A. Nakonechna 1, J. Antipkin 2, T. Umanets 2, V. Lapshyn 2 1) Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom.

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A. Nakonechna 1, J. Antipkin 2, T. Umanets 2, V. Lapshyn 2 1) Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom 2) Institute of Pediatry, Obstetrics and Gynaecology, Kiev, Ukraine INTRODUCTION MATERIALS AND METHODS Heterogeneity in asthma is recognized by different inflammatory cell patterns in airway secretions. However, the role of sputum cells in airway responsiveness in different childhood asthma phenotypes is still unclear. We investigated whether there are differences between children with different asthma phenotypes in: sputum cell profile airway responsiveness measures of severity 245 children aged 6-12 years with bronchial asthma (BA) 57 age-matched healthy controls were observed Diagnosis and assessment of asthma status and criteria for asthma phenotypes based on: Clinical questionnaire (respiratory symptoms, frequency of episodes of asthma, medication) Physical examination Allergy skin prick tests (SPTs)- cat, dog, house dust mite, D. pharine, D.pteronissinus, grass mix, tree mix, Alternaria, Aspergilus, Cladosporium, food allergens (egg, milk, wheat, fish, soya, meat, nuts) Total IgE and antigen specific IgE Lung functions Bronchial hyperreactivity (BHR) tests: Methacholine provocation test- MPT- provocation concentration of methacholine needed to produce a 20% fall in FEV1 Exercised challenge - by 6 minutes running, at 85-90% of maximum heart rate, measured by heart rate monitor. BHR to exercise challenge was defined as a fall in FEV1 of 13% of greater. Induced sputum analysis – method Pizzichini Multivariate regression was used to determine whether sputum cells profile, airway responsiveness and disease severity varied between phenotypes. Sputum cell profile and airway responsiveness vary in different asthma phenotypes in children. These findings suggest a role of inflammatory markers in the phenotypic classification of asthma and determining the severity of disease and therapy in childhood asthma management. Graphs and Tables Among observed patients (245) in our study: Group I – (160 patients)- 65,3% - had atopic asthma Group II – (85 patients)- 34,7% - had non-atopic asthma Diagnosis of atopic BA (Gr.1) was confirmed by: positive SPT (Pic.1) and increased total IgE (398±12 KU/l) and specific IgE levels comparing with normal their rates in Group II (Pic.2) (p<0,001). According to asthma severity, that was assessed by: FEV1, peak expiratory flow (PEF) variability and daily symptom scores (Pic.3 ) the majority of atopic asthma children (Gr.I) had mild-to-moderate asthma (84.4%), while 74,1% of non-atopic group (Gr.II) had moderate-to-severe asthma. By investigation of airway inflammation markers: Atopic asthma children (Gr.I) showed induced sputum eosinophilia, which directly correlated with elevated peripheral blood eosinophils (p<0,001). They presented also increased level of sputum lymphocytes, basophils and mast cells and bronchial epithelial desquamation (Pic.4). Airway hyperresponsiveness strongly associated to higher level of eosinophils in atopic group children (p<0.05). In contrast, non-atopic asthma children (Gr.II) had induced sputum neutrophilia (Pic.4). Neutrophils count directly correlated with asthma severity (p<0.05). The evaluation of bronchial hyperreactivity (BHR) showed: 1) The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20, FEV1) was decreased in all asthmatic children, but more significant in non- atopic asthma group (0,4 mg/ml vs. 2,3 mg/ml; control >20mg/ml) (Table 1). Remarkable, that decreasing of PC20 associated with: lower levels of lung function (percent predicted FEV1 and percent predicted FVC) the occurrence of asthma symptoms (shortness of breath, persistent wheezing, or exercise-induced cough and wheeze) longer duration of asthma This relationship was such that the lower the PC20 - the lower were the level of FEV1 percent predicted, the higher number of symptoms and the longer the duration of asthma (p<0,001). 2) BHR to exercise challenge was defined as a fall in FEV1 more significant in non- atopic comparing to atopic asthmatic group (18-20% vs 12-14%) (Table 1). RESULTS CONCLUSIONS Sputum cells profile and airway responsiveness in different asthma phenotypes in children Abstract 2011 Pic.4 Induced sputum analysis – total and differential cell counts Table 1 - Bronchial hyperreactivity test Atopic asthmaNon-atopic asthmaControl Methacholine provocation test PC20, FEV mg/mlPC20, FEV mg/ml>20 mg/ml Exercised challenge: Fall in FEV %18-20%1-3%