A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation

Abstract

BackgroundWe conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation.MethodsWe compared azithromycin (250 mg alternate days, 12 weeks) with placebo. Primary outcome was FEV1 change at 12 weeks.Results48 patients were randomised; (25 azithromycin, 23 placebo). It was established, post randomisation that two did not have BOS. 46 patients were analysed as intention to treat (ITT) with 33 ‘Completers’. ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal.OutcomeThe ITT analysis (n=46, 177 observations) estimated mean difference in FEV1 between treatments (azithromycin minus placebo) was 0.035 L, with a 95% CI of −0.112 L to 0.182 L (p=0.6). Five withdrawals, who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV1 at 12 weeks. Study Completers showed an estimated mean difference in FEV1 between treatment groups (azithromycin minus placebo) of 0.278 L, with 95% CI for the mean difference: 0.170 L to 0.386 L (p=<0.001). Nine of 23 ITT patients in the azithromycin group had ≥10% gain in FEV1 from baseline. No patients in the placebo group had ≥10% gain in FEV1 from baseline while on placebo (p=0.002). Seven serious adverse events, three azithromycin, four in the placebo group, were deemed unrelated to study medication.ConclusionsAzithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo. This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS.Trial registration numberEU-CTR, 2006-000485-36/GB.

Short-Term Variation of Lung Function and Airway Inflammation in Children and Adolescents with Bronchiolitis Obliterans

“…Systemic steroids, hydroxycholoroquine and inhaled corticosteroids are of limited therapeutic efficacy in BO. Treatment with azithromycin has been shown to be effective in lung and bone marrow transplantation [29,30]. The patients receiving azithromycin demonstrated better FEV1 as well as lower airway neutrophilia and systemic C-reactive protein levels [31,32].…”

Update on Chronic Lung Allograft Dysfunction

“…Five of the six patients in their study demonstrated significant improvement following the addition of AZT to their immunosuppression (mean FEV1 increase of 0.5L) [24]. Since then numerous studies have confirmed the efficacy of AZT, showing that it can reverse and prevent BOS while prolonging the survival of some patients [25-27]. However, not all patients respond to AZT and the understanding of why has revealed another phenotype of CLAD: neutrophilic reversible allograft dysfunction (NRAD).…”

Are the antimicrobial properties of macrolides required for their therapeutic efficacy in chronic neutrophilic airway diseases?

“…In the first paper, Corris et al 11 performed the first randomised controlled trial of azithromycin in the treatment of BOS post lung transplantation. In the second paper, Essilfie et al 12 investigated the effects of clarithromycin in two mouse models of steroid-resistant asthma, and investigated in depth the mechanisms of action.…”

“…In this issue of Thorax, Corris et al 11 report the results of the first RCT of azithromycin therapy in BOS after lung transplantation. Forty-eight patients with BOS were randomised: 25 patients to azithromycin (250 mg alternate days, 12 weeks) and 23 to placebo.…”

“…In summary, by performing a RCT of azithromycin treatment of BOS after lung transplantation, Corris et al 11 have added lung allograft BOS to the expanding list of indications for chronic low-dose macrolide therapy in respiratory medicine. In the domain of experimental asthma, Essilfie et al 12 have developed valuable mouse models of steroid-resistant neutrophilic asthma by combining allergen exposures with bacterial infections.…”