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

Abstract

Sleep disturbances are increasingly recognized in children with cystic fibrosis (CF), including those on highly effective modulator therapy (HEMT), but polysomnographic data remain limited and the factors associated with these disturbances are poorly understood. Single-center retrospective review of polysomnographic data from 2015 to 2025 in children with CF to evaluate associations between sleep outcomes and non-pulmonary comorbidities known to affect sleep including iron deficiency, attention-deficit/hyperactivity disorder (ADHD), and anxiety/depression. Sixty children with CF underwent polysomnography (mean age 8.8 ± 4.6 years) with 58% receiving HEMTs for an average of 2.1 ± 1.4 years. Sleep complaints were common overall: snoring (85%), insomnia symptoms (71%), restless sleep (71%), hypersomnolence (29%). Although snoring was more prevalent in the non-HEMT group ( p = 0.008), children on HEMTs had 4.7-fold higher odds of obstructive sleep apnea (OSA), independent of age, nutritional status, adenoid/tonsillar hypertrophy, and dependence on nocturnal feeds ( p = 0.037). They also had poorer sleep efficiency ( p = 0.028) and more prolonged sleep-onset latency ( p = 0.038) as compared to children not on modulators, even after accounting for age differences between the groups. Adenoid/tonsillar hypertrophy and nocturnal feeding both emerged as being significant predictors of OSA, independent of age, nutritional status, and HEMT use ( p < 0.05). Iron deficiency, present in 70% regardless of HEMT use, was associated with restless sleep ( p = 0.0002) and insomnia symptoms ( p = 0.037). ADHD and anxiety/depression, each present in approximately 22% independent of HEMT, were also associated with multiple subjective and objective markers of disturbed sleep. Iron deficiency, neurodevelopmental/mental health comorbidities appear to be common among children with CF undergoing polysomnography and were associated with both subjective sleep complaints and objective polysomnographic abnormalities. Children receiving HEMTs had greater odds of OSA and differences in sleep architecture compared with those not receiving modulators. Nocturnal feedings also appear to adversely influence sleep in children with CF, independent of HEMT use. These findings highlight the importance of considering non-pulmonary comorbidities when evaluating sleep disturbances in pediatric CF and support the need for prospective longitudinal studies to better characterize these associations.