Original Article 2, Issue 13.3

Improvements in Sleep Apnea Specific-Hypoxic Burden With an Expiratory Pressure-Enhanced Mandibular Advancement Device

http://dx.doi.org/10.15331/jdsm.7454

Kari Lambing, PhD2; Antonella Conflitti, CCPA1,2; Hilary Reiter, DMD1,3; Winston Rajkumar, MD2; Rami Al Metwali, BPharm1; Akash Sharma, BSc, BA1; Paulette Pillersdorf, DDS1; George Abraham, MDS1; Sat Sharma, MD1,2

1Centre for Sleep and Chronobiology, Toronto, Canada; 2Windsor Sleep Disorders Clinic, Windsor, Canada; 3TRS Waterloo Sleep Institute, Waterloo

ABSTRACT

Study Objectives:

The objective of this study was to assess the therapeutic efficacy of an oral appliance combined with an oral expiratory positive airway pressure accessory using sleep apnea–specific hypoxic burden (SASHB) versus apnea-hypopnea index (AHI). Efficacy of this device has not been previously determined using SASHB criteria.

Methods:

Twenty-five adults with moderate obstructive sleep apnea (OSA) completed baseline diagnostic polysomnography (PSG). Participants used the combination at home for 6 months, then underwent repeat in-laboratory PSG while using the combination therapy.

Results:

Treatment with the combination therapy was associated with a reduction in AHI from 23.40±2.26 events/h to 6.98±2.02 events/h (P<0.001) and SASHB from 95.34±13.12%min/h to 22.48±4.08%min/h (P<0.001). Mean AHI reduction was 69.8% and mean SASHB reduction was 76%. The percentage of treatment responders was 92% using an AHI-based definition of therapeutic efficacy (<10 events/h) and 100% using an SASHB-based definition of therapeutic efficacy (<53%min/h) and remained 100% with more stringent criteria of less than 34%min/h. When comparing the percent improvement between the two metrics, improvement was significantly less when using AHI (M=69.83, SD=9.64) than when using SASHB (M=75.73, SD=7.00; t(24)= –2.22, p=0.036).

Conclusions:

Use of AHI criteria would have misclassified several individuals as nonresponders who responded to the expiratory pressure–enhanced mandibular advancement device based on more meaningful SASHB criteria. These results suggest that traditional methods for assessing OSA may be inappropriately restrictive and that the therapeutic efficacy of oral appliance therapy may be higher than previously reported. This study strongly endorses use of clinical benefit along with SASHB reduction as benchmark for efficacy of oral appliance therapy.

Keywords:

Oral Appliance Therapy, O2Vent Optima, ExVent, Sleep Apnea–Specific Hypoxic Burden, Obstructive Sleep Apnea

Citation:

Lambing K, Conflitti A, Reiter H, Rajkumar W, Al Metwali R, Sharma A, et al. Improvements in Sleep Apnea Specific-Hypoxic Burden With an Expiratory Pressure-Enhanced Mandibular Advancement Device. J Dent Sleep Med. 2026;13(3).

INTRODUCTION 

Hypoxia associated with repeated obstructive respiratory events during sleep contributes to oxidative stress, activation of the sympathetic nervous system, and endothelial dysfunction, which can have long-term consequences for cardiovascular health.1 Untreated severe obstructive sleep apnea (OSA) is associated with an elevated risk of long-term major adverse cardiovascular events (MACE; defined as coronary heart disease, heart failure, stroke, or cardiovascular mortality), but that risk can be reduced with continuous positive airway pressure (CPAP) treatment.2 OSA also poses a large economic burden on society, in part through utilization of health care resources for cardiovascular disease.3 Thus, effective treatment of OSA is important not only to reduce the risk of MACE but also to lower health care costs.

Various treatments are available for OSA, but the gold standard is CPAP. There is some evidence of beneficial effects of CPAP on long-term cardiovascular outcomes and mortality, but the long-term benefits of CPAP are hindered by low rates of adherence, which range from 30% to 60% across studies.4, 5 Oral appliance therapy (OAT) is an alternative approach that significantly reduces the apnea-hypopnea index (AHI) across all severities of OSA.5–8  Although both OAT and CPAP lead to improvements in AHI and oxygen saturation, the degree of improvement is often larger with CPAP.5,6 However, when cardiovascular outcomes, such as blood pressure,9 endothelial function,10 and arterial stiffness7, 11 are considered, the two treatments are comparable and produce similar benefits for overall cardiovascular health and mortality. Furthermore, patients generally prefer OAT (with more than 70% of patients preferring OAT over CPAP in one study8), leading to higher self-reported adherence with OAT.8, 12 Improved patient adherence with OAT may ultimately result in comparable long-term outomes.7, 13

Although AHI is the marker typically used to demonstrate therapeutic efficacy of OSA treatment, it is a poor predictor of MACE.14 This is likely at least partly because AHI considers only the frequency of apneas and hypopneas, not the variability, duration, and depth of oxygen desaturation. Thus, other markers have been explored to better assess the overall clinical effects of OSA treatment.15 The sleep apnea–specific hypoxic burden (SASHB) is a novel metric that captures respiratory event–associated oxygen desaturation depth and duration, information that is not included in the frequency counts of AHI. Compared to AHI, SASHB is a better predictor of cardiovascular morbidity and mortality, as well as overall mortality.14, 16 SASHB may also be a better predictor of OSA treatment response. A recent study of OAT found a much higher therapeutic response rate using SASHB as the marker of efficacy (more than 95%), compared to AHI (78%), across all severities of OSA.17

O2Vent Optima is a therapeutic device that incorporates mandibular advancement and an air channel to bypass nasopharyngeal obstruction.18 It can be used with an ExVent accessory that provides oral expiratory positive airway pressure (EPAP).19 This combination therapy passively dilates the airway, resulting in reduced apneas, improved oxygen saturation, and high adherence during long-term therapy.20, 21

The objective of this study was to assess the therapeutic efficacy of MAD with EPAP therapy using SASHB versus AHI as the marker of efficacy. Efficacy of this device has not been previously assessed using SASHB, a metric that may be particularly useful for capturing the nuances of disease improvement that are important for ultimate cardiovascular health.

 

METHODS

Study Design and Participants

This prospective study was conducted at four clinical sites across Canada (Centre for Sleep and Chronobiology – College and Wilson sites Toronto, Windsor Sleep Disorders Clinic, Windsor and TRS Waterloo Sleep Institute, Waterloo). The study is registered at ClinicalTrials.gov (NCT05954026). The study protocol received ethical approval from an Independent Review Board, WCG IRB Connexus. All participants provided written informed consent prior to any study-related procedures.

The final dataset included 25 adults with a diagnosis of moderate OSA (AHI >15 and <30 events/h) who had acceptable dentition (Upon dental examination, the sleep dentist ensured sufficient anchoring value, adequate retentive morphology of teeth, and absence of any significant temporomandibular joint issues) and were considered appropriate candidates for OAT. The exclusion criteria were age younger than 22 years, active oral infection, comorbid sleep disorder, any previous surgical treatment for OSA, previous or concurrent CPAP therapy, or current enrollment in another research study. Nineteen out of 47 participants were excluded either based on inclusion/exclusion criteria or because they did not want to proceed with the OAT. All patients meeting the inclusion criteria were invited to participate in the study. Recruitment was conducted from approximately March to September of 2022. Figure 1 shows the study flowchart.

Study Procedures

 Initial Diagnostic Phase: Patients were initially screened for participation during overnight in-laboratory diagnostic polysomnography (PSG) to confirm the diagnosis of moderate OSA and obtain baseline AHI, SASHB, and other PSG values. Demographic data were collected for all participants, including age, sex, height, weight, prior OSA treatments, current prescription medications (name and dosage), and the presence of severe nasal allergies, sinusitis, or nasal blockages. Participants then completed a dental and clinical examination, after which they were fitted with the appliance.

Home Phase: Participants were instructed on the insertion, removal,  and titration of the device by adjusting the size of the protrusion bands. For the initial jaw position, the bite was registered at 50% of maximal mandibular protrusion. Subsequent titration was overseen by a sleep dentist, who made adjustments as needed for patient comfort and based on whether there was improvement in symptoms, such as snoring and subjective sleep quality. The device has 1-mm protrusion or retrusion bands, and the initial jaw position is set at 50% with band #19, which can be reduced in size to affect protrusion. The bands available for titration ranged from size #21 to #13.

 Participants were asked to wear the combination therapy nightly for 24 weeks and record their usage. They received phone calls from study personnel at 1, 3, 6, and 8 weeks after study entry to assess adherence. Patients additionally reported nightly usage in an online questionnaire. Participants were considered successful users and were considered to have completed the home phase of the study if they met these adherence criteria: device use for 4 or more hours per night on 5 or more nights per week.

Follow-up Phase: Participants meeting the adherence criteria were invited to undergo follow-up in-laboratory PSG, during which they wore the combination therapy. 

Polysomnography and Outcome Measures

 In-laboratory overnight PSG was performed using the Alice 6 LDX Diagnostic Sleep System (Phillips Respironics, Murrysville, PA), which included electroencephalography (frontal, central, and occipital), right and left electrooculography, electromyography (leg), a Pro-Tech Pro-Flow nasal cannula (Phillips Respironics, Murrysville, PA), a pressure transducer for nasal airflow assessment, a piezoelectric vibration sensor for snoring evaluation, thoracic and abdominal respiratory effort belts, a body position sensor, three-lead electrocardiography, and a wrist pulse oximeter. Baseline and follow-up data extracted from the PSG studies included the study date, time at lights off and on, total sleep time (TST), all technologists’ notes, AHI, supine AHI, rapid eye movement (REM) AHI, non-rapid eye movement (NREM) AHI, mean pulse oximetry oxygen saturation (SpO2), nadir SpO2, arousal index, percent hypopneas, and sleep efficiency. PSG results were scored by registered sleep technologists and interpreted by the sleep physicians, who were blinded to the study treatment or even whether the patient was included in the study.   Apnea was defined as a decrease in airflow by ≥90% from pre-event baseline for ≥10 seconds. Hypopnea was defined as a decrease in airflow by ≥30% for ≥10 seconds and accompanied by a ≥3% decrease in SpO2 or an arousal.

SASHB was calculated as previously suggested by Martinez-Garcia et. al.22 Briefly, SASHB was determined from the area under the desaturation curve, defined by an individualized search window. SASHB was calculated as the sum of the desaturation areas divided by the TST. Treatment efficacy was defined as an SASHB <53%min/h, as values exceeding this cutoff have been associated with adverse cardiovascular outcomes in the Osteoporotic Fractures in Men dataset.14 As a stricter criterion, we assessed the lower boundary of the quintile below the quintile in which significant associations with cardiovascular disease risk were found in previous literature. For AHI, therapeutic efficacy was defined as an AHI <10 events/h (no longer meeting the criteria for moderate OSA). Previous research on OAT has used these same cutoff values23. As a stricter criterion, fewer than 5 events/h (no longer meeting criteria for mild OSA) was also investigated.
 

Combination Therapy Device

 This study tests an oral appliance that has been demonstrated to provide safe and efficacious treatment of OSA and high patient compliance23. The appliance consists of two dental trays with connector bands that can be adjusted to titrate the device from 13 mm to 21 mm. The device is composed of medical-grade nylon and is three dimensionally-printed to fit the individual patient based on three-dimensional scans. The MAD provides mandibular advancement and contains an airflow channel that provides an additional open airway to circumvent airway obstruction by the tongue or nasal congestion. The EPAP accessory is a valve that can be inserted into the channel. It allows air to enter freely during inhalation but closes during exhalation, providing EPAP as expired air travels through smaller vents.19 All study participants used medium resistance (yellow) valve that provides an approximate resistance of 5cmH20/L.21
 

Statistical Analysis

 The minimum sample size was determined based on data from a comparable group of patients,24 in whom OAT was associated with a mean AHI change of −8.37 from baseline, with a standard deviation of 7.73. With alpha set at 0.05 and power at 0.80, it was determined that 9 participants would be necessary to observe a significant treatment effect. To account for the imperfect predictability of historical data, a greater number of patients were enrolled to ensure adequate power. Additionally, more patients were collected to account for a relatively high expected dropout rate, or exclusions for screening failure, inappropriate candidates for OAT, nonadherence, technical failures, and patient dropout over the entire duration of the study.

Descriptive statistics were used to report the demographic characteristics of the study participants. Continuous data were reported as mean ± standard deviation. Paired-sample t-tests were used to test for differences between baseline and postintervention sleep and sleep-related respiratory variables. Because multiple tests were conducted, the Benjamini and Hochberg method was used for controlling the false discovery rate, with 12 comparisons.24 Variables that violated normality were square root–transformed. Statistical significance was assumed at a two-sided alpha value of 0.05. All analyses were performed using SPSS Version 29 (IBM Corp., Armonk, New York).
 

RESULTS

The study population included 25 patients, 10 of whom were female. Their mean age was 52.48±12.75 years, and the mean body mass index was 30.45±4.09 kg/m2.

Differences between baseline and postintervention values were determined for several sleep and sleep-related respiratory variables, including AHI and SASHB (Table 1). OAT expiratory pressure enhanced mandibular advancement device (EMAD) was associated with significant reductions in overall AHI, NREM AHI, REM AHI, and supine AHI. The intervention also led to significant decreases in overall SASHB, maximum hypopnea duration, and arousal index (Figure 2).

Beneficial oxygenation effects were also observed with EMAD. Both mean and nadir SpO2 increased significantly from baseline to postintervention (Figure 3). Significance remained after controlling for the false discovery rate using the Benjamini and Hochberg method and after removing outliers for baseline REM AHI (n=1), postintervention REM AHI (n=1), baseline mean SpO2 (n=1), and baseline supine AHI (n=1). Outliers were defined as values greater than 3 standard deviations from the group mean. Thus, these statistical outliers were included in the final analyses. REM AHI and supine AHI were square root–transformed because of non-normality. Because the effects remained significant after this transformation, the nontransformed results are presented. There were no differences between baseline and postintervention for TST, sleep efficiency, and supine sleep duration.

The mean decrease in AHI from baseline to postintervention was 69.8%. AHI decreased by ≥50% in 94% of patients. Therapeutic efficacy of the EMAD combination therapy based on the AHI criteria of fewer than10 events/h postintervention was 92% (Figure 4, A). When more stringent AHI criteria of fewer than 5 events/h post-intervention (incomplete resolution of OSA) were used, the therapeutic efficacy decreased to 20%. The mean decrease in SASHB from baseline to postintervention was 76%. SASHB decreased by ≥50% in 100% of patients. Therapeutic efficacy of the combination therapy based on the SASHB criteria of <53%min/h postintervention was 100% (Figure 4, B). When the more stringent SASHB criteria of <34%min/h were used, the therapeutic efficacy remained at 100%. When comparing the percent improvement between the two metrics, improvement was significantly less when using AHI (M=69.83, SD=9.64) than when using SASHB (M=75.73, SD=7.00; t(24)= –2.22, P=0.036).
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DISCUSSION

This study explored the therapeutic efficacy of 6 months of treatment with an expiratory pressure enhanced mandibular advancement device (EMAD) in adults with moderate OSA. No significant oral appliance tolerability issues were observed during this study, and there were no dropouts due to adverse effects from combination therapy. Treatment was associated with significant reductions in AHI (overall and during NREM, REM, and supine sleep), SASHB, arousal index, and hypopnea duration from baseline to postintervention. Patients also experienced improvements in oxygenation indices, with increases in both mean and nadir SpO2. Therapeutic efficacy was high when AHI was the marker of effectiveness, with a mean decrease in AHI of almost 70%, and 20% of patients experiencing resolution of their OSA. However, efficacy was even higher when using SASHB criteria, with a mean improvement in SASHB of 76% and 100% of patients experiencing a reduction in SASHB to <34%min/h. Overall, the study results demonstrated very high therapeutic efficacy of the EMAD combination therapy for treating moderate OSA.

OAT has been previously shown to reduce AHI, improve minimum SpO2, and reduce the arousal index.5, 25 The study results are consistent with improvements found in previous studies and meta-analyses, revealing comparable performance of the MAD with EPAP to other forms of OAT reported in the literature. Oral appliances increase the size of the upper airway by advancing the tongue and soft palate, while also placing tension on airway muscles to further reduce collapsibility.26 Additionally, nasal EPAP devices (albeit different than the current EPAP device) have been demonstrated to reduce AHI, decrease the oxygen desaturation index, and increase the minimum SpO2.27 Overall, the study findings are consistent with the results reported with other types of OAT, supporting the use of the combination device to improve respiratory-related disturbances in patients with moderate OSA.

This device demonstrated high therapeutic efficacy based on various measures. Efficacy was particularly high based on SASHB criteria.22 With recent concerns that AHI is a poor predictor of cardiovascular health,14 metrics that better predict relevant cardiovascular outcomes are necessary for appropriate selection and optimization of treatment for OSA. The main cutoff value for SASHB used in the current study (53%min/h) is the value previously reported to be associated with an increased risk of cardiovascular-related death.14 At baseline, SASHB of all study participants exceeded this cutoff value, suggesting that all had an increased risk of future cardiac death. However, SASHB fell below this cutoff in all participants postintervention, potentially resulting in a significant decrease in long-term cardiovascular risk. Previous researchers reported a response rate of 100% in patients with moderate OSA treated with OAT when using the SASHB criteria of <60%min/h.17 A recent consensus document from the Portuguese Dental Association and related societies recommended using other metrics (such as hypoxic burden) in addition to AHI when making treatment decisions for OSA.28 Shifting the focus from frequency-based metrics to risk-based metrics is important for the evaluation of treatments and ultimate personalization of medical care, as it assists in identifying responders and nonresponders based on metrics associated with relevant longer-term health outcomes.22 Additionally, SASHB is easily determined by PSG, because it only requires pulse oximetry. Overall, the results revealed substantial improvements in OSA-related respiratory disturbances with OAT. It can be surmised that these improvements may also lead to better cardiovascular outcomes.

No significant changes were observed in some metrics of sleep quality, including sleep efficiency and TST, with therapy. Previous studies also found no changes in these metrics with OAT.5, 25, 29 No significant changes were detected in supine sleep time from baseline to postintervention. Previous research has suggested that the benefits of oral appliances may depend on body position, particularly for supine or prone sleep.30 However, the significant improvements observed in the patients in this study do not appear to reflect increased time spent in a more favorable body position.

This study had several limitations, providing opportunities for future research. It had a within-subjects pre-post design, with no control group to eliminate changes over time unrelated to treatment (such as habituation to sleep studies). Additionally, there was no group with only the MAD, without the additional accessory. As such, the contribution of the EPAP therapy is unknown. The sample size in the current study was relatively small, with a limited range in sleep apnea severity, which limits the generalizability of results. This study also incorporated single-night testing, and so it is possible that natural variability in AHI between nights could partially affect the study results. Further studies could also compare this OAT device to CPAP to investigate whether development of the combination system has helped reduce the efficacy gap between OAT and CPAP. Finally, future research could investigate the effect of EMAD therapy on cardiovascular markers to assess improvements that may validate predictions based on changes in SASHB.

In conclusion, this study analyzed the relationship between AHI, a frequency-based metric, and SASHB, a metric that captures the risk associated with OSA. AHI appeared to misclassify some individuals as nonresponders to combination therapy, despite SASHB being below the threshold of increased cardiovascular risk. SASHB likely provides a more meaningful metric of OSA treatment response than AHI, as it correlates more favorably with associated comorbidities. The study findings suggest that traditional methods of assessing therapeutic efficacy are inappropriately restrictive and that the efficacy of OAT is higher than previously reported. Future research should focus on collecting additional evidence to advance the use of SASHB as a metric of therapeutic outcomes in OSA.

ACKNOWLEGEMENTS

Funding for this trial was provided by a research grant from the Centre for Sleep and Chronobiology, Toronto, Ontario, Canada.

The authors thank BioScience Writers, LLC, for technical writing support.

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SUBMISSION & CORRESPONDENCE INFORMATION

Submitted December 25, 2025
Submitted in final revised form March 26, 2026
Accepted for publication April 5, 2026

Address correspondence to: Dr. Sat Sharma, MD.
Centre for Sleep and Chronobiology
301, 295 College Street
Toronto, ON, M5T 1S2, Canada
Email: ssharma@mts.net
 

DISCLOSURE STATEMENT

All authors reviewed and approved the manuscript.

All authors declare no conflicts of interest.

This work was completed at the Centre for Sleep and Chronobiology, Toronto, Canada; Windsor Sleep Disorders Clinic, Windsor, Canada; TRS Waterloo Sleep Institute, Waterloo.

Funding for this trial was provided by a research grant from the Centre for Sleep and Chronobiology, Toronto, Ontario, Canada.

The manuscript reports on the clinical trial titled “Use of the ExVent Accessory with the O2Vent Optima oral appliance for the treatment of obstructive sleep apnea” https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=91&cx=-yrhiqb

ClinicalTrials.gov registration number: NCT05954026



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