Clinical Instructor
Division of Pulmonary and Critical Care Medicine

Project title: Mechanisms of allograft injury and the development of bronchiolitis obliterans syndrome after lung transplantation

John Belperio, MD - UCLA
Robert Elashoff, PhD – UCLA
Elaine Reed, PhD - UCLA

Multidisciplinary Expertise:
Lung transplantation, acute lung injury, immunology, immune monitoring, chemokine analysis

Project Description:
Chronic rejection or bronchiolitis obliterans syndrome (BOS) is the major factor limiting long-term survival after lung transplantation (LT). The pathogenesis of BOS remains unknown with no effective treatments. Thus, the identification and avoidance of BOS risk factors is critical.  Prior studies of BOS have traditionally focused on the effects of individual “insults” (e.g., infection, acute rejection, ischemia-reperfusion,  gastroesophageal reflux) to the allograft. In contrast, this project will investigate the association between allograft "injury" and the development of BOS. Our preliminary data suggests that the histopathologic patterns of allograft injury are much stronger determinants of BOS development than the various insults causing them. Furthermore, we find that this association may be mediated by an aberrant Type I immune response involving CXCR3/ligands. Gaining a better understanding of the risk factors and mechanisms responsible for BOS development will lead to novel ways to predict, prevent and treat this devastating syndrome.