Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome

Abstract

Chronic rejection is the major problem hampering long-term survival after lung transplantation. Recently, it became clear that patients may develop an obstructive (bronchiolitis obliterans syndrome [BOS]) or a restrictive lung function defect (restrictive allograft syndrome [RAS]), for which specific risk factors are unknown. A retrospective analysis of our lung transplantation cohort was performed (n=380). Patients with an irreversible decline in forced expiratory volume in 1 second were identified and classified as BOS or RAS. Patient characteristics, bronchoalveolar lavage (BAL) cellularity, rates of respiratory tract infection, colonization, acute rejection, and lymphocytic bronchiolitis were compared between BOS, RAS, and stable patients. There were 103 patients suffering from chronic rejection, of which 79 had BOS and 24 were diagnosed with RAS. There were more patients with infection and pseudomonal colonizations in BOS and RAS compared with control (P=0.0090 and P=0.0034, respectively). More patients ever experienced acute and severe acute rejections (A≥2; both P<0.0001) and lymphocytic bronchiolitis (P=0.0006) in BOS and RAS versus control. There were more patients experiencing severe lymphocytic bronchiolitis in RAS compared with BOS (P=0.031). BAL neutrophilia in BOS and RAS were elevated at days 360, 540, and 720 versus control. BOS, but especially RAS patients, experienced more frequent episodes of increased BAL eosinophilia (≥2%; P<0.0001). Acute rejection, lymphocytic bronchiolitis, colonization with pseudomonas, infection, and BAL eosinophilia and neutrophilia are risk factors for the later development not only of RAS but also of BOS.