Change in objective cough count correlates with improvement in patient-reported outcomes of cough in patients with idiopathic pulmonary fibrosis

<bold>Introduction:</bold> In the phase 2a crossover trial (CANAL; <ext-link>NCT04030026</ext-link>), patients with idiopathic pulmonary fibrosis who were treated with oral nalbuphine extended-release tablets had a significant reduction in cough frequency compared with those given placebo. Improvement was also seen in patient-reported outcomes (PROs) of cough. Here we examined the correlation between the change in 24-hr cough count (CC) and change in PROs. <bold>Methods:</bold> The 24-hr CC was derived from 24-hr cough frequency data from a digital cough monitor (VitaloJAK) at baseline and day 21 (end of treatment) in the CANAL trial. EXACT is a 14-item electronic diary, of which 11 items measure patient-reported severity of respiratory systems. EXACT 2 (item 2) captures cough frequency on a scale of 0-4 (0=<italic>not at all</italic> to 4=<italic>almost constantly</italic>). Cough Severity Numerical Rating Scale (CS-NRS) is a self-assessment of cough severity reported on an 11-point Likert Scale (1=<italic>no cough</italic> to 10=<italic>worst possible cough</italic>). Using repeated measures within-patient analysis, the correlation between change in 24-hr CC and change in EXACT 2 and CS-NRS was estimated. <bold>Results:</bold> At end of treatment (n=38), the correlation between change from baseline in 24-hr CC and EXACT 2 was 0.3119 (<italic>P</italic>≤0.0001) and between 24-hr CC and CS-NRS was 0.4531 (<italic>P</italic>=0.0066). The probability of a true positive correlation for EXACT 2 and CS-NRS versus 24-hr CC was estimated to be 99.62%. <bold>Conclusion:</bold> Reduction in objective measures of cough is associated with perceived improvements as reflected by cough PROs, EXACT 2 and CS-NRS. <bold>Funding source:</bold> Trevi Therapeutics