Steps closer to breathing easily
Patients with lung disease have few options. Machines that oxygenate the blood during heart and lung surgery -- and pump it through the body -- have been saving lives for 50 years, but the devices are big, clunky and require the presence of a specialist, making them inappropriate for patients not undergoing such surgery. Partly as a result, nearly 342,000 Americans die of lung disease each year.
Now, physicians and researchers are miniaturizing and refining such technology to create a new generation of artificial lungs, potentially reducing those numbers.
These breathing machines are designed to keep patients alive long enough for their own lungs to recover from illness or for donor lungs to become available. Developers of the devices want to make them “small enough and convenient enough so a patient can walk around and be happy at home,” says Dr. Bartley P. Griffith, chief of cardiac surgery and director of heart and lung transplantation at the University of Maryland Medical Center. Some of these artificial lungs are little bigger than soda cans.
Scott Merz, a bioengineer and chief executive of Michigan Critical Care Consultants, or MC3, a company that manufactures artificial lungs for university labs that test them, said that understanding resistance to blood flow and “waiting for developments in the way of plastics” have been the big obstacles in enhancing the heart-lung machine technology into the high-tech devices under development today.
For instance, in normal lungs, very thin membranes called alveoli separate the air and blood while removing carbon dioxide from the blood and adding oxygen. The new artificial lung prototypes replicate this process with a thin membrane of plastic that allows oxygen and carbon dioxide to pass through, but not blood.
Other advances have included refinements in materials, surface coatings and the management of blood clotting, says Dr. Joseph Zwischenberger, a cardiothoracic critical care physician and chairman of the department of surgery at the University of Kentucky.
Dr. Robert H. Bartlett, professor emeritus of surgery at the University of Michigan, says that all the major universities researching artificial lungs are working on slightly different designs that will meet different needs. Some are intended for very short-term use, generally days to weeks; others are for long-term use, currently up to six months. The devices can completely take over lung function or act as assist devices, only partially replacing lung function. They can rely on the heart to pump the blood through them, or they can have a pump attached.
Some can even be attached to different parts of the body such as directly to the heart or to the femoral vein in the leg or jugular vein in the neck. The devices could also potentially be used, temporarily, with donor lungs that are less than perfect, Bartlett said.
Further, some devices probably would be better at removing carbon dioxide than adding oxygen, and thus would be better for patients with emphysema or asthma, Bartlett added. Other devices would be more suitable for patients with cystic fibrosis, in which the main goal is to add oxygen to the blood. Currently, the only artificial lung being used in humans is the Novalung iLA, or interventional lung assist. It has been studied in clinical trials in Europe and Canada and has been used to treat a handful of U.S. troops injured in Iraq. Merz, whose company helped found Novalung and is working on FDA approval, hopes it will be available in the U.S. next year. The Novalung, which relies on the heart to pump the blood through the device, is designed to provide short-term help to patients who are bedridden with acute lung failure but who still have some lung function.
The other lung devices should be ready for human clinical trials in the next six months to five years.
Bartlett’s lab recently received a $5-million, five-year grant from the National Institutes of Health to refine an artificial lung that would completely take over the job of the lungs and has low enough resistance to blood flow that the heart itself can serve as a pump. The lung is attached to the heart by large tubes through the chest wall and is designed to serve as a bridge to transplant for up to six months. Currently in animal testing, it should be in clinical trials in three to four years.
Keith Cook, a cardiac physiology expert and lead bioengineer on the project at the University of Michigan, said that allowing the heart to serve as a pump reduces the surface area of the artificial lung and makes the blood flow more gently. This reduces the risks of blood clots and rejection by the immune system. A device that lets the heart do its own job also means there’s one less thing that can break.
However, Zwischenberger, who helped develop the Novalung, said that animal testing has suggested recipients might not fare well when they have to rely on their own heart as the pump. His lab is building a machine that would combine a pump and a gas exchange device. Testing on large animals has been successful. Griffith’s lab is using an external pump that spins, helping the blood mix with oxygen. Griffith chose to use a pump because heart failure is present in many patients who have lung failure, and he doesn’t want to worry about putting an extra strain on the heart. He has not only received a five-year NIH grant for a long-term artificial lung, but also is working on a short-term use lung that could be in human clinical trials in two years. Both efforts are undergoing testing in animals.
The University of Pittsburgh lab headed by Dr. Brack G. Hattler is another major lab in the U.S. working on artificial lungs. Hattler is developing an internal catheter that will serve as a partial assist device by providing 50% to 60% of blood oxygenation and carbon dioxide removal, which he says is all that is needed in most patients. He had hoped this device, which was successful in animal testing, would be in clinical trials already, but because of its size, the device requires surgical insertion. Clinicians have requested that it be small enough to be threaded into a vein in a nonsurgical procedure, and Hattler says the science necessary for nonsurgical implanting is still some years away.
In the meantime, Hattler is working with a company on a lung in which the catheter only transports blood, and the oxygenation takes place in an external, spinning pump. This device has been successful in animal testing, and a six-month clinical trial could begin early next year. Hattler hopes the FDA will approve it quickly enough for it to be on the market by the end of 2008.
Researchers in Osaka, Japan, are also working on an artificial lung that has been tested successfully in large animals.
The ultimate goal, Griffith says, is a lung that would work indefinitely, either as bridge to transplant or for “Grandpa Joe who wants to spend the last years of his life being able to breathe.”
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Artificial lungs’ real hurdles
Permanent implantation of an artificial lung seems unlikely, at least in the foreseeable future.
The biggest barrier is biocompatibility -- in essence, anything that is implanted into the body must get along with it.
Artificial lungs have a very complicated “blood contacting surface,” says Dr. Bartley Griffith, chief of cardiac surgery and director of heart and lung transplantation at the University of Maryland Medical Center.
The membranes that separate blood and air are made up of very small tubules, and when the blood flows through these, it often forms clots. These clots can either plug the device and decrease its efficiency, or escape from the device into the body, where they could cause a heart attack, stroke or embolism.
Clotting can be overcome with anticoagulation medication, but the amount required to make an artificial lung safe inside the body would make patients “as fragile as an egg,” essentially preventing them from getting out of bed for fear of bleeding to death, Griffith says.
Artificial lungs that are left outside the body can simply be exchanged when they become plugged up. Griffith calls this a “Sears and Roebuck approach” and compares it to the approach used by the thousands of patients with hemodialysis machines.
“Materials have been fabulous in allowing us to create designs that can efficiently transfer gas to and from the blood safely and to conceive of compact, little devices. But materials have not yet given us anything with an intuitive nature that can prevent blood from clotting,” Griffith says.
-- Alison Williams
