Minority of CF Patients Benefit from Lung Transplants

UNIVERSITY OF UTAH HEALTH SCIENCES CENTER NEWS RELEASE

Embargoed by Journal of the AMA for release at 3 p.m. CST Dec. 4, 2001

For information contact:--Phil Sahm, public affairs 801-581-2517, [email protected]--Theodore G. Liou, M.D., office 801-581-7806, pager 801-339-5589, [email protected]--Bruce C. Marshall, M.D., 801-581-7806, [email protected]--Frederick R. Adler, associate professor of mathematics, 801-581-6848, [email protected]

MINORITY OF CYSTIC FIBROSIS PATIENTS BENEFIT FROM LUNG TRANSPLANTS, UTAH RESEARCHERS SAY

Dec. 4, 2001 -- Most cystic fibrosis (CF) patients who receive lung transplants either gain no benefit from the surgery or would live longer if they kept their own diseased lungs, according to a new study by University of Utah researchers.

The findings, to be published in the December 5 issue of The Journal of the American Medical Association, indicate the criterion most often used to pick transplant candidates fails to identify those cystic fibrosis patients who would benefit most from receiving new lungs.

The researchers propose a more complex set of nine criteria, which they contend not only would identify cystic fibrosis patients who may live longer with transplantation, but might also result in shorter waiting lists for lung transplants.

"Our model will help physicians identify the sickest cystic fibrosis patients-who are the ones most likely to benefit from transplantation," said Theodore G. Liou, M.D., the study's lead author and a lung specialist at the University of Utah School of Medicine. Liou, along with two other U lung specialists, Bruce C. Marshall, M.D., and Barbara C. Cahill, M.D., and U mathematical biologist, Frederick R. Adler, Ph.D., collaborated on the study with three other researchers across the country.

Cystic fibrosis patients, after those with emphysema, comprise the second-largest group of recipients of the 1,000 nationwide lung transplants each year. Approximately 150 CF patients receive transplants annually. But with a transplant costing up to $120,000 plus $30,000 a year for medication and follow-up care, lung transplant surgery that provides no benefit wastes time, effort and money.

Rejection is the most common reason patients die following lung transplantation. The median survival after a lung transplant is 4.6 years.

For their study, the researchers included 468 cystic fibrosis patients nationwide who received lung transplants from 1992 through 1997. Using their new criteria, the researchers divided the patients into five groups and compared each group's five-year survival with a matched group of non-transplanted CF patients.

The sickest transplant patients, with less than a 30 percent expected five-year survival rate, experienced slightly lower survival for the first six months following transplantation. But after five years, these patients were three times more likely to be alive than equally sick patients who had not received transplants, the study found.

Patients with a 30 to 50 percent expected five-year survival rate had lower survival for the first three years after transplantation. Five years after transplantation, the group's survival rate was statistically no different from similar patients who had not received transplants.

The remaining transplant patients, whose expected five-year survival rates ranged from 50 percent to 100 percent, showed a significant survival decrease compared with an equally sick group of non-transplant patients, the authors found. In other words, these patients died sooner than they would have been expected to without a transplant.

The current criterion for determining which cystic fibrosis patients receive lung transplants is based on a measure called Forced Expiratory Volume 1 (FEV 1). FEV 1 is the amount of air, after a full breath, a patient can blow out in one second. Patients with FEV 1 of less than 30 percent of normal are considered likely candidates for lung transplantation. Using this measurement, 1,000 to 1,500 cystic fibrosis patients nationwide may be recommended for the transplant waiting list at any given time. Patients on the list wait an average of two years for a transplant.

Because of the waiting-list length, it appears physicians don't always follow the FEV 1 criterion and that some cystic fibrosis patients may be put on the list prematurely, Marshall said. "If doctors wait until their patients are ready for a transplant, the waiting list is so long, the patient could die," he said.

Although FEV 1 is the best single predictor of survival with CF, it, by itself, doesn't identify the sickest cystic fibrosis patients who would benefit most from a transplant, the researchers concluded. They identified eight other criteria that determine the sickest cystic fibrosis patients and those who would benefit most from a transplant.

Those other criteria include: sex (females with cystic fibrosis tend to be sicker); age (older cystic fibrosis patients generally are sicker); weight (the more underweight someone with cystic fibrosis is, the sicker he or she tends to be); pancreatic function (cystic fibrosis destroys the pancreas in most patients, which makes it more difficult to digest food); diabetes mellitus (this complication makes cystic fibrosis patients more sick); the absence of infection by Staphylococcus aureus; presence of a multi-resistant bacterium called B. cepacia; and the number of acute exacerbations, or worsening of symptoms, the patient experiences.

The authors developed a mathematical model that includes a checklist of these criteria to help determine whether a patient can benefit from transplantation.

Using these criteria might reduce the number of cystic fibrosis patients recommended for the transplantation waiting list from up to 1,500 under the current system to approximately 150, the authors concluded. That, in turn, may shorten the waiting list for all lung transplants, because cystic fibrosis patients who would live longer without a transplant would no longer be considered viable candidates.

But expanding the criteria would take a national policy decision, something that won't happen quickly, the authors said.

While the study assessed survival of CF patients who received transplants, the authors did not address quality of life for transplant recipients. Their study may, however, provide an objective framework for CF patients and their physicians to assess quality of life surrounding transplantation, the researchers said.

Cystic fibrosis is a hereditary disease that attacks multiple systems in the body, including the lungs and gastrointestinal tract. CF causes excess mucus to form in the lungs, turning them into a breeding ground for bacteria. People with the disease typically have a cough that produces phlegm, as well as shortness of breath that limits physical activity. Difficulty with digesting food often leads to malnutrition. There are treatments to slow the progression of the disease, but there is no cure.

In the late 1930s, the median survival age for cystic fibrosis patients was six months. Today, because of advances in medical care, the median survival age is 32.

The Intermountain Cystic Fibrosis Center is the only accredited CF center in the Intermountain Region. The center, based at University of Utah Hospitals & Clinics and Primary Children's Medical Center in Salt Lake City, cares for nearly 400 CF patients.

University of Utah Hospital performs up to 15 lung transplants a year. But transplants for cystic fibrosis patients at the U have been rare, only three to date.

The study authors include: Theodore G. Liou, M.D., and Barbara C. Cahill, M.D., both assistant professors in the U medical school's Division of Respiratory, Critical Care and Occupational Medicine; Liou has received a Schwachman Clinical Investigator Award from the Cystic Fibrosis Foundation; Cahill serves as medical director of the University of Utah Hospital lung transplant program; Bruce C. Marshall, M.D., associate professor in the respiratory division and co-director of the Intermountain Cystic Fibrosis Center; Frederick R. Adler, associate professor of mathematics at the U; Stacey C. FitzSimmons, Ph.D., formerly with the Cystic Fibrosis Foundation, now of FitzSimmons and Associates; David Huang, School of Public Health, University of California at Los Angeles; and Jonathan R. Hibbs, M.D., director of the Microbiology Lab, New York State Department of Health.

University of Utah Health Science CenterOffice of Public Affairs50 N. Medical DriveSalt Lake City, UT 84112(801) 581-7387

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