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Asthma in Non-Affluent Communities

Asthma in Non-Affluent Communities. Renato T. Stein Pontifícia Universidade Católica RS Porto Alegre, Brazil. Worldwide Prevalence of Asthma Symptoms: ISAAC Phase I Data. ISAAC Study. Lancet 1998; 351: 1225–32. Asthma Phenotypes. Stein R et al. Thorax 1997.

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Asthma in Non-Affluent Communities

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  1. Asthma in Non-Affluent Communities Renato T. Stein Pontifícia Universidade Católica RS Porto Alegre, Brazil

  2. Worldwide Prevalence of Asthma Symptoms: ISAAC Phase I Data ISAAC Study. Lancet 1998; 351: 1225–32.

  3. Asthma Phenotypes Stein R et al. Thorax 1997

  4. Risk for Recurrent Wheeze in Children Infected by RSV Early in Life Stein R et al, Lancet 1999

  5. ISAAC Phase II • Thirty study centers in 22 countries • Parental questionnaires (n=54,439) • Skin prick tests (n=31,759) • Serum IgE levels (n=8,951) • Economic development assessed by gross national income per capita (GNI) Weinmayr G et al. AJRCCM 2007 (Atopic sensitisation and the international variation of asthma symptom prevalence in children)

  6. OR for the association of current wheeze with skin prick test reactivity Odds ratio with 95%-confidence

  7. OR for the association of current wheeze with allergen-specific IgE (0.35 kUA/L) Odds ratio with 95%-confidence

  8. ISAAC – Phase II Data, Brazil • Cross sectional studywith questionnaires, skin tests, stool examinations for parasites, BHR • Population n=1199 Age: 10.1 (+ 0.8) Non-atopic asthma is associated with helminth infections and bronchiolitis in poor children Pereira M et al. ERJ June 2007

  9. Brazil data: ISAAC-II • Wheeze past yr: 26% • >4 asthma attacks: 6.5% • Asthma ever: 12.7% • Positive skin tests: 13.3% • Atopic wheeze past yr: 5.4% • Non-atopic wheeze: 20.9%

  10. ISAAC II - Brazil • Current asthma: 9.4% (29% atopic) • Bronchiolitis <2y (E.R. or hospitalized) 6.1%

  11. Analysis for children w questionnaires, SPTs, parasitology tests N=1011 n (%) 495 (49.0) 865 (88.6) 93 (9.6) 852 (84.7) 322 (31.9) 195 (19.3)* 730 (72.2) 474 (46.9) 956 (94.7)* 78 (7.7) 58 (5.8) 273 (27.0) 93 (9.2) 131 (13.0) 63 (6.3) 70 (6.9) Male gender Birth weight ≥ 2500 Born before term Breast feeding ≥ 6 months Current maternal smoking ≥ 8y of maternal schooling ≥ 1 Sibling Humid household Poor neighborhood Maternal asthma Paternal asthma Wheeze past 12 months Active asthma Atopy Bronchiolitis < 2 y.o. Severe asthma (≥ 4 attacks) Pereira M et al. ERJ 2007 (accepted for publication)

  12. Risk factors for wheeze and asthma Multivariate logistic regression Pereira M et al. ERJ 2007 (accepted for publication)

  13. Asthma Phenotypes Stein R et al. Thorax 1997

  14. Inflammatory characteristics in asthmatic children: Induced Sputum • 55 children • Atopic asthma (AA): asthma ever and wheeze in past year + SK+ve • Non-atopic asthma (NAA): asthma ever and wheeze in past year + SK-ve • Non-atopic no-asthma (NANA): no asthma/no wheeze ever + SK-ve Drews A, et al 2007

  15. IS Eosinophil concentration in asthma phenotypes Median (IQ) Drews A, et al 2007

  16. IS Eosinophil >3% in asthma phenotypes Drews A, et al 2007

  17. IS Neutrophil concentration in asthma phenotypes Drews A, et al 2007

  18. Conclusions • Non-atopic asthma may be the most common phenotype in Latin America • Main risk factor for asthma at age 10y: “Bronchiolitis” (RSV & Rhinovirus) early in life • Mostly neutrophilic inflammation

  19. Hypertonic Saline Study • 2000 children with ISAAC phase II questionaires answered • 1199 skin prick tests AND stool samples colected 50 with positive current asthma history in the past 12 months 50 with no history of current asthma AND no history of asthma ever

  20. Bronchoprovocation • 4.5% Hypertonic saline • PFTs • BHR positive: > 15% decline of FEV1

  21. MAIN RESULTS • 17 (17.5%) positive for BHR. • 10 (20.4%) Current wheeze. • 7 (14.6%) Control (non-wheeze). OR (CI 95%) = 1.5 (0.5 – 4.3) ns

  22. RESULTS

  23. Parasitosis vs. BHR

  24. 8 6 4 2 non atopic @ 6yrs atopic @ 6yrs Odds Ratios for Asthma 0 1 ≥2 Number wLRI in first year Synergistic interaction between atopy and wLRI in y1 for persistent asthma Sly, P et al.

  25. Maturation of Immune Responses in Infancy Non-Asthmatic Interferongamma responses(Th1) AtopicAsthmatic Non-AtopicAsthmatic 24-48 0 Age (months) Holt P, Sly P

  26. Genetic Predisposition ALLERGIC PATHWAY Allergen exposure Airway Inflammation Altered Aw Function Th2-driven Immunity ASTHMA IMMATURE IMMUNE SYSTEM Slow TH1 Environment Intensification & low clearance LRTI/ Bronchiolitis Airway Inflammation Altered Aw Function NON-ATOPIC/VIRUS PATHWAY Genetic Predisposition

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