Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics

The mechanisms associated with the development of severe, corticosteroid (C S)-dependent asthma are poorly understood, but likely heterogenous. it was hypothesized that severe asthma could be divided pathologically into two in flammatory groups based on the presence or absence of eosinophils, and that the inflammatory subtype would be associated with distinct structural, phy siologic, and clinical characteristics. Thirty-four severe, refractory CS-d ependent asthmatics were evaluated with endobronchial biopsy, pulmonary fun ction, allergy testing, and clinical history. Milder asthmatic and normal c ontrol subjects were also evaluated. Tissue cell types and subbasement memb rane (SBM) thickness were evaluated immunohistochemically. Fourteen severe asthmatics [eosinophil (-)] had nearly absent eosinophils (< 2 SD from the normal mean). The remaining 20 severe asthmatics were categorized as eosino phil (+). Eosinophil (+) severe asthmatics had associated increases (p < 0. 05) in lymphocytes (CD3+, CD4+, CD8+), mast cells, and macrophages. Neutrop hils were increased in severe asthmatics and not different between the grou ps. The SBM was significantly thicker in eosinophil (+) severe asthmatics t han eosinophil (-) severe asthmatics and correlated with eosinophil numbers (r = 0.50). Despite the absence of eosinophils and the thinner SBM, the FE V, was marginally lower in eosinophil (-) asthmatics (p = 0.05) with no dif ference in bronchodilator response. The eosinophil (+) group (with a thicke r SBM) had more intubations than the eosinophil (-) group (p = 0.0004). Int erestingly, this group also had a decreased FVC/slow vital capacity (SVC). These results suggest that two distinct pathologic, physiologic, and clinic al subtypes of severe asthma exist, with implications for further research and treatment.