(From the May 2015 Issue of PediatricsOnline)
The effectiveness of lung transplantation as a therapy for children with cystic fibrosis has been debated in recent years. Research has showed mixed data related to outcomes after lung transplantation in pediatric patients with CF. Now, a study published in the journal Pediatric Transplantation shows that adolescents aged 16-20 years have the highest mortality rates in this population.
“While there are limited data on outcomes after lung transplant in children with CF, we showed that there is a time period during adolescence where this patient population has a higher risk for death after transplant,” says Don Hayes Jr., MD, MS, medical director of the Advanced Lung Disease program and the Lung Transplant program at Nationwide Children’s Hospital.
Lung transplants for CF patients became controversial when a study published by Liou et al. in 2007 concluded that the majority of pediatric CF patients receiving lung transplants had equal or worse survival compared to those who did not receive a transplant. In 2013, however, Thabut et al. published a study that found a strong survival benefit for adult CF patients who received lung transplants.
Dr. Hayes and his team at Nationwide Children’s hypothesized that there was a time period of high mortality impacting survival for pediatric patients with CF. Indeed, the most important finding of their analysis is the finding that the hazard of post-transplant mortality is highest between the ages of 16 and 20 years among pediatric lung transplant recipients with CF. But this risk declines at later ages. Importantly, the study led by Dr. Hayes also corroborates the benefit in the older CF patients reported by Thabut et al.
They identified a total of 489 pediatric CF patients who were younger than 18 at the time of lung transplant. The survival analysis used post-transplant death or censoring as the outcome and attained age in years as the metric. When post-transplant mortality was plotted over attained age, a window of high risk from 16 to 20 years of age was apparent. A statistically significant difference remained for risk of death between these ages, even when the researchers adjusted the model for potential confounders.
Why this high-risk window exists is a question that Dr. Hayes and his team are working to answer. Factors that likely contribute include physiological differences between adolescent and adult CF patients, nonadherence to therapy and issues related to transitioning from pediatric to adult care, Dr. Hayes suggests. With extensive experience in caring for patients aged 12 to 21 years, Dr. Hayes and his team commonly see patients in this age group participating in risky behaviors despite being educated and understanding the importance of treatments for their health.
“Due to the study design, we cannot determine the cause, but we speculate that it is likely multifactorial. A major factor has to include psychosocial issues, including adherence to therapies,” Dr. Hayes says. “Based on our experience, adolescents with CF have fewer breathing issues and potentially less treatment burden after lung transplantation, leading to a desire to want to escape their chronic illness, so adherence can be an issue for some patients. There may also be physiological issues at play, but that needs further study.”
According to Dr. Hayes, it is of critical importance for children with CF who have undergone lung transplant to work with their health care team to optimize care and identify and avoid risks.
Dr. Hayes is currently working to better define the clinical outcomes of children with CF after lung transplant.
“We are looking at various measures and how they impact outcomes before and after lung transplant at Nationwide Children’s,” Dr. Hayes says. “We also created a harm index — I call it the Lung Transplant Index — we are attempting to improve education about behavioral risk factors and minimize problems related to psychosocial issues through a comprehensive approach to the care of CF patients after lung transplant. We have shown early success and hope to confirm the clinical utility of the index through additional research.”
Hayes D Jr, McCoy KS, Whitson BA, Mansour HM, Tobias JD. High-risk age window for mortality in children with cystic fibrosis after lung transplantation. Pediatric Transplantation. 2015 Mar, 19:206-210.
Liou TG, Adler FR, Cox DR, Cahill BC. Lung transplantation and survival in children with cystic fibrosis. New England Journal of Medicine. 2007 Jul 31, 357:2143-2152.
Thabut G, Christie JD, Mal H, Fournier M, Brugiere O, Castier Y, Rizopoulos D. Survival benefit of lung transplant for cystic fibrosis since lung allocation score implementation. American Journal of Respiratory and Critical Care Medicine. 2013 Jun 15, 187:1335-1340.