A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation

Abstract

Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s (FEV1) in chronic rejection or bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Azithromycin prophylaxis might prevent BOS.A double-blind randomised controlled trial of azithromycin (n540) or placebo (n543), initiated at discharge and administered three times a week for 2 yrs, was performed in 2005-2009 at the Leuven University Hospital (Leuven, Belgium). Primary end-points were BOS-free and overall survival 2 yrs after LTx; secondary end-points were acute rejection, lymphocytic bronchiolitis and pneumonitis rate, prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux, and change in FEV1, airway and systemic inflammation over time. Patients developing BOS were assessed for change in FEV1 with open-label azithromycin.BOS occurred less in patients receiving azithromycin: 12.5 versus 44.2% (p50.0017). BOS-free survival was better with azithromycin (hazard ratio 0.27, 95% CI 0.092-0.816; p50.020). Overall survival, acute rejection, lymphocytic bronchiolitis, pneumonitis, colonisation and reflux were comparable between groups. Patients receiving azithromycin demonstrated better FEV1 (p50.028), and lower airway neutrophilia (p50.015) and systemic C-reactive protein levels (p50.050) over time. Open-label azithromycin for BOS improved FEV1 in 52.2% patients. No serious adverse events were noted.Azithromycin prophylaxis attenuates local and systemic inflammation, improves FEV1 and reduces BOS 2 yrs after LTx.

Overview of Clinical Lung Transplantation

“…The use of azithromycin in a randomized controlled trial has been shown to slow the progression of CLAD, potentially through its anti-inflammatory, antibiotic, or promotility effects, but the exact mechanism is unclear (Yates et al 2005;Murphy et al 2008;Vos et al 2011). Switching classes of immunosuppression may be of some benefit in slowing progression of the disease, but no therapy has yet been shown to reverse the disease process.…”

Chronic lung allograft dysfunction phenotypes and treatment

“…In fact, a randomized placebo controlled prevention trial with azithromycin initiated at hospital discharge following transplantation has shown that patients taking azithromycin demonstrate better pulmonary function, as well as decreased BAL neutrophilia and lower CLAD prevalence (35). A recent post-hoc analysis of this trial revealed that these long-term beneficial effects persisted and that azithromycin was able to significantly postpone the development of CLAD (36).…”

Diagnosis and management of bronchiolitis obliterans syndrome following lung or hematopoietic cell transplantation

“…[5] Prophylactic AZI has also been evaluated as an intervention to prevent BOS in both LTX and HCT recipients. Vos et al [13] published a placebo-controlled RCT that demonstrated significantly improved, BOS-free survival and significantly better preservation of FEV1 in the AZI treatment arm when AZI started prior to hospital discharge following LTX. Additionally, longer term analysis of the treatment arms from this same RCT showed that prophylactic AZI was associated with significantly improved CLAD-free survival, pulmonary function, and functional exercise capacity versus the placebo group.…”