The circadian system contributes to apnea lengthening across the night in obstructive sleep apnea

Study Objective: To test the hypothesis that respiratory event duration exhibits an endogenous circadian rhythm. Design: Within-subject and between-subjects. Settings: Inpatient intensive physiologic monitoring unit at the Brigham and Women's Hospital. Participants: Seven subjects with moderate/severe sleep apnea and four controls, age 48 (SD = 12) years, 7 males. Interventions: Subjects completed a 5-day inpatient protocol in dim light. Polysomnography was recorded during an initial control 8-h night scheduled at the usual sleep time, then through 10 recurrent cycles of 2 h 40 min sleep and 2 h 40 min wake evenly distributed across all circadian phases, and finally during another 8-h control sleep period. Measurements and Results: Event durations, desaturations, and apnea-hypopnea index for each sleep opportunity were assessed according to circadian phase (derived from salivary melatonin), time into sleep, and sleep stage. Average respiratory event durations in NREM sleep significantly lengthened across both control nights (21.9 to 28.2 sec and 23.7 to 30.2 sec, respectively). During the circadian protocol, event duration in NREM increased across the circadian phases that corresponded to the usual sleep period, accounting for > 50% of the increase across normal 8-h control nights. AHI and desaturations were also rhythmic: AHI was highest in the biological day while desaturations were greatest in the biological night. Conclusions: The endogenous circadian system plays an important role in the prolongation of respiratory events across the night, and might provide a novel therapeutic target for modulating sleep apnea.