[Pathophysiology of obliterative bronchiolitis in lung transplants]

Abstract

Introduction: The major obstacle to long-term survival after lung transplantation is chronic graft rejection (CR) which is defined histologically by obliterative bronchiolitis (OB).

State of the art: The causes of post-transplant OB are not fully understood, but there is evidence that this chronic process is influenced by both immunologically mediated injury directed against endothelial and specifically epithelial cells, and alloantigen-independent events, such as cytomegalovirus infection, ischaemic-reperfusion injury and biophysical alterations. The generation of an allogenic immune response seems to be the central event involved in the subsequent development of OB, and prior acute rejection is the strongest risk factor for CR. Whatever the role of each of the factors, injury to the bronchiolar structure is the primary event which triggers an invasion of various inflammatory cells and an increase in pro-inflammatory and chemotactic mediators within the bronchiolar wall. As the process evolves, an uncontrolled repair process, with sub-mucosal fibrous tissue proliferation leading to obstructive airway scarring involving mesenchymal cell and fibroblast replication, and connective-tissue deposition in response to profibrotic cytokines and growth factors released by local tissue. We review here the risk factors and the mechanisms, which are currently recognized in the development of OB.

Perspectives and conclusions: A better understanding of the pathogenesis of CR by combining several techniques should allow detection of OB at a preclinical stage and may ultimately lead to novel preventive and therapeutic strategies for the condition.