Distinguishing asthma phenotypes: Role of age of onset and eosinophilic inflammation

Abstract

Rationale Asthma is a heterogeneous process, yet little is understood regarding phenotypes. Methods Cross-sectional analysis of integrated clinical, physiologic and pathologic data collected from 80 severe asthmatics. Subjects were divided into those with asthma onset before age 12 (n=50) vs after age 12 (n=30), and by the presence or absence of lung eosinophils. Results Early onset asthmatics were significantly more allergic [skin test positivity (98% vs 76%, p<0.007) and allergic symptoms (p-values all <0.02)] than late onset asthmatics. In contrast, late onset asthmatics had lower lung function (p-values=0.05–0.07) than early onset, despite a shorter (p<0.0001) duration of illness. Both groups had a high degree of general asthma symptoms, but those with persistent eosinophils from either age of onset group had significantly more (multiple p-values<0.05). Similarly, the presence of eosinophils in either age of onset group was associated with the lowest lung function (p-values<0.02). Although late onset asthma was associated with the highest numbers of lung eosinophils (p<0.007), only early onset asthma was associated with a lymphocytic/mast cell inflammatory process. Late onset asthma was associated with higher urinary leukotriene levels (p<0.05). Finally, late onset asthmatics without eosinophils had no subepithelial basement membrane thickening, suggesting a different pathologic process entirely. Conclusions Differentiating severe asthmatics on the basis of age of onset and presence or absence of eosinophils identifies phenotypes of asthma which could benefit subsequent genetic and therapeutic studies.