间质性肺疾病中的咳嗽：当前认识与研究空白

文献信息

中文摘要

背景： 慢性咳嗽是间质性肺疾病（ILD）患者最常见且负担最重的症状之一，显著损害生活质量，并且在特发性肺纤维化（IPF）中与疾病进展相关。尽管具有临床意义，但ILD中咳嗽的机制仍未完全阐明，有效的治疗选择有限。本叙述性综述总结了关于ILD谱系中咳嗽的流行病学、病理生理学、临床评估和管理的当前证据。方法：当前数据支持这一概念：ILD相关咳嗽源于咳嗽反射超敏、纤维化肺的机械变形、气道和肺实质炎症、神经重塑以及常见合并症（如胃食管反流病和阻塞性睡眠呼吸暂停）之间复杂的相互作用。还讨论了结缔组织病相关ILD、结节病和过敏性肺炎中的疾病特异性机制。我们回顾了目前可用的咳嗽评估定性和定量方法，包括患者报告结局指标和客观咳嗽监测技术，强调了它们在临床实践和研究中的优势和局限性。最后，我们审视了已确立和新兴的治疗方法。结果：虽然抗纤维化治疗对咳嗽的效果有限且不一致，但最近的随机临床试验为低剂量吗啡和缓释纳布啡治疗IPF相关慢性咳嗽提供了令人鼓舞的证据。非药物干预，特别是物理治疗和言语语言治疗，也显示出有意义的益处。几种针对神经和炎症通路的新型治疗策略目前正在研究中。结论：更好地理解驱动ILD中咳嗽的机制，结合标准化的评估工具和足够把握度的临床试验，对于开发针对这种致残性症状的有效、疾病特异性治疗至关重要。

英文摘要

Chronic cough is one of the most frequent and burdensome symptoms in patients with interstitial lung disease (ILD), substantially impairing quality of life and, in idiopathic pulmonary fibrosis (IPF), being associated with disease progression. Despite its clinical relevance, the mechanisms underlying cough in ILD remain incompletely understood, and effective therapeutic options are limited. This narrative review summarizes current evidence on the epidemiology, pathophysiology, clinical assessment, and management of cough across the spectrum of ILD. Current data support the concept that ILD-related cough results from a complex interplay between cough reflex hypersensitivity, mechanical distortion of the fibrotic lung, airway and parenchymal inflammation, neural remodeling, and common comorbidities such as gastroesophageal reflux disease and obstructive sleep apnea. Disease-specific mechanisms are also discussed in connective tissue disease-associated ILD, sarcoidosis, and hypersensitivity pneumonitis. We review currently available qualitative and quantitative methods for cough assessment, including patient-reported outcome measures and objective cough monitoring technologies, highlighting their strengths and limitations in clinical practice and research. Finally, we examine established and emerging therapeutic approaches. While antifibrotic therapies have shown limited and inconsistent effects on cough, recent randomized clinical trials provide encouraging evidence for low-dose morphine and extended-release nalbuphine in IPF-associated chronic cough. Nonpharmacological interventions, particularly physiotherapy and speech and language therapy, also demonstrate meaningful benefits. Several novel therapeutic strategies targeting neural and inflammatory pathways are currently under investigation. A better understanding of the mechanisms driving cough in ILD, together with standardized assessment tools and adequately powered clinical trials, will be essential to develop effective, disease-specific treatments for this disabling symptom.