An update on the new device's progress and prospects, and results from the survey, will be presented here on June 13 by University of Michigan surgeon and life support pioneer Robert Bartlett, M.D., at the annual meeting of the American Society for Artificial Internal Organs. Bartlett developed the lung with colleagues from the U-M Health System, the U-M College of Engineering, the University of Texas, Northwestern University and MC3 Corp. of Ann Arbor, MI.
At the ASAIO meeting, he will discuss recent design advances that have improved blood flow through the compact chamber, and encouraging results from week-long tests in sheep. He will present plans for the next phase of testing, supported by a new $4.8 million federal grant, which will evaluate the device's ability to totally support sheep lung function for 30 days or more. And he will present results from the survey that shows that the majority of major lung transplant centers would want to participate in an initial clinical trial once pre-clinical testing is complete.
Bartlett's presentation will be part of a larger ASAIO session on artificial lung technology that he will chair. The session will also focus on a University of Pittsburgh device, called IVOX, that is placed within a vein and supports 50 percent of lung function. The U-M lung attaches to the pulmonary artery, can be used in or outside the body, and replaces 100 percent of lung function.
"This generation of long-term, bridge-to-transplant implantable artificial lungs is on the verge of reaching the patients who need it most, and have no other options," says Bartlett, a professor of surgery, director of critical care and head of the extracorporeal life support team at UMHS. "We've overcome the technical hurdles and now must confirm that it can truly take over for failing lungs for a longer time, and with less risk, than current life-support technology. As transplant program leaders tell us, we've never needed these devices more."
More than 13 million Americans have chronic respiratory diseases, such as pulmonary fibrosis and emphysema, for which the only effective treatment is lung transplant. But the shortage of donated lungs means that patients sick enough for a transplant wait an average of two years for an organ, and 80 percent die before receiving one. Currently, 4,000 Americans are waiting for a lung or heart-lung transplant, a number that rises sharply each year. About 1,000 lungs are transplanted in the U.S. each year, alone or in tandem with a heart transplant.
Technology to keep lung failure patients alive during a crisis has steadily improved. But the search for a long-term option to "bridge" lung disease patients to transplant has been frustrating.
In the 1980s, Bartlett led the team that developed the extracorporeal membrane oxygenation, or ECMO, machine now used in intensive care units worldwide to circulate and oxygenate the blood of desperately ill trauma, burn, infection and organ failure patients. Though he and his UMHS colleagues have built the world's most experienced, successful ECMO team, they still realize that ECMO is best for short-term use to get patients through a crisis.
Long-term ECMO use can be risky and costly, as can long-term use of mechanical ventilators, which have been used for decades to help patients whose own lungs are damaged. Half of all patients put on ventilators for acute lung problems die before their crisis is over. And those who survive ventilator or ECMO use have a higher risk of dying before or after a lung transplant.
The U-M artificial lung was recently shown to produce better survival and less lung injury than a conventional ventilator in five-day tests on damaged sheep lungs. The study was led by Bartlett, UMHS pediatric surgeon Ronald Hirschl, M.D., and surgery fellow Jonathan Haft, M.D.
The pre-clinical results have been improved by a new design for the device, based on sophisticated computer modeling and prototyping done by a team led by U-M bioengineering professor James Grotberg, Ph.D.
The alterations have reduced the device's size, made it more flexible, and improved the flow of blood, thereby enhancing the lung's performance and reducing the risk of clotting and infection.
The artificial lung uses no mechanical pump, instead relying on the heart's own pumping force to send blood from the pulmonary artery into the chamber, past the hollow fibers with tiny micropores that exchange oxygen from the air with carbon dioxide from the blood. The lack of a pump cuts costs and reduces damage to blood cells.
"The blood can then flow back to the pulmonary artery and circulate through the lungs for clot-filtering and other benefits, or directly into the heart's left atrium before being sent to the body," explains Bartlett.
Bartlett and his colleagues envision that the device could eventually help lung transplant candidates stay alive and mobile for six months or more, outside the hospital, and allow them to stay healthy enough to remain at the top of the transplant list. It may also prove suitable for burn and smoke inhalation patients, victims of near-drowning, and those with traumatic injuries.
A $4.8 million, five-year grant from the National Institutes of Health's new Institute of Biomedical Engineering will support further development of the device, and pre-clinical and clinical trials.
The devices are made by Michigan Critical Care Consultants, Inc., or MC3, a firm founded by U-M bioengineering alumni and led by Sean Chambers, Ph.D. Pre-clinical studies are being done by Bartlett's team at UMHS, and a team led by Joseph Zwischenberger at the University of Texas Medical Branch in Galveston. Northwestern engineers have contributed to the design.
In preparation for clinical trials, Haft led a survey of transplant program directors at some of the nation's largest lung transplant centers. The findings suggest widespread interest and anticipation, with the vast majority saying they'd want to participate, and a majority saying that animal trials of one month or less, in a few dozen animals, would be sufficient as final pre-clinical testing.
The respondents overwhelmingly said that patients with idiopathic pulmonary fibrosis, a mysterious and deadly scarring of the lungs with no known cause, would be the best candidates for the first clinical trials. They typically have the highest waiting-list death rate, and their disease progresses rapidly without responding to therapy. A Phase I trial of less than 30 participants was considered reasonable, with a goal of bridging 60 percent of participants to transplant.
But because the lung transplant system currently allocates organs based only on waiting time, size of organ needed and blood type, a clinical trial of an artificial lung as a bridge to transplant would require a change to allocation policy for participants. The survey found support for this shift, which would prioritize transplants for those on the artificial lung, among 67 percent of transplant program directors. Still others voiced partial support.
Another potential use for the artificial lung would be in patients who receive a sub-optimal lung transplant, and need lung support after their transplant to determine if the new lung will function.