Lung transplants may shorten, rather than prolong, the lives of children who have cystic fibrosis, according to University of Utah research published Thursday in The New England Journal of Medicine.
The findings are not true of survival for adults with CF who have transplants. And it doesn't mean the transplants should never be done in children, said Dr. Theodore G. Liou, principal investigator and associate professor of internal medicine at the U. School of Medicine. But better ways are needed to decide which children with CF are the best candidates for transplants.
The trick and what calls for more research is figuring out the sickest possible person who will survive transplantation, Liou said. "That turns out to be really hard. The operation is so big, and there are so many risks involved."
Cystic fibrosis creates excess thick mucus in the lungs and gastrointestinal tract, increasing coughing, infection and shortness of breath, as well as leading to malnutrition. Treatment slows, but does not cure, the disease. The median age of death for people with CF is 25, but a few decades ago it was less than a year old. Therapies have improved greatly, Liou said.
The researchers analyzed data from 514 patients 18 and under on the U.S. lung transplantation list from 1992-2002. Only one patient of the 248 who received a lung transplant showed clear benefit. Nearly two-thirds (162) were at higher risk of dying after the procedure, while benefit or increased risk was not clear for the others.
"We shouldn't expect lung transplantation to prolong their lives," said Liou, also of the U.'s Intermountain Cystic Fibrosis Center. "It appears to more often shorten them."
Researchers hope the study will spark discussion and research to determine which children would benefit from new lungs, he said. "Every physician involved with lung transplantation can think of a patient on death's door who popped up and thrived a miracle of modern science. But we don't have a way of reliably finding those patients."
The researchers were startled by and at first questioned the findings, said Liou. The journal's online supplement details the pains they took to verify their results, he said.
They got a boost in credibility from the study's third author, Sir David Cox. Cox, a Ph.D., is one of the 100 most-cited authors in the world and more than 30 years ago created "proportional hazards modeling," a statistical technique that analyzes survival expectations related to such events as lung transplants. They thought he would suggest someone to help them. Instead, he offered to do it himself, guiding and verifying their results from the University of Oxford, where he's a professor.
The study points out the need for CF patients to stick with their standard therapy and medicine regimens to improve their survival chances, said Liou and co-authors Frederick R. Adler, Ph.D., U. professor of biology and mathematics, and Dr. Barbara C. Cahill, associate professor of internal medicine and medical director of University Health Care's Lung Transplant Program.
Using Cox's proportional hazards model on 26 statistical variables that might predict health hazards related to the procedure, they found three that affect after-transplant survival: age at time of transplant, the harm increasing with age through 18; the presence of S. aureus staph infection; and whether a patient had diabetes before the transplant.
The risk of death after lung transplantation increases as children age, especially if the child was infected with S. aureus before or at the time of the surgery. At 17, children with S. aureus had almost a sevenfold increase in their chance of dying after transplantation.
Oddly, while the bacteria hurt survival after a lung transplant, it increases it before, probably competing with and lessening damage from Pseudomonas aeruginosa, a harmful organism that lodges in the airways of CF patients.
Diabetes is a common outcome of lung transplantation, so children who already had the disease didn't get an "added burden" on their survival chance.Researchers were not able to determine quality of life benefits from getting new lungs.
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