Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation.
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.
Miranda
Christina
C
National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, Colorado 80206, USA.
Busacker
Ashley
A
Balzar
Silvana
S
Trudeau
John
J
Wenzel
Sally E
SE
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