Cystic fibrosis

New tool identifies CF kids at high risk of bronchiectasis progression


A promising new tool could help identify cystic fibrosis patients at high risk for bronchiectasis progression and potentially lead the way to risk-based treatment, Australian clinicians say.

The tool, which sorts children into high or low-risk groups based on their median CF-CT score at five or six years old, was developed using data from 171 patients attending Melbourne or Perth hospitals at three months’ and annually from age one.

It showed 78% of children had bronchiectasis (median CF-CT score 3) by age six, with pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first three years of life and lower airway inflammation being key predictors of future development.

While half the group had a predicted score above the median, 68 returned actual scores above three, making them ‘high-risk’ for progression, lead author and Telethon Kids Institute Paediatric Respiratory Medicine Honorary Research Fellow Dr Daan Caudri and his team wrote in Pediatric Pulmonology.

“Dichotomising the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI: 6.3–27) with positive and negative predictive values of 80% (95% CI: 72%–86%) and 77% (95% CI: 69%–83%) respectively”, they wrote.

Identifying patients’ risk of bronchiectasis progression in early childhood could help physicians move toward more personalised care and researchers select high-risk children for interventional trials, Dr Caudri told the limbic.

“A large proportion [of CF patients under six] does have some evidence of lung damage, but only a very small subgroup has quite significant lung disease,” he said.

Despite this, all patients in this age group, to a large extent, get the same medications and treatments.

For example, all children under two get antibiotic prophylaxis and all children become part of an intense follow-up program, he said.

“The wish and the goal is to, even early on, define which children are most likely to benefit from the intense follow-up program. Maybe there is a subgroup that doesn’t need this level of follow-up, but this remains difficult to define.”

Drug selection

The same goal to define those children likely to have progression also has implications for medications.

“One of the most important changes in the CF world is the advent of modified therapy, [such as] the triple therapy (elexacaftor/tezacaftor/ivacaftor) that is now proven to be effective in adults, though not yet in children,” Dr Caudri said.

He expects that, at some point, there’ll be discussion about whether the drug should be given to children with CF, and if so, whether it should be given to all patients or just those that already have or are likely to develop damage.

“In this case, I think this rule could really be of benefit, either to select those that already have the worst damage or to select those who might be included in clinical trials to see if there is any benefit of the medication in this age group,” he said.

While the tool has shown a lot of promise in a group setting, Dr Caudri and his team said it’s not quite ready for clinical or individual use just yet.

Marked variability in disease expression and progression, even among patients with the same CFTR genotype, makes pinning individual risk challenging, the authors wrote. As a result, they felt their model was best suited to group evaluation.

They also wrote that, though the tool was internally validated, “ideally the model should be externally validated before use in clinical care”.

In future, “novel and more accurate biomarkers are needed to better monitor CF lung disease in clinical care”, the authors wrote, but Dr Caudri hopes the tool will help improve treatment delivery in the meantime.

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