title: Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation.
abstract: BACKGROUND
  Asthma is a heterogeneous process, yet little is understood regarding phenotypes.
  
  
  OBJECTIVE
  To determine whether phenotypic differences exist between early-onset, severe asthma as compared with late-onset disease and whether the presence or absence of eosinophilia influences the phenotypes.
  
  
  METHODS
  Cross-sectional analysis of integrated clinical, physiologic, and pathologic data collected from 80 subjects with severe asthma. Subjects were divided into those with asthma onset before age 12 years (n = 50) versus after age 12 (n = 30) and by the presence or absence of lung eosinophils.
  
  
  RESULTS
  Subjects with early-onset, severe asthma had significantly more allergen sensitivity (skin test positivity, 98% vs 76%, P <.007) and more allergic symptoms (P values all <or=.02) than subjects with late-onset asthma. In contrast, subjects with late-onset asthma had lower lung function (P values =.05 to.07) than early-onset, despite a shorter (P <.0001) duration of illness. Both groups had a high degree of general asthma symptoms, but those with persistent eosinophils from either age at onset group had significantly more (multiple P values <.05). Similarly, the presence of eosinophils in either age at onset group was associated with the lowest lung function (P <or=.02). Although late-onset asthma was associated with the highest numbers of lung eosinophils (P <.007), only early-onset severe asthma was associated with a lymphocytic/mast cell inflammatory process. Finally, subjects with late-onset asthma without eosinophils had no subepithelial basement membrane thickening, suggesting a different pathologic process.
  
  
  CONCLUSIONS
  Differentiating severe asthma by age at onset and presence or absence of eosinophils identifies phenotypes of asthma, which could benefit subsequent genetic and therapeutic studies.
authors.affiliation: National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, Colorado 80206, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Miranda
authors.forename: Ashley
authors.initials: A
authors.lastname: Busacker
authors.forename: Silvana
authors.initials: S
authors.lastname: Balzar
authors.forename: John
authors.initials: J
authors.lastname: Trudeau
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
mesh_terms: D017668:Age of Onset; D001249:Asthma / Q000175:diagnosis*; D002452:Cell Count; D003430:Cross-Sectional Studies; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D012129:Respiratory Function Tests; D012720:Severity of Illness Index