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Asma na Inf ância

Asma na Inf ância. Renato T. Stein, M.D. Pontif ícia Universidade Católica Porto Alegre, Brazil. Respiratory System Development. More vulnerable (irritants/virus, pollutants) in the first years

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Asma na Inf ância

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  1. Asma na Infância Renato T. Stein, M.D.Pontifícia Universidade Católica Porto Alegre, Brazil

  2. Respiratory System Development • More vulnerable (irritants/virus, pollutants) in the first years • Higher surface area-to-volume ratio (infants breath more air relative to body weight than older children) • Smaller airways: more deposition of particulate matter • Major lung growth period (50-70% alveoli formed after birth up to ~18 months old)

  3. Infant Pulmonary Function: Prematures FVC Reduced Lung Function in Healthy Preterm Infants in the First Months of LifeFriedrich L, Stein RT, Jones MH et al. Am. J. Respir. Crit. Care Med. 2006

  4. Infant Pulmonary Function: Prematures FEF 25-75 Friedrich L et al. Am. J. Respir. Crit. Care Med. 2006

  5. Pulmonary Growth in Premature Infants Friedrich L, Jones MH et al. . AJRCCM 2007

  6. Impact on Lung Development Allergens, pollutants, air toxics Acute severe Viral Infections

  7. Different “Asthma” Phenotypes

  8. Transient Wheezing by Early Lung Function p<0.0001 % TransientWheezing Quartiles of V’max FRC at 2 months

  9. Persistent Wheezing by Early Lung Function n.s. % PersistentWheezing Quartiles of V’max FRC at 2 months

  10. Lung Function over Time by Classification at Recruitment in the Melbourne Study

  11. Sears et al, NEJM 349:1414 (2003)

  12. FEV1 by Age in Asthmatics and Smokers (Busselton, Australia) James et al, AJRCCM 2005, 171:109

  13. Lung Function at Ages 1, 6, 11 and 16 Years in the Tucson Study Morgan WJ et al. AJRCCM 2005

  14. Hypothetical Representation of the Natural History of Asthma Persistent Asthma Progression Inception Protection Asthma, Not Persistent No Asthma Asthma Initial Phase Remission Exacerbation No Asthma

  15. Hypothetical Representation of the Natural History of Asthma Chronic Asthma ICS? Progression Inception Protection Asthma, Not Chronic No Asthma Asthma Initial Phase Remission Exacerbation No Asthma

  16. CAMP Study Design • Children with “mild to moderate asthma” (symptoms or use of Albuterol 2 times weekly or daily use of asthma medication) • Treated for 4-6 years with Budesonide 200 g bid (N=311) or Nedocromil 8 mg bid (N=312) or matching placebo • Primary outcome: mean change % predicted post bronchodilator FEV1 4-6 years after initiation of treatment N Engl J Med 2000;343:1054-63

  17. Lung Function in the CAMP Study N Engl J Med 2000;343:1054-63

  18. What Is The PEAK Trial? PEAK investigated if inhaled corticosteroids (ICS), when initiated in preschool-aged children at high risk for asthma, can alter the natural history of asthma after ICS are discontinued Guilbert TW et al. NEJM 2006

  19. Treatment Observation PEAK: Study Design Screening/ Eligibility Run-in Year 3 1 month Years 1 & 2 Interim Efficacy Tests Randomize • Randomized, multicenter, double-blind, parallel group, placebo-controlled trial • 285 two and three year olds at high-risk for asthma • Fluticasone 44 g/puff or placebo (2 puffs b.i.d.)

  20. Observation Treatment Episode-free Days During the Entire Study Guilbert TW et al. NEJM 2006)

  21. ICS Effect During Treatment Phase Asthma Exacerbations P<0.001

  22. ICS Effect on IOS (impulse oscillometry) Measures: Reactance at 5 Hz * Greater dynamic lung compliance p=0.008 p=0.83

  23. Conclusions • Changes in airway function (remodeling?) occur early in life in asthma, with little subsequent further deterioration • Daily ICS are effective in preventing exacerbations and controlling symptoms in 2-3 yr olds at high risk for asthma • However, two years of treatment with daily ICS did not change the natural history of asthma in these same children

  24. Asthma Phenotypes Stein R et al. Thorax 1997

  25. Southern Brazil Study:Risk factors for Wheeze and Asthma Risk increases > 50X for children with both Bronchiolitis and Ascaris Pereira M et al. ERJ 2007

  26. 80 60 Sputum eosinophils x 105cells/g 40 *** *** 20 0 No atopy/ no asthma Atopic asthma Non-atopic asthma

  27. IS Neutrophil concentration in asthma phenotypes Pizzichini MM, et al. 2008

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

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