Azithromycin for the Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis: A Randomized Controlled Crossover Trial
Sabina A. Guler, Christian Clarenbach, Martin Brutsche, Katrin Hostettler, Anne-Kathrin Brill, Anke Schertel, Thomas K. Geiser, Manuela Funke-Chambour
Abstract
Abstract Rationale Patients with idiopathic pulmonary fibrosis (IPF) frequently suffer from chronic cough that is difficult to treat, which substantially affects their quality of life. Azithromycin has been demonstrated to relieve chronic cough in some populations; however, this has not been investigated in patients with IPF. Objectives To determine the safety and efficacy of azithromycin for the treatment of chronic cough in patients with IPF. Methods In a double-blind randomized controlled crossover trial, patients with IPF underwent two 12-week intervention periods (azithromycin 500 mg three times per week or placebo three times per week). The primary outcome was the change in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ). Secondary outcomes included cough severity as measured by the Visual Analog Scale (VAS), health-related quality of life as assessed by the St. George’s Respiratory Questionnaire, and objective cough frequency as measured by audiovisual readings from 24-hour respiratory polygraphy. Results Twenty-five patients were randomized (23 men, 2 women); 20 patients completed the study. The mean (standard deviation [SD]) age was 67 (8) years, the mean (SD) forced vital capacity was 65 (16) percent predicted, and the diffusing capacity of the lung for carbon monoxide was 43 (16) percent predicted. The mean (SD) baseline LCQ scores were 11.7 (3.7) and 11.3 (3.3) for the azithromycin period and the placebo period, respectively, and the corresponding mean (SD) cough VAS scores were 5.6 (2.3) and 5.8 (2.1). There was no significant change in the LCQ score or the VAS score with azithromycin or with placebo. Similarly, there was no significant difference between the azithromycin period and the placebo period for change in polygraphy-measured cough frequency. Gastrointestinal adverse effects were more frequent with azithromycin than with placebo (diarrhea, 43% vs. 5%; P = 0.03). Conclusions This randomized controlled trial does not support the use of low-dose azithromycin for chronic cough in patients with IPF.Clinical trial registered with www.clinicaltrials.gov (NCT 02173145).