Azithromycin for the treatment of cough in idiopathic pulmonary fibrosis: A randomized controlled cross-over pilot trial

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) patients suffer from chronic cough, reducing quality of life. Azithromycin (AZM) is an immunomodulatory and anti-inflammatory antibiotic. Retrospective studies suggest a role for AZM in reduction of acute IPF exacerbation. Objective: To determine the effect of azithromycin on self-reported cough and quality of life in IPF. Methods: We performed a double-blind randomized controlled cross-over trial with IPF patients undergoing two 12-week treatment periods (AZT 500mg 3 times/week or placebo). Primary outcome was change in cough-related quality of life measured by Leicester cough questionnaire (LCQ), cough severity was measured by Visual Analog Scale (VAS). Results: Of 25 randomized patients (2 female, 23 male), 19 completed the study. Mean age was 67±8 years, FVC was 65±16%, and DLCO 43±16% predicted. Concomitant treatment included pirfenidone (36%), nintedanib (44%), and home oxygen therapy (36%). One patient died due to disease progression during the study, and two patients dropped out. Adverse effects were more frequently observed with AZM (nausea (16%), diarrhea (37%), abdominal pain (16%)). Neither LCQ scores [Difference after AZM: -0.64, 95%CI -1.53 to 0.25, p=0.15); Difference after placebo: 0.04, 95%CI -0.90 to 0.97, p=0.93] nor cough VAS [Difference after AZM: 0.21, 95% CI -1.05 to 1.46, p=0.73; Difference after placebo: 0.22, 95% CI-0.78 to 1.22, p=0.65] changed significantly with AZM. Conclusion: Low dose AZT does not seem to improve patient reported cough severity and quality of life in patients with IPF, while adverse effects were more frequently observed.