1. The role of inflammation markers, risk factors and measures of severity in different phenotypes of childhood asthma Alla Nakonechna (Liverpool UK), Tanya Umanetz (Kiev Ukraine), Vladimir Lapshin (Kiev Ukraine)

2. 24 July 2009Summer Allergy School, Norwich2 Asthma in children phenotypically heterogeneous disorder; important to determine for correct treatment and prognostic assessment Diagrammatical classification of clinical asthma phenotypes includes: –onset age –inflammatory profile –severity pattern Main childhood asthma phenotypes –transient infant wheezing –non atopic wheezing of the toddler and early school years –persistent IgE-mediated wheezing/asthma –late-onset childhood asthma

3. 24 July 2009Summer Allergy School, Norwich3 Objective investigate whether there are differences between children with different asthma phenotypes in: inflammation markers risk factors measures of severity

4. 24 July 2009Summer Allergy School, Norwich4 Materials and methods 245 children - aged 6-12 years with BA Control group: 57 age matched children Diagnosis, assessment of asthma status and criteria for asthma phenotypes based on: –clinical questionnaire –physical examination –allergy skin prick tests (SPTs) –Total and antigen specific IgE –Lung functions –Bronchial hyperreactivity (BHR) tests Methacholine provocation test – MPT- PC20, FEV1 exercised challenge - by 6 minutes running, at 85-90% of maximum heart rate, measured by heart rate monitor. –Induced sputum analysis – method PizzichiniT

5. 24 July 2009Summer Allergy School, Norwich5 Results Atopic asthma 160 children (65.3%) Non-atopic asthma 85 children (34.7%) 1. Age of starting asthma symptoms Early age (<1 year)4-5 years 2. Age at asthma diagnosis 6-7 yearsAfter 10 years 3. Infection in early age Not so typicalSevere pneumonia 92.9% 4. Frequent respiratory infection in last 2 years 9.6%98.1%

6. 24 July 2009Summer Allergy School, Norwich6 Results Atopic asthmaNon-atopic asthma 5. Tobacco smoke exposure 17.6%87.1% 6. Asthma associated with other diseases Allergic rhinitis 76.3%Chronic tonsillitis 80% Atopic dermatitis 6.5%Rhinosinusitis 69.4% Gastroesophageal reflux 31.8%

7. 24 July 2009Summer Allergy School, Norwich7 Results Atopic asthmaNon-atopic asthma 7. Exacerbations April - JuneAssociated with infection: autumn, winter 8. Body Mass Index Increased in 15.9%Increased in 3.5% 9. Family history of atopy Asthma 45%5.8% Allergic rhinitis 61.25%10.5% Urticaria 8.1%2.3%

8. 24 July 2009Summer Allergy School, Norwich8 Sensitization to allergen Atopic asthmaNon-atopic asthma 10. Sensitization to allergen Positive SPT: 97.5%2.3%

9. 24 July 2009Summer Allergy School, Norwich9 IgE levels Atopic asthmaNon-atopic asthma 11. Total IgE level 398±12 KU/l21±6 KU/l

10. 24 July 2009Summer Allergy School, Norwich10 Lung function Atopic asthmaNon-atopic asthma 12. Severity of asthma Mild/moderate 84.4%Moderate/severe 74.1% Moderate/severe 15.6%Severe 25.9%

11. 24 July 2009Summer Allergy School, Norwich11 Results Atopic asthmaNon-atopic asthma 13. Bronchial hyperreactivity test methacholine provocation test PC20, FEV1 - 2.3 mg/mlPC20, FEV1 - 0.4 mg/ml exercised challenge Fall in FEV1: 12-14%18-20% 14. Induced sputum analysis Eosinophil inflammationNeutrophil inflammation

12. 24 July 2009Summer Allergy School, Norwich12 Total and differential cell counts in induced sputum

13. 24 July 2009Summer Allergy School, Norwich13 Conclusions Asthma risk factors and measures of severity vary between children with different asthma phenotypes (atopic and non-atopic). Inflammation markers suggest a role for monitoring inflammation and therapy in childhood asthma management.