Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry & Biomedical Science, Queen's University Belfast, Belfast, United Kingdom of Great Britain and Northern Ireland.
Clin Transl Med. 2023 Aug;13(8):e1343. doi: 10.1002/ctm2.1343.
Chronic cough is a burdensome condition characterized by persistent cough lasting longer than 8 weeks. Chronic cough can significantly affect quality of life, physical function and productivity, with many people troubled with a cough that lasts for months or even years. People with chronic cough commonly report a persistent urge to cough with frequent bouts of coughing triggered by innocuous stimuli, which has led to the concept of cough hypersensitivity.
Both central and peripheral neural pathways regulate cough, and although mechanisms driving development of cough hypersensitivity are not fully known, sensitization of these neural pathways contributes to excessive cough triggering in cough hypersensitivity. Effective therapies that control chronic cough are currently lacking. Recent therapeutic development has focused on several ion channels and receptors involved in peripheral activation of cough (e.g., transient receptor potential channels, P2 × 3 receptors and voltage-gated sodium channels) or central cough processing (e.g., neurokinin-1 [NK-1] receptors and nicotinic acetylcholine receptors).
These targeted therapies provide novel insights into mechanisms underlying cough hypersensitivity and may offer new treatment options for people with chronic cough. In this review, we explore preclinical and clinical studies that have improved our understanding of the mechanisms responsible for chronic cough and discuss the most promising targeted approaches to date, including trials of P2 × 3-receptor antagonists and NK-1-receptor antagonists.
慢性咳嗽是一种令人痛苦的病症，其特征是持续咳嗽超过 8 周。慢性咳嗽会显著影响生活质量、身体机能和生产力，许多人长期受咳嗽困扰，咳嗽持续数月甚至数年。慢性咳嗽患者常主诉持续的咳嗽欲望，频繁因无害刺激引发咳嗽发作，这导致了咳嗽敏感性的概念。
中枢和外周神经通路均调节咳嗽，尽管导致咳嗽敏感性发展的机制尚不完全清楚，但这些神经通路的敏化导致咳嗽敏感性患者过度触发咳嗽。目前缺乏控制慢性咳嗽的有效疗法。最近的治疗发展集中在参与外周咳嗽激活的几个离子通道和受体（例如瞬时受体电位通道、P2X3 受体和电压门控钠离子通道）或中枢咳嗽处理（例如神经激肽-1[NK-1]受体和烟碱型乙酰胆碱受体）。
这些靶向治疗为咳嗽敏感性的机制提供了新的见解，并可能为慢性咳嗽患者提供新的治疗选择。在这篇综述中，我们探讨了改善我们对导致慢性咳嗽的机制的理解的临床前和临床研究，并讨论了迄今为止最有前途的靶向方法，包括 P2X3 受体拮抗剂和 NK-1 受体拮抗剂的试验。
