Study does not support low-dose azithromycin to treat chronic cough in IPF

Treatment with low-dose azithromycin for chronic cough in patients with idiopathic pulmonary fibrosis did not significantly improve cough-related quality of life, severity or frequency compared with placebo.

“Chronic cough is a common symptom in patients with idiopathic pulmonary fibrosis that impairs quality of life. This cough is often resistant to current drug approaches,” Manuela Funke-Chambour, MD, principal investigator in the department of pulmonary medicine at Bern University Hospital and with the Adult Pulmonary Research Group in the department of biomedical research at the University of Bern, Switzerland, told Healio. “Azithromycin is used in other chronic respiratory diseases associated with cough and has been speculated to reduce cough in idiopathic pulmonary fibrosis as well, but no randomized, placebo-controlled study has investigated this hypothesis before.”

The randomized, double-blind, controlled cross-over trial included 25 patients (mean age, 67 years; 23 men) with IPF. All patients underwent two 12-week intervention periods during which they were randomly assigned azithromycin 500 mg or placebo thrice weekly.

The primary outcome was change in cough-related quality of life, as measured by the Leicester cough questionnaire. Secondary outcomes were cough severity measured using the visual analog scale, health-related quality of life measured by the St. George’s Respiratory Questionnaire and objective cough frequency measured by audiovisual readings from 24-hour respiratory polygraphy.

Twenty patients completed the study.

Mean baseline cough-related quality of life score was 11.7 and the mean objective cough frequency score was 5.6 for those randomly assigned azithromycin and 11.3 and 5.8, respectively, for those assigned placebo. Researchers observed no significant change in cough-related quality of life (mean difference before and after treatment, 0.68; P = .29) or objective cough frequency (mean difference, 0.25; P = .7).

In addition, there was also no significant difference in change in polygraphy-measured cough frequency between the azithromycin and placebo groups.

“We hoped for an improvement of cough under the treatment with azithromycin. This is not the case,” Funke-Chambour said. “Azithromycin treatment in idiopathic pulmonary fibrosis for the indication of cough is thus not justified.”

No serious treatment-emergent adverse events were reported. Among those assigned azithromycin, gastrointestinal adverse events were more frequently reported than in the placebo group, and included diarrhea (43% vs. 5%), abdominal pain (19% vs. 0%) and nausea (19% vs. 5%). Respiratory infection was reported in four (19%) patients assigned azithromycin and three (14%) assigned placebo.

“The clinical problematic for the affected patients remains unresolved,” Funke-Chambour said. “Other drugs or approaches need to be tested to reduce cough in patients with idiopathic pulmonary fibrosis.”

For more information:

Manuela Funke-Chambour, MD, can be reached at manuela.funke-chambour@insel.ch.