Repeated Daily Exposure to Mild Intermittent Hypoxia (dMIH) Enhances the Critical Closing Pressure for 4 Weeks in Adults with OSA

Abstract

Background and Objective: dMIH leads to improved upper airway patency, although it is unknown if this improvement is sustained for a prolonged time period. Enhancement of airway patency could lead to improved breathing stability during sleep in individuals with obstructive sleep apnea (OSA). However, exposure to MIH on a single occasion, immediately prior to the documentation of breathing events, induced breathing instability. This may have occurred because exposure to MIH leads to an increase in the ventilatory response to hypoxia, which induces breathing instability, despite improvements in airway patency. If so, enhanced upper airway patency coupled with mitigation of the ventilatory response to hypoxia could be key to improved breathing stability. In the present investigation, we explored if dMIH and the timing of its administration, coupled with abolishment of natural occurring nocturnal hypoxia, initiated the key responses to improve breathing stability for up to 8 weeks. Methods: 19 participants with OSA were randomly allocated to two groups. One group was exposed to dMIH, while the other group was exposed to sham dMIH. 5 participants in each group were also assigned to nightly use of continuous positive airway pressure (CPAP) for the duration of the study. Participants in the dMIH group were exposed to twelve 2-minute hypoxic episodes (PETO2 ~ 50 mmHg) separated by 2 - minute normoxic intervals (with PETCO2 sustained 2 mmHg above baseline) for 15 days. Participants in the sham group were exposed to compressed room air. Two sleep studies were completed before exposure to dMIH or Sham dMIH, as well as, 4 days, 4 weeks, and 8 weeks after exposure. During the initial study, standard sleep measures of sleep architecture and breathing were obtained (NB participants were not treated with CPAP during these studies). Throughout the second sleep study, measures of the critical closing pressure (PCRIT) were obtained. Results: Anthropometric measures were similar between the two groups [n = 9 vs. n = 10; age - 45.22 ± 8.66 vs. age - 47.1 ± 9.48 years; body mass index - 31.59 ± 5.49 kg/m2 vs. 34.79 ± 4.57 kg/m2; apnea hypopnea index (AHI) - 58.39 ± 17.57 vs. 70.18 ± 22.42 events/hr.; P > 0.18 for all comparisons]. Airway patency was enhanced (i.e., a less positive PCRIT) 4 days (3.01 ± 4.040 vs. 5.79 ± 2.76 cmH2O, P = 0.043) and 4 weeks (2.96 ± 3.38 vs. 5.79 ± 2.76 cmH2O, P = 0.038) after exposure to dMIH compared to baseline. This improvement was not evident in the Sham dMIH group (P > 0.168 for all comparisons). Compared to baseline, there was some evidence that the AHI during non-rapid eye movement sleep was improved in the sub-group of participants that were treated nightly with CPAP throughout the dMIH protocol (57.13 ± 5.06 vs. 40.08 ± 12.54 [4 days] P = 0.07 vs. 35.73 ± 8.19 [4 weeks] events/hr.; P = 0.036). However, this improvement was not evident in the dMIH group as a whole. Conclusion: dMIH led to improvements in upper airway patency that were sustained for 4 weeks. Despite the improved airway patency, no significant improvements in breathing stability were evident in the dMIH group as a whole. However, in a sub-group of participants exposed to dMIH coupled to nightly CPAP some improvements were evident. Whether the reduced AHI in this group is a consequence of improvements in airway patency combined with mitigation of the ventilatory response to hypoxia, via the elimination of nightly hypoxemia, requires further investigation. I01CX000125, IK6CX002287, R01HL142757, R56HL142757. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.