Morphine shows potential as effective cough therapy for pulmonary fibrosis, study finds

In a recent study published in The Lancet Respiratory Medicine, a team of researchers compared the efficacy of the controlled release of low-dose morphine as an antitussive treatment against that of a placebo in idiopathic pulmonary fibrosis patients.

Study: Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial. Image Credit: luchschenF/


Idiopathic pulmonary fibrosis is a lung disease consisting of progressive fibrosis of the lungs, with cough being the most commonly reported symptom.

The cause of this disease remains unknown, and currently, there are no cures for this condition, making it invariably fatal.

The available treatments only address the symptoms and slow the progression of the disease. Cough, which is linked to a rapid progression of the disease, also has significant impacts on the physical, psychological, and social aspects of life.

Chronic cough has often been treated with opioids, and morphine is believed to not only lower the cough reflex but also act on the neural pathways directly in the brain.

Furthermore, lower doses of morphine can be used as an antitussive or palliatively for treating dyspnea, as opposed to its use as an analgesic, which requires higher doses.

Studies investigating the use of low doses of morphine to treat interstitial lung disease and refractory cough have also reported high safety and tolerability.

About the study

In the present study, the researchers evaluated the safety and efficacy of the controlled release of low-dose morphine as an antitussive agent in treating patients with idiopathic pulmonary fibrosis using a placebo-controlled method.

Furthermore, since this study was to establish a proof-of-concept, a two-way crossover trial model was adopted to reduce patient variation and increase statistical power.

This double-blind, randomized, multicenter study was called PACIFY COUGH and was conducted across three centers in the United Kingdom specializing in interstitial lung disease.

Participants between the ages of 40 and 90 years who had been diagnosed with idiopathic pulmonary fibrosis in the last five years and experienced chronic and severe cough lasting more than eight weeks were included in the study.

The cough severity was assessed on the visual analog scale, and a value of 30 mm or more was used as the cut-off for inclusion in the study since previous studies have reported that patients with cough of this severity or higher have significantly lower quality of life.

Lung function tests such as forced vital capacity and diffusion capacity of carbon monoxide were also performed for participant screening.

Other criteria for inclusion in the study consisted of no evidence of being current smokers and high-resolution computer tomography images indicating that the fibroid changes were greater than the level of emphysema.

Comorbidities such as significant renal or hepatic impairment, coronary artery disease, requirement of prolonged oxygen therapy, less than six months of predicted life expectancy, and a history of alcohol or drug use were grounds for exclusion from the study, as was an existing intolerance to morphine.

Patients were randomly assigned to two groups, with one group receiving a controlled release of low-dose morphine. The others received the placebo in period one, and the treatments switched in period two.

The primary outcome was the percentage change in how frequent the coughs were during the daytime or when the patients were awake compared to the baseline measurements.

Patient-reported responses on changes in cough, dyspnea, depression, and interstitial lung disease were the secondary outcomes.


The results showed that the administration of low-dose morphine through controlled release significantly lowered the objective cough counts as compared to the placebo over a period of two weeks.

A 39.4% reduction in objective cough counts was observed after the administration of morphine as compared to that of the placebo.

Furthermore, compared to baseline measurements of 21.6 coughs per hour, the mean frequency of daytime cough decreased to 12.8 coughs per hour after morphine administration, and no similar changes were observed after administering the placebo.

Additionally, 40% of the participants experienced adverse reactions after morphine administration, while only 14% experienced adverse reactions after the administration of the placebo.

However, the major side effects of morphine were constipation and nausea, while the placebo group had one case of death.

Given that the study only administered low-dose morphine for two weeks, the researchers believe that more randomized controlled trials are required to assess the long-term safety profiles of morphine use for idiopathic pulmonary fibrosis.

However, the substantial impact of severe and chronic cough on all aspects of life merits the clinical use of low-dose morphine to reduce these symptoms in the short term in patients with idiopathic pulmonary fibrosis.


Overall, the findings indicated that a treatment option consisting of a controlled release of low-dose morphine can significantly lower the objective cough counts in patients with idiopathic pulmonary fibrosis.

However, more trials are required to understand the long-term safety profile of this treatment.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.


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