Gothenburg, Sweden – Children with cystic fibrosis (CF) who were treated with Kaftrio (elexacaftor/tezacaftor/ivacaftor) maintained stable lung function over one year after reducing the frequency of hypertonic saline and other airway-clearance treatments, according to a prospective multicentre study.
The reduction in treatment frequency was also associated with fewer days of antibiotic use, while respiratory symptoms and the types of bacteria detected in airway cultures remained generally stable. The findings suggest that reducing airway-clearance treatments from twice daily to once daily may be feasible for some clinically stable children receiving Kaftrio, which is sold as Trikafta in the U.S.
“Reducing treatment frequency to once daily may therefore increase flexibility and support a more normal everyday life,” the researchers wrote.
The study, titled “Once-daily hypertonic saline inhalation and airway clearance techniques in children with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor: a prospective multicentre study,” was published in the Journal of Cystic Fibrosis.
Evidence for reducing maintenance therapies remains limited
CF is caused by mutations in the CFTR gene, which result in the production of an absent or dysfunctional CFTR protein. This causes thick, sticky mucus to build up in several organs, particularly the lungs, leading to many of the symptoms associated with the disease.
The introduction of highly effective CFTR modulators, including Kaftrio, has substantially improved lung function, respiratory symptoms, and quality of life for many children with CF.
These improvements have raised questions about whether intensive maintenance treatments, such as hypertonic saline inhalation and airway-clearance techniques (ACTs), need to be continued at the same frequency. However, evidence on safely reducing these therapies remains limited.
To investigate this question, researchers in Sweden followed 46 children with CF between December 2023 and November 2024. The participants were between 6 and 17 years old, with a mean age of 12.1 years, and 63% were boys. They had been receiving Kaftrio for an average of 12.7 months.
Participants reduced hypertonic saline and airway-clearance treatments
Before entering the study, all participants had been prescribed nebulized hypertonic saline twice daily. A short-acting bronchodilator was recommended before the treatment, followed by individually prescribed ACTs.
Positive expiratory pressure mask therapy combined with huffing — a breathing technique designed to help loosen and clear mucus from the airways — was the most commonly used ACT.
Participants and their caregivers were given the option of reducing the prescribed frequency of both hypertonic saline and ACTs from twice daily to once daily for one year.
Lung function remained stable
Overall, lung function remained stable during the 12-month period after treatment frequency was reduced.
The lung clearance index, a measure of how effectively air moves through the lungs, showed a small improvement, but the change was not statistically significant. Forced expiratory volume in one second (FEV1), which measures how much air a person can forcefully exhale in one second, and forced vital capacity (FVC), the total amount of air that can be exhaled after taking a deep breath, also showed no meaningful changes.
Respiratory symptoms remained stable throughout the study, based on the respiratory domain of the Cystic Fibrosis Questionnaire-Revised.
Antibiotic use decreased
The number of days participants required antibiotics fell by 39%, from 47 days to 28.6 days per person over one year. Oral antibiotic use decreased by 33%.
Inhaled and intravenous antibiotics were uncommon during both treatment periods.
The types of bacteria detected in airway cultures were also generally similar before and after the reduction in treatment frequency. Pseudomonas aeruginosa, a bacterium associated with lung disease in people with CF, was detected in two participants during the twice-daily treatment period and in none after treatment was reduced.
Researchers call for individualized treatment decisions
The researchers said the findings suggest that treatment reduction could be considered for clinically stable children with preserved lung function who are receiving Kaftrio.
“For clinically stable children with preserved lung function, treatment reduction may be considered as part of an individualised approach to CF care in the [Kaftrio] era,” they wrote.
However, the researchers emphasized that reducing maintenance therapies should be accompanied by regular monitoring. Sensitive measures may be needed to identify early changes in airway disease before lung function or symptoms deteriorate.
The study also has important limitations. Most participants were clinically stable and had preserved lung function, meaning the findings may not apply to children with more advanced CF or more severe lung disease. Further research is therefore needed to determine which patients can safely reduce airway-clearance treatments and to confirm the long-term effects of doing so.
Contact
Prof. Marcus Svedberg
Gothenburg University, Sweden