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Human and Murine Obliterative Bronchiolitis in Transplant

Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to John F. McDyer, M.D., Room 4B.51, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: jmcdyer{at}jhmi.edu

ABSTRACT

Obliterative bronchiolitis is a devastating illness that limits the long-term success of lung transplantation. Its high prevalence and overall poor response to current therapeutic measures demands further research to elucidate pathogenic mechanisms. Toward this goal, there is a role for animal models to study the mechanisms of obliterative bronchiolitis, such as the murine heterotopic tracheal allograft model. This review compares the tracheal allograft model to human obliterative bronchiolitis pathology and highlights the important mechanisms of airway rejection described using this model. Although certain limitations exist, the pursuit of proof-of-concept studies in this model, as well as other animal models, can provide the basis for genetic and cellular translational human studies directed toward post-transplant obliterative bronchiolitis pathogenesis. To meet these challenges, we call for the establishment of a National Institutes of Health–supported Lung Transplant Network to better orchestrate translational research efforts in obliterative bronchiolitis pathogenesis and treatment, and to advance the field of lung transplantation.

Key Words: allospecific T cells • lung allograft rejection • obliterative airway disease • obliterative bronchiolitis • tracheal transplant

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