Low dose morphine shows promise as effective treatment for chronic cough in people with idiopathic pulmonary fibrosis

Low dose morphine has the potential to treat chronic cough in people with idiopathic pulmonary fibrosis (IPF), according to new research from two National Institute for Health and Care Research (NIHR) Biomedical Research Centres (BRC).

IPF is a condition in which the lungs become scarred and breathing becomes increasingly difficult. Symptoms include a persistent dry cough and breathlessness, which tend to develop gradually and get slowly worse over time. Several treatments can help reduce the rate at which IPF gets worse, but they do not improve symptoms or quality of life.

Morphine is a strong painkiller used to treat severe pain and has been thought to reduce the coughing reflex, acting on the neural pathways in the lungs and brain, in much lower doses than needed for pain relief.

The PACIFY COUGH study is the first to show the benefit of using low dose morphine to treat IPF-related cough, a distressing symptom with significant physical, social, and psychological effects.

Published in The Lancet Respiratory Medicine, this phase 2 clinical study was led by NIHR Manchester BRC and NIHR Imperial BRC, and was funded by The Jon Moulton Charity Trust.

The study took place at the NIHR Manchester Clinical Research Facility (CRF) at Wythenshawe Hospital, NIHR Guy’s and St Thomas’ CRF and NIHR Liverpool CRF, which are based at three NHS specialist centres for interstitial lung disease (a term for different diseases that cause scarring of the lungs) in the UK.

In the study, participants were randomly assigned to receive both a slow-release morphine tablet twice a day, 12 hours apart, or a placebo (with no chemical effects), for 14 days in random order.

Cough frequency was measured using the VitaloJAK cough monitor, a custom built wearable digital recording device with a lapel microphone and contact sensor attached to the breastbone, developed by Vitalograph in collaboration with Manchester University NHS Foundation Trust (MFT).

For all participants receiving morphine, the monitor recorded that daytime cough frequency reduced on average by 39.4 percent when compared with the placebo. For more than 40 percent of participants, cough frequency had reduced by 50 percent or more.

In a follow-up questionnaire, more than half of participants receiving morphine reported that their cough had improved and over a third said their overall quality of life was better.

The study was co-led by Professor Jacky Smith, Respiratory Co-Theme Lead at NIHR Manchester BRC. Prof Smith, who is also Director of the NIHR Manchester CRF, Honorary Consultant at MFT and Professor of Respiratory Medicine at The University of Manchester, said: “IPF symptoms are distressing and debilitating for patients. It can be a socially isolating condition and the stigma around chronic coughing has only got worse since the COVID-19 pandemic as people may think coughing is infectious.

“Morphine is a licensed drug and has the potential to have impact on patients a lot more rapidly than a new therapy because we broadly know about its safety and side effects.

“We were really pleased with the outcome of this study. Longer term studies to show the drug’s durability and side effects should be the focus of future research, so that this treatment can be implemented into clinical practice.”

Study co-lead Professor Philip Molyneaux, consultant respiratory physician and director of the NIHR cardiorespiratory clinical research facility at Royal Brompton Hospital, said: “Cough affects most patients with IPF at some point during the course of their illness. Current therapies are only aimed at slowing down the progression of the disease and provide no symptomatic relief for our patients.

“This new research which has demonstrated that morphine can provide benefits to patients with chronic cough is a massive step forwards towards helping improve the quality of life for patients with IPF.”

Frank Keane, CEO of Vitalograph, said: “Studies of new therapies to treat chronic cough were previously hindered by a lack of tools to measure cough and VitaloJAK was developed to overcome this by collecting highly accurate objective cough data. The positive outcome of this study is great news and demonstrates the value of including cough monitoring in therapeutic research to help realise new treatments for patients.”