title: Pathophysiological characterization of asthma transitions across adolescence.
abstract: BACKGROUND
  Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of transitional adolescent asthma phenotypes in a longitudinal birth cohort.
  
  
  METHODS
  The Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterization included questionnaires, skin tests, spirometry, exhaled nitric oxide, bronchial challenge and (in a subset of 100 at 18-years) induced sputum. Asthma groups were "never asthma" (no asthma since birth), "persistent asthma" (asthma at age 10 and 18), "remission asthma" (asthma at age 10 but not at 18) and "adolescent-onset asthma" (asthma at age 18 but not at age 10).
  
  
  RESULTS
  Participants whose asthma remitted during adolescence had lower bronchial reactivity (odds ratio (OR) 0.30; CI 0.10 -0.90; p = 0.03) at age 10 plus greater improvement in lung function (forced expiratory flow 25-75% gain: 1.7 L; 1.0-2.9; p = 0.04) compared to persistent asthma by age 18. Male sex (0.3; 0.1-0.7; p < 0.01) and lower acetaminophen use (0.4; 0.2-0.8; p < 0.01) independently favoured asthma remission, when compared to persistent asthma. Asthma remission had a lower total sputum cell count compared to never asthma (31.5 [25-75 centiles] 12.9-40.4) vs. 47.0 (19.5-181.3); p = 0.03). Sputum examination in adolescent-onset asthma showed eosinophilic airway inflammation (3.0%, 0.7-6.6), not seen in persistent asthma (1.0%, 0-3.9), while remission group had the lowest sputum eosinophil count (0.3%, 0-1.4) and lowest eosinophils/neutrophils ratio of 0.0 (Interquartile range: 0.1).
  
  
  CONCLUSIONS
  Asthma remission during adolescence is associated with lower initial BHR and greater gain in small airways function, while adolescent-onset asthma is primarily eosinophilic.
authors.affiliation: The David Hide Asthma and Allergy Research Centre, Isle of Wight, UK. sha@soton.ac.uk.
authors.forename: Syed Hasan
authors.initials: SH
authors.lastname: Arshad
authors.forename: Abid
authors.initials: A
authors.lastname: Raza
authors.forename: Laurie
authors.initials: L
authors.lastname: Lau
authors.forename: Khalid
authors.initials: K
authors.lastname: Bawakid
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Susan
authors.initials: S
authors.lastname: Ewart
authors.forename: Veersh
authors.initials: V
authors.lastname: Patil
authors.forename: Graham
authors.initials: G
authors.lastname: Roberts
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kurukulaaratchy
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008168:Lung / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011379:Prognosis; D012074:Remission Induction; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D006113:United Kingdom / Q000453:epidemiology