Endotypes of severe allergic asthma patients who clinically benefit from Anti-IgE therapy

Omalizumab, a recombinant monoclonal anti-IgE antibody, is effective in treatment of severe allergic asthma. We prospectively compared the underlying type 2 cytokines and epithelium derived cytokines in bronchial tissues between omalizumab responsive and non-responsive severe allergic asthma patients. Fourteen of 23 patients with unstable severe allergic asthma improved their asthma control after 4 months of omalizumab treatment (Responders), while 9 failed to improve (Non-Responders). Most of Responders were type 2-high endotype (12/14) with up-regulated expression of IL-33, IL-25 and TSLP in their bronchial tissues, while most of Non-Responders were type 2-low endotype (8/9). Repeated bronchoscopic biopsy was done in 9 responders after omalizumab treatment, and showed a decline in IL-13, IL-33, IL-25 and TSLP expression in the bronchial tissues. Among 14 Responders who continued omalizuamb treatments to a total 12 months, 6 patients achieved a well control of asthma (ACT≥23), while 8 patients required additional treatment for asthma symptoms and had more rhinosinusitis co-morbidities and higher IL-17A expression in their bronchial tissues. Most of severe allergic asthma patients who benefited from omalizumab treatment were IL-33, IL-25 and TSLP aggravated type 2-high endotype. Rhinosinusitis with or without fungus exposure should be evaluated in patients who partially responded to omalizumab treatment.