Better Lung Function in US Than UK Children Linked to Treatment Differences

Children in the U.S. with cystic fibrosis (CF) tend to have better lung function than young people with the disease in the U.K., a new study has found, with researchers saying the disparity is likely due to differences in treatment between the two countries.

In the U.S., children are more likely to receive treatment — and at a younger age — to break up the thick mucus that characterizes CF, the investigators found.

These findings were published in Thorax, in a study titled “Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data.”

A prior study, using data from 2010, also had suggested that CF children in the U.K. tend to have worse lung function than those in the U.S., though no such difference was found among adults. However, researchers were unsure of why this difference existed and why it was only apparent early in life.

In the new study, a team led by researchers at the University of Liverpool used data from U.S. and U.K. patient registries to explore how lung function changed over time — from age 6, when measurements were started, to the end of childhood at age 18. The data, collected between 2003 and 2014, came from the U.S. Cystic Fibrosis Foundation Patient Registry and the U.K. Cystic Fibrosis Registry.

“It is important to understand the causes of the observed differences and it is really exciting that the CF Registry data are available to help us gain potentially valuable insights into optimal treatment and care,” Daniela Schlüter, PhD, the study’s lead author, said in a press release.

In total, the researchers assessed data from more than 12,500 children — 9,463 in the U.S. and 3,055 in the U.K. The two groups were largely similar in terms of demographics. Of note, the researchers restricted their analysis to only children who were homozygous for the F508del mutation in the CFTR gene, which is the gene that’s defective in CF patients. F508del is the most common CF-causing mutation, and being homozygous means the children had the same mutation in both copies — each person has two — of the CFTR gene.

The team used statistical models to assess how lung function — as measured by forced expiratory volume in one second, or FEV1 — changed over time. FEV1 measures how much air a person can exhale during a forced breath.

In line with prior results, the models illustrated that lung function tended to be worse among children in the U.K., compared with their U.S. counterparts. The rate of decline in lung function was faster in the U.K. than in the U.S. Exact differences varied somewhat depending on the specific mathematical models used, but the same general trend was evident across models.

The researchers then looked for differences between the two groups that might account for these results. They found that children in the U.S. were more likely to receive mucolytic therapy — treatments, such as rhDNase and hypertonic saline, that aim to break up the thick mucus that characterizes CF.

Specifically, 73% of children in the U.S. were treated with rhDNase before age six, as compared with 20% in the U.K. By age 18, rates of rhDNase use were 96% in the U.S. and 86% in the U.K.

Hypertonic saline was prescribed for 76% of CF children in the U.S. and for 50% of children in the U.K. before age 18.

“We found that children in the US received more aggressive mucolytic therapy earlier in life than children in the U.K.,” Schlüter said. “Further research will be needed to unpick the impact of different treatment patterns and study further potential underlying causes.”

The team also noted that, while rates of inhaled antibiotic use were generally comparable in the U.S. and the U.K, there was “a big difference in the inhaled antibiotic of choice between the two countries.” Children in the U.S. were more likely to be prescribed tobramycin, while those in the U.K. were more likely to get colistin, also known as polymyxin E, the researchers said.

No significant differences were found in early growth, nutrition, or Pseudomonas aeruginosa infection.

While it cannot be definitively concluded that these differences in treatment account for the variations in lung function, the researchers emphasized that analyzing the different therapies may be a useful starting point for further studies. The team also noted several limitations of their analysis, including the specific group of children studied.

“Our study was limited to people aged 6-17 who were homozygous for the F508del mutation and used data that pre-ceded the licensing of CFTR modulator therapies,” Schlüter said. “Therefore, the results may not apply to people over the age of 18 or those with a different genotype, and the introduction of modulators may have changed the observed trend.”

The emergence of new therapies have improved treatment options for all CF patients, said Rebecca Cosgriff, director of data and quality improvement at the U.K. Cystic Fibrosis Trust.

“Since this study was undertaken, access to modulator therapies has increased dramatically,” Cosgriff said. “Comparative studies will continue to play an important role as we work to ensure people in the UK have the best possible treatment for cystic fibrosis.”