“Finding a specific treatment for chronic cough in IPF could have a huge impact on patients’ lives.”
Philip Molyneaux is Professor of Interstitial Lung Disease at the National Heart and Lung Institute, the Asthma + Lung UK Chair of Respiratory Research, and Director of the NIHR Clinical Research Facility at the Royal Brompton Hospital, where he is also a Consultant in Interstitial Lung Disease.
We spoke to Professor Molyneaux about his ongoing research into the treatment of cough in Idiopathic Pulmonary Fibrosis (IPF), after the conclusion of a successful phase two trial.
Can you summarise your research and what you found in plain language?
We have been trialling a new drug, Nalbuphine ER, for the treatment of cough in patients living with Idiopathic Pulmonary Fibrosis (IPF). IPF is a scarring lung disease and around 80% of people with the condition suffer with chronic cough. This worsens their quality of life and currently there are no treatments available.
We recently ran a phase two clinical trial, in which 165 IPF patients with chronic cough were either given one of three different strength doses of Nalbuphine ER, or a placebo, for six weeks. We recorded the number of coughs-per-hour in each patient over the first and last 24 hours of the study and found that the cough count dropped across all three doses of the drug compared to the placebo, with the strongest dose proving to be the most effective. We also asked patients about their own perception of the rate and severity of their cough; those taking the two stronger doses of the drug noticed a significant decrease in their symptoms.
“Our research shows that the mechanisms we are targeting improve cough, helping us to gain a deeper understanding of IPF and its symptoms.”
Why is this research important? What problem does it address?
Finding a specific treatment for chronic cough in IPF could have a huge impact on patients’ lives. Current treatments are simply borrowed cough treatments for other respiratory conditions. They are often ineffective and trialling them wastes time – something which is in short supply when it comes to IPF, which has a life expectancy of only three and a half years.
Previous studies have shown that cough has a detrimental effect on the lives of patients with IPF. It can contribute to anxiety and depression, as well as causing incontinence and even blackouts. Plus, in the aftermath of the Covid-19 pandemic, coughing has been socially stigmatised. All these things can threaten IPF patients’ quality of life, which is why finding a disease-specific treatment is so important.
What are the most significant findings or outcomes?
Our trial, which recruited at the Royal Brompton Hospital’s Cardiorespiratory clinical research facility, is the first positive head-to-head placebo-controlled study into IPF cough. It shows that there is potentially a treatment which could improve IPF patients’ quality of life, as opposed to simply slowing down the progression of the disease. We hope that Nalbuphine ER could become a useful treatment for IPF cough, but more research is needed to confirm this, and to check the drug’s long-term safety.
How might this research impact policy or the public?
Policy, as all medical researchers will know, must change when a new drug is approved. Nalbuphine ER is a drug that has been used previously, as an injectable post-operative painkiller; our version is in a tablet format, with a different indication. If Nalbuphine ER is approved as a treatment for IPF cough after a phase three trial, treatment guidelines would hopefully change rapidly as there are no other options.
When it comes to the public, cough takes up a lot of healthcare resources, including some people might not expect, such as occupational and speech and language therapists. If IPF patients’ coughs improve, these finite resources will be freed up for others who may need support.
How do these findings advance knowledge or practice in your field?
Our research shows that the mechanisms we are targeting improve cough, helping us to gain a deeper understanding of IPF and its symptoms. While this is crucial as it gives us clues into how IPF cough works and how it can be best treated, there are still many questions to ask.
We are unsure whether Nalbuphine ER will work for all patients with IPF and cough. We don’t know if reducing cough can slow disease progression, nor do we know why some IPF patients cough more than others; perhaps this knowledge will arise tangentially from the work we are doing. Moreover, we are currently only looking at idiopathic pulmonary fibrosis, so there is a possibility that Nalbuphine ER may work for those living with non-idiopathic or familial pulmonary fibrosis too.
Does your work tie into any wider research?
There is so much great research happening around the impact of cough and whether it is the same across all fibrotic lung diseases. From what we can tell, it seems to be very similar to IPF, which suggests that Nalbuphine ER could be used to treat cough in a range of respiratory conditions.
We would also like to look at whether cough comes from the brain, the nerves, or the lungs by conducting MRI scans to observe what happens the brain when someone is coughing and examining changes in lung volume in people with chronic cough.
What are the next steps?
The next step is a phase three trial, looking at a larger patient population for a longer duration to ensure the benefit is sustained. We are hoping to start this study later this year.