Introduction

Lung and heart–lung transplantation have now been performed in over 10 000 patients worldwide with two to three year survival rates of approximately 70%. Despite these remarkable successes, approximately one third of lung transplant recipients develop progressive airflow obstruction and deterioration of graft function, referred to as bronchiolitis obliterans syndrome (BOS). BOS is often associated with a specific histologicallesion, obliterative bronchiolitis (OB), characterized by inflammation and fibrosis of small airways. Clinical and experimental evidence suggests that the alloimmune reaction plays a major role in disease pathogenesis, and OB/BOS is often considered to be synonymous with chronic lung rejection. OB/BOS is usually considered to be analogous to late graft loss after transplantation of other organs [1]. In general, this involves a fibroproliferative process leading to obliteration of tubular structures in the organ. In the heart this is manifested by the development of graft coronary artery stenosis, and in the kidney by chronic vascular and tubular fibrosis. All of these syndromes are believed to share a similar pathogenesis that includes an alloimmune response against donor targets, i.e. they represent forms of chronic graft rejection. However, multiple other factors, including ischaemia and infection, may also play important roles in some lung recipients. Much has been learned regarding chronic lung allograft dysfunction since it was first described in 1984 [2]. This brief review will summarize current understanding of the clinical features, pathogenesis, and treatment of OB/BOS.

Clinical features

The most consistent clinical manifestation of OB/BOS is progressive loss of lung function due to airflow obstruction [3, 4]. Several large multivariate analyses have identified prior episodes of severe or persistent acute rejection as being the most consistent clinical risk factor [5–7].