Consideration of the use of nalbuphine in idiopathic pulmonary fibrosis-associated cough: to cough or not to cough so much?

Cough is very common in idiopathic pulmonary fibrosis (IPF) and reduces quality of life. A low dose of the opioid µ-receptor agonist morphine reduced cough in subjects with IPF in a phase 2 clinical trial. However, the use of morphine for cough may be limited by adverse events (e.g. constipation) and its addiction potential. As a µ-receptor antagonist/partial agonist and κ-receptor agonist, nalbuphine may have less adverse events and be more effective against cough than morphine. In a phase 2b study (CORAL), after 6 weeks, nalbuphine 54 and 108 mg twice daily orally reduced the frequency of cough (by up to 60%), the severity of cough and improved the quality of life in subjects with IPF. Notably, the cough rate remained relatively high with nalbuphine and adverse events were common. Future studies should be directed at doses of nalbuphine or morphine that could possibly cause a greater or similar reduction in cough with a lesser incidence of adverse events. Although, the opioid agonists tested so far are not ideal treatments for cough in IPF, they are probably the best agents available to date. Nevertheless, the search for other agents with improved profiles between benefit and adverse events should continue.