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Project

Translational research on pre-transplant initiation and promt post-transplant continuation of azithromycin treatment to improve early allograft function and outcome after lung transplantation.

The principal cause of late mortality after lung transplantation (LTx) is chronic rejection, which  histologically presents as obliterative bronchiolitis (OB) (1,2) and clinically as a progressive obstructive spirometry, defined as bronchiolitis obliterans syndrome (BOS) (2,3). We recently demonstrated that azithromycin (AZI), when initiated from discharge after LTx on, improved outcome (BOS-free survival), graft function (FEV1) and attenuated both airway and systemic inflammation (4). These data confirmed the anti-inflammatory and imunomodulatory properties of AZI in LTx (5-15). However, early allograft dysfunction, which may be due to donor lung injury or to ischemiareperfusion  injury, was recently also associated with earlier onset of BOS and a worse long-term outcome (16,17). We previously demonstrated that early administration of AZI reduces airway inflammation and oxidative stress in ischemia-reperfusion injury (18); and also reduced pulmonary fibrosis and improved pulmonary function in bleomycin-induced pulmonary fibrosis (19). Macrolides were shown to attenuate acute and chronic rejection in murine cardiac transplantation (20) and in a rat heterotopic tracheal allograft model of OB (21). Finally, macrolide-use is associated with shorter time of mechanical ventilation and a lower 6 month mortality in patients with acute lung injury (22). Given these findings, we believe AZI should be further investigated as a therapy to improve early allograft function and subsequently outcome after LTx.

Date:1 Jan 2014 →  31 Dec 2014
Keywords:transplant, AZITHROMYCIN TREATMENT, lung
Disciplines:Immunology