To demonstrate the efficacy of therapeutic interventions, clinical trials require relatively large numbers of patients. However, the limited number of lung transplants undertaken annually, even by the largest programs, precludes the conduct of such trials at individual centers.
As a result, the Cystic Fibrosis Foundation and National Institutes of Health have formed consortia of lung transplant programs. The goal is to drive research and innovation, standardize protocols, and share best practices by pooling resources. As a member of both consortiums, the Heart-Lung and Lung Transplantation Program actively participates in multiple areas of collaborative research.
One area involves suppression of the host immune response, which is a central aspect of post-transplant protocols to avoid graft rejection. However, lung transplants present a complicating factor. “The lungs are the only organs exposed to the outside atmosphere with every breath and the entire blood circulation,” says Dr. Dhillon. This exposure renders them uniquely vulnerable to immune activation and complications related to graft-versus-host disease (GVHD).
To address this, the program is participating in a clinical trial to assess the effectiveness of an inhaled immunosuppressive regimen. This intervention addresses issues observed with oral treatments, which show limited efficacy, significant toxicities, and increased risk of secondary infections.
Additionally, Dr. Dhillon explains that lung transplants eliminate the supply of oxygenated blood to the lungs. If lungs experience future damage, this absence prevents normal healing and leads to scar tissue formation, which can decrease lung function and hasten graft failure. Research by Mark Nicolls, MD, professor of Pulmonary and Critical Care Medicine, Stanford Medicine, is identifying alternative methods of improving airway function and oxygenation to enhance long-term graft survival.
“The need for collaborations focused on improving transplant outcomes has long been understood and accepted in this field,” says Dr. Dhillon. “We are happy to be actively engaged in such partnerships and research to support these goals.”