Critical pathomechanisms of NSAID-exacerbated respiratory disease (N-ERD) clarified by treatment with omalizumab, an anti-IgE antibody.

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-10-16 DOI:10.1016/j.alit.2024.08.008
Hiroaki Hayashi, Makoto Ishii, Yoshinori Hasegawa, Masami Taniguchi
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Abstract

Characteristic symptoms of NSAID-exacerbated respiratory disease (N-ERD) include asthma, chronic eosinophilic rhinosinusitis with nasal polyposis, cysteinyl LT (CysLT) overproduction and NSAIDs hypersensitivity. Some N-ERD patients present with episodic treatment-resistant extra-respiratory symptoms (CysLT-associated coronary artery vasospasm, gastroenteritis, or skin rash). Even when using standard treatments for respiratory and extra-respiratory symptoms, including systemic corticosteroids and aspirin desensitization, it is difficult to control the clinical symptoms and severe type 2 inflammation involved with mast cells, eosinophils, ILC2s, and platelet activation. Few treatment options are applicable in a clinical setting. Therefore, identifying effective treatments is essential for managing N-ERD patients who suffer from these conditions. Our previous observational study demonstrated 12-month omalizumab treatment of N-ERD was clinically effective against respiratory symptoms. Despite the remaining eosinophilia, omalizumab significantly reduced urinary LTE4 and PGD2 metabolites to near normal levels at steady state. Based on the preliminary study, we demonstrated that omalizumab induced tolerance to aspirin in N-ERD patients 3 months after therapy initiation and suppressed activation of mast cells during 24 h of initiation in a randomized manner. Moreover, omalizumab had significant efficacy against extra-respiratory symptoms at baseline (lacking aspirin exposure) as well as throughout aspirin challenge. This review addresses the latest discoveries related to N-ERD pathogenesis and the significant effectiveness of omalizumab on N-ERD as a mast cell stabilizer. Our findings regarding omalizumab-associated mast cell inhibitory effects are indirect evidence that mast cell dysregulation and, possibly, IgE are pivotal components of N-ERD.

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用抗 IgE 抗体奥马珠单抗治疗非甾体抗炎药导致的呼吸道疾病(N-ERD)的关键病理机制。
非甾体抗炎药加重呼吸道疾病(N-ERD)的特征性症状包括哮喘、慢性嗜酸性鼻炎伴鼻息肉、半胱氨酸LT(CysLT)分泌过多和对非甾体抗炎药过敏。一些 N-ERD 患者会出现发作性治疗耐药的呼吸道外症状(与 CysLT 相关的冠状动脉血管痉挛、肠胃炎或皮疹)。即使对呼吸道症状和呼吸道外症状采用标准治疗方法(包括全身皮质类固醇和阿司匹林脱敏),也很难控制临床症状以及肥大细胞、嗜酸性粒细胞、ILC2s 和血小板活化引起的严重 2 型炎症。适用于临床的治疗方案寥寥无几。因此,找到有效的治疗方法对于管理患有这些病症的 N-ERD 患者至关重要。我们之前的观察性研究表明,对 N-ERD 患者进行为期 12 个月的奥马珠单抗治疗对缓解呼吸道症状有临床疗效。尽管仍存在嗜酸性粒细胞增多,但奥马珠单抗能显著降低尿液中的 LTE4 和 PGD2 代谢物,使其在稳态时接近正常水平。根据初步研究,我们证明奥马珠单抗可诱导 N-ERD 患者在开始治疗 3 个月后对阿司匹林产生耐受性,并以随机方式抑制开始治疗 24 小时内肥大细胞的活化。此外,奥马珠单抗对基线(未接触阿司匹林)和整个阿司匹林挑战期间的呼吸道外症状都有显著疗效。这篇综述探讨了与 N-ERD 发病机制有关的最新发现,以及奥马珠单抗作为肥大细胞稳定剂对 N-ERD 的显著疗效。我们关于奥马珠单抗相关肥大细胞抑制作用的发现间接证明了肥大细胞失调以及 IgE 可能是 N-ERD 的关键组成部分。
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来源期刊
Allergology International
Allergology International ALLERGY-IMMUNOLOGY
CiteScore
12.60
自引率
5.90%
发文量
96
审稿时长
29 weeks
期刊介绍: Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense. The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.
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