Technology aims to improve lung transplant odds

Edward Cantu (right), a Penn transplant surgeon, and Yoshikazu Suzuki, a procurement surgeon, with lungs being reconditioned by the XVIVO system.
Edward Cantu (right), a Penn transplant surgeon, and Yoshikazu Suzuki, a procurement surgeon, with lungs being reconditioned by the XVIVO system. (HUP)
Posted: January 07, 2013

More than any other vital organ offered for transplant, the lung is susceptible to injury that is difficult to prevent, detect, and predict.

To err on the side of caution, 80 percent of organ donors' lungs are rejected as unsuitable, a waste lamented by doctors and patients alike.

Now, the University of Pennsylvania and five other medical centers are testing technology aimed at improving the situation. It involves cleaning and refurbishing donor lungs while the organ "breathes" in a specially designed machine. Lungs that would normally be discarded can be tuned up, evaluated, and, in many cases, reused.

In a recently published clinical study in Canada, 86 percent of risky lungs became acceptable for transplant.

Penn transplant surgeon Edward Cantu believes the advance, made by Sweden-based XVIVO Perfusion Inc., could save thousands of lives a year.

"We could reduce the number of people who die waiting for lungs, and reduce the number who die" because their new lungs fail soon after surgery, he said.

Similar technology, developed by TransMedics of Andover, Mass., is being tested internationally. It keeps donated lungs warm and functioning during transport to a transplant center; normally, lungs are preserved and carried in a cooler. The University of California, Los Angeles in November performed the nation's first transplant using the new system.

Jay K. Bhama, associate director of lung and heart transplantation at the University of Pittsburgh Medical Center, said such innovations "have a lot of potential in terms of improving the utilization of donor lungs, and helping us assess lungs that may not be optimal. It's still in the early phases, so it's going to take some more time to determine what percent of [marginal] lungs can be used."

Lung transplantation remains daunting almost 30 years after the first successful operations in Toronto by transplant pioneer Joel Cooper, who is now at Penn.

Donors' lungs must meet certain criteria, including a limited smoking history, and undergo evaluation with X-rays and other standard tests. But this isn't enough to ensure good outcomes.

Lungs may be injured by physical trauma, cardiac arrest, resuscitation efforts, mechanical ventilation, pneumonia, or the irreversible shutdown of the brain, called brain death. (Most donated organs come from patients who are declared brain-dead.)

The United States has about 8,000 organ donors a year, but only about 20 percent of their lungs are used, national transplant data show. As a result, 15 percent to 30 percent of wait-listed patients die before getting lungs. (International rates are similar.)

Even with this high rejection rate, many of the 1,700 U.S. patients who do get lungs suffer a sometimes fatal, little-understood complication called "primary graft dysfunction." The transplanted lungs just don't work properly, perhaps partly because of the physiological shock of having circulation abruptly restored.

This catastrophe can happen despite a technically flawless surgery. It occurs in about 10 percent of cases at Penn; rates at some centers are two to three times higher.

"This is one of the most painful things for me as a transplant surgeon," Cantu said. "You can do everything absolutely perfectly. You take the patient to the ICU. You talk to the family. Everybody's happy. And 12 hours later, the patient is critically ill."

Cooper was among the first researchers to try to improve out-of-body lung preservation. He developed a cell-free solution that could be pumped through the lung to protect it after removal from the donor.

The XVIVO system being tested at Penn uses a patented solution named for the final developer, Swedish surgeon Stig Steen. Steen Solution helps to cleanse the lung, reduce fluid buildup, and prevent clot formation.

Between 2006 and 2009, Steen Solution was approved for use in Europe, Canada, and Australia. It is circulated through the lung using equipment similar to a standard heart-bypass machine. The organ is continuously evaluated for several hours and then, if the function is satisfactory, transplanted.

In the Canadian clinical study of the process, called "ex vivo lung perfusion," 50 of 58 risky lungs became suitable for transplant. Serious graft dysfunction occurred in 2 percent of them, compared with 9 percent of untreated lungs in a control group. Patients with reconditioned lungs did not have longer hospital stays or worse survival rates.

Chris Jaynes, XVIVO's transplant project manager, said Canadian transplant centers that were using the technology had more than doubled the pool of usable organs. "They've gone to using 45 percent of donated lungs," he said.

In the United States, regulators wanted additional steps to ensure "safety and consistency," Jaynes said. So in 2007, the Food and Drug Administration directed XVIVO to develop a customized machine that transplant centers would have to use with Steen Solution.

The $250,000 result is now at Penn: a five-foot-high device with a ventilator, pump, filters, a computer, and a plastic dome-covered tray for the lungs.

It's not clear how much reconditioning will add to the cost of a lung transplant - Cantu guessed $10,000 to $20,000 - but the hope is that health costs before and after the operation would be reduced.

"Maybe no one dies waiting," Cantu said. "Maybe our lung-transplant outcomes become as good as for kidneys and hearts."

That would be good, indeed. Federal data show that three-year patient survival is about 90 percent for kidney transplants, 80 percent for hearts, but only 68 percent for lungs.

George Schwab, 66, a retired Jenkintown architect who in November became the first recipient of a reconditioned lung at Penn, is thrilled with his outcomes so far.

Chronic obstructive pulmonary disease - suffered by 12 million Americans - had so eroded his lung function that every breath was an exertion. The organ he received normally would have been rejected because it was swollen with fluid, called edema. Instead, the tune-up removed the edema and reassured his surgeons.

Schwab now runs on a treadmill with weights on his hands and feet.

"I was one bout of pneumonia away from death" before the transplant, he said. "My recovery has been amazing."


Contact Marie McCullough

at 215-854-2720 or mmccullough@phillynews.com.

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