A new US study found that lung transplants did not prolong life for the majority of children studied who had cystic fibrosis (CF) compared with CF children who did not undergo lung transplants. However, critics suggest the conclusions may no longer apply because in the US there is a new system for selecting young CF patients for transplants.
The study is the work of lead author Dr Theodore G Liou, associate professor of medicine at the University of Utah School of Medicine in Salt Lake City, and is published in the 22nd November issue of the New England Journal of Medicine.
Cystic fibrosis (CF) is a hereditary disease that affects mainly the lungs and digestive system. The disease causes progressive disability and for some, early death. It is one of the most common life-shortening inherited diseases, affecting 1 in 3,900 children in the US. The disease is more prevalent among Europeans and Ashkenazi Jews, and 1 in 20 people of European descent carry one CF gene.
Liou and colleagues studied 514 patients with CF who were under the age of 18 when they joined a waiting list for lung transplants. The researchers got clinical information on the patients from the CF Foundation national patient registry and the United Network for Organ Sharing (UNOS). The children were on a waiting list for lung transplants between 1992 and 2002.
The results showed that:
- A total of 248 of the 514 children had a lung transplant in the US between 1992 and 2002.
- A statistical method called proportional-hazards modeling identified four variables besides transplantation that were linked with changes in survival.
- Burkholderia cepacia infection decreased survival, whether patients had transplants or not.
- A diagnosis for diabetes before going on the waiting list decreased survival while the patient was on the waiting list, but not after transplant.
- Being older did not affect waiting list survival but decreased post-transplant survival.
- Infection with staphylococcus aureus increased waiting-list survival but decreased post-transplant survival.
- Estimating the effect of tranplant on survival based on age, diabetes status and infection with S. aureus status, revealed that only five patients benefitted, while 315 had a significant risk of harm, 76 patients had an insignificant benefit, and 118 had an insignificant risk of harm.
Liou and colleagues said their study showed there was a clear “improved survival for only 5 of 514 patients on the waiting list for lung transplantation.” They concluded that “Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis,” and called for a prospective, randomized trial to clarify “whether and when patients derive a survival and quality-of-life benefit from lung transplantation”.
A statement from the Cystic Fibrosis Foundation issued on 21st November said that while the study gave important new information about the impact of lung transplants on maximizing the value and success rate of the procedure, its conclusions may not reflect more recent trends because it was conducted at a time when lung allocation was judged on how long a patient had been on the waiting list.
A new organ allocation system was introduced in the US in 2005, after the period studied by Liou and colleagues said the CF Foundation statement. The new system required that children over the age of 11 should be selected based on how sick they were and how much they were likely to benefit from transplant.
The statement from the CF Foundation said:
“While lung transplantation is an important option for CF patients who have severe lung disease and no other treatment options, the study results reinforce the CF Foundation’s approach to treating CF and prolonging life. The key to sustained health and longevity for children with CF is early diagnosis, intervention and comprehensive and sustained multi-disciplinary care. This approach – practised at all CF Foundation-accredited care centers nationwide – has been shown to maximize survival and quality of life in children.”
Dr Preston W. Campbell, executive vice president for medical affairs of the CF Foundation, said that:
“The goal of the CF Foundation is to reach a day when no child with CF should ever need a lung transplant – thanks to advances in treatment and care.”
The CF Foundation is working with Liou and other transplant specialists to find better ways in which lung transplant might help children with CF.
An editorial in the same issue of the NEJM also commented on the study results. Dr Julian Allen, who holds the Robert Gerard Morse Endowed Chair in Pediatric Pulmonary Medicine at The Children’s Hospital of Philadelphia said that:
“The study’s results make it clear that physicians must be more judicious than ever in referring children with cystic fibrosis for lung transplantation, with careful consideration of the severity of the child’s illness.”
Allen said that cystic fibrosis centers must give families appropriate social and psychological support to help them choose the right option for their children.
He also said that the study did not fully explore the impact of lung transplants on quality of life, and the procedure may well have a benefit here. He urged future studies to look carefully at the impact of lung transplants on the quality of life of CF patients, and also measure how closely patients follow the post transplant treatments.
Allen also mentioned the change to the organ allocation system in 2005, and like the CF Foundation, implied the study’s results may not apply to the new arrangement.
“Lung Transplantation and Survival in Children with Cystic Fibrosis.
Liou, Theodore G., Adler, Frederick R., Cox, David R., Cahill, Barbara C.
N Engl J Med 2007 357: 2143-2152
Volume 357:2143-2152, November 22, 2007, Number 21
“Lung Transplantation in Cystic Fibrosis — Primum Non Nocere?”
Allen, Julian, Visner, Gary
N Engl J Med 2007 357: 2186-2188
Volume 357:2186-2188, November 22, 2007, Number 21
Click here for Cystic Fibrosis Foundation.
Written by: Catharine Paddock