The National Heart, Lung, and Blood Institute has awarded Thomas M. Egan, a professor of surgery at the University of North Carolina, a $1.47 million, two-year grant for research on perfusion and ventilation of lungs outside the body before transplant. The research could lead to a significant increase in the number of lungs available for transplant.
Dr. Egan, a surgeon in the UNC Division of Cardiothoracic Surgery, is internationally known for his research on lung transplantation, which has been under way since he came to UNC in 1989 to start its lung transplant program.
His new grant was awarded under the NHLBI’s Translational Research Implementation Program, a two-stage program designed to translate fundamental research ideas into proof-of-concept efficacy testing in patients. This Stage 1 grant is supported by the American Recovery & Reinvestment Act's Grand Opportunities (GO) grants program, for large-scale research projects that the National Institutes of Health says have “a high likelihood of enabling growth and investment in biomedical research and development, public health, and health care delivery.” NHLBI is part of the National Institutes of Health.
Dr. Egan’s project will perfect a technique to perfuse and ventilate human lungs outside the body (ex vivo) to determine if they are suitable for transplant, and will demonstrate safety of transplanting human lungs after ex-vivo perfusion in a pilot clinical study.
Lung disease is the fourth leading cause of death among Americans. Lung transplantation helps patients with end-stage lung diseases and improves survival, but transplants are critically limited by an inadequate supply of suitable lungs from conventional organ donors – people who have been declared brain-dead after a lethal brain injury and have been on ventilation before a controlled cardiac arrest when organs are retrieved for transplant. Lungs that have been offered for donation frequently cannot be used because lung function in the donor is poor, due to inflammation or infection or fluid build-up (edema) that occur after trauma and emergency treatment.
Even if the lungs are suitable for use, they are still vulnerable to problems. During transplant, the stopping and restarting of circulation to the lungs can cause ischemia-reperfusion injury, which damages cells in the lung and leads to problems with lung function after transplant.
Only about 1,400 lung transplant procedures are performed each year in the United States; since 1995, 6,022 people have died while on the waiting list for lung transplants. This week, 1,867 people were on the national waiting list for lung transplants, according to the Organ Procurement and Transplantation Network, part of the U.S. Department of Health and Human Services.
Dr. Egan has designed an ex-vivo perfusion and ventilation circuit in which lungs are placed for evaluation and possible treatment before transplant. Ex-vivo perfusion and ventilation allow for lung function assessment, and also for possible treatment of lungs to reduce ischemia-reperfusion injury in transplant. Thus, the lungs treated this way could have less graft dysfunction or failure and the transplant recipient could have an improved chance of survival. This would revolutionize lung transplantation, and could have a major impact on other types of organ transplants.
Michael Knowles, M.D., a pulmonologist in the UNC Division of Pulmonary and Critical Care Medicine and a collaborator on Dr. Egan’s project, called the research project “groundbreaking.”
“I have been involved in lung transplantation from its inception at UNC, and have seen, first-hand, the suffering and unnecessary death that results from the shortage of lung donors in the U.S.,” Dr. Knowles said in a letter of support for the research.
The project has support of lung transplant physicians at several other universities in the U.S. and Canada as well as from Carolina Donor Services, the organ procurement organization serving most of North Carolina.
For the Stage 1 project, Dr. Egan’s research team will use lungs from conventional organ donors that have been declined for transplant because of concerns about lung function, as well as lungs from DCD (donation after cardiac death) donors, patients who are not brain dead but whose next-of-kin have decided to withdraw life support because the patient's condition is so poor. The lungs will be assessed and treated in the ex-vivo perfusion and ventilation circuit.
In a Stage 2 study, Dr. Egan’s project will also plan a large multi-center clinical trial to use the ex-vivo lung perfusion/ventilation system to evaluate human lungs retrieved after death from non-heart-beating donors, patients who have died of sudden cardiac arrest outside the hospital or in the emergency room. Using animal models, Dr. Egan was the first scientist to show that lungs could be retrieved from non-heart-beating donors after death and safely transplanted. His research has shown that lungs are viable for substantial periods of time after circulation stops, because lung cells do not rely on perfusion (circulation of blood or other fluids) for cellular respiration.
Widespread use of lungs retrieved from non-heart-beating donors followed by ex-vivo assessment could provide much larger numbers of human lungs for transplant that may function better and last longer than lungs currently being transplanted from conventional brain-dead organ donors.
Investigators for the project, entitled “Ex-vivo perfusion and ventilation of lungs to assess transplant suitability,” are:
• Thomas M. Egan, M.D., M.Sc., Professor, Division of Cardiothoracic Surgery, UNC Department of Surgery (Principal Investigator), UNC School of Medicine
• Peadar G. Noone, M.D., Associate Professor, Division of Pulmonary and Critical Care Medicine, UNC Department of Medicine, UNC School of Medicine
• Paul Stewart, Ph.D., Research Associate Professor, Department of Biostatistics, UNC Gillings School of Global Public Health
• Eileen Burker, Ph.D., CRC, Associate Professor, Division of Rehabilitation Counseling and Psychology, Department of Allied Health Sciences, and Adjunct Associate Professor, Department of Psychiatry, UNC School of Medicine
• Benjamin E. Haithcock, M.D., Assistant Professor, Division of Cardiothoracic Surgery, UNC Department of Surgery, UNC School of Medicine
• William K. Funkhouser, M.D., Ph.D., Professor, Department of Pathology and Lab Medicine, UNC School of Medicine
• Katherine Birchard, M.D., Assistant Professor, Department of Radiology, UNC School of Medicine
• R. Duane Davis, M.D., Ph.D., Professor, Division of Cardiothoracic Surgery, Department of Surgery, Duke University School of Medicine
For more information, contact Dr. Egan at (919) 966-3383.
To read the NHLBI release about the grant, click here.