Repeated Daily Exposure to Mild Intermittent Hypoxia Improves Sleep Architecture and Sleep Quality in Individuals with Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) is a common medical condition that affects up to 38% of the adult population globally. There are a number of potential mechanisms that contribute to upper airway collapse leading to sleep disruption. These mechanisms include a reduced tonicity of upper airway muscle activity and an increased ventilatory response to arousal. Previously, we showed that exposure to daily mild intermittent hypoxia (dMIH) increases upper airway patency and the arousal threshold to respiratory stimuli. To extend these findings, we hypothesized that dMIH would (i) result in a decrease in the apnea/hypopnea index (AHI) and reduce the ventilatory response to arousal (VRA) and consequently (ii) improve sleep architecture and perceptions of sleepiness (i.e. Stanford Sleepiness Scale). Methods: Nineteen participants with OSA (AHI > 5) were randomly allocated into three treatment groups, Group 1 - dMIH + nightly continuous positive airway pressure (CPAP) (n = 7), Group 2 – nightly CPAP only (n = 6) and Group 3 - dMIH only (n = 6). Individuals who received MIH were exposed to twelve 2-minute hypoxic episodes (PETO 2 ~ 50 mmHg) separated by two 2-minute normoxic intervals (with PETCO 2 sustained 2 mmHg above baseline) for 15 days. Participants in Group 2 were exposed to compressed room air. Measures of AHI, VRA and sleep architecture were measured from full-night polysomnography exams. These studies were completed before exposure to dMIH or sham dMIH, and 4 days, 4 weeks and 8 weeks after exposure. Results: No difference in age (p = 0.90), body mass index (p = 0.97) or AHI (p = 0.65) were evident between groups 1-3 before treatment. In Group 1, the AHI was reduced 4 days (p = 0.021) and 4 weeks (p = 0.013) following treatment compared to baseline. In addition, in Group 1 the VRA was reduced 4 weeks (p = 0.027) and 8 weeks (p = 0.015) following treatment compared to baseline. These changes were not evident in Group 2 & 3. Furthermore, when the follow-up timepoints were averaged (average of 4 days, 4 weeks and 8 weeks), marked improvement in the percentage of time spent in N2 and N3 was most evident in Group 1 (p = 0.005). Collectively, the improvements outlined above were coupled with a perception of reduced sleepiness in Group 1, 4 days (p = 0.009), 4 weeks (p = 0.014) and 8 weeks (p = 0.014) after treatment, which was not evident in Group 2 & 3. Conclusion: Our results suggest that exposure to dMIH treatment combined with nightly CPAP use results in improved upper airway patency as evidenced by a significant decrease in the AHI. These changes were coupled with a reduced VRA and improved sleep architecture. These modifications resulted in a perception of reduced sleepiness. These data indicate that dMIH combined with CPAP may have beneficial effects related to OSA severity and sleep disruption that are not evident following treatment with dMIH or CPAP alone. J.H.M. is supported by the United States Department of Veterans Affairs (I01CX000125, IK6CX002287) and the National Institute of Heart, Lung and Blood (R01HL085537) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.