New Approach May Dramatically Improve Damaged Lungs to be Used for Transplants

 

Scientists at Columbia University and Vanderbilt University have been working on ways to revive damaged lungs for the last eight years. In a study published in Nature Medicine, they describe how they were able to successfully restore badly damaged lungs in order to use them for lung transplants.

The authors of the study note that patients who are on waiting lists for lung transplants “face high wait-list mortality, as injury precludes the use of most donor lungs.” A process known as ex vivo lung perfusion (EVLP) can improve the quality of donor’s lungs that are marginal but extending room temperature (normothermic) support past six hours has been difficult.

In their research, they placed each damaged lung in a plastic box. The attached a respirator to the lung, allowing it to “breathe.” The lung was then connected to a vein in the neck of a live pig. This allowed for the blood to flow through the vessels in the lung. They found that within 24 hours, the lungs appeared viable and laboratory tests confirmed that the lungs had been resuscitated.

The researchers are now investigating the possibility of using humans instead of a pig. A catheter in the patient’s neck would transfer blood to the damaged lung, which would be in a respirator in the room.

Although a long way from being ready for clinical use, it’s an approach that is showing quite a bit of promise, particularly in the face of significant need. In the U.S. in 2018, 2,562 lung transplants were performed. In the same year, 3,134 patients were added to the wait-list. Meanwhile, about 365 patients died waiting for a transplant lung to become available or were too ill to undergo surgery.

And unfortunately, the COVID-19 pandemic is increasing the need for lung transplants. In June, a lung transplant for a COVID-19 patient, a woman in her 20s, was the first person to receive a double-lung transplant as a result of COVID-19. She received the transplant at Northwestern Memorial Hospital in Chicago. The woman was otherwise healthy, but after contracting COVID-19, spent almost two months in intensive care on a ventilator and an ECMO machine that pumps and oxygenates blood outside the body. The woman eventually eliminated the virus from her system, but was in severe condition and her lungs were irreversibly damaged.

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Of the experiments with pigs, Zachary N. Kon, surgical director of the lung transplant center at New York University Langone Center, told The New York Times, “Would I consider doing this? Absolutely. It’s a transformative idea that would allow a jump forward in the field.”

David W. Roe, a lung transplant surgeon at Indiana University, told the Times, “This is all on the outer cusp, but I don’t think it is out of the realm of possibility. It all makes sense.”

The lead author of the new study, Matthew D. Bachetta, a lung transplant surgeon at Vanderbilt, indicated that with current surgery standards, only about 20% of donated lungs are usable. If there was a way to increase that to 40%, the waiting list for transplantable lungs could be eliminated.

The criteria for eligibility are high because of limited supply. Typically, medical centers rule out patients 70 years of age or older, people who are frail, and even teenagers if their frailty is caused by damaged lungs.

“If we could expand the donor pool,” Bacchetta said, “we could avoid a lot of waiting-list deaths and could be more open-minded about who could have a transplant.”

One of the researchers in the group, Gordana Vunjak-Novakovic, from Columbia, tried to bioengineer lungs by removing all the cells from the lungs, which left a scaffold to build new lungs from.

“It looked very cool, but it was leaky,” Vunjak-Novakovic said. “This caused a massive loss of blood. This was telling us that, unlike other tissues, you cannot make a lung in the lab.”

But researchers at the University of Toronto had developed a way to resuscitate lung by filtrating the damaged lungs with a clear nutrient fluid and hooking the lungs to a ventilator. It worked reasonably well, but the lungs could only be maintained for hours, not days. And not many lungs can be fixed that way.

Funjak-Novakovic and her group developed this new method to improve on the Toronto technique and appears to be successful.