People who need a lung transplant can only wait and hope that a donor organ will materialize in time. But all too often, time runs out.
In response to the United States' critical shortage of donor organs, researchers have been racing to develop artificial organs that would serve as a "bridge" to transplantation. One such device is the BioLung, which may be tested in people soon.
Robert Bartlett, MD, surgeon at the University of Michigan Medical Center, leads the research on the BioLung, and Michigan Critical Care Consultants (MC3), a company in Ann Arbor, Mich., makes the device. Bartlett is well known in this field: He is credited with inventing the current generation of artificial breathing machines.
For eight years, the Ann Arbor team, with support from scientists at other universities, has been trying to invent a device that can do what today's machines cannot: supply 100% of a patient's oxygen needs by using the heart's own pumping power. "It took those eight years of iterations to meet those design requirements," says Scott Merz, president of MC3.
The system now used in hospitals is known as ECMO, or extracorporeal membrane oxygenation. ECMO machines take over the functions of both the lungs and heart, pumping blood and exchanging carbon dioxide for oxygen outside the body. Bartlett says ECMO works well for patients who have had respiratory failure because of infections, such as pneumonia, or trauma, such as smoke inhalation. They only need to stay on the machine briefly, until their lungs have healed enough to begin breathing normally.
While ECMO is a short-term lifesaver, it's not good for long-term use. Many people whose lungs are in such bad shape that they need a transplant -- such as sufferers of severe emphysema, cystic fibrosis, and pulmonary fibrosis -- do not survive on ECMO long enough to match them with a donor organ.
To keep the blood moving through the machine without clotting, patients get a blood-thinning drug. The blood thinner can cause bleeding. If blood clots do form, they can damage the brain and other vital organs. What's more, Merz says the mechanical pumps used in ECMO damage red blood cells -- the cells that carry oxygen.
The BioLung, however, does not use a mechanical pump, nor does blood ever leave the body. A little larger than a soda can, it is implanted in the chest. The patient's own heart pumps blood into the device, which is packed with hollow plastic fibers perforated with holes so tiny that only gas molecules can pass through them. As blood filters through the fibers, carbon dioxide escapes through the holes and is replaced by oxygen from the surrounding air. Then the blood may go directly back to the heart to be pumped to the rest of the body, or it may take a spin through the patient's lungs first.
There are advantages and drawbacks either way: Directing blood through the lungs may help filter out blood clots, because the lungs have a natural ability to do so. Also, the fresh supply of oxygen to the lung tissue may help heal it. But that puts a heavier load on the heart, raising the risk for heart failure. By sending the blood directly to the heart instead, it is possible for the artificial lung and the natural lungs to share in breathing. But that could let clots enter the bloodstream.
The BioLung is not meant to be a lifelong replacement for diseased lungs. At best, researchers hope to buy time for those awaiting a transplant and let them live relatively normal lives while they wait, rather than be tethered to a heavy life-support unit.
After nearly a decade at the drawing board, "We are looking at what we consider final design changes," Merz says. Clinical trials may get under way in one to two years. The National Institutes of Health recently granted Bartlett $4.8 million to continue the research.
Early animal studies have been promising. In the latest study, University of Texas researcher Joseph Zwischenberger, MD, tried out the BioLung on sheep whose lungs had been badly burned by inhaling smoke. Six of the eight sheep on the BioLung survived five days, whereas only one of six sheep on an external breathing machine survived that long.
Meanwhile, Bartlett has been testing the waters for future human trials. "What we wanted to do was see what the transplantation centers were thinking," he says. So he sent them a survey.
Thirty-one transplant centers completed the survey -- and those were responsible for 72% of all lung transplants in the United States in 1999. Most said they would like to see the BioLung studied in fewer than 25 animals for 30 days before beginning to test the device on humans. Almost all of them said they would support and participate in a clinical trial.
"The FDA would have the final word," Bartlett says. "This is just a start."
A one-month study on two dozen animals may seem hasty, but the situation is dire. Last year, 1,054 people received lung transplants, but 477 died on the waiting list. As of August this year, 3,797 people were still waiting to be matched to a donor.
Most of the transplant centers that responded to Bartlett's survey said the device should be tested first on people with idiopathic (meaning "of unknown cause") pulmonary fibrosis. Among the sickest of these patients, few survive longer than three months.