By Kathleen Yount

Respiration has two parts: inspiration and expiration.

Air flows in and out of the lungs, taking sustenance into our bodies and delivering our leftovers back to the world. The flow of our breath, from our first cry to our last exhale, is our most basic function, connecting heart and brain to life as we know it.

Gordon Weeks goes with the flow. Or, at least, he does when it comes to matters of life and breath.

But he is also a survivor, which is why on April 12, at age 56, he celebrated his first rebirthday. It marked a year of living on someone else's lungs, a year since he was snatched back from the foggy line where life rubs shoulders with death.

His story is one of hundreds in the Duke Transplant Center, where the model of moving bench discoveries to bedside care takes on a new speed.

Thanks to the interchange of clinical practice and research innovation, patients for whom transplant wasn't possible a decade ago are now surviving longer and thriving after surgery.

Mr. Weeks goes south

Weeks and his wife, Shauna, live with their 10-year-old daughter on Cape Cod, Massachusetts, where Gordon used to spend much of his free time surfing.

Then one day he just stopped.

"I couldn't paddle out anymore," he says. "Didn't have the drive." He had no idea that the problem was his lungs -- as for many people with idiopathic pulmonary fibrosis, or IPF, it took years to make that diagnosis.

In November 2006, Weeks's brother Doug died from IPF. At that point Gordon himself had already been battling the disease for at least 10 years, and he and Shauna began to search for their only hope for meaningful treatment: lung transplant.

They applied to the transplant program at a hospital in nearby Boston, but waiting list was too long.

"They basically told us there wasn't anything they could do for [Gordon]," says Shauna, so the couple set out to find someone who could.

"I looked up Duke's outcomes online and they were the best. So I put Gordon and my daughter in the car and we drove to North Carolina."

That was March 19, 2007 -- one of the last days of winter. Gordon wouldn't see Cape Cod again until after midsummer.

The drive was tough, says Gordon.

"Shauna drove straight through -- 13 hours, and at one point we had to pull off of I-95 in the middle of Washington, DC, because I was so sick. Shauna had no idea what was happening to me."

What was happening was an escalating collapse of Gordon's respiratory system.
In the lungs of people with IPF, something -- no one yet knows what -- upsets the healing and repair processes in certain cells of the alveoli sacs. This thin, delicate tissue is gradually but inexorably scarred, and ultimately the alveoli can no longer broker the blood's precious exchange of oxygen for carbon dioxide.

The prognosis for IPF is always poor, but the process can take decades to reach a life-threatening stage; Gordon calls the disease a "sneaky one, a faker."

There's no pain, and no sensation that you aren't getting enough air (at least early on). Mostly, he says, it's a disease of frustration.

"You just sit around a lot more than you used to." And then, sometimes all at once, "the disease can just slam you."

In the lobby of the Millennium Hotel in Durham, where Shauna was checking in the road-weary family, that's what happened.

"I started shaking all over," says Gordon.

EMTs were called and he was admitted to Duke University Hospital, where the transplant team took over.

"I basically appeared to them out of nowhere, essentially waltzed in off the street totally unannounced," says Gordon, "but they immediately took me in and started rooting for me."

Gordon was stabilized and then spent the next week undergoing the rigorous physical and psychological evaluation for transplant.

"I remember that the whole transplant team gathered around Gordon's bed," says Shauna. "I was so sure they were coming to tell us that they couldn't do the transplant.

"And then one of the team members said, 'Mr. Weeks, you're having a very bad air day, and you needed a lung transplant yesterday. We're here to help."

Gordon then began the pre-transplant rehabilitation program at Duke's Center for Living, which helps lung transplant patients get strong before their surgeries. All transplant patients are required to do four hours of cardiovascular rehab training, every day, for 24 days prior to their operation and for 24 days afterward.

"The whole Duke team is really adamant about exercise," Gordon says.

So, as the Weeks family awaited a pair of lungs, Gordon hit the gym.

At this point, no one knew just how close he was to dying.

Waiting for the call

"We were desperados in desperate times," Gordon says of his peers awaiting lung transplant.

Particularly, he says, at the Center for Living gym, where patients walk the treadmills, ride bikes, and lift weights, always with oxygen tanks in tow.

Those awaiting transplant range from young people with cystic fibrosis -- some of whom get multi-organ transplants -- to older people with emphysema and IPF patients like Gordon.

One woman Gordon got to know had a disease that actually turned her blue. She, Gordon says, waited several weeks for her transplant -- but that's an exception to the rule.

The waiting time of lung transplant patients at Duke is unusually short -- about two weeks, in most cases.

Robert D. Davis, MD, a cardiothoracic transplant surgeon and director of the Duke Transplant Center, says the short wait is made possible by the program's ability to procure about three times more lungs from donors than most other American programs.

"A lot of that has to do with the fact that we'll consider organs that other people won't," says Davis.

That doesn't mean that they take lungs that are sub-par, he says, but that they have the resources and manpower to travel to a hospital that has a potential donor match.

Davis says that when surgeons physically go to look at potential donor organs, "you can do things to optimize the lung function before procurement. It allows us to use a lot of organs that are viable, but might not sound so over the phone."

The national standards for allocating donor lungs were changed in May 2005.
Originally the allocation was done on a sort of first-come, first-served basis, but the revisions now give highest preference to patients whose odds of survival after transplant are good and whose survival without transplant is dire.

And there wasn't much about the Weeks case that wouldn't turn out to be dire. On the fourth morning of his rehab training, Shauna called the paramedics.

As Gordon puts it, "I was tanking."

"Mr. Weeks's illness had progressed to the point that the trip and the transplant evaluation were too much stress on him," says Duke pulmonologist Scott Palmer, MD, who is medical director of the lung and heart-lung transplant teams.

"By the time he got to us, his survival could have been measured in weeks."

Back in the hospital, Gordon was put on a ventilator to help him breathe. But the ventilator quickly proved inadequate; it was giving Gordon oxygen, but his lungs couldn't do anything with it.

"They called my wife and more or less said, 'Please come quickly, your husband is about to die,'" says Gordon.

But he wasn't afraid at any point in those last moments of consciousness. "I really went through the whole thing like a piece of wood floating in a river," he says.

"I just thought, well, I'm putting myself in their hands and God's, and it's going to be fine, one way or another."

Uncharted waters

"The first time I met the transplant surgeon, they had just coded my husband," says Shauna.

Davis told her that they were entering uncharted waters: most patients who are at this stage of IPF are no longer good transplant candidates.

But, Davis said, if lungs became available in the next five days, they would perform the surgery.

Meanwhile, Gordon would have to be put on ECMO -- extracorporeal membrane oxygenation, which is essentially a last-resort therapy for patients whose lungs are simply unable to function.

It's a rather gruesome-looking scenario: large catheters are run in through the neck and out through the groin, so that they can capture blood from the large veins and run it through the machine's belly.

Much like a heart bypass or dialysis machine, ECMO is the mechanical means to do what the body's own system cannot -- in this case, to filter the blood's carbon dioxide and replace it with oxygen.

ECMO can be a lifesaving tool for some patients, particularly premature babies with still-forming lungs, because it provides a bridge to keep the body going if the lungs simply need to go off-duty for a while. But Gordon's lungs weren't going to get any better -- his lungs were gone.

Gordon meets his match

"I'm still not sure what it was about me that made them decide to do the transplant -- I was so sick," Gordon says.

Davis explains that such a choice is made by gestalt: The weeklong evaluation gives the team -- which includes surgeons like Davis, pulmonologists like Palmer, nurses, transplant coordinators, and social workers -- a chance to assess a variety of physical, psychological, and social support factors that help them determine whether the patient has a reasonable chance for a successful recovery after transplantation.
Lung transplant surgery is a huge commitment, on the part of the patient, the patient's family, the hospital, and the organ donation service.

Ideally, Davis says, the final decision to go through with a transplant isn't made in an emergency situation, but in those cases "it often has a lot to do with how healthy the patient was before the crisis," he says.

"Gordon was in reasonably good physical condition before he took the sudden downhill turn."

The fact that Gordon suffers from IPF also made transplantation a clearer choice, according to Palmer.

"We knew we were giving him a survival benefit, because he had no survival left with his lungs. There are other diseases where we really debate about how much of a benefit we're offering."

For example, the number of emphysema patients receiving transplants has gone down in the last five years, for two reasons: first, emphysema patients are not as sick as patients with illnesses such as IPF, and second, it's not as clear whether their survival and quality of life will be better if they are transplanted sooner rather than later.

"We want to maximize everyone's life expectancy," says Palmer, "so we want to time the transplant so that they really are at the end of the road with the lungs they have, and that they can have a good recovery and good quality of life after transplant.

"There's no crystal ball to it, and sometimes it's hard to know what's best."

After all, the surgery is no small affair.

"To make the recovery easier, they make the incision from armpit to armpit; they open you up like a clam," says Gordon.

His own turn on the table came after four days on ECMO -- Shauna says it was just as he was starting to look "really bad," if it was possible to look worse than he already did.

Gordon's surgery was as arduous as the family's drive from Cape Cod three weeks before: it took 14 hours and, when Gordon began to hemorrhage at one point, more than 100 units of blood.

Kidney envy

Even from his most precarious moments in surgery, Gordon had great odds. Fifty percent of Duke lung transplant patients survive at least eight years following their surgery (the national figure is four years).

Davis attributes these outcomes to a number of factors: only double-lung transplants are performed (their outcomes are better than single-lung transplants); the team does a large volume of transplants (also associated with better outcomes); and they employ a clinical protocol to help prevent the new lungs from injury due to gastric reflux.

"Some of it is also the sum of all sorts of little processes," Davis says. "The expertise and dedication of the physicians, the coordinators, the team aspect of delivering care -- we're still doing the same protocol as institution X, but we're doing it better."

But as good as Duke's lung stats are, they still aren't as good as the average successes for heart, or kidney, or liver transplants, which function successfully for up to 14 years.

Palmer notes that, worldwide, lung transplants have the lowest numbers in terms of both incidence and successful outcomes.

"But to me, that means we have the most opportunity to make an impact," he says.
"We don't want to just do more lung transplants. We want to extend the longevity and quality of our transplants."

Most lung transplant patients eventually succumb to either infections or, most commonly, chronic transplant rejection: at some point, the immune system registers that the transplanted organ is foreign material.

Thinking it's doing its duty, it sends its cellular troops to attack the infidel. Immunosuppressive drugs are used to keep this response in check, but often the body's impulse to defend itself simply takes over.

"Kidneys now have about a 10 percent acute rejection rate at six months," says Palmer, "and we still have about 50 percent acute rejection at six months."
He explains that, for lungs, the current immunosuppressive medications aren't making the grade.

"Lung transplant has basically just been borrowing all the drugs from kidney transplant, because they're all we've got. But the reality is that they don't work as well for us."

Some other mechanisms are at play in lung transplant failure -- the question that preoccupies Palmer and Davis, who each lead research teams on lung rejection, is what these mechanisms are, and how they can be dampened down to keep patients like Gordon alive.

Innate impulses

Why transplanted lungs succumb to rejection faster than other solid organs is a tricky question.

At first glance, the immune response makes no sense: of all the solid organs, our lungs are designed to deal with foreign matter.

The average person inhales about 26,000 times a day, taking in about 14,000 liters (or 150 bathtubs' worth) of air. With every inhale, we breathe in foreign materials along with our essential oxygen -- gasses and chemicals, particulates and microbes of varying sizes. And our lungs are set up to capture all this foreign material while not overreacting to it.

"The normal process is that the immune system operates to just get rid of the junk -- swallow it up in macrophages and dispose of it," Davis says.

But in a transplanted lung, because the lung itself is not 'self,' these injuries that otherwise would not have any consequence trigger an immune reaction that could degrade the lung and ultimately cause failure.

"We get what seems on the surface to be classic immunologic rejection," says Davis.

When a transplanted heart, lung, or liver is rejected, it's taken down by the body's adaptive immune system: T cells and antibodies are sent out specifically to attack any cell that registers as this foreign type.

Palmer says that in the lungs a different sort of immune rejection may be at work.
"Because the lungs are constantly exposed to the environment, they have an intrinsic set of defense mechanisms that are there to deal with all the stuff you're breathing in."

This is known as innate immunity, and it's a more generic immune response, involving inflammation, a cascade of antagonizing proteins, and a flood of white blood cells.

"My idea is that this facet of the immune system plays a central role in orchestrating and regulating rejection in lung transplant."

It's a new idea, and one that will take time to prove. Palmer is currently looking at how genetic variations correlate to innate immune responses and rates of rejection after transplant.

"The hope would be that someday we could better gauge your risk for rejection after transplant based on some of these genetic variations in your innate immune system," perhaps clearing up the crystal ball to help select which patients might benefit most from transplantation.

Gut reactions

Any toxins, pollution, and infections that a lung transplant patient breathes in have the potential to trigger lung injury and rejection episodes.

But the battle most often begins with the gut.

Lung transplant patients have a high incidence of gastric reflux disease, which puts them at high risk for aspiration events, in which reflux travels into the lungs, sounding the immune system's alarms.

Davis says the high rate of reflux is in large part because the vagus nerve -- which, among many other things, regulates gastric function -- takes a beating during a lung transplant surgery.

Also, patients with end-stage lung disease have a greater amount of reflux in general.

"It may result from coughing and changes in pressure in the abdominal cavities at this stage of disease," he says.

"And the reflux may contribute to the lung disease by injuring the lungs when it's inhaled. We know it's related, and it could also be causative."

Davis's research includes investigating what happens at the point of injury.

"There's a certain amount of bacteria in the aspirate material," he says. "We're looking at whether the protein coats of these bacteria are what's triggering the immune attack on the lung."

Though conclusive explanations of the hows and whys of reflux and aspiration injury are still being fleshed out, it's inarguably a condition that lung patients want to avoid.

Duke has developed very aggressive clinical procedures to prevent aspiration injuries, says Davis, including a surgical stomach-wrapping procedure -- just as it sounds, the stomach is wrapped around the esophagus to prevent reflux from moving into the lungs.

"Our protocol seems to play a large part in our outcomes," Davis says, "and we're taking the observations we're seeing in the clinics back to the laboratory, so that we can use basic research to answer some of the still-unanswered questions."

All hail the inhale

The first breaths Weeks took with his new lungs were not his own; they were the mechanized inspirations and expirations of the ventilator, to which he remained connected for four days after his surgery.

"It was really frustrating," he says. "I'd look over and see that my oxygen level was good, but it felt like I wasn't breathing at all. As Dr. Davis puts it, it takes some time for the lungs to fly."

Weeks spent six more weeks in intensive care, beginning to recover from extreme muscle weakness and adjust to the immunosuppressive drugs that will be his lifelong companions.

"Getting up [for the first time after surgery] was probably the hardest thing ever," he says.

Not because of pain, but because of sheer weakness: before his downward spiral, Gordon was a tall, strong 250 pounds; when he left North Carolina he was down to 160.

"Every day is a different healing," he says. "There are definitely steps in the healing process, and for me it's been a long staircase."

Gordon left the hospital the weekend of July 4, 2007, and went back to the rehab at the Center for Living he'd left so abruptly in April.

He says the staff there taught him -- firmly -- how to bring his body back to life after such a close courtship with death.

"I was so weak that I showed up [to rehab] in a wheelchair. And David Best said to me, 'You're not coming in on a wheelchair anymore. Get yourself a walker if you need to.'

"And so I did, and I used it for a while. Then one day he said, 'Get rid of that walker!' So I kicked it to the side as I walked in the door, and that's where it stayed."

Scott Palmer has two pictures of Gordon Weeks: one taken when he was on ECMO -- about as far from the New England surf as he could be -- and one taken recently at his home in Cape Cod, where he's built back up to 190 pounds and is able to spend most days on the job, which for him is splitting wood -- about as far from ECMO as one could imagine.

Palmer says that, though Gordon's story is particularly hair-raising at times, it's still typical of the everyday miracles he sees in the Duke Transplant Center.

"When I started doing lung transplant," he says, "I told my patients that they have a 50 percent chance of living five years.

"Now I tell them eight years, and it's pretty amazing to see that change in 10 years."

"It's not for the faint of heart," says Gordon of this process of surgical rebirth. "But the drive to live is so strong -- you don't want to let go. And as much as it hurts, and as weak as you are, there is always tomorrow to heal, to get better. Every day you do get stronger."

And his lungs, so far, have kept him flying. "I like to talk to them -- thank them, and thank the person who gave them, even though I don't know who that person is.
"I keep going back to how incredible that part of it is. One forfeits his or her life, but gives life to another, and there are people here who can make it happen."

For more information about organ transplant services at Duke, call the transplant office at 919-684-5926.

Gordon and Shauna Weeks found Duke's transplant outcomes information (and that of other hospitals) on the Web site for UNOS, the United Network for Organ Sharing.
Read more about that organization at unos.org

This article was first published in the Summer 2008 edition of DukeMed Magazine.