Azithromycin and bronchiolitis obliterans syndrome after lung transplantation: is prevention better than cure?

Abstract

Although lung transplantation is now accepted as an established therapy for selected patients with end-stage lung disease, long-term survival after lung transplantation remains limited by the development of bronchiolitis obliterans syndrome (BOS) in >50% of recipients 1. BOS is the clinical manifestation of an inflammatory bronchiolitis associated with fibrotic remodelling of the small and medium-sized airways, and is characterised by progressive loss of allograft function with development of airflow obstruction 2, 3. Until recently, the development of BOS was associated with an irreversible and relentless decline in lung function, which either eventually stabilised at a very low level or, in many patients, progressed to end-stage respiratory failure, accounting for the commonest cause of death after the first post-transplant year. BOS has historically been attributed to the effects of ongoing alloimmune injury as both the frequency and severity of acute rejection episodes have been associated with increased risk 4. These observations lead to the paradigm that BOS is chronic rejection of the transplanted lung and, consequently, intensification of immunosuppression was used as an attempted therapy in many affected recipients. These approaches offered, at best, a slowing in the progression of the condition in some, but also contributed to infective complications that undoubtedly added to the overall mortality risk from BOS. Over the last decade, a number of clinical trials of more intensive immunosuppressive regimes from the time of transplant or after onset of BOS have failed to impact on the incidence of BOS or regaining of lost function 5, 6. More recently, however, it has been appreciated that nonalloimmune insults to the lung allograft, such as the lung injury of primary graft dysfunction, viral and bacterial infections, and aspiration injury, also increase the risk of developing BOS 7. This suggests that cross-talk between innate …