Effect of azithromycin on bronchial wall thickness in severe persistent asthma: A double-blind placebo-controlled randomized clinical trial

Background: Azithromycin reduced airway remodeling in animal models of asthma. However, its effect on human subjects has not been studied yet. This study aimed to investigate the effect of long-term treatment with azithromycin on airways wall thickness in patients with severe persistent asthma. Methods: In this randomized, double-blind, placebo-controlled clinical trial, patients with severe persistent asthma received azithromycin (250 mg, BID, three days a week), prednisolone (5 mg, BID), or placebo for eight months in three separate groups in addition to the standard therapy. The improvement in right upper lobe apical segmental bronchus (RB1) wall thickness obtained by high resolution computed tomography was set as the primary outcome. Secondary outcomes included: cough severity, dyspnea severity, asthma control test (ACT) score, asthma exacerbation rate, pulmonary function tests, and fractional exhaled nitric oxide (FENO). Results: Seventy-eight out of ninety randomized subjects completed eight months of treatment with azithromycin (n = 25), prednisolone (n = 27), or placebo (n = 26). Bronchial wall thickness percentage did not change significantly in any of the groups. However, the inner radius and lumen area of azithromycin and prednisolone-treated subjects increased significantly (p < 0.05 for both). Azithromycin also significantly improved the dyspnea severity, ACT score, FENO, and FEV1, FEF25-75, and FEV1/FVC (p < 0.05 for all). Cough severity or asthma exacerbation rate did not change significantly after eight months of treatment with azithromycin. Conclusion: Long-term treatment with azithromycin increased lumen radius and lumen area in patients with severe persistent asthma. However, there was no significant change in wall thickness in any of the treatment groups.