Eosinophil-mucus interplay in severe asthma: Implications for treatment with biologicals

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-03-13 DOI:10.1016/j.alit.2024.03.001
Carmen Venegas Garrido, Manali Mukherjee, Sarah Svenningsen, Parameswaran Nair
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Abstract

Airway mucus is a hydrogel with unique biophysical properties due to its primary water composition and a small proportion of large anionic glycoproteins or mucins. The predominant mucins in human mucus, MUC5AC and MUC5B, are secreted by specialized cells within the airway epithelium both in normal conditions and in response to various stimuli. Their relative proportions are correlated with specific inflammatory responses and disease mechanisms. The dysregulation of mucin expression is implicated in numerous respiratory diseases, including asthma, COPD, and cystic fibrosis, where the pathogenic role of mucus has been extensively described yet often overlooked. In airway diseases, excessive mucus production or impaired mucus clearance leads to mucus plugging, with secondary airway occlusion that contribute to airflow obstruction, asthma severity and poor control. Eosinophils and Charcot Leyden crystals in sputum contribute to the mucus burden and tenacity. Mucin may also contribute to eosinophil survival. Other mechanisms, including eosinophil-independent IL-13 release, mast-cell activation and non-type-2 (T2) cytokines, are also likely to participate in mucus pathobiology. An accurate assessment of mucus and its clinical and functional consequences require a thorough approach that includes evaluation of cellular predominance in sputum, airway cytokines and other inflammatory markers, mucus characteristics and composition and structural and functional impact measured by advanced lung imaging. This review, illustrated with clinical scenarios, provides an overview of current methods to assess mucus and its relevance to the choice of biologics to treat patients with severe asthma.

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严重哮喘中嗜酸性粒细胞与黏液的相互作用:生物制剂治疗的意义
气道粘液是一种具有独特生物物理特性的水凝胶,其主要成分是水和一小部分大型阴离子糖蛋白或粘蛋白。人体粘液中最主要的粘蛋白是 MUC5AC 和 MUC5B,由气道上皮内的特化细胞在正常情况下和对各种刺激做出反应时分泌。它们的相对比例与特定的炎症反应和疾病机制相关。许多呼吸道疾病都与粘蛋白表达失调有关,包括哮喘、慢性阻塞性肺病和囊性纤维化。在气道疾病中,粘液产生过多或清除受损会导致粘液堵塞,继发气道闭塞,从而造成气流阻塞、哮喘严重程度和控制不佳。痰中的嗜酸性粒细胞和夏科-莱登结晶会加重粘液负担,并使粘液更加顽固。粘蛋白还可能有助于嗜酸性粒细胞存活。其他机制,包括嗜酸性粒细胞无关的 IL-13 释放、肥大细胞激活和非 2 型(T2)细胞因子,也可能参与粘液病理生物学。要准确评估粘液及其临床和功能性后果,需要采取全面的方法,包括评估痰液中的细胞优势、气道细胞因子和其他炎症标记物、粘液特征和组成以及先进肺部成像测量的结构和功能影响。本综述结合临床案例,概述了目前评估粘液的方法及其与选择生物制剂治疗重症哮喘患者的相关性。
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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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