Long-term effect of azithromycin in bronchiolitis obliterans syndrome

• Published in: BMJ open respiratory research Vol. 6; no. 1; p. e000465
• Main Authors: Gan, C.Tji-Joong, Ward, Chris, Meachery, Gerard, Lordan, James Laurence, Fisher, Andrew J, Corris, Paul A
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.10.2019; BMJ Publishing Group
• Series: Original research
• Subjects: Adult; Antibiotics; Azithromycin - pharmacology; Azithromycin - therapeutic use; Bronchiolitis Obliterans - drug therapy; Bronchiolitis Obliterans - mortality; Bronchiolitis Obliterans - physiopathology; Cell cycle; Consent; Cystic fibrosis; Disease Progression; Double-Blind Method; Female; Forced Expiratory Volume - drug effects; Heart; Humans; Lung Transplantation; Lung transplants; Male; Middle Aged; Outpatient care facilities; Patients; Survival Rate; Syndrome; Time Factors; Transplants & implants; Treatment Outcome; lung transplantation
• ISSN: 2052-4439; 2052-4439
• DOI: 10.1136/bmjresp-2019-000465

IntroductionAzithromycin stabilises and improves lung function forced expiratory volume in one second (FEV1) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV1, BOS progression and survival .MethodsEligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV1, BOS free progression and overall survival.ResultsFEV1 in the placebo group improved after open-label azithromycin and was comparable with the treatment group by 6 months. FEV1 decreased after 1 and 5 years and was not different between groups. Patients (n=18) with rapid progression of BOS underwent total lymphoid irradiation (TLI). Progression-free survival (log-rank test p=0.40) and overall survival (log-rank test p=0.28) were comparable. Survival of patients with early BOS was similar to late-onset BOS (log-rank test p=0.74).DiscussionLong-term treatment with azithromycin slows down the progression of BOS, although the effect of TLI may affect the observed attenuation of FEV1 decline. BOS progression and long-term survival were not affected by randomisation to the placebo group, given the early cross-over to azithromycin and possibly due to TLI in case of further progression. Performing randomised placebo-controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe.