Cough in idiopathic pulmonary fibrosis

Abstract

Many patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably "multifactorial" and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF.

FIGURE 1

Pathophysiology of cough. TRPV1: transient receptor potential vanilloid 1; TRPA1: transient receptor potential ankyrin 1; RAR: rapidly adapting receptor; SAR: slowly adapting receptor. Reproduced from [17] with permission from the publisher.

FIGURE 2

Interactions between idiopathic pulmonary fibrosis (IPF), gastro-oesophageal reflux disease (GORD), obstructive sleep apnoea (OSA) and cough. 1: traction leading to a weaker lower oesophageal sphincter tonus [45]; 2: microaspiration inducing epithelial damage [38, 46]; 3: restriction inducing instability of the upper airway [39]; 4: intermitted hypoxaemia promoting profibrotic mechanisms [49]; 5: increased cough reflex sensitivity [–31]; 6: pressure causing stretch injury and activation of fibrotic mechanisms [31]; 7: microaspiration causing an inflammatory reaction blocking the airway [53]; 8: obstruction increasing trans-diaphragmatic pressure [51, 52]; 9: aspiration directly and acid reflux indirectly stimulate the cough reflex [6, 47]; 10: cough increasing trans-diaphragmatic pressure [47]; 11: less central inhibition and inflammation increasing cough reflex sensitivity [54].