Trushenko Natalia V, Suvorova Olga A, Schmidt Anna E, Chikina Svetlana Y, Levina Iuliia A, Lavginova Baina B, Avdeev Sergey N
Pulmonology Department, Sechenov First Moscow State Medical University (Sechenov University), Healthcare Ministry of Russia, Trubetskaya St. 8, Build. 2, Moscow 119991, Russia.
Pulmonology Scientific Research Institute, Federal Medical and Biological Agency of Russia, Orekhovyy Boulevard 28, Moscow 115682, Russia.
Diagnostics (Basel). 2025 Apr 29;15(9):1139. doi: 10.3390/diagnostics15091139.
Chronic cough is a common symptom in patients with interstitial lung diseases (ILDs), which significantly affects health-related quality of life (HRQoL). The prevalence of chronic cough varies from 30% to almost 90% in different ILDs, with the highest rate in patients with idiopathic pulmonary fibrosis. However, the pathophysiology of cough in ILDs remains poorly understood, with multiple proposed mechanisms contributing to its development. This knowledge gap complicates both clinical assessment and treatment, as current therapeutic strategies target general cough mechanisms rather than ILD-specific pathways. This review synthesizes existing data to clarify distinct cough mechanisms across ILD subtypes and identify opportunities for more targeted therapeutic strategies in this challenging patient population. Moreover, cough can be a clinical marker of disease severity and a predictor of ILD progression and transplant-free survival. Effective cough-specific therapeutic options that consider potential mechanisms, comorbidities, and individual effects on HRQoL are needed for cough associated with ILD. Therefore, the aim of this review was to analyze the prevalence, the impact on HRQoL, the pathophysiology, and the management of chronic cough in ILDs. We performed a comprehensive search in PubMed, MEDLINE, Embase, and the Cochrane Library. This review included randomized clinical trials, observational studies, systematic reviews, and meta-analyses in adults with chronic cough comparing ILD types. The following were excluded: commentaries, letters, case reports and case series, conference abstracts, and studies and publications lacking cough-specific outcomes. Several approaches to reduce cough frequency and severity were described: antifibrotic agents, neuromodulators, opiates, inhaled local anesthetics, oxygen, speech therapy, and anti-reflux therapy. Some therapeutic approaches, such as oral corticosteroids and thalidomide, can cause significant side effects. Novel agents, such as P2X3 receptor antagonists, which are in phase III trials (COUGH-1/2), show promising results for refractory cough and may benefit ILD-related cough. Thus, a comprehensive assessment of cough is required for effective cough treatment in patients with ILDs considering possible mechanisms and individual impact on QoL.
慢性咳嗽是间质性肺疾病（ILD）患者的常见症状，严重影响健康相关生活质量（HRQoL）。不同ILD中慢性咳嗽的患病率从30%到近90%不等，特发性肺纤维化患者的患病率最高。然而，ILD中咳嗽的病理生理学仍知之甚少，有多种机制被认为与咳嗽的发生有关。这一知识空白使临床评估和治疗都变得复杂，因为目前的治疗策略针对的是一般咳嗽机制，而非ILD特异性途径。本综述综合现有数据，以阐明不同ILD亚型的独特咳嗽机制，并确定在这一具有挑战性的患者群体中采取更具针对性治疗策略的机会。此外，咳嗽可能是疾病严重程度的临床标志物，也是ILD进展和无移植生存期的预测指标。对于与ILD相关的咳嗽，需要有考虑潜在机制、合并症以及对HRQoL个体影响的有效的针对咳嗽的治疗选择。因此，本综述的目的是分析ILD中慢性咳嗽的患病率、对HRQoL的影响、病理生理学及管理。我们在PubMed、MEDLINE、Embase和Cochrane图书馆进行了全面检索。本综述纳入了比较ILD类型的成人慢性咳嗽随机临床试验、观察性研究、系统评价和荟萃分析。以下内容被排除：评论、信函、病例报告和病例系列、会议摘要以及缺乏咳嗽特异性结局的研究和出版物。文中描述了几种降低咳嗽频率和严重程度的方法：抗纤维化药物、神经调节剂、阿片类药物、吸入性局部麻醉剂、氧气、言语治疗和抗反流治疗。一些治疗方法，如口服糖皮质激素和沙利度胺，可能会引起严重的副作用。新型药物，如处于III期试验（COUGH - 1/2）的P2X3受体拮抗剂，对难治性咳嗽显示出有希望的结果，可能对ILD相关咳嗽有益。因此，对于ILD患者的有效咳嗽治疗，需要考虑可能的机制和对生活质量的个体影响，对咳嗽进行全面评估。
