabetes onset in a Results: 15 clinics were held, this consisted of 38 appointments for 21 Swedish cohort of cystic fibrosis patients different patients (14 female). All patients were on insulin, their median 1 2 1 3 2,4 2 R. Utorova , A. Sioofy Khojine , T. Pincikova , L. Hjelte , H. Hyöty , HbA1c, age, BMI and FEV1 were: 61 mmol/mol (7.7%); 31 years; 22.5 kg/m M. Flodström-Tullberg1. 1Karolinska Institutet, Department of Medicine and 59%. 80% of the virtual CFD clinics were led by the CF nurse specialist 2 and/or CF dietitian, who are non-medical prescribers. Huddinge, Center for Infectious Medicine, Stockholm, Sweden; University of 20 online surveys were sent out, response rate 45%. All respondents found Tampere, Faculty of Medicine and Life Sciences, Department of Virology, Tampere, Finland; 3Karolinska University Hospital Huddinge, Stockholm CF the virtual CFD service useful with 67% being very satisfied with the 4 service. Of the appointments, 33% replaced booked CFD clinics and the Center, Stockholm, Sweden; Fimlab Laboratories, Pirkanmaa Hospital District, remaining were for additional support. Saving time, by not having to travel Tampere, Finland to the hospital, was cited as the most liked thing about the virtual service. Objectives: Cystic Fibrosis-Related Diabetes (CFRD) is a major CF 56% of respondents would spend more than 2 hours travelling to the complication with unknown etiology. In type 1 diabetes, enterovirus (EV) hospital and back home to attend appointments. 33% of respondents saved infections (Coxsackieviruses B (CVBs) in particular) have been suggested to more than €20 on travel costs. Issues with sound or video quality were trigger disease development. In a small British study, EV was detected in experienced by 12% of respondents. pancreatic islets of deceased paediatric CF patients with CFRD but not in Conclusions: CFD clinics can be successfully led by non-medical profes- those without. Based on these findings we hypothesised that there could sionals experienced in CFD care, this allows for more sequential and be a temporal relationship between EV infections and CFRD diagnosis. The frequent appointments to support patients with CFD. Avirtual service saves aim of this study was to assess this possible association. patients both time and money. Increasing this service provision would Methods: The study included a cohort of patients with and without CFRD benefit more patients. However, the quality of the audio-visual equipment/ followed at Stockholm CF centre. When possible, each patient with CFRD software used needs further attention. was matched with one to three patients without CFRD for age, gender and genotype. The majority of the CFRD patients (62%) were homozygous for P256 the F508del mutation. Serum samples from CFRD onset and one year Is there a gap in the knowledge of adults with Cystic Fibrosis-Related before that were analysed for the presence of acute EV infection (viremia) Diabetes (CFRD) regarding correct insulin injection technique? using PCR and previous infection with the six known CVB serotypes using E.F. Nash1, J.L. Whitehouse1,A.Syed2, H. Sunsoa1. 1University Hospitals ELISA and a plaque neutralisation assay. Birmingham NHS Foundation Trust, West Midlands Adult Cystic Fibrosis Results: Viral RNA was not detectable in any patient but one. Serological Centre, Birmingham, United Kingdom; 2University Hospitals Birmingham NHS analysis indicated CVB4 and CVB5 to be most common serotype in patients Foundation Trust, Department of Endocrinology, Birmingham, United Kingdom both with and without CFRD (46% seropositivity). CVB6 was the least frequent serotype (20% seropositivity). CVB infections in the year before Objectives: CF-Related Diabetes (CFRD) affects 40–50% of CF adults and CFRD diagnosis were equally frequent in individuals that developed CFRD insulin is the main treatment. To obtain maximal benefit and to avoid and controls, regardless of genotype. diabetes complications, correct insulin injection technique (IIT) is vital. Conclusion: EV viremia was uncommon in individuals with CF and was not Incorrect IIT increases the risk of reduced insulin absorption, localised associated with CFRD diagnosis. CVB infections were common in CF, but the tissue damage, fatty deposits (lipohypertrophy) and impaired diabetes infections were not more frequent in patients who developed CFRD and neither were they associated with CFRD. Because we analysed a single Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S129 serum sample prior to CFRD onset, a role of EVs in the etiology of CFRD 21.0 and CFRD: 22.6 kg/m2, p = 0.003). The same pattern was observed for cannot be fully excluded. Further investigations with longer longitudinal the fat-free mass index (NGT: 17.4, INDET: 16.5, IGT: 14.7 and CFRD: analysis and histological studies would be of benefit. 16.3 kg/m2, p < 0.001). The fat mass index did not differ between groups (NGT: 6.5, INDET: 5.0, IGT: 5.1 and CFRD: 5.0 kg/m2, p = 0.14). HOMA-IR was P258 unchanged across the different groups of glucose tolerance (p = 0.2). Do smoking habits of parents of cystic fibrosis children differ from Conclusion: Prior to CFRD, severity of glucose tolerance was correlated parents of diabetes mellitus type 1 children? with a reduction in muscle mass, but not fat mass. In CFRD muscle mass M. Lafont1, C. Morin2, A. Rabeau3, M. Michelet1, A. Arrouy1, M. Mittaine1. was gained, most likely as a result of insulin treatment. Insulin resistance 1CHU Toulouse, Pneumologie Pédiatrique-CRCM Pédiatrique, Toulouse, France; was similar across groups suggesting that insulin deficiency rather than 2CHU Toulouse, Service de Diabétologie Pédiatrique, Toulouse, France; 3CHU resistance cause the loss of muscle mass prior to CFRD onset. Toulouse, Unité de Coordination du Sevrage Tabagique, Toulouse, France P260 Objectives: Second hand smoke (SHS) is harmful for children’s health, with Elevated circulating sphingosine 1-phosphate in CFTR-F508del well-known consequences on cystic fibrosis (CF). Inflammation mechan- patients: a new biomarker leading to cystic fibrosis-related bone isms induced by SHS have been recently highlighted in CF patients. In 2017, disease? in France, 26,9% of adults smoke every day. Some works have studied CF 1 1 1 1 1 J. Sergheraert , M.-L. Jourdain , C. Guillaume , J. Braux , C. Mauprivez , patient exposure to SHS, but none of them studied parent’s smoking habits 2 3 1 1 1 S. Audonnet , D. Hubert , J. Jacquot , F. Velard . Université Reims and attempts. Champagne Ardenne, EA 4691 ‘Biomatériaux et Inflammation en Site Osseux’, The aim of this study was to compare the smoking parental prevalence in a 2 Reims, France; Université Reims Champagne Ardenne, URCACyt, Reims, group of CF children to a group of diabetes mellitus (DM) type 1 children 3 France; Hôpital Cochin, Service de Pneumologie, CRCM, Reims, France (another chronic disease without pulmonary involvement). The secondary objectives were to determine the impact of the diagnosis announcement Objectives: Personalised therapies and progresses in treatments increase on their smoking habits, and how many of them discussed it with the life expectancy of patients suffering from cystic fibrosis (CF). Comorbidities paediatrician treating their child. like CF-related bone disease (CFBD) complexifies the pathology burden, Methods: We have interviewed 91 parents of CF children and 136 parents even early in life (Jacquot et al.,2016). Research of clinical biomarkers of of DM children at the university hospital of Toulouse, France, using a bone homeostasis is a new challenge. Spingosine-1-phosphate (S1P), as a written questionnaire from October 2019 to January 2020. soluble bioactive lypophospholipod mediator involved in bone metabol- Results: Parental smoking prevalence was 33% (30/91) in CF group versus ism, could represent an interesting target. The present work aims to 23, 5% (32/136) in DM group (ns). After diagnosis, 23% CF smoking parents determine if serum S1P may be considered as a biomarker for CFBD in quit vs 20% of DM parents (ns) and 50% of CF active smoking parents vs CFTR-F508del patients. 46,8% in DM group attempted to quit. Results: In serum from CFTR-F508del patients (n = 5, aged 29 to 37 yrs), we Interestingly, significantly more CF parents reported having discussed their observed a significantly increased S1P level, as compared to healthy smoking habits with the paediatrician following their child than DM controls (n = 6, aged 36 to 61 yrs) (9.1 vs 5.8 ng/mL, p < 0.05). Of particular parents (46,1% vs 15,4 %; p < 0,001). interest, F508del CFTR corrector-treated patients (Orkambi®, n = 5, aged 21 Conclusion: Despite the well-known harmful effects of SHS on CF patients, to 39 yrs) showed a significant ( p < 0.05) 40% reduced serum S1P parents of CF patients do not smoke less than parents of DM patients. The concentration, independently of patients inflammatory status as compared diagnosis announcement didn’t induce more quitting or attempts to quit in to untreated patients (serum IL-6, -8 and TNF-α levels were not impacted the CF group. Smoking was more often discussed with paediatricians and remained higher than in healthy donors, p < 0.05 for all three among CF parents than DM parents, but still insufficiently. The paediatri- cytokines). We also evidenced that F508del-CFTR patients (n = 12, aged cian may be a key actor to help reducing parental smoke of children 29 to 40 yrs) exhibited a significantly increased RANK+ monocytes suffering chronic pathology. The impact of his intervention should be proportion (57% vs 38%, p < 0.05) with higher RANK+ coverage on each studied, especially in CF. cell (a 90% increase, p < 0.05) compared to that observed in monocytes from healthy donors (n = 13, aged 19 to 69 yrs). P259 Discussion: S1P plays a major role in bone homeostasis thanks to its Muscle mass correlates with diabetes status in cystic fibrosis involvement in osteoblasts/OCs communication. Elevation of blood S1P B.U. Nielsen1, D. Faurholt-Jepsen1, T. Pressler1, P.S. Oturai2, T.P. Almdal3, concentration in CFTR-F508del patients, accompanied with a rise of high I.H.M. Mathiesen1. 1Rigshospitalet, Dept. of Infectious Disease, Copenhagen, RANK OCs precursor monocytes may indicate S1P as a potential Denmark; 2Rigshospitalet, Dept. of Clinical Physiology, Nuclear Medicine and biomarker of early CFBD. More, the decrease of serum S1P level in PET, Copenhagen, Denmark; 3Rigshospitalet, Endocrinology, Copenhagen, Orkambi-treated CFTR-F508del patients leads us to speculate that this Denmark mediator might be CFTR-regulated. Vaincre la Mucoviscidose and Vertex Inc. provided funding supports. Objectives: A gradual decline in insulin secretion results in CF-Related Diabetes (CFRD) in up to 50% of the adult CF population. Prior to insulin P261 treatment, severity of glucose tolerance is correlated with weight loss The association of VDR polymorphisms (TaqI, BsmI and FokI) and possibly due to a reduction in the anabolic hormone insulin. We aimed to vitamin D levels in children with cystic fibrosis study the correlation between glucose tolerance status and body-, muscle- 1 1 1 1 2 A. Zodbinova , E. Kondratyeva , N. Petrova , E. Zhekaite , N. Ilyenkova , and fat mass in CF. 2 3 3 1 V. Chikunov , S. Dolbnya , L. Klimov . FSBSI, Research Centre for Medical Methods: In a cross-sectional study in adult (≥18 years) CF patients, 2 Genetics, Moscow, Russian Federation; Voino-Yasenetsky Krasnoyarsk State glucose tolerance was categorized as either normal (NGT): 2-hour 3 Medical University, Krasnoyarsk, Russian Federation; Stavropol State Medical <7.8 mmol/L, indeterminate (INDET): 1-hour >11.0 and 2-hour University, Stavropol, Russian Federation <7.8 mmol/L, impaired (IGT): 2-hour ≥7.8 and ≤11.0 mmol/L or CFRD: 2- hour >11.0 mmol/L based on plasma glucose from an oral glucose tolerance Low levels of vitamin D (vit D) in cystic fibrosis (CF) patients have been test. Insulin resistance (HOMA-IR) was derived from fasting plasma glucose confirmed in many studies. Vitamin D receptor (VDR) regulates the activity and plasma insulin and dual energy X‐ray absorptiometry estimated fat- of vitamin d-sensitive genes. Polymorphism c.152T>C (FokI) results in the and fat-free mass index (kg/m2), the latter as an indicator of muscle mass. production of a shortened VDR protein. Variants c.1206T>C (TaqI) and Variations across groups were tested with ANOVA. c.1174+283G>A (BsmI) can affect gene expression. Results: Among 93 participants, 29 (31.2%) had NGT, 18 (19.4%) had an Objectives: To assess the effects of three VDR gene polymorphisms on vit D INDET, 21 (22.6%) had an IGT and 25 (26.9%) had CFRD. In correspondence levels in CF children. with severity of glucose tolerance, BMI declined in the prediabetes groups, Methods: 211 CF patients and 112 healthy volunteers were examined INDETand IGT, but reversed in the CFRD group (NGT: 24.9, INDET: 22.8, IGT: during winter. Vit D level was assessed by ELISA (Euroimmun AG, S130 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Germany). VDR gene polymorphisms were analyzed using restriction P263 fragment length polymorphism. Statistical analysis was performed Impaired bone mineralisation in children with cystic fibrosis using ANOVA, non-parametric methods with the Kruskal-Wallis H test, T. Jakovska Maretti1, I. Arnaudova Danevska1, S. Momchilovikj1, chi-squared test. Levels of vit D based on the joint effect of polymorphisms E. Gjinovska-Tasevska1. 1Institute for Pulmonary Diseases in Children, Cystic were analysed using Multifactor dimensionality reduction. Fibrosis, Skopje, North Macedonia, The Republic of Results: The association of this variant TaqI with the level of vit D in CF patients was revealed: the concentration of vit D is statistically significantly Objectives: Bone turnover during growth may be of value in the lower in patients with the CC genotype (21.9 ng/ml) than with the TC identification of individuals who may be at risk for osteoporosis later in genotypes (29.0 ng/ml, p = 0.017) and TT (29.9 ng/ml, p = 0.014). Significant life. But more attention should be given to the effects of the disease on bone differences in the level of vit D in CF patients having different genotypes turnover and bone mineral status especially in young patients with cystic according to variants FokI and BsmI have not been established. The fibrosis (CF). association of vit D levels and the three studied variants of the VDR gene Aim: Aim of the study was to assess bone formation and resorption process was investigated. In CF patients - carriers of the genotypes GG (BsmI) and with bone markers in children with cystic fibrosis. TT (FokI), the level of vit D is higher by 13.4 ng/ml from the average, while Materials and methods: The study included 25 clinically stable children in healthy people it increases by 6 ng/ml from the average. Among CF with CF who regularly attended the Department for cystic fibrosis at the patients, a risk group for vit D deficiency is the genotypes GG (BsmI) and CC Institute for pulmonary diseases in Skopje, R. North Macedonia. Control (FokI) (a decrease of 8.3 ng/ml from the average), in contrast to the healthy group was presented with 21 healthy children at the same age. Serum group (a decrease of 1.6 ng/ml from the average). osteocalcin (OC), β cross laps, 25OHD and PTH were determined by ELISA Conclusion: Thus, the severity of vit D deficiency in CF is determined not assays in CF group (mean age 8.25 ± SD1.9 y.) and in age-match controls only by the influence of exogenous causes, but also by genetic factors. (7.5 ± 1.9 y.). Results: Vitamin D in CF group was (23.83 ± 10.9 ng/ml versus 25.6 ± 11.53 P262 in control group, p = 0.57), OC (70.88 ± 34.24 ng/ml v.100.02 ± 47.98, Height-adjustment methods for lumbar spine bone density in youth p = 0.01) βcrosslaps (1.35 ± 0.72 ng/ml v.1.54 ± 0.73, p = 0.37) and PTH with cystic fibrosis (37.39 ± 25.5 pg/ml v. 36.76 ± 25.73, p = 0.92). In the study we didn’t find 1 2 3,4 4,5 4,5 significant difference for 25OHD between CF and healthy controls. OC in Z. Munsar , Z. Zysman-Colman , J. Kindler , B. Zemel , V. Stallings , 1, 4 1 children with CF correlates significantly with the control indicates a A. Kelly . Children’s Hospital of Philadelphia, Division of Endocrinology, 2 decreased formation rate whereas resorption rate is normal. Philadelphia, United States; Children’s Hospital of Philadelphia, Division of 3 Conclusion: Our results suggest that there is a possibility of a very early Pulmonary Medicine, Philadelphia, United States; The Children’s Hospital of 4 onset of impaired bone mineralization in CF. Serum levels of osteocalcin Philadelphia, Philadelphia, United States; University of Pennsylvania 5 can be used for predicting osteopenia in children with CF. Perelman School of Medicine, Philadelphia, United States; Children’s Hospital of Philadelphia, Division of Gastroenterology, Hepatology and Nutrition, P264 Philadelphia, United States Bone mineral density, dietary intake and physical activity in cystic Objectives: Areal bone mineral density (aBMD) from dual-energy X-ray fibrosis patients absorptiometry (DXA) overstates bone deficits in short youth. As a result, M. Gur1, 2, G. Diab1, 3, B.-Y. Ronen1, 2, M. Hanna1, G. Rozen3, F. Daud4, ECFS recommends height adjusting DXA bone outcomes in youth with CF. Z. Keidar4, Y. Toukan1, 2, K. Masarweh1, V. Nir1, G. Gut1, L. Bentur1,2. How this should be done is unknown. We compared two height 1Rappaport Children’s Hospital, Rambam Health Care Campus, Pediatric adjustment methods, bone mineral apparent density (BMAD) and Pulmonary Institute and CF Center, Haifa, Israel; 2Rappaport Faculty of 3 height-for-age Z-score (HAZ) adjusted aBMD (BMDHAZ), and their relation- Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Rappaport ships with stature and age. Children’s Hospital, Rambam Health Care Campus, Clinical Nutrition Unit, Methods: Secondary analysis of lumbar spine DXA obtained at 0 and 12 Haifa, Israel; 4Rambam Health Care Campus, Nuclear Medicine Institute, Haifa, months in pancreatic-insufficient CF youth ages 5–18 y who participated in Israel a nutritional supplement study. Subjects were categorized by HAZ (short: < −1; tall: >1; average: −1 to 1) and age (5-<10 y vs. ≥10 y). Sex- and age- Objectives: The risk of low bone mineral density (BMD) in CF is increased due to poor nutritional status and increased inflammation. Our aim was to specific BMAD and BMDHAZ Z-scores were calculated using published Bone Mineral Density in Childhood Study reference data and compared using evaluate the correlations between BMD, dietary intake, physical activity paired t-test and chi2. Measurements were compared across groups based and quality of life (QOL) in CF patients. Methods: A prospective single centre study assessing BMD, lung functions, on HAZ (ANOVA) and age (t-test). Associations of BMAD-Z and BMDHAZ-Z with HAZ were assessed using linear mixed-effects regression. Differences vitamin D levels. nutritional intake (food frequency questionnaire), hand- grip strength (HGS), 6 minute walk test (6MWT), habitual physical activity between baseline BMDHAZ-Z and BMAD-Z were plotted against HAZ to assess for relative bias over the height spectrum. (smart watches worn for 7 days) and QOL (SF-36 questionnaire), as well as Results: Data [mean(SD)] were available for 110 subjects [57% male, 88% the correlations between BMD and the other parameters. Caucasian, 34% F508del/F508del] with baseline weight-Z = −0.39(±0.78), Results: Thirty-two CF patients, mean age 18.3 ± 8.3 years, FEV1 HAZ = −0.41(±0.92) and BMI-Z = −0.2(±0.77). Baseline BMAD-Z [−0.4(±1)] 75.3 ± 18.3% predicted, lung clearance index (LCI) 12.2 ± 3.5. Mean − − vitamin D levels were 29 ± 12.9 ng/ml, and 18 (56%) patients had levels < was lower vs BMDHAZ-Z [ 0.22(±1.1)], p < 0.01. 33% had BMAD-Z < 1vs − 30 ng/ml. Ten (31%) and 11 (34%) patients had osteopenia (BMD z-score < 21% with BMDHAZ-Z < 1, p = 0.04. No significant difference across HAZ or −1) and osteoporosis (BMD z-score<−2), respectively. Hip BMD z-score age categories were found for either BMAD-Z or BMDHAZ-Z. No significant associations with HAZ were found. Inspection of the plot of BMD -Z correlated with HGS (r = 0.438, p = 0.042) and marginally with FEV1% HAZ 2 minus BMAD-Z vs HAZ revealed a negative bias, with a larger absolute predicted (r = 0.349, p = 0.059). Hip BMD (gr/cm ), hip BMD z-score and difference as HAZ increased. spine BMD z-score correlated with SF-36 general health domain (r = 0.368, p = 0.038; r = 0.502, p = 0.005; r = 0.432, p = 0.014, respectively). No Conclusion: BMAD-Z and BMDHAZ-Z address stature-related confounding of aBMD outcomes in youth with CF but do not perform equivalently. correlation was found between BMD, 6MWT results and physical activity Prospective studies could determine their ability to predict fracture. (assessed by smart watches). Conclusion: A substantial number of CF patients have low BMD. BMD correlated with muscle strength and quality of life, and did not correlate with physical activity, as assessed herein. Further larger multi-centre studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S131

P265 with higher value (720 mcg/L). That was a CF patient with known renal Normonatremic sodium depletion and pulmonary function in cystic disease at that time. The RBP values in the CF group were 1–720 mcg/L fibrosis patients (mean 70.2) and in the control group 3–234 mcg/L (mean 81). I. Bambir1, A. Ladic1, L. Omerza1, I. Markelic1, A. Vukic Dugac1,2, Conclusion: The results of the study could not confirm that urinary RBP in D. Tjesic - Drinkovic1, 2, D. Tjesic - Drinkovic1, 2. 1Cystic Fibrosis Centre children with CF is a good indicator of early kidney damage. We had a good Pediatrics and Adults - University Hospital Centre Zagreb, Zagreb, Croatia; sample size to obtain a power of the study of 100%. 2University of Zagreb School of Medicine, Zagreb, Croatia Objectives: Spot-urine ratio of sodium and creatinine (UNa/Cr) <17 mmol/ L/mmol/L points to normonatremic sodium depletion (NNaD), a condition Nutrition/Growth recognised in CF patients. NNaD could contribute to additional mucus thickening and therefore worsening of lung function. We investigated the P267 UNa/Cr in paediatric and adult patients and looked for possible association An evaluation of the nutritional status of Irish adults attending the with FEV measurements. 1 National Referral Centre for Adult Cystic Fibrosis in 2019 Methods: We collected basic demographic, anthropometric and laboratory 1 ’ 1 1 1 1 data (plasma Na, BUN, spot urine Na and Cr) and FEV measurements from R. Fitzpatrick ,L.OShaughnessy , C. Kalnoki , E. McKone , T. Nicholson , 1 1 1 ’ 36 paediatric and adult patients seen during 2019 in our CF centre. Patients C. Gallagher . St Vincent s University Hospital, National Referral Centre for Adult Cystic Fibrosis, Dublin, Ireland were divided in subgroups depending on percent predicted FEV1 values: – group A (FEV1 < 60%), group B (FEV1 60 80%), and group C (FEV1 >80%). Objectives: The aim of this study was to evaluate the nutritional status, ’ Descriptive statistics, Chi-square and Fisher s exact test were performed assessed by BMI, of a cohort of Irish adult Cystic Fibrosis patients, and to “ ” (statistical package R ). compare the results to the World Health Organisation (WHO) categories for Results: Twenty adults and 16 children were included in the analysis, all BMI, the internationally recommended targets for BMI for adults with CF normonatremic and with normal kidney function. Two subjects had (22 kg/m2 and 23 kg/m2 for females and males respectively), and the UNa < 20 mmol/l, indicating kidney Na conservation. Pathological UNa/Cr results of a similar study conducted at the same centre in 2014. ratio was found in 13 adults and 7 children, or 20/36 (55%) patients. 26/36 Methods: A retrospective review of the dietetic and medical records was had suboptimal BMI; 15 of them NNaD as well. Low UNa/Cr ratio across undertaken for patients who attended the National Adult Referral Centre in FEV1-subgroups was found in 8/17(47%), 4/6 (66%) and 8/13 (62%) patients 2019 and who had a dietetic review. BMI (kg/m2) was calculated using the in groups A, B and C, resp. There was no significant association between most recent weight and height. BMIs were classified based on WHO UNa/Cr ratio and FEV1 subgroups (chi:0.942, p = 0.3). categories and internationally recognised BMI targets for CF. The results of Conclusion: The observed high proportion of pathological UNa/Cr in all the current study were then compared with those of the 2014 study. ages speaks in favour of NNaD as a lasting problem in some CF patients. Results: There was sufficient data to calculate BMIs for 323 patients. 182 Although previously described in literature, poorer weight gain was not were male, age range 18–67, mean age was 33 years. related with NNaD in our subjects (p = 0.7). We did not find a significant BMI was distributed across all WHO categories. relation of UNa/Cr and FEV1 categories. However, lung function decline is While, similar to 2014, the majority of patients (64%) were classified as connected to many factors (chronic infection, pulmonary exacerbation rate, “normal weight” using the WHO cut offs (BMI ≥ 18.5–24.9 kg/m2), a large nutrition, adherence to therapy etc.), that were not taken in consideration proportion of patients (52% female, 45% male) had BMIs less than those in our analysis. Further studies are justified in order to elucidate the clinical recommended for optimal outcomes in CF. 26 patients (8%) had a spectre of NNaD. BMI < 18.5 kg/m2, compared with 11% in 2014. Of these patients only 10 (38%) had a feeding gastrostomy in place for nutritional support. P266 By contrast 91 patients (28%) were classified as either overweight, or obese Retinol-binding protein in urine, an indicator of early kidney damage (7.1%). This is an increase from 19.7% in 2014. in children with cystic fibrosis Conclusion: The results of this study demonstrate the heterogeneity of 1 1,2 3 4 1,5 1 J. Tate , M. Jaksic ,W.Wong ,J.Lewis , C. Byrnes . Starship Children’s nutritional status of a large cohort of Irish adults with CF. 2 Health, Respiratory, Auckland, New Zealand; University of Aucland, Increasingly widespread use of CFTR modulators may have been a 3 Paediatric, Auckland, New Zealand; Starship Children’s Health, Renal, contributor to the growing number of Irish adult CF patients who are 4 Auckland, New Zealand; Canterbury Health Laboratories, overweight and obese. More research is needed to determine body 5 Immunobiochemistry, Christchurch, New Zealand; University of Adelaide composition of this cohort and to monitor changes in nutritional status Auckland, Paediatrics, Auckland, New Zealand overtime. Objectives: Children with Cystic Fibrosis (CF) are at risk of renal damage secondary to the high doses of antibiotics and other medications used as P268 intensive treatment for acute respiratory infections. Our current tests to Nutritional status in patients <19 years of age with cystic fibrosis 1 1 1 1 detect renal dysfunction are not very sensitive (e.g. GFR) or are difficult to M.F. Bernatene , M.I. Nabais Robalo , J. Herrera . Hospital del Torax Dr. do in children (e.g. creatinine clearance). We were trying to determine the Antonio Cetrangolo, Unidad de Fibrosis Quistica, Florida, Argentina presence of early renal damage by the use of a more sensitive, non-invasive Objectives: In our study we evaluated the nutritional status in patients <19 test. In recent years attention has been directed towards evolution of years of age with cystic fibrosis (CF), we identified epidemiological urinary enzymes as non-invasive biomarkers of renal tubular damage. One characteristics and their relationship with pulmonary function. The early of those markers is urinary retinol-binding protein (RBP) which gets diagnosis of nutritional status allows an integral intervention to be carried released from tubular cells in the case of tubular cell damage. out, in order to provide adequate and timely dietetic-therapeutic guidance, Methods: A prospective, single blind study conducted during 2016/2017 prolong patients’ expectations and quality of life. looking for RBP level in urine samples of CF children. The samples were Methods: Descriptive, longitudinal and retrospective study of 45 patients taken at annual review, at the time of clinical stability, no acutely unwell with CF < 19 years of age treated between 2016 and 2019. The nutritional patients were included. The participants were recruited from CF Clinic in status was classified as: undernourished, low weight risk, normal weight Starship hospital. The controls were healthy siblings of CF patients and and overweight, by anthropometric index (weight, height, body mass index orthopaedic patients from fracture clinic with no known renal issues and (BMI)). Pulmonary function was assessed through the percentage of the no comorbidities. Morning samples were taken in clinics, sent to the Lab forced expiratory volume predictive in the first second (FEV ). with an identification number, age and gender only. 1 Results: From the total patients evaluated, 93.3% had pancreatic insuffi- Results: We had 67 CF patients (34 female), age 1–18 years (mean age 10 ciency and 64% were male. The anthropometric evaluation showed that years) and 51 control participants (25 female), age 2.5–18 years (mean age 15.56% were undernourished in 2016 and increased to 20% in 2019. Of 10 years). Normal urinary RBP was <250 mcg/L. There was just one sample these, 6.66% were diagnosed with CF-Related Diabetes and received enteral S132 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 feeding during the four years, presenting function moderate to severe tests. When stratified for RFS risk; six (16%) high risk, one (3%) at risk and pulmonary. The median BMI/E percentile in patients 6 to 19 years old was 30 (81%) low risk. Of those at high risk, three (50%) were high risk due to a 43.75 in 2016; 41.11 in 2017, 37.13 in 2018 and 38.41 in 2019. The median of BMI < 16.5 kg/m2, one (17%) for >15% weight loss, one (17%) for BMI < 18.5%

FEV1 was 88.97% in 2016, 89.89% in 2017, 86.14% in 2018 and of 83.14% in and >10% weight loss and one (17%) with low baseline magnesium. Only 2019. one person was identified as having little to no nutrition in the five days Conclusion: Patients who presented a decrease in weight for their age had prior but did not meet criterion threshold for weight loss and BMI. a concomitant loss of FEV1, while patients who gained weight, maintained Conclusion: Criteria in the UK for assessing RFS risk in people with cystic or increased their FEV1, this shows the close relationship between nutrition fibrosis may not be reliable as they are based on generic guidelines. and lung function. Patients with undernourishment did not achieve their Prolonged nutrition deprivation does not appear in this data set be goal and some with low weight risk got worse, so it is necessary to plan common. People with CF are prone to under-nutrition (low BMI) which is new early intervention strategies to achieve a lower degree of lung multifactorial, but not often associated with micronutrient deficiencies and involvement and better quality of life. may not lead to symptomatic RFS. It may be worth exploring biochemical RFS appearance and developing CF specific RFS guidelines may be of P269 benefit. Exploring gastrointestinal symptoms in paediatric patients with cystic Reference fibrosis and impact on quality of life A. Tierney1,S.O’Connell1, D. Daly2. 1University of Limerick, School of Allied [1] National Collaborating Centre for Acute Care 2006. Nutrition Health, Limerick, Ireland; 2University Hospital Limerick, Nutrition and support in adults Oral nutrition support, enteral tube feeding and Dietetics, Limerick, Ireland parenteral nutrition

Objectives: As life expectancy increases in Cystic Fibrosis (CF), gastro- P271 intestinal (GI) symptoms are more prevalent. The burden of overall care An assessment of Pancreatic Enzyme Replacement Therapy (PERT) and in particular managing GI symptoms has an effect on Health-related knowledge in children and adults with cystic fibrosis Quality of Life (HRQoL) in patients with CF. The aim of this study is to P. Manu Djan1, C. Ng1, D. Sills2, A.R. Smyth1. 1University of Nottingham, investigate the prevalence of GI symptoms and their impact on generic Division of Child Health, Obstetrics and Gynaecology, Nottingham, United health related quality of life in paediatric patients with CF. Kingdom; 2Nottingham University Hospitals NHS Trust, Wolfson Cystic Fibrosis Methods: Cross-sectional study. Paediatric outpatients with CF aged Unit, Nottingham, United Kingdom between 5–17 years attending the CF clinic in University Hospital Limerick (UHL) were eligible for the study. The Paediatric Quality of Life Objectives: PERT dosing relies on education from the CF team and there InventoryTM (PedsQLTM) Gastrointestinal Symptoms Scale and the The can be variations dependant on reported symptoms and patient experi- PedsQLTM 4.0 Generic Core Scales (higher scores indicates better HRQoL) ences. We aimed to assess the PERT knowledge of people with CF at our were completed by participants. tertiary centre. Results: Eleven patients with CF completed the questionnaires, median age Methods: A service evaluation questionnaire was designed and distributed – 11 years (5 15 years), majority of participants male (81%), average FEV1 between October and December 2019. Patients attending their usual CF 84%, median BMI 81st centile, 72% homozygous F508delta and 81% of clinic at Nottingham University Hospitals NHS Trust were approached and participants did not have a hospital admission in at least 3 years. A diverse verbally consented. The questions asked were the same as those asked range of GI symptoms were experienced by the group in the weeks prior to routinely in clinic by the CF dieticians to evaluate their understanding and receiving the questionnaire with 72% reporting feeling pain in their confidence of PERT dosing. Their responses were compared with their stomach, 54% reporting hurt when passing a stool, 45% not being able to medical notes. eat some foods and 45% having a lot of gas. No patient reported blood in Results: The questionnaire received 104 responses, 36 from the paediatric stools and stomach pain when eating. Four patients (36%) who experienced service and 68 from the adult service. 47% (49/104) of the patients were some level of symptom for an average of 27 of the individual items in the GI taking Creon 10 000. 31% (32/104) of patients were taking Creon 25 000 symptom questionnaire reported feeling scared, angry and found it hard to and 15% (16/104) of patients were taking Creon 10 000 and Creon 25 000. pay attention in school. Of the 104 patients, 49 had their recommended PERT dosage documented

Conclusion: BMI, FEV1 and rate of hospital admission indicate participants by the CF dietician. Within this group, 64% (32/49) were confident in their in this study were generally healthy, however still experienced varied GI knowledge of PERT dosing but 19% (5/26) of adults and 56% (13/23) of symptoms that may impact quality of life. Further analysis is planned to children and young people were not compliant with recommended PERT assess the association with symptom frequency and diet quality in this dosing. cohort. Conclusion: Optimising PERT dosing is essential in pancreatic insufficient CF. Despite education from CF teams, there are discrepancies in what PERT P270 patients are taking and what healthcare professionals believe they should Refeeding risk in cystic fibrosis (Part 1): a sample evaluation of be taking. Further evaluation and development of educational resources refeeding risk of people admitted to hospital may be of benefit. D. Sills1, M. Mitchell-Whyte1,J.Dewar1, H. Barr1. 1Nottingham University Hospitals Trust, Nottingham, United Kingdom P272 High dose vitamin D supplementation: the patient knows best Objectives: Evaluate local prevalence of refeeding syndrome (RFS) based D. Proud1, R.I. Ketchell1, D. Lau1, M. Rezaie1, M. Lea-Davies1, J. Duckers1. on NICE1 RFS criteria. 1Cardiff & Vale University Health Board, Cardiff, United Kingdom Methods: Retrospective data examining RFS risk was collected from adult CF patients admitted to the Wolfson CF Centre. Data was collected for Objectives: Patients with cystic fibrosis (CF) commonly experience people with CF admitted between 1st August and 18th September 2018. suboptimal vitamin D levels, a suspected risk factor of bone disease. Data collected included height, weight, BMI, percentage weight change Consequently, high dose vitamin D (HDVD) regimens are prescribed. over past 3–6 months and nutritional intake, allowing stratification for RFS Debate continues regarding the optimal regimen. The aim of this study is to risk using NICE1 guidelines. Relevant RFS related biochemistry was evaluate the efficacy of various HDVD regimens. collected, where available. Methods: The previous HDVD regimen (PR) provided 100000 iu/week/6 Results: Thirty-six people were admitted during the period, 37 sets weeks. In 2016 local guidelines were revised offering the patient the option of data were available as one person was admitted twice. Median BMI of either daily (DR) or monthly (MR) HDVD. Levels <30 nmol/L received a 19.5 kg/m2 ± 4.95 kg/m2, ranging between 13.1 kg/m2 and 35.1 kg/m2. loading dose (DR 4000 iu/day/10 weeks, MR 50000 iu/week/6 weeks) Percentage weight change 3–6 months prior to admission −1.4% ± 7% followed by a maintenance dose (DR 1000 iu/day, MR 25000 iu/once/ ranging from −16.5% to 17.8%. Four people (11%) had baseline RFS blood Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S133 month). Those with levels between 30–50 nmol/L commenced onto the DR P274 or MR maintenance dose. Vitamin replacement therapy in adults with cystic fibrosis Vitamin D levels were initially assessed at annual review (AR). Those with C.A. Stackhouse1, R.A. Floto1,2. 1Royal Papworth Hospital NHS Foundation suboptimal levels were offered the option of DR or MR. The target was to Trust, Adult Cystic Fibrosis Centre, Cambridge Centre for Lung Infection, retest all vitamin D levels at 2 time points, the first in line with guidelines Cambridge, United Kingdom; 2Molecular Immunity Unit, Department of (3–6 months post dose change) and the following AR. Medicine, University of Cambridge, Cambridge, United Kingdom Results: 129 patients received HDVD (57 female, 113 (88%) pancreatic – – Approximately 85% of patients with cystic fibrosis (CF) require fat soluble insufficient, mean age 29 years (17 59), mean FEV1 63% (11 117%). Mean retest time for the first time point was 6 months. Number of patients per vitamin replacement (ECFS, 2016). Fat soluble vitamin deficiency can affect regimen was PR 45, DR 52 and MR 32. Mean levels (nmol/L) at baseline vision and bone health (CF Trust, 2016). There is debate as to the weren’t significantly different (p > 0.05) between regimens PR 29.7 (SD appropriate dose of fat-soluble vitamins for patients with CF (CF Trust, 9.8), DR 27.7 (10.1), MR 29.6 (12.0). 2016; ESPEN, 2016; TSANZ, 2017). Compliance with CF treatment regimens All patients were tested at time point 1 and mean improvement in levels is known to be low at 3% (Kettler, 2002). Adherence is further challenged by above baseline compared. No significant difference was observed. large quantities of commercial vitamin capsules required for adequate At the second AR number of patients tested per regimen was PR 45 (100% of vitamin levels. initial group), DR 41 (79%), MR 23 (72%). Mean improvement above Objectives: We sought to introduce a combined multivitamin (DEKA) to CF baseline was PR 13.5 nmol/L (SD17.4), DR 28.8 (23.6), MR 17.5 (24.0). patients at Royal Papworth Hospital. Our aim was to investigate the effect of Comparing regimens only DR v PR showed a significant difference routine vitamin supplementation with DEKA on fat soluble vitamin levels. (p0.001). Methods: 144 patients commenced 1 × DEKA essential capsule and Conclusion: Daily HDVD appears the most popular patient choice and long 1 × DEKA soft gel plus capsule between November 2017 and May 2018. term appears to be more effective at sustaining vitamin D levels. Patients who were pregnant or underwent lung transplantation were excluded. Fat soluble vitamin levels were recorded at baseline and at 1 year P273 post commencement of treatment. Analysis was limited to 117 patients A comparison of vitamin levels in patients taking a combined cystic who had complete data sets. Fat soluble levels were measured at baseline fibrosis-specific supplement to separate supplements in a paediatric and at 1 year after commencing DEKA. Mean results were compared using a cohort Student Paired T Test. 1 1 2 3 1 Results and conclusions: C.J. Woodland , C.A. Berry , A. Lilley , K.W. Southern . AlderHey Children’s NHS Foundation Trust, Nutrition and Dietetics, Liverpool, United Kingdom; 2AlderHey Children’s NHS Foundation Trust, Pharmacy, Liverpool, United Kingdom; 3University of Liverpool, Department of Women’s and Children’s N = 117 Vitamin A Vitamin E E/Chol Vitamin D3 Health, Liverpool, United Kingdom (SD) (SD) ratio(SD) (SD)

Objectives: In our Paediatric CF network we evaluated the change from Baseline 1.48 (0.55) 23.1 (8.6) 6.4 (1.9) 67.5 (28.4) 1 year 1.54 (0.50) 26.7 (9.3) 8.2 (8.4) 85.5 (27.6) delivering fat soluble vitamins in a variety of preparations, requiring 6 p = 0.20 p = <0.001 p = 0.02 p = <0.001 tablets daily, to a combined preparation Paravit CFTM, as a small liquid volume or up to a maximum of 2 capsules daily. This was implemented [Results] between November 2017 and April 2018. The objectives of this audit were TM to determine if serum vitamin levels could be maintained with Paravit CF Our analysis shows levels of Vitamin D3, Vitamin E and Vitamin E/ and to compare the serum vitamin levels from 2017, before the change and cholesterol ratio, but not Vitamin A, were significantly increased after 1 in 2019 once established on Paravit CFTM. year of DEKA supplementation. We conclude that DEKA provides Methods: A retrospective audit of the serum levels of Vitamin A, D and E appropriate fat-soluble vitamin therapy for adults with CF. from all pancreatic insufficient patients was completed. For patients References previously taking separate supplements, their vitamin levels from 2017 were compared to the 2019 levels. ESPEN (2016) Guidelines on nutrition care for infants, children, and Results: 63 patients were taking Paravit CFTM in 2019 and of these 11% had adults with cystic fibrosis. Clinical Nutrition (35) pp. 557–577. abnormal Vitamin A levels, 6% had abnormal Vitamin D levels and all Kettler L (2002) Determinants of Adherence in Adults with CF. Thorax vitamin E levels were normal. (57) pp. 459–464. 50 patients had levels from 2017 and 2019 to compare. Vitamin E levels in TSANZ (2017) Nutrition Guidelines for CF in Australia and New both years were all within the normal range (6.9–41.5 umol/L) and the Zealand. Vitamin A and D are below. P275 Impact of administration mode of Pancreatic Enzyme Replacement Vitamin A* Vitamin D** Therapy (PERT) on abdominal pain, bowel habits and Quality of Life Mean umol/L %high(n) %low(n) Mean nmol/L %high(n) %low(n) (QoL) in children and adolescents with cystic fibrosis: a randomised cross-over intervention study – – 2017 1.21(0.66 0.98) 14 (7) 14 (7) 65 (22 117) 0 16 (8) G. Brekke1, A.M. Terp Raun1, C. Mølgaard2,3, T. Pressler4, M. Skov4. – – 2018 1.23(0.5 2.27) 2 (1) 10 (5) 81 (30 155) 0 4 (3) 1University Hospital Rigshospitalet, Pediatric Nutrition Unit and Copenhagen 2 [Vitamin A and D results.] CF-Center, Copenhagen, Denmark; University of Copenhagen, Copenhagen, 3 *Vit A: 1–6 yrs 0.7–1.5 umol/L/7–12 yrs 0.9–1.7 umol/L/13–19 yrs 0.9–2.5 umol/L. Denmark; University Hospital Rigshospitalet, Pediatric Nutrition Unit, 4 **Vit D: Deficient < 25 nmol/L/Insufficient 25–50 nmol/L/Adequate >50 nmol/L. Copenhagen, Denmark; University Hospital Rigshospitalet, Copenhagen CF- Center, Copenhagen, Denmark Conclusion: This audit suggests Paravit CFTM can maintain vitamin levels in TM Objectives: Gastrointestinal (GI) symptoms are often reported by cystic CF patients and be as effective as separate supplements. Paravit CF fibrosis (CF) patients. There seem to be a relation to pancreas insufficiency reduces the burden of tablets for patients; therefore more research is (PI), but it is unclear whether it is related to the administration of required to determine health behaviours, impact on adherence and pancreatic enzyme replacement therapy (PERT). The recommendations for potential to improve vitamin levels, especially Vitamin D using Paravit TM taking PERT varies worldwide indicating uncertainty to whether ingestion CF . prior to, under or after meals is the optimal timing of PERT. The aim of this study was to investigate if abdominal pain, dysfunctional bowl habits and Quality of Life (QoL) related to GI symptoms are affected by the timing of S134 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

PERT administration; prior to or after meals, in CF patients aged 0–17 y at CF specialist Centre. We performed bioelectrical impedance analysis using Copenhagen CF-Center. multi frequency a whole-body bioelectrical impedance analyser, Tanita MC Methods: All CF patients with PI were invited to the study in Feb.-Apr. 780 MA, (Tanita Corporation, Tokyo-Japan). At annual assessment absolute

2019. Participants were randomized to 4 weeks of PERT prior to meals FEV1, weight, height, phase angle, body fat percentage and fat free mass followed by 4 weeks of PERT after meals or vice versa. Before, between and were measured. Fat free mass and total body weight were divided by the after each period anthropometrics and assessment of GI symptoms, bowel square of height for each participant to determine BMI and fat free mass habits and QoL were done. Data was analysed using a linear mixed model. index. The study was approved by the Ethics Committee of Region Hovedstaden, Results: One hundred and twenty-four sets of data were available from 103

Denmark. patients. There was a positive weak correlation between absolute FEV1 and Results: 34 PI patients accepted to participate in this study. There was no BMI (r = 0.19, p = 0.032). Absolute FEV1 was positively correlated with fat significant difference in the primary endpoint, abdominal pain, that timing free mass index (r = 0.34, p < 0.001) and phase angle (r = 0.34, p < 0.001). of PERT was changed from prior to meals to after meals, which was also not Phase angle strongly and positively correlated with fat free mass (r = 0.69, the case for the secondary endpoints, dysfunctional bowel habits and QoL. p < 0.001) and fat free mass index (r = 0.69, p = <0.001), whilst it was At an individual participant level abdominal pain developed differently negatively correlated with body fat percentage (r = −0.33, p = <0.001). and with great variation between subjects. Some participants experienced Phase angle was also positively correlated with absolute FEV1 (r = 0.33, pain with less frequency, duration or intensity when taking PERT after p = <0.001). meals, while for others the opposite occurred. Conclusion: BMI as a marker of nutritional status is associated with Conclusion: No significant difference was found when timing of PERT pulmonary function in people with CF, yet in this data set the correlation for changed from prior to after meals or vice versa. For some CF patients it may, absolute FEV1 and BMI was weaker than for absolute FEV1 and fat free mass after an individual assessment, be considered whether changing timing of index and phase angle. Moreover, a strong correlation for phase angle is of PERT from prior to after meals may have a positive effect on GI symptoms. interest especially as a prognostic marker as it provides information on cell mass and integrity. These findings may benefit from larger prospective P276 studies to confirm these findings and determine the long-term clinical Bioimpedansometry in children with cystic fibrosis consequences in CF and phase angle may be better suited due to the I. Sokolov1, O. Simonova1, S. Polyakov1, N. Burkina1, Y. Gorinova1. 1Federal assumptions made by bioelectrical impedance analysis equations. State Autonomous Institution of Russian Federation Ministry of Health ‘National Medical Research Center for Children’s Health’, Moscow, Russian P278 ® Federation Use of an appetite stimulant (Periactin ) in paediatric patients with cystic fibrosis Objectives: To conduct an integrated assessment of the body composition 1 1 2 3,4,5 3 1 J. Grunert , N. van der Haak , C. La Vanda , N. Farrow ,A.Tai . Women’s in children with CF using the bioimpedansometry method. and Children’s Hospital, Nutrition Department, North Adelaide, Australia; Methods: The study included 47 CF children, aged 3 to 16 years, 26 of them 2 Women’s and Children’s Hospital, SA Pharmacy, North Adelaide, Australia; with moderate form of CF, 21 children with severe form. All children 3 Women’s and Children’s Hospital, Department of Respiratory and Sleep underwent an integral assessment of body composition by bioimpedanso- 4 Medicine, North Adelaide, Australia; University of Adelaide, Robinson metry using the ABC-01 Medass apparatus. 5 Research Institute, Adelaide, Australia; University of Adelaide, Adelaide Results: The BMI in 8 children (17%) is higher than normal, in 16 patients Medical School, Adelaide, Australia (34%) is average and in 23 children (49%) is lower than normal. Skinny body weight (kg) includes the analysis of all types of tissues, except fat. This Objectives: To assess the effectiveness of cyproheptadine (Periactin®)asan indicator is within the age norm in 18 children (38%), it was below the age appetite stimulant on improving the nutrition status of patients with CF norm in 29 children (62%), which indicates to a low level of muscle mass in with suboptimal nutrition. the body. Active cellular body weight (kg) indicates to the level of protein Methods: A retrospective audit was conducted to assess the effect of components of nutrition. In 21 children (45%) it corresponds to the average Periactin® on nutrition status (change in BMI z-score) in paediatric patients level, in 26 children (55%) it is below the average level, which proves that with CF at the Women’s and Children’s Hospital. Lung function (change in more than half of children with CF suffer from insufficient or unbalanced FEV1 (%predicted)) and dose-response relationship were considered as diet. The level of skeletal muscle mass (kg) characterise general physical secondary outcomes. Inclusion criteria: patients with CF prescribed development. It was lower than normal in 7 children (15%), in 25 children Periactin® from 2013–2018 for a period ≥12 months. Exclusion criteria: (53%) the level of the indicator is normal, and in 15 children (32%) it is patients who were concurrently prescribed oral or enteral nutrition higher than the average level (children who are engaged in various types of support. Pharmacy records were used to identify those prescribed sport). Periactin®. Growth parameters (weight, height), pancreatic status, CF

Phase angle (deg.) reflects the state of the cells, its overall performance and genes, lung function (FEV1 (% predicted)), CF-Related Diabetes (CFRD) metabolic rate. In 23 children (49%), it was within normal limits (25–75 status +/− treatment, use of oral or enteral supplementation, CFTR percentiles), in 17 patients (36%) it was < 25 percentile, and only in 2 modulator use and Periactin® dose were obtained via medical records children (4%) it is > 90 percentile. These 2 patients had a severe form of CF and electronic databases. BMI and BMI z-scores were calculated. but were involved in various types of sport on regular basis. Results: Fifteen patients were included in the analysis. Fourteen (93%) were Conclusion: Bioimpedansometry allows to assess the general condition of pancreatic insufficient. No patients had CFRD. No patients were on CFTR the patient and his condition at the cellular level. These data help to choose modulators. The daily dose of Periactin® prescribed ranged from 0.1– appropriate methods for improving the physical status of the CF child. 0.32 mg/kg. Mean BMI z-score at commencement of Periactin® was −1.06, and increased to −0.15 after 12 months on Periactin® (p < 0.001). Mean P277 change in BMI z-score in the 12 months prior to commencement of Evaluation of body composition measures in cystic fibrosis: moving Periactin® was −0.52, compared to +0.91 in the 12 months after ® beyond body mass index for assessing nutritional status commencing Periactin (p < 0.001). Mean change in FEV1 (%predicted) in ® D. Sills1, M. Mitchell-Whyte1,J.Dewar1, H. Barr1. 1Nottingham University the 12 months prior to commencement of Periactin was −6.2 compared to ® Hospitals Trust, Nottingham, United Kingdom +2.79 in the following 12 months on Periactin (p = 0.07). There was no correlation found between dose of Periactin® and change in BMI z-score Objectives: To evaluate body composition measures using bioelectrical (r = 0.031). impedance analysis in adults with CF. Conclusion: These results suggest Periactin® is effective at improving the Methods: In 2018 bioelectrical impedance analysis was introduced as part nutrition status of paediatric CF patients with suboptimal nutrition. of standard practice during annual assessment for adults with at a UK adult Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S135

P281 Conclusions: Paravit-CF is well-tolerated and the majority of patients Body composition in adults with cystic fibrosis – are measurements demonstrate unchanged or improved vitamin levels compared to their taken using single frequency and multifrequency devices previous preparations. This is achieved at a reduced cost, with a reduced interchangeable? burden of care. Further consideration is required for those patients with D. Proud1,L.Tan2, D. Lau2, R.I. Ketchell2, H. Jones3, M. Rezaie2, J. Duckers2. low levels, particularly of vitamin E, on Paravit-CF. 1Cardiff & Vale University Health Board, Llandough, United Kingdom; 2Cardiff & Vale University Health Board, Cardiff, United Kingdom; 3Cardiff University, P284 Cardiff, United Kingdom The impact of eating habits in different geographic regions on the body mass index of Croatian cystic fibrosis patients Objectives: Nutritional status is known to affect pulmonary function and 1, 2 3 4 4 4 A. Vukic Dugac , A. Ladic , I.K. Crnogorac , A. Dobric , L.T. Dobric , bioelectrical impedance assessment (BIA) has become increasingly 4 5 1 1 L. Tanackovic , I. Bambir , I. Lalic , T. Odobasic Palkovic , popular as a tool to assess body composition and thus nutritional status. 4,5 4,5 1 D. Tjesic-Drinkovic , D. Tjesic-Drinkovic . University Hospital Centre However, a number of variations of BIA devices are available utilising either Zagreb, Clinic for Respiratory Disorders ‘Jordanovac’, Zagreb, Croatia; single-frequency (SF) or multi-frequency (MF) technology. To date, it is not 2 University Hospital Centre Zagreb, School of Medicine, Zagreb, Croatia; known how SF and MF BIA compare in adult patients with cystic fibrosis 3 University Hospital Centre Zagreb, Department of Gastroenterology, Zagreb, (CF). The aim of this study is to compare and evaluate SF and MF BIA 4 5 Croatia; University of Zagreb, School of Medicine, Zagreb, Croatia; University technology in adult patients with CF. Hospital Centre Zagreb, Department of Pediatrics, Zagreb, Croatia Methods: SF and MF BIA were performed on the same patient on the same day when attending their annual review. SF BIA was performed using a Eating a balanced diet is essential for people with cystic fibrosis. Tanita bc418ma whilst MF BIA was performed using a Bodystat Quadscan Maintaining a good nutritional status can help a person improve their 4000 device. BIA results compared included estimated total body water well-being, keep their symptoms under control, and fight infections. The calculated as a percentage of total weight (TBW%), fat mass (FM) and fat results of our study also suggest that when it comes to the nutritional status free mass (FFM) both measured in kilograms (kg). of CF patients, we have to consider the eating habits of different regions in Results: 112 patients (43 female), 93 (83%) pancreatic insufficient, mean country. – age 30.3 years (range 17 59), mean forced expiration in 1 second (FEV1) Objectives: Most patients with cystic fibrosis (CF) require a higher energy 73% predicted (range 12–133) underwent both SF and MF BIA. TBW%, FM and protein intake than their healthy peer group. There are few data on and FFM measurements were significantly different when measured using dietary intakes of adult patients. The aim of this study was to determine the SF and MF (TBW% p < 0.01, FM p < 0.001, FFM p < 0.001). difference in BMI among Croatian CF patients, depending on the Conclusion: BIA technology can be informative regarding body compos- differences in eating habits in various regions of the country. ition changes over time in an individual. However, SF and MF BIA data may Methods: Data for this study were derived from paediatric and adult not be interchangeable therefore caution must be applied when interpret- sources. Patients’ medical records were evaluated and analysed using R: A ing different BIA data. With suitably developed conversion equations it language and environment for statistical computing (2015). BMI was may be possible to compare different BIA results thus improving the calculated from measured weight and height. Croatia was divided into 5 potential to utilise BIA technology in multicentre studies regardless of different geographical regions, according to climatic conditions and eating device used. habits. A one-way between subjects ANOVAwas conducted to compare the effect of a specific region on a BMI, with a significance set at p < 0.05. P283 Results: Fifty-three paediatric (25F, 28M) and 38 adult (20F, 18M) CF Results of a change in vitamin supplementation for cystic fibrosis patients were included in the study. Mean age and BMI of paediatric cohort patients in a tertiary paediatric centre were 11.6 years and 17.22 kg/m2 respectively, while in adult cohort mean 2 A.A.M. Hafiz1, A. Forster1, E. Turner1, E. Sheppard1, S. Wilkinson1, A. Maitra1, age and BMI were 24.9 years and 21.2 kg/m . There was no statistically A. Shawcross1. 1Royal Manchester Children’s Hospital, Manchester, United significant difference in BMI across different Croatian regions for paediatric Kingdom population (F (4,48) = 2.43, p = 0.06), contrary to adult population ((F3,34) = 3.34, p = 0.03). Post hoc comparisons, using the Tukey HSD test, Background: Children with cystic fibrosis (CF) who are pancreatic indicated that the significant difference existed between central and insufficient (PI) require supplementation of fat-soluble vitamins. mountainous Croatian region (p = 0.02). Previously, this required multiple supplements which increases the burden of medication, and dosing appropriately can be challenging. P285 Royal Manchester Children’s Hospital (RMCH), a large tertiary paediatric CF Lower residual fat malabsorption and improved growth in children centre in Northwest England, switched to Paravit-CF due to cheaper costs, with cystic fibrosis treated with a novel oral lipid technology easier dosing consistent with recommendations and reduced medication supplement burden. 1, 2 1 1, 2 1,2 1 V. Stallings , A. Tindall , A. Maqbool , M. Mascarenhas , J. Schall . Objective: We aimed to compare patients’ results for blood vitamin levels 1 Children’s Hospital of Philadelphia, Div. of Gastroenterology, Hepatology and of vitamins A, D and E to ensure levels remained therapeutic after the 2 Nutrition, Philadelphia, United States; University of Pennsylvania, Perelman switch to Paravit-CF. School of Medicine, Philadelphia, United States Methods: All PI patients under our centre were identified. Medical records were reviewed to determine the patients’ dose and preparations of vitamin Objectives: Malabsorption and optimizing growth/nutritional status in supplementation prior to the switch, and Paravit-CF dose afterwards. patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) is a Vitamin levels at the annual review appointment prior to the switch and 3– challenge. A highly absorbable lipid (LYM-X-SORB™, now Encala™, Envara 6 months after switching were compared. Health Inc, Wayne, PA) improved fat absorption, growth, choline and Results: 138 patients will be included in final analysis (mean age 8.45 y, essential fatty acid (EFA) status in a 12-month double-blind randomised 55% male). Data from 75 patients has been analysed to date with the placebo-controlled trial. Coefficient of fat absorption (CFA) increased by 6% remaining due by February 2020. 57% of patients switched from standard over 12 months with Encala. This secondary analysis is to determine Encala dosing of multiple vitamin supplements to a standard dose of Paravit-CF effectiveness in subjects with varying CFA. with vitamin levels remaining normal both pre-and post-change. Of those Methods: This analysis was restricted to subjects with baseline CFA and a patients requiring a higher than standard dose of vitamins A&D prior to the 3-month visit (n = 66, 10.5 ± 3 yrs, 40% female). Encala and placebo/ switch, or with low levels of vitamin A or D on a standard dose, 92% now comparator (COMP) had similar calorie (303–456 kcal/d) and fat (11– have normal levels on a standard dose of Paravit-CF. However a total of 13/ 18 g/d). CFA was from 72-hour stool and weighed food records. Subjects 75 (17%) of patients to date show low levels of vitamin E on Paravit-CF. S136 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 were divided by baseline CFA: lower (≤88%, median) and higher CFA (above P287 median). Height, weight, BMI Z-scores and plasma FA were assessed. Impact of switching to a single multivitamin preparation on vitamin Results: In those with lower CFA, Encala treatment improved CFA levels and patient satisfaction significantly (+7.5%), with a significant drop in stool fat (−5.7 g/24 hrs), A.M. Connolly1, H.L. Seymour1, M.K. Dooney1, 2. 1Blackpool Teaching no change in fat intake, significantly increased linoleic acid (+20%) and α- Hospitals NHS Foundation Trust, Blackpool Adult Cystic Fibrosis Service, linolenic acid (+56%). Total FA increased (+20%) in lower CFA group vs. no Blackpool, United Kingdom; 2Manchester University NHS Foundation Trust, change in COMP. Weight and BMI Z-scores significantly increased in lower Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom CFA group with Encala. In the lower baseline CFA, COMP treatment group, CFA and EFA did not change; growth status improved less than with Encala. Objectives: Malabsorption of fat soluble vitamins is likely in most people For subjects with higher CFA, CFA did not change with either treatment, with cystic fibrosis (CF), particularly those who are pancreatic insufficient. although EFA and growth improved, with relatively greater improvement Thus there is a need for daily supplementation with vitamins A, D, E and with Encala treatment. K. Previously this involved taking numerous dosage forms of three different Conclusion: Subjects with greater fat loss had a statistically and clinically medications for adults with CF. Recently all-in-one multivitamin prepara- meaningful increase in CFA (+7.5%) with Encala treatment and improved FA tions have become available which can reduce this tablet burden. We and growth. Encala treatment resulted in weight gain and improved aimed to assess the impact of rolling out Paravit CF™ in our adult cohort on nutritional status in participants with CF/PI and likely will provide such serum vitamin levels and patient satisfaction. benefits to patients with other exocrine pancreatic diagnoses. Methods: All applicable people with CF offered the opportunity to switch to Paravit CF™ capsules from traditional vitamin supplements. Serum P286 vitamin A, D and E levels compared from most recent annual review prior Impact of Mycobacterium abscessus infection on nutritional status in to switch and at annual post switch with minimum 6 months elapsed children and adolescents with cystic fibrosis: a single-centre audit following start of Paravit CF™. Individuals asked to complete a structured 1 1 1 2 3 2 questionnaire pre and post Paravit CF™ initiation assessing knowledge of M. Creedon ,E.Owen,K.O’Brien , C. Dawson , M. Riley , E. Kavaliunaite . 1 vitamin supplements, self-reported adherence and ease of use. Great Ormond Street Hospital for Children NHS Trust, Dietetics, London, 2 Results: 28 people switched to Paravit CF™ (100% uptake). 24 completed United Kingdom; Great Ormond Street Hospital for Children NHS Trust, 3 questionnaires obtained. Daily vitamin tablet burden pre 3.9 vs post 2.2 Respiratory Unit, London, United Kingdom; Great Ormond Street Hospital for (43.6% reduction). Average serum vitamin A level pre 1.63 vs post 1.65 Children NHS Trust, Lung Function Unit, London, United Kingdom p = 0.87 (n = 22), vitamin D pre 51.8 vs post 56.7 p = 0.16 (n = 25) and Objectives: Prevalence of non-tuberculous mycobacterium (NTM) infec- vitamin E pre 20.8 vs post 19.7 p = 0.42 (n = 24). Hypovitaminosis observed tion in the UK CF population has increased from 1.3% to 4.3% (UK CF registry for vitamin A pre 14.3% vs post 14.3%, vitamin D pre 48% vs post 40%, 2010–2018). Chronic Mycobacterium (M. abscessus) is most prevalent in vitamin E pre 8.3% vs post 12.5%. No high serum levels observed. 33.3% adolescence and associated with lung function decline, however little has knew what doses of vitamins they took pre switch vs 91.7% post switch. been reported on the impact on nutritional status. Self-reported adherence improved from 78.0% pre to 83.9% post. Aims: To review the nutritional status of patients 2 years prior to the Conclusion: Paravit CF™ is non-inferior to traditional vitamin supple- diagnosis of M. abscessus and at the time of diagnosis, identifying mentation at achieving normovitaminosis A, D and E. It offers a simpler and predisposing nutrition factors. easier to manage alternative that reduces vitamin tablet burden in adults Methods: Retrospective chart review of all patients managed at a CF with CF. Its potential effect on serum vitamin K levels still needs to be specialist centre with 2 isolates of M. abscessus identified at a subspecies researched. level between 2017–2019. Growth parameters: weight, BMI, and lung function measurements were recorded longitudinally at time points P288 annually from 2 years pre first isolate until treatment was initiated. Evaluation of dietetic service provision in UK paediatric cystic fibrosis Secondary comorbidities were recorded: CF diabetes and liver disease. care: how are we doing? Results: Seven children (4 girls) were diagnosed with M. abscessus, Median J. Lowdon1, C. Stackhouse2, V. Bara3, G. UK CF dietitians group4. 1Leeds age 14.17 years at treatment initiation. All were pancreatic insufficient (PI). Children’s Hospital, CF Unit, Leeds, United Kingdom; 2Royal Papworth Patient 1 had an optimal BMI, the rest had low BMI pre diagnosis and Hospital, Dietetic Dept, Cambridge, United Kingdom; 3Royal Brompton & received nutrition support. Five of the patients had CF diabetes. Two Harefield Hospt, Dietetic Dept, London, United Kingdom; 4British Dietetic patients had regular admissions for IV antibiotics and were gastrostomy Association, Birmingham, United Kingdom fed. Conclusion: Nutritional risk factors for NTM were exhibited by all the Objectives: To asses dietetic staffing levels and service provision in UK patients (increasing age, lower BMI, PI, CF diabetes and liver disease) The paediatric Cystic Fibrosis (CF) services. Despite the number of patients with effect of M. abscessus on nutritional status was variable. Further studies are CF increasing (CF Trust 2018), recommended dietetic staffing levels have needed in this vulnerable group of patients to prevent nutritional decline. not been updated (CF Trust 2011). Dietitians are required to adhere to the CF Trust Standards of Care (CF Trust 2011, CF Trust 2016), to provide regular, specialist review.

Table 1. (abstract: P286) BMI Z-score

Patient M. abscessus Age at 2 year pre 1st 1 year pre 1st M. abscessus M. abscessus CF Diabetes CF Liver Nutrition Support subspecies diagnosis isolate isolate 1st isolate treatment Disease (Years) (BMI z-score) (BMI z-score) (BMI z-score) initiation (BMI z-score)

1 abscessus 5.6 1.91 1.84 0.98 1.53 N N None 2 abscessus 13.9 −0.73 −0.84 −0.54 −0.63 Y Y Supplements Gastrostomy 3 abscessus 11.5 −0.66 0.28 −0.06 −0.14 N N Supplements 4 massiliense 14.9 −1.78 −1.3 −1.53 −1.75 Y N Supplements Gastrostomy 5 abscessus 15.5 −1.68 −0.96 −1.18 −0.62 Y Y Supplements 6 massiliense 14.2 −1.36 −1.31 −1.72 −2.06 Y N Supplements 7 massiliense 16.6 −0.47 −1.1 −0.76 −0.96 Y Y Supplements Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S137

Methods: Data from 119 members of the UK CF dietitians group was P290 collected via a Survey MonkeyTM questionnaire emailed in March 2019. Successful trial with an appetite stimulator in 2 siblings with cystic Data was separated into adult (59) and paediatric (60) respondents. fibrosis with persistent failure to thrive and poor appetite Results: N = 19. Shared care (13), full care (5), adults and paediatrics (1). I. Claes1, S. Van Meerbeeck1, T. Havermans1, M. Proesmans1. 1University Response rate 32%. Hospital Leuven, Leuven, Belgium 12 centres (63%) reported insufficient (IS) staffing levels, 7 centres reported sufficient staffing (S). IS mean 0.1 whole time equivalent (WTE) per 14 Objectives: In Cystic Fibrosis (CF), an intensive nutritional therapy is patients (7.5–28), S mean 0.1 WTE per 11 patients (3–17). Staffing needed to maintain adequate growth and weight. It is well known that a variations ranged from 0.1 WTE for a mean of 12 patients (3–28) in good nutritional status is associated with a better long-term outcome. shared care settings, to 0.1 wte for a mean of 15 patients (7.5–19.5) in full Despite all treatment modalities and feeding intervention, some children and shared care settings. Main differences between the 2 groups: 100% S with CF have persistent and severe failure to thrive. group were able to review ad hoc patients all/most of the time vs 33% IS Methods: 2 siblings (n = 2) with CF (F508del homozygous; boy, age 9 and group; 100% S group were able to attend specialist clinics all/most of the girl, age 8 years) with severe failure to thrive since birth despite maximal time vs 38% IS group; provision of home/school visits, 80% S group offer treatment, were studied. Their treatment includes a high dose PERT, PPI, these some/all the time vs 42% IS group. hyper caloric diet, enteral feeding and regular admissions to a rehabilita- Conclusion: Dietetic services across the UK vary considerably in terms of tion centre. Parent-CF team relations were tense and trust in parents’ service provision. We conclude that this can affect patient care, where ability was questioned. The children were prescribed Cyproheptadine ® services with a lower WTE to patient ratio are unable to provide consistent (Periactin ), an antihistamin used to treat allergies with an improved services. Further work is needed to assess how this may affect patient appetite as side effect. The 2 siblings were treated in a 3 weeks on and 1 outcomes, such as body mass index and the long-term impact that this may week off schedule (to prevent tolerance) over 3 months. have. Results: A significant difference in appetite and food intake was assessed since the start of Cyproheptadine, particularly during the 3 weeks active References treatment. The children’s nutritional status evolved in 3 months from BMI CF Trust 2011 Standards for the Clinical Care of Children and Adults z-score −1.5 to −0.6 for the boy and −1.5 to −0.4 for the girl (table 1). The with Cystic Fibrosis. children did not show other frequent side-effects like sleepiness or CF Trust 2016 Nutritional Management of Cystic Fibrosis dizziness. CF Trust 2015 UK Cystic Fibrosis Registry Annual Data Report 2018. Table 1. Weight, height and BMI P289 The effect of Paravit-CF® on serum vitamin A (Retinol) and vitamin D Baseline 3 Baseline 3 (25-Hydroxyvitamin D3) levels in adults with cystic fibrosis Boy month Girl month (n = 1) change (n = 1) change C. Landers1. 1St. Vincent’s University Hospital, Cystic Fibrosis National Referral Centre, Co. Dublin, Ireland Weight z-score −2.9 −2.0 −2.3 −1.4 Height z-score −2.5 −2.4 −1.9 −1.8 Objectives: Analysis of vitamin A and D3 levels in a cohort of adults with CF BMI z-score −1.5 −0.6 −1.5 −0.4 showed 60% had vitamin A deficiency and 20% had vitamin D levels approaching toxicity. A new fat-soluble multi-vitamin, Paravit-CF® is small, Conclusion: Cyproheptadine had a positive effect on appetite and weight tasteless and odourless. It has a lower vitamin D content and better vitamin gain in these 2 children. This treatment was also beneficial for the parent- A bioavailability compared to other CF-specific supplements. Paravit-CF® team relations and for the family as well, because of the reduction of stress could improve the balance of vitamin A and D levels in this group. at mealtimes. It may be a potential medicine to treat children with CF with Aim: To assess the efficacy of Paravit-CF® in improving the balance of a persisting failure to thrive. It is interesting to investigate whether this also serum vitamin A and D levels in adults with CF. applies to other children with CF in the future. Methods: Retinol, vitamin D3, CRP and RBP were measured in 22 patients with stable disease who met the inclusion criteria: Symptomatic vitamin A deficiency (n = 2), vitamin D3 level of >80 mmol/L and a biochemical vitamin A deficiency (n = 11), or poor compliance with vitamins (n = 9). Paravit-CF® was prescribed to replace Dekaplus Softgel (n = 16), Aquadek Physiotherapy chewable (n = 4) or an over the counter multivitamin (n = 2). Measurements were repeated at 3–6 months. P291 Results: At baseline,100% of subjects had vitamin A deficiency. Overall, 60% An update from the UK Cystic Fibrosis and Exercise Network of vitamin A levels had improved to some extent at follow up. Three H. Douglas1, O. Tomlinson2, A. Ahlquist3, J. Shelley4. 1UCL Great Ormond improved to within normal range, nine subjects improved but remained Street Institute of Child Health, University College London, London, United sub-clinically deficient and three did not change. Mean vitamin A Kingdom; 2Children’s Health and Exercise Research Centre, Sport and Health increased from 1.16 umol/L (±0.4) to 1.37 umol/L (± 0.6) which reached Sciences, University of Exeter, Exeter, United Kingdom; 3Nuffield Health, statistical significance (p = 0.17). Epsom Gateway, Ashley Avenue, Epsom, Surrey, United Kingdom; 4Physical Four patients had vitamin D levels <50 mmol/L at baseline. Two improved Activity Exchange, Research Institute for Sport and Exercise Sciences, Liverpool but remained deficient, two improved to within normal range. Six patients John Moores University, Liverpool, United Kingdom had baseline vitamin D3 within normal range and at follow up. All vitamin D levels that were approaching toxicity at baseline, had improved to normal Objectives: The UK Cystic Fibrosis (CF) and Exercise Network have hosted range at follow up. Mean baseline vitamin D was 79.13 mmol/L (±36) and annual meetings since 2016 to provide a peer support system and facilitate 79.41 mmol/L (±22) at follow up. There was no statistically significant sharing of best practice. The network has tracked and highlighted change in vitamin D levels. discrepancies in exercise provision and the roles and responsibilities of Conclusion: Paravit CF improved serum vitamin A retinol levels and clinical staff within UK CF care. Results from the 4th annual network maintained 25-Hydroxyvitamin D3 levels within normal range in adults meeting survey are provided. with CF. Methods: 46 delegates attended, representing 28 European institutions (NHS = 20, University = 5, Charity = 2, Other = 1). Delegates completed a survey, providing quantitative and qualitative data relating to clinical practice and meeting evaluation. Results: All 2019 respondents reported that the meeting will inform future practice, citing the opportunity to network and share best practice as key S138 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 features. The individuals primarily responsible for exercise testing and Methods: A questionnaire about the amount of days with ≥60 min daily prescription in each centre have been reported annually between 2016– PA per week, the duration and intensity levels (minutes) and interest in 2019, with a physiotherapist being reported as responsible in 75%, 79%, 48% PA was sent to all paediatric CF patients treated at Hannover Medical and 50% of centres, and an exercise ‘technician’ in 25%, 16%, 30% and 43% of School. 34 boys [b] and 54 girls [g] aged 3–17 y were evaluated. centres respectively. 2019 respondents reported discussing exercise with Correlations between age, sex, BMI Z-Score and lung function (GLI- patients at every (64%) or at least every other (16%) clinical visit, which is Score) were examined. comparable to previous meetings. 72% of respondents reported feeling Results: 88 CF patients (aged 10.7 ± 4.4 y) participated (BMI Z-Score ‘ ’ − – confident in discussing exercise, however 96% felt that further training, 0.45 ± 0.93; FVC 91.5 ± 16.9%; FEV1 84.4 ± 22.6%; MEF25 75 68.3 ± 35.1%). qualifications and guidance would be beneficial, with 100% also wanting to Summarised only 6.8% (b = 8.8%; g = 5.6%) do as much PA as recommended attend future meetings. A workshop discussing accreditation for exercise by WHO. Duration of PA with moderate activities (≥3 METs) is 56.1 ± 31.0 professionals working in CF was reported as ‘useful’ by 88% of respondents. min/day (b = 68.9 ± 33.9; g = 47.9 ± 25.9). Main reasons for less PA are lack of Conclusion: The network has documented an increase in exercise time (44%), motivation (25%), no individual offerings (23%) and less technicians working in CF, with increasing responsibility in the provision knowledge about the benefits of PA (11%). The age group 11–17 y is less of exercise. The annual meetings facilitate sharing of best practice, with a active than the younger ones. desire for future events to focus on practical approaches to exercise Conclusion: Patients with CF in our study do less PA than recommended prescription, sharing of case studies, pursuit of accreditation and and the compared group. Boys are more active than girls, with increasing standardisation of exercise technician roles. age the inactivity grows. Average PA (min/day, ≥3 METs) indicates that if the patients are active, they do it with higher duration and intensity level to P292 compensate lack of time. Because of therapy burden a high rate of “Just move it … move it”: a multidisciplinary motivational approach to motivation and organisation is necessary to implement PA into daily life. improve the physical activity in children with cystic fibrosis Therefore a continuous PA evaluation, sport consulting, motivation and V. Sputael1, V. Gaspar1, S. Namane1, C. Knoop2, L. Hanssens1. 1Hôpital des support for individual activities should be a permanent component in Enfants Reine Fabiola, Institut de Mucoviscidose de l’Université libre de healthcare of patients with CF. Bruxelles, Brussel, Belgium; 2Hôpital Erasme, Institut de Mucoviscidose de l’Université libre de Bruxelles, Brussel, Belgium P294 The level of physical activity, lung function and exercise capacity of Purpose: Regular physical activity (PA) is an important component in the children and adolescents with cystic fibrosis compared to healthy therapeutic management of patients with cystic fibrosis (CF) to improve controls their respiratory function and physical status. The purpose of this study 1 1 1 1 1 P.M. Rovedder , M. Cardoso , G. Motter , C. Taffarel , A.P. Kasten , was to evaluate the PA of our CF paediatric patients and the impact of a 1 1 1 C. Schimdt , P.J.C. Marostica . Universidade Federal do Rio Grande do Sul, multidisciplinary project –“Just move it … move it”, using the motivational Porto Alegre, Brazil interviewing (MI) to undertake or increase the PA. The effect on the clinical, nutritional and functional parameters was also studied. Objective: To evaluate level of Physical Activity (PA), lung function and Methods: This is a longitudinal study including children with CF aged more functional capacity in children and adolescents diagnosed with CF and than 6 years. At 0 and 6 months, the body mass index (BMI), spirometric compare them with those of healthy children and adolescents. values and pulmonary exacerbations were collected as well as the duration Methods: The study had a cross-sectional design with a control group. of extracurricular PA and the maximum oxygen uptake (VO2max) Patients with CF were followed at the Children’s Pneumology Outpatient measured by a 15-meter shuttle run test. A MI was performed during Clinic and were matched for age and sex with healthy controls from a local each study and routine visit by the physiotherapist, dietician and paediatric public school. The evaluations included daily step count, the shuttle walk pulmonologist to improve the PA of the patients. Depending on the test and spirometry. increase of the PA, the patients were classified in two groups: a group Results: 70 children and adolescents were evaluated, 35 diagnosed with without change and a second one with an increase of minimum one hour. CF and 35 healthy controls. The overall mean age was 11.6 ± 2.9 years. Results: Nineteen children were included (girls: 58% and mean age: There was no significant difference in level of PA between the 9.9 ± 2.8 years). Before the start of the project, the mean estimated VO2max patient and control groups. Gender analysis revealed no significant and time of extracurricular PA were respectively of 47.7 ± 3.2 ml/kg/min difference in level of PA between the groups or within the CF group. The and 1.8 ± 1.6 hours/week. Ten patients (52.7%) increased their regular PA CF group values were significantly lower than the control group for BMI

(mean 1.9 h/week) between the both visits. No significant difference was (p = 0.04), percentage of predicted FEV1 and FEV1 Z-score (p = 0.02 and observed for the BMI, exacerbations, spirometric values and VO2max p = 0.010). between the groups. Conclusion: In this sample, children and adolescents with CF had the same Conclusion: Our CF paediatric population seems to be more active level of PA as their healthy peers. Boys and girls with CF had similar level of compared to literature. “Just move it … move it” seems positively impact PAwhen stratified by sex, as well as when compared to healthy peers of the ’ the PA in children with CF. As opposed to the literature, we don t find any same gender. Differences were observed between BMI, FEV1 and some statistically significant effect of this increase of PA on nutritional, functional functional capacity test variables between the groups. or clinical parameters after 6 months. An additional evaluation after one year may be interesting. P295 The value of exercise guidelines post-exercise testing in adult patients P293 with cystic fibrosis Physical activity in children and adolescents with cystic fibrosis – do K. Lavery1, L. Carson1, C. Loughran1, L. Murphy1, C. Addy1,2. 1Belfast Health they move enough? and Social Care Trust, Belfast, United Kingdom; 2Queen’s University Belfast, F. Junge1, 2, T. Hellmuth1, L. Stein1, 2, S. Junge1. 1Medical School Hannover, Centre for Medical Education, Belfast, United Kingdom Pediatric Pneumology, Neonatology and Allergology, Hannover, Germany; 2 Objectives: Exercise testing is important in CF and recommended by the CF Medical School Hannover, Institute of Sports Medicine, Hannover, Germany Trust. Tests performed in our centre include Modified Shuttle Walk, Chester Objectives: World Health Organization (WHO) recommends moderate to Step, 6-Minute Walk, and One-Minute Sit-to-Stand. Patients are encour- intensive physical activity (PA) of 60 min/day for children and adolescents. aged to exercise as part of their CF management, but many patients are not Results of German health survey show, that 26% of participants (aged 3–17 aware of the exercise level required or appropriate precautions. To address years [y]) are active for 60 min/day. PA for patients with CF provides this we aimed to determine the value of post exercise test exercise benefits, e.g. better lung function and improved quality of life. Therefore guidelines in adult (≥17 years) patients with CF. our primary research question was how physically active are children and Methods: Post-exercise test guidelines were introduced in August 2017. adolescents with CF compared to WHO recommendations. These outlined individual targets for aerobic and resistance training, Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S139 posture exercises, and appropriate precautions. In April 2019, a retrospect- exacerbation. Physical exercise is seen as central to the physiotherapy ive audit of exercise tests in this 20-month period (n = 88) was performed. management of these patients. However, no standardised exercise test has Post exercise test, patients continuing to exercise completed a question- been adopted nation-wide in this population. naire to assess attendance rate, value of the exercise guidelines, and Methods: A retrospective notes audit of all CF patients, over the age of 5 benefits felt from exercise. and able to do lung function, that were admitted for a course of IVAB to our Results: Post-exercise test 53% (n = 47) patients were interested in unit. They had completed a standardised 6-minute exercise test within 48 receiving exercise guidelines for an exercise scheme, independent gym, hours of admission and again before discharge. personal trainer, or hospital-based programme, with 66% (n = 31) com- Results: A paired sample t test was performed which found a highly pleting the audit questionnaire. significant improvement in distance travelled during the 6 minute exercise Of audited patients, 71% (n = 22) attended an exercise scheme, 13% (n = 4) test between admission mean (S.D) = 552.157(34.633) and discharge mean attended a hospital based programme, 10% (n = 3) an independent gym, 3% (S.D) = 611.161 (35.126) when controlling for individual patient. t (n = 1) acquired a personal trainer, and 3% (n = 1) didn’t start exercise. (88.39) = 3.486, p < 0.001. There was also a strong correlation between 6 Average length of attendance was 6 weeks. Of the 20 (67%) patients who Minute Exercise Test (meters) and FVC when accounting for the age of the received exercise guidelines, 80% (n = 16) stated they were useful. The individual. majority of patients, 70% (n = 21) felt benefit from their exercise Conclusion: 6-Minute Exercise Test significantly improved throughout programme, 20% (n = 6) felt no benefit, and 10% (n = 3) failed to comment. admission, illustrating an increase in exercise tolerance during the patient’s Conclusions: Over half the patients attending exercise tests in our centre stay. A strong correlation between the 6-minute exercise test distance and took up the offer of commencing an exercise routine for an average of 6 FVC was noted therefore demonstrating the tests sensitivity to detect weeks post-test. Most patients who received exercise guidelines felt they change in this patient group. Further investigation into the 6-minute were useful and over two thirds of the patients felt benefit from their exercise test including normative values would be of benefit. exercise routine. P298 P296 Annual changes in aerobic fitness are biased between normative Association of peripheral muscle strength with exercise capacity and equations in children and adolescents with cystic fibrosis use of antibiotics in patients with cystic fibrosis O.W. Tomlinson1, 2, A.R. Barker1, J. Trott2, P.J. Oades2, N.J. Withers2, N. Evangelista Campos1, F.M. Vendrusculo1, M.F. Gheller1, C.A. Williams1,2. 1Children’s Health and Exercise Research Centre, Sport and I. Silveira de Almeida1, N. Acosta Becker1, J.P. Heinzmann-Filho1, Health Sciences, University of Exeter, Exeter, United Kingdom; 2Royal Devon M. Pérez Ruiz2, M.V. Fagundes Donadio1. 1Pontifícia Universidade Católica do and Exeter NHS Foundation Trust, Exeter, United Kingdom Rio Grande do Sul, Centro Infant, Laboratory of Pediatric Physical Activity, Porto 2 Objectives: Peak oxygen uptake (VO ) is an important prognostic Alegre, Brazil; Universidad Europea de Madrid, Facultad de Ciencias de la 2peak parameter in CF. Three equations are recommended by the ECFS to Actividad Física y Fisioterapia, Madrid, Spain – characterise VO2peak as a percent of predicted (%Pred) Jones (1985), Objectives: To evaluate the association of peripheral muscle strength with Orenstein (1993) and Werkman (2014), with previous cross-sectional exercise capacity and use of antibiotics (ATB). research showing poor agreement between equations. However, longitu- Methods: Cross-sectional study including patients with cystic fibrosis (CF) dinal agreement between equations is unknown and therefore explored in aged ≥6 years. Patients underwent peripheral muscle strength evaluation this analysis. (biceps, quadriceps and hamstrings) and performed a cardiopulmonary Methods: Two years of sequential cardiopulmonary exercise testing (CPET) exercise test (CPET). In addition, demographic, anthropometric, genetic, data were retrospectively analysed in 18 children and adolescents (<18 lung function, and total days of ATB use within one year of tests were years) with CF (11 male, 13.9 ± 2.2 years). Agreement between equations in collected. All legal guardians signed the consent form. Descriptive annual change in VO2peak (%Pred) was classified discretely based upon analysis and the Spearman correlation test were used. Significance was set direction of change (i.e. increase/decrease). Only 4/18 patients were at p < 0.05. characterised using the Jones equation (requires age ≥15 years). All 18

Results: Forty-seven patients with a mean age of 15.9 ± 6.5 years and FEV1 patients were characterised using the Orenstein and Werkman equations (%) of 80.6 ± 25.2 were included. The median muscle strength was 14, 17 (requires age <18 years). −1 and 7 kg for biceps, quadriceps and hamstrings, respectively. The mean Results: Absolute VO2peak increased by 0.19 L.min (p = 0.031), whereas −1 −1 peak oxygen uptake (VO2peak) was 36.6 ± 7.0 mL/kg/min, ventilatory VO2peak relative to body mass did not (0.31 mL kg .min , p = 0.83) in the equivalents for oxygen uptake (VE/VO2) was 27.8 ± 4.8 and carbon dioxide year between CPETs. Direction of VO2peak (%Pred) varied (mean ± SD, range): − − − − production (VE/VCO2) was 24.7 ± 3.9. Significant correlations (p < 0.05) 2.2 ± 3.5%, 0.2 to 7.5% (Jones); +2.2 ± 10.4%, 17.3 to 21.3% (Orenstein); − − were found for biceps strength with VE/VO2 (r = 0.58) and VE/VCO2 +1.2 ± 23.6%, 33.7 to 77.5% (Werkman). Between the Jones and Orenstein − (r = 0.59) at anaerobic threshold (AT) and with VO2 (r = 0.37), VE (r = 0.78), equations, 100% of directional changes were in agreement (all reported − VE/VCO2 (r = 0.61) at peak exercise. Quadriceps strength correlated with reductions in VO2peak). Between the Jones and Werkman equations, 50% of − − VE/VO2 (r = 0.63) and VE/VCO2 (r = 0.62) at AT and with VE (r = 0.71) and directional changes were in agreement. Between the Werkman and − VE/VCO2 (r = 0.58) at peak. The strength of the hamstrings correlated with Orenstein equations, there was 72% agreement. − − VE/VO2 (r = 0.52) and VE/VCO2 (r = 0.51) at AT and with VE (r = 0.60) and Conclusion: This analysis highlights discrepancies in characterising − VE/VCO2 (r = 0.49) at peak exercise. In addition, we have also found direction of annual changes in VO2peak as %Pred in children and adolescents − significant weak correlations of biceps (r = 0.32) and hamstrings (r = with CF, which could impact upon treatment options if VO2peak is wrongly −0.31) strength with the total days of ATB use in the following year. over- or under-estimated, dependent upon use of differing equations. Conclusion: The results show that peripheral muscle strength is associated Standardised reporting of CPET data is an imperative focus for CF teams and with exercise capacity, especially with ventilatory efficiency. However, data a single equation should therefore be selected for use. suggests a weak correlation between peripheral muscle strength and the need for ATB use in CF patients. P299 Use of the Polar™ H10 Heart Rate Sensor during the Modified Shuttle P297 Walk Test in children with cystic fibrosis: can we demonstrate maximal Change in 6-minute exercise test in children with cystic fibrosis response? admitted for intravenous antibiotics and physiotherapy R. O’Connor1, E. Raywood2, H. Douglas2, E. Main2,C.Pao1. 1Royal London L. Lowndes1, C. Hamilton1, K. Lock1, D. McShane1. 1Addenbrookes Hospital, Children’s Hospital, London, United Kingdom; 2UCL Great Ormond Street Cambridge, United Kingdom Institute of Child Health, London, United Kingdom Objectives: Hospital based IV antibiotics and physiotherapy are routinely Objectives: Cardiopulmonary exercise testing (CPET) is the gold standard used in patients with cystic fibrosis presenting with respiratory exercise test for children with cystic fibrosis (CF), but is not widely available S140 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 clinically and requires specialist equipment. The 25 level Modified P301 Incremental Shuttle Walk Test (MSWT), a commonly used field test, is Yoga as exercise for cystic fibrosis inpatients often described as a submaximal test due to difficulty in assessing whether T. Jenkins1, Z. Beverley1, A. Jones1. 1Royal Brompton and Harefield NHS Trust, a maximal effort has been made using standard SpO2 and heart rate (HR) Cystic Fibrosis Department, London, United Kingdom monitoring. We investigated the use of a Polar™ H10 HR sensor to assess whether maximal effort was achieved. Background: The importance of physical activity and exercise is well Methods: Thirty children (6–16 years; mean ± SD 9.9 ± 2.8) with a range of documented in CF. Yoga in CF can improve lower back pain, thoracic kyphosis, stress incontinence, ease of clearance, body image, fitness, lung disease severity (FEV1 92 ± 14.61%pred; mean ± SD) underwent exercise testing at one recruitment site as part of Project Fizzyo. Each anxiety and sleep (CF trust, 2017). participant wore a Polar™ H10 HR sensor chest strap throughout the Objectives: Assess patient reported benefits, uptake and feasibility of MSWT. A Dynamap pulse oximeter was attached immediately after structured and supervised yoga sessions in an inpatient adult CF termination of the MSWT (if the participant missed two bleeps or was population. unable to continue). Maximal HR from the Polar™ sensor and Dynamap Methods: Structured yoga sessions delivered by physiotherapists or an pulse oximeter were compared and the Children’s OMNI scale of perceived exercise practitioner were offered to CF patients admitted over a 4-week exertion score was recorded. period as an alternative to usual exercise sessions. Sessions were guided by Results: The mean MSWT distance was 1057 ± 230 mSD, equating to levels an exercise sheet of 30 postures with individual sessions tailored to the 10–15 on the MSWT. 90% of participants (27/30) achieved a HR of ≥180 patient abilities or contraindications. Patients were encouraged to (mean 193.23; range 174–215) on the Polar™ sensor demonstrating the complete additional independent sessions. A short questionnaire assessing ability of the MSWT to generate a maximal exercise response. By contrast, subjective benefits, enjoyment, and likelihood to continue yoga at home using a pulse oximeter, only 37% (11/30) demonstrated a HR ≥ 180 bpm was completed on discharge. (mean 174.55; range 142–203). 16 (53%) of the tests were classified Results: 41 patients were admitted during the 4-week period. 14 patients differently depending on which HR measure was used. The median OMNI (11 females) with a median FEV1 55% (IQR 31) completed between 1–4 score post-MSWT was 9/10. sessions of supervised yoga and 7 patients completed independent Conclusion: Continuous use of a Polar™ H10 Heart Rate Sensor improves sessions. A median of 26 (IQR 4.25) out of 30 yoga poses were completed the accuracy of maximal test definition during the MSWT in children with in each session. Reasons for not completing yoga were: medically unwell CF compared with pulse oximetry. In this study the MSWT elicited a (10), declined (8) or not being asked due to early discharge (6). maximal HR in the majority of children with CF with peak HR values in Median enjoyment of yoga rated on a visual analogue scale (VAS) (0 = no keeping with CPET. enjoyment to 10 = most enjoyment) was 8 (IQR 2.75). The median likelihood to continue at home on a VAS (0 = not likely, 10 = most likely) P300 was 7 (IQR 4.4). Reported benefits of yoga included improved flexibility Cardiorespiratory fitness and physical activity levels in the current (n = 9), improved posture (n = 7), breathing (n = 7) and reduced stress paediatric population with cystic fibrosis (n = 6). 1 2 3 1 Conclusion: Yoga was a feasible and enjoyable exercise intervention in this M. Burghard , H.G.M. Heijerman , C.K. van der Ent , T. Takken , 1 1 small cohort of inpatients with CF. Offering yoga to inpatients required no H.J. Hulzebos . Wilhelmina Children’s Hospital, Child Development and 2 increase in service provision and minimal training due to the structured Exercise Center, Utrecht, Netherlands; University Medical Centre Utrecht, 3 exercise sheet and meant patients felt confident continuing yoga Lung Department, Utrecht, Netherlands; Wilhelina Children’s Hospital, independently. Pediatric Pulmonology, Utrecht, Netherlands Objectives: To explore physical related variables in the current paediatric P302 population with Cystic Fibrosis (CF), dividing the population in fit (F) and Developing an ecological approach to physical activity promotion in not-fit (NF) patients. adults with cystic fibrosis Methods: During the period 2016–2019 cardiopulmonary exercise testing J. Shelley1, 2, Z. Knowles1, L. Boddy1, C. Stewart1,F.Frost2,3, D. Nazareth2,3, 2,3 1 1 was used to determine oxygen uptake (VO2max) as a measure for M. Walshaw , E. Daswon . Liverpool John Moores University, Sports and 2 cardiorespiratory fitness (CRF). Fit patients were defined when VO2max Exercise Science, Liverpool, United Kingdom; Liverpool Heart and Chest was ≥82% of predicted. Spirometry was used to measure forced expiratory Hospital, Department of Respiratory Medicine, Liverpool, United Kingdom; 3 volume in 1 second expressed in percentage predicted (ppFEV1), physical Institute of Infection and Global Health University of Liverpool, Liverpool, activity (PA) was measured with self-report regarding the amount of days United Kingdom one was at least moderately physically active for at least 60 min/day. Fatigue was measured with the general fatigue subscale of the Paediatric Quality of Objectives: Studies investigating physical activity (PA) in adults with Cystic Life multidimensional fatigue scale. Patients were defined severely Fibrosis (CF) have primarily researched the delivery of exercise training fatigued when the score was ≤2 SD below the norm. Several types of interventions, which often don’t include long-term PA promotion. This between group tests were used to explore differences between F and NF study aimed to 1) Understand the ecological correlates of PA in adults with patients. CF, 2) utilise a formative approach to inform the development of an Results: A total of 68 patients (52.9% male) with a median age of 15.3 years intervention to promote PA, 3) involve individuals with CF, their families – th – and clinicians in the research process. (25 75 percentile 13.0 16.9 years) and mean ppFEV1 85.5% (±17.8) participated in the study. More than half of the patients (52.9%) was not fit. Methods: Phase 1: semi-structured interviews explored perceptions of PA This group (n = 36) was older (p = 0.021), had higher fatigues scores among adults with CF (n = 11: 6 Male, 5 Female, aged 33.2 ± 7.1 years with a (p = 0.003), and had lower PA levels (p = 0.038), compared to the F-group Forced Expiratory Volume in one second of 54 ± 17% predicted). (n = 32). When combining fitness level and level of fatigue, the NF and Phase 2: adults with CF (n = 9) and family members and clinicians (n = 3) fatigued group (n = 13) was older (p = 0.005), had higher BMI (0.023), lower participated in separate focus groups to discuss perceived barriers, facilitators and opportunities for PA identified during phase 1 in order to ppFEV1 (0.026), and lower ventilatory anaerobic threshold (p = 0.002), compared to the F and not-fatigued group (n = 30). The NF and fatigued inform the development of an intervention to promote PA. Thematic group had a close to significant lower reported PA level (p = 0.056). analysis was used to generate themes centred on the PRECEDE-PROCEED Conclusions: CRF is reduced in a large part of our current paediatric CF model. population. In patients with higher CRF and higher PA levels, fatigue is less Results: Participants with CF perceived that PA was beneficial in managing the physical and psychological manifestations of CF reported as barriers to experienced and ppFEV1 is better preserved. Maintaining and improve- ment of CRF and PA levels remain, even in this decade, important aspects in PA. Enjoyment of PA and the support of exercise professionals and family the treatment of paediatric patients with CF. were positive correlates of PA. Participants with CF, their families and clinicians suggested that PA interventions should aim to improve the overall ‘well-being’ of individuals with CF which encompassed Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S141 improvements in key outcome measures, managing symptoms and Results: In this cohort 47% were male and mean ppFEV1 was 54%. Eighty engaging individuals with CF to increase PA. The transition to adult care eight percent (n = 30) agreed PA was an essential part of CF care and 56% was identified as an important period for support. (n = 19) found it enjoyable. The median amount of time spent on PA was 60 Conclusion: The promotion of PA in adults with CF may not be best to 90 minutes per week and 26% (n = 9) performed more than the achieved through the delivery of a single intervention but as part of routine recommended amount (150 minutes) of PA per week. The most common CF care. Exercise professional led PA promotion should begin during types of exercise performed were walking on the flat (n = 21), high pace paediatric care and be reinforced throughout an individual’s life with walking (n = 8) and jogging (n = 7). Most enjoyable activities were walking additional support during adolescence. 23% (n = 8), running 14% (n = 5) and swimming 11% (n = 4). The common barriers to PA were tiredness (n = 21), breathlessness (n = 15), followed by P303 time constraints and dislike of PA (both n = 9). Participants preferred to A comprehensive framework sustains patients living with cystic exercise alone 44% (n = 15) rather than with others 21% (n = 7). Most fibrosis to engage in countless physical activities lifelong, from muscle participants 62% (n = 21) would like an individualised exercise programme training – bench to outside activities specific to their needs. 1 1 Conclusion: Most adults with CF agree PA is essential to CF care and find it G. Thöni . Mon APACFTR, Exercise Physiology in Health and Chronic Diseases, enjoyable but multiple barriers exist. Following this successful pilot the Adapted Physical Activity for Patients Living with Cystic Fibrosis, Montbazin, questionnaire will now be distributed to all adults at our centre to help France identify ways to improve PWCF participation with exercise. Objectives: Physical activity (PA) is a major health determinant in Cystic Fibrosis (CF). Recent noteworthy progresses in their cares opened new P305 perspectives in patients’ lives. Health-Enhancing Physical Activity (HEPA) Evaluation of maximum exercise capacity and its relationship to lung promotion in CF patients may be increasingly considered throughout their volumes and capacities and body composition of children with cystic lifespan. We aim to propose to local, national/European stakeholders, a fibrosis comprehensive framework to promote long-term active lifestyles in all CF P.M. Rovedder1, G. Motter1, C. Ricachinevsky1, M. Cardoso1, M. Simon1, patients, whatever their age, health/functional status, or dwelling place. C. Taffarel1, P.J.C.Marostica1. 1Universidade Federal do Rio Grande do Sul, Porto Methods: A pilot PA intervention has been implemented in a local CF Alegre, Brazil centre on the basis of i. best PA clinical practices elsewhere, Objective: To evaluate the oxygen uptake at peak exercise (VO2 peak) and ii. evidence from behavioural strategies, and to correlate with lung volume and capacity and body composition of iii. comprehensive policies of European WHO and HEPA networks. children and adolescents with CF. Methods: Cross-sectional study with CF patients treated at the paediatric After 5-yrs, an ‘ecological’ model (i.e. with multi-sector and -level pulmonology outpatient clinic of a public hospital in Porto Alegre, aged ≥7 partnership) has been produced to support PA promotion in CF patients. years up to 18 years. Study assessments included: cardiopulmonary stress The model targets the patient himself, his/her family, peers, caregivers and testing, plethysmography, and body composition assessment using body environmental factors (school, club, NGOs, laws…). bioimpedance. Results: The action plan includes regular interviews, educational or PA Results: Thirty patients were studied, with a mean peak VO2 of sessions, in/out hospital, individualised to patients’ needs and motivation. 1.511 ± 0.539 litres in the population studied. Correlation analysis showed Innovative remote sessions by videoconferencing were tested and a strong correlation between peak VO2 in litres and lean mass (r = 0.77 and disseminated. Collective outdoor PAs are questioned. Local equipment, p < 0.001), and strong and inverse correlation with fat percentage (r = −0.77 caregivers’ HEPA programs, training for PE teachers/Sport trainers, grants and p < 0.001).), a strong correlation with FVC in litres (r = 0.72 and or national PA plan for CF patients are considered. The model appeared p < 0.001) and FEV1 also in litres (r = 0.69 and p < 0.001). We observed a feasible, well-tolerated and efficient in changing factors associated to more strong correlation between load (W) and lean mass and during CPET long-term behavioural changes. (r = 0.64 and p < 0.001), and inversely with fat percentage (r = −0.64 and Conclusion: This comprehensive framework may help CF centres, national/ p < 0.001). This study showed that patients with higher lean body European organisations and policymakers to encourage CF patients to composition have a better performance on cardiopulmonary testing, become/remain physically active all over their lifespan. In the near future, contributing to greater exercise tolerance. PA-related medical lobby could be probably lightened with the widespread use of new active multi-therapies but PA will probably remain a key choice P306 for health and well-being in CF patients as in the general population. Current fitness levels of adolescents with cystic fibrosis in Malta compared to European Eurofit normative data 1 1 2 3 1 P304 C. Falzon , D. Carabott Pawley , P. Sammut , V. Massalha . Mater Dei 2 A questionnaire to assess views, practices and barriers to physical Hospital, Physiotherapy Department, Msida, Malta; Mater Dei Hospital, 3 activity in adults with cystic fibrosis Department of Paediatrics, Msida, Malta; Ministry for Health, Physiotherapy 1 1, 2 1 1, 3 1 Services, Valletta, Malta K. Crawford , C. Addy , S. Caskey , D.G. Downey . Northern Ireland Regional Adult Cystic Fibrosis Centre, Belfast Health and Social Care Trust, Objectives: In line with CF care guidelines, paediatric physiotherapy 2 Belfast, United Kingdom; Centre for Medical Education, Queen’s University, services at the acute general hospital in Malta are implementing fitness 3 Belfast, United Kingdom; Centre for Experimental Medicine, Queen’s testing and exercise prescription in conjunction with airway clearance University, Belfast, United Kingdom techniques. The service aims to evaluate fitness levels in Maltese children with CF, identify muscular and/or aerobic limitations which will provide Objectives: Physical activity (PA) is beneficial to people with Cystic Fibrosis basis for accurate treatment and exercise prescription, and observe changes (PWCF) with positive effects on exercise capacity, lung function and health in fitness or health status. Following established fitness tests allows for the related quality of life. Significant barriers to PA exist for PWCF but comparison with normative data for European children. information on these barriers in adults is limited. A questionnaire was used Methods: There are 5 registered Maltese children with CF (5–14 years). 2 to identify opinions, current practices and barriers to PA specific to an adult boys and 1 girl (10–13 years) are participating in this on-going longitudinal CF population. project. During an annual physiotherapy session, anthropometric data is Methods: Guidance on PA in CF and published data on barriers in children/ collected and EUROFIT fitness battery is performed following standardised adolescence were used to design a 13-point questionnaire for PWCF methodology. Scores are compared to European normative data and a attending the NI Regional Adult CF Centre. Questions assessed views on fitness profile is compiled. importance, enjoyability, current practices, barriers to and future interest Results: A cross-sectional view of the fitness status of CF youths was in PA. Questionnaires were distributed to a pilot cohort (n = 34). obtained. Fitness scores varied depending on the fitness aspect tested. A Demographics were recorded. S142 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 general low to average score ranging from P5-P60 was noted when cough (n = 1). A further 12 patients (35%) went on to stop treatment at a compared to European counterparts. Higher scores were noted in upper median of 10 (range 5–40) months due to bronchoconstriction (n = 5), limb speed and agility (S&A) in both sexes and in lower limb S&A in boys. massive haemoptysis (n = 1), transplantation (n = 1), adherence issues Low cardiovascular fitness was noted except in 1 boy who trains football. (n = 1) and unrelated death (n = 4) with an overall discontinuation rate of He reached an average score (P50). 61%. Discontinuation rates according to lung function at initiation of IM

Conclusion: Limitations include lack of Eurofit normative values for the were as follows: 80% of patients with FEV1 < 30% pred, 78% of patients with – Maltese paediatric population and the validity and reliability of some FEV1 30 50% and 55% of patients with FEV1 > 50% pred. Median duration of fitness tests being used especially the 20 metre-shuttle-run test. This will treatment for each cohort was 19 (range 7–26) months, 8 (range 5–11) improve with possible future access to CPET. Despite these limitations, full months and 12 (range 9–40) months respectively. fitness profiles also looking at muscular fitness were obtained. This Conclusion: Whilst IM is shown to be well tolerated in the short term provides an insight on current CF youths’ fitness status, observation of discontinuation rates are higher with use beyond 1 year. There is a trend for progression or regression in health status, and prescription of individual higher rates of intolerance in patients with more severe disease, treatment and exercise programs to improve CF care practice. particularly where lung function is outside licence parameters.

P307 P309 Hacka Health 4 CF: the next chapter using co-design and partnerships The use of Dry Powder Mannitol (DPM) – experience at a large adult S. Rand1, A. Ahlquist2, G. Balmer1, J. Kent1, J. Wilcock2, G. Shaw1, cystic fibrosis centre A. Copeland1. 1Innerstrength Health Ltd, Dublin, Ireland; 2Nuffield Health, T. Penrose1, E. Scott1, M. Ledson1, M. Walshaw1, D. Nazareth1. 1Liverpool Epsom, United Kingdom Heart & Chest Hospital, Liverpool, United Kingdom

Objectives: Physical activity (PA) and exercise are key components in the Objectives: Although DPM for inhalation (Bronchitol®) has been licensed management of children and young people (CYP) with cystic fibrosis (CF). in the UK since 2012 for use in pwCF as a mucolytic agent, uptake has been Hacka Health 4 CF (Innerstrength Health (IH) Ltd) is a novel physiotherapy limited. We have steadily increased its use in our large adult CF unit technology solution designed to remotely monitor and support adherence (n = 347), and now report our experience. to PA and exercise. The objectives were 1) to continue to use a co-design Methods: We reviewed its use 2018–19, looking at the reasons for approach to develop the final iteration of the Hacka Health 4 CF technology initiation, patient acceptability, short and long-term use, and side effects. and 2) to begin recruitment to a non-comparative pilot study to investigate Results: Thirty-five pwCF underwent a test dose of DPM, 31 (89%) during the impact of Hacka Health 4 CF on PA, exercise and fitness in CYP with CF. an inpatient stay: Methods: An ongoing partnership with Fluxx Ltd (a service innovation 1 failed the test dose, 2 declined continuation due to difficulty using the company) and IH was utilised to design the final iterations of the platform. breath actuated inhaler, and 1 (FEV1 < 30%) died after a prolonged A new partnership with the Nuffield Health (NH) CF programme, an admission (death not related to drug). In the remaining 27, it was used in innovative collaboration with 12 NHS trusts to provide gym membership an acute pulmonary exacerbation where there was deterioration/difficulty and personal training for CYP with CF and their families was established. with chest clearance despite other therapy. Of these, 22 (79%) used DPM as Ethical approval was applied for to undertake a 3 month project an adjunct to rhDnase and 5 (18%) due to rhDnase intolerance. Six (22%) did investigating the impact of Hacka Health 4 CF on PA and exercise levels not wish to continue DPM after discharge, but would consider it for future in CYP with CF. exacerbations, 21 (75%) continued DPM after discharge but 9 of these (40%) Results: Unique and valuable insights from the CYP with CF were used to subsequently stopped it (at 5–98 days), 5 permanently. The remaining 4 co-design and co-produce the final iteration of the Hacka Health 4 CF found DPM over-effective and reverted back to their previous mucolytic platform. Hacka Health 4 CF was integrated and operational procedures therapy (at 18–106 days) but would consider its use in a future were embedded into the pre-existing NH CF Programme. Ethical approval exacerbation. Twelve remained on DPM as their sole long-term mucolytic was granted. CYP with CF aged 13–16 years from the NH CF programme therapy. were invited to participate in the pilot study. To date n = 17 CYP have Of the 4 pwCF commenced as outpatients, 3 were to reduce the treatment consented and have been successfully on boarded to the platform. burden while travelling abroad, and 1 through personal choice. Conclusion: Using a unique co-design approach a final iteration of Hacka Specialist Physiotherapist and pwCF feedback was positive with chest Health 4 CF has been created to meet the unique needs of the users of the clearance benefit reported using DPM alongside rhDnase in the short term. technology. Novel partnerships between Fluxx Ltd and NH have allowed for Starting DPM at an inpatient stay provided appropriate training and unique opportunities to develop. Previously unmeasured PA and exercise specialist support to its continued independent use. behaviours are now monitored in the NH CF programme and the impact Conclusions: We have found DPM to be a safe and effective mucolytic and usability of the technology is under investigation. therapy. Importantly, we have found benefits when using this drug in acute exacerbations and continue to explore this option. P308 Long-term tolerability of inhaled mannitol in adults with cystic fibrosis P310 A. Gates1, J. Faulkner1, L. Warnock1, W.G. Flight1. 1University Hospitals Oxford Real-world use of inhaled mannitol in cystic fibrosis: patient-led dose NHS Foundation Trust, Oxford Adult Cystic Fibrosis Centre, Oxford, United modification Kingdom A. Gates1, J. Faulkner1, L. Warnock1, W.G. Flight1. 1University Hospitals Oxford NHS Foundation Trust, Oxford Adult Cystic Fibrosis Centre, Oxford, United Objectives: Inhaled mannitol (IM) has been established as an add-on Kingdom therapy to best standard care following NICE technology appraisal guidance (2012). It is licenced for use in CF adults >18 years, FEV1 > 30% Objectives: Inhaled mannitol (IM) is an established mucolytic therapy for predicted. Whilst there have been a few studies reporting short term use adults with CF but it often has a high discontinuation rate with long term there has been no published evidence reporting longer term use. use. We aimed to review current use of IM at our centre in adults with CF Methods: Retrospective study of adults with CF prescribed IM at our centre established on long-term treatment. between September 2013 and August 2019. Data on short and long-term Methods: Data on clinical parameters, use of inhaled muco-actives, tolerability were collected. adverse events and dosing schedules was collected through semi- Results: 34 patients were initiated on IM during the study period. Median structured interviews and retrospective review of clinical records. – age was 28 years (18 70 years) and mean baseline FEV1 of 57%-predicted Results: 12 patients (7 female) were currently prescribed IM with a median – (SD 23.8). 94% (n = 32) passed the Bronchitol Initiation Dose Assessment age of 32 (range 20 45) years and mean baseline FEV1 %-predicted 66% (BIDA) with 73% continuing as part of maintenance treatment following (27.8). Median duration of treatment was 31 (range 1–68) months. 8/12 review at 6 weeks. Reasons for discontinuation at <6 weeks were (66%) patients were also prescribed rhDNase. All patients had discontinued bronchoconstriction (n = 5), patient choice/adherence issues (n = 3) and Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S143

nebulised hypertonic saline (HTS): 6/12 reduced clinical effect, 4/12 Results: 28 CF adults, median age 36 and best FEV1% predicted in the past bronchoconstriction, 1/12 dislike and 1/12 reason unknown. 12 months 63%, completed questionnaires. Reasons for commencing SNI 4/12 (33%) were taking IM intermittently. Reasons for intermittent use were: rhinosinusitis symptoms 16/28 (57%); nasal/sinus surgery 4/28 included: use during exacerbation only (n = 2); adherence issues (n = 1) (14%); nasal dryness/soreness related to and not related to LTOT/NIV use 3/ and alternating with HTS (n = 1). 7/12 (58%) of patients were taking IM as 28 (11%) and 1/28 (4%) respectively; other 4/28 (14%). 25/28 (89%) reported prescribed (400 mg twice daily) with 1/12 (8%) taking 400 mg once daily. symptomatic benefits from SNI. Symptoms best relieved in order were The remaining 4 patients (33%) reported reducing the dose to balance blocked nose, nasal discharge and facial pain/pressure, reduced/loss of bronchoconstriction with clinical effectiveness (range 5–10 capsules b.d. smell, headache and sneezing, itchy nose. Other benefits reported were – when stable, 0 7 capsules b.d. during exacerbations). There was no clear increased exercise tolerance 4/25 (16%), increased SpO2 1/25 (4%), link between dose adjustment and baseline lung function. 2/12 (17%) improved tolerance of LTOT/NIV 2/25 (8%). Of the 3/28 who reported no patients reported an episode of moderate volume haemoptysis while on benefits, one was using SNI as ‘cold’ prophylaxis, one for an acute infection treatment with IM. and one for hayfever symptoms. 5/28 (18%) patients each reported one Conclusion: IM was tolerated across a wide range of CF disease severity in adverse effect; saline in ear canal; increased pain/pressure in sinuses; nasal this cohort. Adjustment of IM dose and frequency of treatment by adults stinging if very congested; increased nasal drip, feeling drowsy. 9/28 (32%) with CF was common. Further research with larger studies is required to used SNI only during an acute infection. Of the 19/28 who used it assess the efficacy of IM at non-standard doses. throughout the year, 8/19 (42%) used it once daily or more, 6/19 (32%) several times a week, 1/19 (5%) once a week, 4/19 (21%) several times a P311 month or less. The effect of Simeox airway clearance technology on resting Conclusion: The majority of the patients studied reported symptomatic hyperinflation in cystic fibrosis patients benefits from 0.9% SNI and it was generally well tolerated. Further M. Proffit1, M. Magni1, G. Desbois2, L. Morin3. 1La Bulle Kine, Respiratory and investigation with greater numbers of patients is warranted. Pediatric Rehabilitation Center, Nice, France; 2Kiné Respi Assistance, Respiratory Physiotherapy Center, Lyon, France; 3Physio-Assist, Medical P313 Affairs, Aix-en-Provence, France Experiences of the Nuvoair home spirometry, a pilot study L. Lannefors1, 2, S. Höglund2, P.Ericson2,3, M. Gilljam2,3. 1Göteborg University, Objectives: Bronchial drainage is a key component of prophylactic chest 2 Dept of Physical Therapy, Gothenburg, Sweden; Gothenburg CF Centre, physiotherapy performed in patients with cystic fibrosis (CF), to reduce 3 Sahlgrenska University Hospital, Gothenburg, Sweden; Göteborg University, recurrent pulmonary exacerbations and lung function decline. Evaluation Respiratory Medicine, Gothenburg, Sweden of new airway clearance techniques (ACTs) is required to understand the physiological effects of these technologies on respiratory function. Objectives: A pilot study to assess the potential use of Nuvoair home Aim of this study was to assess the effects of new Simeox technology on spirometer as a complement to spirometry in clinic or an alternative to resting lung hyperinflation in CF patients with stable respiratory function. currently used home spirometer after lung transplantation. Methods: Adult CF patients receiving prophylactic chest physiotherapy Methods: Selected patients were invited to participate. Patients were with Simeox device (Physio-Assist, France) assisted by respiratory instructed to do spirometry once daily the first week, then three times/ physiotherapists were included consecutively in 2 centers. Patients week for six weeks, then individual instructions were given. A brief performed under physiotherapist supervision 3 valid measurements of questionnaire was completed after the trial. resting inspiratory capacity (IC) with a computerized stand-alone spirom- Results: Twelve patients (3 males, 4 lung transplanted) with a mean age of – eter (Spirolab, MIR) before and 15 30 min after one single 20-min drainage 32 (SD 8) years and a mean FEV1 of 52 (SD 25) percent predicted were session with Simeox. Mean of 3 IC values was calculated for pre and post included. Except for some initial technical problems all patients found the evaluation in each patient. spirometer and the App easy to use, a good tool for CF and better than Results: 21 CF patients were included in the study: 10 males (26.7 ± 6.3 y) currently used home spirometer after transplantation. They also appre- and 11 females (26.9 ± 8.1 y). Variability of IC measurements was correct for ciated the possibility with Nuvoair to upload results to a homepage both pre and post evaluation (mean coefficient of variation <5%). 10 accessible to the CF staff. All patients wanted to keep the spirometer after patients had baseline IC% pred. <80% (60 ± 15%). Change in mean IC was the test period with the intention of routine use. The CF staff appreciated increased significantly by 110 ± 140 ml and 4 ± 5% pred. (p < 0.005). 11 easy access to home spirometry data, the possibility to postpone selected patients had an increase of IC% pred ≥5% (220 ± 90 ml; 9 ± 4%). Evolution of clinical visits and the use of Nuvoair as a paedagogic tool. IC was similar according to gender, centre or baseline IC. Conclusion: The Nuvoair homespirometer is a good complement in CF Conclusions: Inspiratory capacity at rest was improved in CF patients after care. The use of the tool has to be individualised. one single drainage session with Simeox technology suggesting a direct effect on lung hyperinflation reduction. This physiological mechanism may P314 have significant impact on the evolution of lung function in CF and should Introduction of nebulised levofloxacin in an adult cystic fibrosis centre be confirmed with long-term data. C. Fordyce1, H. Langman1, H. Green1, A. Jones1. 1Manchester University NHS Foundation Trust, Manchester Adult Cystic Fibrosis Centre, Manchester, United P312 Kingdom Patient reported use, effects and tolerance of 0.9% saline nasal ® irrigation (SNI) in a large UK adult cystic fibrosis centre Objectives: Levofloxacin nebuliser solution (Quinsair ) was licenced for 1 1 1 1 1 use in England in 2018 as a 4th line antipseudomonal nebulised therapy in S. Cameron ,C.Brown, N. Rodgers , A. Purba , R. MacDonald-Johns , 1 1 1 1 1 1 the treatment of cystic fibrosis. At Manchester Adult Cystic Fibrosis Centre K. Jozlowski , V. Carrolan , J. Pond ,N.Patel, J. Whitehouse , R. Rashid , ® 1 1 (MACFC), Quinsair was first used in our patient cohort in January 2019. We E.F. Nash . West Midlands Regional Adult Cystic Fibrosis Centre, Birmingham, aimed to evaluate the introduction of Quinsair® in a large adult cystic United Kingdom fibrosis centre. Background: SNI is often recommended as an adjunct to the medical Methods: All patients identified for trial of Quinsair® had a test dose management of rhinosinusitis and is used by CF adults attending our completed by a trained physiotherapist in line with MACFC challenge centre. However, there is currently minimal evidence relating to the use protocol. An inhaled or nebulised bronchodilator was administered pre- and effects of SNI in the CF population. therapy in accordance with the Clinical Commissioning Policy. A 28-day Objectives: To determine in our population reasons for commencing 0.9% course was commenced if successful at test dose. Spirometry was SNI, effects, tolerance and frequency of use. completed after 28 days to assess response to therapy. Methods: Patients attending the centre between January-December 2019, Results: 9 patients received a test dose of Quinsair® between January 1st currently using SNI or who had used it consistently in the recent past, 2019 and December 31st 2019 (male n = 6, Female n = 3), with mean FEV1 at completed a bespoke questionnaire. time of challenge of 32.8% (range 20%–81%). 3/9 failed at challenge,1 due to S144 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 intolerability of taste, 1 due to haemoptysis post challenge and 1 due to a Methods: 53 patients (aged 3 to 18) have been enquired through a drop in FEV1 (7%), FVC (12%) and subjective chest tightness. 1 patient with questionnaire by direct administration. This questionnaire collected multiple drug intolerances passed at challenge but only used therapy information about the patient’s profile, their practice of nasal irrigation, during inpatient admissions to augment treatment in the absence of and any information or training they had access to on the subject. intravenous antibiotics. 5 patients commenced therapy post challenge. 4/5 Results: The results were lower than the team’s expectations (47% of had stable FEV1 at 4-week review and no adverse symptoms were reported. patients do nasal irrigation and 39% daily). Nonetheless, some leads are 1 died within the first month of use secondary to Influenza A and therefore emerging. It seems patients who benefit from more than 3 sessions of no follow up data was recorded. physiotherapy a week practice a better nasal irrigation ( p = 0,032). Conclusion: In comparison to patient population size, there has been a Likewise, patients who followed a training with the CF French physios small uptake of this treatment at MACFC with majority of use in patients association, in collaboration with the French CF foundation seem to have a with lower lung function. Tolerability at challenge has been variable use that is in line with recommendations ( p = 0,015). although it must be noted that this is a small sample size. Quinsair® Conclusion: This study has shown the need to establish means to improve continues to be an option for patients who meet criteria, including those these practices. The team is considering setting up a therapeutic education with severe lung disease. We will continue to assess long term efficacy of workshop on nasal irrigation. The results also encourage more collabor- the treatment. ation with liberal physiotherapists and to offer trainings to patients and families more regularly. P315 Impact of posaconazole treatment on exercise capacity in children with P317 Aspergillus lung disease in cystic fibrosis Patient experience and satisfaction with 0.9% saline nasal irrigation N. Dayman1, N. Mistry1, M.I. Ahmed2,3, E. Gaillard2,3. 1University Hospitals of (SNI) in a large UK adult cystic fibrosis centre and potential barriers to Leicester, Leicester, United Kingdom; 2University of Leicester, Department of use 3 Respiratory Sciences, Leicester, United Kingdom; University Hospitals of S. Cameron1,C.Brown1, N. Rodgers1, A. Purba1, R. MacDonald-Johns1, Leicester, Department of Paediatric Respiratory Medicine, Leicester, United K. Jozlowski1, V. Carrolan1, J. Pond1, N. Patel1, J. Whitehouse1, R. Rashid1, Kingdom E.F. Nash1. 1West Midlands Regional Adult Cystic Fibrosis Centre, Birmingham, Objectives: Pulmonary exacerbations are associated with reduced United Kingdom maximal exercise capacity, which improves with antibiotic management. Background: Adults with CF attending our centre often anecdotally report Similar evidence of impact of antifungal treatments on exercise tolerance is the benefits of 0.9% SNI in relieving nasal and sinus symptoms, whilst missing. Aspergillus lung disease has been reported as worsening cough, reporting a reluctance for more frequent use due to the inconvenience of repeated Aspergillus isolation and decline in lung function with subopti- the process involved. mal response to broad spectrum antibiotics (Liu et al 2013). We assessed Objectives: To investigate formally patients’ experience and satisfaction the impact of 3-month treatment with posaconazole on exercise tolerance with 0.9% SNI, adherence with protocols and potential barriers to use. in children with Aspergillus lung disease using the 3-minute step test. Methods: Patients attending the centre between January–December 2019, Methods: Children were evaluated using a sub-maximal 3-min step test currently using SNI or who had used it consistently in the recent past, performed pre- and post-treatment. Changes in breathlessness scores, completed a bespoke questionnaire. heart rate (HR) and oxygen saturations (SaO2) during the step test and lung Results: 28 CF adults, median age 36 and best FEV % predicted in the past function including LCI were recorded before and after posaconazole 1 12 months 63%, completed questionnaires. 17/28 (61%) patients reported treatment. SNI was an important part of their CF care, 17/28 (61%) that it improved Results: Eight children diagnosed with Aspergillus lung disease (4 boys; QOL, 23/28 (82%) that it caused no adverse effects and 24/28 (86%) that median age 10 years (range 3–17 years)) between June 2017–January 2020 performing it was easy. Saline preparation at home and in hospital was were enrolled in this study. After 3 months of treatment with posacona- reported as easy by 14/27 (52%) and 11/15 (73%) respectively. However, zole, objective and subjective breathlessness scores did not change recommended saline preparation protocol was not followed by 18/27 (67%) significantly (median 15 count breathlessness score from 3 to 5 and patients at home (using boiled, cooled water) and 4/15 (27%) in hospital median BORG scale from 14 to 13 respectively). Maximum HR reduced (using pre-packaged 0.9% sterile saline). Recommended SNI equipment (median 137 bpm to 128 bpm, p > 0.05), no significant change in SaO2 was cleaning and sterilisation protocols were not followed by 9/27 (33%) and noted. 16/26 (62%) respectively. 16/27 (59%) reported not using SNI as often as FEV improved in all 8 patients between 2–25% from baseline (p < 0.05). In 1 liked/required. Barriers to increased use were time for boiling and cooling 4 children with improved BORG scores, FEV improved by median 6.3% 1 water for saline preparation 11/16 (69%), time for equipment care 1/16 (6%) (range 2.3–25.3%) compared to those with worsening BORG scores (median and burden of use in addition to other CF treatments 4/16 (25%). 21/28 9.5% range 0–15%, p > 0.05). Paired LCI measurements were available in 4 (75%) reported provision of pre-packaged saline at home would enable children and improved by a median of 16% (range 7–17.7%). increased frequency of use. Conclusion: Treatment with posaconazole for Aspergillus lung disease did Conclusion: Patients often find 0.9% SNI beneficial but this can be out- not show any significant changes in 3-min step test outcomes; treatment weighed by the inconvenience of preparing saline solution. Provision of was associated with improvement in lung function and LCI. 3-min step pre-packaged sterile saline would reportedly enable more frequent use. test can be used as an additional useful tool to evaluate treatment Ongoing education around patient adherence to saline preparation and responses in CF. equipment care protocols is a priority. P316 Assessment of the practices of nasal irrigation by patients with cystic P318 fibrosis in the paediatric resource centre in Amiens Aerobika Oscillating PEP device for airway clearance therapy (ACT): an audit of clinical experience and patient reported outcomes (PRO) in T. Pinto1,2, C. Rames1. 1CHU Amiens, Amiens, France; 2UPJV,2IS, Amiens, France cystic fibrosis (CF) In CF, the upper airways, when obstructed, cannot function properly and B. Button1, 2, L.M. Wilson1, 2, M. Poulsen1, J.W. Wilson1,2. 1The Alfred Hospital, can be a cause of many complains from patients. They can also become an Respiratory Medicine, Melbourne, Australia; 2Monash University, Medicine, important germ’s reservoir. This is the reason why, for the past few years, Nursing and Health Sciences, Melbourne, Australia their hygiene and clearance have been a major concern. Objectives: The goal of this work is to study the different ways nasal Objectives: irrigation is practiced by patients at the Amiens centre. Thus, this 1. To describe the introduction and physiotherapy practice; assessment will allow us to know whether their practices match the 2. to evaluate patient reported outcomes (PRO) of the Aerobika for current recommendations. regular ACT over 2 years. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S145

Methods: Patients were given the Aerobika and educated about its use. P320 Resistance settings and dosage were individualised. VAS scales with Assessment of the short-term effectiveness of the use of positive and anchors from −5 (less effective) to −1; to 0 (no difference); to +1 to +5 oscillating positive expiratory pressure in bronchial drainage in (more effective than usual ACT) were used. patients with cystic fibrosis Results: 80 patients (47 female) used the Aerobika for regular ACT. Data J. Prusak1, 2, K. Warzeszak1, K. Slaby1, P. Kurzeja2, A. Pogorzelski1. 1Institute described as mean (SD), range. Age: 34.3(10.5) 19–67 years; FEV151.8(18.4) for Tuberculosis and Lung Diseases, Rabka-Zdroj, Poland; 2Podhale State 23–96%; FVC 70.0(15.7) 46–113 %; BMI 21.4(2.5)17.7–28.5). Patients College of Applied Sciences, Nowy Targ, Poland completed the PRO form after using the Aerobika for at least 3 months. Usual ACT devices used prior to Aerobika were: PEP devices 44/80 = 55% The aim of the study was to assess the effectiveness of autogenic drainage [PEP mask 39%; PEP with mouthpiece 61%]; OscPEP 41/80 = 51%: [Flutter using selected devices generating positive (PEP S system) and oscillating 78%; Acapella 22%]. Mucolytics used: 46/80 = 58% of subjects: hypertonic positive expiratory pressure (Aerobika OPEP,Flutter). The study involved 24 saline (HS) 6% by 65%; HS 3% by 20%; 0.9% by 15% of subjects. Results of VAS patients with cystic fibrosis (15 female and 9 male) with a mean age of scales: 21.2 ± 7.4 years in the period from January to November 2019. Spirometric a. Resistance setting: +1 (most resistance) 46% of subjects; mid resistance measurements were used before and after a 4-day cycle of drainage setting 29%; −5 (least resistance) 25% of subjects. procedures with monitoring of the expectorated secretion. A random b. Effectiveness of Aerobika versus usual ACT +2.3(2.1)−5 to +5; criterion for the selection of the drainage device was used, provided that c. Sputum volume cleared: +1.8(2.1) −5 to +5; the patient does not use the same at home and there is no contraindication d. How clear/free breathing: +2.1(1.8)−5 to+5; to its use. All tests and the drainage cycle were carried out from the first to e. Effort required: +2.1(2.0) −2 to +5; the fourth day after admission to the Institute for Tuberculosis and Lung f. How tiring Aerobika: +1.8(1.9) −3 to +5. Diseases in Rabka-Zdroj. The average value of the FEV1 index (L) in the g. Time for ACT: +1.6(2.4) −5 to +5; whole group was 1.76 ± 0.8 before and 1.98 ± 0.8 after the treatment cycle h. Easy to use: +4.1(1.6) −2 to +5; (p = 0.0002) which constituted 56.1% before and 63.4% after (p = 0.0003). i. Aerobika for regular ACT: +3.8(2.2) −5 to +5; The MEF25 index improved from 0.42 to 0.55 (l/s) (p = 0.008). The mean j. Adherence: +1.3(3.4) −5 to +5; value of sputum collected was 59.3 ± 61 ml. The studies showed no k. Disliked Aerobika: 8/80 (preferred PEP). correlation between the amount of secretions collected (in the Aerobika group – 84.2 ml, PEP group – 32.5 ml, Flutter – 61.4 ml) and the Aerobika combined with mucolytics: 71/80 (89%) [HS 6% = 46% HS improvement rate of FEV1, which was the highest in the group using PEP 3% = 17%; 0.9% = 37%. Types of nebulisers used included the AeroEclipse (n = 8) and amounted to 0.34 L. This result was significantly different 51% of subjects; the AeronebGo 46%; EFlow 3%. The BPA free plastic device (p = 0.012) from that obtained in the group using the Aerobika OPEP (n = 8, is durable, easy to disassemble, wash, reassemble and use. FEV1 pre/post = 0.08 L). In the Flutter group (n = 8) the improvement for Conclusions: The Aerobika was well received by patients as an efficient and FEV1 was 0.23 L. A negative correlation was found between the amount of effective ACT device able to be combined with mucolytics to save time. secretions collected and the initial values of indicators assessing airflow in − the respiratory tract (for FEV1% pred., r = 0.64, p = 0.0009). The results of preliminary studies suggest that the effectiveness of bronchial drainage is P319 more dependent on the size of obstructive disorders than the type of device Effect of shake-fire delay on the amount of delivered dose from a pMDI used. albuterol HFA and valved holding chamber 1,2 1 1 A. Berlinski , R. Qaqish . University of Arkansas for Medical Sciences, P321 2 ’ Pediatrics, Little Rock, AR, United States; Arkansas Children s Research Respiratory physiotherapy for children and adolescents with cystic Institute, Pediatric Aerosol Research Laboratory, Little Rock, United States fibrosis – is there a link between adherence and clinical health status? Objectives: Albuterol metered dose inhaler (pMDI) with a valve holding T. Hellmuth1, F. Junge1, A.-M. Dittrich1, S. Junge1. 1Hannover Medical School, chamber (VHC) is used by patients with cystic fibrosis. Previous studies, Pediatric Pneumology, Allergology and Neonatology, Hannover, Germany done with full canisters of pMDI suspensions, showed an increased in Objectives: Respiratory Physiotherapy (RPT) is an important part of CF-care delivered dose (DOSE) when a shake-fire (S-F) delay occurred. In this study, but International recommendations on the amount and content of RPT we evaluated the effect of S-F delay across the life of the canister. We differ. In a pilot study parents of children with CF aged 0–6 y where asked hypothesized that a higher and lower DOSE will occur at the beginning and on this topic. Results indicate that only 17.5% of children are practicing RPT at the end of the canister’s life respectively. at home on a daily basis while 90% experience pulmonary symptoms. On Methods: Three new albuterol pMDIs (Ventolin HFA, 90 μg/actuation, 200 this basis the aim was to assess how much and what kind of RPT is done by doses, GSK) connected to a VHC (Optichamber Diamond, Philips all CF-patients aged 0–17 y at a German CF-outpatient centre and to Respironics) and operated with a 30 s S-F delay were compared to 3 examine if there are correlations between adherence for RPT and clinical inhalers of same brand/lot connected to VHC and operated without S-F health status. delay. Ten puffs were actuated into the VCH connected to a drug recovery Methods: The Respiratory-Physiotherapy-Questionnaire was sent to 195 apparatus (30 L/min suction) with 30 s interval between puffs and 5 s families asking about RPT at home and in private practice. Clinical data shacking time. Canisters were studied from 200 to 0 remaining doses. e.g. age, FEV1, BMI were generated from routine outpatient data Albuterol mass was determined via spectrophotometry (276 nm). The collection. number of values of DOSE with S-F delay that were outside the X̄± 99%CI Results: N = 104 questionnaires (53.3%) were sent back (age 9.7 ± 5.1 y). DOSE without S-F delay was determined. The number of DOSE values in the RPT at home is done on a daily basis by most patients (n = 26) followed by S-F delay group that were 20% higher or lower than the mean of the no S-F n = 21 only practicing it when symptoms increase and n = 12 who never do delay group was determined. A p value <0.05 was considered statistically it. Content of RPT mainly consists, next to physical activity, of breathing significant. exercises for patients aged 0–5 y; therapeutic body positions, Flutter/ Results: The mean 99%CI DOSE without S-F delay was 437 μg 416–458 μg. Cornet for patients aged 6–11 y; therapeutic body positions and autogenic DOSE with S-F delay was above, or below 99%CI 41%, and 41% of times drainage for patients aged 12–17 y. Main reasons for reduced adherence are respectively. DOSE with S-F delay was greater or lower than 20% than the lack of motivation (n = 35) and time (n = 34). Dividing the sample in three mean DOSE without S-F delay 29% and 47% of times respectively. Decline in groups (high/moderate/low adherence) shows that patients with high DOSE begun when 110 doses were remaining. adherence are practicing more RPT per day (p < 0.01) and for a longer Conclusions: Using an albuterol HFA pPMDI with 30 s shake-fire delay period per session (p < 0.01). Patients with low adherence have a better with VHC resulted in higher than expected DOSE at the beginning of FEV1 than patients with moderate (p = 0.018) or high adherence canister life, and lower than expected DOSE at the end of the canister life. (p = 0.035). We recommend instructing patients using pMDI with VHC to re-shake the pMDI if it is not immediately actuated after having shaken it. S146 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Conclusion: Although clinical experience indicates an impact of RPT on difficult to evaluate and therefore, clinicians use mostly self-reported pulmonary progress there is less evidence to objectify it. Correlations measures. However, several studies has shown that patients overestimate between adherence and health status (e.g. better lung function = less need adherence. to practice RPT at home?) can be used to develop interventions to improve Adherence is defined as “The extent to which the patient’s behaviour adherence, e.g. education on preventive effects. matches agreed recommendations from the prescriber”. In a study from 2009, the self-reported degree of adherence to respiratory treatments was P322 84%. In another study from 2011, self-reported data was compared to the Using the CFHealthHub digital health system to provide distance electronic monitoring of nebulised medications. The resulted median self- nebuliser adherence support: a 6-month service evaluation comparing reported adherence rate was 80%, whereas median adherence measured by uptake and changes in adherence from support offered within normal nebulizer download was 36%. working hours compared to in the evening This study (as part of a larger 24-week study) aimed to assess the patients C. Carolan1, C. Clarke1, C. Girling2, F. Edenborough1, R. Curley1, M. Wildman1. self-reported adherence for their physiotherapy routine. 1Sheffield Teaching Hospitals, Sheffield, United Kingdom; 2SCHARR University Methods: CF patients (ages 8–16) completed a self-reported treatment ® of Sheffield, Sheffield, United Kingdom diary 2 weeks prior to starting a Play Physio device, which is a device and associated app that can be attached to any oscillatory PEP device. Background: Many specialist CF units provide care for patients over large Results: The average self-reported adherence to physiotherapy was geographical areas. Many patients also have school or work responsibilities approximately 82%, with over 30% of the patients reporting to be 100% which make attending clinics difficult. CFHealthHub is an online adherence adherent and over 40% between 82 and 97%. platform that equips clinicians with the ability to support patients with Conclusion: It has been found that patient-reported adherence was higher taking nebulisers from a far. This report considers patient engagement to than that perceived by the health team. distance support, exploring the impact of tailoring support to patients routine via out of hour contact. We report adherence change following P324 behaviour change interventions. Hospital in the Home (HITH) telehealth and home visit hybrid Objectives: We compared the difference between distance adherence physiotherapy model support offered within normal working hours compared to in the evening. 1,2 1, 2 1, 2 1 C. Benz , M. Wallace , A. Elliott . Children’s Hospital at Westmead, Methods: Three hours of dedicated time weekly was allocated to both: 2 Physiotherapy, Westmead, Australia; Sydney Children’s Hospital Network, • Normal working hours (NWHs) clinic (Thursday 9am–12) Hospital in the Home, Sydney, Australia • Out of hours (OOHs) clinic (Tuesdays 4pm–7) • Some patients received both OOHs and NWHs support Sydney Children’s Hospital Network (SCHN) Hospital in the Home (HITH) • Patient uptake and adherence was collated over a 6-month period. We has become an important part of the care continuum for young people with also collected patient feedback. CF, with significant increases in demand. Telehealth has the potential to increase efficiency and access for patients under HITH, in both metropol- Results: Over 6 months 63 patients were contacted with outcomes as itan and regional areas. below: Objectives: Pilot a new telehealth and home visit model of care (MOC) to • Patients discharged back to clinic n = 19 improve efficiency and increase physiotherapy (PT) access to patients • Patients with on-going support n = 15 under HITH. Assess i) Patient/carer satisfaction ii) increases in patient • Patients not engaging n = 29 access to PT iii) efficiency through a comparison of occasions of service OOHs support demonstrated a greater number of patients discharged, a (OOS)/month and travel time and distance saved. greater increase in adherence and greater engagement. Method: Pilot study consisted of bidaily (BD) PT treatments to all CF Discussion: CFHealthHub provides a platform to have open and honest patients on HITH. Metropolitan patients received one face to face and one adherence discussions with patients, allowing behaviour change to happen telehealth session per day and regional patients, one or two telehealth from a distance. Providing OOHs support improved outcomes and was sessions. Outcomes: Satisfaction survey, BD physio enabled admissions, preferred by patients number of regional admissions where PT access was enabled, comparison of mean OOS/month pre and post telehealth; and travel time and distance P323 saved. Adherence to treatment in cystic fibrosis: the reliability Results: The pilot ran from Nov 2017 to Nov 2018, see Table 1 for of self-reported data participant demographics. Telehealth enabled BD PT in all in area admissions. In the six months preceding implementation of telehealth a A. Russo1, L. Lowndes2, D. McShane2. 1Universita degli Studi di Salerno, mean of 137 OOS per month were performed, in the 2018 corresponding Fisciano, Italy; 2Addenbrookes Hospital, Cambridge, Cambridge, United period this increased to 170 OOS. Telehealth treatment saved an estimated Kingdom 319 hours (13 days) and 14 693 km of driving. Patient/Carer satisfaction and Objectives: Studies on Cystic Fibrosis have shown an increase mean perceived effectiveness with Telehealth was a median 10/10. survival to up to 47.3 years but these patients have an ever increasing treatment burden: the calculated average number of treatments per day is 7, taking an average of 108 minutes. Treatment regimens are also very

Table 1. (abstract: P322) Outcomes of intervention for patients discharged (19/63), receiving on-going care (15/63) or not engaging with the service (29/63).

Patients discharged back to routine care Patients receiving on-going support Patients not engaging with adherence support

Number of patients Adherence pre Adherence post number receiving Adherence pre Adherence post Total number of Percentage discharged on-going support patients not against number of engaging contacts made

OOHs 9 50% 93% 7 23% 36% 6 20% NWHs 6 57% 73% 3 46% 53% 15 52% OOHs + NWHs 4 42% 83% 5 24% 29% 8 38% Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S147

Table 1. makes daily CF exercise more entertaining and improves the efficiency of Participant Demographics. Median (Range) inhalation (increased mucus disposal and up to ⅓ time reduction with compressor nebulisers. Users can also follow their adherence plan, share it N Gender Age HITH Regional Metropolitan Telehealth with their parents and physiotherapist; win virtual rewards and explore (m/f) Admissions Sessions entreating educatory scenarios of real-life situations. 41 10/31 12.5 (5–18) 56 9 47 16 (1–30) Conclusion: Based on feedbacks; surveys and in-field research, we are confident CF Hero can build more positive attitude to daily routines for CF teenagers and assist parents of younger children. It proved its potential to Conclusion: Telehealth is a feasible, acceptable and efficient method of make therapy more efficient and thus help preserve lung functions. Our delivering PT to CF patients. This pilot of the telehealth and home visit next goal is to confirm results in a study conducted by CF HCPs firstly in the hybrid MOC for HITH PT found satisfaction and perceived effectiveness Czech Republic. We can expect data by the ECFS conference in Lyon. were rated high, with increased PT access for patients on HITH and Expansion to Germany is planned for 2020 with the support of local increased efficiency of HITH PT. associations. CF Hero team is working on additional features and content that will increase app lifecycle, further engage users and boost motivation P325 of patients to take better care of themselves. (e.g.: an online community Physiotherapy home care: satisfaction and health-related quality of life where patients will be able to interlink; share their accomplishments and in a group of cystic fibrosis patients best practices; chat-bot that will answer most common patients’ M. De Marchis1, I. Piermarini1, B. Giacomodonato1,F.Majo2, S. Graziano3, questions). F. Ciciriello2, E. Montemitro2, M. Rivolta1, F. Boldrini3, A. Ianni4, P. Tabarini3, V. Lucidi2, P.Leone1. 1Bambino Gesù Children’s Hospital, Unit of Physiotherapy P327 of Cystic Fibrosis Center, Rome, Italy; 2Bambino Gesù Children’s Hospital, Cystic Estimating adherence with nebulised therapies: a challenge for people Fibrosis Unit, Rome, Italy; 3Bambino Gesù Children’s Hospital, Unit of Clinical with cystic fibrosis and healthcare professionals 4 Psychologist Unit of Cystic Fibrosis Center, Rome, Italy; Freelancer L. Warnock1, J. Faulkner1, W.G. Flight1. 1Oxford Adult Cystic Fibrosis Centre, Physiotherapist, Rome, Italy Oxford, United Kingdom ’ Objectives: To assess the effects of home-based physiotherapy s interven- Objective: People with CF(PwCF) often have high treatment burden and tion in people with CF. low adherence to nebulised therapies. The CFHealthHub (CFHH) RCT used ’ Methods: CF patients followed at Bambino Gesù Children s Hospital were objective adherence data to support PwCF to address this issue. Transition enrolled if living within 100 km from the Centre and monitored within a from the RCT to the CFHealthHub Data Observatory (CFHH-DO) offered the period of six months. The physiotherapy home care program consists of a opportunity to assess the accuracy of adherence estimates by PwCF and 60 minutes session once a week of respiratory rehabilitation (Pep-mask, healthcare professionals (HCPs). autogenous drainage, aerosol, nasal washings, etc.) together with the Method: Participants in the CFHH RCT control group joining the CFHH-DO ’ physiotherapist. Patients satisfaction was evaluated with an ad hoc at our centre were included. Adherence data from the final 3 months of the questionnaire consisting in a three-points Likert Scale administered after RCT were compared to estimates of adherence made by PwCF and HCPs the intervention. QoL was measured through the CFQ-R before and after from the CF MDT. HCPs were given the patient’s name and nebuliser the intervention. We used the Wilcoxon-Mann Whitney non-parametric prescription before estimating adherence. Confidence in the estimate was ’ test to evaluate the significance of the difference in the CFQ-R s domain rated from 1–5 (5 = very confident). PwCF estimated their percentage scores before and after the physiotherapy home care programme. adherence at the CFHH-DO consent visit. Estimates were made before Correlation between answers in CFQ-R domains was explored with the adherence data were accessible at our site. Spearman test. Results: 14 PwCF participated with median age 21.5 years. 7 (50%) were Results: Ten CF patients were enrolled (M/F 3/7, mean age 17.7 years, female. Participants were prescribed a median of 2 (range 1–7) nebulised SD ± 7.32 years; FEV1 90,1 ± 22,5% of predicted) from 1st March 2018 to treatments per day. 17 HCPs responded including 6 nurses, 6 physiothera- 23rd October 2018. 10/10 patients (100%) declared satisfaction and willing pists, 2 physicians, 2 dietitians and 1 pharmacist. to continue the home-care program in the specific questionnaire. We found Median measured adherence was 28% (IQR 14%–43%). Median (IQR) self- ’ a statistically significant increase in the treatment burden s domain score of reported adherence by PwCF was 50% (38%–78%) compared with a median CFQ-R (p < 0,05); Spearman correlation analysis showed that physical estimate of 39% (32%–46%) by HCPs. Median (IQR) estimated adherence by domain is related to the domain of respiratory symptoms, which decrease HCP discipline was: nurses 42% (38–45%); physiotherapists 40% (24–52%); after treatment (r = 0,783, p < 0,01). physicians 38% (20–55%); dietitians 30% (22.5–55%) and pharmacist 50% Conclusion: Physiotherapy home care could be a good therapeutic option (40–60%). Median confidence score of HCPs in their estimate was 2/5 ’ for CF patients. Patient s in our study were satisfied of the program and (range 1–4). There was no significant association between confidence and showed increase in QoL perceiving lower burden in the management of the accuracy of estimate (r2 = 0.009). pathology. Further studies are needed to evaluate this home service as a Conclusion: PwCF and HCPs were unable to accurately predict nebuliser good tool to improve quality of life and respiratory outcomes. adherence. There was wide variety in estimations between individual HCPs and inconsistency in whether adherence was over or underestimated. Our P326 study reinforces the need for objective adherence data in routine CF care. CF Hero – smartphone coach and friend (annual evaluation) M. Vosecký1, J. Mihule1. 1The Czech Cystic Fibrosis Association, CF Hero P328 Project, Prague, Czech Republic Set-up and use of non-invasive ventilation for adults with cystic fibrosis: an exploratory survey of UK cystic fibrosis physiotherapists Objectives: CF Hero project was founded in early 2017 by Marek Vosecký 1 1 1 1 (CF patient father); Jan Mihule (adult CF patient) and The Czech Cystic L. Warnock , A. Gates , W.G. Flight . Oxford Adult Cystic Fibrosis Centre, Fibrosis Association. Its objective is to increase adherence of teenagers to Oxford, United Kingdom inhalations and physiotherapy and slow down their lung deterioration. Background: Non-invasive ventilation (NIV) is widely used in advanced CF Methods: CF Hero is a smartphone application that contains gamification but there are limited resources to guide its set-up or use for ACT or exercise. “ ” mechanisms through which it aims to overcome the age of defiance ; Method: Links to an online survey were emailed to a named lead build good habits; educate young patients and improve frequency and physiotherapist at each UK centre listed on the CF Trust website. efficiency of their physiotherapy. It is now available in the Czech Republic Results: 18/29 (62%) of centres responded. 69% of respondents ranked and Slovakia. pressure support most commonly used for overnight ventilation (OV) over Results: 160 active app users; rating of 4,6 stars and numerous positive AVAPs/iVAPS (19%) or pressure control (13%). Blood gases (41%) and comfort feedbacks. 2/3 of users are willing to share data for the study purposes. App (35%) were ranked most important factors influencing starting pressure S148 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 and an individualised approach was favoured. Most frequently used OV physiotherapeutic interventions could be optimised. The interventions interfaces were full face mask (FFM) (59%), nasal mask/pillows (NM) (29%), involve evaluation and optimisation of: mobilisation of mucus, inhalation hybrid mask (6%). therapy, physical activity, musculoskeletal physiotherapy, pelvic floor – – Maximum IPAP pressures were 22 25 cmH2O (18%), 33 38 cmH2O (29%) physiotherapy, adherence, non-invasive ventilation, and patient perceived with 53% having no set limit. Comments suggested IPAP was individualised requirements. in line with radiology. Three centres commented on use of AVAPs mode Results: At baseline 86 CF patients median age 30 years (range 19–63) were suggesting this may be preferred when delivering higher pressure. included, 50M/36F. 71 completed a CPET. The median Vo2peak%pred were – – 52% reported using EPAP pressures of 4 6 cmH2O for OV with 24% 87,8% (range 38 142). The most frequent corrected interventions were: reporting they may use up to 10 cmH2O. inhalation therapy (55%), physical activity (41%) and mobilisation of mucus Most frequently used interfaces for ACT were mouthpiece (63%), NM (22%) (47%). After one year follow up: 20 patients were tested (more results will or FFM (18%). If using for ACT 87% reported they would make some change be available later). The median Vo2peak%pred were 86% (range 51–125). In to parameters. IPAP, EPAP, Ti and target volume were most frequently the physiotherapeutic control the most frequent corrected interventions at increased, with less consensus around rise time and expiratory trigger. follow up were: physical activity (50%), mobilisation of mucus (35%), Inspiratory trigger was often decreased and back up rate was frequently inhalation therapy (25%) and adherence (25%). reduced. Respondents were not questioned if NIV was used with a Conclusion: The results showed that there was no change in the vo2peak% recognised ACT which may have influenced responses. pred in one year but the interventions in the physiotherapeutic treatment During exercise with NIV there was less manipulation of settings. changed from focus on inhalation therapy to physical activity. The Parameters that were altered included IPAP,rise time, Ti and target volume. physiotherapeutic adjustments helps the CF patients to optimise their Conclusion: This survey provides insight into NIV use for CF in the UK. treatment and they learn from the adjustments. There are areas of consensus but also variation in practice around IPAP limits. NIV use with ACT and exercise is typically individualised explaining P331 the variability in report of parameter manipulation. Successful development of physiotherapy within a new Adult Cystic Fibrosis Service at Blackpool, UK P329 N. Pickering1, T. Saba1. 1Blackpool Teaching Hospitals NHS Foundation Trust, To evaluate adherence to NIV for airways clearance at the All Wales Blackpool Adult Cystic Fibrosis Service, Blackpool, United Kingdom Adult Cystic Fibrosis Centre (AWACFC) Objectives: In 2015 UK Regional Specialist Commissioners selected A. Johnson1, C. Paul1, J. Duckers1, C. Bridges1. 1University Hospital Llandough, Blackpool as the site of the first new Adult Cystic Fibrosis Service (BACFS) All Wales Adult Cystic Fibrosis Centre, Cardiff, United Kingdom in England in over 30 years in collaboration with Manchester Adult Cystic Objectives: To compare reported use versus actual use of NIV for airways Fibrosis Centre (MACFC). A Clinical Specialist Physiotherapist was clearance techniques (ACT). Use of NIV to augment airway clearance is an appointed using pump priming funds to address the BACFS population established treatment option and not limited to those using NIV for (presently 41 patients) needs and achieve Cystic Fibrosis (CF) Trust nocturnal ventilation (CF Trust, 2017). Within the AWACFC, the Breas VIVO Standards of Care and NICE Guidance, with mentorship from MACFC. 50 is used to establish suitable settings for an individual’s ACT following Methods: Key goals were to: assessment by a Physiotherapist. 1. establish a clinical physiotherapy service Methodology: Individuals completed a questionnaire asking them to 2. define role within the multidisciplinary team and wider CF community report frequency, duration and prescription of NIV for ACT during the week. 3. forge links with MACFC/Blackpool physiotherapy services VIVO data was downloaded and previous 3 months usage compared to Results: questionnaire results. 1. Clinical physiotherapy service established by: Results: Data was collected over a 6-month period, 11 individuals (10 • consultations (Feb 17– Dec 19): – – outpatients – 301 male). Age range 20 47 years. Mean FEV1 47% predicted (22 74%) and Mean BMI 22.7 kg/m² (16.9–28.6) at VIVO setup. VIVO settings included inpatients – 528 (44 admissions) – – annuals – 52 IPAP (20 30 cmH2O) and PEEP (2 5 cmH2O). Reasons for starting therapy included reduced lung function, chest x-ray changes, increased sputum nebuliser challenges – 33 and difficulty managing current ACT regime. • selecting equipment for in/outpatient services – spirometry, Average actual use per week was 30%, however, average reported use was respiratory, exercise equipment and negotiating ward storage 58%. Average treatment duration ranged from 2 minutes, 48 seconds to 31 • excellent patient feedback minutes. Prescription of VIVO use was twice daily for 6 of 11 patients, once 2. Role established by: daily for 4 of 11 patients. • core member of BACFS service development team Conclusion: The VIVO was reported as beneficial for ACT by all. Reported • regular contributor to local, regional and national CF and non CF adherence is higher than the actual usage data. There is variation in meetings reported prescribed use. Future practice should involve clear prescriptive • infection control leadership including cohorting and sputum documentation by a physiotherapist and regular review of technique, surveillance settings and usage. VIVO data is key to monitor adherence and evaluation • leading service development of sinonasal and CPEX pathways for continued home use. 3. Forged links by: • close working relationship with Blackpool and Manchester P330 colleagues including training and mentorship • The physiotherapeutic treatment in adult patients with cystic fibrosis – negotiating with local Physiotherapy Management non funded one-year follow up backfill inpatient cover for annual leave, weekend working, out of hours on call L. Dannemann1, L. Philipsen1, T. Pressler1. 1Rigshospitalet (Copenhagen • negotiating access to Specialist Physiotherapy Musculoskeletal University Hospital), Copenhagen, Denmark and Urogynaecological services Objectives: To establish the level of work capacity and need for • providing CF specific training for local physiotherapists physiotherapeutic treatment/adjustments in the Cystic Fibrosis (CF) Conclusion: Development of specialist services within the current UK NHS Centre in Copenhagen we have implemented a yearly physiotherapeutic climate can be challenging but achievable with good negotiating skills, consultation including a cardio pulmonary exercise test (CPET). These clinical/managerial working relationships and support from the commis- results will be followed and evaluated once a year to adjust each treatment. sioners. This model can be used to develop other specialist services. Methods: We registered the changes after one year follow up on vo2peak% pred and physiotherapeutic treatment. We systematically registered where Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S149

P332 Conclusion: Although our survey showed that 98% of UK centres are The impact of ear lobe blood gas sampling at home on hospital carrying out exercise testing only 58% are doing so at Annual Review. Only attendance and clinical care outcomes 48% centres offer CPET despite the increasing amount of evidence and H. Parkinson1, 2, R. Heise2, K. Channon1, 2, C. Elston2. 1Kings College Hospital, guidelines to support it being the exercise testing method of choice. Physiotherapy Department, London, United Kingdom; 2Kings College Hospital, Adult Cystic Fibrosis Service, London, United Kingdom P334 Advanced care planning in cystic fibrosis: current practice in UK centres Introduction: CF@home provides multidisciplinary specialist care at home G. Goode1, P. Wilson1, B. Underhill1, N. Shafi1, D. Watson1. 1Barts Health NHS to patients attending Kings College Hospital Adult Cystic Fibrosis (CF) Trust, London, United Kingdom Centre. Ear lobe blood gas (EBG) sampling is feasible and safe in the home setting (Channon et al 2018) and is a routine part of the service offered to Background: Advanced care planning (ACP) is a process that helps to align patients by CF@home. This aspect of the service has developed and is care with future wishes of those with serious or chronic illness and is key in utilised to both assess patients need for oxygen and non-invasive improving end of life care. Life expectancy in Cystic Fibrosis (CF) is ventilation (NIV) and support the set up and titration of oxygen and NIV increasing and end of life decision making is a crucial part of care. There is in the home environment, where clinically indicated. limited evidence on ACP in CF, previous studies have shown it often occurs Objectives: To review the effect of performing EBG sampling at home on late and the process varies greatly between centres. health care utilisation and clinical care outcomes. Methods: An anonymous online questionnaire on ACP practice was shared Methods: A retrospective case note review of all patients who had EBG with physiotherapists in UK CF centres in December 2019, data collection is sampling at home between August 2018 and December 2019. ongoing. Results: 28 EBG sampling visits were performed to 12 patients. Results: A total of 11 responses showed that ACP is completed by either a Outcomes of visits: variety of MDT members (7/11), consultant led (2/11), CNS led (1/11) or 1. Confirmed oxygen not required = 4 physiotherapist led (1/11), with decision on who completes it being either 2. Confirmed oxygen prescription adequate = 9 consultants (4/11), CNS (1/11) MDT discussion (4/11) and only 2 reported 3. Confirmed NIV settings optimal = 6 patient led or the most trained member of the team. No training for ACP 4. Identified need to change settings and change made at home = 7 was reported by 6, and the other 5 used online courses or a study day. Most 5. Assisted identification of clinical deterioration which necessitated ACPs were completed in a variety of settings (8/11) or solely inpatient (3/ admission = 1 11). 7/11 respondents reported using the CF Trust ACP document. ACP was 6. Other = 1 initiated by transplant discussions, annual reviews, deterioration in health or very end stage disease. Patient feedback showed mostly positive experiences (5/11) or mix feelings (2/11) with some not gaining feedback Of the 28 visits performed, 17 avoided an elective hospital admission (4/11). (where previously a patient would have required admission to achieve the Conclusion: The preliminary survey results show there is a disparity in same outcome) and 11 avoided the patient attending the hospital for an current practice of completing ACP in UK CF centres. There appears to be a additional outpatient attendance. No adverse events reported. lack of training occurring for clinicians completing ACP which is Conclusion: EBG sampling in the home allows the safe and timely recommended by the CF Trust. assessment of patients requiring oxygen and NIV in the home environ- Further information on the confidence of clinicians completing ACP and ment. It allows both titration and alteration of oxygen and NIV prescrip- patient feedback, including when to start discussions and in what setting to tions without the need for additional hospital attendance or admission. It have ACP,may be beneficial to highlight specific training needs and develop has the benefit of reviewing the patient in their own environment, allowing this area of CF care. a more accurate clinical picture of a patient’s oxygen or NIV use and response in the context in which it is used. This study supports the ongoing provision of this clinical service. Nursing/Psychosocial Issues P333 A survey of cardiopulmonary exercise testing in UK cystic fibrosis clinics 1 1 1 1 1 P335 N. Murray , N. Collins , E. Dixon ,C.Brown. Royal Brompton Hospital, Barriers and facilitators to adherence with nebulised antibiotics among Paediatric Physiotherapy, London, United Kingdom adolescents with cystic fibrosis in the community Objectives: It is recommended that all patients with Cystic Fibrosis (CF) R. Dakin1, P. Hemingway1. 1University of Nottingham, School of Health undertake an exercise test once a year (Cystic Fibrosis Trust, 2017). Sciences, Nottingham, United Kingdom Cardiopulmonary Exercise Testing (CPET) is considered the gold standard of exercise testing and can provide guidance on prognosis and individual Objectives: To explore the barriers and facilitators to adherence with exercise counselling (Hebestreit, 2015). As part of a benchmarking exercise nebulised antibiotics (NA) among adolescents with cystic fibrosis (CF) in we undertook an electronic survey to see if this recommendation was the community. reflected in current practice. Methods: This research takes the form of an extended literature review. To Methods: An electronic survey was sent to the UK membership of ACPCF in search for literature, the databases utilised were CINAHL, Scopus, PsycINFO May 2019 – Aug 2019. 64 hospitals replied, representative of 83% of the UK and ASSIA (2018–2019). Relevant literature was screened for eligibility specialist centres. against refined inclusion and exclusion criteria. Each study was appraised Results: 48% (n = 31) of centres offer CPET for patients with CF (56% adult, using the Holland and Rees (2010) qualitative/quantitative frameworks to 40% paediatric centres). 65% (20) centres use Godfrey Cycle Ergometer determine the quality of the evidence. Ethical approval was not required Protocol, 13% use Bruce Protocol and 13% use Ramp Protocol. 61% (19/31) due to the secondary nature of this research. centres offer CPETat Annual Review. Other criteria for offering CPET include Results: The following themes were identified: exercise tolerance concerns, pre-transplant, drug trials and breathing Lifestyle pattern abnormalities. Professionals referring patients for testing were • Structured routines together with regular and predictable schedules mainly Physiotherapists (74%) or Doctors (61%). Reasons given for not CPET facilitate adherence. However, having too much structure such as a testing included Lack of equipment (20), Lack of funding (25), Lack of schedule with no breaks or a schedule that begins too early is likely to trained personnel (21), Lack of interest (3), Lack of space (11), Cross- increase fatigue, ameliorating non-adherence. infection risk (4) and Time Consuming (3). Centres that didn’t offer CPET • Schedule variation and unstructured routines constitute barriers to (n = 33) reported using field test such as Shuttle walk (6MSWT, ISWT, adherence. 10nMSWT) 87%, Step Test (iStep, 3 min step, Chester step) 32%, Treadmill • Adolescents are more likely to adhere to their NA during term-time and 6%, Cycle 9%. Only 1 centre said that they didn’t carry out exercise testing. weekdays in comparison to holiday periods and weekends. S150 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Family Support P337 • Maternal supervision, but not paternal supervision, is highly predictive Easy Medicines for Burden Reduction and Care Enhancement: using of improved adherence. real time adherence data to optimise inhaled therapies in adults with • Adolescents reported that they utilised intentional non-adherence as a cystic fibrosis. The UK National EMBRACE programme strategy to rebel against over-protective parenting and their parents’ A. Bevan1, M. Tahir2, B. Miller3, H. Dunn1, J. Taylor4, D. Sweis5, N. Bush6, mandated adherence. J. Gadsby7, S. Morrow8, J. Johnson9, S. Poole10, C. Jones11, A. Lawson12, E. Young13, I. Davids13, C. Girling14, M.J. Wildman15, EMBRACE. 1University Anxiety and Depression Hospital Southampton NHS Foundation Trust, Pharmacy, Southampton, United • The presence of an anxiety disorder was significantly related to better Kingdom; 2Sheffield Teaching Hospitals, Pharmacy, Sheffield, United Kingdom; adherence to NA. 3Nottingham University Hospitals NHS Trust, Pharmacy, Nottingham, United • Adherence to NA was lower among adolescents with a depressive Kingdom; 4Royal Victoria Infirmary, Pharmacy, Newcastle, United Kingdom; disorder and those whose mothers exhibited depressive symptoms. 5York Teaching Hospital NHS Foundation Trust, Pharmacy, York, United Kingdom; 6Hull University Teaching Hospitals NHS Trust, Pharmacy, Hull, United Kingdom; 7University Hospitals Leicester NHS Trust, Pharmacy, Conclusion: The barriers and facilitators reported in this review identify 8 areas for intervention by children’s community nursing teams seeking to Leicester, United Kingdom; University Hospital of North Midlands, Pharmacy, Stoke, United Kingdom; 9Norfolk and Norwich University Hospital NHS ameliorate adherence and self-management strategies among adolescents 10 with CF. Foundation Trust, Pharmacy, Norwich, United Kingdom; Oxford University Hospitals NHS Foundation Trust, Pharmacy, Oxford, United Kingdom; 11University Hospitals Bristol NHS Foundation Trust, Pharmacy, Bristol, United P336 Kingdom; 12University Hospitals Plymouth NHS Trust, Pharmacy, Plymouth, “Nobody knows what the patient is actually taking!” Understanding United Kingdom; 13University of Sheffield, Sheffield, United Kingdom; nebuliser regimens in an adult cystic fibrosis centre: a systems 14University of Sheffield, Sheffield Clinical Trials Research Unit, Sheffield, optimisation project United Kingdom; 15Sheffield Teaching Hospitals, Sheffield, United Kingdom S. Dawson1,2, S. Millward1, L. Parr1, B. Miller1, K. Barnett1,J.Dewar1. 1Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; Introduction: Nebulised medicines are prescribed for people with cystic 2Staffordshire University, Stoke-on-Trent, United Kingdom fibrosis (pwCF) to maintain lung health. Objective adherence measured with chipped nebulisers within CFHealthHub (CFHH) is around 30% in Background: CFHealthHub (CFHH) is a digital behaviour change platform adults with CF but medicine possession ratio (MPR) is around 60%. Real that automatically collects date- and time-stamped nebuliser-use data. time drug use data via CFHH allows savings to be realised by just in time Accurate adherence data requires an accurate record of prescriptions, but it drug delivery. Savings might be invested in tailoring drug delivery to is often unclear what treatment is actually being taken. patient need thus reducing the burden on pwCF by having timely Objectives: Using the Dartmouth Microsystems approach to systems medicines supply. This is an important Lind Alliance priority. optimisation, we aimed to improve the accuracy of our record of CF patient Objectives: To compare calculated MPR with actual adherence in pwCF on nebuliser prescriptions using Plan-Do-Study-Act (PDSA) cycles. a single inhaled therapy over a 1 year period and analyse the gap and Methods: PDSA cycles included: associated cost difference between medicines supply and actual usage for st 1. standardising alternating treatment regimens to 1 of the month; and specific nebulised therapies. 2. developing a Nebuliser Prescription Change Form to record new Methods: Medicines supply (primary, secondary and homecare) data were treatment regimen; alternating antibiotic dates (if applicable); and collected from 56pwCF from 12 adult CF centres in England over a 1 year change reason. All completed forms were audited. period. Each patient had a MPR calculated from the first supply after consent. Final supplies were truncated to a maximum of 365 days. Actual Results: Between Feb–Dec 2019, 67 changes were made to 58 patient adherence data were downloaded from CFHH. The gap between MPR and prescriptions (Table 1). actual adherence was calculated and cost analysis undertaken using 2019 UK list prices. Table 1. Results: We will describe a supply/use gap analysis on 56 patients (54% Most frequently documented reasons for changing CF patient nebuliser prescriptions – in a UK adult CF Centre. female, age range 17 68 years). The difference between adherence data from CFHH, that measures actual doses taken, and drug supply calculated Reason Number of using MPR will be presented. The results will include financial calculations. changes Conclusion: CFHealthHub is providing real time inhaled therapy data in around 60% of adult units in the UK and using that data to optimise Eradication of Pseudomonas 18 “ Lung function (e.g. decline/maintenance) 15 medicines provision might help achieve easy medicines for burden Not tolerating current nebuliser treatment 12 reduction and care enhancement” (EMBRACE). Adherence concerns (e.g. swapped onto dry powders/pre-mixed 10 treatment/one with fewer doses) P338 Add in alternating antibiotic treatment (e.g. if on continuous 5 Is pulmonary medication adherence affected by disease severity among treatment or alternating month on/off with no other treatment) adult patients with cystic fibrosis? Other (e.g. to treat bug; new diagnosis of CF; chest clearance) 7 E. Hatziagorou1, K. Manika2, S. Kyrvasili1, E. Kouroukli1, E. Sourla2, I. Lialias1, S.-C. Kotoulas2, M. Sionidou2, I. Kioumis2, J. Tsanakas1. 1School of Medicine, For patients on alternating regimens (N = 38), most agreed to alternate on Aristotle University of Thessaloniki, CF Unit, Hippokration Hospital, 1st (N = 21; 55%); five alternated every 28 days/when finished supply Thessaloniki, Greece; 2School of Medicine, Aristotle University of Thessaloniki, (13%); two alternated on another set day (5%). CF Unit, Pulmonary Dept, G Papanikolaou Hospital, Thessaloniki, Greece It was unclear when 10 patients (26%) alternated as this was not recorded. Background: Poor treatment adherence is common in cystic fibrosis (CF) Missing data included: number of doses; alternating treatment name/date. and may lead to worse health outcomes. Not currently captured: stopped treatments (including date/reason); ‘as Aim: To evaluate associations of adherence to pulmonary medications with needed’ treatments (e.g. Hypertonic saline); CFHH adherence data; disease severity (FEV ), age and health-care use among adults with CF. treatment escalation pathway. 1 Methods: We evaluated 55 adults with CF over 5 years. A 12-month Conclusions: Progress has been made to improve the accuracy of our medication possession ratio (MPR) was computed for each pulmonary record of CF patient nebuliser prescriptions, and thus adherence data. medication and then averaged for a composite MPR (cMPR) for each Standardising alternating treatment dates is acceptable to patients, can patient. The cMPR was categorised as low (> 0.50), moderate (0.50–0.80), or inform clinical decision-making and enable accurate monitoring of patient adherence. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S151

high (>0.80). FEV1% predicted, BMI, pulmonary complications, days of towards all clinic assessments informed by FEV1, BMI and adherence to hospitalization and number of pulmonary exacerbations were recorded. optimise diagnosis and management. Results: Mean (range) age of the study group was 28.9 (18–61) years, BMI – 2 – 21.9 (16.3 21.6) kg/m , FEV1% predicted 73.6 (28.5 125.0) %, mean days of P340 iv antibiotics per year was 12.0 (0–36,75). Nine patients (16.3%) were Adherence to physiotherapy, mental health and quality of life among receiving one inhaled medication, 22 (40%) were receiving two inhaled children with cystic fibrosis medications and 24 (43.7%) were receiving 3 inhaled medications. Mean E. Hatziagorou1, A. Miloglou2, L. Nousia1, E. Kouroukli1, A. Christara2, cMPR was 74.6% (35–100). Low cMPR was found among 10.7% of the J. Tsanakas1. 1School of Medicine, Aristotle University of Thessaloniki, CF Unit, patients, while moderate and high cMPR was found among 41.1% and 48.2% Hippokration Hospital, Thessaloniki, Greece; 2Interantional Hellenic of the patients, respectively. Adherence was inversely correlated to FEV1% University, Physiotherapy Dept, Thessaloniki, Greece predicted (r2 = 0.274, p < 0.05). Adherence was not found to be related to age of the patients, number of inhaled medications, number of pulmonary Aim: To assess the correlation between adherence to physiotherapy, exacerbations and days of iv antibiotics. quality of life, anxiety and depression in children with cystic fibrosis (CF). Conclusions: High adherence was found among our study group. Worse Methods: The Manchester Cystic Fibrosis Compliance Questionnaire, the adherence to pulmonary medications was found among patients with mild DISABKIDS Quality of Life Questionnaire, PHQ-9 Depression Health disease. It is very important to address the need to comply with the Questionnaire and finally Generalized Anxiety Disorder (GAD-7) medical instructions and get the inhaled medication from the early stages Questionnaire were used in order to assess adherence to physiotherapy, of the disease, to delay chronic lung infection and lung function quality of life, depression and anxiety among children with CF. deterioration. Results: 46 children with cystic fibrosis (mean age 12 years, mean FEV1% 95.4%) were evaluated. The majority of children (46.8%) reported performing physiotherapy once or twice a day, daily, 38.3% reported P339 performing physiotherapy 4–5 times a week. 13% and 30% of the children Embedding objective adherence data available on CFHealthHub into a and their parents, respectively expressed anxiety, while 7% and 26% of the weekly MDT meeting: a quality improvement project children and their parents respectively expressed depression. Depression S. Dawson1,2,J.Dewar1. 1Nottingham University Hospitals NHS Trust, 2 showed a significant correlation with quality of life (CF impact, CF Nottingham, United Kingdom; Staffordshire University, Stoke-on-Trent, treatment, r2 = −0.456, p = 0.002, r2 = −0.372, p = 0.012, respectively and United Kingdom CF exclusion, CF medication, general) (r2 = −0.413, p = 0.015, r2 = −0.369, 2 Objectives: CFHealthHub (CFHH) is a digital behaviour change platform p = 0.032, r = −0.552, p = 0.001). Significant correlation was found 2 that automatically collects date- and time-stamped nebuliser-use data. between depression and adherence to physiotherapy (r = −0.29, p = Using the Dartmouth Microsystems approach to systems optimisation, we 0.047). In addition, a negative correlation was found between anxiety and 2 2 aimed to embed CFHH into a weekly one-hour MDT meeting by viewing quality of life (exclusion, general) (r = −0.379, p = 0.025, r = −0.494, p = 0.003). adherence data for every patient discussed. Having FEV1, BMI & adherence at every consultation transforms clinical assessment and management. We Conclusions: Anxiety and depression have a negative effect on the quality used Plan-Do-Study-Act (PDSA) cycles to record outcomes. of life and adherence to physiotherapy among children with cystic fibrosis. Methods: A survey established baseline views about the meeting. It is very important for the CF team to screen for depression and anxiety in PDSA cycles included: order to improve both quality of life and adherence to treatment among 1. Introducing ‘effective meeting skills’; patients with CF. 2. Making CFHH visible on a large screen. P341 Impact of nurse-conducted education on adherence improvement in Improvement was measured by: post-meeting MDT evaluations (mean adult patients with cystic fibrosis rating 0–10; what went well; what could have been better); and percentage 1 2 2 1 of patients whose CFHH adherence data was viewed. T. Odobasic Palkovic , D. Tjesic-Drinkovic , D. Tjesic-Drinkovic , I. Godic , 1 1 1 1 1 Results: 17 surveys were completed (3 Doctors; 4 Nurses; 7 Allied health I. Lalic , A. Sajnic , S. Karabatic , A. Vukic Dugac . University Hospital Centre ‘ ’ professionals; 3 Other). Zagreb, Clinic for Respiratory Disorders Jordanovac , Zagreb, Croatia; 2 A shared purpose of the meeting was identified: to discuss adult CF University Hospital Centre Zagreb, Department of Pediatrics, Zagreb, Croatia inpatients, home IV patients, and some community patients. Survey results Objectives: Failure or forgetting to follow prescribed treatment can lead to highlighted what worked well (e.g. valued by MDT; opportunity to discuss significant exacerbation of the disease. The aim of this study is to highlight patients; well-attended; structure); what could be better (e.g. time the importance of patient education and the role of a nurse in improving management; meeting roles/agenda/actions); suggestions for improve- adherence. ment (e.g. time management; meeting roles/agenda/actions; access to Methods: 12 male and 14 female adult patients with cystic fibrosis aged information). between 18 and 36 years participated in this study. Each patient was Mean MDT evaluations of the meeting improved from 6.5 to 8. The educated by a nurse on the importance of respiratory clearance, percentage of patients whose adherence data was viewed on CFHH in the medication, inhaler maintenance and demonstration of inhaler therapy meeting increased from 0% to 57% (see Table 1). use, the role of nutritional support and maintaining optimal body weight. Conclusions: Making small changes to the structure of this weekly one- Two questionnaires were taken, prior and 4 months after education. hour MDT meeting has improved its effectiveness and has enabled objective adherence data on CFHH to be reviewed. We are working

Table 1. (abstract: P339) Mean MDT evaluation and the number (and percentage) of patients whose adherence data was viewed on CFHH in each meeting.

Date of meeting 13/11/2019* 20/11/2019 27/11/2019 04/12/2019 11/12/2019 18/12/2019 08/01/2020

Mean MDT rating 0–10 (N = number of MDT 6.5 (N = 19) 7.3 (N = 15) 7.8 (N = 13) 7.6 (N = 17) 8.1 (N = 14) 7.5 (N = 13) 8 (N = 16) members present) Number (and percentage) of patients whose 0 (0%) 10 (42%) 5 (26%) 2 (14%) 5 (50%) 4 (19%) 12 (57%) adherence data was reviewed on CFHH

*Baseline S152 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Adherence was assessed using Morisky, Green and Levine scale (MGL) and variables, predictors of Patient Engagement, that is based on establishing the Culig Scale. an effective partnership with patients and their caregivers, for improving Results: Results obtained at the beginning using MGL scale show that 65% adherence to medical prescriptions and alliance with healthcare team of patients (17 out of 26) occasionally forgot to take prescribed treatment. 4 (Forbat et al., 2009). Primary objective of the study is to investigate the months later after structured education, results of second questionnaire engagement of patients affected by CF and that of their caregivers, show 16,9% improvement as 13/24 patients forgot to take prescribed Secondary objectives are to explore the relationship between patient and ̌ treatment. Culig scale also indicates forgetfulness as main reason for non- caregiver engagement, and clinicians’ involvement towards healthcare adherence and 18% improvement after 4 months. Both results are not system and doctor-patient relation. statistically significant. Methods: This is an observational cross-sectional study composed of a Conclusion: Results of this study are not statistically significant due to quantitative phase (through administration of questionnaires to patients, short period between surveys and small sample which was used. There is caregivers and clinicians), and a qualitative phase (through interviews to no hard evidence indicating that each specific nurse intervention led to patients and adolescent patients’ caregivers). Quantitative data collected significant improvements like increase in adherence and knowledge of will be developed through descriptive and multivariate statistical analysis; one’s disease but ultimately, this study shows patient’s benefits and qualitative data will be analysed with IPA (Interpretative necessity of nurse conducted education. Phenomenological Approach). Results: Results collected until now prove that a considerable group of P342 patients (66% of the sample) is in a positive phase of the engagement, Development of a pilot trial of a novel tele-coaching intervention to acting in a proactive manner towards the disease. We have noticed also a improve treatment adherence in cystic fibrosis low adherence to pharmacological therapies in 55% of the sample. ’ D. Polineni1, J. Lindwall2, E. Muther2, K. Durkin3, C. Ahrabi-Nejad3, Furthermore, our expected result regards the clinicians active role with E. Ruvalcaba4, E. Nelson5, M. White1, E. Bord6, A. Goodman4, K. Riekert4, the consequent effect on the management of the disease and the C. Duncan3. 1University of Kansas Medical Center, Kansas City, United States; improvement of therapeutic success potentiality. 2University of Colorado, Denver, United States; 3West Virginia University, Conclusions: This study aims to identify psychological factors that affect a Morgantown, United States; 4Johns Hopkins University, Baltimore, United good clinical practice and contribute to promote the engagement in CF ’ States; 5National Institute for Children’s Health Quality, Boston, United States; patients and their caregivers, adequately supported by Psychologist s 6Boston Children’s Hospital, Boston, United States intervention. In this way, we wish to achieve suitable tools for being validated in multicentre studies to sustain the importance of Patient Objectives: People with cystic fibrosis (PwCF) are prescribed complex Engagement. chronic treatments regimens with adherence rates ranging 50–80%. It is anticipated that treatment adherence will remain a long-term health P345 concern, even with CFTR modulator therapy. Tele-health is a nascent area Maintenance flushing interval time of totally implantable venous for PwCF to partner with CF care-teams in improving disease self- access devices (TIVADs): is it time to review the evidence and change the management. We developed a stakeholder-engaged personalised, 6- guidance? month tele-coaching intervention to improve treatment adherence. The S. Hope1, B. Nahid1, A. McGowan1. 1North West Midlands Cystic Fibrosis objectives of this pilot trial were to: a) train care-team members to tele- Centre, Stoke-on-Trent, United Kingdom coach PwCF using a novel behavioural intervention, and b) examine feasibility and acceptability of the intervention in PwCF and tele-coaches. Objectives: Totally implantable venous access devices (TIVADs), are widely Methods: Two rounds of focus groups were conducted with adolescents used in people with cystic fibrosis (CF). They facilitate long-term venous and young adults (AYA) with CF (age 14–25 years), parents of adolescents access, permit almost unlimited physical activity and can improve quality with CF, and members of CF care-teams to inform development and of life. Current guidelines and protocols, usually based on the manufac- finalisation of the tele-coaching intervention. To ensure face and content turer’s recommendation, is that 4–6 weekly flushing is necessary to validity, cognitive debriefing was completed for a survey tool (Cystic maintain patency and function. Our objective is to demonstrate that a Fibrosis Care Behaviours Survey) that guides personalisation of the longer interval between maintenance flushing may still be medically safe, intervention. An in-person training was developed for CF care-team cost-effective and could increase patient adherence. members who would serve as coaches. Sites from the Cystic Fibrosis Methods: This retrospective study examined the flushing intervals of all 33 Foundation Success with Therapies Research Consortium were recruited to adult CF patients who have TIVADs, at the Royal Stoke University Hospital. pilot coach training and tele-coaching in AYA with CF. Data was collected from 1/8/2017 to 31/8/2019 (761 days) and was entered Results: Six U.S. CF care programs and 12 care-team providers serving as into an Excel spreadsheet. Data included date of TIVAD access, determining tele-coaches were selected to participate in a pilot study commencing in if it was a routine maintenance flush, blood sampling or for intravenous February 2020. Primary outcomes are patient attrition, recruitment and antibiotic therapy. The number of days of therapy were included and feasibility, and satisfaction with the intervention. Secondary outcomes intervals calculated. Four patients had incomplete data and so were include changes in treatment adherence as measured by objective excluded from the results. monitoring of airway treatments and airway clearance. Results: The data of 29 patients was analysed and none of the patients had Conclusion: We report development of a trial for improving treatment adhered to current guidelines of 4–6 weekly maintenance flushing. adherence in AYA with CF, using a stakeholder-informed personalised tele- Individual flush intervals ranged from 36 to 152 days. Overall number of health intervention incorporating evidence-based behavioural strategies. flushes over the 761-day period ranged from 7 to 21 and the mean flush interval was 66 days (9.3 weeks). There were no infections or occlusions P344 during this time. Patient engagement is a key factor for the management of cystic Conclusion: Our results suggest that 4–6 weekly flushing of TIVADs may be fibrosis excessive and that extending the flush interval time to 8 weeks would be R. Ciprandi1, R. Casciaro1, R. Pescini1,F.Cresta1, S. Garuti1, F. Favilli1, medically safe, beneficial to patients, reduce costs of nurse time, clinic time G. Graffigna2, S. Barello2, C. Castellani1. 1IRCCS Giannina Gaslini Institute, and consumables and potentially improve adherence. This is supported by Genova, Italy; 2Catholic University of the Sacred Heart, Milano, Italy evidence from studies with TIVADs in oncology patients. We strongly advocate that the recommendations for maintenance flushing are Objectives: With this study, promoted in the clinical trials of 2019, by reviewed in CF guidelines and protocols for patients with TIVADs. Italian Cystic Fibrosis Foundation, we intend to study different psychosocial Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S153

P346 operatively to look further into quality of life pre- and post-sinus surgery. A review of recording of antibiotic-related adverse reactions and To potentially use the SNOT-22 tool more frequently with patients who allergies in adults with cystic fibrosis across paper and electronic have a recurring history of sinus disease as a preventative measure, and to medical records look at FEV1 and FVC over a longer period of time to see whether this is an J. Faughey1, E. Moore1, D. O Neill1. 1Belfast Health and Social Care Trust, CF indicator of recurrent sinus disease. Unit Level 8 Belfast City Hospital, Regional Adult CF Centre, Belfast, United Kingdom P348 An insight into the confidence and skills needed to provide care at the Objectives: Adverse events and allergies related to antibiotics are common end of life for people with cystic fibrosis in PWCF. Accurate recording of these events is essential to patient safety 1 2 3 3 2 E. Harris-Skillman , S.J. Chapman , A. Lowney , M. Miller , W.G. Flight . and future antibiotic prescribing. Many centres use a combination of paper 1 2 University of Oxford, Clinical Medicine, Oxford, United Kingdom; Oxford and electronic records, discrepancies between records can arise. Analysis of University Hospitals NHS Foundation Trust, Oxford Adult Cystic Fibrosis Centre, the level of discrepancy between electronic and nursing documentation of 3 Oxford, United Kingdom; Oxford University Hospitals NHS Foundation Trust, antibiotic adverse effects across our adult PWCF population was Palliative Medicine, Oxford, United Kingdom performed. Methods: In Northern Ireland, a regional ECR (NIECR) covers medical Objectives: Providing optimal end-of-life care to patients with cystic attendances across healthcare settings. The recording of antibiotic adverse fibrosis (CF) is challenging. There is limited evidence to guide who should events is normally performed by the General Practitioner. In addition, deliver this care and how CF multi-disciplinary teams should interact with nursing records are maintained for all attendances at the Adult CF Centre. specialist palliative care services. We sought to assess the knowledge, An initial comparison of nursing and NIECR antibiotic records in a small experience and preparedness of both CF and palliative care professionals in cohort (n = 15) identified sufficient discrepancies to warrant analysis across delivering end-of-life care to people with CF. the entire centre population (n = 300). Methods: An electronic questionnaire was distributed to all members of Results: In the initial cohort (n = 15), 56 antibiotic adverse event episodes the adult CF and palliative care teams at our centre. were recorded in paper records. Of these 52% (n = 29) were not recorded in Results: A total of 35/63 (55.6%) health care professionals responded (19 the individual’s NIECR, and would not have been visible to healthcare members of the CF team,16 members of the palliative care team). Reported professionals outside the CF centre. levels of preparedness were low for both teams: only 11% of CF team In the follow-on cohort, 22% (n = 66) of antibiotic adverse events were members and 19% of palliative care team members felt fully prepared to recorded in nursing records, but not on NIECR. Of most importance 1% deliver end-of-life care to adult CF patients. Furthermore, 58% of CF team (n = 3) had confirmed anaphylactic reactions to antibiotics not recorded in members had received no (21%) or minimal (37%) general palliative care NIECR. Only 0.6% (n = 2) had antibiotic adverse events on NIECR not present training. Similarly, 69% of the palliative care team respondents had received in paper records. no CF-specific palliative care training. All respondents indicated a desire for All reviewed paper and electronic records have been updated to ensure additional education. CF team members preferred further education in conformity. Processes for updating NIECR have been updated to allow all general end-of-life care issues while palliative care team members specialist nursing staff to access and update NIECR. emphasised a need for more CF-specific knowledge. Conclusion: Local and regional records conformity in recording of Conclusions: Few members of either team felt fully prepared to deliver CF antibiotic adverse events is crucial to clinical governance processes and end-of-life care and many desired additional education. The teams patient safety. Regular review of this information is essential to ensure expressed complementary knowledge gaps, suggesting that both could patient safety is maintained, and appropriate antibiotics prescribed. benefit from increased collaboration and sharing of specialist knowledge. This study has uncovered an important gap in training amongst many of P347 those delivering end-of-life care to CF patients and has significant clinical

A quantitative data collection study looking at the impact on FEV1 and implications, especially given the recognised need to provide palliative care FVC pre- and post-sinus surgery in paediatric and adult cystic fibrosis input earlier in the disease course. A UK-wide survey is underway to patients within the North West Midlands Cystic Fibrosis Centre expand the dataset and to allow comparison between centres with A. Capewell1, K. Perickathara1, A. McGowan1. 1North West Midlands Cystic differing access to education. Fibrosis Centre, Stoke-on-Trent, United Kingdom P349 Objectives: Chronic sinusitis is common in people with cystic fibrosis (CF). “More tools in the tool box”: innovating palliative care for adult Within the last 12 months our centre has worked closely with the Ear Nose patients with cystic fibrosis in a regional UK unit and Throat (ENT) team to treat our patients with sinus disease. We want to 1 1 1 1 P. Curtis , K. Haynes , C. Davis . University Hospital Southampton NHS determine whether FEV and FVC is impacted a minimum of 6 weeks after 1 Foundation Trust, Hospital Palliative Care Team, Southampton, United surgery. Kingdom Methods: Relevant data was collected from patients who have undergone

ENT surgery in the last 12 months. Once collated, the FEV1 and FVC were Objectives: Our Hospital Palliative Care Team (HPCT) has worked with the compared pre-surgery, and at least 6 weeks post-surgery. This will be Cystic Fibrosis (CF) Team for many years mainly in clinical crises. In January visually displayed in the form of a bar chart to demonstrate changes to FEV1 2018 we created 8 hours of dedicated clinical nurse specialist and and FVC. consultant time per week to deliver proactive early input for symptom Results: The spirometry results for 11 adult patients and 2 paediatric control and end of life planning. We have assessed the impact of this patients aged 9+ who had ENT surgery in 2018–2019 were collated. 1 change. patient had not performed spirometry after sinus surgery so was therefore Methods: Quality improvement (QI) methods were used to devise the new excluded from analysis. In 9 out of 10 patients (90%) FEV1 was improved 6+ model of working and through mixed methodologies assess the impact. weeks post-surgery, and 7 out of 10 patients (70%) had improved FVC. Activity data was collected for 4 years. Qualitative, semi-structured surveys

Conclusion: 90% of patients FEV1 improved 6 weeks+ post-surgery which collected over 3 months explored patient experience and staff perceptions highlights the importance of monitoring sinus symptoms. Regular sinus of the new model. Survey results were thematically analysed. reviews are likely to help distinguish between chest related illness and Results: Referrals to the HPCT rose from 22 and 23 in 2016 and 2017 to 41 sinus related illness. An annual ENT review would be appropriate for long- and 66 in 2018 and 2019. Patient feedback was hard to obtain; several too term management of sinus symptoms, with the aim to continue to unwell and some surveys not returned. The 3 completed surveys supported maintain and improve patient’s lung function and decrease the number of the new model describing trust in the palliative care team and unexpected exacerbations. benefit. 30 staff responded but 1 response too broad to analyse. Both Teams Further research recommendations: Future recommendations would be identified positive impact of early palliative care dispelling ‘the myth that to include completion of SNOT-22 questionnaire both pre- and post- it’s all about dying’. 15/16 CF Team and 6/13 HPCT respondents highlighted S154 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 communication, collaboration and responsiveness as strengths. Over 50% coordinator in ANP. Each centre is specialised either in paediatric, adult, felt the new model provided holistic care and ‘more tools in the tool box’. respiratory rehabilitation or post transplantation care. Other themes were the value of HPCT as an external perspective; Results: The responsibilities and skills that were identified are mainly improvements in advance care planning and staff support/education. clinical, and aim to improve the quality, safety and fluidity of patient care. There were perceived weaknesses in co-ordination between the 2 teams. Organisation protocols, which are required by law, are written by the health Although the CF Team identified insufficient dedicated palliative care time, care teams in order to define the boundaries of autonomous practice when the HPCT were concerned about reduced opportunities for developing caring for stable patients. An important aspect of ANP in France is that the their skills. roles and responsibilities combine those of Clinical Nurse Specialists and Conclusion: The proactive model of working has resulted in tripling of CF Nurse Practitioners. Other activities and skills therefore include research, referrals to the HPCT. Feedback from CF and HPCT Teams is positive with training, guidance and leadership. The main facilitators are the trust, ideas for improvement. We are re-designing methods for patient feedback support and engagement from the health care team that stem from years of and continuing the QI cycle. multi-disciplinary and collaborative work. Barriers follow the practical, political and logistical challenges of introducing a new profession within P350 the health care system. Bereavement: a ‘time to remember’ event for families bereaved by cystic Conclusion: The implementation of ANP in French CF centres comple- fibrosis ments and expands on the existing resources and skills that are specific to A. Anderson1, M. Fawdon1, Z. Booth1, R. Hodgson1, S. Parker1, CF care. It requires strong engagement and dedication and can serve as an N. Goodfellow1, R. Quibell1, S. Bourke1. 1Royal Victoria Infirmary, Adult Cystic example for other fields of practice. This initial assessment may be useful Fibrosis Centre, Newcastle upon Tyne, United Kingdom for a future evaluation of the costs, benefits and challenges of ANP in France. Background: The death of young adults with CF is an emotional trauma for family, friends and the CF team. P352 Methods: As part of palliative care and bereavement support we held a Successful development of diabetes services within a new Adult Cystic ‘time to remember’ event for families and friends. This was held on a Fibrosis Service at Blackpool, UK Sunday in a church and consisted of religious and non-religious 1 1 2 1 1 1 J. Knowles , H. Seymour , I. Dalal , T. Saba , M. Etumi . Blackpool Teaching components: music (hymns, songs), readings (poetry and prose), and 2 Hospitals, Blackpool, United Kingdom; Blackpool Teaching Hospitals, reflections by a relative and a doctor. The remembrance included the Paediatric Diabetes Unit, Blackpool, United Kingdom reading of the names of those who had died as their picture was displayed, the lighting of candles and the placement of memory cards on a tree. Objectives: In 2015 UK Regional Specialist Commissioners selected Refreshments were then served, a cake with a CF emblem was distributed, Blackpool as the site of the first new Adult Cystic Fibrosis Service (BACFS) and the CF team met with families. Attendees were asked to evaluate the in England in over 30 years in collaboration with Manchester Adult Cystic event. Fibrosis Centre (MACFC). A Diabetes Nurse Specialist (15 hrs/month) was Results: There had been 86 deaths in 15 years. Many relatives were no appointed to develop a CF Diabetes (CFD) service and achieve Cystic longer contactable; 29 families accepted the invitation and 24 attended; 11 Fibrosis (CF) Trust Standards of Care and NICE Guidance, with mentorship were unavailable; 8 declined as ‘too upsetting’, ‘remember privately’ or ‘too from MACFC and support from Blackpool Paediatric Diabetes service. soon’; many of these sent photos and asked for the person’s name be read Methods: Key goals were to: out. Overall 80 people (14 staff; 66 relatives) attended. Two current patients 1. Establish a CFD service whose sibling had died attended. Members of the paediatric CF and 2. Develop protocols and resources palliative care teams also attended. Evaluation by families was strongly 3. Educate patients and clinicians positive: ‘lovely event’, ‘emotional but amazing,’‘great comfort from celebrating her life’, ‘nice to meet CF team again’, ‘hope it helped CF team’. Results: Some negative themes were ‘too difficult’, ‘too religious,’‘didn’t know other 1. CFD service • families and new team members’. Staff attending rated the event highly, at 41 patients: 11 have CFD and 12 have impaired glucose tolerance • a mean score 9 (range 8–10) on a scale 1–10. Positive comments were ‘good Outpatients: 4 weekly CFD clinic started Feb 2019 with consulta- to meet relatives’, ‘very moving’, ‘nice to include paediatric teams’; tions, assisting CF Specialist Nurse in non CFD clinics to inform negative themes were ‘sometimes difficult to recognise relatives’, ‘hymns patients of role of CFD team not known’. Staff at the event received universally positive feedback and 2. Protocols and resources • did not identify any concerns. One iPro device purchased and 4 CGMS done • Conclusions: The event was judged to have been a very positive experience Freestyle Libre devices purchased and 10 patients monitored • by both relatives and staff who attended. 6 CFD annuals completed 2019 since July as well as supporting newly transitioned patients to BACFS • P351 Joint policy writing with MACFS The introduction of Advanced Nursing Practice in French cystic fibrosis 3. Education • centres faces many challenges and opportunities Close working relationship with CF dietitian, nurse and doctors • Regular contributor to journal club, local and MACFS meetings as S. Gonsseaume1, E. Burnet2,3, N. Goriot-Raynaud4,5, V. Houdouin1,3, well as UK CF L. Mely4, C. Vallier4, N. Carlier6, V. Boussaud6, M. Gerardin1. 1Robert Debré Diabetes Nurse Specialist meetings University Hospital, AP-HP, CF Centre, Paris, France; 2Cochin Hospital, • Ward staff training Pulmonology Department, Paris, France; 3Paris University, Paris, France; • Patient education delivered for carbohydrate counting and 4Renée Sabran Hospital, Cf Centre, Giens, France; 5Aix Marseille University, insulin dose adjustment using recognised Apps and books e.g. Marseille, France; 6Cochin Hospital, Post Transplant Care Unit, Paris, France Carbs and Cals and newly developed resources Objectives: Advanced Nursing Practice (ANP) was legally recognised by the • Visits to other local specialist CF centres MACFS and Liverpool French Health Authorities in July 2018. Since then, the goal has been to Heart and Chest Hospital. determine how it can best answer unmet needs. Nurse Coordinators Conclusion: Development of specialist services within the current UK NHS working in CF Centres have a unique role to play in the development of ANP climate can be challenging but achievable with good communication and and in defining new responsibilities and skills. This paper aims to identify negotiating skills, clinical/managerial working relationships and support the actions that have been taken to implement ANP in CF care in France and from colleagues and commissioners. to describe the associated barriers and facilitators. Methods: Data was gathered from three French CF centres that are engaged in introducing ANP and have invested in training an experienced nurse Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S155

P353 handling. 28 self-cared patients would like to update their knowledge after “There’s no place like home”: formalising the provision of home IV our study; 20 who don’t practice self-care are interested in being trained. antibiotics for people with cystic fibrosis in Northern Ireland Conclusions: Self-care is frequent, mainly with patients with Port and V. Mills1, S.J. Hanna2,D.O’Neill1, J. McLornan3, S. Caskey1, D.G. Downey1,4, meets a real need of the CF patients. Patients don’t inform systematically CF C. Addy1,5. 1Belfast Health and Social Care Trust, Adult CF Centre, Belfast, centre about their decision to do so. Self-care must be more monitored and United Kingdom; 2Belfast Health and Social Care Trust, Pharmacy Department controlled by the CF team. Belfast City Hospital, Belfast, United Kingdom; 3Belfast Health and Social Care Trust, Regional Repiratory Centre, Belfast, United Kingdom; 4Queen’s P355 University Belfast, Centre for Experimental Medicine, Belfast, United Kingdom; Nebulised colistin for patients with cystic fibrosis – time for change? 5Queen’s University Belfast, Centre for Medical Education, Belfast, United L. Wooldridge1, M. Desai1. 1Birmingham Women’s and Children’s NHS Kingdom Foundation Trust, Respiratory and Cystic Fibrosis, Birmingham, United Kingdom Objectives: In an ever-aging CF population, review of care for pulmonary exacerbations (PEx) is required. Antimicrobial stewardship, reduced intra- Objective: It is our common practice to treat all inpatients with CF with venous antibiotics (IVAB) antibiotic exposure and a drive towards greater colistin including prophylactically in those who are Pseudomonas provision of home-care are of increasing importance. A review of Home aeruginosa (Pa) naïve. We also give prophylactic colistin to other siblings provision highlighted the need for a formal pathway to achieve these goals. with CF when one isolates Pa. This practice arose from concerns that Methods: The “There’s no place like home” multi-disciplinary project was inpatients had acquired Pseudomonas aeruginosa during hospital stays and designed to improve the safety and quality of home IVAB provision for were at higher risk of acquiring it when living with other people with CF. people with CF (PWCF) cared for at the NI Regional Adult CF Centre. Using However, this has led to some of our patients being excluded from research plan-do-study-act methodology, home IVAB Consent & Competency forms, studies. It was our objective to compare our practice with UK centres. Patient Information Leaflets (PIL) and a formal home IVAB care pathway Method: An electronic survey containing 10 questions relating to the were created to facilitate implementation. indications for use of nebulised colistin were sent to all 19 tertiary Results: The home IVAB care pathway comprises confirmation of PEx, paediatric centres in the UK. exclusion of alternative causes for clinical deterioration and an antimicro- Results: The audit identified that no centre was giving colistin to inpatients bial stewardship decision tree prior to prescription of IV antibiotics. This who were Pa naïve. However, every response indicated that colistin was decision tree outlines options for alternatives to IVAB, approaches to given to inpatients receiving anti pseudomonal intravenous antibiotics, as reducing IVAB exposure and risk reduction for all PWCF being considered per our own practice. Furthermore a response of 80% identified that in CF for home IVAB therapy. sibling groups, colistin was not used prophylactically should one or more Suitability for performing home IVAB is formally assessed with the PWCF isolate Pa. completing a consent and competency form prior to home administration. Conclusion: The response rate to this survey was low and further Individuals receive a patient held home IVAB and PIL containing instruction reminders will be sent out to obtain a more comprehensive view of UK on safe administration, hand hygiene and infection control precautions and practice. Our practice of giving colistin to inpatients colonised with Pa who contact in the case of emergency. were receiving Intravenous antibiotics concurs with that in other centres. Conclusion: A formalised home IVAB process and care pathway is now in However, this audit identified that we were not in line with other centres by place, to improve competency, safety and stewardship of home IVAB. In the giving all our CF inpatients colistin. Also, the practice of giving prophylactic next six months, the aim is to increase by 50% the number of PWCF offered colistin to CF sibling groups was out of line with most other respondents. home IVAB through this pathway. Further investigation into sibling Pseudomonas acquisition rates is required to determine whether it is safe to stop our current practice to allow more P354 eligibility to future studies. Home IV antibiotic course in a large cystic fibrosis adult centre in France: prevalence of self-care P356 D. Ali Mehidi1, R. Panzo1, J. Champreux1, P.-R. Burgel1, R. Kanaan1, Can nurse-provided education affect improvement of lung function C. Dupont1. 1Pulmonary Department and Cystic Fibrosis Centre, Cochin and nutritional status in adult patients with cystic fibrosis? Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France T. Odobasic Palkovic1, D. Tjesic-Drinkovic2, D. Tjesic-Drinkovic2, I. Godic3, I. Lalic3, A. Sajnic3, S. Karabatic3, A. Vukic Dugac3. 1Clinical for Respiratory Background: In 2017, 227 patients in 469 patients followed by our centre 2 Disorders, Zagreb, Croatia; University Hospital Centre, Department of had at least one IV antibiotic course a year. 7418 days of home IV antibiotic 3 Pediatrics, Zagreb, Croatia; University Hospital Centre, Clinical for Respiratory course were realised in 2017. Organised by the CF team, treatments are Disorders ‘Jordanovac’, Zagreb, Croatia provided by private homecare nurses. However, some patients say they make some cares themselves. Objectives: Adult cystic fibrosis (CF) patients have increased lung Objective: To precise the frequency of self-care in adult CF patients during manifestations. Failure in following prescribed treatment can lead to home IV antibiotic course, patient’s training, which care are provided, the significant decrease of lung functions while low body mass index (BMI) can impact on their quality of life. lead to worsening of the disease. The aim of this study was to show that Methodology: In our CF centre, patients who have at least one home I.V. nurse-conducted structured training can raise patients’ adherence and antibiotic course in 2019 completed an auto survey (13 questions). awareness of the importance of daily and lifelong treatment. Results: From May to December 2019, 152 patients (mean age: 34-years- Methods: This study was conducted at the Clinic for Pulmonary diseases old) answered the survey. 71/152 (47%) of patients carry out self-care and Jordanovac, Clinical hospital centre Zagreb on a sample of 26 patients with it’s wanted by patients (32%, 49/152), by the private homecare nurse (4,5%, cystic fibrosis aged between 18 and 36 years, (12/26 male and 14/26 6/71) or both (10,5%, 16/71). female). Nurses educated each patient on the importance of respiratory 63% of audited patients with a port, 31% of those with a peripheral inserted clearance, medication, inhaler maintenance, demonstration of inhaler central catheter (PICC), 45% of those with a short peripheral cannula (SPC) therapy use, the role of nutritional support and maintaining optimal body practice self-care. Patient fills elastomeric pump (EP) dedicated to infuse weight. Lung functions; forced expiratory volume in 1 second (FEV1) and the treatment in 16%, primes EP’s extension line in 64%, flushes the catheter BMI were measured prior to education and again 4 months later. and connect the EP in 35,5%, disconnects the EP and flushes in 40%, inserts Results: After nurse-conducted education, FEV1 value increased by 5,27% the non coring needle in 1%, removes it in 6,5%, removes the SPC in 5%. while BMI increased 2,31%. Difference in values was not statistically Because of self-care, patients feel more free in their daily life (59/71), rarely significant but correlation shown statistically significant medium positive tired (6/71) and do not feel insecure (61/71). 44 say they have been trained connection between those variables. to do the techniques but only one had a real training session about port Conclusion: Although the difference in FEV1 and BMI values are not statistically significant, results indicate some improvement. This study S156 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 suggests a significant role for the nurse in patient care as one of the main procreation, or due to CF symptoms, fatigue, treatments, transplant members of the multidisciplinary team. Further research involving higher perspective and management at work. CF parents’ main concerns are number of patients over more time is required. their children’s well-being and the proper way to communicate with them about their disease. P357 Conclusion: The analysed content already provides interesting under- Who you gonna call?………specialist nurses standing of CF parents and spouses’ experience. More focus groups are to A.L. Hopkins1, A. Smith1, R.I. Ketchell1, D. Lau1, J. Duckers1. 1Cardiff & Vale be conducted in spring 2020, including more spouses and patients with University Health Board, All Wales Adult Cystic Fibrosis Centre, Penarth, United lung transplant. They will complete this current knowledge, which will be Kingdom used to develop recommendations and therapeutic interventions. NCT04133246. Supported by Association Grégory Lemarchal. Sponsor Background: At the All Wales (cystic fibrosis) CF Centre the clinical nurse APHP. specialists (CNS) provide a telephone triaging service for patients (300) Monday to Friday 9–5. Collectively we have found that our patients use us P359 as a first point of contact for all types of health and non-health related Adapting to a diagnosis of cystic fibrosis: a psychosocial group for issues. At times this feels a little overwhelming. parents - providing information, affirmation and social support We thought we would examine this in the context of the fivefold 1 2 3 4 1 J. Byrne , M. Tonge , M. Connolly , S. Bradish . Galway University Hospital, responsibility as laid out in National Consensus Standards for the 2 Cystic Fibrosis Services, Galway, Ireland; Galway University Hospital, Nursing Management of cystic fibrosis (2001). 3 Paediatrics, Galway, Ireland; Galway University Hospital, Cystic Fibrosis and Aim: Are patients’ expectations realistic with regards to the defined role of 4 Paediatrics, Galway, Ireland; Galway University Hospital, Galway, Ireland a clinical nurse specialist? Is there a mismatch between expectations and reality? Objectives: Recent ECFS Best Practice Guidelines advise that CF teams Methods: Anonymous questionnaire handed out to a random selection of should actively support parental coping, resilience and positive mental patients in clinics over a 4 month period. (Target size of 30). health. In particular, the guidelines identify adaptation to diagnosis as a key CNS team documented ‘unusual’ requests from patients, usually, but not potential point of vulnerability for parents. This professional-led, psycho- always on the telephone. social educational group for parents of children recently diagnosed with CF Results: A random selection of 30 patients attending various outpatient (<5 years) aimed to enhance parental coping, well-being and psychosocial clinics over a period of 4 months. adaptation to CF by providing information, affirmation and social support From this sample 27 (90%) stated that the CNS service would be their first to parents, with a central focus on parent’s experience of receiving and point of contact for advice. The reasons given were as follows: 17 (56%) that adapting to a diagnosis, and the parent’s own well-being within this. we had specialist knowledge and 9 (30%) stated that we offered a greater Method: A series of four psychosocial educational sessions were held: The understanding and a more rapid response than other services. content of the group programme was informed by the research base Documentation by the CF CNS team provided a flavour of non CF related regarding the psychosocial needs of young children with CF and their issues ranging from advice re: insect bites to Kennel cough! families. Each group session had a different focus. There was a particular Conclusions: The results from our sample did not reveal a gulf between emphasis on parental well-being, coping and resilience throughout the patient expectations of our role and the five-fold responsibility model. four group sessions. It is however evident that we are the first point of contact for many CF and Evaluation: Fourteen parents attended over the course of the four Non-CF problems. We have an increasing patient population and in order evenings. Anonymous feedback was very positive. The majority said that for a successful triaging service to continue it will be vital to develop clear the group was ‘extremely useful’, ‘helped them adjust to a diagnosis of a guidelines for both patients and the CNS team. chronic health condition’ and increased their sense of social connected- ness. Parents highlighted that it was useful to hear about how others had P358 felt after being given a diagnosis. They also said that the message regarding How do cystic fibrosis patients experience parenthood? An explorative the importance of their own well-being in order to look after their children study was important to them and had made an impact. A. Jacob1, D. Hubert2, D. Grenet3, H. Abdoul4, C. Flahault1,5,6. 1Université de Discussion: This evaluation of a professional-led, structured parent group Paris, Institut de Psychologie, Boulogne-Billancourt, France; 2Hopital Cochin, focussing on parental well-being and adaptation to a diagnosis of CF APHP, Service de Pneumologie, Paris, France; 3Hopital Foch, Service de suggests that this is a good way of supporting parental well-being, Pneumologie, Suresnes, France; 4Hopital Cochin, APHP, Paris, France; 5Hôpital resilience and coping. Européen George Pompidou, Paris, France; 6Hôpital Gustave Roussy, Villejuif, France P360 “You learn more about life”: siblings’ experiences of cystic fibrosis Objectives: Improvement in health outcomes and the increase in life 1 2 3 4 1 J.A. Glazner , M.M. Jessup , A.L. Quittner , S.M. Sawyer . The Royal expectancy for people with CF allows an increasing number of patients to Children’s Hospital, Department of Respiratory and Sleep Medicine, become parents. Only a few studies have assessed the impact of parenthood 2 Melbourne, Australia; The University of Queensland, Faculty of Health and on CF patients’ health and daily life. Our study aims to deepen the 3 Behavioural Sciences, Brisbane, Australia; Nicklaus Children’s Research understanding of the experience of parenthood of CF patients and to 4 Institute, Nicklaus Children’s Hospital, Miami, United States; The Royal describe for the first time their spouses’ experience in order to detail Children’s Hospital, The University of Melbourne, Melbourne, Australia parents and spouses’ needs. Methods: CF parents of two French adult CF centres were invited to Objectives: Daily CF treatment is time-consuming and requires an participate alone or with their spouse to a unique 2-hour focus group. inordinate amount of parental involvement, raising questions about the Groups were audio-recorded and transcribed for analysis. A thematic experiences of the well siblings. analysis of content was conducted. Methods: As part of a larger study that examined parental differential Results: Four focus groups have been conducted including 17 patients (2 treatment of siblings in families caring for a child with CF, 39 older well men) aged 32 to 61 years (mean = 42), and 4 male spouses, aged 32 to 50 siblings aged between 7 and 15 years responded to four open-ended years (mean = 47). CF parents had 1 to 3 children (3 months to 37 years old, questions. The questions explored what happens when the sibling with CF mean = 10). The analysis of the two first groups reveals 6 main themes is admitted to hospital, the positive and negative aspects of having a sibling (each with subthemes): child project and procreation, parenthood with CF and what would make it better or easier for the well siblings. representations, children, spouses, daily management, history of the Results: Thematic content analysis of participants’ responses revealed a illness. The groups’ content emphasises the positive aspect of parenthood lifeworld characterised by redefinition of routines, relationships and for people who could not picture their life without children, and the major normalcy. The effects of CF were filtered as positive (special activities, role spouses play in the whole adventure. Difficulties are described during knowledge/empathy) or negative (imposition/impact, emotional Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S157 disadvantage, differential treatment), an often incongruous, iterative percentage (M) = 42.17%, SD = 3.92). Students in a CF-class have better process. For example, daily routines were disrupted by hospitalisation of knowledge of CF than Non-CF class students [M = 50.33% (SD = 3.95) vs the sibling with CF. While some well siblings found it “fun” staying with M = 37.17% (SD = 3.79), p < 0.001]. Overall, 50.42% of teenagers have heard wider family, for others it was a negative feeling of being “shipped off” to of CF, surprisingly only 65.18% of CF class students actually have. In 28.89% others. Participants’ deliberations of what would make things easier for of the cases a fellow student in the CF-class indicates not to know anybody them included the desire for contact with other siblings and the need for a with CF. Overall, 34.54% knows someone with CF; 49.44% knows that CF is cure. not contagious and 53.63% knows that CF patients need follow-up in a Conclusion: CF exerts converse positive and negative impacts on well specialised CF centre. More than 90% of the respondents, both in the CF siblings. Closer attention should be paid to well siblings, particularly (92.59%) and Non-CF class (94.19%), do not know that CF is incurable. given the importance of sibling relationships across the expanding life Almost half of the teenagers (47.9%) indicate that their knowledge of CF is course of CF. poor. Conclusion: Knowledge of CF is low in general in the teenage population. P361 Adolescents with a fellow with CF in their class have better knowledge than What influences participation in clinical trials by people with cystic those without. However, almost one third of fellow students in a CF class fibrosis? A national delphi study decline that they know someone with CF, suggesting that not all CF patients R. Dobra1, 2, S. Elborn1, 2, S. Madge1, 2, L. Allen3, C. Saunders1,2, S. Goundry3, inform their peers about their illness. Future research should focus on the J. Davies1,2. 1Imperial College London, London, United Kingdom; 2Royal reasons why CF-teenagers withhold their diagnosis and whether mental Brompton Hospital, Department of Cystic Fibrosis, London, United Kingdom; well-being of CF-students in general would improve if knowledge among 3Clinical Trials Accelerator Platform, London, United Kingdom peers would increase.

Background: Trial pipeline expansion means more people with CF are P363 participating in trials. Understanding what influences trial participation Patients create knowledge: patient science for research into rare from a patient perspective can be used to optimise enrolment and diseases – a citizen science study in the field of cystic fibrosis retention, make trials more accessible, improve satisfaction and minimise J. Gardecki1,N.Heyen2, O. Eickmeier3,T.Bratan2, D. Eidt-Koch4, research burden. Little attempt has been made to determine factors M. Schlangen5, C. Smaczny1, G.G.U. Rohde1, T.O.F. Wagner6. 1University influencing participation in CF trials. Hospital Frankfurt, Goethe-University Frankfurt, Pulmonology & Allergology, Aims: To determine factors influencing trial participation and understand Christiane Herzog CF-Center, Frankfurt/Main, Germany; 2Fraunhofer Institute the relevance of these factors in the current CF trial landscape. for Systems and Innovation Research ISI, Competence Center Emerging Methods: We used literature review, semi-structured interviews and focus Technologies, Karlsruhe, Germany; 3Goethe University Children’s Hospital, groups to identify factors influencing trial participation. A framework was Pediatric Allergology, Pulmonology & Cystic Fibrosis, Frankfurt/Main, developed comprising 113 statements divided into 12 domains such as Germany; 4Ostfalia University of Applied Sciences, Faculty of Public Health ‘ ’ ‘ ’ Motivation to take part and Barriers to participation . This formed the Services, Wolfsburg, Germany; 5German Cystic Fibrosis Association, Cystic basis of an online Delphi process to create a consensus on which statements Fibrosis Institute, Bonn, Germany; 6University Hospital Frankfurt, Goethe- the CF community think apply in the current landscape. 30 people with CF, University Frankfurt, Frankfurt Reference Center for Rare Diseases (FRZSE), 27 parents and 30 HCPs from 17 centres were selected as panellists. Frankfurt/Main, Germany Results and conclusions: Some findings will be familiar (eg the highest ranked motivation to participate in trials is to access novel drugs). Others Objectives: Medical research is usually planned, conducted and evaluated give insight into how controversial issues (eg placebos, washouts and by health professionals. Patients serve mainly as a data source. Their payment) are viewed by the CF community. The novel evidence could expertise of living with a chronic disease has not been adequately involved inform trial design and guide ethics boards. The study identifies key so far. Especially when the illness influences everyday issues, the patients priorities to improve trial experience and accessibility. Some improve- may not only give answers, but help to ask the right research questions. The ments require a fundamental overhaul of trial design moving forward (eg Patient Science Project is a citizen science venture to explore everyday increased use of remote monitoring to reduce visits). The study also problems of patients and parents affected by cystic fibrosis. In previous identifies many priorities which would be simple to implement (e.g. citizen science projects in Germany, patients usually only assisted. In the making sure it is easy to contact the trials team). The study reveals development of research questions or priorities, they were mostly not discrepancies in how HCPs and patients perceive factors, particularly involved. The majority of the citizen science activities take place in the field within the domains ‘Motivation to participate’ and ‘Experiences of trials of ecosystem research. The Patient Science Project addresses both gaps: It ending’. Challenging their assumptions by better understanding the not only provides a citizen science study in the health sector, but also patient voice may help HCPs better support patients in trials. includes the citizens in the whole research process. Methods: 12 citizen researchers, namely CF patients and parents of P362 affected children, design, conduct and evaluate research at eye level with A Belgian survey comparing the knowledge of cystic fibrosis in 2 CF-specialists and other scientists. Typical and most important everyday different groups of teenagers problems of CF patients are systematically recorded and analysed. The S. Braun1, H. Eyns1, S. Daelemans1, L. Peeters1, E. De Wachter1. 1UZ Brussel, CF group designed a questionnaire covering daily problems in the areas of Clinic, Brussels, Belgium professional activity, living, mobility & travel, social environment & leisure and CF therapy & care. The CFQ-R was included to get valid data of Health- Objectives: Investigate knowledge of CF in a teenager population and Related Quality of Life (HRQoL). The survey was available online from Jul- compare this between 2 groups: adolescents with a fellow student with CF Sep 2019. It was completed by 902 individuals (51% patients, 49% parents). (“CF-class”) and a group without a fellow student with CF (“Non-CF-class”). Results: Data collection is completed. First results will be presented during We hypothesise that CF-class adolescents have better knowledge of CF the ECFS Congress. disease compared to Non-CF-class students. Conclusion: This study enables people affected by CF to participate in Methods: A questionnaire (Q) to determine the knowledge of CF was research at the highest level and thereby creates new insights in important developed and distributed among different schools after obtaining everyday problems as well as identifies where CF patients and parents see informed consent. Written Qs contained 6 demographic and 12 knowledge specific needs for support and orientation in dealing with these conflicts. questions, giving three possibilities: Y/N/I don’t know. Results: In total, 359 completed Q were obtained: 135 (37.6%) CF-class; 224 (62.4%) Non-CF class. Overall knowledge of CF was below average (Mean in S158 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P364 Results: Patients’ evaluation forms explored the therapeutic value of the Efficacy of having an activity coordinator in an adult cystic fibrosis art project which will be presented alongside the staff satisfaction survey ward about enabling an art project within a busy hospital ward. S. Ghufran1, K. Casey1, A. Mills2,M.Dawes2. 1Nottingham University Conclusion: Art projects can allow people with cystic fibrosis to have a Hospitals NHS Trust, Clinical Psychology, Nottingham, United Kingdom; positive therapeutic experience during their hospital admission where 2Nottingham University Hospitals NHS Trust, Respiratory, Nottingham, United they can learn new skills and have some ‘me’ time away from their essential Kingdom but demanding treatment regimes. Next steps may be to consider other types of therapeutic activities that can be undertaken during ward In order to respond to this service user feedback a charity bid was admissions. successfully carried out leading to the employment of an Activity Coordinator for 25 hours per week. As this is a pioneering project it was P366 important to evaluate the service provided. Intervention of a socio-aesthetician in the healthcare of patients with Objectives: To examine the impact of creative activity on mood while on a cystic fibrosis two-week inpatient stay at the Cystic Fibrosis unit. 1 2 1 1 1 A. Pesle , C. Lamaud , W. Azaiz , S. Gonsseaume , V. Houdouin , To explore if levels of anxiety decrease for patients if they are involved in a 1 1 1 L. Leclainche , M. Gerardin . CF Centre, Hopital Robert Debre AP-HP, North- therapeutic activity during an inpatients stay. 2 University of Paris, Paris, France; CEW, Paris, France Methods: All inpatients in the Wolfson Cystic Fibrosis centre from April 2019 to May 2019 where approached by the activity coordinator to Cystic fibrosis, as other chronic illness, can deal a blow to one’s self-esteem participate in various organised activities. Eight patients were given GAD-7 and body image. To improve patients self-esteem, workshops with a socio- and PHQ-9 along with service user feedback questionnaires start and end aesthetician (SA) were proposed. of admission. Aim: The objective of this study was to evaluate socio-aesthetic practices Results: Patient Health Questionnaire-8 (PHQ-8) and Generalised Anxiety on cystic fibrosis patients, between February 2019 and December 2019. Disorder-7 (GAD-7). The PHQ-8 seeks to measure depression symptom Methods: Individual aesthetic care was offered to patients over 11 years severity and the GAD-7 seeks to measure anxiety symptom severity. Both and to hospitalised patients mothers by a SA. An evaluation before and after mental health measures showed an overall improvement in scores the care was made by the SA and exchanges were held with the healthcare observations of the negative impact that the isolation often has on a team (psychologist, doctor, coordinator nurse). patient’s mental health. Results: From February 2019 to December 2019, 14 patients (11 girls and 3 Quotes from service user feedback questionnaire: boys) and 8 hospitalised patients mothers requested the services of the SA, • “[The Activity Coordinator] made the admission more enjoyable. my for 54 workshops. 40% were held in the hospital room and 60% in a stay in hospital a lot more bearable as with being isolated can make you consultation room. 9 patients received only 1 care, 8 received 2, and 5 feel lonely/depressed”. received 3 or more. The services requested were 17 body massages, 14 • “Helped ‘mental’ health/settle down/time pass quicker and something beauty advices (skin care, make-up), 13 facial care, 3 make-ups, 1 foot care, to look forward to”. 1 hand care, 1 hair removal. Patients almost unanimously found that the care was beneficial. Before the care, to the question: ”How do you feel?”, The above quotes suggest that the Activity Coordinator is instrumental in 38% answered fair, 48% good and 14% excellent. After the care, 10% reducing the impact of the isolation on CF patients during their admission. answered good and 90% excellent. On the benefits felt, 82% were relaxed, Conclusion: The Activity Coordinator role provides a tremendous benefit 71% soothed and all felt a sensation of well-being. All patients were left ’ to the patients mental and physical health. Results indicate that engaging with a pleasant sensation to the touch, to the quality of listening and to the in therapeutic activity which is not treatment related while inpatient on respect of the comfort. The services lasted 45 min. The duration was the cystic Fibrosis ward does have a positive effect on mood and reduces considered completely appropriate in most cases. Only 5 patients thought anxiety in patients, leading to a better patient experience overall. it was too short. 100% wanted to repeat. Conclusion: The SA is a truly integrated staff person, and much valued. The P365 study needs to be completed in order to continue the assessment of the Evaluation of Colour Blast! A ward-based art project for people with care, the long-term benefits to patient well-being and the and the point of cystic fibrosis view of healthcare professionals. 1 1 1 1 1 1 R. Fallon , A. Worthington , C. Rourke , A. Bowling , A. Tansinda , A. Jones , Funded by Vaincre la Mucoviscidose. A.K. Webb1. 1Manchester University NHS Foundation Trust, Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom P367 Understanding psychosocial parameters affecting level of physical Objectives: To explore and evaluate the impact of a ward-based art project activity in adults with cystic fibrosis for people with cystic fibrosis during their hospital admissions. 1 1 2 3 1 2 Methods: A questionnaire and online survey was conducted with patients O. Fasan , A. Masson , S. Mandigout , F. Thomas , J. Languepin , B. Borel . 1 attending a large regional cystic fibrosis centre in the north west of England Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), CHU 2 to explore their views about what type of creative activities they would like Limoges, Limoges, France; Université de Limoges, Laboratoire HAVAE, EA6310, 3 to do on the ward during inpatient stays. Following this, patients voted on Limoges, France; Société Arise’Up, Saint Just le Martel, France different projects, with the majority choosing Colour Blast! The centre Objective: The aim of this study was to understand psychosocial factors commissioned Start Inspiring Minds, an art and wellbeing organisation, for related to the level of physical activity (PA) in adults with cystic a freelance artist to facilitate the art project with patients on the ward fibrosis (CF). during their hospital admissions. The project had 4 stages: designs for a Methods: This study included patients of Limoges CF centre. Each patient ‘ ’ Bee Sculpture ; Caligraphy; Mosaics; Ceramics. The artist visited patients was wearing a wearable sensor (Actigraph GT3X) for 7 consecutive days to on the ward and gave them the opportunity to participate in aspects of the analyse spontaneous daily PA level. The patient responded to a question- art project, with artwork either guided by the artist or done independently naire of 64 questions developed on the basis of 3 questionnaires, with by the patient using materials supplied by the artist. The artwork was supplementary questions to record patient’s psychosocial and socio- finalised by the artist for display on the ward, or for patients to take home. professional data. The responses of each subject generated, by multiple ‘ ’ The finished Bee Sculpture was varnished for the ward garden. Evaluation correspondence analysis, a scatter point, with data correlating to subject’s forms were given to patients who participated in the artwork and an online PA level. satisfaction survey was distributed to staff at the Cystic Fibrosis centre to Results: A total of 13 patients were included (mean age: 32 ± 12 years), obtain staff views. whose analysis of PA level revealed a significant disparity between patients (23.98 minutes/day (min 2.5–58.1max). The analysis of the questionnaire Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S159 revealed an impact of psychosocial and socio-professional characteristics Results: N = 165, (95 male, 52%) mean age 8.3 years (0.9–15.8 years). 93% of on individual PA level. The impact of CF on planned blood tests (154) were completed, 81% (133) had an MDT 1. daily activities or discussion, 95% of the results (146) were documented as being discussed 2. body image would seem to be an important factor in the patient’sPA with the families, 83% (110) received an AR letter. 93% (143) of all planned level as well as the socio-professional category. blood tests were done within 3 months of the due date; of discussions with the families, 97% (142) were discussed within 3 months of the bloods being ’ Conclusion: The disparity observed in the patient s PA level requires more done; 81% (108) of patients had an MDT discussion within 3 months of detailed analysis of psychosocial parameters. First, the results allow to being fed back to the families; 94% (103) received their AR letter within 3 formulate the hypothesis that the barriers to PA practice would be also months of their MDT discussion. Overall, from bloods being done at the linked to the impact of the disease on body image and on self-esteem. start of the AR process, to the family receiving their letter, 73% (80) had Moreover, the socio-professional category would also be a major factor in completed the AR process within 6 months and 7% (8) took 9 months or ’ patient s PA level, by impacting the perception of disease and PA level. more to complete the AR process. However, this original approach requires a larger sample and a control Conclusion: This review has highlighted shortfalls in our AR process and group to confirm these first hypotheses. where improvements can be made. We have now developed a robust system to track patients within the AR process, with the aim to improve P368 patient care. Standards are now being developed and audited. Parents’ experiences when their child is diagnosed with cystic fibrosis in the newborn screening program Reference P.B. Nielsen1, C.S. Jensen1,2,3, H.V. Olesen1. 1Aarhus University Hospital, CF Trust 2011 Standards for the Clinical Care of Children and Adults Paediatrics and Adolescent Medicine, Aarhus, Denmark; 2Aarhus University, with CF in the UK Clinical Medicine, Aarhus, Denmark; 3Aarhus University Hospital, Research Centre for Emergency Medicine, Aarhus, Denmark P370 Objectives: The aim of this study was to gain knowledge about the parents’ Staggering! The future for cystic fibrosis clinic structure? experiences with everyday life after having a child diagnosed with cystic E. Shepherd1, M. Allenby1. 1University Hospital Southampton, Southampton, fibrosis (CF); focusing on the very first start getting the diagnosis and the United Kingdom experience of the patient continuity of care in the months after. Objectives: A review of outpatient clinic appointments at the Wessex adult Methods: The study takes a phenomenological-hermeneutical approach. CF centre highlighted significant inefficiencies. Due to limited physical Semi-structured interviews with parents to 15 newborn children were space current clinic structure is that three patients arrive at 2 pm and three conducted and narrative analysis was used. more arrive 90 minutes later. Patients are seen by the MDT in no particular Results: The analysis revealed three themes: order and this has been shown to result in significant idle time for both 1. Getting the diagnosis; There was a profound difference in the parents’ patients and staff. A quality improvement initiative was undertaken using experience depending whether the diagnosis was communicated by a PDSA (plan, do, study, act) cycles to improve clinic flow and efficiency. physician from the CF-team or by a paediatrician on another hospital. Methods: The initial PDSA cycle was tested in two clinics. Patients were 2. The first meeting and the relationship with the cystic fibrosis scheduled to arrive at 25-minute intervals and clinicians were asked to see specialist team; The doctors’ and nurses’ considerable knowledge patients in a set sequence with an allotted time allowance per patient and calmness meant everything for the parents. Most families voiced determined based on previous analysis. Total scheduled clinic time per that they did not wish to be hospitalized at their first consultation in patient was 85 minutes. the CF centre where they were informed about the diagnosis. Results: With the introduction of sequential clinics patient idle time However, reflecting on this retrospectively they felt it was the right reduced from 38 minutes (range 1 minute to 109 minutes, 36% of total decision. clinic time) to 21 minutes (range 9 to 48 mins, 25% of total clinic time). 3. The families’ new everyday life after the diagnosis; Most parents Median clinic time was 82 mins (range 52 to 107 mins). 5/6 patients described having anxiety and concern for the child’s future. The reported improved idle time in the sequential clinics. parents experienced totally different views, ranging from seeing the All patients were seen by clinicians in sequence and on average clinicians child as healthy and just having some challenges to wishing the child spent 3 minutes less time with each patient than their allotted time. Staff was not born. feedback was positive with 8/9 reporting that they found it helpful to see Conclusion: Parents’ experiences when their child is diagnosed with cystic patients in a pre-specified order and felt it improved clinic flow. Clinicians fibrosis in the newborn screening program, shows important elements that reported feeling under pressure to see patients within their allotted time ought to be implemented in the patient continuity care, and that the cystic but also valued the improved efficiency. fibrosis specialist team is of fundamental importance to the parental ability Conclusion: The use of staggered arrival times and a set clinician sequence to accept and to cope with the diagnosis and the new living conditions. significantly reduced patient idle time and improved clinic flow. However, the lack of flexibility in the model could cause problems, for example, if P369 patients were late for their appointment or clinicians needed longer than Annual review process at the Leeds Paediatric Cystic Fibrosis unit: how their allotted time. Further PDSA cycles are required to optimise the clinic are we doing? model. J. Lowdon1, J. Costello1. 1Leeds Children’s Hospital, CF Unit, Leeds, United Kingdom P371 The experience of adult cystic fibrosis patients about their care Objectives: All patients with cystic fibrosis (CF) should be offered a pathways comprehensive annual review (CF Trust 2011). It had been observed that 1 1 1 1 2 1 S. Therouanne ,T.Perez , O. Le Rouzic , J. Vanneste , M. Seillier ,A.Prevotat . some of our patients do not receive a full annual review (AR) and for others, 1 2 CHU Lille, Adult CF Centre, Lille, France; Lille University, Lille, France the process had taken several months to complete. No standards presently exist for our AR process. We decided to investigate how many patients Introduction: Cystic Fibrosis (CF) is a complex chronic condition. received a full AR, review time lines within the process and how outcomes Improvement in treatments and care coordination have been increasing could be improved. Standards can then be developed and audited. patients’ lives expectancy, consequently the number of adults’ patients Methods: Patient notes were reviewed (paper and electronic) for 2018 having more comorbidities. Current medicine is thought in terms about AR, to identify: completion of blood tests, results discussed with pathways of cares, health and lives. Legislation advise to hear more the family, multidisciplinary team (MDT) discussion completed and an AR users’ voice in health services. The objective of the study was to assess the letter sent to families. This information was recorded on an electronic experience of French CF adult patients followed in Lille, about their whole spread sheet. care pathways. S160 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Methods: That prospective and qualitative study has consisted in semi- P373 structured interviews of 14 patients who have been chosen for their An online dialogue as a way to evaluate transition from paediatric to particularly complex pathways. The interview guide and evaluation criteria adult outpatient care in cystic fibrosis patients are based on literature. A.M. Tiesinga-van der Lijn1, K.J. Kroon1, G.H. Koppelman1, H. v.d. Vaart1. Results: Patients are the main coordinator of their own care pathways. CF 1UMC Groningen, Groningen, Netherlands centre healthcare professionals are seen as coordinators of support and bring the expertise. The main difficulty for the patient is to integrate the Objectives: In 2016, the UMCG started a new transition outpatient clinic to care pathway in their life course. Between the daily treatments and the improve the transition to adult care. It included shared consults of the coordination of care between the different health professionals (home and paediatric and the adult care givers. Since segregation of CF-patients limits hospital), CF patient have a serious care burden to bear. The disease a group conversation and a questionnaire gives less information and no requires great organization. CF Centres have to help them to spare time in interaction between patients and CF care givers, we choose to evaluate our the hospital care pathways. Patients express their will for empowerment. A transition clinic with a so called “online dialogue”. lever of the care pathway is a “work of agreement” found with home Methods: An online dialogue is a secured online environment in which healthcare professionals. This study also highlights the importance of a people anonymously can reply or react to questions or reactions. We therapeutic alliance between patients and physicians, regardless of invited two groups, 1 with CF patients and 1 with parents/caregivers. They compliance or not to treatment. were contacted by phone. When they agreed to participate, the date, link Conclusion: CF Adult patients are the pilots of their cares pathways. The and online password were sent by email. During the dialogue, the patients therapeutic alliance is essential to integrate treatments and care more or caregivers saw the question or proposition and were invited to respond. easily into their life course, and to avoid breaks in this course of care. A true An objective chairman was in charge of putting the questions online. The and efficient partnership between patients and healthcare professionals members of the CF-team were in the same room as the chairman. After the has to be created to reach better success in fitting care pathways, taking all online dialogue, patients and caregivers were asked to comment on this their needs into account. method as a tool to evaluate quality of care. Results: 9 patients and their parents/caregivers were asked to participate. 3 P372 patients and 4 parents agreed. The online dialogue lasted 1 hour for each Transition: the rights and wrongs according to young adults group. Everyone responded to the questions and evaluated the dialogue as 1 1 2 1 1 “sufficient” or “good”. 6 participants were enthusiast to participate again in T. Havermans , C. Ruelens , E. Vleugels , R. Thewissen , F. Hoebrechts , 1 1 1 the future. A full report with all statements and responses became available L. Dupont , M. Proesmans . UZ Leuven, CF Centre, Leuven, Belgium; 2 to the CF-team. All members were enthusiastic about the online dialogue Katholieke Universiteit Leuven, Leuven, Belgium as a method to evaluate Objectives: A well-established transition program is associated with CF-care. increased satisfaction, more independence, and increased self-manage- Conclusion: An online dialogue seems to be a patient friendly, informative ment (Coyne et al, 2017). The present research aims to evaluate a single and interesting alternative method to evaluate CF-care. Unfortunately, the centre’s transition program through the eyes of young adults who have group was small which limited the discussion and might not reflect the transitioned over the past 5 years. whole CF population. It would be interesting to repeat this dialogue in a Method: Young adults were invited to discuss experiences with transition- larger group of patients. ing and give recommendations for improvement. Medical parameters included FEV1%predicted (FEV1), BMI and number of hospitalizations. P374 Results: 31 patients transferred of whom 28 participated in the transition Evaluation of anxiety levels in a paediatric cystic fibrosis population 1,2 1, 2 1,2,3 4,5 6 2,7,8 program (see table 1). BMI improved, FEV1 declined (p < 0.01). Few patients K. Paida , I.R. McKay , M.J. Coffey , N. Kasparian ,T.Katz , C.Y.Ooi . spontaneously recalled being prepared for transfer, but nearly all felt 1Univ. of New South Wales (UNSW), School of Women’s and Children’s Health, positive about the adult clinic, e.g. ‘more freedom’. Most patients felt an Medicine, Randwick, Australia; 2Evaluating the Alimentary and Respiratory evaluation after transfer would be valuable and made suggestions for Tracts in Health and Disease (EARTH) Research Program, Randwick, Australia; improvement, e.g. meeting the head nurse from the adult clinic. Valued 3Sydney Children’s Hospital, Sydney, Australia; 4Cincinnati Children’s Hospital items of the program were: 1. the tour in the adult centrea; 2. practical Medical Center, Cincinnati Children’s Center for Heart Disease and the information on the adult’s team organisation and 3. information from Developing Mind, Division of Behavioral Medicine & Clinical Psychology and social work regarding work, insurance or benefits. the Heart Institute, Cincinnati, United States; 5University of Cincinnati College 6 Table 1. of Medicine, Department of Pediatrics, Cincinnati, United States; Sydney Transition data from medical file (n = 31) and interview n = 28) Children’s Hospital Randwick, Dept. of Nutrition and Dietetics, Sydney, Australia; 7Univ. of New South Wales (UNSW), 4Molecular and Integrative At transition At interview Cystic Fibrosis (miCF) Research Centre, Sydney, Australia; 8Sydney Childrens Hospital, Dept. of Gastroenterology, Sydney, Australia Age (mean; SD) 18.1 (0.6) 21.1 (1.6) School/work student = 16; work = 11; combined = 2; Objectives: Several studies involving adults and adolescents with cystic unemployed = 2 fibrosis (CF) have demonstrated increased levels of anxiety and depressive FEV % pred. 86.7 (16.9) 78.4 (21.3) 1 symptoms, and lower health-related quality of life (HRQOL) compared with BMI 21.6 (2.5) 22.3 (2.9) Time since transition 36.2 months (18.7) healthy peers. Less is known, however, about the mental health and HRQOL range 1–66 of younger paediatric patients with CF. This study aims to fill this gap. Mean nr. of hospitalisations 3.2 (range 0–18) Methods: This is the preliminary cross-sectional analysis of data collected since transfer as part of a larger prospective longitudinal cohort study underway at Transition contacts Social work = 23; Nurse = 24; Tour ward = 20; Sydney Children’s Hospital. Data was collected for both CF and healthy Meeting adult Physician = 6 control (HC) participant groups using age-appropriate surveys provided by Preparation sufficient Yes = 23 No = 5 the Spence Children’s Anxiety Scale and analysed against validated Australian population norms. For participants under 8 years, data was Conclusion: Nearly all patients were satisfied with their transfer. Recall of collected through parent-proxy reported surveys and for participants older the transition process and program was not spontaneous. This suggests than 8 years, child-reported data was collected. that transition is part of their normal development, expected, and Results: The sample comprised of 44 CF (23 males (52%), mean (SD) age of imbedded into their care. To further optimize individual transitions, a 8.2 (5.0)) and 37 HC (19 males (51.3%), mean (SD) 8.2 (5.3)). Mean T-scores post-transfer evaluation is planned, as well as the inclusion of knowledge scores reported for each anxiety symptom cluster by parent-proxy- and self-management assessment tools. reported and child-reported data (generalised anxiety, p = 0.19, 0.90; social anxiety, p = 0.15, 0.70; obsessive compulsive disorder, p = 0.38, Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S161 p = 0.51; panic disorder p = 0.35, 0.81; fear of physical injury, p = 0.13, 0.62) referrals for those scoring in the moderate to severe range 3) implemen- did not differ significantly between CF and HC groups. Separation anxiety tation successes; and 4) plans for sustainability of the screening program. was also similar between HC and CF groups in child-reported data only Results: Approximately 20% of adolescents and adults endorsed suicidal (p = 0.11). In parent-proxy reported data, the HC group reported higher ideation in both years; 100% of centres reported having a plan to address separation anxiety scores compared with CF patients (p = 0.05). Even so, suicidal ideation and 98–99% of centres tracked those endorsing this both groups symptom levels were not clinically significant. symptom. Percentage of centres rating themselves as adequately trained to Conclusion: Despite currently having a small sample size, these prelim- intervene or refer patients scoring in the moderate to severe range inary results suggest a potential difference between the paediatric CF improved from 83% in 2017 to 88% in 2018. In 2017, 36% of MHCs provided population, and the adolescents and adults investigated in existing interventions in clinic and 14% referred to outside providers, increasing in literature. 2018 to 54% and 19%, respectively. Top rated successes in 2018 were: 1) early identification of symptoms, 2) improved access to psychological P375 services, and 3) reduced stigma about mental health challenges. Adults with cystic fibrosis: mental health and patient experiences of Sustainability plans included: billing for services, institutional support, the cystic fibrosis treatment and philanthropy. L. Backström Eriksson1, 2. 1Karolinska Institutet, Department of Clinical Conclusion: A significant number of adolescents and adults endorsed Neuroscience/Division of Psychology, Stockholm, Sweden; 2Karolinska suicidal ideation, however, nearly all CF centres had a plan to address and University Hospital, Stockholm CF-Center, Stockholm, Sweden track this. Training to intervene or make referrals in more severe cases improved. Given the prevalence of several mental health symptoms, efforts Objective: Sweden has a CF population with pronounced survival rate and are underway to sustain annual mental health screening in CF centres. a high proportion of adults. Acknowledgement: Cystic Fibrosis Foundation. The aim of this thesis was to explore mental health and patient experiences of the CF treatment among Swedish adults with CF. P377 Methods and results: Study I, cross-sectional, n = 129 and published Results of 2018’s mental health screening among 156 adults at two studies in Belgian/British/German adult CF-patients and corresponding cystic fibrosis centres in Sweden GP-data, HADS. Binary logistic analysis: No risk for anxiety/depression. 1 1 2 2,3 S. Järvholm , M. Gilljam , I. deMonestrol , L. Backström Eriksson . ANOVA: anxiety was slightly elevated in the Swedish CF-sample, but only 1 Gothenburg, CF-Center, Adult Clinic, Sahlgrenska University Hospital, in the women. 2 Gothenburg, Sweden; Stockholm CF-Center, Karolinska University Hospital, Study II, cross-sectional, n = 68, HADS + CFQ-R, Structural Equational 3 Stockholm, Sweden; Division of Psychology, Karolinska Institute, Stockholm, Modelling (SEM): individuals with severer cftr mutation classes with age/ Sweden parallel deterioration of health get poorer psychological wellbeing (PW). Exercise had a positive effect on PW only if it also had a positive effect on Objectives: Anxiety and depression is common among persons with CF health. and guidelines suggest annual screening for mental health problems Study III, longitudinal, n = 68, HADS, Latent Growth Modelling (LGM): (Quittner et al., 2016). However the present knowledge is multifaceted anxiety, especially when combined with depression, was associated with a regarding differences in vulnerability regarding to age, gender and cultural faster decline in lung function. differences. The objective of this study was to assess levels of anxiety and Study IV, qualitative, n = 12. Semi-structured interviews; ‘older’ (32–55 yrs) depression among adults from 18 years. non-transplanted adults. Inductive content analysis: three themes; Methods: Adult patients (n = 250 < 18) attending two CF centres in Sweden ‘Prioritize and manage health – a life condition’, ‘Aspiration for and (Stockholm, Gothenburg) during 2018, representing 59 % of the adult possibility to a ‘normal life’ and ‘The CF centre – a constant partner’. Swedish CF-population, were asked to complete the GAD-7 and PHQ-9 Conclusion: No elevated risk for anxiety/depression, but individuals with forms at the time of their annual review. The screening results were genetically severer CF get with age/poorer health lower PW, also recorded in the national CF-register. The forms were reviewed within a individuals exercising a lot without maintaining health. Anxiety can give week and a clinical action plan was made for patients with high scores. a faster decline in lung function. Prioritization of health is a life condition, Results: In total 156 individuals (62 %) were screened for anxiety and and aspiration/possibility for a ‘normal life’ can result in stress. Partnership depression (53 % males, 10 % lung transplanted). Median age was 32 years with the CF-centre including the patients’ perspective facilitate the (min 18; max 76). The median for GAD-7 was 2 (min 0; max 18) and for patients’ coping with the life condition. PHQ-9 it was 3 (min 0; max 18) There were 9 patients (5 %) scoring > 10 for GAD-7 and 17 (10 %) >10 for PHQ-9 indicating moderate or severe P376 symptoms of anxiety and/or depression. Six patients had elevated scores Prevalence and treatment of severe mental health symptoms at 120 for both. No significant differences were found when comparing gender cystic fibrosis centres: clinician preparation to intervene and sustain and/or age (18–29, 30-) regarding levels of anxiety (p = 0.22, p = 0.36) and mental health screening depression (p = 0.81, p = 0.94) in contrast with results from a previous A. Quittner1, S. Hussain2, E. Muther3, J. Abbott4, L. Tillman5, M. Schechter6, study which found an elevated risk for anxiety among young adults (<30) S. Hempstead7, P. Lomas7, B. Smith8. 1Nicklaus Children’s Hospital, Research (Järvholm et al,. 2020). Institute, Miami, United States; 2Nicklaus Children’s Hospital, Research Conclusion: Although the results are reassuring, these differ from norm Institute, Miami, United States; 3University of Colorado, Children’s Hospital of population since the common gender and age differences were not found. Colorado, Denver, United States; 4University of Central Lancashire, Preston, The strain of living with CF maybe merges these differences. The non- United Kingdom; 5Cystic Fibrosis Foundation, Community Advisor, Bethesda, participating proportion was fairly large although the screening was United States; 6Virginia Commonwealth University, Children’s Hospital of structured and was considered to be important both among staff and Richmond, Richmond, United States; 7Cystic Fibrosis Foundation, Bethesda, patients. This indicates not noticed obstacles in implementing a well- United States; 8State University of New York, Child & Adolescent Psychiatry, functioning screening. Buffalo, United States

Objectives: To intervene or refer those with moderate to severe symptomatology; To evaluate sustainability of mental health screening programs at U.S. CF Centres receiving seed funding from the CF Foundation. Methods: An 80-item survey was sent to 120 CF centres that received funding for a Mental Health Coordinator in 2017 and 2018. CF centres reported on 2 years of data. Questions systematically evaluated: 1) endorsement of suicidal ideation, 2) ability to provide interventions/ S162 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

P378 several CFQ-R domains: Vitality, Eating, Body, Role, Respiratory and Psychosocial impact of Mycobacterium abscessus infection in adults Digestive (p < 0.05). Strong evidence of convergence has been found with cystic fibrosis between the GI Symptom Tracker scales and the CFQ-R Digestive domain S.F.H. Zaki1, W.G. Flight2, K.S.A. Chapman2, S.J. Chapman2. 1University of (r = −0.48, −0.55, −0.28, −0.24), p < 0.05. Oxford, Medical Sciences Division, Oxford, United Kingdom; 2Oxford University Conclusion: This is the first study in CF that examines potential links Hospitals NHS Foundation Trust, Oxford Adult Cystic Fibrosis Centre, Oxford, between psychological, GI symptoms and HRQoL. Abdominal Pain and United Kingdom Stools scales have the higher scores highlighting that both are recapitu- lating the worst pattern of symptoms. We have found consistent Background: Cystic fibrosis (CF) patients are at higher risk of psychological associations between depression/anxiety and worse scores on the GI morbidity. We hypothesised that Mycobacterium abscessus infection may measure. As expected, worse GI symptoms were related to worse HRQoL. lead to a further psychological burden, perhaps due to complex treatment regimens or enhanced measures to prevent cross-infection. P380 Methods: Patients with CF and a history of M. abscessus infection attending Quality of life in Bulgarian cystic fibrosis patients – now and then our centre were identified. The HADS and the CFQoL scores at annual 1,2 3 1 G. Petrova , S. Shopova . University Hospital Alexandrovska, Pediatric review before and after diagnosis of M. abscessus infection were compared. 2 Clinic, Sofia, Bulgaria; Medical University Sofia, Pediatric Department, Sofia, Age- and sex-matched controls with CF but no history of M. abscessus 3 Bulgaria; Medical University Sofia, Sofia, Bulgaria infection were identified. Most recent HADS and CFQoL scores in the two groups were compared, with better psychological wellbeing represented Objectives: With the new therapeutic options and improved health care in by lower HADS and higher CFQoL scores. the last decades it is expected that cystic fibrosis (CF) patients have better Results: 25 patients with a history of M. abscessus infection and 25 controls Quality of life (QoL). were included. The groups were well matched with mean age 30.0 We aimed to see whether QoL in Bulgarian CF patients had been improved (SD = 11.0) in the M. abscessus group and 29.6 years (SD = 9.7) among in 2019 compared to the data we have from 2006. controls. M:F ratio was 15:10 in both groups. Mean FEV1%-predicted was Methods: In September we conducted a study for QoL in 78 CF patients by 60.1% (SD = 21.9) in the M. abscessus group and 69.1% (SD = 23.1) among using a short version of the WHO questionnaire for QoL. All 31 questions controls. Mean BMI was 21.6 kg/m2 (SD = 5.3) and 21.5 kg/m2 (SD = 3.8) were analysed separately and as whole, as well we compared them two by respectively. two. Due to heterogeneity of the matters in the questions we grouped them Mean HADS score in the M. abscessus group was 13.0 (SE = 3.0) compared to in several areas to analysed different aspects of life: physical appearance, 7.8 (SE = 1.7) for controls. The mean CFQoL score was 68.8 (SE = 5.1) in the emotional health, social interactions, health care and social status. M. abscessus group compared with 71.5 (SE = 4.6) for controls. When The results were compared with previous study of 36 CF patients with the including all recorded questionnaire scores, there was an inverse same tool, conducted in 2006. correlation between HADS and CFQoL scores (R2 = 0.657, n = 110) with Additionally, for the group in 2019 more detailed questionnaire for psycho- individual patient R2 values ranging from 0.0006 to 0.8751. social support was also used. 7/25 (28%) patients had complete HADS and CFQoL data before and after M. Results: Surprisingly, the results in 2019 were lower than the ones in 2006 abscessus infection. Mean HADS was 7.7 (SE = 2.4) before and 8.1 (SE = 2.8) in regards self-esteem of the health, physical health, emotional functioning after M. abscessus infection while the mean CFQoL increased from 71 and total QoL score. The results for social interaction and health care (SE = 7.8) to 79 (SE = 6.5). however were better in 2019. All this could be explained mainly with the Conclusions: M. abscessus infection in adults with CF may be associated wide internet invasion in everyday life so the patients can exchange with lower psychosocial status. Larger studies could confirm this information faster and could find better support in special closed patient association and explore possible causes. groups. However again the information also brings all the news for the newest therapy options which are not available yet in Bulgaria. Comparing P379 themselves to CF patients from other countries Bulgarian patients are Relationship between psychological symptoms, gastrointestinal anxious and frustrated for being deprived by gene-modulator therapy, symptoms, and Health-Related Quality of Life in cystic fibrosis (HRQoL) special nutrition supplements, some inhaled antibiotics, lack of working S. Graziano1,2, F. Ciciriello2, F. Alghisi2, D. Righelli3, A.L. Quittner4, lung transplant program. F. Boldrini1, 2, V. Lucidi2, P.Tabarini1, 2. 1Bambino Gesù Children’s Hospital, Unit Conclusion: The Bulgarian CF patients in 2019 have better knowledge for of Clinical Psychology, Rome, Italy; 2Bambino Gesù Children’s Hospital, Unit of the disease and the treatment options, but due to many obstacles they face Cystic Fibrosis, Rome, Italy; 3National Research Council, Institute for Applied at home they do estimate their QoL much lower than the “ignorant” Mathematics ‘M. Picone’, Naples, Italy; 4Nicklaus Children’s Hospital, Nicklaus patients back from 2006. Children’s Research Institute, Miami, United States P381 Objectives: CF patients report substantial gastrointestinal symptoms (GI), Cystic fibrosis – better late than never even if they are taking enzyme replacement therapy. Recently in the US, a 1 1 1 1 1 G. Aldous , J. Daniels , D. Nazareth , M. Walshaw . Liverpool Heart & Chest standardised measure, the GI Symptom Tracker, has been developed and Hospital, Adult CF Service, Liverpool, United Kingdom validated. The Italian adaptation was completed. Given new evidences that psychological symptoms can increase inflammation in individuals with Introduction: With the increased awareness of the CF condition in adults chronic disease, this study aimed to evaluate the relationship between GI and the availability of tests for less common CFTR mutations, more symptoms, depression/anxiety, and HRQoL. attention has been placed on the late diagnosis of the adult pwCF. We Methods: We recruited 79 consecutive CF patients with pancreatic wished to explore in more detail the characteristics of this cohort of pwCF insufficiency (F/M = 44/35; mean/SD age = 26/9.7), aged 14 years and who have a late diagnosis. older. We excluded patients with other chronic diseases or on intravenous Method: We reviewed the clinical records of the last 12 consecutive pwCF antibiotics. All patients completed: Italian GI Symptom Tracker, PHQ-9, diagnosed as adults cared for at our large Adult CF Centre (n = 347), looking GAD-7, CFQ-R+14. at referral source, genotype, lung function, infection status, imaging, and Results: Elevated scores on GI Symptom Tracker scales were found: other comorbidities. Abdominal Pain (mean/SD = 54/16); Stools (mean/SD = 59/16); Eating Results: Four (age range 31–42 years, 3 male) were referred via fertility Challenges (mean/SD = 42/15); and Adherence Challenges (mean/SD = 42/ services, 7 [33–55 years, 4 male] via a respiratory clinic and 1 male age 56 15). Elevated depression and anxiety were found (46%, 35%). Correlations years with abdominal symptoms and a strong family history. As regards indicate that all GI Symptom Tracker scales (Abdominal Pain, Stools, Eating genotype, 8 were DF508 heterozygous, 5 had at least 1 copy of R117H and 3 Challenges, Adherence Challenges) were significantly, positively correlated had 1 gene with a positive sweat test. Median FEV at diagnosis was 77% with PHQ-9 scores (r = 0.35, 0.41, 0.49, 0.46); and GAD-7 scores, (r = 0.27, predicted [range 35–117], 6 were infected with PsA, 5 with Staph aureus, 0.18, 0.16, 0.36), p < 0.05. More GI symptoms were also associated with and 2 with Hemophilus. Half had radiological evidence of bronchiectasis, Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S163 half were pancreatic sufficient, and 4 were subsequently diagnosed with indicated that such support would be very (23%) or extremely useful (42%) CFRD. All of these patients have been offered support from the CF for parent/caregivers and/or siblings. psychology team and are at various stages of accessing it. The CF MDT were surveyed to explore their thoughts on current mental Conclusions: CF people with a late diagnosis have a more heterogeneous health service provision. presentation, with fewer typical manifestations and less severe CFTR All rated the clinic “below average” or “far below average” in meeting the mutations. Although the majority are still referred via chest physicians mental health needs of patients and families. 92% felt ill-equipped to there are an increasing number being referred via fertility services. provide mental health care and 85% said they had insufficient time to do so. Psychological co-morbidity is an issue and requires expert input from the 80% believed mental health affected a caregiver’s ability to provide care and CF psychology service. 90% believed a child’s mental health affected their ability to comply with treatments. P382 These results have guided a successful submission to the hospital to Development of a new information resource on body image for people improve mental health services through the provision of increased staff with cystic fibrosis and time allocation. J. Ali1, H. Davis Bollard1,A.Taylor1. 1Cystic Fibrosis Trust, London, United Kingdom P384 Mental health changes in patients starting Orkambi treatment? Objectives: To develop a new information resource about body image, an A first-year follow up area that can be particularly challenging for people with cystic fibrosis. The 1, 2 1, 3 1 1 L. Backström Eriksson , I. de Monestrol , C. Laine . Karolinska University aim of the resource was to provide support and encouragement to adults 2 Hospital, Stockholm CF-center, Stockholm, Sweden; Karolinska Institutet, with CF dealing with body image issues, and to encourage discussion of the Department of Clinical Neuroscience/Division of Psychology, Stockholm, topic. 3 Sweden; Karolinska Institutet, Department of Clinical Science, Intervention Methods: The Cystic Fibrosis Trust consulted with people with CF and and Technology/Division of Paediatrics, Stockholm, Sweden experts from the CF multidisciplinary team including psychologists, dietitians and physiotherapists to develop the content. Feedback was also Objectives: Some case reports and studies propose a worsening mental received from the Trust’s Clinical Advisory Group and Youth Advisory health status in some individuals starting treatment with the new CFTR Group. The resulting booklet features four case studies (two male, two modulating drugs. It is therefore of importance to follow up and explore female) who were photographed for the resource and shared their stories how mental health is affected in CF-patients using these medications. relating to body image, along with quotes from other people with CF. Topics The aim of this study was to longitudinally investigate mental health, with covered included sweating, scarring, coughing, use of oxygen, looking regard to indicators of anxiety and depression, and its association with lung young, and use of ports. The booklet was designed in the style of a function, in CF-patients during their first year of Orkambi treatment. magazine, to create an appealing and informal resource that would Methods: Patients at Stockholm CF-centre, Sweden, have consecutively encourage discussion on the subject matter. It was complemented by a since August 2018 in connection to their annual check-up started with short film featuring the case studies on the Cystic Fibrosis Trust’s website, Orkambi. As a part of their first year Orkambi follow up patients who are and additional web content. The booklet, entitled Body Image and Cystic +12 years of age complete questionnaires measuring indicators of anxiety Fibrosis, was published in July 2019. and depression. The questionnaires are completed at baseline, and at 3- Results: The booklet was published online on 29th July 2019. In the first and 12 months follow up. Youths (12–17 yrs) complete Becks Youth week of its launch it was downloaded 618 times and 42 copies were Inventory (BYI-II) anxiety (BAI-Y) and depression (BDI-Y). Adults (≥18 yrs) ordered in print. As of 17th January 2020, the booklet had been complete Patient Health Questionnaire (PHQ-9) and General Anxiety downloaded 1,182 times and 302 copies ordered in print. Feedback on Disorder 7-item scale (GAD-7). Data collection is ongoing. Multi-level the booklet has been very positive; its publication also stimulated modelling will be used to fit models to data. discussions across the Trust’s social media channels. Preliminary results: In total 46 individuals (11 youths, 35 adults) have Conclusion: Body image is a topic of relevance to many people with CF and initiated the data collection. Until December 2019 39% of the sample had a magazine-style publication worked well with the content and appealed fulfilled the data collection, 46% of the total sample had participated in the to the target audience. The Cystic Fibrosis Trust is now exploring data collection until the 3 months follow up. The majority of the remaining development of a further resource for younger people with CF who can participants will fulfill the data collection during spring 2020. Data will be also experience body image challenges. analysed as close to the ECFS conference to ensure a high representative- ness. Results will be presented at the conference. P383 Conclusions: The results from the present study will increase knowledge Exploring the need for enhanced mental health services in a paediatric of possible effects of the CFTR modulators on mental health. This cystic fibrosis clinic knowledge will help CF care to develop an adequate level of psychological S. Hunt1, A. Kench1, S. Simonds1, C. Boyton1, A. Middleton1,R.O’Connor1. follow up and support to the group of patients starting treatment with 1The Children’s Hospital at Westmead, Respiratory Clinic, Sydney, Australia these medications.

The Cystic Fibrosis (CF) clinic at the Children’s Hospital at Westmead P385 provides care for 210 patients with a large multidisciplinary team (MDT). Screening of depression and anxiety disorders in cystic fibrosis patients Current dedicated CF psychosocial services include a 0.5FTE social worker. and their parents This falls well below Australian and international recommendations of 1 2 2 2 H.H. Mursaloglu , P. Ergenekon , C. Yilmaz Yegit , Y. Gokdemir , approximately 1.5 FTE per social worker and psychologist for clinics of this 2 2 2 1 E. Erdem Eralp , F. Karakoc , B.T. Karadag . Marmara University, Istanbul, size. In 2014 Quittner et al reported anxiety and depression in the CF 2 Turkey; Marmara University, Paediatric Pulmonology, Istanbul, Turkey population and parent caregivers to be 5 times higher than the general population. In response the international CF community made recom- Objectives: Depression and anxiety symptoms in patients with cystic mendations for mental health care of people with CF. fibrosis (CF) and their caregivers are 2–3 times higher than normal Objectives: To assess CF family and MDT satisfaction with access to population. The aim of this study is to assess the prevalence of anxiety and psychosocial services in the clinic. depression disorders and to determine possible risk factors in CF patients Method: A survey conducted in 2018 was completed by 104 families (49%). and their parents at Marmara University CF centre. They were asked about current mental health service provision. Methods: The study included 132 CF patients. Patient Health Questionnaire Results: 53% indicated they were rarely or never asked about their child’s (PHQ-9) and Generalised Anxiety Disorder Questionnaire (GAD-7) were mental health. While 68% of families rated their child’s mental health as used to screen depression and generalized anxiety disorders. The excellent, 63% said psychological support through the CF Clinic would be questionnaires were completed by 51 CF patients (aged >12 years) and very (27%) or extremely (37%) useful. Furthermore, 66% of respondents 130 parents of CF patients (aged 0–17 years). S164 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Results: While moderate to severe depression were seen in 25.5% of resulted in a change in practice. The most common results outside the patients, 33.7% of mothers and 14.6% of fathers; moderate to severe anxiety normal range were a raised IgE level, and this was most commonly in the were present in 17.6%, 21.8% and 8.5%, respectively. None of the third AR year. In 13 out of 26 clinically significant LFT results across all ages, demographic characteristics were identified as a predictor of depression raised liver transaminase levels resulted in the initiation, or a change in or anxiety. GAD-7 scores have shown higher incidence of anxiety in dose, of ursodeoxycholic acid therapy, making this the blood test that mothers of patients with chronic methicillin-resistant Staphylococcus prompted a change in management most often. aureus. Additionally, hospitalisation in the last 12 months was statistically Conclusions: The majority of blood tests undertaken in well pre-school significant in PHQ-9 scores of fathers. children with CF do not lead to a change in management. Following these Conclusion: Depression and anxiety were common in CF patients and their results, we changed our practice. We will undertake routine AR venous parents. These results show the importance of depression/anxiety screen- blood tests at ages 1, 3 and 5. At 2 and 4 years of age we will limit AR blood ing tests and psychosocial support in patient follow-up. testing to liver function tests only (via a capillary sample). Blood tests will continue to be ordered if there is clinical concern. We will monitor this P386 change prospectively with the hope of further reduction in testing over Children and adolescents with cystic fibrosis: overcoming procedures time. with less pain and anxiety K.B. Kjeldsen1, L. True1. 1Rigshospitalet (Copenhagen University Hospital), P388 BørneUngeKlinikken, Copenhagen, Denmark Psychosocial status and psychological issues in patients with cystic fibrosis Objectives: In Copenhagen CF Centre, we treat approximately 100 patients 1 1,2 1 1 aged 0–18 years. They are seen at a monthly visit and must participate in B. Minova Georgieva , M. Veleska , T. Jakjovska . Institute for Respiratory Diseases in Children, CF Department, Skopje, North Macedonia, The Republic examinations and treatments when necessary; Laryngeal suction, blood 2 tests, and intravenous treatment. Many patients react to these of; Institute for Respiratory Diseases, Kozle, CF Department, Skopje, North procedures with anxiety, physical and psychological reactions. Macedonia, The Republic of Our aim is to reduce and prevent pain and anxiety when patients Background: Psychosocial isolation is common among patients with CF participate in various procedures in the CF Centre. chronic illness itself, poor psychosocial functioning leads to poor quality of Methods: Existing advice has been discussed and implemented in our life. Our goal is to monitor the psychosocial status and their psychological daily work. New approaches have been introduced; offering the child/ issues to improve the mental health and quality of life of patients with adolescent an ice cream or a present after a procedure, consistent use of Cystic Fibrosis. EMLA, the nurse staff has been certified in using laughing gas (Nitrous Material and methods: oxide). Furthermore, virtual reality (VR) glasses, with a specific game, has • We used the medical records of the CF patients who regularly visited been purchased. For patients with severe anxiety, individual contracts the CF Department at the Institute of respiratory diseases in children- between them, the parents and the staff has been developed. The contract Skopje. describes the strategies and tools, that can be offered to overcome the • Surveys that represent the psychosocial status and needs of patients. procedure. • Individual sessions and counselling. Results: Several patients have tried different approaches during the last 6 months. Almost every patient aged 0–18, have been introduced to EMLA, Results: The study included 31 patients (15 were male and 16 female) they have been offered age-appropriate rewards after a procedure, and during their hospitalisations at CF department. Each patient faces a approximately 50 children aged 4–15 have tried VR glasses. rejection and stigmatisation of the environment. 16 of them have trouble 5 patients tried laughing gas before laryngeal suction and vaccinations. finding deeper emotional bonds and friendships. None of them have any Contracts have been individually developed with two patients. extra hobbies in spare time. 71% are unemployed and has opinion that the Conclusion: Experiences show that our focus and the actions introduced state of R.N. Macedonia should provide them with jobs and regular helps the patients overcoming the procedures with less pain and anxiety. vacations. Common to patients are responses that include fear, insecurity, Next step is to interview patients, parents and nurses focusing on their anxiety, illness understanding, and general questions about their future. experience of the new approaches. These data will contribute in developing Positive attitudes are shared by those with stable emotional relationships a catalogue containing inspiration and tools, adapted to age and and adolescents in the school environment as opposed to those without a development, helping patients, parents and staff to reduce pain and emotional partner. anxiety. For poster presentation, the data from the interviews will be Conclusion: By identifying the emotional needs of these patients, the presented. health are team can better assist them in improving their quality of life. Gradually these young people develop trust and relationships. They P387 become self-aware and capable of social connections and develop Can we reduce the frequency of annual review blood tests in pre-school isolation-reduction techniques. children with cystic fibrosis? 1 1 2 1 V. Sadlers , S. Richmond , K.W. Southern . Alder Hey Children’s NHS P389 2 Foundation Trust, Liverpool, United Kingdom; University of Liverpool, The baseline psychological need of a paediatric cystic fibrosis Liverpool, United Kingdom population 1 1 1 1 Objectives: A key part of the care of children with CF is an annual review S. Jones , L. Smith , K. Ainsworth . Sheffield Children’s Hospital, Paediatric (AR), consistent with national guidelines. Blood tests are a routine Cystic Fibrosis, Sheffield, United Kingdom component of the AR, and can be challenging, especially in the pre- Objectives: In recognition of the psychological demands of Cystic Fibrosis school age group, and can be associated with the development of (CF), national and international guidelines (CF Trust, 2011; Conway, et al, significant procedural anxiety. We assessed annual reviews undertaken 2014) state that people with CF should have access to specialist integrated in pre-school children in our clinic and critically reviewed outcomes and responsive Psychology support within a multi-disciplinary team associated with blood tests. (MDT). In Sheffield (UK) there has been an unfortunate break in the Methods: Case notes were retrospectively reviewed for patients provision of an integrated Clinical Psychologist within the Paediatric CF aged between 5 and 10 years with a confirmed diagnosis of CF within team. As the majority of paediatric CF Centres in the UK have a dedicated our centre. Clinical Psychologist, the Sheffield population presents a unique oppor- Results: We identified 34 children each with five pre-school AR years, in tunity to assess the baseline psychological needs of the population. whom 1340 blood tests were ordered. 137 blood tests were unsuccessful or Methods: All clients (152) who are under the care of the Sheffield insufficient and not repeated. 162 results were reported as outside the Paediatric CF team will be approached to complete a baseline screening of normal range and deemed to be clinically significant and 33 of these their current psychological well-being during a 3-month period. Clients Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S165 will complete the Revised Children’s Anxiety and Depression Scale (RCADS; patient completed Short form 36 Health Survey Questionnaire (SF-36) Bruce & Chorpita, 2003) and CF Questionnaire – Revised UK Edition (CFQ- before and 4 months after education. R; Quittner, Buu, Watrous & Davis, 2002). Questionnaires will be Results: Four months after individual education, there was a 7% increase in administered either during routine clinic visits, or sent out to clients number of patients who responded their overall health was better than homes via post. before. Questionnaires indicate a positive trend in improving perception of Results: Results will be available in May 2020 following a 3-month one’s health and quality of life although there were no statistically screening window. Analysis will look at baseline trends in the data. Should significant differences after education. sufficient data be collected then further analysis looking at sub-popula- Conclusion: Although results are not statistically significant, patient’s tions will be conducted. education is an important part of treatment and eventually improvement Conclusion: This study will shed light on the baseline psychological need of quality of life. Results are impacted by a small sample, surveys are done within a paediatric CF population which has not had dedicated Psychology anonymously and answers are subjective which is not ideal. Quality of life input for a number of years. Results will allow the service to consider which survey was conducted only 4 months after education although the areas of need could be targeted and to plan work accordingly. We plan to assumption is to compare condition after one year. Further studies are revisit the screening programme again next year to investigate any impact needed. of having dedicated Psychology provision on the mental health of paediatric CF patients. The results of this study will help other centres P392 setting up a CF Psychology service when planning their service model. An investigation into the psychosocial challenges and quality of life in an adult cystic fibrosis population P390 S. Purewal1, H. Egan1, M. Mantzios1, R. Keytes1, E.F. Nash2, A. Regan2. Language matters: cystic fibrosis publications and their terminology 1Birmingham City University, Social Sciences/, Birmingham, E. Hoodless1,F.Frost1, M. Walshaw1, D. Nazareth1. 1Liverpool Heart and Chest United Kingdom; 2Birmingham Heartlands Hospital, Cystic Fibrosis, Hospital, Respiratory, Liverpool, United Kingdom Birmingham, United Kingdom

Objectives: Cystic fibrosis is a lifelong condition where people living with it Objectives: Patient views and experiences about the psychosocial have multiple interactions with healthcare professionals. As such, it is challenges faced as an adult with CF were investigated alongside the imperative that there is mutual respect and trust, and as part of this the impact on both health and well-being. There will also be a focus upon the language used, both verbal and non-verbal, is pivotal. Often communica- approach and attitude taken towards such challenges, exploring the roles tion can be stigmatising, hurtful and have a detrimental effect on clinical of mindfulness and self-compassion. These methods intend to inform the outcomes. People living with conditions such as CF wish to be acknowl- development of future interventions which aim to improve the quality of edged and treated as individuals, and not defined by their health life for the adult CF population. circumstances. Methods: 20 patients were either recruited as an outpatient or an inpatient Methods: To look at this further we searched Pubmed for all English from two regional adult CF centres over a three-month period. Semi- language articles relating to CF pertaining to humans published between structured interviews were conducted either in a private room at the centre January 2018 and October 2019. We looked for the terms ‘patient’ and in which the CF patient attends or if preferred via telephone and was ‘disease’, and where people with CF (pwCF) were referred to as ‘sufferers/ recorded using an audio-recording device. On average the interviews lasted suffering’, ‘subjects’, ‘participants’ or being ‘burdened’. We also searched for 40 minutes. Demographics and spirometry results (FEV1% predicted, for the word ‘cystics’, and finally where the terminology of ‘individual/ FVC), body weight, body mass index (BMI), current medications and people/young person with’ was used. comorbidities were recorded. Results: We found 1356 abstracts of basic science or clinical origin. The Results: [ongoing – will be ready by June] most common terms used were ‘patient’ (48%) and ‘disease’ (24%). People Conclusion: [ongoing – will be ready by June] were referred to as subjects in 5%, sufferers in 1%, and participants in 4%: none were labelled as cystics. The desired terminology of ‘individuals/ P393 people with cystic fibrosis’ was used in only 10% of articles. Cystic fibrosis path: a new educational tool for paediatric patients with Conclusion: Our results show that healthcare professionals managing cystic fibrosis building on participation and dialogue pwCF need to adapt the way in which they refer to these people. S. Diemer1, M. Mårtensson1, K. Björkman1, C. Hansen1. 1Skåne University Greater sensitivity is required to acknowledge that each and every Hospital, Lund, Sweden person is an individual, and not simply a ‘patient’. It is reassuring that the outdated term ‘cystics’ was not used at all in this timeframe. Other Objectives: Cystic fibrosis (CF) treatment is time consuming and complex. impersonal terms such as ‘subject’ should also be confined to historic In order to improve outcome for paediatric CF patients a high adherence literature. People living successfully with their condition do not want to be during adolescence and a well-prepared transition to the adult CF centre depicted as sufferers or under a burden, as this makes assumptions about are needed. At CF centre Lund we searched for a new education tool that their lives. can be used as early as age 7 to ensure well educated and competent CF patients at the time of transition. P391 Methods: In an online survey we asked our paediatric CF patients what was Can nurse-provided education improve quality of life in patients with important for them in their contact with the CF centre. We also engaged cystic fibrosis? our paediatric CF patients on how to build an educational training tool. 1 2 2 1 Results: Twenty patients, ages 10–18 years old, answered an online survey T. Odobasic Palkovic , D. Tjesic-Drinkovic , D. Tjesic-Drinkovic , I. Godic , 1 1 1 1 1 about the importance and experience in the fields of knowledge, I. Lalic , A. Sajnic , S. Karabatic , A. Vukic Dugac . University Hospital Centre participation, adherence and dialogue at the CF centre. Zagreb, Clinic for Respiratory Disorders ‘Jordanovac’, Zagreb, Croatia; 2 Most important for our paediatric CF patients was adherence (100%), University Hospital Centre Zagreb, Department of Pediatrics, Zagreb, Croatia followed by participation (70%), knowledge (68%) and dialogue (48%). In Objectives: Cystic fibrosis (CF) is a chronic progressive disease and patient terms of reported experience, 84% of our paediatric CF patients estimated education on the importance of lifelong treatment is very important to their knowledge high, 68% their participation high, 90 % their adherence improve the quality of life. The aim of this study is to show if nurse- high and 71% reported a good dialogue with the CF care team. provided education can improve quality of life in patients with CF. Our CF patients insisted that a training tool should be time efficient, up-to- Methods: 12 male and 14 female adult patients of Clinic for Pulmonary date and should improve competencies about CF. diseases Jordanovac were recruited for this study. Each patient received We developed a CF path starting at the age of 7 years and continuing in nurse-provided education on importance of respiratory clearance, medi- three steps until the age of 18 years. The CF path involves the whole CF Care cation, inhaler maintenance and demonstration of inhaler therapy use, the team at the Lund CF centre and builds on participation, dialogue and role of nutritional support and maintaining optimal body weight. Each transfer of competencies. At each clinical visit we discuss a topic at the age S166 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 relevant CF path together with our paediatric patient. Each CF path consists Type of Internal Picture of the Disease (IPD) (23.4%). A child is emotionally of two parts – a knowledge and an ability that we want to transfer to our stable, not fixed on the disease and might have a wide range of interests. paediatric CF patients. Mothers realistically estimate physical and emotional state of a child, take Conclusion: Early educational interventions are important to ensure into account his/her actual psychological needs. IPD with a Risk of competent patients with CF at the time of transition. The CF path is a new Maladaptation (66.6%). A child exhibits anxiety and unstable emotional time efficient tool for patient education that builds on participation and state, inadequate attitude towards disease shapes, and the range of dialogue. interests and activities narrows. It results from inconsistent manner of interaction, when parents fail to take into account child’s personal and age- P394 specific needs in full. Are children with cystic fibrosis given the necessary support to thrive Maladaptive Type of IPD (10%). A child is sulk, strongly fixed on his/her academically in primary school? physical state, and the range of interests is narrow. Parents’ attention is 1 1 1 1 1 overly fixed on the matters of treatment, mothers are focused on personal K.R. Jakobsen , H.W. Olesen , S. Højer , C.D. Dyekjær , P. Bonde , 1 1 feelings, are prone to communicate their anxiety to a child, underestimate M. Jeppesen . Aarhus Universitetshospital, Aarhus N, Denmark or overestimate his/hers actual physical capacities. Objectives: The aim of the study was to investigate if children with CF Conclusion: Child’s internal picture of the disease shapes under the attending primary school, had CF related school absenteeism, and whether influence of close adults and reflects their attitude towards the disease. The the children were limited academically by CF-related school absenteeism. purpose of work with a psychologist is teaching mothers a skill to minimize Methods: All parents to children with CF attending primary school, from negative impact of their feelings towards the disease on a child and a skill to 1–9 grade were invited to participate. 2 families who did not read or write focus on a child’s psychological needs. Timely medical and psychological Danish, were excluded. aid increases compliance positively affects a child’s and his/hers family’s An electronic questionnaire was distributed. emotional state, improves health condition and quality of life. 51 parents received the questionnaire. 49 parents responded, equivalent to 96%. P396 Areas of interest were the amount of CF related school absenteeism Examination of social media use in adults with cystic fibrosis and its throughout the last year (2018), causes of absence (cough, anxiety, teasing, application toward patient education: Twitter for CF #TOCF home treatment, fatigue, abdominal ache), are children affected academ- 1 2,3 4 5 6 A. Anand , R. Brydges , E. Kangasjarvi , P. Abhyankar , J. Sykes . ically by school absenteeism, and are children receiving extra teaching due 1 University of Toronto/St Michaels Hospital, Medicine, Division of Respirology, to school absenteeism. 2 Toronto, Canada; University of Toronto/St Michaels Hospital, Director of Average age 11 years. 71%(35) are homozygous. 3 Research, Allan Waters Family Simulation Centre, Toronto, Canada; University Results: of Toronto/The Wilson Centre, University Health Network, Medicine, Toronto, • 57% (28/49) of the children were having CF-related school absenteeism 4 Canada; University of Toronto/St Michaels Hospital, Centre for Faculty every month, besides 8–10 days of school absenteeism yearly, due to CF 5 Development, Faculty of Medicine, Toronto, Canada; University of clinic visits. 6 Newfoundland, Faculty of Medicine, Toronto, Canada; St Michaels Hospital, • As children grow older, CF-related school absenteeism increases: 1–3 Respirology, Toronto, Canada grade 33% (5/15), 4–6 grade 60% (9/15), 7–9 grade 74% (14/19) • Most frequent cause of school absenteeism was fatigue. Significant advances in Cystic Fibrosis (CF) care have resulted in adult • 29% (14/49) of parents believe extra teaching is needed. patients outnumbering children. In addition to their care needs, adult CF patients have unique educational needs. The infection control standards in 8% (4/49) of the children receive extra teaching in school. CF require modified approaches to delivering education to many patients at • As children grow older, the need of extra teaching in primary school once. We explored how education delivered via social media platforms – – – increases: 1 3 grade 20% (3/15), 4 6 grade 13% (2/15), 7 9 grade 47% might benefit CF adults. (9/19) Objectives: We aimed: ’ Conclusion: More than half of the children, had CF-related school 1. to investigate CF patient s usage patterns and attitudes toward social absenteeism every month. 29% of the children were limited academically, media, specifically, Twitter; and and only 8 % received extra teaching. 2. to assess the educational impact &experience of #TOCF on our patient Most frequent cause of school absenteeism was fatigue. population. An effort is needed to make children with CF thrive academically in school. We need to look at length of schooldays, extra teaching in school, and Methods: We circulated an anonymous needs assessment on social media parents’ loss of earnings. usage to the Toronto Adult CF patients. Survey results were summarised and analysed using the Mann-Whitney test for continuous variables and P395 Fisher’s exact test for categorical variables. We also collected analytics Special features of the internal picture of the disease among primary using the hashtag #TOCF, and conducted semi-structured interviews with school children suffering from cystic fibrosis social media and #TOCF users, as well as non-users to evaluate impact and 1 2 1 1 1 potential barriers. A. Gerasimova , T. Sviridova , S. Lazurenko , A. Buslaeva . National Medical Results: In 346 surveys, we found the majority used Facebook (91.4%), with Research Center for Children’s Health Federal State Autonomous Institution of only 33.6% using Twitter. Overall, 48.6% of participants expressed interest the Russian Federation Ministry of Health, Special Psycholigy, Moscow, Russian 2 in social media-based education for CF. Our interview data (n = 9 Federation; Federal State Autonomous Institution «National Medical Research participants) revealed that #TOCF sessions were found to be informative Center of Children’s Health» of the Ministry of Health of the Russian Federation and trustworthy due to knowing the source providers. Themes related to Moscow, Russian Federation, Special Psychology, Moscow, Russian Federation benefits included: education opportunities, sense of community, and Objectives: 30 junior children suffering from cystic fibrosis and their 30 “normalising” CF. Themes related to barriers included: irrelevant content, mothers. privacy concerns, worry of healthcare professional’s judgments in sessions, Methods: Analysis of medical and psychological documentation, method time constraints and character limitations. of diagnostics of a child’s attitude towards disease, questionnaire of Conclusion: Thus far, #TOCF appears to have positive uptake in this patient parents’ attitude. population. Potential improvement areas include using other social media Results: Combination of psychological features of a child and ability of a platforms, promoting the sessions more and considering asynchronous parent to take into account child’s objective health condition and focus on chats. Further innovations can refine how #TOCF can offer multidirectional, his/hers psychological needs determine the types of a child’s IPD: Adaptive impactful education to adults with CF. Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168 S167

P397 Conclusion: Most of the patients were able to work or study, a large group Victorian professional development for educators full-time. Notably only 8% had full long-term sickness compensation. J. Willis1,N.Bate1, K. Barnett1, J. Glazner2. 1Monash Health, Clayton, Australia; Further studies are recommended to examine medical aspects and 2The Royal Children’s Hospital, Parkville, Australia psychosocial factors in correlation with occupation. It would also be of interest to assess the impact on quality of life when balancing work, family Objectives: Children spend 6 hrs a day, 195 days per year, at school. During and managing CF. this time their teachers are responsible for them to provide education but also to manage any particular care each child might require. Imagine being P399 a teacher of a child with a chronic illness. Not only are you as the teacher The benefits of benefit advice: a collaborative approach to benefit responsible for this child’s education but also for their management of advice in Northern Ireland their illness during their school year. Cystic Fibrosis is a chronic illness A. Calvert1, M. McCafferty1, A.-M. McGrade2,D.O’Neill1, A.-M. McCann3, which affects more than 3379 people in Australia (Australian Cystic Fibrosis 3 2 1, 4 1 data Registry, 2015). Of these,1787 people are under the age of 19, therefore B. Donaldson ,A.Reid , C. Addy . Northern Ireland Regional Adult CF Centre, Belfast, United Kingdom; 2Northern Ireland Regional Paediatric CF being educated at a school or by educators. It is therefore very important to 3 educate these educators for these children with cystic fibrosis. Centre, Belfast, United Kingdom; Advice Space, Belfast, United Kingdom; 4 ’ Methods: Previously, both Monash Health and The Royal Children’s Queen s University Belfast, Belfast, United Kingdom Hospital have provided separate days. The annual day (we have had 4 Objectives: Relieving the financial burden of living with CF is of high days) was well received and always well attended. However, there was a importance to people with CF(PWCF). UK welfare reforms, combined with limited number of people able to attend from rural areas. We decided to an enlarging CF population make meeting the demand for benefit advice combine our resources and our knowledge to present this educational day increasingly challenging. A collaborative approach to benefit advice, together. The day was presented live at Monash Health and The Royal combining CF social work (SW) teams, with skilled welfare advisors was Children’s Hospital and streamed live to 5 ‘hubs’ throughout rural Victoria. implemented across Northern Ireland (NI) to address this. Results: Information was well received by 150 attendees. We presented live Methods: In 2015, a partnership between the paediatric/adult CF SW to 120 people across the 2 live sites and then streamed to 5 hubs teams, and the Advice Space agency was established. CF SW and Advice throughout rural Victoria. Space advisors underwent a reciprocal education programme to increase Conclusion: In 2020, we plan to stream live to more attendees. Following the advice quality given by both teams. A collaborative benefits service was the evaluation, we established that 1 day was very long for some people. created allowing joint access to support from both teams. In 2016, with the Therefore, we will run fortnightly sessions from 4–5 pm. This will allow introduction of new Personal Independence Payments (PIP), the service attendees to gather as a group within their own school or to be interactive widened its scope to provide education and a point of direct contact for PIP in the presentations from their own home. We will continue to evaluate assessors, ensuring accurate information was available to decision makers this education process. We will present 7 sessions each with different within the benefit system. topics. Results: Since 2015, PWCF and their families have accessed the service over 950 times. Since its introduction in 2016, over 500 contacts regarding PIP P398 assessment have been made. Since it’s start, in totality, £956,269.26 in Most adult patients with cystic fibrosis at Stockholm Cystic Fibrosis benefits has been awarded to PWCF in NI. One individual received £12,000 Centre have a full-time or part-time occupation in back-payments. M. Möller1, M. Al Shakirchi1, L. Backström Eriksson1, L. Hjelte1, A. Törnberg1, Service feedback has been overwhelmingly positive. PWCF have high- I. Durand De Monestrol D’Esquille1. 1Karolinska University Hospital, lighted reduced financial stress, anxiety, increased ability to make Stockholm CF Centre, Stockholm, Sweden informed financial decisions, and ease of making future work/health choices. The understanding and empathy shown by the advisors, combined Objectives: To give an overview of the occupation of adult CF patients at with their knowledge of the complexity of CF were also emphasised. Stockholm CF Centre. Conclusions: This collaborative benefit support service has been of critical Methods: Occupational data were collected from the Swedish National CF importance in assisting PWCF to navigate an increasingly complex benefit Registry. Data were retrieved from the most recent entry from patients who system and relieve the financial burden of living with CF, including met a social worker at their annual check-up between the years 2015–2019. reducing the financial impact of welfare reform. Meeting a social worker is optional at the annual check-up. The data covered 120 out of the 155 patients ≥18 years at Stockholm CF Centre. From P400 the 120 patients 12 were excluded due to not being eligible for work (3 on Money, money, money: does the UK government’s benefit reform maternity leave, 2 with old-age pension and 7 studying at collage level). Of underestimate the care needs of adults with cystic fibrosis? the remaining 108 patients aged 19–62 years (median 32 years), 45% 1 1 1 1 (n = 49) were females and 55% (n = 59) males. In the group 46% (n = 50) C. Oliver , S. Fenemore , E. Shepherd . University Hospital Southampton, were F508del homozygotes, 34% (n = 37) heterozygotes and 20% (n = 21) Adult Cystic Fibrosis, Southampton, United Kingdom had other combinations of CFTR mutations. Seventeen patients were Objective: Under UK law CF is considered a disability and in 2013 the UK transplanted (2 liver,15 lungs). government changed the way financial support was calculated for people Results: In the group of 108 patients 68% (n = 74) were working,16% (n = 17) with disability. Disability living allowance (DLA) was replaced by personal studying, 5% (n = 5) unemployed, 8% (n = 9) had long-term sickness independence payments (PIP), which had different eligibility criteria. compensation (pension) and 3% (n = 3) were on short term sick leave. A Many people with CF (PWCF) who were previously receiving ‘middle’ or total of 84% (n = 91) were either working or studying; 62% (n = 56) of them ‘high’ DLA awards have received reduced or no awards with PIP. The new at full time capacity, 16% (n = 15) at part time >50% and 22% (n = 20) at part PIP process has required significant social worker (SW) input to support ≤ time 50%. No gender differences were seen. In the group with patients through it, particularly if the initial awards are considered to transplanted patients 71% (n = 11 of 17 total) were working or studying. underestimate the persons’ care needs. Age distribution displayed below. Method: A review of 45 PIP awards was undertaken; some PWCF had previously had a DLA award whilst others were claiming for an award for Age Group 19–29 30–39 40–49 50–62 Total the first time. The review analysed the previous level of DLA and current years years years years group level of PIP awarded, any mandatory reconsideration of initial PIP awards and the number of PIP awards that went to appeal. Size of age group, % (n) 40 (43) 33 (36) 12 (13) 15 (16) 100 (108) Working/studying, % (n) 88 (38) 86 (31) 85 (11) 69 (11) 84 (91) Full-time occupation, % (n) 76 (29) 58 (18) 46 (5) 36 (4) 52 (56)

[Age distribution] S168 Posters / Journal of Cystic Fibrosis 19S2 (2020) S55–S168

Results: 14 initial PIP awards went to mandatory reconsideration and of these 10/14 were increased, with 4 unchanged. 9 PIP awards subsequently went to DLA care awards PIP care initial award DLA mobility PIP mobility initial appeal after mandatory reconsideration. Two outcomes remain pending prior to PIP awards prior to award and 6/7 awards have been increased. The PIP process is estimated to take an PIP average of 5 hours SW support (range 2–8 hours) per case. Conclusion: A significant majority of people were given a reduced care low care = 9 no award = 22 no award = 21 no award = 22 award when assessed for PIP. However, over 70% of PIP care or mobility middle care = 8 standard award = 5 low award = 6 standard award = 5 awards were increased at mandatory reconsideration and a further 6 PIP high care = 30 enhanced award = 18 middle award = 1 enhanced award = 18 high award = 19 care or mobility awards were subsequently increased after appeal. This suggests that initial assessments are systematically underestimating the [Outcome of PIP care and mobility awards] accurate care and mobility needs for PWCF. Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Author Index

A. Hadi, H., S80 (P089) Altintas, D. U., S64 (P035) Bailey, I., S50 (ePS5.05) A. Sultan, A., S80 (P089) Altintas, D., S72 (P060) Baiocco, N., S56 (P005), S63 (P029) A.L. Silva, I., S18 (WS11.2) Alton, E. W. F. W., S51 (ePS5.09) Baiwir, D., S113 (P202) Aalbers, B., S115 (P209), S117 (P216) Alves, P. C., S84 (P103) Baker, E., S22 (WS13.3) Abbott, J., S161 (P376) Amaral, M. D., S114 (P204), S21 (WS12.5) Balla, A., S21 (WS12.5) Abdel-Aziz, M. I., S115 (P207) Amato, A., S23 (WS13.6) Ballinger, K., S16 (WS10.1) Abdoul, H., S156 (P358) Amaxilati, D., S4 (WS03.1) Ballmann, M., S26 (WS15.5) Abdulahi, H., S12 (WS07.4) Ambrogi, F., S106 (P178) Balmer, G., S142 (P307) Abdulwahab, A., S55 (P002), S80 (P089) Amelina, E., S58 (P011), S64 (P032), S66 (P039), Balogh, I., S21 (WS12.5) Abhyankar, P., S166 (P396) S69 (P049), S78 (P083), S84 (P101), Bambir, I., S47 (ePS4.03), S48 (ePS4.09), Achimastos, D., S109 (P186) S86 (P109), S91 (P124), S104 (P170), S130 (P265), S135 (P284) Acosta Becker, N., S139 (P296) S1 (WS01.3), S34 (WS21.6) Bandeira, T., S104 (P169) Adamidi, T., S65 (P037) Anagnostopoulou, P., S65 (P037) Bara, V., S136 (P288) Addy, C., S98 (P149), S112 (P197), S138 (P295), Anand, A., S166 (P396) Baran, E., S90 (P122), S122 (P235) S141 (P304), S154 (P353), S167 (P399), Anastasovska, V., S59 (P016) Barbier, A., S22 (WS13.4) S5 (WS03.3), S7 (WS04.4) Anderson, A., S154 (P350) Barcellandi, P., S47 (ePS4.05) Adler, F. R., S73 (P064), S78 (P082) André, E., S90 (P121) Bareil, C., S33 (WS21.3) Adriaens, N., S119 (P223) Antipova, L., S69 (P052) Barello, S., S152 (P344) Adyan, T., S58 (P011), S64 (P032) Antoine, M., S108 (P185) Barer, M., S52 (ePS6.02) Afanasieva, M., S78 (P080), S91 (P124) Arets, B., S105 (P173), S115 (P209), S117 (P216) Baridon, M. D. l. A., S90 (P122) Afridi, H., S82 (P097) Armengaud, J., S79 (P084), S92 (P130) Barker, A. R., S139 (P298), S27 (WS16.4) Aguilar-Aranda, A., S72 (P061) Arnaud, A., S93 (P134), S96 (P143) Barker, K., S58 (P012) Ahlquist, A., S137 (P291), S142 (P307), Arnaudova-Danevska, I., S61 (P023), S127 (P253), Barnett, K., S150 (P336), S166 (P397) S28 (WS16.5) S105 (P174), S130 (P263) Barr, H., S46 (ePS4.01), S53 (ePS6.04), S76 (P075), Ahmed, M. I., S144 (P315) Arrouy, A., S129 (P258) S132 (P270), S134 (P277), S16 (WS10.2), Ahrabi-Nejad, C., S152 (P342) Artemenko, N., S87 (P112) S17 (WS10.6) Ainsworth, K., S164 (P389) Ascenzioni, F., S96 (P142) Barreto, C., S104 (P169) Aissat, A., S9 (WS05.4) Asfour, F., S78 (P082) Barrett, D. A., S53 (ePS6.04) Aksenova, E., S78 (P083), S84 (P101) Asherova, I., S60 (P020), S86 (P110), S4 (WS03.2) Barrett, P., S51 (ePS5.09) Al Khal, A. L., S80 (P089) Ashworth, E., S96 (P141) Barrio Gómez de Agüero, M., S105 (P176), Al Shakirchi, M., S167 (P398) Aslan, A. T., S72 (P060) S112 (P198) Al-Aloul, M., S73 (P063) Assael, B. M., S108 (P183) Barry, L., S99 (P152) Alameeri, A., S84 (P102) Atanasova-Nadjinska, M., S127 (P253) Barry, P. J., S97 (P147), S65 (P036), S104 (P172), Aldous, G., S162 (P381) Attfield, R., S23 (WS14.2) S74 (P067), S75 (P072) Alexander, R., S114 (P206) Audonnet, S., S129 (P260) Bartell, J., S14 (WS08.5) Alfeis, N., S15 (WS09.1) Audrézet, M.-P., S16 (WS09.5), S33 (WS21.2), Bartholmai, B., S107 (P181), S109 (P189) Alghamdi, N., S79 (P086) S33 (WS21.3), S34 (WS23.1) Barton, R. C., S79 (P086) Alghisi, F., S162 (P379), S4 (WS03.2) Aujoulat, F., S81 (P090) Bassotti, G., S39 (ePS1.10) Ali, J., S163 (P382) Aureli, M., S19 (WS12.1) Bastien, S., S92 (P128), S92 (P129), S93 (P131) Ali Mehidi, D., S155 (P354) Averna, M., S113 (P201) Bate, N., S166 (P397) Alicandro, G., S4 (WS03.2) Avetisyan, L., S69 (P049), S78 (P080), S87 (P114), Bateman, K., S68 (P046) Alimova, I., S58 (P011), S64 (P032) S88 (P116) Baxter, F., S51 (ePS5.09) Alison, J., S27 (WS16.3) Avril, H., S109 (P186) Baycheva, M., S75 (P071), S124 (P241) Allangawi, M., S80 (P089) Axten, J. M., S29 (WS17.5) Bayfield, K., S107 (P181), S109 (P189) Allard, P.-M., S52 (ePS6.03) Azaiz, W., S158 (P366) Baykova, G., S58 (P011) Allen, D., S88 (P117), S89 (P118), S89 (P119), Azar, M., S30 (WS18.1) Beaufils, F., S5 (WS03.4) S89 (P120) Azevedo, P., S72 (P059) Beauruelle, C., S76 (P076), S82 (P095) Allen, L., S119 (P224), S157 (P361) Beauvillard, D., S4 (WS02.5) Allenby, M., S102 (P163), S159 (P370), Baatallah, N., S8 (WS05.1) Bedi, R., S8 (WS04.6) S4 (WS03.1) Bacher, P., S20 (WS12.2) Beekman, J., S19 (WS11.4), S18 (WS11.2) Allenet, B., S66 (P041) Backström Eriksson, L., S49 (ePS5.02), Bekkema, R., S105 (P173) Almdal, T. P., S129 (P259) S161 (P375), S161 (P377), S163 (P384), Bell, N., S68 (P046) Alnaimi, A., S55 (P002) S167 (P398) Bell, S. E. J., S89 (P118), S89 (P119) Alpern, A., S50 (ePS5.05) Badel-Berchoux, S., S93 (P132) Belleguic, C., S55 (P003) Al-Samkari, H., S2 (WS01.6) Badovinac, M., S83 (P099) Bellinghausen, C., S44 (ePS3.07) Altenburg, J., S115 (P207) Bähner, V., S106 (P179) Bellis, G., S55 (P003) S170 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Belmans, D., S31 (WS19.1) Botti, M., S60 (P018) Burghard, M., S140 (P300), S16 (WS10.3), Bena, C., S1 (WS01.2) Bouchet, S., S100 (P155) S27 (WS16.2) Bene, Z., S21 (WS12.5) Boudet, A., S81 (P090) Burke, F., S123 (P237) Benencia, M. E., S90 (P122) Boudreau, V., S42 (ePS2.10), S125 (P244), Burkina, N., S134 (P276) Bentur, L., S130 (P264) S25 (WS15.1), S25 (WS15.2) Burmistrov, E., S78 (P080), S88 (P116) Benz, C., S146 (P324), S12 (WS07.2), S12 (WS07.3) Bourgani, E., S62 (P027) Burnet, E., S154 (P351), S26 (WS15.6) Bergamini, G., S108 (P183) Bourguignon, L., S99 (P153) Burns, P., S80 (P088) Bergenmar-Ivarsson, E., S49 (ePS5.02), Bourke, S., S154 (P350) Buscarlet Jardine, L., S66 (P041) S49 (ePS5.03), S50 (ePS5.04) Bournissen, F., S88 (P115) Bush, A., S51 (ePS5.09), S94 (P137) Bergeron, C., S42 (ePS2.10), S125 (P244), Boussaroque, A., S16 (WS09.5) Bush, N., S150 (P337) S25 (WS15.2) Boussaud, V., S154 (P351), S26 (WS15.6) Buslaeva, A., S166 (P395) Bergougnoux, A., S16 (WS09.5), S33 (WS21.3) Bower, J. K., S21 (WS13.1) Butler, D., S101 (P160) Berlinski, A., S145 (P319) Bowling, A., S158 (P365) Butti, M. F., S90 (P122) Bernardi, T., S93 (P132) Boyadjian, M., S93 (P131) Button, B., S39 (ePS1.09), S144 (P318), Bernatene, M. F., S131 (P268) Boychenko, E., S58 (P011), S64 (P032) S27 (WS16.1) Berry, C. A., S133 (P273) Boyton, C., S107 (P181), S109 (P189), S163 (P383) Butyugina, I., S91 (P124), S33 (WS21.4) Bertello, U., S39 (ePS1.07) Boytsova, Y., S69 (P052) Buzina, W., S84 (P104) Bertini, M., S34 (WS21.5) Bradish, S., S156 (P359) Bye, P., S27 (WS16.3) Berwick, A., S118 (P218) Bradley, C., S98 (P149), S112 (P197), S5 (WS03.3) Byrne, J., S156 (P359) Bettiol, M., S82 (P094) Bragonzi, A., S109 (P187) Byrnes, C., S131 (P266) Bevan, A., S150 (P337) Bramley, L., S6 (WS03.6) Beverley, Z., S140 (P301), S12 (WS07.5) Brandt, S., S92 (P130) Caballero, J. D. D., S81 (P091), S82 (P096), Beynon, J., S40 (ePS2.01) Bratan, T., S157 (P363) S85 (P105), S94 (P135) Beynon, R. J., S103 (P168) Braubach, P., S44 (ePS3.04), S44 (ePS3.07) Cabet, F., S33 (WS21.3) Bianchi, L., S63 (P029) Braun, C., S1 (WS01.1) Cafora, M., S19 (WS12.1) Bianco, B., S80 (P088), S13 (WS08.1) Braun, S., S157 (P362) Cahalan, R., S27 (WS16.1) Bienvenu, T., S16 (WS09.5), S33 (WS21.3) Braux, J., S129 (P260) Cahill, B. C., S110 (P191) Bierlaagh, M., S18 (WS11.2) Bréant, V., S99 (P153) Cai, S., S28 (WS17.1) Bieth, E., S33 (WS21.3) Brekke, G., S133 (P275) Caimmi, D., S20 (WS12.3), S30 (WS18.4), Biglia, C., S111 (P196), S1 (WS01.2) Bremer, W., S50 (ePS5.06) S32 (WS21.1) Bingol, A., S64 (P035), S72 (P060) Brendell, R., S119 (P224) Cakir, E., S64 (P035), S72 (P060) Birnbaum, D., S41 (ePS2.04) Brennan, A. L., S40 (ePS2.01), S40 (ePS2.02) Calcaterra, A., S96 (P142) Bittenglová, R., S110 (P192) Brennecke, P., S108 (P184) Calcaterra, E., S108 (P183) Bizzotto, G., S120 (P227) Brewington, J., S113 (P203) Caley, L., S40 (ePS2.03), S35 (WS23.3) Björkman, K., S165 (P393) Briani, F., S19 (WS12.1) Callebaut, I., S8 (WS05.1) Blackburn, C., S100 (P158), S101 (P159) Briaud, P., S92 (P128), S92 (P129), S93 (P131) Caltepe, G., S64 (P035), S72 (P060) Blaha, D., S96 (P143) Bridges, C., S148 (P329) Calum, H., S45 (ePS3.08) Blaikie, L., S51 (ePS5.09) Bright-Thomas, R. J., S37 (ePS1.01), S40 (ePS2.02), Calvert, A., S167 (P399) Blanco Aparicio, M., S105 (P176), S112 (P198) S65 (P036) Calzona, M. C., S122 (P235) Blanc-Potard, A., S91 (P127) Brinkman, P., S52 (ePS6.01), S115 (P207) Camara, B., S20 (WS12.3) Blasi, F., S110 (P190), S111 (P196) Brisin, V., S66 (P039) Cámara, M., S53 (ePS6.04), S76 (P075) Boardman, S., S103 (P166), S7 (WS04.5) Brivio, A., S39 (ePS1.10) Camera, E., S60 (P018) Boddy, L., S140 (P302) Brix, A., S19 (WS12.1) Cameron, S., S143 (P312), S144 (P317) Boëlle, P.-Y., S68 (P048) Brockbank, S., S44 (ePS3.05) Campana, S., S60 (P018) Bogomolova, T., S85 (P106) Brodlie, M., S51 (ePS5.09), S36 (WS23.5) Campbell, C. D., S117 (P217) Boldrini, F., S147 (P325), S162 (P379) Bronsveld, I., S115 (P209), S117 (P216) Camus, L., S92 (P128), S92 (P129), S93 (P131) Bondarenko, N., S91 (P125) Brown, C., S143 (P312), S144 (P317), Can, D., S64 (P035), S72 (P060) Bondarenko, T., S66 (P039) S149 (P333) Can, E., S42 (ePS2.09) Bonde, P., S166 (P394) Brown, L., S3 (WS02.4), S51 (ePS5.09) Candanedo Carpinteiro, J. A., S46 (ePS4.01) Bonhoure, A., S42 (ePS2.10), S125 (P244), Brown, M. C., S70 (P054) Cano, L. M., S102 (P165) S25 (WS15.2) Brown, S., S48 (ePS4.08) Cantón, R., S82 (P096), S85 (P105) Bontemps, V., S51 (ePS5.08) Brownlee, K., S51 (ePS5.09), S119 (P224) Cao, H., S28 (WS17.1) Boon, M., S14 (WS08.4), S18 (WS11.1) Bruce, K. D., S53 (ePS6.04), S76 (P075) Capaldo, C., S82 (P095) Booth, J., S118 (P221), S32 (WS19.6) Bruce, M., S23 (WS14.1) Capewell, A., S153 (P347) Booth, Z., S154 (P350) Bruni, A., S56 (P005) Caplin, N., S107 (P181), S109 (P189) Boraso, M., S108 (P183) Brydges, R., S166 (P396) Cappiello, F., S96 (P142) Borawska - Kowalczyk, U., S60 (P019), Buchvald, F., S11 (WS06.6) Carabott Pawley, D., S141 (P306) S17 (WS10.5) Budzinskiy, R., S60 (P020), S86 (P109), S86 (P110) Cardoni, L., S2 (WS01.6) Bord, E., S152 (P342) Bui, S., S90 (P123), S100 (P155), S5 (WS03.4) Cardoso, M., S138 (P294), S141 (P305) Borel, B., S158 (P367) Bukharova, T., S57 (P009) Cariani, L., S109 (P187) Borisenko, T., S69 (P052) Bulatenko, N., S57 (P009) Carlier, N., S154 (P351), S26 (WS15.6) Borisov, A., S58 (P011), S64 (P032) Bulatova, I., S86 (P109) Carlon, M. S., S18 (WS11.3) Borruso, A., S63 (P031), S6 (WS04.2), Bulfamante, A., S117 (P215) Caro, P., S81 (P091) S10 (WS06.4) Bull, A., S114 (P205) Caroff, A., S4 (WS02.5) Borzani, I., S117 (P215) Bundy, L., S121 (P228) Carolan, C., S146 (P322), S23 (WS14.2), Borzova, Y., S85 (P106), S86 (P109), S86 (P110) Burat, B., S113 (P202) S24 (WS14.4) Bos, L. D. J., S115 (P207), S52 (ePS6.01) Burge, A., S39 (ePS1.09) Carpentier, I., S101 (P162) Bosaeus, L., S39 (ePS1.07) Burgel, P.-R., S5 (WS03.4), S115 (P208), Carricart, M., S42 (ePS2.10) Bosher, O., S66 (P042) S116 (P210), S155 (P354), S26 (WS15.6), Carrolan, V., S67 (P044), S143 (P312), S144 (P317) Botta, B., S96 (P142) S36 (WS23.6) Carroll, M., S121 (P228), S4 (WS03.1) Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182 S171

Carson, L., S138 (P295) Clancy, J., S113 (P203) D’Ascenzo, M. V., S122 (P235) Carta, F., S39 (ePS1.10) Clarke, C., S146 (P322) Da Silva, J., S115 (P208), S116 (P210) Carter, S., S43 (ePS3.02) Claustres, M., S32 (WS21.1), S33 (WS21.3) Daccò, V., S117 (P215) Carveth, H., S110 (P191) Clegg, M., S2 (WS02.1) Daelemans, S., S62 (P028), S157 (P362) Casciaro, B., S96 (P142) Clifton, I., S41 (ePS2.05), S126 (P251), Dagorne, M., S34 (WS23.1) Casciaro, R., S113 (P201), S152 (P344), S21 (WS12.6), S26 (WS15.4) D’Agostino, G., S109 (P188) S120 (P226) Clouzeau, H., S5 (WS03.4) Daines, C., S118 (P221), S32 (WS19.6) Casey, K., S157 (P364) Cobanoglu, N., S64 (P035), S72 (P060) Dakin, R., S149 (P335) Caskey, S., S98 (P149), S112 (P197), S141 (P304), Cobo, F., S38 (ePS1.04) Dalal, I., S154 (P352) S154 (P353), S5 (WS03.3) Coffey, M. J., S103 (P166), S160 (P374), D’Alessandro, V., S82 (P094), S109 (P188) Casserly, B., S27 (WS16.1) S6 (WS03.6), S7 (WS04.5) Dalton, J., S41 (ePS2.06) Castellani, C., S113 (P201), S152 (P344) Coffey, N., S123 (P237) Daly, D., S132 (P269) Castillo Corullón, S., S105 (P176), S112 (P198) Colangelo, C., S23 (WS13.6) Damnotti, C., S70 (P054) Catalano, F., S56 (P007), S34 (WS21.5) Collet, C., S5 (WS03.4) Danahay, H., S29 (WS17.4) Cathcart, F., S12 (WS07.5) Collingwood, S., S29 (WS17.4) Daniels, J., S162 (P381) Catherinot, E., S30 (WS18.4) Collins, L., S27 (WS16.1) Daniels, T., S121 (P228), S4 (WS03.1), Caudri, D., S6 (WS04.1) Collins, N., S149 (P333) S16 (WS10.1) Caverly, L., S30 (WS18.1) Collins, S., S127 (P254), S128 (P255) Danilina, G., S78 (P083) Caverni, E., S39 (ePS1.10) Collobert, M., S33 (WS21.2) Dannemann, L., S148 (P330) Cavicchi, M. C., S60 (P018) Colomba, J., S42 (ePS2.10), S125 (P244) Darnaud, L., S99 (P154) Cavinato, L., S96 (P142) Colombo, C., S39 (ePS1.10), S117 (P215), D’Ascenzo, V., S90 (P122) Cavusoglu-Doran, K., S29 (WS17.2) S4 (WS03.2) Daswon, E., S140 (P302) Cazares, A., S14 (WS08.6) Coltey, B., S41 (ePS2.04) Daud, F., S130 (P264) Celebi, E., S64 (P035), S72 (P060) Commun, C., S52 (ePS6.03), S93 (P134), Dauletova, J., S66 (P039) Centeio, R., S114 (P204) S96 (P143) Davage, H., S43 (ePS3.02) Cerofolini, A., S56 (P007), S34 (WS21.5) Connolly, A., S84 (P102) Dave, K., S71 (P057) Cerrudo, V., S82 (P096) Connolly, A. M., S136 (P287) Davids, I., S150 (P337) Chachi, E., S105 (P175) Connolly, M., S156 (P359) Davies, J. C., S94 (P137), S157 (P361), Champreux, J., S155 (P354) Connon, M., S51 (ePS5.09) S52 (ePS6.01), S51 (ePS5.09), S54 (ePS6.10), Chandler, J. D., S6 (WS04.1) Connors, J., S2 (WS01.6) S11 (WS06.5) Channon, K., S148 (P332) Constant, C., S104 (P169) Davis, C., S153 (P349) Chansard, A., S51 (ePS5.08) Conti, J., S56 (P007), S34 (WS21.5) Davis Bollard, H., S163 (P382) Chapman, K. S. A., S161 (P378) Copeland, A., S142 (P307) Dawes, M., S157 (P364) Chapman, S. J., S127 (P252), S153 (P348), Coppinger, J., S43 (ePS3.02) Dawidziuk, M., S60 (P019) S161 (P378) Corbani, S., S56 (P006) Dawood, S., S118 (P219) Charlwood, J., S29 (WS17.4) Cordioli, S., S108 (P183) Dawson, C., S51 (ePS5.09), S136 (P286) Charman, S. C., S74 (P067), S75 (P072), Cordovilla Pérez, R., S105 (P176), Dawson, S., S150 (P336), S151 (P339) S22 (WS13.5) S112 (P198) Dayman, N., S52 (ePS6.02), S144 (P315) Chelabi, R., S20 (WS12.3), S30 (WS18.4) Coriati, A., S36 (WS23.6) De Backer, J., S31 (WS19.1) Chen, Z. R., S28 (WS17.1) Cornell, A. G., S31 (WS19.2) De Boeck, K., S18 (WS11.1), S18 (WS11.3) Chepurnaya, A., S64 (P032) Corradi, S., S96 (P142) De Canck, E., S90 (P121) Chepurnaya, M., S58 (P011) Corry, H., S127 (P252) De Carli, P., S49 (ePS5.01), S51 (ePS5.08) Cherniak, A., S58 (P011), S69 (P052), S86 (P110), Corti, F., S117 (P215) De Freitas Coelho, P., S37 (ePS1.03) S86 (P109), S104 (P170) Corvol, H., S68 (P048) De Gregorio, F., S23 (WS13.6) Chernevich, V., S78 (P083) Cosgriff, R., S73 (P065), S74 (P066), S74 (P067), De Jaegere, A., S123 (P238) Chernukha, M., S69 (P049), S78 (P080), S75 (P072), S35 (WS23.4) De Keersmaecker, L., S18 (WS11.3) S87 (P114), S88 (P116) Costa, S., S120 (P226) De Keyser, H., S49 (ePS5.01), S51 (ePS5.08), Chevalier, B., S8 (WS05.1) Costa Colomer, J., S105 (P176), S112 (P198) S22 (WS13.5) Chiarelli, L. R., S97 (P146) Costello, J., S159 (P369) De Kiviet, C., S115 (P209), S117 (P216) Chikunov, V., S58 (P013), S60 (P020), S66 (P039), Costi, C., S65 (P037) De Luca, D., S44 (ePS3.04) S123 (P236), S129 (P261) Cotton, F., S100 (P156) De Marchis, M., S147 (P325) Chilvers, M., S31 (WS19.2) Coucke, R., S51 (ePS5.08) De Miranda, S., S71 (P058) Chiron, R., S45 (ePS3.10), S20 (WS12.3), Coudrat, A., S20 (WS12.3) De Monestrol, I., S49 (ePS5.02), S49 (ePS5.03), S30 (WS18.4), S79 (P084), S81 (P090), Cousins, E., S119 (P224) S50 (ePS5.04), S76 (P073), S163 (P384), S87 (P111), S92 (P130), S32 (WS21.1) Cowlard, J., S59 (P015) S4 (WS03.2), S22 (WS13.2), S32 (WS19.5) Chmiel, J. F., S45 (ePS3.10) Cox, D. W., S77 (P077), S101 (P160) De Roos, N., S16 (WS10.3) Choyce, J., S67 (P044) Crawford, K., S141 (P304) De Santis, F., S31 (WS18.6) Christ, F., S18 (WS11.3) Creedon, M., S136 (P286) De Sario, A., S32 (WS21.1) Christara, A., S151 (P340) Cresta, F., S113 (P201), S152 (P344) De Tullio, R., S113 (P201) Christophersen, L., S45 (ePS3.08), S93 (P133) Crnogorac, I. K., S47 (ePS4.03), S135 (P284) De Wachter, E., S62 (P028), S157 (P362) Chuchalin, A., S78 (P083), S84 (P101) Cronin, K., S126 (P249), S116 (P212) De Winter-de Groot, K., S70 (P053), S115 (P209), Ciciriello, F., S147 (P325), S162 (P379) Cucchetto, G., S10 (WS06.4) S117 (P216) Cigana, C., S109 (P187) Cunningham, J., S118 (P220) Deber, C. M., S8 (WS05.2) Cinel, G., S64 (P035), S72 (P060) Cunningham, S., S12 (WS07.5) Debyser, Z., S18 (WS11.3) Cipolli, M., S56 (P007), S63 (P031), S108 (P183), Curley, R., S146 (P322), S23 (WS14.2), Degiacomi, G., S97 (P146) S6 (WS04.2), S10 (WS06.4), S34 (WS21.5) S24 (WS14.4) Degrugillier, F., S9 (WS05.4) Ciprandi, R., S152 (P344) Curran, M., S27 (WS16.1) Dehillotte, C., S41 (ePS2.04), S81 (P093), Cirilli, N., S56 (P005), S63 (P029) Curtis, P., S153 (P349) S33 (WS21.3), S36 (WS23.6) Cirillo, D. M., S109 (P187), S31 (WS18.6) Cuyx, S., S18 (WS11.1) DeJonge, H., S56 (P007), S34 (WS21.5) Claes, I., S137 (P290) Czerska, K., S55 (P001) Del Campo, R., S81 (P091), S82 (P096), S94 (P135) S172 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Delfino, D., S120 (P227) Drevinek, P., S114 (P204) Eppe, G., S113 (P202) Delhaes, L., S5 (WS03.4) Drzymala-Czyz, S., S121 (P230) Ercan, O., S64 (P035), S72 (P060) Demichelis, S., S1 (WS01.2) Duan, R., S28 (WS17.1) Erdem Eralp, E., S163 (P385) Demir, E., S72 (P060) Duckers, J., S71 (P056), S156 (P357), Erenchun, L., S109 (P188) DeMonestrol, I., S161 (P377) S41 (ePS2.07), S100 (P157), S116 (P211), Ergenekon, P., S163 (P385) Demuyser, T., S90 (P121) S121 (P229), S132 (P272), S134 (P281), Ericson, P., S143 (P313), S22 (WS13.2) Deneuville, E., S55 (P003), S34 (WS23.1) S148 (P329) Erlich, J., S103 (P166), S7 (WS04.5) Denis, A., S66 (P040), S25 (WS15.3) Düesberg, U., S69 (P051) Ershova, E., S106 (P177) Dennersten-Kvist, U., S28 (WS16.6) Dufernez, F., S33 (WS21.3) Ersson, K., S28 (WS16.6) Dentice, R., S27 (WS16.3) Dumitrescu, O., S99 (P153) Erzutova, M., S60 (P020), S69 (P049) Denton, M., S82 (P097) Dumke, M., S47 (ePS4.04) Eschenhagen, P., S69 (P051), S85 (P107), Desai, M., S120 (P225), S155 (P355) Dumont, Y., S30 (WS18.4) S97 (P148), S111 (P194), S20 (WS12.2) Desbois, G., S143 (P311) Duncan, C., S152 (P342) Escobar, C., S92 (P130) Descalço, A., S104 (P169) Dunk, R., S71 (P057) Esen, D., S64 (P035) Desjardins, K., S125 (P244) Dunn, H., S121 (P228), S150 (P337) Etcheverry, N., S47 (ePS4.05) Desmazes-Dufeu, N., S41 (ePS2.04) Dunstan, C., S71 (P056) Etherington, C., S41 (ePS2.05), S126 (P251), Destoop, M., S62 (P028) Duperray, I., S101 (P162) S21 (WS12.6), S26 (WS15.4) Dewar, J., S46 (ePS4.01), S53 (ePS6.04), Dupont, C., S87 (P111), S92 (P130), S155 (P354) Etienne, I., S100 (P156) S132 (P270), S134 (P277), S150 (P336), Dupont, L. J., S123 (P238), S160 (P372), Etumi, M., S154 (P352) S151 (P339), S16 (WS10.2), S17 (WS10.6) S18 (WS11.1), S14 (WS08.4) Eustace, J. A., S126 (P249), S116 (P212) Dgetluck, N., S45 (ePS3.10) Durč, P., S63 (P030) Evangelista Campos, N., S37 (ePS1.03), Di Paolo, M., S111 (P196) Durand De Monestrol D’Esquille, I., S167 (P398) S139 (P296) Di Tria, R., S1 (WS01.2) Durieu, I., S101 (P162), S108 (P185), S118 (P221), Evans, H., S4 (WS03.2) Diab, G., S130 (P264) S1 (WS01.1), S25 (WS15.3), S32 (WS19.6) Eyns, H., S157 (P362) Diamantea, F., S62 (P027) Durkin, K., S152 (P342) Diemer, S., S74 (P068), S165 (P393) Durupt, S., S1 (WS01.1) Fabrizzi, B., S56 (P005), S63 (P029) Diez-Vega, I., S38 (ePS1.04) Dwyer, T., S27 (WS16.3) Fage, D., S100 (P156) Dijoux-Franca, M.-G., S52 (ePS6.03), S93 (P134), Dyachkova, A., S58 (P011) Fagundes Donadio, M. V., S37 (ePS1.03), S96 (P143) Dyck, K., S95 (P138) S139 (P296) Dimalaluan, M., S75 (P069) Dyekjær, C. D., S166 (P394) Fairley, D. J., S88 (P117), S89 (P118), S89 (P120) Dinh, Q., S45 (ePS3.10) Dziubecki, M., S70 (P054) Fajac, I., S45 (ePS3.10), S118 (P221), S119 (P222), Diomede, L., S108 (P183) S19 (WS11.5), S32 (WS19.6) Dittrich, A.-M., S42 (ePS2.08), S44 (ePS3.04), Eadson, C., S24 (WS14.4) Falke, J.-N., S44 (ePS3.04) S124 (P242), S145 (P321), S13 (WS08.2), Earlam, K., S22 (WS13.5) Fallon, R., S158 (P365) S15 (WS09.1) Eber, E., S84 (P104) Fältström, C., S76 (P073) Dixon, E., S149 (P333) Echahidi, F., S90 (P121) Falzon, C., S141 (P306) Dobra, R., S157 (P361) Edelman, A., S8 (WS05.1) Fanchini, A., S67 (P043) Dobric, A., S47 (ePS4.03), S135 (P284) Edenborough, F., S146 (P322), S23 (WS14.2), Fanen, P., S9 (WS05.4), S33 (WS21.3) Dobric, L. T., S47 (ePS4.03), S135 (P284) S24 (WS14.4) Fangous, M.-S., S54 (ePS6.08) Doeleman, W., S27 (WS16.2) Edgar, J., S60 (P021) Fanis, P., S65 (P037) Dogru, D., S64 (P035), S72 (P060) Edmondson, C., S51 (ePS5.09) Fanton, A., S71 (P058) Dolbnya, S., S48 (ePS4.07), S129 (P261) Edwards, E., S100 (P158), S101 (P159) Farell, J., S114 (P206) Dolce, D., S60 (P018) Efremova, A., S57 (P009) Farge, A., S33 (WS21.3) Doléans-Jordheim, A., S52 (ePS6.03), S92 (P128), Egan, H., S165 (P392) Farhat, R., S56 (P006) S92 (P129), S93 (P131), S93 (P134), Egger, M., S84 (P104) Farias, M., S64 (P034), S113 (P199) S96 (P143), S99 (P153) Eickmeier, O., S157 (P363) Farinazzo, A., S56 (P007), S34 (WS21.5) Domenjod, C., S81 (P090) Eidt-Koch, D., S157 (P363) Farinha, C. M., S29 (WS17.2) Dominguez, F., S90 (P122) Einarsson, G. G., S78 (P081), S79 (P085), Farrell, P. M., S58 (P014), S61 (P022), S61 (P024), Dompeling, E., S119 (P223) S14 (WS08.4), S88 (P117), S89 (P118), S34 (WS23.1) Donadio, M. V. F., S38 (ePS1.04) S89 (P119), S89 (P120) Farrow, N., S134 (P278) Donaldson, B., S167 (P399) El Seedy, A., S56 (P006) Fasan, O., S158 (P367) Donnelly, S., S43 (ePS3.02) Elbahnsi, A., S8 (WS05.1) Faughey, J., S152 (P346) Donnikov, M., S59 (P017) Elbert, A., S58 (P014), S61 (P022), S61 (P024), Faulkner, J., S142 (P308), S142 (P310), Dooney, M. K., S107 (P180), S111 (P193), S21 (WS13.1) S147 (P327) S136 (P287) Elborn, J. S., S78 (P081), S14 (WS08.4), S88 (P117), Faurholt-Jepsen, D., S95 (P140), S129 (P259) Dopfer, C., S15 (WS09.1) S89 (P118), S89 (P119), S89 (P120), Fauset-Jones, J., S3 (WS02.4) D’Orazio, C., S108 (P183) S157 (P361), S45 (ePS3.10), S79 (P085) Favilli, F., S152 (P344) Dos Reis Vidal, P., S37 (ePS1.03) Ellemunter, H., S47 (ePS4.04), S50 (ePS5.06) Fawdon, M., S154 (P350) Douglas, H., S137 (P291), S139 (P299), Elliott, A., S146 (P324), S12 (WS07.2), Fayon, M., S100 (P155), S5 (WS03.4) S28 (WS16.5) S12 (WS07.3) Fejes, Z., S21 (WS12.5) Douglas, L. E. J., S29 (WS17.5) Elsen, S., S92 (P128) Felton, I., S128 (P255) Doumit, M., S6 (WS03.6), S12 (WS07.2) Elston, C., S148 (P332) Fenemore, S., S167 (P400) Dousova, T., S114 (P204) Emiralioglu, N., S64 (P035), S72 (P060) Ferec, C., S55 (P003), S33 (WS21.3) Downey, D. G., S86 (P108), S98 (P149), Emma, M., S125 (P246) Férec, C., S16 (WS09.5), S33 (WS21.2), S112 (P197), S154 (P353), S5 (WS03.3), Enakpene, E., S110 (P191) S34 (WS23.1) S141 (P304), S7 (WS04.4) Enaud, R., S5 (WS03.4) Fergelot, P., S33 (WS21.3) Doyle, G., S75 (P070) Endre, Z., S103 (P166), S7 (WS04.5) Ferland, G., S25 (WS15.2) Doytcheva, P., S108 (P184) Endres, A., S44 (ePS3.07) Fernández, A., S47 (ePS4.05) Drennan, P., S99 (P152) Ensinck, M., S18 (WS11.3) Fernandos, C., S128 (P255) Drevait, M., S20 (WS12.3), S30 (WS18.4) Ent van der, K., S105 (P173) Ferrari, G., S23 (WS13.6) Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182 S173

Ferrario, M., S122 (P235) Galkina, V., S57 (P008), S34 (WS21.6) Golihina, T., S66 (P039) Ferro, F., S72 (P059) Gallagher, C., S84 (P102), S131 (P267) Golubtsova, O., S60 (P020), S86 (P110) Ferron, M., S25 (WS15.2) Gallet, P., S100 (P155) Gómez García de la Pedrosa, E., S85 (P105) Festini, F., S60 (P018) Galliot, S., S96 (P144) Goncharova, S., S69 (P049) Figueroa, W., S14 (WS08.6) Galodé, F., S5 (WS03.4) Gonsseaume, S., S158 (P366), S154 (P351) Filimonova, T., S58 (P011), S64 (P032) Gambazza, S., S39 (ePS1.10), S106 (P178) Goode, G., S149 (P334) Filippova, T., S69 (P052) Gandia, P., S99 (P154) Goodfellow, N., S154 (P350) Filloux, A. A. M., S94 (P137) García Bournisen, F., S111 (P195) Goodman, A., S152 (P342) Finocchiaro, J. A., S47 (ePS4.05) García Clemente, M., S105 (P176), S112 (P198) Goralski, J., S118 (P221), S32 (WS19.6) Fisher, N., S58 (P014), S61 (P022), S61 (P024) Garcia Darderes, M. G., S70 (P054) Gordillo-Altamirano, F., S53 (ePS6.06) Fishwick, R., S38 (ePS1.05) Gardecki, J., S157 (P363) Gorinova, Y., S69 (P049), S123 (P239), Fitzgerald, D., S107 (P181), S109 (P189) Gardner, A. I., S36 (WS23.5) S134 (P276), S33 (WS21.4) Fitzgerald, P., S44 (ePS3.05) Garnett, J., S45 (ePS3.09) Goriot-Raynaud, N., S154 (P351) FitzMaurice, T. S., S98 (P151), S102 (P164), Garuti, S., S152 (P344) Görlich, D., S95 (P138) S118 (P219), S8 (WS04.6) Gaspar, V., S138 (P292) Gorman, C., S125 (P246) Fitzpatrick, R., S107 (P181), S109 (P189), Gastal, S., S90 (P122) Goryainova, A., S69 (P049), S56 (P004) S131 (P267) Gaston, V., S33 (WS21.3) Gosling, M., S29 (WS17.4) Flahault, C., S156 (P358) Gates, A., S37 (ePS1.02), S142 (P308), S142 (P310), Gospodinova, B., S105 (P175), S124 (P241) Fleischer, E., S51 (ePS5.09) S147 (P328) Goss, C. H., S7 (WS04.3), S119 (P222) Fleming, C., S116 (P212) Gauchet, A., S66 (P041) Gosset, P., S54 (ePS6.08) Flemming, C., S126 (P249) Gavillet, H., S80 (P088), S13 (WS08.1) Goundry, S., S157 (P361) Fléron, M., S113 (P202) Gazina, V., S91 (P125) Gouriou, S., S77 (P078), S14 (WS08.3), Fletcher, O. L., S94 (P137) Geel, A., S119 (P223) S54 (ePS6.08), S76 (P076) Flight, W. G., S37 (ePS1.02), S127 (P252), Gehring, S., S106 (P179) Goutelle, S., S99 (P153) S147 (P327), S147 (P328), S153 (P348), Gembitskaya, T., S58 (P011), S64 (P032), Gozdzik-Spychalska, J., S121 (P230) S161 (P378), S142 (P308), S142 (P310) S53 (ePS6.05), S87 (P112), S87 (P113) Graeber, S. Y., S19 (WS11.4) Flodström-Tullberg, M., S128 (P257) George, C., S24 (WS14.5) Graffigna, G., S152 (P344) Floto, R. A., S133 (P274) George, S., S101 (P161) Gramegna, A., S111 (P196) Flume, P., S45 (ePS3.10), S7 (WS04.3), Georgieva, M., S124 (P241) Grasemann, H., S28 (WS17.1) S19 (WS11.5) Georgiou, A., S65 (P037) Grasso, A., S110 (P190) Flynn, E., S101 (P161) Gerardin, M., S158 (P366), S154 (P351) Gray, R. D., S43 (ePS3.03), S118 (P218), Fogarty, A., S53 (ePS6.04), S76 (P075) Gerasimova, A., S166 (P395) S20 (WS12.4) Ford, J., S29 (WS17.4) Gerritsen, M. G., S52 (ePS6.01) Graziano, S., S147 (P325), S162 (P379) Fordyce, C., S143 (P314) Gesuele, A., S39 (ePS1.10) Green, H. D., S97 (P147), S143 (P314), S2 (WS02.1) Forrester, D. L., S53 (ePS6.04) Gheller, M. F., S139 (P296) Grehn, C., S42 (ePS2.08), S69 (P051), S97 (P148), Forster, A., S135 (P283) Ghigo, A., S9 (WS05.3) S20 (WS12.2) Forti, F., S19 (WS12.1) Ghirga, F., S96 (P142) Grenet, D., S71 (P058), S156 (P358), S30 (WS18.4) Fothergill, J. L., S80 (P087), S98 (P150), S96 (P141), Ghufran, S., S157 (P364) Grenga, L., S79 (P084), S92 (P130) S98 (P151), S77 (P079), S14 (WS08.6) Giacomodonato, B., S147 (P325) Grigoletto, A., S120 (P227) Fox, A., S35 (WS23.2) Gil, M. F., S82 (P094) Grimhusen, M., S76 (P073) Francalanci, M., S60 (P018) Gilchrist, F. J., S38 (ePS1.05) Gross, J. E., S69 (P050) Franchi, A., S113 (P201) Gillan, J. L., S43 (ePS3.03), S20 (WS12.4) Gruca, S., S106 (P179) Francis, C., S71 (P056) Gilljam, M., S143 (P313), S161 (P377), Grumov, D., S78 (P080), S88 (P116) François, A., S76 (P076) S22 (WS13.2), S32 (WS19.5) Grunert, J., S134 (P278) Fraziano, M., S31 (WS18.6) Gilmartin, G., S18 (WS11.2), S19 (WS11.5) Gubareva, T., S86 (P109) Frédérick, R., S15 (WS09.2) Gilpin, D. F., S14 (WS08.4), S88 (P117), S89 (P118), Gueganton, L., S55 (P003) Fremy, E., S32 (WS21.1) S89 (P119), S89 (P120) Guenkova, N., S105 (P175), S124 (P241) Fritsch, N. C., S97 (P147) Ginter, E., S57 (P008), S34 (WS21.6), S69 (P049) Guet-Revillet, H., S81 (P093), S99 (P154) Fronia, N., S50 (ePS5.06) Gintsburg, A., S78 (P080), S78 (P083), S84 (P101), Guglani, L., S6 (WS04.1) Frost, F., S73 (P063), S80 (P087), S98 (P150), S88 (P116) Guillaume, C., S129 (P260) S98 (P151), S114 (P205), S140 (P302), Gioia, B., S52 (ePS6.03), S93 (P134), S96 (P143) Guillot, L., S68 (P048) S165 (P390), S26 (WS15.5), S77 (P079) Giordani, B., S23 (WS13.6) Guilloux, C.-A., S54 (ePS6.08), S76 (P076) Füllekrug, J., S30 (WS17.6) Girling, C., S146 (P322), S150 (P337), Gulmans, V. A. M., S51 (ePS5.07), S70 (P053), Fuller, L., S39 (ePS1.09) S24 (WS14.4) S70 (P055) Funnell, L., S39 (ePS1.07), S67 (P045), Girodon, E., S16 (WS09.5), S33 (WS21.3) Gupta, A., S119 (P222) S128 (P255) Girón Moreno, R. M., S105 (P176), S112 (P198), Gupta, G. D., S9 (WS05.5) Furman, E., S69 (P049), S64 (P033) S38 (ePS1.04) Gur, M., S130 (P264) Furstová, E., S63 (P030), S114 (P204) Girotti, C., S122 (P235) Gustafsson, P., S11 (WS06.6) Fustikj, S., S59 (P016), S124 (P240) Gjinovska-Tasevska, E., S61 (P023), S105 (P174), Gut, G., S130 (P264) S127 (P253), S130 (P263) Guy, E., S82 (P097) G Downey, D., S19 (WS11.5) Glazner, J. A., S156 (P360), S166 (P397) Guzzardella, A., S110 (P190) G Mainz, J., S105 (P176), S112 (P198) Goble, P., S41 (ePS2.07) Guzzetti, L., S82 (P094) Gadsby, J., S150 (P337) Godic, I., S151 (P341), S155 (P356), S165 (P391) Gaedcke, S., S44 (ePS3.04) Godoy, A., S90 (P122) Haarman, E. G., S52 (ePS6.01) Gaillard, E., S52 (ePS6.02), S144 (P315) Godreuil, S., S30 (WS18.4) Haber, E., S84 (P104) Gaillyová, R., S15 (WS09.4) Gogoleva, E., S86 (P109) Habington, A., S77 (P077) Gaimolenko, I., S66 (P039) Gohy, S., S15 (WS09.2) Hadchouel-Duverge, A., S62 (P026) Galanternik, L., S88 (P115) Gokdemir, Y., S163 (P385) Hafiz, A. A. M., S135 (P283) Galban, C., S107 (P181), S109 (P189) Goldbeck, A., S50 (ePS5.06) Hagan, M. O., S126 (P250) Galici, V., S60 (P018) Goldshtein, D., S57 (P009) Hager, A., S74 (P068), S76 (P073) S174 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Hall, A., S48 (ePS4.08) Hird, B., S60 (P021) J Barr, J., S53 (ePS6.06) Halle, O., S44 (ePS3.04) Hirsch, E., S9 (WS05.3) Jacob, A., S156 (P358) Halliday, G., S23 (WS14.1) Hirtz, S., S19 (WS11.4) Jacobs, F., S100 (P156) Halliday, N., S53 (ePS6.04) Hites, M., S100 (P156) Jacquot, J., S129 (P260) Halperin, A. V., S81 (P091), S85 (P105) Hjelte, L., S76 (P073), S128 (P257), S167 (P398), Jadkauskaite, L., S102 (P163) Hamilton, C., S39 (ePS1.08), S139 (P297) S22 (WS13.2), S32 (WS19.5) Jaffé, A., S6 (WS03.6), S7 (WS04.5), S103 (P166) Hanafin, P., S31 (WS19.3) Ho, M. W.-Y., S29 (WS17.5) Jain, R., S119 (P222) Hankins, C., S121 (P229) Hodgson, R., S154 (P350) Jakjovska, T., S61 (P023), S105 (P174), Hanna, M., S130 (P264) Hoebrechts, F., S160 (P372) S127 (P253), S164 (P388) Hanna, S. J., S154 (P353) Hoel, L., S28 (WS16.6) Jakobsen, K. R., S166 (P394) Hansen, C. R., S74 (P068), S165 (P393), Hofland, R., S115 (P209), S117 (P216) Jakovska Maretti, T., S130 (P263) S12 (WS07.4), S22 (WS13.2) Hogardt, M., S44 (ePS3.07) Jaksic, M., S131 (P266) Hansen, G., S44 (ePS3.04), S15 (WS09.1) Hogg, C., S94 (P137) Jalusic-Gluncic, T., S47 (ePS4.03) Hanssens, L., S138 (P292) Höglund, S., S143 (P313) Janssens, H. M., S52 (ePS6.01), S6 (WS04.1), Haq, I. J., S36 (WS23.5) Høiby, N., S45 (ePS3.08), S84 (P103), S93 (P133) S70 (P053) Harcourt, D., S4 (WS02.6) Højer, S., S166 (P394) Jarblad, A., S76 (P073) Hardisty, G. R., S43 (ePS3.03), S118 (P218), Holbrook, J., S21 (WS12.6) Jarosz-Griffiths, H., S21 (WS12.6) S20 (WS12.4) Hollander-Kraaijeveld, F., S16 (WS10.3) Järvholm, S., S49 (ePS5.02), S161 (P377) Hardouin, P., S79 (P084) Holmgaard, D. B., S45 (ePS3.08) Jass, J., S80 (P089) Harlander, M., S83 (P099) Holz, F., S42 (ePS2.09) Jaudszus, A., S40 (ePS2.03) Harman, V. M., S103 (P168) Homola, L., S63 (P030) Javadpour, S., S77 (P077) Harmanci, K., S64 (P035), S72 (P060) Honeybourne, D., S53 (ePS6.04) Jayaraj, R., S13 (WS07.6) Harris, W., S22 (WS13.3) Hong, G., S85 (P107) Jehl, F., S93 (P132) Harrison, P. T., S29 (WS17.2) Honoré, I., S26 (WS15.6) Jehlička, P., S110 (P192) Harrison, V., S107 (P182) Hoodless, E., S165 (P390) Jenkins, R., S121 (P229) Harris-Skillman, E., S153 (P348) Hope, S., S152 (P345) Jenkins, T., S140 (P301) Harrisson, J., S54 (ePS6.10) Hopkins, A. L., S121 (P229), S156 (P357) Jenkinson, E., S4 (WS02.6) Hart, A., S127 (P252) Hoppe, J., S31 (WS19.2) Jensen, C. S., S159 (P368) Harvey, A., S12 (WS07.3) Horati, H., S6 (WS04.1) Jensen, J. L., S110 (P191) Hasan, N., S69 (P050) Horsley, A. R., S97 (P147) Jensen, K., S2 (WS01.4) Hasiak Santo, A., S73 (P062) Horsley, A., S80 (P088), S13 (WS08.1) Jeppesen, M., S166 (P394) Hatfield, L. R., S13 (WS08.1), S80 (P088) Houdouin, V., S158 (P366), S154 (P351) Jessup, M. M., S156 (P360) Hatziagorou, E., S116 (P213), S150 (P338), Howlett, C., S116 (P212), S126 (P249) Jiang, J., S19 (WS11.5) S151 (P340), S9 (WS06.1) Hristov, I., S105 (P175), S124 (P241) Jirmo, A. C., S44 (ePS3.04) Havermans, T., S137 (P290), S160 (P372) Hsu, M.-C., S119 (P222) Johnson, A., S148 (P329) Hawkes, S., S8 (WS04.6) Hu, J., S28 (WS17.1) Johnson, J., S150 (P337) Hayes, K., S49 (ePS5.01), S51 (ePS5.08), Hubert, D., S129 (P260), S156 (P358) Jones, A. M., S97 (P147), S40 (ePS2.02), S7 (WS04.4) Hughes, D., S51 (ePS5.09) S65 (P036), S78 (P081), S79 (P085), Hayes, M., S123 (P237) Hulzebos, E., S27 (WS16.2) S103 (P168), S104 (P172), S74 (P067), Haynes, K., S153 (P349) Hulzebos, H. J., S140 (P300) S75 (P072), S80 (P088), S127 (P254), Hector, A., S91 (P126) Hunt, S., S163 (P383) S143 (P314), S158 (P365), S2 (WS02.1), Hedborg, A., S22 (WS13.2), S28 (WS16.6), Hussain, S., S161 (P376) S13 (WS08.1), S140 (P301), S12 (WS07.5) S32 (WS19.5) Hutchinson, I., S122 (P231) Jones, C., S150 (P337) Hedtfeld, S., S43 (ePS3.01) Hyöty, H., S128 (P257) Jones, G., S102 (P163) Heidenreich, K., S95 (P138) Jones, H., S116 (P211), S134 (P281) Heijerman, H. G. M., S70 (P053), S115 (P209), Ianni, A., S147 (P325) Jones, L., S124 (P243) S117 (P216), S118 (P221), S16 (WS10.3), Ianowski, J. P., S28 (WS17.1) Jones, S., S164 (P389) S32 (WS19.6), S52 (ePS6.01), S140 (P300) Iansa, P., S63 (P031) Jonigk, D., S44 (ePS3.04), S44 (ePS3.07) Heinzmann-Filho, J. P., S139 (P296) Iazzi, M., S9 (WS05.5) Joris, S., S22 (WS13.5) Heise, R., S148 (P332) Ibarra, L., S83 (P100), S88 (P115) Jourdain, M.-L., S129 (P260) Hellmuth, T., S138 (P293), S145 (P321) Ibrahim, E., S80 (P089) Journel, H., S55 (P003), S34 (WS23.1) Heltshe, S., S7 (WS04.3) Ides, K., S31 (WS19.1) Jozlowski, K., S143 (P312), S144 (P317) Hemingway, P., S149 (P335) Ignatova, A., S123 (P239) Jubin, V., S1 (WS01.1) Hempstead, S., S161 (P376) Ignatyeva, M., S69 (P052) Jumas-Bilak, E., S87 (P111), S92 (P130) Hendriks, H., S70 (P053) Ilenkova, N., S58 (P013), S123 (P236), S66 (P039) Junge, F., S138 (P293), S145 (P321) Henneberg, K.-Å., S95 (P140) Ilivitzki, A., S117 (P214) Junge, N., S124 (P242) Herencias, C., S94 (P135) Ilyenkova, N., S60 (P020), S48 (ePS4.07), Junge, S., S138 (P293), S145 (P321), S15 (WS09.1) Hernández-Raygoza, R., S72 (P061) S129 (P261) Jurascheck, A., S27 (WS16.1) Hernon, F., S77 (P077) Imperi, F., S96 (P142) Justice, E., S67 (P044) Herrera, J., S131 (P268) Incardona, C., S70 (P054) Herrmann, J. L., S30 (WS18.4) Ioannou, P., S65 (P037) K. van der Ent, C., S18 (WS11.2) Héry-Arnaud, G., S54 (ePS6.08), S76 (P076), Iqbal, N., S107 (P180), S111 (P193) Kadioglu, A., S96 (P141) S77 (P078), S82 (P095), S14 (WS08.3) Iribarne, M. E., S90 (P122) Kahl, B., S95 (P138) Heyen, N., S157 (P363) Irigoyen, N., S47 (ePS4.05) Kallinich, T., S42 (ePS2.09) Higelin, K., S95 (P138) Irving, S., S11 (WS06.5) Kalnoki, C., S131 (P267) Higton, A., S118 (P220) Islam, R., S103 (P167) Kanaan, R., S155 (P354), S26 (WS15.6) Hildage, J., S2 (WS02.1) Ismatullin, D., S81 (P092), S83 (P098) Kangasjarvi, E., S166 (P396) Hillen, B., S106 (P179) Iturbe Fernández, D., S105 (P176), S112 (P198) Kanukova, N., S86 (P109) Hindinger, C., S47 (ePS4.04) Ivakhnenko, E., S58 (P011) Kapotina, L., S78 (P083) Hinzpeter, A., S8 (WS05.1) Ivleva, V., S66 (P039) Kapranov, N., S69 (P049) Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182 S175

Kar, S., S103 (P167) Kondratenko, O., S69 (P049), S81 (P092), Laine, C., S49 (ePS5.02), S49 (ePS5.03), Karabatic, S., S151 (P341), S155 (P356), S83 (P098), S85 (P106) S50 (ePS5.04), S163 (P384) S165 (P391) Kondratyeva, E., S48 (ePS4.07), S57 (P008), Lakhova, E., S58 (P011) Karadag, B. T., S163 (P385) S57 (P009), S57 (P010), S58 (P011), Lalau, G., S33 (WS21.3) Karakoc, F., S163 (P385) S58 (P013), S60 (P020), S64 (P032), Lalic, I., S135 (P284), S151 (P341), S155 (P356), Kardava, C., S53 (ePS6.05), S87 (P112), S64 (P033), S69 (P049), S69 (P052), S165 (P391) S87 (P113) S78 (P083), S86 (P109), S86 (P110), Lamaud, C., S158 (P366) Karimova, I., S86 (P110) S87 (P114), S88 (P116), S106 (P177), Lamireau, T., S5 (WS03.4) Kartsonaki, C., S73 (P064) S123 (P236), S129 (P261), S4 (WS03.2), Lammers, A., S52 (ePS6.01) Kashirskaya, N., S86 (P110), S88 (P116), S34 (WS21.6), S66 (P039) Lammertyn, E., S49 (ePS5.01), S51 (ePS5.08) S57 (P008), S57 (P009), S58 (P011), Konovalova, L., S69 (P052) Lamoureux, C., S76 (P076) S64 (P032), S69 (P049), S69 (P052), Konstan, M., S45 (ePS3.10) Landers, C., S75 (P070), S137 (P289) S4 (WS03.2), S34 (WS21.6), S66 (P039) Koppelman, G. H., S70 (P053), S160 (P373) Lange, J., S95 (P138) Kasparian, N., S160 (P374) Koren, I., S117 (P214) Langman, H., S143 (P314) Kasten, A. P., S138 (P294) Korkmaz, P., S64 (P035), S72 (P060) Languepin, J., S158 (P367) Katrine Drasbæk Philipsen, L., S95 (P140) Korneeva, T., S69 (P049) Lannefors, L., S143 (P313), S28 (WS16.6) Katsagoni, C., S17 (WS10.4) Kos, R., S52 (ePS6.01) Lannibois, C., S122 (P234) Katz, T., S49 (ePS4.10), S160 (P374), S6 (WS03.6) Kose, M., S64 (P035), S72 (P060) Lara-Reyna, S., S21 (WS12.6) Kavaliunaite, E., S136 (P286) Kosti, C., S62 (P027) Larsson, P., S49 (ePS5.03), S50 (ePS5.04) Keidar, Z., S130 (P264) Kostyuk, S., S106 (P177) Lasareva, A., S78 (P083) Keijzers, N., S119 (P223) Kotoulas, S.-C., S150 (P338) Lau, D., S156 (P357), S41 (ePS2.07), S100 (P157), Kelly, A., S130 (P262) Koucky, V., S10 (WS06.3) S116 (P211), S132 (P272), S134 (P281) Kelly, A.-M., S40 (ePS2.02), S65 (P036) Kouis, P., S65 (P037) Lauwers, E., S31 (WS19.1) Kemper, A., S106 (P179) Kouroukli, E., S150 (P338), S151 (P340), Lavery, K., S138 (P295) Kench, A., S163 (P383) S9 (WS06.1), S116 (P213) Lavigne, J.-P., S81 (P090) Kendall, V., S2 (WS02.1) Koutsokera, A., S54 (ePS6.07) Lavoie, A., S42 (ePS2.10), S25 (WS15.2) Kennedy, B., S107 (P181), S109 (P189) Kovalenko, L., S59 (P017) Lavrova, A., S69 (P049) Kennedy, L., S27 (WS16.1) Kovalev, V., S58 (P011), S64 (P032) Lawrence, P., S104 (P171) Kennedy, S., S103 (P166), S7 (WS04.5) Kozlov, A., S58 (P011), S64 (P032), S81 (P092), Lawson, A., S150 (P337) Kent, J., S142 (P307) S83 (P098), S85 (P106) Lazareva, T., S87 (P112), S87 (P113) Kent, T., S38 (ePS1.06) Kozlova, E., S86 (P110) Lazurenko, S., S166 (P395) Keogh, R. H., S73 (P064), S26 (WS15.5), Kozyreva, L., S58 (P011) Le Berre, R., S54 (ePS6.08), S76 (P076), S74 (P066) Kraneveld, A. D., S52 (ePS6.01) S77 (P078), S14 (WS08.3) Keown, K., S86 (P108) Krantz, C., S22 (WS13.2), S32 (WS19.5) Le Bihan, J., S4 (WS02.5) Kerbrat, M., S4 (WS02.5) Krasovskiy, S., S58 (P011), S64 (P032), S66 (P039), Le Martelot, M.-T., S4 (WS02.5) Ketchell, R. I., S41 (ePS2.07), S156 (P357), S69 (P049), S86 (P109), S86 (P110), Le Rouzic, O., S159 (P371) S100 (P157), S132 (P272), S134 (P281) S91 (P124), S1 (WS01.3), S33 (WS21.4), Lea-Davies, M., S100 (P157), S116 (P211), Ketev, K., S105 (P175), S124 (P241) S34 (WS21.6) S132 (P272) Keytes, R., S165 (P392) Krasovsky, S., S64 (P033), S78 (P080), S104 (P170) Leal, T., S113 (P202), S15 (WS09.2) Khatami, A., S53 (ePS6.06) Krasynk, M., S35 (WS23.2) Leclainche, L., S158 (P366) Kilgore, M. B., S6 (WS04.1) Kreideweiss, S., S45 (ePS3.09) Ledeneva, L., S69 (P052) Kiliç, M., S64 (P035), S72 (P060) Kremer, L., S30 (WS18.4) Ledneva, V., S57 (P009), S60 (P020), Kilinç, A. A., S64 (P035), S72 (P060) Kreslová, M., S110 (P192) S66 (P039) Kindler, J., S130 (P262) Krogh Johansen, H., S14 (WS08.5) Ledson, M., S142 (P309) King, G., S107 (P181), S109 (P189) Kroon, K. J., S160 (P373) Lee, A., S74 (P067), S75 (P072) Kinsey, L., S2 (WS02.1) Kruijswijk, M., S115 (P209), S117 (P216) Lee, A. J., S78 (P081), S79 (P085), S14 (WS08.4) Kinyaikin, M., S69 (P049) Krzyzanowska-Jankowska, P., S121 (P230) Lee, T., S100 (P158), S101 (P159) Kioumis, I., S150 (P338) Kubáň, P., S63 (P030) Leemans, G., S31 (WS19.1) Kirvassili, S., S9 (WS06.1) Kular, R., S66 (P042) Leggieri, E., S111 (P196) Kitzis, A., S56 (P006) Kulebina, E., S123 (P239) Lemaire, B., S81 (P090) Kjeldsen, K. B., S164 (P386) Kunda, M., S78 (P083), S84 (P101) Lemonnier, L., S41 (ePS2.04), S71 (P058), Klaassen, H., S18 (WS11.3) Kunzelmann, K., S114 (P204) S33 (WS21.3), S36 (WS23.6), S81 (P093) Kleinfelder, K., S56 (P007), S34 (WS21.5) Kurzeja, P., S145 (P320) Lennon, J., S43 (ePS3.02) Klimko, N., S86 (P110) Kutsev, S., S57 (P009), S58 (P011), S64 (P032), Leone, P., S147 (P325) Klimov, L., S48 (ePS4.07), S129 (P261) S57 (P008), S60 (P020), S69 (P049), Lepissier, A., S109 (P186), S7 (WS04.4) Klopp, J., S106 (P179) S34 (WS21.6) Lerche, C. J., S45 (ePS3.08), S93 (P133) Knoll, R. L., S106 (P179) Kutubudin, F., S46 (ePS4.02) Leroy, S., S90 (P123), S32 (WS21.1) Knoop, C., S100 (P156), S118 (P221), S138 (P292), Kyrvasili, S., S116 (P213), S150 (P338) Lestan, D., S83 (P099) S32 (WS19.6) Levy, C. E., S84 (P103) Knowles, J., S154 (P352) La Vanda, C., S134 (P278) Lewin, A., S97 (P148) Knowles, Z., S140 (P302) Laborde, N., S122 (P234) Lewis, J., S131 (P266) Knox, A. J., S53 (ePS6.04), S76 (P075) Labouret, G., S122 (P234) L’Hostis, C., S33 (WS21.2), S34 (WS23.1) Kochergina, T., S86 (P109) Lacombe, J., S25 (WS15.2) Li, J., S28 (WS17.1) Koegler, H., S45 (ePS3.09) Ladaurade, A., S62 (P026) Li, M., S9 (WS05.3) Kolarova - Yaneva, N., S62 (P025) Ladeveze,̀ V., S56 (P006) Lialias, I., S150 (P338), S9 (WS06.1) Kolbasin, L., S59 (P017) Ladic, A., S47 (ePS4.03), S48 (ePS4.09), Lialias, J., S116 (P213) Kolpen, M., S95 (P140) S130 (P265), S135 (P284) Lilley, A., S76 (P075), S133 (P273) Komlev, N., S58 (P011) Lafont, M., S129 (P258) Lim, W. Y., S41 (ePS2.05) Kondakova, J., S60 (P020) Lagrafeuille, R., S54 (ePS6.08) Lim, Y. W., S126 (P251), S26 (WS15.4) Kondakova, Y., S69 (P049), S106 (P177) Lai, H., S5 (WS03.5) Lindberg, U., S22 (WS13.2), S32 (WS19.5) S176 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Lindblad, A., S49 (ePS5.02), S49 (ePS5.03), Máiz Carro, L., S105 (P176), S112 (P198) Mavin, E., S45 (ePS3.09) S50 (ePS5.04), S4 (WS03.2), S22 (WS13.2), Majo, F., S120 (P226), S147 (P325), S23 (WS13.6) Mayell, S., S104 (P171) S32 (WS19.5) Majoor, C., S70 (P053), S115 (P207), S118 (P221), Mazzucchelli, G., S113 (P202) Lindsay, F., S13 (WS07.6) S32 (WS19.6), S52 (ePS6.01) Mc Carthy, M., S126 (P249) Lindwall, J., S152 (P342) Major, E., S121 (P228) McCabe, D., S118 (P218) Liou, T. G., S73 (P064), S78 (P082), S110 (P191) Mak, D., S51 (ePS5.09) McCafferty, M., S167 (P399) Lipuma, J., S30 (WS18.1) Makarov, V., S97 (P146) McCann, A.-M., S167 (P399) Lisowska, A., S121 (P230) Makhmutova, V., S69 (P052) McCann, C., S8 (WS04.6) Livnat, G., S117 (P214) Maksimycheva, T., S48 (ePS4.07) McCarthy, C., S29 (WS17.4) Livnat-Levanon, G., S113 (P203) Malá, M., S63 (P030) McCarthy, M., S116 (P212) Ljagusha, D., S66 (P039) Malerba, G., S95 (P139) McCarthy, Y., S116 (P212) Llanes, C., S96 (P144) Malik, F., S73 (P065), S74 (P066) McCaughan, J., S86 (P108) Lleo, M. M., S95 (P139) Malinge, M.-C., S33 (WS21.3) McClenaghan, E., S22 (WS13.5) Llerena, C., S66 (P041), S66 (P040), S67 (P043) Mall, M. A., S30 (WS17.6), S119 (P222), McColley, S. A., S58 (P014), S61 (P022), Lo Sciuto, A., S96 (P142) S19 (WS11.4), S114 (P206) S61 (P024), S31 (WS19.2) Loberto, N., S19 (WS12.1) Mambetova, A., S66 (P039) McCormick, J., S51 (ePS5.09) Lobjanidze, K., S44 (ePS3.04) Mancone, C., S96 (P142) McDermott, J. A., S126 (P250) Lock, K., S139 (P297) Mandigout, S., S158 (P367) McDermott, M., S21 (WS12.6) Loffreda, A., S9 (WS05.3) Manetti, F., S97 (P146) McDonnell, C., S27 (WS16.1) Loffredo, M. R., S96 (P142) Manfredi, M., S113 (P201) McGowan, A., S152 (P345), S153 (P347) Logue, C., S40 (ePS2.01) Mangoni, M., S96 (P142) McGrade, A.-M., S167 (P399) Loman, N., S77 (P079) Manika, K., S150 (P338) McIntosh, L., S118 (P218) Lomas, P., S161 (P376) Mankieva, L., S58 (P011) McKay, I. R., S6 (WS03.6), S160 (P374) Lomax, S., S8 (WS04.6) Manonelles, G., S83 (P100), S88 (P115) McKenna, D., S3 (WS02.4) Lombrail, P., S67 (P043) Mansfield, M., S126 (P251), S26 (WS15.4) McKenna, J. P., S88 (P117), S89 (P118), S89 (P120) Lopes, C., S72 (P059) Mantsiou, C., S116 (P213), S9 (WS06.1) McKenna, M., S3 (WS02.4) Lopez, M., S16 (WS09.5) Mantzios, M., S165 (P392) McKeown, C., S98 (P149), S112 (P197), López-López, S., S38 (ePS1.04) Manu Djan, P., S132 (P271) S5 (WS03.3) Lord, C., S13 (WS07.6) Manuel, E., S114 (P206) McKone, E., S131 (P267), S43 (ePS3.02), Lord, R. W., S78 (P081), S79 (P085), S103 (P168) Maqbool, A., S135 (P285) S84 (P102) Lore’, N. I., S109 (P187) Marakhonov, A., S57 (P008), S69 (P049) McLornan, J., S154 (P353) Lotti, V., S56 (P007), S34 (WS21.5) Marchandin, H., S79 (P084), S81 (P090), McMahon, L., S2 (WS01.6) Loughran, C., S138 (P295) S87 (P111), S92 (P130), S30 (WS18.4) McMullan, C., S118 (P218) Loukou, I., S17 (WS10.4) Marchetti, P., S75 (P069) McNally, P. N., S43 (ePS3.02), S101 (P160), Lowdon, J., S136 (P288), S159 (P369) Maremshanova, F., S66 (P039) S122 (P231), S77 (P077) Lowndes, L., S39 (ePS1.08), S139 (P297), Marengo, E., S113 (P201) McNamara, J. J., S31 (WS19.2) S146 (P323) Margaroli, C., S6 (WS04.1) McNamara, P. S., S103 (P168) Lowney, A., S153 (P348) Marguet, C., S90 (P123) McNeilly, F., S108 (P184) Lowry, P., S44 (ePS3.05) Mariani, A., S39 (ePS1.10) McParland, C., S5 (WS03.3) Lowther, M., S24 (WS14.4) Markelic, I., S48 (ePS4.09), S130 (P265) McShane, D., S39 (ePS1.08), S139 (P297), Lubovich, S., S83 (P100), S88 (P115), S111 (P195) Marostica, P. J. C., S138 (P294), S141 (P305), S146 (P323) Lucca, F., S6 (WS04.2), S10 (WS06.4) S64 (P034), S113 (P199) McTavish, D., S11 (WS07.1) Lucidi, V., S147 (P325), S162 (P379) Marouvo, J., S27 (WS16.3) Meade, C., S116 (P212) Lumb, A., S127 (P252) Marshall, B., S85 (P107) Mechold, U., S94 (P136) Lund, T. K., S2 (WS01.4) Mårtensson, M., S74 (P068), S165 (P393), Medhurst, N., S73 (P065), S74 (P066), Lyamin, A., S64 (P032), S81 (P092), S83 (P098), S12 (WS07.4), S28 (WS16.6) S22 (WS13.5) S85 (P106) Marti, L., S94 (P136) Medina-Mendoza, O. M., S72 (P061) Lynch, V., S125 (P246) Martin, C., S26 (WS15.6) Medvedeva, O., S78 (P080), S88 (P116) Martin, K. J., S107 (P180), S111 (P193) Megarbane, A., S56 (P006) MacDonald, K., S23 (WS14.1) Martin, S. L., S29 (WS17.5) Mehta, A., S21 (WS12.6) MacDonald-Johns, R., S143 (P312), S144 (P317) Martín de Vicente, C., S105 (P176), S112 (P198) Mekki, C., S33 (WS21.3) MacDuff, N., S66 (P042) Martínez Martínez, M., S105 (P176), S112 (P198) Melanie, A., S44 (ePS3.04) Macek Jr., M., S21 (WS12.5) Martínez Redondo, M., S105 (P176), S112 (P198) Melotti, P., S56 (P007), S63 (P031), S95 (P139), Madden, E., S116 (P212) Martiniano, S. L., S58 (P014), S61 (P022), S108 (P183), S15 (WS09.2), S34 (WS21.5) Madej, P., S17 (WS10.5) S61 (P024) Mely, L., S154 (P351), S32 (WS21.1) Madge, S., S71 (P057), S39 (ePS1.07), S67 (P045), Martinon, F., S21 (WS12.6) Melyanovskaya, Y., S57 (P009), S57 (P010), S157 (P361) Marvig, R., S14 (WS08.5) S58 (P011), S64 (P032) Magalhaes, M., S32 (WS21.1) Marx, V., S95 (P138) Mendez, A. C., S70 (P054) Maggi, T., S63 (P029) Marzuki, M., S103 (P167) Meneghelli, I., S108 (P183) Magni, M., S143 (P311) Mas, E., S122 (P234), S5 (WS03.4) Menetrey, Q., S87 (P111), S92 (P130) Mahenthiralingham, E., S121 (P229) Masarweh, K., S130 (P264) Menin, L., S63 (P031), S6 (WS04.2), Maher, R. E., S103 (P168) Mascarenhas, M., S135 (P285) S10 (WS06.4) Mailhot, M., S25 (WS15.2) Masoud-Landgraf, L., S84 (P104) Menna, L., S90 (P122) Main, E., S139 (P299) Massalha, V., S141 (P306) Mention, K., S29 (WS17.2) Mainguy, C., S93 (P131), S1 (WS01.1), Masson, A., S158 (P367) Mergni, G., S60 (P018) S25 (WS15.3) Mathiesen, I. H. M., S129 (P259) Merkus, P., S70 (P053) Mainz, J. G., S123 (P238), S40 (ePS2.03) Matthaiou, A., S65 (P037) Mescheryakov, V., S59 (P017) Maitland-van der Zee, A. H., S115 (P207), Mauch, R., S84 (P103) Mesinele, J., S68 (P048) S52 (ePS6.01) Maumus, P., S122 (P234) Messore, B., S111 (P196), S1 (WS01.2) Maitra, A., S60 (P021), S135 (P283), S13 (WS08.1) Mauprivez, C., S129 (P260) Mezei, Z. A., S21 (WS12.5) Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182 S177

Michalet, S., S52 (ePS6.03), S93 (P134), Moussouni, M., S91 (P127) Nitsche, O., S106 (P179) S96 (P143) Moustaki, M., S17 (WS10.4) Nixon, W., S120 (P225) Michel, P., S67 (P043) Muilwijk, D., S51 (ePS5.07), S70 (P055) Nogaret, P., S91 (P127) Michel, S., S115 (P209), S117 (P216), S119 (P223) Mukhina, M., S69 (P049) Nolan, G., S104 (P172) Michelet, M., S129 (P258) Müller, C., S15 (WS09.1) Nolasco da Silva, M. T., S84 (P103) Michels, M., S64 (P034), S113 (P199) Munaretto, R., S56 (P005) Noordhoek, J., S70 (P053) Middleton, A., S107 (P181), S109 (P189), Munck, A., S62 (P026), S16 (WS09.5) Nosbaum, A., S1 (WS01.1) S163 (P383), S12 (WS07.2), S12 (WS07.3) Munck, S., S18 (WS11.3) Nosotti, M., S110 (P190) Mielus, M., S60 (P019), S17 (WS10.5) Muñoz Muñoz, L., S97 (P146) Nousia, L., S116 (P213), S151 (P340) Mignault, D., S125 (P244) Munsar, Z., S130 (P262) Nouwade, K., S52 (ePS6.03) Mignot, B., S31 (WS19.1) Murabito, A., S9 (WS05.3) Nove-Josserand, R., S1 (WS01.1) Mihule, J., S147 (P326) Murad, A., S13 (WS07.6) Novikova, O., S69 (P052) Mikhailichenko, K., S104 (P170) Muraleva, N., S86 (P109) Nowak, J. K., S121 (P230) Milczewska, J., S10 (WS06.2) Murali, S., S5 (WS03.5) Nowicka, A., S121 (P230) Miller, B., S150 (P336), S150 (P337) Murphy, D. M., S116 (P212) Nugent, A., S125 (P246) Miller, M., S153 (P348) Murphy, L., S138 (P295) Nuijsink, M., S70 (P053) Mills, A., S157 (P364) Murphy, R. A., S94 (P137), S54 (ePS6.10) Nwokoro, C., S48 (ePS4.08), S59 (P015) Mills, V., S125 (P246), S154 (P353) Murphy, S., S122 (P232) Millward, S., S150 (P336) Murray, B., S44 (ePS3.05) O’Donnell, S., S77 (P077) Miloglou, A., S151 (P340) Murray, N., S149 (P333) O’ Grady, E., S75 (P070) Minova Georgieva, B., S164 (P388) Murris, M., S99 (P154), S32 (WS21.1) O’ Leary, F., S123 (P237) Minso, R., S15 (WS09.1) Murris-Espin, M., S90 (P123) O Neill, D., S152 (P346) Mistry, H., S67 (P044) Mursaloglu, H. H., S163 (P385) O’Reilly, R., S77 (P077) Mistry, N., S144 (P315) Muther, E., S152 (P342), S161 (P376) O’Sullivan, N., S77 (P077) Mitchell, J., S104 (P172) Myrtle, A., S3 (WS02.4) Ołtarzewski, M., S55 (P001), S60 (P019), Mitchell-Whyte, M., S125 (P245), S132 (P270), S17 (WS10.5) S134 (P277), S16 (WS10.2), S17 (WS10.6) Nabais Robalo, M. I., S131 (P268) Oades, P. J., S139 (P298), S27 (WS16.4), Miteva, D., S105 (P175) Naehrlich, L., S22 (WS13.4), S35 (WS23.2) S38 (ePS1.06) Mitra, S., S79 (P086) Nagakumar, P., S120 (P225) Oates, G., S22 (WS13.3) Mittaine, M., S99 (P154), S122 (P234), Nagy Jr., B., S21 (WS12.5) O’Brien, K., S136 (P286) S129 (P258), S5 (WS03.4) Nahid, B., S152 (P345) O’Brien, S., S14 (WS08.6) Modha, D., S52 (ePS6.02) Nährlich, L., S42 (ePS2.08) O’Carroll, M., S19 (WS11.5) Modl, M., S84 (P104) Nair, R., S52 (ePS6.02) Ochirova, N., S58 (P011) Moe, A. P., S110 (P191) Naisbitt, D., S114 (P206) O’Connell, S., S132 (P269) Mohamed, A., S32 (WS21.1) Namane, S., S138 (P292) O’Connor, L., S39 (ePS1.07), S67 (P045) Mohammed Hoessein, F., S115 (P209) Nash, E. F., S67 (P044), S76 (P075), S124 (P243), O’Connor, R., S139 (P299), S163 (P383) Moisan, S., S33 (WS21.2) S128 (P256), S143 (P312), S144 (P317), Odinaeva, N., S69 (P052), S86 (P110) Molchanova, O., S86 (P110) S165 (P392), S53 (ePS6.04) Odinokova, O., S58 (P011), S64 (P032) Moledina, S., S24 (WS14.3) Nath, N., S40 (ePS2.01) Odobasic Palkovic, T., S47 (ePS4.03), S135 (P284), Mølgaard, C., S133 (P275) Naumenko, Z., S104 (P170) S151 (P341), S155 (P356), S165 (P391) Molin, S., S14 (WS08.5) Nave, V., S101 (P162) Oganesyan, I., S86 (P109) Molle, V., S92 (P130) Nazareth, D., S46 (ePS4.02), S73 (P063), Ogese, M., S114 (P206) Möller, M., S167 (P398) S77 (P079), S80 (P087), S98 (P150), Oh, R., S49 (ePS4.10) Momchilovikj, S., S61 (P023), S105 (P174), S98 (P151), S102 (P164), S114 (P205), O’Hagan, J., S108 (P184) S127 (P253), S130 (P263) S118 (P219), S140 (P302), S142 (P309), Ohlmann, C., S1 (WS01.1) Moncivaiz, J., S113 (P203) S162 (P381), S165 (P390), S8 (WS04.6) Olden, C., S51 (ePS5.09) Montan, M., S74 (P068), S12 (WS07.4) Nazzari, E., S117 (P215) Olesen, H. V., S159 (P368), S166 (P394) Montegue, T., S101 (P160) Nedkova, V., S62 (P025), S105 (P175), S124 (P241) Olivares, E., S93 (P132) Montemitro, E., S147 (P325) Neerincx, A. H., S52 (ePS6.01), S115 (P207) Oliver, C., S167 (P400) Moore, E., S125 (P246), S152 (P346) Negrone, V., S90 (P122) Oliver, M., S4 (WS03.2) Moore, J. E., S86 (P108) Nekludova, G., S104 (P170) O’Mahony, M., S117 (P217) Moreau, J., S20 (WS12.3), S30 (WS18.4) Nelson, E., S152 (P342) Omerza, L., S48 (ePS4.09), S130 (P265) Moreau, K., S92 (P128), S92 (P129), S93 (P131) Neocleous, V., S65 (P037) Omrani, A., S80 (P089) Morelli, P., S96 (P142) Neri, A. S., S60 (P018) Onay, Z. R., S72 (P060) Mori, G., S120 (P227) Neumann, K., S69 (P051) O’Neill, D., S125 (P246), S154 (P353), S167 (P399) Mori, M., S96 (P142) Ng, C., S132 (P271) Onyon, C., S107 (P182) Morin, C., S129 (P258) Nguyen Ngoc, V.-T., S52 (ePS6.03) Ooi, C. Y., S160 (P374), S4 (WS03.2), S6 (WS03.6), Morin, L., S143 (P311) Nicholls, S., S77 (P079) S103 (P166), S7 (WS04.5) Morisse Pradier, H., S30 (WS18.4) Nicholson, T., S131 (P267) Opron, K., S30 (WS18.1) Mornon, J.-P., S8 (WS05.1) Nick, J. A., S69 (P050) Orchard, C., S118 (P220) Morosini, M. I., S81 (P091) Nickolaus, P., S45 (ePS3.09) Orenti, A., S106 (P178), S22 (WS13.4), Morrison, L., S11 (WS07.1) Nicolas, J.-F., S1 (WS01.1) S35 (WS23.2) Morrissy, D., S126 (P249), S116 (P212) Nielsen, B. U., S129 (P259) Orioli, T., S60 (P018) Morrow, S., S150 (P337) Nielsen, K., S11 (WS06.6) Orlov, A., S69 (P052), S60 (P020) Moser, C., S45 (ePS3.08), S93 (P133) Nielsen, P. B., S159 (P368) O’Shaughnessy, L., S131 (P267) Moskowitz, S. M., S118 (P221), S32 (WS19.6) Nietert, M., S15 (WS09.2) Osipova, E., S86 (P109) Moskvina, D., S69 (P052), S60 (P020) Nijs, M., S18 (WS11.3) Ostmann, A., S113 (P203) Mosnier-Pudar, H., S26 (WS15.6) Nikitina, M., S69 (P052) Østrup Jensen, P., S95 (P140) Moss, R. B., S85 (P107) Nikolova, M., S105 (P175), S124 (P241) O’Sullivan, N., S101 (P160) Motter, G., S138 (P294), S141 (P305) Nir, V., S130 (P264) Oturai, P. S., S129 (P259) S178 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Owen, C. A., S31 (WS19.2) Pesevska, M., S59 (P016) Pranke, I., S8 (WS05.1) Owen, E., S136 (P286) Pesle, A., S158 (P366) Preato, S., S56 (P007), S34 (WS21.5) Oxley, H., S2 (WS02.1) Petlichkovski, A., S124 (P240) Preis, T., S91 (P126) Ozcan, G., S64 (P035), S72 (P060) Petrocheilou, A., S17 (WS10.4) Prella, M., S54 (ePS6.07) Ozcelik, U., S64 (P035), S72 (P060) Petrov, A., S69 (P052) Pressler, T., S129 (P259), S148 (P330), Ozdemir, A., S64 (P035), S72 (P060) Petrov, V., S66 (P039) S11 (WS06.6), S14 (WS08.5), S19 (WS11.5), Ozdogan, S., S64 (P035), S72 (P060) Petrova, A., S66 (P039) S133 (P275), S2 (WS01.4) Petrova, D., S66 (P039) Prévost, G., S93 (P132) Padoan, R., S4 (WS03.2), S23 (WS13.6) Petrova, G., S75 (P071), S105 (P175), S124 (P241), Prevotat, A., S159 (P371) Paff, T., S52 (ePS6.01) S162 (P380) Price, A., S51 (ePS5.09) Pagin, A., S33 (WS21.3) Petrova, N., S57 (P008), S57 (P009), S57 (P010), Prieto, A., S94 (P135) Paida, K., S160 (P374), S6 (WS03.6) S58 (P011), S64 (P032), S69 (P049), Proesmans, M., S137 (P290), S160 (P372), Paillasseur, J.-L., S115 (P208), S116 (P210) S129 (P261), S34 (WS21.6) S18 (WS11.1), S19 (WS11.5) Paiola, G., S10 (WS06.4) Pfister, E., S124 (P242) Proffit, M., S143 (P311) Palange, P., S111 (P196) Pfleger, A., S84 (P104) Protasova, T., S66 (P039) Pandit, C., S107 (P181), S109 (P189) Phan, J. L., S115 (P207) Proud, D., S116 (P211), S132 (P272), S134 (P281) Pandya, S., S46 (ePS4.02) Philip, K., S28 (WS17.1) Provot, C., S93 (P132) Panzo, R., S155 (P354) Philipsen, L., S148 (P330) Prugnieres, G., S109 (P186) Pao, C., S59 (P015), S139 (P299) Phylactou, L. A., S65 (P037) Pruliere-Escabasse,̀ V., S9 (WS05.4) Pao, C. S., S48 (ePS4.08) Piacentini, G., S6 (WS04.2) Prusak, J., S145 (P320) Parker, S., S154 (P350) Piazza, M., S6 (WS04.2) Purba, A., S143 (P312), S144 (P317) Parkinson, H., S148 (P332) Pible, O., S79 (P084) Purewal, S., S165 (P392) Parr, L., S150 (P336) Picard, A.-C., S119 (P222) Pust, M.-M., S13 (WS08.2) Parrott, H., S39 (ePS1.07) Pickering, N., S148 (P331) Pyaterkina, O., S58 (P011), S60 (P020) Pasca, M. R., S97 (P146) Pickles, J., S2 (WS02.1) Pashkevich, A., S69 (P052) Piel, F. B., S35 (WS23.4) Q.Innes, A., S28 (WS16.5) Paskin, L., S120 (P225) Piérard, D., S90 (P121) Qaqish, R., S145 (P319) Passarelli Mantovani, R., S95 (P139) Piermarini, I., S147 (P325) Quaglio, D., S96 (P142) Passiu, M., S108 (P183) Pighetti, E., S2 (WS01.6) Quetant, S., S20 (WS12.3) Pasut, G., S120 (P227) Pincikova, T., S128 (P257) Quibell, R., S154 (P350) Patarin, J., S109 (P186) Pineau, F., S32 (WS21.1) Quick, J., S77 (P079) Patel, J., S4 (WS03.1) Pinegina, Y., S69 (P049) Quintana Gallego, E., S105 (P176), S112 (P198) Patel, N., S124 (P243), S143 (P312), S144 (P317) Pinsault, N., S66 (P041) Quiri, F., S56 (P007), S34 (WS21.5) Paterson, S. L., S40 (ePS2.02), S65 (P036) Pintani, E., S56 (P007), S63 (P031), S10 (WS06.4), Quittner, A. L., S32 (WS19.6), S118 (P221), Patrone, M., S113 (P201) S34 (WS21.5) S156 (P360), S161 (P376), S162 (P379) Patwa, R., S53 (ePS6.06) Pinto, T., S144 (P316) Quon, B., S85 (P107), S19 (WS11.5) Patzer, J., S84 (P104) Pipeva, A., S23 (WS14.2) Paul, C., S148 (P329) Pirson, J., S100 (P156) Rabasa-Lhoret, R., S42 (ePS2.10), S125 (P244), Pauro, F., S34 (WS21.5) Pistocchi, A., S19 (WS12.1) S25 (WS15.1), S25 (WS15.2) Pavlinova, E., S69 (P049) Pivkina, N., S91 (P125) Rabeau, A., S129 (P258) Pavlov, P., S86 (P110) Plant, B. J., S126 (P249), S116 (P212) Radix, S., S93 (P134), S96 (P143) Pearce, A., S4 (WS02.6) Plaseska Karanfilska, D., S59 (P016) Raimondi, A., S9 (WS05.3) Pearson, C., S16 (WS10.1) Poerio, N., S31 (WS18.6) Ramalho, A. S., S18 (WS11.3) Pearson, L., S126 (P251), S26 (WS15.4) Pogorzelski, A., S145 (P320) Ramasli Gursoy, T., S64 (P035), S72 (P060) Peat, R., S8 (WS04.6) Pohunek, P., S10 (WS06.3) Ramel, S., S55 (P003), S76 (P076), S82 (P095), Peckham, D., S40 (ePS2.03), S41 (ePS2.05), Pokojová, E., S63 (P030) S4 (WS02.5), S20 (WS12.3), S34 (WS23.1) S126 (P251), S79 (P086), S21 (WS12.6), Poletaeva, O., S3 (WS02.2) Rames, C., S144 (P316) S26 (WS15.4), S35 (WS23.3) Polikarpova, S., S69 (P049), S91 (P125) Ramm, G., S4 (WS03.2) Pedrazzi, M., S113 (P201) Polineni, D., S152 (P342) Ramon-Garcia, S., S97 (P146) Peeters, C., S90 (P121) Polyakov, A., S58 (P011), S64 (P032) Rand, S., S142 (P307), S28 (WS16.5) Peeters, L., S62 (P028), S157 (P362) Polyakov, D., S69 (P052) Rao, G., S31 (WS19.3) Pekcan, S., S64 (P035), S72 (P060) Polyakov, N., S88 (P116) Rao, N., S58 (P012) Pellen, N., S55 (P003) Polyakov, S., S134 (P276) Rao, S., S120 (P225) Peng, L., S6 (WS04.1) Ponce-Alonso, P. M., S94 (P135) Rashid, R., S124 (P243), S143 (P312), S144 (P317) Penrose, T., S142 (P309) Pond, J., S143 (P312), S144 (P317) Ratjen, F., S31 (WS19.2) Perceval, M., S66 (P041), S101 (P162) Ponomareva, N., S69 (P052) Rault, G., S55 (P003), S67 (P043), S82 (P095), Perch, M., S2 (WS01.4) Ponomaryova, T., S69 (P052) S34 (WS23.1) Percudani, R., S120 (P227) Poole, S., S150 (P337) Ravamehr-Lake, D., S8 (WS05.2) Pereira, L., S104 (P169) Poplawska, K., S106 (P179) Ravenni, N., S60 (P018) Perenovska, P., S105 (P175), S124 (P241) Porcella, A., S111 (P196) Ravzhaeva, E., S86 (P109) Peres, A., S128 (P255) Portnov, N., S87 (P114) Raynal, C., S16 (WS09.5), S33 (WS21.3) Perez, F., S90 (P122) Postek, M., S10 (WS06.2) Raywood, E., S139 (P299) Perez, T., S159 (P371) Potapova, N., S66 (P039) Rea, R., S127 (P252) Pérez, E., S81 (P091) Potter, K. J., S25 (WS15.1) Reboul, M.-P., S33 (WS21.3) Pérez Ruiz, M., S38 (ePS1.04), S139 (P296) Potter, K., S42 (ePS2.10) Reed, A., S71 (P057) Perickathara, K., S153 (P347) Pougheon, D., S67 (P043) Regan, A., S165 (P392) Perkins, R., S75 (P069), S2 (WS01.6) Poulsen, M., S39 (ePS1.09), S144 (P318) Regan, K., S50 (ePS5.05) Perticaroli, F., S56 (P005) Poupon-Bourdy, S., S66 (P040) Reichelt, C., S95 (P138) Pescini, R., S152 (P344) Prados Sánchez, C., S105 (P176), S112 (P198) Reid, A., S86 (P108), S167 (P399) Pesenti, A., S110 (P190) Praet, A., S99 (P153) Reihill, J. A., S29 (WS17.5) Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182 S179

Reisinho, M. C., S3 (WS02.3) Ruíz de Valbuena, M., S105 (P176), S112 (P198) Schäfer, H., S97 (P148) Reix, P., S93 (P131), S99 (P153), S1 (WS01.1), Ruíz-Gutierrez, H. H., S72 (P061) Schall, J., S135 (P285) S25 (WS15.3) Rusakova, E., S78 (P080), S88 (P116) Schechter, M., S161 (P376) Remus, N., S62 (P026) Ruscitti, P., S90 (P122) Scheffold, A., S20 (WS12.2) Remy Dunyach, C., S81 (P090) Rushton, Z., S38 (ePS1.05) Schelenz, S., S54 (ePS6.10) Ren, C. L., S58 (P014), S61 (P022), S61 (P024) Russell, L., S58 (P012) Schimdt, C., S138 (P294) Rendall, J., S125 (P246) Russell, P., S29 (WS17.4) Schlangen, M., S50 (ePS5.06), S157 (P363) Rentería, F., S47 (ePS4.05), S82 (P094), Russo, A., S39 (ePS1.08), S146 (P323) Schmidt, A., S91 (P126) S109 (P188) Rutherford, C., S98 (P149), S112 (P197), Schmidt, M. N., S11 (WS06.6) Resch, G., S54 (ePS6.07) S5 (WS03.3) Schmitt, C., S109 (P186) Revel’-Muroz, N., S86 (P110) Rutland, S., S22 (WS13.3) Schnapp, Z., S117 (P214) Reyhan Onay, Z., S64 (P035) Ruvalcaba, E., S152 (P342) Schneider-Futschik, E., S31 (WS19.3) Reynaerts, A., S113 (P202), S15 (WS09.2) Rybalkina, M., S69 (P049) Scholte, B. J., S6 (WS04.1) Reynaud, Q., S67 (P043), S101 (P162), Ryzhova, N., S78 (P083), S84 (P101) Schöndorf, D., S124 (P242) S25 (WS15.3) Schotman, S., S115 (P209), S117 (P216) Rezaie, M., S134 (P281), S132 (P272) Saba, T., S148 (P331), S154 (P352) Schroeder, V., S45 (ePS3.09) Riabova, O., S97 (P146) Sabater, J., S29 (WS17.4) Schubert, R., S44 (ePS3.07) Ribeiro, A. F., S84 (P103) Saczuk, N., S86 (P110) Schultz, H. H. L., S2 (WS01.4) Ribeiro, J. D., S84 (P103) Sadlers, V., S164 (P387) Schulz, A., S15 (WS09.1) Ribeiro Batista Barbosa, R., S37 (ePS1.03) Safonova, T., S69 (P049) Schumacher, M., S44 (ePS3.04) Ricachinevsky, C., S141 (P305) Sagwal, S., S44 (ePS3.06) Schutz, S., S77 (P078), S14 (WS08.3) Richmond, S., S164 (P387) Sahadevan, A., S84 (P102) Schwartz, F. A., S93 (P133) Ridge, P. C., S117 (P217) Saidakova, S., S78 (P083) Schwarz, C., S42 (ePS2.08), S42 (ePS2.09), Riekert, K., S152 (P342) Sajnic, A., S151 (P341), S155 (P356), S165 (P391) S50 (ePS5.06), S69 (P051), S85 (P107), Righelli, D., S162 (P379) Salcedo Posadas, A., S105 (P176), S112 (P198) S97 (P148), S111 (P194), S19 (WS11.5), Riley, D., S37 (ePS1.01) Saleem Khan, M., S35 (WS23.4) S20 (WS12.2) Riley, M., S136 (P286) Saleh, R., S77 (P077) Schwarz, S., S91 (P126) Ringshausen, F., S15 (WS09.1) Saliou, P., S82 (P095) Sciolla, M., S1 (WS01.2) Rise, P., S108 (P183) Saliu, F., S109 (P187) Scotet, V., S55 (P003), S16 (WS09.5), Rits, S., S2 (WS01.6) Salmona, M., S108 (P183) S34 (WS23.1) Riva, C., S31 (WS18.6) Salobir, B., S83 (P099) Scott, E., S98 (P151), S142 (P309) Rivett, D. W., S13 (WS08.1), S80 (P088) Salomon, J. J., S30 (WS17.6) Seddon, P., S51 (ePS5.09) Rivolta, M., S147 (P325) Salvatore, D., S23 (WS13.6) Segonds, C., S81 (P093) Rizzetto, S., S109 (P187) Sammartino, J. C., S97 (P146) Seibold, W., S119 (P222) Rizzo, G., S109 (P187) Sammut, P., S141 (P306) Seillier, M., S159 (P371) Rizzo, R., S108 (P183) Sams, T., S93 (P133), S95 (P140) Selvadurai, H., S53 (ePS6.06), S107 (P181), Roberts, A., S121 (P229) San Millán, Á., S94 (P135) S109 (P189) Robertson, J., S118 (P218), S23 (WS14.1) Sánchez-López, J., S85 (P105) Semple, T., S11 (WS06.5) Robinson, N. J., S43 (ePS3.03), S20 (WS12.4), Sandage, D., S50 (ePS5.05) Semykin, S., S56 (P004), S69 (P049) S118 (P218) Sanders, D., S7 (WS04.3) Sen, V., S64 (P035), S72 (P060) Robinson, P., S107 (P181), S109 (P189) Sandri, A., S95 (P139) Senior, P. A., S25 (WS15.1) Robinson, R., S39 (ePS1.09), S118 (P219) Sandri, M., S6 (WS04.2) Sergheraert, J., S129 (P260) Robinson, T., S107 (P181), S109 (P189) Sands, D., S55 (P001), S60 (P019), S10 (WS06.2), Sergienko, D., S66 (P039) Robson, A., S60 (P021) S17 (WS10.5) Sermet-Gaudelus, I., S62 (P026), Rocheblave, L., S93 (P134), S96 (P143) Sandvik, R. M., S11 (WS06.6) S109 (P186), S8 (WS05.1), Rodella, L., S56 (P007), S34 (WS21.5) Sanseverino, M. T., S64 (P034), S113 (P199) S49 (ePS5.01), S51 (ePS5.08), Rodgers, N., S143 (P312), S144 (P317) Sanseverino, P. B., S64 (P034), S113 (P199) S7 (WS04.4), S16 (WS09.5) Rödiger, J., S44 (ePS3.04) Santo Ramalho, A., S18 (WS11.1), Seroklinov, V., S66 (P039), S60 (P020) Rodrigues, T., S72 (P059) S18 (WS11.2) Serrero, M., S41 (ePS2.04) Rodriguez, E., S83 (P100) Santos, L., S29 (WS17.2) Servel, N., S8 (WS05.1) Rodriguez, V., S83 (P100), S88 (P115), S111 (P195) Sanz, V., S38 (ePS1.04) Setchell, K., S12 (WS07.5) Rodriguez Hortal, C., S28 (WS16.6) Sapan, N., S64 (P035), S72 (P060) Sewall, A., S21 (WS13.1) Roehmel, J., S114 (P206) Sapiejka, E., S121 (P230) Seymour, H. L., S136 (P287), S154 (P352) Rohde, G. G. U., S44 (ePS3.07), S157 (P363) Saralegui, C., S81 (P091), S94 (P135) Shadrina, V., S60 (P020), S64 (P033), S69 (P049), Romanenko, N., S69 (P049) Sarouk, I., S18 (WS11.1) S106 (P177) Ronen, B.-Y., S130 (P264) Sasorith, S., S33 (WS21.3) Shafi, N., S149 (P334) Rönsholt, F. F., S2 (WS01.4) Satsuk, N., S59 (P017) Shaginyan, I., S78 (P080), S87 (P114), Ros, M., S120 (P226) Sauer-Heilborn, A., S15 (WS09.1) S88 (P116) Rose Cash, M., S90 (P122) Saunders, C., S157 (P361), S11 (WS06.5) Shah, M., S75 (P069) Rossi, M., S31 (WS18.6) Sauty, A., S54 (ePS6.07) Shakirova, G., S58 (P011) Rota, I., S111 (P196) Savage, J., S118 (P221), S32 (WS19.6) Sharma, N., S4 (WS02.6) Rouault, K., S33 (WS21.2) Save, J., S54 (ePS6.07) Shaw, G., S142 (P307) Round, C., S119 (P224) Savi, D., S111 (P196) Shaw, K. L., S67 (P044) Rourke, C., S158 (P365) Savic, S., S21 (WS12.6) Shaw, M., S102 (P164), S118 (P219) Rovedder, P. M., S138 (P294), S141 (P305) Sawicki, G., S75 (P069) Shaw Núñez, E., S3 (WS02.4) Rowe, S., S22 (WS13.3) Sawyer, S. M., S156 (P360) Shawcross, A., S135 (P283) Rozen, G., S130 (P264) Sbaragli, G., S63 (P029) Sheikhi, A., S27 (WS16.1) Rudolf, I., S124 (P242), S13 (WS08.2) Scambler, T., S21 (WS12.6) Shelley, J., S137 (P291), S140 (P302) Ruelens, C., S160 (P372) Scansani, S., S110 (P190) Shepherd, E., S159 (P370), S167 (P400) Ruffin, M., S68 (P048) Scaravilli, V., S110 (P190) Sheppard, E., S135 (P283) S180 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Sherman, V., S48 (ePS4.07), S57 (P009), Smyth, A. R., S76 (P075), S53 (ePS6.04), Sýkora, J., S110 (P192) S58 (P011), S60 (P020), S69 (P049), S132 (P271) Sýkorová, A., S110 (P192) S87 (P114), S88 (P116), S106 (P177), Snell, C., S50 (ePS5.05) S57 (P008), S34 (WS21.6), S86 (P110), Snowball, J., S127 (P252) Tabarini, P., S147 (P325), S162 (P379) S69 (P052) Sobczyńska-Tomaszewska, A., S55 (P001) Tabberner, M., S120 (P225) Sherrard, L. J., S88 (P117), S89 (P118), S89 (P119), Sokolov, I., S134 (P276) Taccetti, G., S60 (P018) S89 (P120) Solé Jover, A., S105 (P176), S112 (P198) Tacchetti, C., S9 (WS05.3) Shevlyakova, A., S69 (P049) Soloviev, A., S78 (P080) Taffarel, C., S138 (P294), S141 (P305) Shimmin, D., S126 (P251), S26 (WS15.4) Sommer, L., S14 (WS08.5) Taggart, C. C., S86 (P108), S44 (ePS3.05) Shin, K., S2 (WS01.6) Sommerburg, O., S124 (P242) Tahir, M., S150 (P337) Shinkareva, V., S66 (P039) Sontag, M., S58 (P014), S61 (P022), S61 (P024) Tai, A., S134 (P278) Shirazi, T., S41 (ePS2.06) Sorio, C., S56 (P007), S108 (P183), S34 (WS21.5) Takken, T., S140 (P300) Shopova, S., S162 (P380) Sourla, E., S150 (P338) Talimtzi, P., S9 (WS06.1) Short, C., S11 (WS06.5) Southern, K. W., S104 (P171), S133 (P273), Tamay, Z., S64 (P035), S72 (P060) Shoshan, N. B., S39 (ePS1.08) S164 (P387) Tamburri, L. M., S102 (P165) Shteinberg, M., S117 (P214) Sowerby, C., S82 (P097) Tamm, S., S15 (WS09.1) Shulyak, I., S69 (P052) Spahn, S., S30 (WS17.6) Tan, L., S116 (P211), S134 (P281) Shumkova, G., S1 (WS01.3) Speight, L., S71 (P056), S41 (ePS2.07), S116 (P211) Tana Aslan, A., S64 (P035) Sid Ahmed, M., S80 (P089) Speight, T., S22 (WS13.5) Tanackovic, L., S47 (ePS4.03), S135 (P284) Sikora, N., S86 (P110) Spence, C. D., S14 (WS08.4) Tandar, A., S110 (P191) Silfverplatz, Å., S76 (P073) Spillman, L. N., S126 (P250) Tanner, K., S73 (P065), S74 (P066) Sills, D., S46 (ePS4.01), S125 (P245), S132 (P270), Spirevska, L., S59 (P016), S124 (P240) Tansinda, A., S158 (P365), S2 (WS02.1) S132 (P271), S134 (P277), S16 (WS10.2), Spoletini, G., S41 (ePS2.05), S21 (WS12.6) Tate, J., S131 (P266) S17 (WS10.6) Sputael, V., S138 (P292) Taylor, A., S163 (P382) Silva, A. M., S104 (P169) Stackhouse, C. A., S126 (P250), S133 (P274), Taylor, J., S150 (P337) Silva, I. A. L., S114 (P204) S136 (P288) Taylor, K., S126 (P251), S26 (WS15.4), Silva Filho, L. V., S73 (P062) Stagaki, E., S62 (P027) S103 (P166), S7 (WS04.5) Silveira de Almeida, I., S139 (P296) Stahl, M., S124 (P242) Temming, S., S69 (P051), S97 (P148) Simanova, T., S60 (P020) Stähle, B., S50 (ePS5.06) Tenero, L., S6 (WS04.2) Simbo, A., S94 (P137) Stallings, V., S130 (P262), S135 (P285) Teper, A., S83 (P100), S88 (P115), S111 (P195) Simmonds, N. J., S71 (P057), S35 (WS23.4) Stamatova, A., S59 (P016), S124 (P240) Terheggen, S., S70 (P053) Simon, M., S141 (P305) Stanke, F., S43 (ePS3.01), S15 (WS09.1) Terlizzi, V., S60 (P018) Simon, S., S9 (WS05.4) Stanojevic, S., S36 (WS23.6) Terp Raun, A. M., S133 (P275) Simonds, S., S163 (P383) Starinova, M., S57 (P010), S58 (P011), S60 (P020), Terpstra, F. J., S94 (P137) Simonneau, B., S9 (WS05.4) S64 (P032), S66 (P039), S69 (P049), Terrail, N., S30 (WS18.4) Simonova, O., S69 (P049), S78 (P083), S84 (P101), S69 (P052), S86 (P110) Tersmette, J., S105 (P173) S123 (P239), S134 (P276) Starodubtceva, O., S86 (P109) Terzikj, M., S59 (P016) Simpson, K., S71 (P056) Stashkevich, T., S60 (P020), S66 (P039) Tetard, A., S96 (P144) Singh, J., S53 (ePS6.06) Stefanelli, R., S96 (P142) Tetard, C., S5 (WS03.4) Singh, M., S44 (ePS3.06) Stein, L., S138 (P293) Tetlow, L., S60 (P021) Singleton, P., S13 (WS07.6) Steinkamp, G., S47 (ePS4.04) Tetz, G., S53 (ePS6.05), S87 (P112), S87 (P113) Sinkov, E., S1 (WS01.3) Stepanenko, T., S69 (P052) Tetz, V., S53 (ePS6.05), S87 (P112), S87 (P113) Sionidou, M., S150 (P338) Stephenson, A., S36 (WS23.6) Therouanne, S., S159 (P371) Sioofy Khojine, A., S128 (P257) Sterk, P. J., S52 (ePS6.01) Thewissen, R., S160 (P372) Sipione, B., S109 (P187) Stewart, C., S140 (P302) Thickett, K., S66 (P042) Sismanlar Eyuboglu, T., S64 (P035), Stewart, I., S76 (P075) Thomas, F., S158 (P367) S72 (P060) Stezhkina, E., S58 (P011), S64 (P032) Thomas, M., S36 (WS23.5) Sitch, A., S67 (P044) Still, J., S126 (P247) Thomas, T., S6 (WS03.6) Sivam, S., S99 (P152) Stolpe, C., S15 (WS09.1) Thomsen, K., S45 (ePS3.08), S93 (P133) Sixhöj, A., S76 (P073) Stone, T. A., S8 (WS05.2) Thomson, A., S49 (ePS4.10) Siyanova, E., S78 (P080), S88 (P116) Straub, C., S109 (P186) Thomson, L., S122 (P232) Skachkova, M., S69 (P049) Strecker, L., S113 (P203) Thöni, G., S141 (P303) Skalicka, V., S10 (WS06.3) Strehlow, A.-L., S50 (ePS5.06) Thrane, S., S54 (ePS6.10) Skalland, M., S7 (WS04.3) Strenger, V., S84 (P104) Thursfield, R., S51 (ePS5.09), S104 (P171) Skorupa, W., S121 (P230) Strong, M., S69 (P050) Thyssen, C., S95 (P140) Skov, M., S133 (P275), S11 (WS06.6), Struwe, P., S108 (P184) Tian, S., S21 (WS13.1), S31 (WS19.2) S14 (WS08.5) Sturt, J., S127 (P254) Tiddens, H. A. M. W., S6 (WS04.1) Slaby, K., S145 (P320) Subedi, D., S53 (ePS6.06) Tierney, A., S132 (P269), S27 (WS16.1) Smaczny, C., S50 (ePS5.06), S157 (P363) Sudakaran, S., S5 (WS03.5) Tiesinga-van der Lijn, A. M., S160 (P373) Smink, M., S119 (P223) Sunsoa, H., S124 (P243), S128 (P256) Tillman, L., S161 (P376) Smirnov, I., S123 (P239) Surkov, A., S123 (P239) Timofeeva, O., S91 (P125) Smirnova, V., S58 (P011), S64 (P032) Surowiecka, M., S17 (WS10.5) Tindall, A., S135 (P285) Smith, A., S156 (P357) Sutharsan, S., S19 (WS11.5) Tirouvanziam, R., S6 (WS04.1) Smith, B., S161 (P376) Svanekær, T., S93 (P133) Tjesic-Drinkovic, D., S47 (ePS4.03), S135 (P284), Smith, C. M. T., S40 (ePS2.01) Sviridova, T., S166 (P395) S151 (P341), S155 (P356), S165 (P391), Smith, J. A., S78 (P081), S79 (P085), S103 (P168) Svistushkin, V., S1 (WS01.3) S47 (ePS4.03), S135 (P284), S151 (P341), Smith, L., S164 (P389), S35 (WS23.3) Sweis, D., S150 (P337) S155 (P356), S165 (P391), S48 (ePS4.09), Smith, O., S125 (P246) Syed, A., S124 (P243), S128 (P256) S130 (P265), S48 (ePS4.09), S130 (P265) Smith, T., S73 (P065), S74 (P066) Sykes, J., S166 (P396), S36 (WS23.6) Tofeec, K., S40 (ePS2.01) Smith, W. D., S94 (P137) Sykes, L., S96 (P141) Togochakova, O., S58 (P011) Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182 S181

Toin, T., S25 (WS15.3) Van Mourik, P., S18 (WS11.2), S19 (WS11.4) Wallis, C., S51 (ePS5.09) Tokou, I., S17 (WS10.4) Van Oirschot-van de Ven, M., S115 (P209), Walshaw, M., S46 (ePS4.02), S80 (P087), Toledano, M. B., S35 (WS23.4) S117 (P216) S98 (P150), S98 (P151), S102 (P164), Tomba, F., S56 (P007), S34 (WS21.5) Van Raemdonck, D., S14 (WS08.4) S114 (P205), S118 (P219), S140 (P302), Tomlinson, O. W., S137 (P291), S139 (P298), Van Rens, J., S22 (WS13.4), S35 (WS23.2) S142 (P309), S162 (P381), S165 (P390), S27 (WS16.4), S38 (ePS1.06) Vanaudenaerde, B., S14 (WS08.4) S8 (WS04.6), S14 (WS08.6) Tonge, M., S156 (P359) Vandamme, P., S90 (P121) Wang, C., S118 (P221), S32 (WS19.6) Topal, E., S64 (P035), S72 (P060) Vandenesch, F., S92 (P128), S92 (P129), Warburton, L., S58 (P012) Törnberg, A., S167 (P398), S28 (WS16.6) S93 (P131) Ward, C., S45 (ePS3.09) Tortoli, E., S31 (WS18.6) VanDevanter, D., S45 (ePS3.10), S7 (WS04.3) Ward, M., S43 (ePS3.02) Touilin, F., S4 (WS02.5) Vanneste, J., S159 (P371) Wardle, O., S52 (ePS6.02) Toukan, Y., S130 (P264) Vasileva, T., S69 (P049) Warnecke, G., S44 (ePS3.04) Touqui, L., S94 (P136), S97 (P145) Vasilyeva, E., S58 (P011), S60 (P020), S64 (P032) Warnock, L., S37 (ePS1.02), S142 (P308), Touzet, S., S66 (P040), S25 (WS15.3) Vasilyeva, N., S85 (P106) S142 (P310), S147 (P327), S147 (P328) Towns, S., S107 (P181), S109 (P189) Vasilyeva, T., S57 (P008), S60 (P020), Warzeszak, K., S145 (P320) Trajkovska, M., S124 (P240) S34 (WS21.6) Watkinson, J., S58 (P012) Trappe, A., S43 (ePS3.02) Vazquez, M., S88 (P115) Watson, D., S149 (P334) Trefil, L., S110 (P192) Vecherkovskaya, M., S53 (ePS6.05), S87 (P112), Wdowik, J., S101 (P162) Treggiari, D., S56 (P007), S63 (P031), S87 (P113) Webb, A. K., S104 (P172), S158 (P365) S34 (WS21.5) Vechorko, V., S91 (P125) Webb, K., S53 (ePS6.04), S76 (P075) Tremblay, F., S42 (ePS2.10), S125 (P244), Velard, F., S129 (P260) Webster, M., S45 (ePS3.09) S25 (WS15.1) Velázquez, M., S85 (P105), S82 (P096) Weersink, E. J. M., S115 (P207), S52 (ePS6.01) Tridello, G., S63 (P031), S108 (P183) Veldhoen, E., S105 (P173) Weilputz, M., S107 (P181) Trishina, S., S58 (P011) Veleska, M., S164 (P388) Weinheimer, O., S107 (P181), S109 (P189) Trott, J., S38 (ePS1.06), S139 (P298) Velo-Suarez, L., S77 (P078), S14 (WS08.3) Weldon, S., S44 (ePS3.05) True, L., S164 (P386) Veltman, M., S6 (WS04.1) Welsh, M., S28 (WS17.1) Tsanakas, J., S150 (P338), S151 (P340), Vendrusculo, F. M., S37 (ePS1.03), S139 (P296) Welte, T., S15 (WS09.1) S116 (P213), S9 (WS06.1) Verhulst, S., S31 (WS19.1) Wertheim-Tysarowska, K., S55 (P001) Tugcu, G. D., S64 (P035), S72 (P060) Verleden, G. M., S14 (WS08.4) West, N., S45 (ePS3.10), S7 (WS04.3) Tümmler, B., S43 (ePS3.01), S13 (WS08.2), Verleden, S. E., S14 (WS08.4) Westrupp, N., S51 (ePS5.09) S15 (WS09.1) Vermeulen, F., S18 (WS11.1), S15 (WS09.2) Whitaker, P., S21 (WS12.6) Tunney, M. M., S78 (P081), S79 (P085), Verroken, A., S90 (P121) White, B., S45 (ePS3.10) S14 (WS08.4), S88 (P117), S89 (P118), Veschetti, L., S95 (P139) White, E., S38 (ePS1.05) S89 (P119), S89 (P120) Vételé, F., S99 (P153) White, H., S40 (ePS2.03), S35 (WS23.3) Turel, M., S83 (P099) Viard, C., S122 (P234) White, M., S152 (P342) Turner, E., S135 (P283) Vicenzi, M., S110 (P190), S111 (P196) Whitehouse, J. L., S67 (P044), S76 (P075), Tuyindi, J., S11 (WS06.5) Villa, J. R., S38 (ePS1.04) S53 (ePS6.04), S128 (P256), S124 (P243), Twigg, M., S44 (ePS3.05) Vincken, S., S100 (P156) S143 (P312), S144 (P317) Twisk, J., S27 (WS16.2) Vinohradská, J., S15 (WS09.4) Whiteley, S., S41 (ePS2.06) Vion Genovese, V., S66 (P041) Whiteson, K., S115 (P207) UK CF dietitians group, G., S136 (P288) Virdee, G., S48 (ePS4.08) Widger, J., S49 (ePS4.10) Uluer, A., S50 (ePS5.05), S2 (WS01.6) Vleugels, E., S160 (P372) Wiehlmann, L., S43 (ePS3.01), S13 (WS08.2) Ulyanova, L., S57 (P009), S66 (P039) Vodovozova, E., S69 (P052) Wielputz, M., S109 (P189) Underhill, B., S149 (P334) Voldby, C., S11 (WS06.6) Wilcock, J., S142 (P307) Urbani, A., S97 (P146) Volpi, S., S108 (P183), S6 (WS04.2), S10 (WS06.4) Wilcox, M., S79 (P086) Urvantseva, I., S59 (P017) Volta, L., S90 (P122) Wildman, M. J., S146 (P322), S23 (WS14.2), Useckaite, Z., S43 (ePS3.02) Vonk, A. M., S19 (WS11.4) S24 (WS14.4), S150 (P337) Ushatskaya, O., S69 (P052) Vonk, A., S18 (WS11.2) Wilhelmsson, S., S28 (WS16.6) Utorova, R., S128 (P257) Voronin, S., S69 (P049) Wilkinson, S., S135 (P283) Voronina, O., S69 (P049), S78 (P083), S84 (P101) Williams, C. A., S139 (P298), S27 (WS16.4), V. Cordero, C., S18 (WS11.1) Voronkova, A., S57 (P008), S58 (P011), S38 (ePS1.06) V.d. Vaart, H., S160 (P373) S64 (P032), S66 (P039), S69 (P049), Williams, E. J., S2 (WS01.5) Valaskova, I., S15 (WS09.4) S69 (P052), S78 (P080), S86 (P110), Williams, P., S53 (ePS6.04), S76 (P075) Valeri, A., S4 (WS02.5) S87 (P114), S106 (P177), S34 (WS21.6) Willis, J., S166 (P397) Vallet, S., S54 (ePS6.08) Vorup-Jensen, T., S54 (ePS6.10) Wilson, C., S41 (ePS2.07) Vallier, C., S154 (P351) Vos, R., S123 (P238), S14 (WS08.4) Wilson, J. W., S144 (P318) Van Brunt, K., S118 (P221), S32 (WS19.6) Vosecký, M., S147 (P326) Wilson, L. M., S144 (P318) Van der Ent, C. K., S51 (ePS5.07), S140 (P300), Vukic Dugac, A., S47 (ePS4.03), S48 (ePS4.09), Wilson, P., S149 (P334) S70 (P055), S115 (P209), S117 (P216) S130 (P265), S135 (P284), S151 (P341), Winstanley, C., S77 (P079), S80 (P087), Van der Gast, C., S80 (P088), S13 (WS08.1) S155 (P356), S165 (P391) S98 (P150), S98 (P151), S14 (WS08.6) Van der Haak, N., S134 (P278) Wadsworth, L., S37 (ePS1.01) Winter, I., S16 (WS10.3) Van der Heijden, D. C., S51 (ePS5.07) Wagner, T. O. F., S157 (P363) Wirsching, S., S106 (P179) Van der Meer, R., S70 (P053), S119 (P223) Walchshofer, N., S93 (P134), S96 (P143) Wisniewska, A., S52 (ePS6.02) Van der Vaart, H., S70 (P053), S119 (P223) Walicka-Serzysko, K., S10 (WS06.2) Withers, N. J., S139 (P298), S27 (WS16.4), Van Dorst, J., S6 (WS03.6) Walker, C., S48 (ePS4.08) S38 (ePS1.06), S41 (ePS2.06) Van Haarst, A. D., S103 (P167), S108 (P184) Walkowiak, J., S121 (P230) Woillard, J.-B., S100 (P155) Van Hal, S., S99 (P152) Wallace, M., S146 (P324), S12 (WS07.2) Wojsyk-Banaszak, I., S121 (P230) Van Holsbeke, C., S31 (WS19.1) Wallenburg, J., S51 (ePS5.09) Wolfender, J.-L., S52 (ePS6.03) Van Hoorenbeeck, K., S31 (WS19.1) Waller, I., S104 (P172) Wong, C., S21 (WS12.6) Van Meerbeeck, S., S123 (P238), S137 (P290) Wallin, K., S12 (WS07.4), S28 (WS16.6) Wong, W., S131 (P266) S182 Author Index / Journal of Cystic Fibrosis 19S1 (2020) S169–S182

Woodland, C. J., S133 (P273) Yenina, Y., S69 (P052) Zhekaite, E., S48 (ePS4.07), S66 (P039), Woodward, S., S127 (P254) Yiallouros, P., S65 (P037) S129 (P261), S78 (P080) Wooldridge, L., S155 (P355) Yilmaz Yegit, C., S163 (P385) Zhestkov, A., S81 (P092), S83 (P098) Worsdell, K., S68 (P046) Young, E., S150 (P337) Zhou, Z. P., S28 (WS17.1) Worthington, A., S158 (P365) Young, G., S80 (P087) Zhuhovitsky, V., S78 (P080), S88 (P116) Wosniok, J., S42 (ePS2.08) Yu, L., S107 (P181), S109 (P189) Zigangirova, N., S78 (P083) Wozniacki, L., S55 (P001) Yuksel, H., S64 (P035), S72 (P060) Zil’ber, I., S86 (P110) Wright, L. L., S77 (P079), S14 (WS08.6), Zilber, I., S86 (P109) S98 (P151) Zabner, J., S28 (WS17.1) Zimbric, M., S30 (WS18.1) Wu, R., S58 (P014), S61 (P022), S61 (P024), Zahigian, R., S21 (WS13.1), S31 (WS19.2) Zinchenko, R., S57 (P008), S57 (P009), S58 (P011), S21 (WS13.1) Zahreldin, K., S80 (P089) S64 (P032), S69 (P049), S34 (WS21.6) Wybo, I., S90 (P121) Zain, N. M. M., S53 (ePS6.04), S76 (P075) Zodbinova, A., S48 (ePS4.07), S57 (P009), Zainal Abidin, N., S36 (WS23.5) S58 (P011), S64 (P032), S129 (P261) Yaacoby-Bianu, K., S117 (P214) Zaki, S. F. H., S161 (P378) Zolin, A., S106 (P178), S22 (WS13.4), Yagubyants, E., S58 (P011), S60 (P020) Zaragoza, S., S83 (P100), S88 (P115), S35 (WS23.2) Yakovleva, V., S58 (P011), S64 (P032) S111 (P195) Zomer, D. D., S70 (P053), S70 (P055), S119 (P223) Yalcin, E., S64 (P035), S72 (P060) Zattera, E., S90 (P122) Žolnir, M., S83 (P099) Yanev, N., S62 (P025) Zavataro, L., S60 (P018) Zybert, K., S55 (P001), S60 (P019), S17 (WS10.5) Yannakoulia, M., S17 (WS10.4) Zelenski, S., S75 (P071) Zyryanov, S., S106 (P177) Yazan, H., S64 (P035), S72 (P060) Zemel, B., S130 (P262) Zysman-Colman, Z., S130 (P262) Guide for Authors Editorial Board For submissions to the Journal of Cystic Fibrosis please consult the Guide for Authors at www.elsevier.com/locate/jcf TheEditor-in-Chief: Official Journal of the European Cystic Fibrosis Society Scott Bell‚ Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Queensland, Australia DescriptionDeputy Editors: The JournalCarlo of Castellani, Cystic Fibrosis Cystic is Fibrosis the official Centre, journal Azienda of theOspedaliera European Universitaria Cystic Fibrosis Integrata Society. Verona, The journalPiazzale is devoted Stefanito promoting 1, Verona, the Italyresearch and treatment of cystic fibrosis. To this end the journal publishes original scientificPatrick articles, Flume editorials,, Medical case Universityreports, short of Southcommunications Carolina, Charleston, and other informationSouth Carolina, relevant USA to cystic fibrosis. TheFounding journal also Editor: publishes news and articles concerning the activities and policies of the ECFS as well as those of other societiesHarry relatedHeijerman to the, Dept.ECFS. of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands Editorial Board: Audience Pediatricians,Janice pulmonologists, Abbott, UK gastroenterologists, internists,Geraint microbiologists, Rogers, Australia pharmacologists, immunologists, psychologists,Scott basic Blackman, scientists, USA physiotherapists, dieticiansSteven and Rowe,nurses dealing USA with the investigation and treatment of cystic fibrosis.Pierre-Régis Burgel, France Laura Sherrard, UK Neelkamal Chaudhary, USA Anne Stephenson, Canada EditorialAleksander Board Edelman, France Cliff Taggart, UK Editor-in-Chief:Pascale Fanen, France Daan Touw, The Netherlands ScottNiels Bell ‚Høiby, Adult Cystic Denmark Fibrosis Centre, The PrinceMichael Charles Tunney, Hospital, N. Queensland, Ireland Australia Deputy Editors:Paul McCray, USA Donald Van Devanter, USA C. Castellani,Marianne Cystic Muhlebach, Fibrosis Centre, USA Azienda OspedalieraMichael Wilschanski, Universitaria Integrata Israel Verona, Piazzale StefaniGerald 1, Verona, Pier, Italy USA Jeffrey Wine, USA P. Flume, Medical University of South Carolina, Charleston, South Carolina, USA Felix Ratjen, Canada Susannah King, Australia Founding Editor: StatisticalH.G.M. Heijerman Advisers:, Dept. of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands EditorialChristine Board: Etherington, United Kingdom Christoph Meisner, Germany EditorJ. Abbott, In Chief, UK Cystic Fibrosis Research News:F. Ratjen, Canada D.Harry Bilton, Heijerman UK ‚ Dept. of Pulmonology,G. HagaRogers, Teaching Australia Hospital, The Hague, The Netherlands S. Blackman, USA S. Rowe, USA N. Chaudhary, USA M. Schwarz, UK G. Cutting, USA A. Stephenson, Canada C. Taggart, UK A. Edelman, France D.J. Touw, The Netherlands I. Fajac, France M. Tunney, N. Ireland N. Høiby, Denmark D. Van Devanter, USA P. McCray, USA M. Wilschanski, Israel M. Muhlebach, USA J. Wine, USA J. Pier, USA S. King, Australia Statistical Advisers: C. Etherington, United Kingdom C. Meisner, Germany Editor In Chief, Cystic Fibrosis Research News: H.G.M. Heijerman‚ Dept. of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands

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