A Most Delicate Balance

Vol. 18 • Issue 3 • Page 10

What is Michael Parsley doing right?

Parsley, 50, was diagnosed in 1988 with a rare condition for men: rheumatoid arthritis. Rarer still, it eventually resulted in bronchiolitis obliterans.He waited 2 1/2 anxious years for donor lungs.

“The obliterans was so bad I was on oxygen 24 hours a day and slept with (bilevel positive airway pressure) at night,” he recalled. “I would have to stop three or four times walking up the stairs. It felt like someone had his hands around my throat. You can’t exhale all the air out, so carbon dioxide builds up. It’s like suffocating yourself. My lung function was down to 15 percent.”

After a frustrating series of chronic sinus infections, followed by sinus surgery, Parsley was summoned to Philadelphia’s Temple University Hospital in December 2003, where he received two new lungs. Then, two years after his lung transplant, he needed a kidney transplant.

Yet today, five years after getting two new lungs and three years after getting his brother’s kidney, Parsley has this to say: “My life is back to pretty much normal. The sinus infections are over. I’m not anemic. I have no problems of any kind. It’s a miracle.”

Given lung recipients’ relatively poor survival rates – only half of them live five years – we ask again: What is Michael Parsley doing right?

Exercise, common sense

Parsley “has always been meticulous about taking care of himself,” said his pulmonologist, Gerard Criner, MD, director of Temple University’s section of pulmonary and critical care medicine and its Lung Center. “Michael is diligent with his own care, compliant with his meds. He always had a healthy diet, and he exercised. He has a great family and a pro-active attitude.”

Always a sports/fitness guy, Parsley was working the exercise bike just five days after being transplanted. “I try in summer to bike 15 miles a day,” he said. “I take my dog for a mile-and-a-half walk year round. I use an exercise bike during winter. I just hit 50 a few months ago. I find I’m more active than many healthier people my age.”

Parsley uses common sense to avoid infection, a deadly threat in transplant patients. “Avoid large groups of people, especially during flu season,” he said. “Try to avoid shaking hands. Washing your hands is a huge thing. They tell you ‘Your hands have poison on them.’ I’ve been very fortunate. I’ve only had one sinus infection in five years.”

Parsley is clearly exceptional. Survival rates for lung transplants, Dr. Criner conceded, may never equal those of heart, kidney, or liver transplants because the lungs are open to the environment with each breath. Still, survival has improved 3 percent to 5 percent each decade for a while now, thanks to better antibiotics and more precisely targeted immunosuppression techniques, he said.

Comprehensive follow-up

Some of the best survival rates in the field occur at one of America’s oldest transplant centers: The New York-Presbyterian Center for Lung Disease and Transplantation at Columbia University Medical Center in New York.

Between 2001 and 2008, the program performed 274 lung transplants, with a one-year survival rate of 92 percent, compared to 82 percent nationally, and a three-year survival rate of 78 percent, compared to 65 percent nationally.

The secret is a commitment to comprehensive follow-up care, blood and diagnostic testing, and infusion treatments for special medications.

“Routine post-op care is fairly intensive for all patients,” Medical Director Selim Arcasoy, MD, explained. “Our average hospital stay is about two to three weeks. Once patients go home they come back weekly, sometimes twice a week, for 12 weeks. We obtain chest radiographs, laboratory tests, PFTs, review patients’ written records, medication lists, vital signs – all this for the first three months.”

Regardless of how well or poorly they do, patients have surveillance bronchoscopies at six weeks, then at three, six, nine, and 12 months post-op. If patients have pneumonia, rejection, or another major complication, “we see them weekly but get blood tests even more often to assess kidney and liver functions, electrolytes, cell counts, lipid levels, drug levels, and also check for replication of viral particles in the blood, particularly Cytomegalovirus and Epstein-Barr virus,” Dr. Arcasoy said.

Slow, steady increase in function

In single-lung transplantation, lung function peaks at approximately six months and plateaus thereafter, according to Dr. Arcasoy. For double-lung, it peaks around 12 to 18 months then plateaus.

?”There is no one FEV1that suits all patients,” he said. “We like to see a steady increase or stability in lung function on weekly and, eventually, monthly PFTs until the values plateau.”

Some patients show a decline once they plateau, prompting a bronchoscopy to look for narrowing or softening of the airways, infection, or rejection. “We also look at FVC and mid-expiratory flows,” Dr. Arcasoy said. “Some patients have rejection centered within their small airways, and mid-expiratory flows may decline before FEV1or FVC.”

Infection and rejection threaten all transplant patients. “Patients may acquire infections directly because the lungs remain exposed to infectious particles through inhalation, sinuses, or the digestive tract,” he said. “Gastroesophageal reflux and other exogenous stimuli may also inflame the airways because of immune stimulation.”

Rejection can be acute or chronic. Acute is more inflammatory and reversible with high doses of systemic corticosteroids or lympholytic medications. Acute rejection occurs in 50 percent to 75 percent of patients in the first year; chronic rejection affects more than half by five years.

“Chronic rejection in the lung is much harder to reverse, partially because our detection techniques are limited to PFTs and bronchoscopy and neither technique allows early detection,” he said. “By the time we diagnose bronchiolitis ?obliterans syndrome or chronic lung allograft dysfunction, it is usually very difficult to reverse.”

Immunosuppressive drugs

“Clinicians must achieve a delicate balance within each patient, giving them enough immunosuppressives so they don’t suffer organ ?rejection but not too much so they can stave off infections,” Dr. Arcasoy observed.

Research may create other ways to induce tolerance in recipients besides immunosuppressive drugs that invite infection and entail toxic side effects such as kidney or liver problems and high blood pressure. “New drugs are needed, but how quickly we’ll get them I’m not sure,” he said.

For now, clinicians must set the lowest, safest possible targets for immunosuppression. “Like most things in life, it’s about getting more out of doing less,” Dr. Criner said.

Promising alternatives

Several tantalizing alternatives to lung transplantation offer promise, especially to patients with chronic obstructive pulmonary disease.

For a small subset of COPD patients, lung volume reduction surgery (LVRS) is a very effective alternative, Dr. Arcasoy allowed. “It’s much easier and involves no toxic immunosuppressive meds,” he said. The downside is the effects may not last long; three to five years after surgery the gain in lung function may start to disappear. Transplant patients get a much larger gain in lung function compared to LVRS patients. The disadvantage is the difficulty of maintaining that gain over the years.

LVRS “is a victim of bad press and the perception that it has no perceived benefit,” Dr. Criner said. Moreover, evaluating patients who make the best candidates for LVRS is challenging for the community practitioner, requiring patients to be referred to large medical centers.

Meanwhile, a company experimenting with another promising alternative to lung transplantation, one-way endobronchial valves, has gone bankrupt and is trying to sell its assets, Dr. Criner said. “Hopefully, someone will pick that technology up because there are some patients who will benefit from it.”

Dr. Criner praised two other tried-and-true COPD therapies: pulmonary rehabilitation (PR) and smoking cessation. The clinical trial several years ago that demonstrated the benefit of LVRS in some patients had a welcome side effect: It found that PR helps even the most severe emphysema patients. “That was an important factor that helped convince Medicare to cover PR beginning next year,” he said.

Smoking cessation, Dr. Criner added, is “obviously the most important thing you can do. The Lung Health Study has shown smoking cessation results in an 11.5 percent increased survival at 14 years of follow-up. It’s the one t?herapy that decreases the rate of progression of emphysema and one of the few that improves s?urvival.”

Michael Gibbons is senior associate editor of ADVANCE. He can be reached at [email protected].