Cough in Interstitial Lung Disease: Current Knowledge and Research Gaps.
TL;DR
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.
Abstract
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.