Chronic lung allograft dysfunction following lung transplantation: Challenges and solutions

Chronic rejection is a major cause of death after the first year following lung transplantation. Bronchiolitis obliterans (BO) is the most common pathologic finding on biopsy, characterized by fibrous granulation tissue, which obliterates the lumen of the bronchiole. Clinically, in the absence of tissue for pathology, BO syndrome refers to a progressive irreversible drop in the forced expiratory volume in 1 second. Recently, a broader definition of chronic rejection, termed “chronic lung allograft dysfunction”, has been used to encompass a more inclusive definition of posttransplant dysfunction. Recently, the lung transplant community has come to realize that chronic rejection may be the final common result after repetitive epithelial insults. Acute rejection, infection, and alloreactivity to mismatched HLA antigens are a few of these insults that damage the surface of the bronchioles. Recent evidence of autoimmunity to the normally hidden structural proteins collagen V and K-α1 tubulin have been correlated with a BO phenotype as well, perhaps correlating the epithelial damage with a mechanism for developing BO lesions. Many immunomodulatory medications and treatments have been studied for effectiveness for the treatment of chronic lung allograft dysfunction. New drugs, which more precisely target the immune system, are being developed and tested. Further study is required, but recent advances have improved our understanding of the pathogenesis and potential intervention for this common and deadly complication of lung transplantation.