Lungs are the most difficult organs to procure and transplant. Only one out of five donors that provide organs of any kind provide suitable lungs, placing an even greater demand on an organ donation system in which nearly 1,700 people in the United States are on the waiting list for lung transplants. Despite this scarcity of suitable donor lungs, more are transplanted every year, aggravating the situation.
Lungs are highly susceptible to various injuries and infections in the late stages of the donor’s life, and physicians don’t have much time to improve them in donors before procurement. To overcome these challenges, transplant specialists need a way to prepare the donated lungs before transplanting them. This may improve the quality and function of the lungs, and reduce the risk of inadvertently exacerbating an existing injury or triggering a reaction that could jeopardize the long-term success of the procedure. A new process called ex vivo lung perfusion, or EVLP, could be the answer.
Lungs may sustain damage during the process to transfer them from the donor and prepare them for the recipient. They can collapse during that process, and, as surgeons begin to ventilate them after transplant, they may not re-expand properly. Fluid can build up and affect the function of the lung tissue, and brain death of the donor can trigger an inflammatory effect in the lung tissue that can jeopardize the transplanted lung as well.
In addition to these more obvious factors, a number of less-well understood cellular processes happen in the lungs after a donor’s death that can decrease the odds of a successful transplant. Lungs may be dysfunctional for multiple reasons, and up to two out of 10 lungs show signs of such limitations within 72 hours after being transplanted.“The issue is, you may notice preexisting injuries of multiple different etiologies in the donor, some of which may be reversible and we may understand and see, and some of which may be more like the tip of an iceberg,” said Christopher Wigfield, MD, Surgical Director of the lung transplant program at the University of Chicago Medicine.
To make matters worse, these microscopic and more diffuse complications may not become apparent until after the lungs are re-perfused, or connected to the blood flow and airways of the recipient.
“Someone once described this as loading and cocking a gun, and then when you get lungs perfused again in the donor, it goes off and you get the opposite of recovery,” Wigfield said.
EVLP involves placing the donor lungs into a perfusion system that gradually circulates a special solution through the blood vessels to slowly warm them up after transport and establish normal tissue flow. After a certain point, physicians can then re-ventilate the lungs in a gradual, controlled process, expanding them more deliberately than if they had done it directly in the recipient. The process also gives physicians a chance to remove any excess fluid from the lungs, and possibly treat them with antibiotics to stem any nascent infections before transplant.
Shaf Keshavjee, MD, from University Health Network in Toronto, demonstrates the EVLP system at a TEDMED presentation in 2010 (including a cameo by Martha Stewart)
The system is in use in several countries in Europe and in Canada, but has only recently been approved by the FDA for use in the United States. Wigfield has personal expertise with the procedure: He and his colleagues used EVLP during a procurement procedure in 2012, in which the donor lungs were transported to Toronto for the process and then brought back and transplanted successfully in the recipient (they published a subsequent case study in the American Journal of Transplantation). He has proposed making the University of Chicago Medicine one of the first sites in the United States to use EVLP outside of clinical trials, taking part in a regional collaboration with other academic medical centers and organ procurement organizations in the Midwest. The partnership could defray the hefty $250,000 up front cost of the system, and centralize expertise and donor care in one location to optimize results and benefit for recipients.
The goal, he said, is not just to make lung transplants go more smoothly, but also to allow more of them to happen. EVLP allows physicians to take some donor lungs that normally wouldn’t be considered to be in good enough shape for transplant and “recondition” them. Wigfield estimates that this could increase the number of available donor lungs by 30 percent.
“We are currently looking at about 20 to 30 percent risk of a patent’s dying while they are waiting for lungs. That’s where we would like to see the impact,” he said. “Reducing that to a minimum would be a huge success.”