Bronchiolitis obliterans: the Achilles heel of lung transplantation

Operative mortality in lung transplantation in many centers has decreased to less than 10%. Despite this improvement in early survival, delayed graft failure related to chronic graft rejection continues to limit the survival and function of lung transplant recipients. Chronic lung transplant rejection Bronchiolitis obliterans (BO) is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The histological changes are manifest by a progressive obstructive ventilatory defect on spirometric testing. Histologic diagnosis of BO is difficult due to sampling. The term BO syndrome has been developed to allow clinical diagnosis using spirometric criteria. BO is an alloimmune phenomenon, aggravated by airway ischemia, and infection but predicted by frequent and severe acute vascular rejection. It is characterized by increased expression of TGF beta and other cytokines on airway epithelial cells, increased expression of class II antigens in the airways, lymphocytic bronchiolitis, and bronchial epithelial cell proliferation mediated by numerous cytokines. Airway neutrophilia, and activation of neutrophilis with release of their granules into the airway is a precursor of progressive BO. Loss of normal protective mechanisms--leukocyte antiproteases--against this oxidative insult may be an integral part of disease progression. To date treatment of BOS is infrequently successful. Better understanding of the pathophysiology, and earlier recognition of BO may result in improved long term patient and graft survival and function.