Retrospective polysomnography links modulators to apnea odds in children with cystic fibrosis

Children with cystic fibrosis who were receiving highly effective modulator therapy had 4.7-fold higher odds of obstructive sleep apnea in a retrospective polysomnography study than children in the comparison group who were not receiving modulators. The association remained significant after the researchers accounted for age, nutritional status, adenoid or tonsillar hypertrophy, and dependence on nocturnal feeds. The modulator-treated group also had poorer sleep efficiency and longer sleep-onset latency, with both differences remaining significant after adjustment for age. The findings concern children referred for overnight sleep testing, so they do not establish that modulator therapy caused the observed abnormalities.

The single-center study reviewed polysomnographic data collected from 2015 to 2025 for 60 children with cystic fibrosis. Their mean age was 8.8 years, with a standard deviation of 4.6 years. Fifty-eight percent were receiving highly effective modulator therapy and had done so for an average of 2.1 years, with a standard deviation of 1.4 years. Researchers examined associations between measured sleep outcomes and non-pulmonary conditions known to affect sleep, including iron deficiency, attention-deficit/hyperactivity disorder, anxiety or depression, adenoid or tonsillar hypertrophy, and nocturnal feeding. Because the investigation was retrospective and observational, its results identify statistical associations within the referred cohort rather than causal effects.

Sleep-related complaints were common throughout the group. Snoring was reported for 85% of the children, symptoms of insomnia and restless sleep were each reported for 71%, and hypersomnolence was reported for 29%. Snoring was more prevalent among children who were not receiving modulators, with a p-value of 0.008, even though the modulator-treated children had higher adjusted odds of polysomnographically measured obstructive sleep apnea. Adenoid or tonsillar hypertrophy and nocturnal feeding were each significant predictors of obstructive sleep apnea independently of age, nutritional status, and modulator use. These findings show that the prevalence of a reported symptom and the presence of an objective sleep abnormality did not follow the same pattern in this sample.

Iron deficiency was present in 70% of the children regardless of whether they were receiving modulators. It was associated with restless sleep, at a reported p-value of 0.0002, and with insomnia symptoms, at a p-value of 0.037. Attention-deficit/hyperactivity disorder and anxiety or depression were each present in approximately 22% of the cohort, independent of modulator use. Both were associated with multiple subjective and objective markers of disturbed sleep. The analysis therefore linked several non-pulmonary conditions with different aspects of sleep disturbance, although the reported findings do not demonstrate that any of these conditions caused the associated symptoms or abnormalities.

Several limitations constrain the interpretation and generalizability of the results. The sample was small, originated from one center, and included only children with cystic fibrosis who had been referred for polysomnography. Referral may have selected children with a greater burden of sleep complaints or medical complexity, and the design cannot determine whether unmeasured factors contributed to the group differences. The groups also differed in age, although the principal analyses adjusted for age and the obstructive sleep apnea result remained significant after accounting for the other included variables. Overall, the data support further investigation of sleep disturbance in children with cystic fibrosis receiving highly effective modulators and of the associations with iron deficiency, neurodevelopmental and mental health conditions, adenoid or tonsillar hypertrophy, and nocturnal feeding. The authors called for prospective longitudinal studies to characterize these relationships more clearly.

Subject of Research: Sleep disturbance and obstructive sleep apnea in children with cystic fibrosis receiving highly effective modulator therapy

Article Title: Sleep disturbances in children with cystic fibrosis on highly effective modulator therapy referred for polysomnography

Article References: Shakkottai, A. (2026). Sleep disturbances in children with cystic fibrosis on highly effective modulator therapy referred for polysomnography. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07594-9

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07594-9

Keywords: cystic fibrosis, children, polysomnography, sleep disturbance, obstructive sleep apnea, highly effective modulator therapy, iron deficiency, ADHD, anxiety and depression, nocturnal feeding, Sleep, disturbances