The National Heart, Lung, and Blood Institute convened a Working Group of investigators on June 14 -15, 2004, in Bethesda, Maryland to identify the opportunities for scientific advancement, including basic and clinical research, in lung transplantation. The Working Group participants first discussed clinical issues related to donor organ procurement, how to increase the donor pool by using lung grafts from non-heart-beating donors, increasing public awareness and acceptance of donor status, and initiating treatment to minimize lung ischemia and reperfusion injury. These presentations underscored that better standardization of organ procurement protocols, improved ways to assess the functional quality of the donor organ, and a more uniform patient database were needed.
As there are several new treatment protocols to improve the host's acceptance or tolerance of the allograft lung, these were reviewed in the context of ameliorating acute rejection and later development of bronchiolitis obliterans syndrome (BOS) which usually causes graft failure from chronic rejection. Non-immunlogic strategies to improve allograft tolerance were presented which included therapy with statins and macrolide antibiotics, and preventing gastro-esophageal reflux.
Presentations and discussions next delved into basic science mechanisms of manipulating the lung graft and host with immune inductions to improve tolerance. Dissecting the immunopathogenesis of BOS underlies basic research that probes affected tissue and cells injured by rejection. Thus, an update about deranged or overstimulated innate immunity was given in terms of chemokine profiles, proteomics and regulatory T-cells that impact on endothelial and epithelial surfaces of the transplanted lung.
After the Working Group reviewed the current status of lung transplantation, further discussion provided the Institute with recommendations for new research opportunities to improve preserving and creating a more functional graft, better accuracy of clinical prognosis, and investigating host rejection mechanisms.
The general recommendations of the Working Group are to:
Co-chair: Thomas M. Egan, M.D., The University of North Carolina at Chapel Hill
Co-chair: David S. Wilkes, M.D., Indiana University School of Medicine