Background: Idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) represent two prevalent forms of interstitial lung diseases (ILDs), where a persistent cough is a common and distressing symptom. The prognostic significance of cough in IPF is still a subject of contention and effective antitussive interventions remain elusive. The pathogenesis of cough in HP is thought to be linked to alveolar inflammation; however, the application of steroids, a common therapeutic strategy, lacks studies to confirm its efficacy.
Methods: A prospective observational cohort study was conducted in newly diagnosed patients, utilising both subjective and objective measures of cough to characterise its burden and evaluate the effects of existing disease-modifying treatments on cough, namely antifibrotic agents for IPF and steroids for HP. Additionally, the potential antitussive efficacy of 5mg twice daily morphine sulphate (MST) for 14 days was examined in IPF patients through a multicentre, randomised, placebo-controlled crossover trial.
Results: Worse baseline cough severity analogue scale (VAS) and Leicester Cough Questionnaire (LCQ) scores were associated with diminished survival in IPF. A cough VAS ≥ 30/100 mm was associated with a 2.8-times increased mortality risk. Meanwhile, the HP cohort had a similar cough burden to the IPF group and alveolar inflammatory signal was not associated with cough. As for the treatment of cough, current disease-modifying therapies had limited effects in both groups. However, low-dose MST reduced daytime cough frequency by 39% and improved all cough-related patient reported outcomes in IPF patients.
Conclusion: Cough severity represents a prognostic marker in IPF and a VAS score of 30/100 mm should be adopted in future clinical trial design. Low-dose MST has proven to be an effective short-term intervention for alleviating cough in IPF patients. Additionally, given the similar cough burden in HP, there exists a clear unmet need to discover effective antitussives in these patients.