A small shift in temperature could have a big effect on how lung transplants are performed worldwide

TORONTO -

Canadian transplant scientists say they may be able to help boost the number of lungs available for transplants, all with a simple tweak of temperature. 

They've been conducting studies that show that storing lungs at 10 C, warmer than the current standard of 4 C, is better for lungs harvested for transplant. They've also created a world-first cooler that they say stays at 10 C, boosting the shelf life of a donor’s lungs from six hours to up to 36 hours, and perhaps longer.

"There's a huge interest in people all over the world because...it's a simple solution. It's not that complex," said Dr. Shaf Keshavjee, a thoracic surgeon and chief of innovation at the University Health Network (UHN).

According to the most recent data available from the Canadian Institute for Health Information, more than 220 people are waiting across the country for a lung transplant. 

The cooler, called the X-port, has allowed the transplant team from UHN to collect donor lungs from further afield, because the traditional six- to eight-hour window during which ice kept lungs viable for transplant is now gone. 

"We've been to California, we've been to Nevada. We've been to Arizona. I think hopefully this would allow also going to different continents," said Dr. Marcelo Cypel, surgical director of the transplant program at UHN, who helped design the technology.

It looks much like any white plastic picnic cooler except that it is on wheels, and there is a GPS tracker and temperature gauge on the side. Once opened, transplant surgeon Cypel showed CTV News a lung that had been harvested for transplant, surrounded by a series of novel gel packs that keep the contents at a steady 10 C.  

"There is no electricity here," he told CTV News.

Another twist: the donor lung would be implanted in a recipient the following morning, almost 18 hours after retrieval – almost three times longer than usual.

Normally, transplants are performed as an emergency, not as scheduled, surgery. Often they are performed overnight, or force the cancellation of other surgeries.

"I think that's huge," said Dr. Ed Cantu, the associate director of Lung transplantation at Penn Medicine in Philadelphia and a spokesperson for the International Society of Heart and Lung Transplantation, where the Canadian work was first presented in 2022.

"It's no longer about how fast you can get patients into the operating room," he told CTV News, because doctors have more time to find the right match and time to get the lungs there.

"Having the opportunity to extend that window of allocation may make more organs available to more centres," he added.  

The idea that warmer might be better for organs was first floated some three decades ago, but fell by the scientific wayside. That's because ice on its own has been effective at slowing down the deterioration and death of the organ.

But the small viability window means that many organs are lost in the process. Eighty per cent of lungs never make it to the donor and are unsuitable for transplant, according to the International Society for Heart and Lung Transplantation.

In 2020, the Consensus Statement from ISHLT on Donor Heart and Lung Procurement also warned against the risks of tissue damage from ice.

Some companies designed coolers to keep the lungs physically away from the ice chips, but the Toronto-made cooler is the first to come up with an altogether different system after finding 10 C was the “sweet spot" for lung health.

“We looked at four degrees, eight degrees, and 10 degrees was far better,” said Keshavjee.

Tests showed lung cells – and in particular, the mitochondria, which produce energy inside the cells – maintained their function with signs the inflammation and injury to the lungs were diminished.

"So you may actually give some benefit of actually prolonging the preservation time versus rushing to do the transplant immediately, which is completely a change in paradigm,” said Cypel.

Doctors in Toronto say they have now completed transplants involving about 70 patients using the new, warmer lung storage, turning those procedures into planned, elective surgery, with good results.

A preliminary study was presented showing no difference compared to traditionally stored lungs. A formal study is pending publication.

Rick Collins was part of the study after a genetic disease destroyed his lung capacity. The 72-year-old man from Clarington, Ont., Ontario received new lungs warmed to 10 C in late 2021. His recovery, he says, was surprisingly quick.

"The doctors (said) that I was supposed to be three weeks in the hospital…and I was there nine days," he told CTV News.

While he can't say if it was because of the warmer storage, the early evidence has prompted the Toronto team to design its own cooler to expand the use of the technique, since there are no others that maintain a temperature of 10 C, without ice, over many hours

In a factory in Mississauga, Ont., there are about 30 containers ready to ship out to centres in Austria, Spain, and Canada, for a 300-patient trial comparing patients given warmer lungs stored for longer to those given lungs that have been transported with standard 4 C ice storage. But there are already orders being fielded from transplant centres that aren’t part of the study.

"We realized that the only way we can bring these inventions to help patients is to commercialize it, make it available, get it regulatory-approved so that hospitals will buy it, and that's what's happening," said Keshavjee.

Each unit costs an estimated $10,000 said Rick Mangat, the CEO of TRAFEROX Technologies in Mississauga, with disposable coolers also now on the drawing board.

The goal is to make it available to transplant centres around the world to boost the 6,000 lung transplants done a year.

"We anticipate that market should be at least double, if not triple, that size, given the wait list, and I think this is just going to help people make more of these lungs available,” said Mangat, who has partnered with the research team and the hospital.

It's part of an ongoing revolution in transplant medicine to make more organs available, and to store them for longer. The Canadian team has already developed a more elaborate system, called an Ex-Vivo lung perfusion unit , that uses a ventilator to keep lungs on oxygen and fluids, to keep them functioning while flushing them with nutrients that reduce inflammation. The device, Torex, recently received approval for sale by Health Canada.

The next step, says Dr. Cypel, is to work to see if the warmer temperature can be used to extend the storage of hearts, livers and kidneys, part of an international race to keep organs viable until they are needed to save lives.