Tracheomalacia and Bronchomalacia in Children (TF-2016-21)

Tracheomalacia and bronchomalacia in children (TF-2016-21)

TOPIC ALLOCATION July 2017. Key question numbers and final section headings

QUESTION AND FINAL TOPIC HEADING RESPONSIBLE TF MEMBERS 1. What is the definition of tracheal (TM) and major Deborah Snijders

bronchial malacia (BM) and what classifications of Kostas Douros severity exist?

INTRODUCTION 2. What are the causes of tracheo-bronchomalacia (TBM)? Ahmad Kantar CONDITIONS ASSOCIATYED WITH TBM Andrew Bush 3. What is the spectrum of clinical presentation, severity Ernst Eber and clinical course – to include any studies on the Rafaella Nenna untreated natural history of this condition? CLINICAL SYMPTOMS AND SIGNS 4a.In children suspected of having TBM, can pulmonary Ann Chang function tests be used to diagnose TBM Ahmad Kantar 4b. In children with known TBM, what are the pulmonary function abnormalities ROLE OF LUNG FUNCTION 5. How do we use Imaging to diagnose TM & BM? [To Efthymia Alexopoulou include tracheobronchography] Derek Roebuck ROLE OF IMAGING 6a. How do we use Bronchoscopy [rigid and flexible] to Fabio Midulla diagnose TM & BM? Kostas Douros 6b. What influence does a general anaesthetic have on the diagnostic testing for TBM ROLE OF BRONCHOSCOPY 7. Which medical therapies have been suggested for the Jayesh Bhatt management of TBM and co-morbidities [e.g. wheezing, Andrew Bush endobronchial infection, atelectasis?] MEDICAL THERAPIES 8. What is the role for respiratory physiotherapy? Anna-Maria Charatsi PHYSIOTHERAPY Julie Depiazzi 9. How and when should we treat TM & BM by internal Derek Roebuck stenting? Juan Anton-Pacheco SURGERY INCLUDING STENTING 10. What surgical strategies have been suggested for the Juan Anton-Pacheco management of TBM – eg aortopexy, tracheopexy, external splints, tracheal resection, tracheostomy. SURGERY INCLUDING STENTING 11. What is the indication for long term ventilatory support Mark Everard either by tracheostomy or non-invasive interface and Ian Brent Masters what ventilator strategies have been trialled? VENTILATORY SUPPORT 12. What is the parent and patient perspective? Courtney Coleman PARENT AND PATIENT PERSPECTIVE Barbara Johnson

PRISMA: QUESTION 3 Clinical Symptoms and Signs

524 abstracts identified by searchers*

467 studies excluded by title 22 studies excluded by abstract

35 full texts retrieved for further evaluation of eligibility

8 studies excluded. Reasons: no clinical symptoms and signs reported.

27 studies met inclusion criteria

*Keywords: (tracheomalacia or bronchomalacia) and (symptoms or "clinical presentation" or "severity" or "clinical course" or “natural history”) Limited to: Publication dates: from 01/01/1997 to 01/06/2017 Species: Humans Languages: English

PRISMA QUESTION 8 - PHYSIOTHERAPY

Search terms

Tracheomalacia OR bronchomalacia OR tracheobronchomalacia OR malacia OR tracheal abnormalities OR tracheal diseases

AND

Physiotherapy OR physical therapy OR physical therapy modalities OR airway clearance OR positive pressure and physiotherapy

Exercise tolerance OR exercise therapy

Administration inhalation OR nebulisation OR saline solution hypertonic OR deoxyribonuclease I OR nebulised dornase alfa OR nebulised hypertonic saline

Records identified Additional records identified through search through other sources (n = 289) (n = 169)

Records after duplicates removed Records excluded (n = 215) Not humans, English (n = 56)

Records screened (titles and abstracts) Records excluded (n = 159) (n = 120)

Full text articles excluded (N = 31) Full text articles assessed for eligibility No relevant outcomes (n = 8) (n = 39) Adult participants (n= 3) Case study (n = 3) Expert opinion/Review (n = 3) Full text not available (n = 6) Potential studies for analysis (n = 8) Language other than English (n = 6) RCT (n = 1) Duplicate (n = 1) Systematic Review (n = 3) Older than 20 years (n = 1) Other (n = 4)

Studies used for final analysis (n = 4) RCT (n = 0) Systematic Review (n = 1) Other (n = 3)

Question 3: Clinical Symptoms and Signs

1st author, Setting; Inclusion Description Main aim(s) of study Primary findings relating to Main study Method of publication Study criteria; of cohort KQ limitation confirmation of year design Exclusion or TBM and type definitions Adil 2012 Tertiary 130 consecutive TM: 25 1 “to identify the most 19% of infants with Retrospective Fluoroscopy and/or referral preterm and term infants common area(s) of laryngomalacia had TM study; different direct laryngoscopy centre; infants with supraglottic collapse” methods of and bronchoscopy retro- laryngomalacia, 2 “to compare airway confirmation of under general spective as diagnosed by findings in term and preterm TM anaesthesia airway endoscopy infants” between June 3 “to evaluate the incidence 2004 and August of secondary airway lesions” 2009 Boogaard Tertiary All flexible TM: 63 1 “to estimate the incidence Types of symptoms and clinical Retrospective Flexible 2005 referral bronchoscopies children; of primary airway malacia features study bronchoscopy centre; performed TBM: 49 in the general population” under general retro- between 1997 and children; 2 “to estimate the predictive anaesthesia; airway spective 2004 (n=512); BM: 24 value of clinical diagnosis of malacia was malacia defined as children malacia by paediatric diagnosed by visual collapse of at least pulmonologists” inspection of 50% of the airway 3 “to characterise the airway shape and lumen, during presenting symptoms and dynamics during expiration, cough findings in patients spontaneous or spontaneous diagnosed with primary breathing without breathing, or a airway malacia” positive ratio of cartilage endexpiratory to membranous pressure, or during wall area of < 3:1. coughing. Carden Review TM and TBM in NA “a comprehensive review of Types of symptoms, severity, NA NA 2005 children and both the adult and paediatric natural history adults forms of the disease” and “review of the various modalities that are used for diagnosis as well as the state

of the art of treatment” Choo 2013 Review Tracheomalacia/ NA NA Types of symptoms, severity, Adult literature NA Tracheobroncho- natural history malacia and hyperdynamic airway collapse Dessoffy Retro- 236 children with 9 children 1 “to establish the frequency 4% of children with Retrospective Airway endoscopy 2013 spective achondroplasia, with TM or of airway malacia in a achondroplasia had TM or TBM study; different or clinical who were TBM cohort of children with methods of examination initially assessed achondroplasia” confirmation of between 1985 and 2 “to assess its interactions TM or TBM 2012 with other known breathing abnormalities in these individuals” Doshi 2007 Case NA NA To describe symptoms of Types of symptoms Case report Bronchoscopy report TM in an infant Finder Retro- Patients with 17 children “to determine the natural Natural history Retrospective Bronchoscopy 1996 spective primary BM (age at history of primary BM in study under light diagnosis of infants and children” sedation? BM: 3 months-17 years) Fraga 2016 Review Primary NA NA Time of onset and types of NA NA (congenital) and symptoms, severity secondary (acquired) TM and TBM Hiebert Systematic Articles 11 articles 1. “to identify risk factors TBM in 4.6% of children with Heterogeneity Bronchoscopy 2016 review and addressing reviewed; that may predict clinically recurrent croup between studies meta- bronchoscopy in 5 articles significant findings on and lack of analysis children with (455 patients) bronchoscopy in children specificity in recurrent croup included in with recurrent croup” patient meta-analysis 2. “to note the frequency of reporting. bronchoscopy findings in Selection bias of general” the patients. Hysinger Review Focus on TM NA 1. “to distinguish congenital Types of symptoms, natural NA NA 2

2015 TM from acquired TM”; history, associated diseases 2. “to define respiratory mechanics that affect airway compliance”; 3. “to describe the formation and maturation of the paediatric central airway”; 4. “to describe advantages and disadvantages of the various methods of diagnosing paediatric TM”; 5. “to understand the current available treatment strategies for paediatric TM” Javia 2016 Review Congenital/primar Neonates NA Types of symptoms and clinical NA NA y and features, associated conditions acquired/secondar y TM Keng 2017 Case NA 83-year-old NA Delayed onset of symptoms Case report, NA report woman adult patient Kompare Retro- Incl: <60 months 70 children “to examine associated TM in 20%, BM in 43% and Retrospective Flexible 2012 spective, of age with cough, findings and clinical TBM in 11% of patients with study, no control bronchoscopy using specialty wheeze, and/or outcome in young children protracted bacterial bronchitis group topical lidocaine clinic noisy breathing with prolonged cough, and intravenous present for at least wheeze, and/or noisy procedural sedation 1 month without breathing in whom high other diagnoses colony counts of potentially for whom BAL pathogenic bacteria were cultures grew at cultured from least 104 cfu/mL bronchoalveolar lavage of a specific (BAL) during diagnostic organism flexible fibreoptic Excl: asthma, CF, bronchoscopy” and other chronic diseases TM or BM

diagnosed when segmental collapse such that the airway narrowed to a slit during expiration in the absence of suction through the bronchoscope’s channel. Kugler Review TM in children NA NA Types of symptoms NA NA 2013 and adults Maeda Review TM in children NA “to present the technical Types of symptoms NA NA 2017 aspects of diagnosis and treatment of the most common paediatric airway disorders” Masters Tertiary Children with the 299 children 1. “to describe an extensive Types of symptoms and clinical No detailed Flexible 2002 referral endoscopic with malacia experience of various forms features, associated conditions description of bronchoscopy centre; diagnosis of disorders of laryngomalacia, symptoms and during spontaneous observatio laryngomalacia, tracheomalacia, and signs breathing under nal study TM or TBM; bronchomalacia” gaseous general TM defined as “a 2. “to explore some of the anaesthesia membranosa interrelationships that exist deformity in the between these conditions trachea” with respect to their BM defined as anatomical sites and “an appearance of associations” deformity in the large right or left main-stem bronchi, and/or their respective divisions at the lobar or segmental

level. Masters Tertiary Children with Cases: 81 “to prospectively examine Children with malacia have an Sample size Bronchoscopy with 2008 referral chronic children (0.2- the relationship between site increased likelihood of spontaneously centre; respiratory 12.4 years) and size of lesions with their respiratory illness frequency, breathing oxygen case- symptoms of Controls: 35 respiratory symptoms and severity, significant cough, and and sevoflurane control cough, stridor, or children (0.2- illness frequency” tendency for delayed recovery. general anaesthesia study wheeze present 17.3 years) Neither the site nor the severity for >3 weeks that of malacia exhibited any underwent significant dose effect on bronchoscopy respiratory illness profiles. Malacia defined as a deformity of the airway recorded at the end-expiratory point McNamara Review Primary and NA NA Types of symptoms and clinical NA NA 2004 secondary TM features, natural history Peh 2006 Case NA 4-week-old NA Delayed onset of symptoms Case report Bronchoscopy report infant Peters 2005 Case NA 20-month-old “to discuss the differential Types of symptoms and clinical Case report Bronchoscopy report and boy diagnosis and clinical features review evaluation, and propose a new pathophysiological mechanism by which obstructive sleep apnea causes TM” Rohde Case NA 15-month-old “to stress the importance of Types of symptoms Case report Autopsy 2005 report boy considering laryngo-tracheobronchomalacia as a cause of death in infancy and early childhood” Santiago- Retro- Incl: Children Cases: 62 1. “to describe the Airway malacia in 52% of Retrospective Bronchoscopy on Burruchag spective with recurrent children (12- bronchoscopic changes in children with recurrent lower study; control spontaneous a 2014 case- pneumonia, 144 months) children with recurrent airway infection group not breathing under control chronic wet or Controls: 29 lower airways infection” normal healthy sedation-analgesia 5 cohorts productive cough, children (5- 2. “to investigate the children and local study persistent 168 months) prevalence of lower airway anaesthesia atelectasis, or malacia” bronchiectasis 3. “to assess their Excl: prevalence in a control Bronchopulmonar group without recurrent y dysplasia, lower airways infection” prematurity, difficult to control asthma, CF, immunodeficienc y, genetic syndromes, neuromuscular, CNS or heart disease, airways or digestive tract malformations, severe scoliosis, protracted endotracheal intubation, tracheotomia or endobronchial aspiration syndrome Airway malacia considered to be present when >50% dynamic collapse of the airways lumen during expiration on spontaneous breathing or during cough,

without suctioning Snijders Review Congenital and NA “to provide an update on Types of symptoms and clinical NA NA 2015 acquired TM diagnosis of TM in features children” Vicencio Short TM NA NA Types of symptoms and clinical NA NA 2006 review features Weinberge Review TM NA “to increase awareness of Causes of cough in children with NA NA r 2007 common and uncommon TM entities that have resulted in inappropriate diagnoses of asthma” Yalcin Tertiary Incl: Patients with 34 children 1. “to review experience Clinical presentation, associated Retrospective Bronchoscopy 2005 referral chronic with TM with flexible bronchoscopy disorders study under mild sedation centre; respiratory and/or BM for the assessment of TM and topical retro- symptoms who and BM in children who anaesthesia spective underwent presented with chronic bronchoscopy respiratory problems” between February 2. “to evaluate their clinical 1999 and and radiological November 2003. characteristics and their Excl: Asthma, association with other cystic fibrosis disorders” TM defined as an appearance of deformity and narrowing of the trachea’s cross- sectional area by, at least, more than 25% on expiration; BM defined as an appearance of deformity in the right or left main

bronchi, and/or their divisions at the lobar and segmental levels, and narrowing of their cross- sectional areas by, at least, more than 25% on expiration Zgherea Tertiary Incl: Children 197 children 1. “to determine the 9 (14.1%) of children with Retrospective Flexible 2012 referral with wet cough of frequency of lower purulent bronchitis and 6 study; no bronchoscopy centre; more than 4 respiratory tract bacterial (13.3%) of children with reliable data on under light sedation retro- weeks’ duration, infections in children with nonpurulent bronchitis had TM the prevalence spective unresponsive to wet cough” of certain therapy, referred 2. “to analyse the comorbidities; for bronchoscopy bronchoscopic findings in symptoms of Excl: Cystic these children” children with fibrosis, primary TM not provided ciliary dyskinesia, immunodeficienc y syndromes, genetic syndromes, major airway abnormalities, muscle weakness, neurologic disorders, aspiration, asthma TM defined as collapse of at least 50% of the tracheal lumen during expiration

NA, not applicable;

LITERATURE REVIEW: QUESTION 4B KQ 4b: In children with known TBM, what are the pulmonary function abnormalities?

1st author, Setting; Inclusion Description Main aim(s) of study Primary findings relating to Main study Method of publication Study criteria; of cohort KQ limitation confirmation of year design Exclusion or TBM and type definitions Abdel Retro- Incl: children with N=20 “Assess the efficacy of Tidal expiratory flow values Data was Flexible 2007 spective TM who had mean aortopexy in the long term, (TEF25%); median of cohort estimated from bronchoscopy, aortopexy age=29-mo the clinical results and estimated at 66.5 %pred (range the graph spontaneous Excl: aortic arch (range 0.25, respiratory function…” 15, 103) provided. No breathing anomalies; 11 years) other PFT data TM not defined provided Beardsmor Cohort Incl; children with 16 children in 1. “Assess the relationship Increased (>2 z-score) total gas TM undefined In one child, e esophageal cohort but between clinical findings volume in 2 of the 3 children; endoscopic 1994 atresia- only 3 had and respiratory function in Increased total airway resistance confirmation tracheoesophageal TM infants following repairs of in 2 of the 3 children mentioned; other 2 fistula presenting confirmed esophageal atresia- method not to surgical tracheoesophageal fistula; described service; 2. Determine the value of TM not defined respiratory function tests in elucidating mechanisms of respiratory disturbances and in predicting clinical outcome” Boogaard Cross TM=“collapse of 45 of the 115 1. Estimate the incidence of Mean % pred (SD) Proportion with Flexible 2005 section at least 50% of the children with primary TBM FVC=99.3 (15.9) FVC and FEV1 bronchoscopy; airway lumen, TM had PFT. 2. Estimate the predictive FEV1=91.5 (19.9) abnormality not primary TM during expiration, Mean age of value of a clinical diagnosis FEV1/FVC=87.7 (14.2) provided cough or this group not of TBM by pediatric PEF=74.7 (19.4) spontaneous described pulmonologists 3. MEF25=62.2 (31.3) breathing, or a Characterize symptoms and Pre and post broncho-dilation ratio of cartilage findings in patients with undertaken in 35, all values to membranous primary TBM showed increased in mean values wall area of < but no significant change 3:1” 1

Davis Cross TM=50% tracheal 6 infants (3- In children with TM, to Children with TM Bronchoscopy 1998 section narrowing at 10 mo old) determine whether the Mean FVC=104%pred (SD 10) (type undefined) bronchoscopy with increase in V’max FRC with Mean V’50=56%pred (SD 18) moderate to CPAP could be explained by Mean V’75=53%pred (SD 17) severe TM; the increase in FRC with Controls Controls: 2- CPAP (0, 4, 8 cm H20) Mean FVC=93%pred (SD 21) 12 mo old Mean V’50=112%pred (28) Mean V’75=108%pred (23) Johnston Pre, post NA; Child with R To study animal model of After stenting- expiratory total 2 children but Bronchoscopy 1980 Sx, TM undefined ligamentum tracheomalacia and describe pulmonary resistance decreased only 1 with PFT (type unspecified); Case study arteriosum, 2 children with symptomatic by 104%; inspiratory equivalent data. Child also vascular ring L aortic arch, TM changed by 1% had VSD and divided at 3-mo R descending (PFT at ~18 mo) tracheostomy followed by aorta decannulated external rib stent after TM stented over TM at 12 mo Moore Cross Incl: Children 19 children; To determine “whether Mean %pred (95%CI), no Flexible 2012 section with TBM (21 of median age children with TBM have abnormal in cohort bronchoscopy 66 invited 9.4 years persisting respiratory FEV1=81% (72, 91), 7 participated (range 7.6– symptoms and/or deﬁnable FVC=96% (87, 105), 4 Excl: 14.3) abnormalities of lung FEV1/FVC%=73 (67, 78), 13 laryngomalacia; function on long-term FEF25-75=54% (43, 64), 15 TM undefined follow-up” PEF=60% (49, 70), 14 Classical TBM flow-volume loop seen in 4 (22%) Mannitol challenge negative in 13 of 15 (93%); 1 of 2 had significant bronchodilator responsiveness Olbers Cross Inclusion: Group of 13 1. Assess the prevalence of Of those with known TM Other PFTs in Authors stated 2015 section children born with of 26 children respiratory morbidity in (n=13), 3 had FEV1/FVC below TM group not “diagnosis of TM esophageal atresia who had TM children born with 2 SD, described and requires X-ray who have reached esophageal atresia 10 had FEV1/PEF ratio of >8 TM undefined ﬁndings or aged 7 years; 2. Examine the cause this bronchoscopy”; TM undefined morbidity using pulmonary that was not and esophageal function routinely but done tests. in many

Panitch Case study 3 children in Child with To study pulmonary Reduced (V’maxFRC) c.f. Changes Rigid 1990 series but only 1 repaired mechanics of 3 children published norms; described may bronchoscopy included as 2 had laryngo- with intrinsic TM after Methacholine improved not be specific other concurrent trachea- bronchoconstrictor and V’maxFRC by 14.4%, Albuterol to TM{57} significant lung esophageal bronchodilator reduced V’maxFRC by 31.6%; disease and cleft repaired saline did not alter VmaxFRC. tracheostomy; at 1-mo TM undefined Shell Case study Child with Sx to rotate aorta anteriorly and Fluoroscopy 2001 TM related to to the left; followed by MRI innominate Pre Sx FEF25-75=28%, artery post=69%; compression Pre Sx V’maxFRC=19%, post=57%; Pre Sx FVC 114%, post 116% Uchida Case series NA; 3 children Description of 3 children Flow-volume curves TM undefined Chest CT with 2009 TM undefined with double mistreated as poorly #1: plateau of expiratory limb angiogram showing aortic arch controlled asthma whereby #2: plateau of inspiratory and airway compression analysis of flow-volume expiratory limbs (undefined) curve suggested diagnosis #3: plateau of expiratory limb Weber Retro- Children with life- 8 of the 32 in To report on children with FEV1 Rigid or flexible 2002 spective threatening TM cohort had life-threatening TM treated pre-aortapexy=52% pred, SD 4% bronchoscopy who had PFT done with aortopexy post=82% ± 3% spontaneous aortopexy; (not post PFT undertaken 2 weeks to breathing TM undefined specifically 3-mo post aortopexy described) CPAP= continuous positive airway pressure; Excl=exclusion; Incl=inclusion; mo=months; NA=not applicable; PFT=pulmonary function test; pred=predicted; Sx=Surgery; TBM=trachea-broncho-malacia; TM=tracheomalacia; V’maxFRC=maximal flow at functional residual capacity

Summary of data • Lung function cannot be used to diagnose TBM but provides supportive diagnosis • Sensitivity and specificity of any PFT cannot be determined • Although many studies show some have a degree of expiratory airway obstruction; not all have. • Obstruction pattern defined by reduction in FEV1, V’max FRC, PEF, MEF, TEF, airway resistance, abnormality in flow-volume loops • FVC not affected or may be elevated, TGV elevated • AHR present in some children

Limitation of data • Need PFT related to TBM severity; • Limited studies- many small number; only 2 cohorts

LITERATURE REVIEW ON QUESTION 5 - RADIOLOGY How do we use imaging to diagnose TM & BM? [to include tracheobronchography]

1st author, Setting; Inclusion criteria; Description of Main aim(s) of Primary Main study Method of publication study design exclusion or cohort study findings limitation confirmation of year definition relating to KQ TBM and type Austin J, Review Do not describe 2003 papers search Berrocal T, Review Do not describe 2004 papers search Fraga JC, Review Do not describe 2016 papers search Sanchez Prospective Children with a 22 children To study Fluoroscopy Small cohort of Flexible MO, 2012 study suspected airway underwent sensitivity, detected TM in children Bronchoscopy abnormality and with fluoroscopy and specificity and 5/21 children. clinical symptoms Flexible predictive Airway including stridor, Bronchoscopy ratios of airway fluoroscopy was chronic cough, (FB). TM was fluoroscopy poorly sensitive recurrent pneumonia, found in 21 compared with (23.8%) but persistent pulmonary children by FB. FB. highly specific infiltrates or (100%) and atelectasis. positive likelihood ratio was 8.6

Berg E, Retrospective Children with stridor 39 children, To determine The sensitivity Small cohort of Endoscopy 2008 study who underwent both endoscopic the sensitivity of fluoroscopy children. The endoscopy and findings: 13 with and specificity in the diagnosis sample sizes fluoroscopy within a airway stenosis, of airway of within each 5y time period. 11 with fluoroscopy in laryngomalacia, diagnostic laryngomalacia, the diagnosis TM, airway subgroup were 7 with airway of pediatric stenosis, and even smaller (eg, mass lesion, 5 laryngotracheal an airway mass there were only 5 with abnormalities. was 27%, 20%, patients in the tracheomalacia. 69%, and 43%, tracheomalacia respectively. group). The specificity for the same diagnoses was 100%, 94%, 100%, and 100%, respectively. Airway fluoroscopy appeared to have low sensitivity but high specificity in detecting airway abnormalities.

Lee EY, Case series Infants with 5 symptomatic To assess the TM was Limited cohort Bronchoscopy 2008 (Retrospective mediastinal aortic infants feasibility of confirmed in 3 review and vascular anomalies underwent paired out of 5 infants analysis of referred for paired paired inspiratory – at the level of radiologic and inspiratory-expiratory inspiratory – expiratory mediastinal clinical data) MDCT. expiratory MDCT for aortic vascular MDCT, while 4 evaluating TM anomaly. The underwent among CT results were bronchoscopy symptomatic concordant with as well. infants with the results of mediastinal bronchoscopy aortic vascular in all patients anomalies. who underwent bronchoscopy.

Lee EY, Retrospective Pediatric patients with 15 children, To determine 8 of 15 patients 1. Small cohort. Bronchoscopy and/or 2008 study respiratory symptoms underwent the prevalence diagnosed with 2. Not equal paired inspiratory- who underwent paired paired of TM TM, results number of expiratory MDCT inspiratory- expiratory inspiratory- associated with concordant with cases from MDCT and were expiratory different types Bronchoscopy. each type of diagnosed with MDCT, while 9 of mediastinal Symptomatic vascular mediastinal aortic underwent aortic vascular pediatric anomaly. vascular anomalies. bronchoscopy anomalies in patients with 3. Retrospective as well. symptomatic mediastinal study. children using aortic vascular paired anomalies have inspiratory- a relatively high expiratory prevalence of MDCT. TM. Paired inspiratory- expiratory MDCT should be considered part of the routine preoperative evaluation of TM.

Ngerncham Retrospective Infants who had 18 patients To compare Overall 1. Small Intraoperative M, 2015 study esophageal atresia underwent paired diagnostic population Diagnostic (EA) and underwent paired inspiratory- accuracy of size. Laryngoscopy and MDCT as inspiratory- expiratory dynamic airway 2. Retrospective Bronchoscopy preoperative expiratory MDCT with MDCT nature of evaluation of TBM MDCT. intraoperative compared to study. prior to aortopexy. Diagnostic DLB was 91%. 3. No normal Laryngoscopy MDCT is highly control group and accurate and to be Bronchoscopy reliable non- compared. (DLB) in the invasive assessment of modality for TBM in evaluating TBM. symptomatic pediatric patients with EA. Lee EY, Review Do not describe 2009 papers search Long FR, Retrospective Pediatric patients, 87 children To describe the Full inflation 1. Retrospective Controlled-ventilation 2001 study who underwent underwent technique and CVCT was study, which CT conscious sedation conscious utility of a non- useful in did not and controlled- sedation and invasive evaluating compare ventilation CT (CVCT) CVCT of the method called tracheal and prospectively of the chest over a 2- chest. controlled- bronchial the CVCT with year period, because ventilation CT stenosis, the quiet they could not (CVCT) for bronchial wall breathing cooperate with breath obtaining thickening, early technique. holding. motion-free full- bronchiectasis, 2. CVCT inflation and bronchial fistula, requires the end-exhalation extend of use of images of the interstitial sedation. lung in infants fibrosis and and young lung nodules. children. End exhalation CVCT was useful in evaluating TM and air trapping. Goo HW, Retrospective Pediatric patients with 27 children with To investigate If a cross 1. Bronchoscopy Bronchoscopy 2013 study TM who underwent bronchoscopic the accuracy of sectional area not performed free-breathing cine- evidence of TM, free breathing change of the in controls. CT. and a control cine-CT for trachea of 2. Only a few group (n=320) diagnosis of 31.6% was slices of the underwent free TM in young used as a cut- entire trachea breathing cine- children with off value for the were CT. bronchoscopy diagnosis of evaluated. as reference TM the 3. A standard. sensitivity, reproducibility specificity and study of the accuracy of measurement cine-CT were s was not 96.3% (26/27), performed. 97.2% 4. Sedation (311/320) and might 97.1% influence (337/347), tracheal respectively. collapse on Free-breathing cine-CT. cine-CT has potential to provide the diagnosis of TM in young children. Tan JZ, Case series Pediatric patients with 8 infants: 4 with To evaluate the Volumetric CT Retrospective Bronchoscopy or 2013 (Retrospective complex clinical TM, 4 without dynamic enables four- study with a small Bronchography study) respiratory tracheobronchial volumetric CT dimensional sample group. presentation who abnormalities (four- assessment for were referred for (proved with dimensional paediatric TBM dynamic assessment bronchoscopy or technique) in without of their airways, at a bronchography). the intubation or tertiary paediatric All underwent assessment of patient centre. dynamic the paediatric cooperation and volumetric CT airway. at low radiation (four- dose. dimensional technique). Greenberg Retrospective Infants with congenital 23 infants with To evaluate the DP-CTA is 1. Small cohort. Dynamic Pulmonary SB, 2014 study heart disease who congenital heart efficacy of DP- uniquely suited 2. Comparative CTA (Cine-CT) underwent Dynamic disease and CTA to provide for bronchoscopi Pulmonary CTA (DP- persistent unique comprehensive es not CTA) for evaluation of respiratory information for and performed in unexplained distress: 17 with patient care in simultaneous enough persistent respiratory TBM proved by newborns and evaluation of patients. distress. DP-CTA (cine- infants with airway and 3. No long term CT). congenital vascular follow up heart disease abnormalities in available. and persistent infants. respiratory distress. Lee S, 2014 Retrospective Infants who 17 infants who To evaluate the In 10 children 1. 11/17 Flexible study underwent both chest underwent both use of a non- TM was bronchoscopi Bronchoscopy CT and bronchoscopy bronchoscopy breath held 3D- confirmed. es were within 1 week. and 3D-CT- CT Sensitivity performed bronchoscopy: bronchoscopy was<75% in after CT and in detecting detecting the TBM in infants. laryngomalacia, pulmonologist TM and BM. was not Specificity and blinded. PPV was 100% 2. Diffuse airway in narrowing is layngomalacia difficult to and TM. detect in the VR images. 3. A selection bias may have occurred from excluding the patients with severe artifacts in the CT scan. 4. Small cohort of infants.

Su SC, Prospective Children aged<18 53 children A Comparison VB detected TM 1. Preselection Flexible 2017 study years scheduled for evaluated for of Virtual in 20patients. of patients Bronchoscopy having both FB airway Bronchoscopy Sensitivity of with a (Flexible abnormalities: (VB) versus FB 54.1% (95%CI diagnosis of Bronchoscopy) and TM was in the 37.1–70.2), TBM. MDCT. confirmed in 37 Diagnosis of Specificity 2. Duration of at FB. TBM in 87.5% (95%CI anesthesia Children. To 60.4–97.8), and was longer by determine positive the time FB sensitivity, predictive value occurred. specificity, PPV 90.9% (95%CI 3. 7 children who and NPV. 69.4-98.4). underwent VB cannot MDCT without replace FB as sedation gold standard received for detecting gaseous TBM in children. anesthesia for FB. 4. Inability to standardized lung volumes and airway pressure during FB and VB. Deacon Retrospective Pediatric patients with 71 pediatric To describe the Rate of TM Hospital records Rigid JWF, 2017 study TM, confirmed by rigid patients with clinical detection on reviewed was laryngobronchoscopy (Data were laryngobronchoscopy, TM: 28 had presentation of CTA is 42,9% variable and collected over a 3,5-year chest CTA. children with sometimes retrospectively period. TM and to incomplete. by reviewing analyse the the medical benefits to record files) patient management of investigations used in the diagnosis and imaging of TM. Lee EY, Retrospective All pediatric patients 20 standard- To assess the TM was 1. Retrospective Bronchoscopy 2010 study who underwent dose and 20 effects of diagnosed by study. (Retrospectively paired inspiratory and reduced- radiation dose CT in 7 patients 2. Subjective and randomly expiratory MDCT expiratory dose, reduction on who underwent grading of the identify studies for the paired the standard-dose confidence pediatric evaluation inspiratory- assessment of and 6 patients level in patients) of clinically suspected expiratory the tracheal who underwent measuring the TM, on the basis of MDCT studies lumen on reduced-dose tracheal clinical signs and performed for expiratory paired lumen. symptoms. the evaluation of MDCT images inspiratory- 3. Different suspected TM in of pediatric expiratory machines paediatric patients MDCT studies. used in the patients (aged referred for CT results were population. <18 years). evaluation for concordant with TM. the results of bronchoscopy in all 32 patients who underwent both procedures. The radiation dose can be reduced by 23% while maintaining similar diagnostic confidence for assessment of the tracheal lumen compared to a standard-dose technique in pediatric patients.

Javia L, Review Do not describe 2016 papers search. Faust RA, Prospective, Pediatric and adult A cohort of 10 To investigate The imaging Small cohort of Endoscopy 2001 controlled study patients, with pediatric the feasibility of findings children. respiratory symptoms patients, 10 using cine-MRI correlated with scheduled for having adult patients, techniques to patient’s both Endoscopy and and 10 normal dynamically endoscopy. TM cine-MRI. volunteers: image the was depicted in underwent static human airway 8 pediatric MRI, as well as and to assess patients. Airway cine-MRI. laryngeal and cine-MRI has tracheal the potential to patency and provide novel function. data regarding laryngeal and tracheal patency and function. Faust RA, Case series Pediatric and adult 2 pediatric + 1 To apply cine- Both techniques Very limited Bronchoscopy 2002 patients in respiratory adult patients MRI to confirmed TM in cohort. distress underwent underwent both evaluate all cases, both bronchoscopy bronchoscopy patients with mainly at the and cine-MRI. and cine-MRI. respiratory level of the distress who innominate exhibited artery. Cine- tracheal MRI provides compression at extremely rapid the level of the acquisition for innominate functional artery. imaging of tracheal patency during the respiratory cycle, while it may provide additional insight into innominate artery compression syndrome.

Ciet P, Retrospective Children suspected of 12 children To evaluate the TBM was 1. Retrospective Flexible 2014 study having TBM underwent cine- feasibility of diagnosed in 7, study. Bronchoscopy or (Retrospective underwent cine-MRI. MRI: TBM was spirometer- confirmed with 2. Limited chest CT image analysis) diagnosed in 7. controlled cine- bronchoscopy cohort. MRI as an or chest CT. alternative to Spirometer cine-CT. controlled cine- MRI is a promising technique to assess TBM in children and has the potential to replace bronchoscopy. Rimell FL, Retrospective Children with various 49 children: 45 To determine Discrepancies 1. Retrospective Bronchoscopy 1997 study distal airway disorders underwent both the role of MRI between MRI study. (Study was over a 3-year period, endoscopy and and how it and endoscopy 2. No detailed based on a who underwent MRI MRI, while14 relates to noted in 7, while description of chart review) for the evaluation of underwent endoscopy as 2 false negative TBM patients. the airway. fluoroscopy as well as to other results noted in well. imaging fluoroscopy. modalities in Magnetic the evaluation resonance of pediatric imaging was the airway most accurate disorders. modality in defining extrinsic airway abnormalities. Fluoroscopy combined with barium swallow plays an important role as a screening examination.

QUESTION 6: LITERATURE REVIEW BRONCHOSCOPY The role of bronchoscopy to diagnose and grade TB and TB

1st author, Setting; Inclusion criteria; Description of Main aim(s) of study Primary findings Main study limitation Method of publication Study design Exclusion or cohort relating to KQ confirmation of TBM year definitions and type Lee Case series Children with N=5 To assess technical In patients who 1. Small number of FB, spontaneous 2007 MAVA referred for mean age 4.1- feasibility of paired underwent patients breathing paired mo (range 2 inspiratory-expiratory bronchoscopy there 2. The technique inspiratory- weeks – 6 MDCT for evaluating was concordance require cooperation expiratory MDCT months) TM among infants with between MAVA bronchoscopic findings and MDCT findings Sanchez Case series Children with a 22 children To study sensitivity, TM was found in Small cohort of children FB 2012 suspected airway median age 33 specificity and 21 children, abnormality and months range 1- predictive ratios of fluoroscopy with clinical 187. airway fluoroscopy detected TM in 5 symptoms (4 with compared with FB children. Airway including stridor, inspiratory, 2 fluoroscopy was chronic cough, expiratory and 8 poorly sensitive recurrent biphasic stridor, (23.8%) but highly pneumonia, 13 chronic specific (100%) persistent wheeze, 8 and positive pulmonary cyanotic likelihood ratio was infiltrates or episodes) 8.6 atelectasis

Lee Case series Infants under 12 17 patients mean To evaluate the use of a In 10 children TM 1. 17 bronchoscopies FB 2013 Retrospective months old who age 2 months, non-breath held 3D-CT- was confirmed. were performed after CT study underwent both range 1-11 bronchoscopy to Sensitivity was and the pulmonologist chest CT and months. detecting TM in infants <75% in detecting was not blinded. bronchoscopy laryngomalacia, 2. Diffuse airway within 1 week TM and BM. narrowing is difficult to Specificity and detect in the VR images. PPV was 100% in 3. A selection bias may 1

layngomalacia and have occurred from TM excluding the patients with severe artifacts in the CT scan Case series Children aged <18 56 children To determine VB cannot replace 1.Preselection of patients FB Su years scheduled for median age 2.5 sensitivity, specificity, FB as gold standard with a diagnosis of TBM 2016 having both FB and years, range 0.8- PPV and NPV of VB for detecting TBM 2. Duration of anesthesia MCDT, undertaken 14.3 years. compared to FB in in children was longer by the time 30-min to 7-days of diagnosis TBM FB occurred. each other. 3. 7 children who underwent MDCT without sedation received gaseous anesthesia for FB 4. Inability to standardized lung volumes and airway pressure during FB and VB Carden Review Do not describe 2005 papers search

Snijders Review Do not describe 2015 papers search Kugler Review Do not describe 2014 papers search Masters Review Do not describe 2009 papers search Wright Review Do not describe 2003 papers search Austin Review Do not describe 2003 papers search Fraga Review Do not describe 2016 papers search Yie Tan Review Do not describe 2011 papers search 2

Nemes Review Do not describe 2014 papers search Masters Prospective Children with CRS Patients:116 Prospectively examine The RR of illness 1. The tools for the FB under 2008 case control of cough, stridor or children (77 relationship between frequency was 2.1 bronchoscopic sevofluorane general study wheeze present for male), 81 with TM lesions and their (95% CI 1.3 to 3.4) measurement. anesthesia. End > 3 weeks who TM, median age respiratory illness and of significant 2. Clinical illness expiratory airway underwent FB. 2.1 years, range profile cough 7.2 (95% CI outcome scales. images were recorded 0.2 -17.3 years. 1.01 to 27.22) for 3. Sample size 10 mm from the Controls: 31 the malacia group object and were healthy children while the CARIFS measured using day 1 score was histogram mode 1.66 (95% CI, 1.1 technique. to 2.56) compared to control subjects. Malacia type and severity of lesions were not associated with increased rates of illness or worse clinical profile Majid Prospective Adult patients with 10 adult patients To test inter and intra Inter and intra 1. Video images Dynamic FB 2014 observational suspected TM (median age 65 observer agreement (23 observer correlation that are pilot study years, 6 female) pulmonologist) of coefficients were: susceptible to with suspected dynamic FB data PT 0.85 (0.002) and distortions TM estimating the degree of 0.92 (<0.001); MT 2. Lumen size was TB collapse obtained at 0.68 (0.03) and estimated by five different sites 0.82 (0.004); DT antero-posterior during exhalation or 0.89 (<0.001) and diameter and not excessive dynamic 0.95 (<0.001); quantitatively airway collapse. RMSB 0.72 (0.02) measured by and 0.8 (0.02); cross-sectional LMSB 0.92 area. (<0.001) and 0.96 3. Small number of (<0.001). adult patients Asai Case report A child who A 22 month old Description of a case of Obstruction due to One case FB 2001 presented airway child with an airway obstruction with TBM during

obstruction due to erythematous hypoxia during emergence from TM during lesion on the emergence from anesthesia emergence from right arm anesthesia due to anesthesia. scheduled for unexpected TBM resection of the cutaneous lesion under anesthesia with sevoflurane Oh Case report A child who A 12 yr old boy Description of a case of Obstruction due to 1. One case FB 2002 presented with MS who TM in a child with MS TM after beginning 2. No description of unexpected TM was scheduled who undergo surgery operation general anesthesia after beginning of for a spine for scoliosis the operation fusion operation because of scoliosis under general anesthesia Okuda Case report A child who A 1 yr old girl Description of a case of Obstruction during 1. One case FB 2000 presented airway with suspected TM who undergo FB during induction obstruction congenital TM for a suspected and after GA during induction scheduled for congenital TM and after anesthesia FB under GA with secifluorane Eastwood Case series Adult patients 16 adult subjects To measured Isoflurane 1. Small number of LFT 2002 recruited from while supine and collapsibility of upper anesthesia is patients those undergoing spontaneously airways in associated with 2. Difficulties in the minor surgical breathing on spontaneously breathing decreased muscle application of the procedures not nasal positive during inhalational activity and technique involving the head airway pressure anesthesia with increased or neck and suitable isofluorane in order to collapsibility of the for GA examine the site and upper airway administered via a mechanism of collapse face mask and the influence on them of anesthetic depth Eastwood Case series Adult patients 12 white adult 1. To determine Increasing depth of 1. Small number of LFT

2005 recruited from volunteers the effect of propofol anesthesia patients those undergoing varying is associated with 2. Difficulties in the minor surgical concentrations increase application of the procedures not of propofol on collapsibility of the technique involving the head upper airway upper airway or neck collapsibility and the mechanisms responsible for it. 2. To identify the effects of anesthesia on central respiratory drive to upper airway dilator muscles 3. To determine whether a sufficient dose of propofol could produce complete flaccidity of the upper airways Hillman Case series Adult healthy 9 healthy adult To determine how The progression of 1. Small number of LFT 2009 volunteers volunteers upper collapsibility effects during slow patients changes during slow stepwise induction 2. Difficulties in the stepwise induction on of anesthesia with application of the anesthesia with propofol does not technique propofol occur in smooth continuity but disproportionate changes in upper airway collapsibility in a

narrow propofol concentrations in each subjects Masters Case series 1.Reliability 1. Reliability 1. To describe a new 1. Validation Factors that govern FB and computer 2005 testing: children testing: 18 method to define and results showed very tissue reflectance and who had children, median measure airway lumen high levels of absorption of light undergone FB age 30 months, using a FB and a agreement of during the respiratory for chronic range 2-127 computer software. measurements at all cicle while under cough months 2. Describe intra and distance anesthesia can be 2. In vivo 2. In vivo inter-observer 2. Good inter and compounded by the measurement: measurements: reliability, validation intra observer physical effects of the children who 35 children > 3 and application of the reliability instruments, the type of undergone FB months of age. technique 3. The cross light, airway suctioning, for protracted 3. Compare airway size sectional area and disease processes or chronic measurements using assessed at low cough and or different light intensity is wheeze methodologies. more likely to be representative of the true cross sectional area than that captured at normal operating light

Okazaki Case series Infants with and Cases: 8 infants Static pressure/area Tracheal 1. Insufficient control of FB and LFT 2004 without TM with TM relationships of the collapsibility of tracheal smooth muscle Controls: 4 trachea in infants with infants with TM tone that could be infants without TM were obtained and can be influenced by anesthesia TM tested if the relationship quantitatively 2. Overestimation of the quantitatively describes assessed by the lower airway pressure collapsibility of the static pressure/area area because the trachea relationship of the collapsibility site may trachea have shifted to the endoscope tip with the pressure decrease 3. Difficult to estimate

the relative contribution of tracheal stenosis because the method only assesses collapsibility of the trachea 4. Deformation of endoscopic image is inevitable for obtain a wide angle view 5. Small number of patients Loring Case series Adult patients Patients: 80 To quantify central In TBM central 1. Small number of FB and LFT 2006 referred to FB for adult patients airway collapsibility airway collapse is patients suspected TBM (34 men), mean and relate it to not closely related 2. The trachea age 63 year, expiratory flow to airflow transmural pressure range 29-94 limitation in patients obstruction and may have been years with TBM expiratory flow affected by the Controls: 4 adult limitation at rest presence of the healthy often occurs in bronchoscope and volunteers (2 peripheral airways local anesthetic men, age range without central solution 33-47 years) airway collapse. 3. The method may overestimates airway size and underestimates airway narrowing Negerncham Case series. Infants who had 18 children (8 To compare MDCT MDCT is highly 1. MDCT depends MDCT and RB (2015) Retrospective esophageal atresia male), median with intraoperative FB accurate and on patient study who underwent age 8 months, in the assessment of reliable non cooperation. MDCT as range 1month- TBM in children who invasive modality 2. Radiation preoperative 11 years. had esophageal atresia for evaluating TBM exposure evaluation of TBM prior to artopexy Review MDCT: multidetector CT, MAVA: mediastinal aortic vascular anomalies, TM: tracheomalacia, BM: broncomalacia, VR: volume rendering, TBM: trachea bronchomalacia, CRS: chronic respiratory symptoms, RR: relative risk, TB: tracheobronchial, DAC: dynamic airway collapse, PT: proximal trachea, MT: mild

7 trachea, DT: distal trachea, RMSB: right main stem bronchus, LMSB: left main stem bronchus, MS: Marfan syndrome, GA: general anesthesia, LFT: lung function testing, RB: rigid bronchoscopy

QUESTION 8 Respiratory physiotherapy systematic search

Search terms

Tracheomalacia OR bronchomalacia OR tracheobronchomalacia OR malacia OR tracheal abnormalities OR tracheal diseases

AND

Physiotherapy OR physical therapy OR physical therapy modalities OR airway clearance OR positive pressure and physiotherapy

Exercise tolerance OR exercise therapy

Administration inhalation OR nebulisation OR saline solution hypertonic OR deoxyribonuclease I OR nebulised dornase alfa OR nebulised hypertonic saline

LITERATURE REVIEW Tracheomalacia and physiotherapy Inclusion Method of 1st author, Setting; Study criteria; Description of Main aim(s) of Primary findings Main study confirmation of publication year design Exclusion or cohort study related to KQ limitation TBM definitions Finder, 1997 Retrospective not specified N = 17, mean age To determine the All patients had Descriptive study Bronchoscopy = 38 mo (range 3 natural history of physiotherapy. All mo - 17 y) with primary patients aged bronchomalacia bronchomalacia more than 5 years had exercise limitation Goyal, 2012 Systematic review RCTs related to 1 study examined To evaluate the No RCTs Related to not specified symptoms about role of efficacy of medical identified about symptoms rather associated with rDNase and surgical role of than the impact of primary or intrinsic therapies for physiotherapy physiotherapy TM children with intrinsic (primary) TM Davis, 1998 Cross-sectional TM=50% tracheal N = 6, mean age In infants with TM, continuous Small cohort Bronchoscopy narrowing at 6.8 mo (range 3- to determine positive expiratory bronchoscopy 10 mo) with whether the pressure (CPAP) moderate to increase in V’max increases maximal severe TM; FRC with CPAP expiratory flow at Controls: N = 5, could be explained functional residual mean age 6.4 mo by the increase in capacity FRC with CPAP secondary to

(0, 4, 8 cm H20) increasing lung volume

Sirithangkul, 2010 Observational Incl. children with N = 40, mean age To determine the Children with CEF25-75 were History, clinical case-control study OA/TOF with 12.5 y (range 8 - effectiveness of TOF: PEP=5: calculated from symptoms corrective surgery; 18 y); Controls: N increasing levels +18.8% increase cough flow-volume Excl. complex = 21, mean age of PEP during CEF25-75 curve congenital 13.1 y coughing to PEP=10: +11.7% abnormalities enhance increase CEF25- (spinal deformity, expiratory flow 75 PEP=15: congenital heart and improve +0.5% increase disease or efficiency of the CEF25-75 neurological cough in children PEP=20: -2.4% impairment) with TOF decrease CEF25- 75 Controls: PEP=5: -3.1% decrease CEF25- 75 PEP=10: -6.3% decrease CEF25- 75 PEP=15: - 22.2% decrease CEF25-75 PEP=20: -19% decrease CEF25- 75

1 LITERATURE REVIEW QUESTION 9: STENTS 1st author, Study design Number Type(s) of Outcome (survival at Complications Attempted Main study publication of stent time of report) stent retrieval limitation year patients Soong 2018 retrospective unclear BEMS unclear for TBM patients tracheal perforation at time of optional data combined with (>21) stent removal, granulation stenting for other tissue, infection, stent fracture indications Sztano 2016 retrospective 3 absorbable 2/3, 67% stent fragmentation, infection, required for small series airway obstruction complications presented as review of complications Anton- retrospective 3 absorbable 3/3, 100% granulation tissue no small series Pacheco 2016

de Trey retrospective 15 BEMS, 11/15 (73%) stent fracture, infection, optional (28%) data combined with 2016 absorbable airway obstruction stenting for vascular compression Anton- retrospective 19 BEMS, unclear for TBM patients stent migration, granulation optional data combined with Pacheco silicone tissue, infection stenting for other 2008 (DumonTM, indications PolyflexTM) Yang 2006 retrospective 3 not stated 1/3 (33%) not stated 1/3 small series, poor description of patients Airway retrospective 2 BEMS 2/2 (100%) not stated unclear small series Reconstruct ion team 2005 Valerie retrospective 14 BEMS 13/14 (93%) death during stent removal 9/14 (64%) small series 2005 Geller 2004 retrospective 9 BEMS 5/9 (55%) airway haemorrhage, infection no small series

Nicolai 2001 retrospective 4 BEMS, SEMS 1/4 (25%) pneumomediastinum, yes small series difficult stent removal, granulation tissue, stent 1

collapse with coughing Furman retrospective 2 BEMS 1/2 (50%) granulation tissue no small series 1999 Filler 1998 retrospective 8 BEMS 8/8 (100%) granulation tissue 6/8 (75%) small series Tsugawa retrospective 2 SEMS 2/2 (100%) stent too short 1/2 (50%) small series, 1997 experimental device (not available for clinical use) Santoro retrospective 3 BEMS 1/3 (33%) no small series 1995 Mair 1990 retrospective 2 SEMS, plastic 1/2 (50%) infection no small series, polymer experimental device (not available for clinical use) TBM = tracheobronchomalacia; BEMS = balloon-expandable metal stent; SEMS = self-expanding metal stent

LITERATURE REVIEW: QUESTION 9 - SURGERY

1st author, Setting; Inclusion criteria Description Main aim(s) of study Primary findings relating to Main study Method of publication Study of cohort KQ limitation confirmation of year design TBM and type Jennings Retro- children with TM N=41 To determine the outcomes The partial sternotomy technique Variation in Flexible 2014 spective who underwent median age- among three different had the most reliable resolution patient bronchoscopy, cohort aortopexy 7.5 mo surgical approaches of symptoms and populations, spontaneous (range 1-136) for performing an aortopexy no recurrence requiring ages at breathing reoperation. operation, surgical teams, use of intraoperative bronchoscopy to assess results. Briganti Retro- children with 7 children Usefulness of preoperative Dynamic fiberoptic Short series of Flexible 2006 Spective esophageal Mean age: imaging by dynamic bronchoscopy and CT scans cases bronchoscopy and cohort atresia- 25.2 mo fiberoptic bronchoscopy and allowed CT scan with 3-D tracheoesophageal (range 2-103) spiral multilayer computed us to describe 3 morphological reconstruction fistula presenting tomography with 3- variations of thoracic TM segmentary TM dimensional reconstruction

Filler Retro- children with 32 children Surgical outcomes of Aortopexy provides long-term Chest x-ray, 1992 Spective esophageal atresia aortopexy relief of severe symptoms of esophagogram, and cohort tracheoesophageal tracheomalacia associated with bronchoscopy. fistula (EA-TEF) EA-TEF in almost all affected who underwent children surgery for severe tracheomalacia Morabito Cohort children with 16 children Surgical outcomes of Sustained tracheal improvement Bronchoscopy 2000 significant aortopexy and/or and resolution of the life- (type undefined) symptoms of TM tracheopexy threatening features of TM undergoing aortopexy and/or tracheopexy Arnaud Case study Children with TM 4 children To review initial experience All patients were relieved of larger and Bronchoscopy 1

2014 and EA/TEF with thoracoscopic their symptoms, and no prospective undergoing aortopexy. recurrence was noted. study with a thoracoscoic longer follow-up aortopexy to confirm these preliminary results, needed Shieh Retro- Children 98 patients To review patient outcomes Tracheomalacia scores on Flexible 2017 spective undergoing median age of of posterior tracheopexy for bronchoscopy improved bronchoscopy with cohort posterior 15mo (IQR 6- tracheomalacia significantly in all regions of the standardized tracheopexy for 33months) trachea and bronchi (p<0.001). dynamic airway tracheomalacia 9.2% had persistent airway evaluation by with posterior intrusion requiring reoperation, anatomical region intrusion usually with aortopexy. Morrison Case study 3 children with 3 children Assess the application of These infants no longer This report was Bronchoscopy and 2015 severe TBM 3D printing technology to exhibited life-threatening airway not designed for CT scan with treated with a 3D- produce a personalized disease and demonstrated definitive testing multiplanar printed medical device for treatment resolution of both pulmonary of device safety. reconstruction personalized of TBM and extra-pulmonary Further patient bioresorbable complications of their TBM. accruement and medical device analysis under a US/ FDA- enabled clinical trial will be necessary.

PATIENT AND PARENT PERPECTIVE

HTTPS links to internet sources

1. Mumsnet thread: “Anyone's newborn suffered from laryngeal stridor?”. 2011. Accessed 5 April 2018. https://www.mumsnet.com/Talk/childrens_health/1123789-Anyones-newborn- suffered-from-laryngeal-stridor 2. Mumsnet thread “floppy windpipe”. 2005. Accessed 5 April 2018. https://www.mumsnet.com/Talk/general_health/63818-floppy-windpipe 3. Mumsnet thread “any experts on breathing problems in small babies?”. 2009. Accessed 5 April 2018. https://www.mumsnet.com/Talk/childrens_health/694506-any-experts-on- breathing-problems-in-small-babies 4. Baby Center Community thread “Tracheomalacia”. 2010. Accessed 6 April 2018. https://community.babycenter.com/post/a21491171/tracheomalacia 5. Mumsnet thread “laryngomalacia in newborn; anyone any advice please?”. 2006. Accessed 5 April 2018. https://www.mumsnet.com/Talk/general_health/137371-laryngomalacia-in- newborn-anyone-any-advice-please 6. Mumsnet thread “My 4 month old diagnosed with laryngeal or trachea malacia - anyone got any experience?”. 2009 - 2011. Accessed 5 April 2018. https://www.mumsnet.com/Talk/childrens_health/714854-My-4-month-old- diagnosed-with-laryngeal-or-trachea-malacia 7. Megan Horwath. I Know You, Tracheomalacia. The Mighty. 2015. Accessed 6 April 2018. https://themighty.com/2015/03/i-know-you-tracheomalacia/ 8. MedHelp thread “Tracheal-Malaysia”. 2011. Accessed 5 April 2018. https://www.medhelp.org/posts/Ear--Nose--Throat/TRACHEAL- MALAYSIA/show/7360#post_7143465 9. Mamapedia thread “How to deal with infant with tracheomalacia?”. 2008. Accessed 6 April 2018. https://www.mamapedia.com/article/how-to-deal-with- infant-with-tracheomalacia