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La storia naturale dell’asma fernando maria de benedictis

AOU “Ospedali Riuniti” - Ancona Ospedale Materno-Infantile di Alta Specializzazione “G. Salesi” SOD Pediatria. La storia naturale dell’asma fernando maria de benedictis. The natural history of asthma: questions to answer. When does asthma begin in childhood? Do children outgrow asthma?

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La storia naturale dell’asma fernando maria de benedictis

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  1. AOU “Ospedali Riuniti” - Ancona Ospedale Materno-Infantile di Alta Specializzazione “G. Salesi” SOD Pediatria La storia naturale dell’asma fernando maria de benedictis

  2. The natural history of asthma: questions to answer • When does asthma begin in childhood? • Do children outgrow asthma? • May asthma relapse after disappearance? • What about late-onset asthma? • Is there anything that can modify the course of asthma?

  3. A community-based study of the epidemiology of asthma Yunginger, ARRD 1992;146:888

  4. Remission rates of asthma symptoms during adolescence in cohort studies 70% 67% 50% 45% Nicolai, 2001 Anderson, 1986 Peat, 1989 Withers, 1998

  5. It is often not asthma that is outgrown, but the paediatrician…. Levison, JACI 1991

  6. The natural history of asthma: the need of prospective, long-term studies • May describe disease progression through its full course • May identify unbiased associations between specified • exposures and subsequent development of disease outcomes • May help to understand the effect of therapies on modifying • the course of the disease

  7. British 1958 asthma and wheezing study UK cohort of 18.553 subjects followed from birth until 33 yrs 880 children who had wheezing before the age of 7 yrs 50% % of asthma attacks in the previous year 27% 18% 10% 10% Strachan, BMJ 1996;312;1195

  8. The Melbourne asthma study (1964-1999) Longitudinal study of 403 subjects from the age of 7 yrs to 42 yrs - Eczema - Hay fever - Atopy Phelan, JACI 2002;109:189

  9. The New Zealand asthma study Cohort study of 1037 unselected subjects from age 9 to 26 yrs 15% 15% 12% 9% 21% 28% 27% Female sex Smoking Early age of onset Atopy BHR Sears, NEJM 2003;349:1414

  10. German Multicenter Allergy Study 815 unselected newborns and 499 at high risk of atopy followed from birth to 13 yrs No difference Non-atopic Atopic 46% 10% Prevalence of current wheeze in children with any wheezing episode at school age stratified for atopy at school age Illi, Lancet 2006;368:763

  11. CAMP study 1041 asthmatic children 5 to 12 yrs Trial of anti-inflammatory treatments for 5 yrs, and then a 4-year follow up 55% Severity of asthma Allergicsensitization Lowlungfunction BHR 39% 6% Covar, JACI 2010;125:359

  12. CAMP study 1041 asthmatic children 5 to 12 yrs Trial of anti-inflammatory treatments for 4 to 6 yrs and then a 4-year follow up Covar, JACI 2010;125:359

  13. Pattern of asthma in adults with a history of childhood asthma 85 subjects with asthma in childhood evaluated 17 to 30 years after immunotherapy Limb, JACI 2005;115:61

  14. Tucson Children Respiratory Study Cohort of 846 subjects followed from birth to 22 years 14.0 OR for asthma at age 22 yrs 7.4 4.6 4.1 2.1 1.4 Stern, Lancet 2008;372:1058

  15. The Melbourne asthma study (1964-1999) * *p <0.01 vs controls * At each year of review, the degree of lung function abnormality paralleled the initial frequency of wheeze = The early loss of lung function did not appear to progress ! Phelan, JACI 2002;109:189

  16. The New Zealand asthma study Cohort study of 1037 unselected subjects followed from birth until 26 yrs The slopes of change in FEV1:FVC were similar in each wheezing group (“tracking”), thus indicating that impairment of lung function in patients with persistent asthma occurred in early childhood, before the first measurement at the age of 9 years. Sears, NEJM 2003;349:1414

  17. Tucson Children Respiratory Study Cohort of 425 subjects followed from birth to 16 years Morgan, AJRCCM 2005;172:1253

  18. Tucson Children Respiratory Study Cohort of 846 subjects followed from birth to 22 years FEV1/FVC ratio and asthma at age 22 yrs by age at first asthma diagnosis Stern, Lancet 2008;372:1058

  19. Determinants the progressive loss of lung function in asthmatics • In asthmatic children, reduced lung function becomes apparent around school age • In asthmatic subjects, there is no further progression of lung function impairment from childhood up to adolescence and adulthood (“tracking”) • Airway inflammation and changes in airway structure (“remodeling”) are considered to be responsible for reduced lung function • Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with asthma

  20. German Multicenter Allergy Study 815 unselected newborns and 499 at high risk of atopy followed from birth to 13 yrs p<0.05 * atopic wheeze vs no wheeze * atopic wheeze vs non-atopic wheeze * * * FVC % FVC/FEV1 % FEV1 % * * * * * The differences in pulmonary function between the different classes persist after bronchodilator MEF75 % MEF50 % * * MEF25 % * * * * * * * * * * * 10 yr 13 yr 10 yr 13 yr 10 yr 13 yr 7 yr 7 yr 7 yr Baseline lung function at different ages stratified for wheezing at 5-7 years Illi, Lancet 2006;368:763

  21. Adolescents with clinical remission of asthma, inflammation and bronchial hyperreactivity 21 with active asthma; 21 with asthma remission; 18 controls MCH challenge and FeNO van den Toorn, AJRCCM 2000;162:953

  22. Italian Study on asthma in young adults Cross-sectional study of 18.837 young adults Cumulative probability of remission The minority of persons with early-onset asthma who do not recover represents approximately 35% of prevalent cases of the young adult population (20-44 year of age). De Marco, JACI 2002;110:228

  23. Males Females Incidence of asthma/100.000 pts Gender differences for the incidence and pattern of asthma Osman, Arch Dis Child 2003;88:5879

  24. The New Zealand asthma study Sex differences in childhood- and adolescent-onset wheeze F vs M, p <0.001 Wheeze between ages 10 and 26 M vs F, p <0.001 Wheeze by age 10 The influence of parental atopy on the development of wheeze differs between males and females and between childhood- and adolescent-onset wheeze Mandhane, AJRCCM 2005;172:45

  25. The natural history of asthma: what do we know? • Three of 4 school-aged children with asthma have outgrown • disease by mid-adulthood • Risk of persistence/relapse increases with severity, sensitization, • smoking and female sex • Children with asthma have reduced lung function by early school • age. The lung function seems to track at a fixed percentile. • Neither primary (manipulation of environmental factors) nor • secondary (use of anti-inflammatory drugs) prevention can • effectively halt the long term disease progression of asthma

  26. The natural history of asthma: what is still unknown? • Whether the earlyloss of lungfunction in asthmais a cause • or a consequence of the disease • Whichis the relationshipbetweenairflowlimitation in the • neonates and development of asthma • The direction of causalitybetweeninfantbronchialresponsiveness • and asthma • Long termcohortstudiesstartingbeforebirthmay gain power from • deepphenotyping with objectiveassessment of the disease • Analyticapproaches are needed to achieve more than just interestingobservations of statisticallysignificantassociations

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