Mild Intermittent Hypoxia Reduces the Critical Closing Pressure and Continuous Positive Airway Pressure Resulting in Improved Treatment Adherence
Authors: Panza Gino Severio , Puri Shipra , Rimar Caroline , Lin Ho-Sheng , Mateika Jason 
Published: April 2020

Study ObjectivesAdherence to continuous positive airway pressure (CPAP) therapy is low in part because of patient discomfort initiated by high therapeutic pressures (TP). Improved adherence could ultimately lead to more effective treatment of co‐morbidities linked to sleep apnea. Daily exposure to mild intermittent hypoxia (MIH) initiates long‐term facilitation of upper airway (UA) muscle activity. Initiation of this form of plasticity could increase UA patency and as a result decrease the TP required to treat obstructive sleep apnea (OSA). Therefore, we investigated if repeated daily exposure to MIH reduces the TP and UA critical closing pressure (passive = PCRIT, active = ACRIT). Likewise, we examined if reductions in the TP were linked to improved CPAP adherence.MethodsNine hypertensive males with OSA were treated with twelve 2‐minute episodes of hypoxia (PETO2 ≈ 50 mmHg) separated by 2‐minute intervals of normoxia each day for a period of 15 days over 3 weeks (i.e. 5 days/week). PETCO2 levels were sustained at 1–3 mmHg above baseline during MIH administration. Five matched participants were exposed to a sham protocol comprised of 2‐minute episodes of room air. Both groups were treated with in‐home CPAP during the 15 day protocol. Prior to exposure to MIH the critical closing pressure and TP were determined. Mid‐way and at the end of the protocol, measures of the critical closing pressure and TP were repeated. If the TP was reduced following measures at the mid‐point of the protocol, the in‐home TP was adjusted accordingly.ResultsFollowing MIH, the TP was reduced (12.3 ± 0.6 to 9.9 ± 0.6 cmH2O (p ≤ 0.001) which was accompanied by a reduction in PCRIT (4.9 ± 0.8 to 1.3 ± 0.7 cmH2O, p ≤ 0.001) and ACRIT (3.6 ± 0.7 to 0.7 ± 0.9, p ≤ 0.01). Additionally, in‐home CPAP adherence improved in the latter half of the study as the hours per night (4.0 ± 0.7 vs 5.5 ± 0.7, hours/night, p ≤ 0.05) and the number of days associated with CPAP therapy greater than 6 hours/night increased following MIH (22.0 ± 8.0 vs 36.0 ± 10.0 percent of available days, p ≤ 0.05). No changes in TP, critical closing pressure, or adherence were found in the sham group. After the protocol, hours per night (5.5 ± 0.7 vs 3.11 ± 0.9, p = 0.06) and the number of days of CPAP therapy greater than 6 hours (3.2 ± 0.9 vs 0.6 ± 0.6, p = 0.06) trended towards significance when compared to sham. However, the MIH group had significantly greater in‐home CPAP use of greater than 4 days when compared to sham following the study protocol (5.3 ± 0.9 vs 1.4 ± 0.7, p ≤ 0.01). A significant correlation between the change in TP (Post‐Pre) and hours of night the CPAP was worn (fraction of baseline) was found following MIH (R2 = 0.8, p ≤ 0.01).ConclusionMIH improved upper airway patency as suggested by the reduction in TP and decrease in critical closing pressures. The reduced TP was coupled to improvements in CPAP adherence. Improved CPAP adherence might ultimately lead to improved treatment of co‐morbidities linked to sleep apnea.Support or Funding InformationDepartment of Veterans Affairs (I01CX000125 & 15SRCS003 JHM, 1IK1RX002945 GSP), and National Institutes of Health (R56HL142757 & R01HL142757 JHM).