Lung Transplantation: The Role of Azithromycin in the Management of Patients with Bronchiolitis Obliterans Syndrome

Abstract

Bronchiolitis obliterans syndrome (BOS) is the leading cause of death in lung transplant recipients (LTR). BOS is thought to result from chronic immunologic/inflammatory insults leading to peri-bronchiolar leukocyte infiltration, with a subsequent exuberant tissue re-modelling and fibro-obliteration of the luminal space of the allograft airways. Diagnosis is based on functional criteria and severity is graded on the degree of Forced Expiratory Volume in 1 second (FEV1) impairment. Current strategies to improve pulmonary function once BOS is established have demonstrated little or no impact on disease progression and re-transplantation remains the only therapeutic option. Among the alternative treatments which have been attempted in the last few years, long-term azithromycin treatment seems to be the most promising therapeutic device for BOS treatment. Azithromycin is a macrolide antibiotic, endowed with a broad spectrum of anti-inflammatory/immunomodulatory activities. Long-term oral azithromycin therapy can significantly improve FEV1 in about 42% of patients with established BOS. Moreover, reduced neutrophilia, chemokine release and bacterial exacerbations have been demonstrated. These observations suggest that the drug can down-regulate pulmonary inflammation, even if the precise underlying mechanisms still need to be determined.