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长效毒蕈碱拮抗剂在哮喘中的支气管扩张和抗炎作用:欧洲变态反应和临床免疫学会立场文件

The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper.

作者信息

Agache I, Adcock I M, Akdis C A, Akdis M, Bentabol-Ramos G, van den Berge M, Boccabella C, Canonica W G, Caruso C, Couto M, Davila I, Drummond D, Fonseca J, Gherasim A, Del Giacco S, Jackson D J, Jutel M, Licari A, Loukides S, Moreira A, Mukherjee M, Ojanguren I, Palomares O, Papi A, Perez de Llano L, Price O J, Rukhazde M, Shamji M H, Shaw D, Sanchez-Garcia S, Testera-Montes A, Torres M J, Eguiluz-Gracia I

机构信息

Faculty of Medicine, Transylvania University, Brasov, Romania.

Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK.

出版信息

Allergy. 2025 Feb;80(2):380-394. doi: 10.1111/all.16436. Epub 2024 Dec 16.

Abstract

As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals. In addition to bronchodilation, LAMA also exert anti-inflammatory and anti-fibrotic effects by inhibiting muscarinic receptors present in neutrophils, macrophages, fibroblasts and airway smooth muscle cells. Thus, besides bronchodilation, LAMA might provide additional therapeutic effects, thereby supporting an endotype-driven approach to asthma management. The Position Paper, developed by the Asthma Section of the European Academy of Allergy and Clinical Immunology, discusses the main cholinergic pathways in the lung, reviews the findings of significant clinical trials and real-life studies on LAMA use in asthma, examines the placement of these drugs in asthma clinical guidelines, and considers the potential for personalised medicine with LAMA in both adult and paediatric asthma patients.

摘要

由于胆碱能神经支配是迷走神经张力增加和黏液分泌增多的主要原因,吸入长效毒蕈碱拮抗剂(LAMA)是治疗慢性阻塞性肺疾病和哮喘的一大支柱。通过阻断肺中表达的毒蕈碱受体,LAMA可改善肺功能,并减少尽管接受了吸入性糖皮质激素和长效β2受体激动剂治疗但仍控制不佳的哮喘患者的病情加重情况。哮喘指南推荐将LAMA作为在开始使用生物制剂之前添加的第三种控制药物。除支气管扩张作用外,LAMA还通过抑制中性粒细胞、巨噬细胞、成纤维细胞和气道平滑肌细胞中存在的毒蕈碱受体发挥抗炎和抗纤维化作用。因此,除支气管扩张作用外,LAMA可能还具有其他治疗效果,从而支持基于内型驱动的哮喘管理方法。欧洲变态反应和临床免疫学会哮喘分会编写的这份立场文件讨论了肺中的主要胆碱能途径,回顾了关于LAMA用于哮喘治疗的重要临床试验和真实世界研究的结果,审视了这些药物在哮喘临床指南中的地位,并探讨了LAMA在成人和儿童哮喘患者中实现个性化医疗的潜力。

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