Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
College of Medicine, Taipei Medical University, Taipei, Taiwan.
Clin Exp Allergy. 2019 Jan;49(1):44-53. doi: 10.1111/cea.13248. Epub 2018 Sep 11.
Omalizumab, a recombinant monoclonal anti-IgE antibody, was developed for the treatment of severe allergic asthma. Not all these patients respond to omalizumab.
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.
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.
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.
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.
奥马珠单抗是一种重组单克隆抗 IgE 抗体，用于治疗严重过敏性哮喘。并非所有这些患者对奥马珠单抗治疗有反应。
本研究旨在评估奥马珠单抗治疗应答和无应答的严重过敏性哮喘患者的促炎细胞因子谱是否存在差异。
前瞻性研究通过免疫组织化学、Western blot 和 PCR 分析，检测奥马珠单抗治疗前后严重过敏性哮喘患者支气管组织中的 2 型细胞因子和上皮衍生细胞因子。
23 例不稳定严重过敏性哮喘患者中有 14 例在接受奥马珠单抗治疗 4 个月后哮喘控制得到改善（应答者），而 9 例未改善（无应答者）。大多数应答者为 2 型高表型（12/14），其支气管组织中 IL-33、IL-25 和 TSLP 表达上调，而大多数无应答者为 2 型低表型（8/9）。在奥马珠单抗治疗后，9 例应答者重复支气管镜活检，显示支气管组织中 IL-13、IL-33、IL-25 和 TSLP 表达下降。在继续接受奥马珠单抗治疗 12 个月的 14 例应答者中，6 例哮喘得到良好控制（ACT≥23），而 8 例患者需要额外的哮喘症状治疗，且支气管组织中存在混合嗜酸性粒细胞和中性粒细胞炎症和更严重的鼻-鼻窦炎共病。
从奥马珠单抗治疗中获益的大多数严重过敏性哮喘患者为 IL-33、IL-25 和 TSLP 加重的 2 型高表型。对于奥马珠单抗部分应答的患者，应评估是否存在鼻-鼻窦炎或混合嗜酸性粒细胞和中性粒细胞气道炎症。
