ii4 Spoken sessions Spoken sessions ........................................................................... Thorax: first published as on 28 November 2005. Downloaded from of variable airflow obstruction: methacholine PC20,8 mg/ml, increase Airway inflammation in asthma: in FEV1 of 15% or greater following inhalation of 200 mg of salbutamol and/or peak flow amplitude as percent of mean over 14 days of .20%. basic and clinical science Endobronchial biopsies were taken from 11 patients with non- eosinophilic asthma, 12 patients with eosinophilic asthma, and 10 normal control subjects. The patients with non-eosinophilic asthma and S1 INCREASED TACHYKININ LEVELS IN THE AIRWAYS OF six patients with eosinophilic asthma entered a randomised, double ASTHMATIC PATIENTS AND CHRONIC COUGH blinded, placebo controlled cross over study of inhaled mometasone PATIENTS WITH COEXISTENT GASTRO- 400 mg once daily for eight weeks. Patients with eosinophilic asthma OESOPHAGEAL REFLUX DISEASE had a median 23 bronchial submucosal cells positive for major basic protein per mm2 which was higher than both normal controls (0 cells/ 2 2 R. N. Patterson1, B. T. Johnston1, L. G. Heaney1,2, L. P. A. McGarvey1. mm , p = 0.043) and patients with eosinophilic asthma (4.4 cells/mm , 1Department of Medicine, Queens University Belfast, Belfast, N Ireland; p = 0.016). Submucosal mast cells numbers were not different between 2Regional Respiratory Centre, Belfast City Hospital, Belfast, N Ireland the groups. However airway smooth muscle mast cell numbers were higher in eosinophilic asthma (8 cells/mm2) and non eosinophilic 2 2 Background: Gastro-oesophageal reflux disease (GORD) may aggra- asthma (9 cells/mm ) compared to normal controls (0 cells/mm , vate airway diseases including asthma and chronic cough. One p = 0.016). There were no significant differences in the number of postulated mechanism is via a vagally mediated distal oesophageal- submucosal cells positive for neutrophil elastase. The subepithelial layer tracheobronchial reflex associated with airway sensory nerve activation thickness was 10.3 mm in patients with eosinophilic asthma compared to and tachykinin release. In this study we tested the hypothesis that patients 5.8 mm in non eosinophilic asthma and 5.1 mm in normal controls with airways disease and GORD have increased airway tachykinin (p = 0.002). Eight weeks’ treatment with inhaled mometasone led to a net levels compared to those without GORD. 5.5 doubling dose improvement in methacholine PC20 in patients with Methods: The study population consisted of 32 patients (all non-smokers) eosinophilic asthma and a 0.5 doubling dose improvement in the non- attending the chest clinic at the Belfast City Hospital. Sixteen subjects with eosinophilic asthma group (mean difference 5.1 doubling doses, 95% CI asthma (eight female, mean age 55.2 years, FEV1 61–112% predicted) 1.1 to 9.1; p = 0.018). There was a net 1.0 point improvement in Juniper and 16 with non-asthmatic chronic cough (11 female, mean age asthma quality of life following treatment with inhaled mometasone 61.8 years, FEV1 80–127%predicted) were recruited randomly and compared to placebo in the eosinophilic asthma group and a 0.2 underwent 24 hour oesophageal pH monitoring. GORD was defined as improvement in the non-eosinophilic asthma group (mean difference increased total oesophageal acid exposure (% total time .4.9% at the 0.9, 95% CI 0.27 to 1.43; p = 0.008). distal probe). All subjects underwent sputum induction and differential Non-eosinophilic asthma represents a pathologically and clinically cell count were obtained and concentrations of substance P (SP), distinct disease phenotype which is characterised by absence of http://thorax.bmj.com/ Neurokinin A (NKA), albumin, and a2-macroglobulin were measured in eosinophilic airway inflammation in sputum and bronchial biopsies, sputum supernatants. normal subepithelial layer thickness, and resistance to the effect of short Results: Comparing all subjects, the mean SP and NKA levels were term treatment with inhaled corticosteroids. significantly higher in patients with GORD compared to those without GORD (SP; 1433.97 pg/ml versus 905.95 pg/ml, p = 0.026, NKA, 81.04 pg/ml v 49.13 pg/ml, p = 0.014). Significantly increased tachykinin levels were also measured when asthmatic patients with MAST CELL MIGRATION TO TH2 STIMULATED AIRWAY GORD were compared to those without GORD, (SP; 1508.37 pg/ml v S3 SMOOTH MUSCLE FROM ASTHMATICS 736.68 pg/ml, p = 0.035, NKA; 103.15 pg/ml v 56.77 pg/ml, p = 0.02). Although SP and NKA levels were also increased in the 1 1 2 1 2 on September 25, 2021 by guest. Protected copyright. cough patients with GORD this did not reach statistical significance, (SP; A. Sutcliffe ,D.Kaur,A.J.Ammit,L.Woodman,J.L.Black, A. J. Wardlaw1, P. Bradding1, J. M. Hughes2, C. E. Brightling1. 1Institute 1534.71 pg/ml v 1088.75 pg/ml, p = 0.198, NKA, 55.99 pg/ml v for Lung Health, Leicester, UK; 2Respiratory Research Group, Faculty of 49.77 pg/ml, p = 0.709). There was a trend towards a significant Pharmacy and Department of Pharmacology, University of Sydney, Australia increase in % neutrophils in the asthmatic patients with GORD compared to those without reflux (82.1% compared to 54.6%, p = 0.074) with no Background: Mast cell microlocalisation within the airway smooth difference in inflammatory cell counts among cough patients. No muscle (ASM) bundle is an important determinant of the asthmatic difference in albumin or a-2 macroglobulin levels were noted in GORD phenotype. We have reported that activation of mast cell CXCR3 by patients compared with those without GORD in either the asthma or ASM derived CXCL10 is an important mechanism mediating mast cell cough group. migration towards ASM in asthma. We hypothesised that mast cells may Conclusion: Such observations have not previously been reported and also migrate towards Th2 stimulated ASM from asthmatic donors. suggest sensory nerve activation in the airways of respiratory patients Methods: Primary ASM from subjects with (n = 7) and without (n = 5) with GORD. Inhibiting tachykinin release may provide an alternative asthma were stimulated with IL-1b, 4, and 13 alone and in combination. therapeutic option for reflux associated respiratory disease. We investigated: (1) mast cell migration towards the supernatants derived from these ASM cultures using chemotaxis assays with and without chemokine receptor blockers for CCR3, CXCR1, 3 and 4; genistein or pertussis toxin and (2) the concentration of CCL11, CXCL8, S2 CLINICAL AND PATHOLOGICAL FEATURES OF NON- CXCL10, TGF-b, and SCF in these supernatants measured by ELISA. EOSINOPHILIC ASTHMA: A DISTINCT ASTHMA Results: HMC-1 cells migrated towards stimulated ASM supernatant PHENOTYPE ASSOCIATED WITH INHALED from the subjects with asthma, but not to non-asthmatics for all of the CORTICOSTEROID RESISTANCE activation conditions (p,0.0001). Similarly ASM supernatant stimulated with IL-1b, 4, and 13 from asthmatics was chemotactic for human lung M. A. Berry, A. Morgan, R. H. Green, C. E. Brightling, A. J. Wardlaw, mast cells (HLMC) (2.4-fold compared with control media; p = 0.007), I. D. Pavord. Department of Respiratory Medicine, Glenfield Hospital, Groby but not ASM supernatant from non-asthmatics (1.3-fold; p = 0.45). The Road, Leicester, UK HMC-1 and HLMC migration was mediated predominantly through the combined activation of CCR3 and CXCR1. The concentration of CCL11 Non-eosinophilic asthma has been identified as a potentially important and CXCL8, but not the other chemotaxins measured, was markedly clinical phenotype since there is some evidence that it is associated with increased after stimulation. However, the concentration of all of the a poor response to inhaled corticosteroid therapy. No studies have chemotaxins was not increased in ASM cultures from asthmatics investigated the underlying airway immunopathology and there are no compared to non-asthmatic controls. data from placebo controlled studies examining the effect of inhaled Conclusion: These results demonstrate that stimulated asthmatic ASM corticosteroids. We set out to address these issues. All patients with is chemotactic for mast cells, but suggest that either an additional asthma were symptomatic and had one or more of the following markers mediator is released from the asthmatic ASM that facilitates CCR3 and www.thoraxjnl.com Spoken sessions ii5 CXCR1-mediated migration or alternatively an inhibitory mediator is Results: The density of tissue eosinophils was higher in subjects with released by non-asthmatic ASM that attenuates mast cell migration. confirmed wheeze compared to controls (median density in confirmed Supported by: Asthma UK & DoH Clinician Scientist Award. wheeze 1.07 (range 0–3.51)% v reported wheeze 0.72 (0–2.04)% v controls 0 (0–1.05)%, p,0.05 confirmed wheeze v controls). No other differences in tissue inflammation were found between groups. The RBM was significantly thicker in the confirmed wheezers compared to S4 DELETERIOUS EFFECT OF DIESEL FINE PARTICULATE controls, (p,0.05; median thickness in confirmed wheeze 4.6 (range Thorax: first published as on 28 November 2005. Downloaded from EXPOSURE IN OXFORD STREET ON ASTHMA 2.9–7.7) mm v reported wheeze 3.5 (2.4–5.4) mm v controls 3.4 (2.0– 4.7) mm). J. E. McCreanor1, J. Stewart-Evans1, J. Zhang2, M. J. Nieuwenhuijsen1, Conclusion: These data demonstrate that the characteristic pathological M. Svartengren3,P.Ohman-Strickland2,L.Jarup1,K.F.Chung1, features of asthma in adults and school aged children are already P. Cullinan1. 1Imperial College, London, UK; 2University of Medicine and present in a group of preschool children (median age 31 months) but Dentistry of New Jersey, New Jersey, USA; 3Karolinska Institute, Stockholm, only in those with severe, confirmed wheeze. Sweden 1. Barbato A, Turato G, Baraldo S, et al. Airway inflammation in childhood asthma. Am J Respir Crit Care Med 2003;168:798–803.