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

摘要

Background Omalizumab, a recombinant monoclonal anti-IgE antibody, was developed for the treatment of severe allergic asthma. Not all these patients respond to omalizumab. Objective This study aimed to evaluate whether the proinflammatory cytokine profiles in the severe allergic asthma patients were different between who responded and nonresponded to omalizumab therapy. Methods A prospective study was conducted to examine type 2 cytokines and epithelium-derived cytokines in the bronchial tissues by immunohistochemistry, Western blot and PCR analysis among patients with severe allergic asthma before and after omalizumab therapy. Results Fourteen of 23 patients with unstable severe allergic asthma improved their asthma control after 4 months of omalizumab treatment (Responders), while nine failed to improve (Non-Responders). Most of Responders were type 2-high endotype (12/14) with upregulated 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 nine 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, six patients achieved a well control of asthma (ACT = 23), while eight patients required additional treatment for asthma symptoms and had more rhinosinusitis comorbidities and a mixed eosinophilic and neutrophilic inflammation in their bronchial tissues. Conclusion Most of the severe allergic asthma patients who benefited from omalizumab treatment were IL-33, IL-25 and TSLP aggravated type 2-high endotype. Rhinosinusitis or with a mixed eosinophilic and neutrophilic airway inflammation should be evaluated in patients who partially responded to omalizumab treatment.