Low-dose morphine relieves cough in idiopathic pulmonary fibrosis

In patients with idiopathic pulmonary fibrosis (IPF)-related cough, treatment with low-dose controlled-release morphine leads to reduced daytime cough frequency and better quality of life, according to data from the phase II PACIFY COUGH crossover trial.

PACIFY COUGH included 44 IPF patients (mean age 71 years, 70 percent men) with self-reported cough lasting >8 weeks and a cough visual analogue scale (VAS) score of 30 mm or higher. These patients were randomly assigned to receive either controlled-release morphine 5 mg or placebo, administered orally twice daily for 14 days. After a 7-day washout period, the patients were switched to the alternative treatment.

At baseline, the patients had moderately impaired lung function, with mean forced vital capacity (FVC) of 2.7 L, mean predicted FVC of 82 percent, and mean predicted diffusion capacity of carbon monoxide of 48 percent. A total of 43 patients completed morphine treatment, and 41 completed placebo treatment.

Intention-to-treat analysis showed that compared with placebo, morphine was associated with a 39.4-percent (95 percent confidence interval [CI], –54.4 to –19.4; p=0.0005) reduction in objective awake cough frequency.

Mean daytime cough frequency dropped from 21.6 coughs per hour at baseline to 12.8 coughs per hour with morphine, whereas the frequency remained unchanged with placebo from 21.5 h to 20.6 coughs per hour. Overall treatment adherence was similar at 98 percent in the morphine and placebo groups.

Adverse events occurred in 40 percent of patients in the morphine group and in 14 percent of patients in the placebo group. The main side-effects of morphine were nausea (14 percent) and constipation (21 percent). One patient in the placebo group died.