NHLBI Working Group
Lung Allograft Transplantation: New Science and Clinical Advances
Executive Summary
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:
- Establish a multi-center collaborative network to enhance the standards
of clinical protocols, to understand the disease of BOS, including a
lung tissue repository to assist in the characterization of the disease,
and to conduct clinical trials.
- Increase use of the present donor pool of lung organs (utilization
in US is about 15% versus 30-40% in European countries). Public policy
issues should increase awareness of organ donation.
- Develop methods to better assess quality of donor lungs before transplantation.
- Assess new strategies for creating tolerance in the recipient and
optimizing immunosuppression with pharmcogenomic methods and
- Identify better biomarkers and other proteomic tests to assess histologic
onset of BOS before patient symptoms develop.
- Investigate methods to ameliorate ischemia/reperfusion injury in
the allograft lung.
- Target research into the whole spectrum of graft dysfunction: primary
failure, acute rejection and BOS. This would focus on innate and adaptive
immunity and the emerging awareness that autoimmunity is involved in
the rejection response.
- Continue to assess and develop relevant animal models that reflect
the immulogic changes that occur in acute and chronic phases of huma
allograft rejection.
Working Group Members
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
Members
- William M. Baldwin, M.D., Johns Hopkins Medical Institutes
- William Burlingham, Ph.D., University of Wisconsin
- Steven R. Duncan, M.D., University of Pittsburgh
- Robert L. Fairchild, Ph.D., Cleveland Clinic Foundation
- Jay A. Fishman, M.D., Massachusetts General Hospital
- David A. Flockhart, M.D., Ph.D., Indiana University School of Medicine
- Joe G. N. Garcia, M.D., Johns Hopkins University School of Medicine
- Marshall I. Hertz, M.D., University of Minnesota
- Shaf Keshavjee, M.D., University of Toronto
- Sadis Matalon, Ph.D., University of Alabama at Birmingham
- Kenneth R. McCurry, M.D., University of Pittsburgh
- Scott M. Palmer, M.D., Duke University Medical Center
- G. Alexander Patterson, M.D., Washington University School of Medicine
- David J. Pinsky, M.D., University of Michigan
- Jonathan B. Orens, M.D., The John Hopkins Hospital
- Dirk E. M. Van Raemdonck, M.D., Ph.D., University of Gasthuisberg,
Belgium
- Stig Steen, M.D., University Hospital of Lund, Sweden
- Robert M. Strieter, M.D., University of California, Los Angeles
- Adriana Zeevi, Ph.D., University of Pittsburgh
NHLBI Staff
- Herbert Reynolds, M.D., Division of Lung Diseases
July 2004
|