Background: The majority of patients with idiopathic pulmonary fibrosis (IPF) report cough and it is associated with significant negative physical, social and psychological consequences.

Objective: We examined the use of low dose controlled-release morphine sulfate (MST) as an antitussive therapy.

Methods: PulmonAry Fibrosis (PAciFy) Cough was a multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial of MST in subjects with IPF. Key inclusion criteria included a self-reported cough (> 8 weeks) with a cough visual analogue scale (VAS) score ? 30/100 mm. Patients were randomised (1:1) to either placebo twice daily or MST 5mg twice daily for 14 days. Patients then underwent crossover after a 7-day washout period.

Results: Among the 44 patients who were randomized (mean age 71 years; 70% men), 43 completed the morphine arm and 41 completed the placebo arm. The primary endpoint was percent change in objective awake cough frequency at day 14 of treatment. MST reduced awake cough frequency by 39.4% compared to placebo (95% CI, -54.4 to -19.4; P < 0.001). Furthermore, MST treatment led to improvements in cough VAS (-16.1mm, P < 0.001), Leicester Cough Questionnaire (1.8 points, P < 0.001), Living with IPF (L-IPF) Impacts (-5.2, P = 0.033) and L-IPF cough domain (-10.8, P < 0.001). The main side effects of MST were nausea (14%) and constipation (21%). One serious adverse event (death) occurred during the placebo arm.

Conclusion: MST is an effective antitussive in patients with IPF. Given the established safety profile of morphine in IPF these findings are rapidly translatable into clinical practice.