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Biomedicine

Fixing Lungs Outside the Body

A technique may double the number of lungs available for transplant.

Lung transplant offers hope of a longer life for patients with end-stage respiratory diseases such as emphysema and cystic fibrosis, with some surviving for years following surgery. But due to chronic shortages of viable organs for transplant, only about 25 percent of patients on waiting lists receive new lungs. However, a new out-of-body lung-repair technique developed at the Toronto General Hospital may dramatically increase the number of lungs that can be used in transplants and improve surgical outcome.

Breathing life: Lung tissue is preserved in the Toronto XVIVO Lung Perfusion System developed at the Toronto General Hospital with the aim of repairing lungs prior to transplant. The technique allows for lungs to be removed from a donor and kept at body temperature while being assessed for function and transplant outcome.

In an operating room at the hospital, the technology can keep a pair of human lungs slowly breathing inside a glass dome attached to a ventilator, pump, and filters. The lungs are maintained at normal body temperature of 37 °C and perfused with a bloodless solution that contains nutrients, proteins, and oxygen. The organs are kept alive in the machine, developed with Vitrolife, for up to 12 hours while surgeons assess function and repair them.

Normally, as few as one in ten lungs available for transplant is usable, and even those may not work properly when grafted. “The system allows you to assess the lungs, to diagnose what’s wrong with them, and then repair them,” says Shaf Keshavjee, who directs the hospital’s Lung Transplant Program. “Therefore, we’re transplanting lungs that have a more predictable outcome.”

The shortage of donor organs is partly the result of outdated preservation techniques. Organs are conventionally cooled after harvesting, which inhibits their function and poses risk of injury. While the Toronto system isn’t the first to eschew cooling preservation for lungs, it improves upon a technique to recondition nonviable lungs developed at Lund University Hospital, in Sweden. The Toronto system can maintain the lung outside the body for much longer and poses less risk of injury, according to the researchers. “We’re keeping it in a protective setting without adding more injury so it can begin to heal,” says Keshavjee.

An effective lung preservation and repair system would have a major impact on the lives of thousands of patients in the United States waiting for donor lungs. Keshavjee says that the number of acceptable donor lungs can be doubled through the system.

Following years of lung transplant and repair experiments on lungs in mice, rats, and pigs, last December, Keshavjee’s team used the technique to successfully transplant unacceptable human donor lungs into a 56-year-old man with respiratory illness. Since then, six other patients have received lungs treated with the technique as part of a clinical trial. “They’ve all done superbly, every single one of them,” says Keshavjee. “We’re now able to use lungs that we couldn’t use before.”

Other experts hail the Toronto technique but caution that more work is needed on how to fix lungs, stop the inflammatory response in grafting, and improve mortality in transplant patients.

“The Toronto system seems to re-create normal lung function outside the body,” says Jacques-Pierre Fontaine of Brown University’s cardiothoracic-surgery division. “If we can keep the organ outside the body longer with minimal ischemic damage, we can go farther to get a lung.” However, says Fontaine, “the real test” will be how well the patients do with the transplanted lungs. “Proof will be in the survival data.”

Joshua Sonnet, director of lung transplant at Columbia University Medical Center, agrees that the Toronto system is an improvement that brings existing technology to the next level, where it can act as a springboard to wider use. “We have two major problems: an organ shortage–and this [Toronto] system helps with that immediately, if we can start to recondition some lungs. More importantly, the other problem is having those organs last a long time. Mostly, they don’t last because of chronic rejection and the side effects of medicines we use to keep them from getting rejected. So as we’re able to manipulate these organs out of the donor body, we’re able to do things and improve them so not only do they work immediately better and can [they] be transplanted, but, even more exciting, they work.”

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