(127) Exploring the Impact of Highly Effective Modulator Therapy on Sleep in Children with Cystic Fibrosis

Background: Cystic fibrosis (CF) is an autosomal recessive chronic respiratory disorder that affects approximately 1 in 3200 live births among Caucasians. Obstructive sleep apnea (OSA) is increasingly being identified as a comorbid condition of consequence among individuals with chronic lung disease, including those with CF. The widespread use of highly effective modulator therapy (HEMT), including ivacaftor and elexacaftor/tezacaftor/ivacaftor, has led to dramatic improvements in nutritional status, lung function and quality of life. The objective of this study is to explore the effects of HEMT on sleep in children with CF.

Methods: This was a retrospective analysis of polysomnographic data and medical records from 2009-2022 in children with CF followed at the Children’s Health Pediatric CF Center in Dallas, TX.

Results: Polysomnographic data were available for 49 children with CF. Mean age of the subjects at the time of polysomnography was 7.0 +/- 4.4 years. Most of our subjects were White/Caucasian (87.8%), but our CF group also included Black/African Americans (8.2%) and Other (4.1%). Of the CF group, 28.6% were Hispanic. Most of our subjects had at least one copy of delF508 mutation (79.6%). Twenty-eight subjects (57.1%) were on HEMT at the time of the study and five subjects (10.2%) were on a different modulator. A diagnosis of OSA was present in 36.7% of subjects with CF. Sleep duration was less in the OSA group as compared to those without OSA (378.3 vs 428.2 minutes). Sleep onset latency was longer (41.9 vs 32.4 minutes) and sleep efficiency was poorer (80% vs. 86%) among those with OSA. Interestingly, the body mass index (BMI) percentile in the OSA group was lower than that of the non-OSA group (54^th vs. 62^nd percentile). Of the 28 subjects on HEMT, only 4 underwent polysomnography after initiation of HEMT. Frequency of OSA post-HEMT was higher as compared to pre-HEMT in our limited sample (50% vs. 33.3%). Polysomnographic data was available post-therapy for all five subjects on a non-HEMT modulator and 60% were diagnosed with OSA in that group.

Conclusions: With improvements in lung health, nutritional status and overall life-expectancy afforded by the use of HEMT, a new comorbid condition, OSA, is quickly emerging in patients with CF. In our limited sample, we found an increase in OSA frequency following use of modulators. A larger study is needed to further elucidate the impact of HEMT on frequency and severity of OSA.

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