Repeated daily exposure to mild intermittent hypoxia increases the auditory and tactile arousal thresholds in patients with obstructive sleep apnea

Background: Exposure to repeated daily mild intermittent hypoxia (MIH) leads to an increase in upper airway patency coupled to a reduction in continuous positive airway pressure (CPAP) used to treat obstructive sleep apnea (OSA). These modifications are associated with an increase in CPAP adherence. In addition, treatment with MIH might impact other factors that influence adherence, including the arousal threshold. Indeed, we showed that exposure to MIH resulted in an increased respiratory arousal threshold. Objective: The present study was designed to extend these findings to determine if increases in the arousal threshold to auditory or tactile stimuli increase after exposure to MIH. These modifications could be advantageous and contribute to increases in CPAP adherence that were previously observed. Methods: A total of 19 participants with OSA, with an apnea-hypopnea index > 5 (AHI), were recruited and randomly allocated to two groups. One group was exposed to repeated daily MIH, while the other group was exposed to sham MIH. Participants in the MIH group [n = 9; age - 45.22 ± 8.66 years; body mass index - 31.59 ± 5.49 kg/m2; apnea hypopnea index (AHI) - 58.39 ± 17.57 events/hr.] 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 [n = 10; age - 47.1 ± 9.48 years; body mass index - 34.79 ± 4.57 kg/m2; AHI - 70.18 ± 22.42 events/hr.] were exposed to compressed room air. Arousal thresholds were measured objectively during sleep using auditory (ear inserted headphones) (MIH - n = 5; Sham -n = 9) and tactile (digital pressure algometer) (MIH - n = 8; Sham - n = 10) stimulation, while participants were treated with therapeutic levels of CPAP. These measures were obtained during sleep studies completed before exposure to MIH or sham MIH, and 4 days, 4 and 8 weeks after exposure. Results: Body mass index (p = 0.18), age (p = 0.66) and AHI (p = 0.22) were similar between the two groups prior to therapy. A significant increase in the tactile threshold measured on the left side was observed 4 days [1.89 ± 1.08 vs. 2.81 ± 1.23 pound-force (Ibf), p = 0.005] and 4 weeks (1.89 ± vs 1.08 ± 1.48 Ibf, p = 0.024) after therapy in the MIH group. This improvement was not evident after 8 weeks (p = 0.16). No difference in the tactile threshold was evident at any point following exposure to sham MIH (P > 0.128 for all comparisons). There was a significant increase in the auditory threshold immediately after treatment with MIH compared to baseline (54.00 ± 2.24 vs. 67.00 ± 11.51 dB, P = 0.031), which was not evident 4 or 8 weeks after therapy. A significant correlation between the auditory and tactile arousal thresholds was also evident when all time points were included (R = 0.48, P = 0.015). The auditory threshold values were similar at all time points in the Sham MIH group (P > 0.52 for all comparisons). Conclusion: Our results suggest that exposure to repeated daily exposure to mild intermittent hypoxia results in an increase in the auditory and tactile arousal threshold level immediately after exposure to MIH, which was sustained for 4 weeks in the case of the tactile threshold. The increase in the auditory and arousal threshold could contribute to the improved adherence to CPAP that we previously reported was evident after repeated daily exposure to MIH. 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.