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Abstract

Objective:

This feasibility study examined the initial-use safety and potential utility of a novel noninvasive oral pressure therapy (OPT) system designed to reduce airway obstruction during sleep.

Methods:

This was a single-center, proof-of-concept, single-treatment-night study in which subjects with obstructive sleep apnea (OSA) underwent a baseline polysomnography (PSG) study followed by PSG during use of an OPT system. The OPT system is composed of a bedside console, a polymer mouthpiece, and a flexible tube connecting the mouthpiece to the console. The console contains a pump that creates vacuum intended to pull the soft palate anteriorly and stabilize the tongue to reduce obstruction during sleep.

Results:

Fifty-four men and 17 women, aged 53.2 ± 11.5 years (mean ± SD) had a baseline apnea–hypopnea index (AHI) greater than 5 events per hour. OPT was generally well tolerated with no serious adverse events. OPT significantly decreased AHI from 34.4 ± 28.9 events per hour (mean ± SD) at baseline to 20.7 ± 23.3 (p < 0.001). Treatment produced an AHI less than 10 in 48% of the subjects. OPT significantly improved oxygen desaturation index (p < 0.001) and increased the percentage of the night with oxygen saturation of 90% or greater (p = 0.028). Stage-N1 sleep shifts, total sleep-stage shifts, awakenings and the percentage of sleep time spent in N1 sleep were significantly reduced with treatment.

Conclusion:

This proof-of-concept study suggests that OPT can produce clinically relevant relief of OSA in certain subjects who are readily identified by PSG during trial use of the noninvasive system. OPT shows promise as a new treatment option for OSA in appropriate patients.

Keywords

apnea–hypopnea index obstructive sleep apnea oral pressure therapy oxygen desaturation index polysomnography therapy vacuum

Introduction

Obstructive sleep apnea (OSA), the most common sleep-related breathing disorder, produces cyclical respiratory events during which airflow is temporarily restricted or blocked due to pharyngeal airway obstruction. This precipitates a reduction in the restorative effect of sleep, with symptoms of frank daytime sleepiness, leading to a marked increased risk of motor vehicle and industrial accidents [Young et al. 2002]. Patients with OSA are also at a significantly increased risk for negative impact on measures of memory, cognition, psychomotor performance, and mood disturbance [Adams et al. 2001]. Chronic untreated OSA, over a period of years, yields significant increased risks of cardiovascular disease, including hypertension, cardiac arrhythmias, atherosclerotic heart disease, myocardial infarction, stroke, and death [Levy et al. 2009; Punjabi et al. 2009].

Epidemiological study results indicate that OSA is highly prevalent in adults. Approximately 1 in 5 adults have at least mild OSA and 1 in 15 have OSA of moderate or worse severity [Young et al. 2002]. Despite the existence of many medical device and surgical therapeutic options for OSA, there remains a large population that suffers without adequate treatment. Nonsurgical treatments include continuous positive airway pressure (CPAP), oral appliances (i.e. mandibular advancement devices) [Clark et al. 1996; Ferguson et al. 2006], and nasal appliances [Colrain et al. 2008]. Pharmacotherapy has had a very limited role as a primary treatment of OSA [Jayaraman et al. 2008]. Surgical treatment methods include radiofrequency and laser volumetric reduction of the soft palate and tongue, uvulopalatopharyngoplasy, palatal implants, maxillomandibular advancement, tongue suspension implants, and tracheotomy [Johnston et al. 2002; Woodson, 2002; Kuhnel et al. 2005].

Oral pressure therapy (OPT) is a new concept for relieving airway obstruction to treat OSA. This feasibility study explored the safety and potential utility of a novel noninvasive OPT system designed to reduce airway obstruction. The system is composed of a bedside console, a custom thermoformed polymer mouthpiece, and a flexible tube connecting the mouthpiece to the console. The console contains a pump that is intended to create a vacuum in the oral cavity to pull the soft palate anteriorly and stabilize the tongue to reduce obstruction during sleep.

Methods

Participants

Subjects between the ages of 21 and 80 years were recruited from the patient database of a single center, the Peninsula Sleep Center, Burlingame, CA. Patients meeting minimal criteria for the diagnosis of OSA, including an untreated apnea–hypopnea index (AHI) minimum of 5 events per hour, were included. Patients were excluded if they had any of the following conditions: oral or dental infection or a condition that would limit the use of the mouthpiece; inadequate nasal airflow; unstable medical conditions other than uncomplicated OSA; clinically significant disease which might pose additional risk to the subject or confound study results; pregnancy or intention to become pregnant during the study. Subjects with an irregular sleep–wake schedule or a nonnocturnal sleep schedule were excluded. There were no additional inclusion or exclusion criteria. Specifically, patients could be naive to treatment, actively use CPAP, or have used CPAP in the past. Patients were contacted in a consecutive fashion, and invited to participate in the research. Any prior diagnosis of OSA was reviewed and documented as source data.

Protocol design and study sequence

This study was a single-center, noncontrolled, nonrandomized, proof-of-concept, single-treatment-night study in which subjects underwent a baseline nontreatment nocturnal polysomnography (PSG) evaluation followed by a second PSG during OPT treatment. Approval from the Western Institutional Review Board (Olympia, WA) ethical committee was obtained and the study was conducted in accordance with the US Food and Drug Administration (FDA) regulations on Good Clinical Practice. After a full explanation of the study procedure, written informed consent was obtained, inclusion and exclusion criteria were confirmed and a brief exam of the oral cavity was performed. Dental impressions were obtained and a thermoformed polymer mouthpiece was produced for each subject. The mouthpiece was inserted in the subject’s mouth and evaluated by the subject and technician for fit and comfort. Full-night PSG without the device was performed to establish an untreated baseline. Subsequent to this baseline study, full-night PSG was performed with the device. The study site scheduled both PSG nights in close succession, if accommodated by the subject’s availability.

Device description

The system (ApniCure, Inc., Redwood City, CA, USA) is composed of three components: an oral interface, a pump, and a tubing set. The oral interface is a mouthpiece that incorporates a lip seal and a connector. The pump applies continuous negative pressure to the oral interface. The pump consists of a vacuum pump, pump controller, and pressure measurement component. The tubing set connects the oral interface to the pump. The system provides negative pressure to the oral cavity. The negative pressure generated by the console and conveyed via tubing through the mouthpiece into the oral cavity is intended to create a pressure gradient to draw the soft palate anteriorly into contact with the tongue, improving airflow during sleep as shown in Figure 1. The patient breathes normally through the nose while asleep. The negative pressure in the oral cavity is isolated from the nasal–pharyngeal airway by the natural seal that occurs between the soft palate and tongue. Adequate nasal patency, to allow closed-mouth breathing, is required for use of the device. The mouthpiece can be easily removed or inserted by the patient at any time. The console includes a reservoir for the collection of excess saliva.

Figure 1.

Device description. With the mouthpiece in place, gentle oral vacuum creates a pressure gradient intended to displace the soft palate against the tongue to relieve airway obstruction during sleep. The natural seal of the soft palate against the tongue isolates the oral cavity from the airway. The patient breathes normally through the nose.

Polysomnography

Nocturnal PSG was conducted with standard lights-off time between 9:30 p.m. and 11:00 p.m. and lights-on time between 6:00 a.m. and 7:30 a.m. PSG data were collected using Nellcor Puritan Bennett Sandman SD32 PSG equipment and Sandman Elite software (Natus Medical Embla, San Carlos, CA). Standard clinical PSG using the American Academy of Sleep Medicine 2007 protocol [Iber et al. 2007] was conducted with the following signals collected on each night: electroencephalogram (C3-M2, C4-M1, O1-M2, O2-M1, F3-M2, and F4-M1, with grounds placed at Fz and Cz); electrooculogram (both eyes); electromyogram (bilateral submentalis); electrocardiogram (right clavicle to left fourth intercostal space); abdominal and thoracic effort (via ProtechzRIP [Pro-Tech zRIP, Philips Respironics, Murrysville, PA] respiratory inductance plethysmography); left and right leg movement (anterior tibialis electromyogram); nasal airflow (cannula); nasal/oral airflow (thermocouples); oxygen saturation (fingertip transmission oximetry); and body position (visual assessment via integrated Sandman video). The pump was set to produce a negative pressure of approximately 25 inH₂O at the console.

PSG data were scored manually by a single remote scorer. Scoring was according to American Academy of Sleep Medicine standard criteria [Iber et al. 2007]. Specifically, AHI was calculated as the sum of the number of apnea events and hypopnea events divided by the total hours of sleep. The oxygen desaturation index (ODI) selected for reporting in this study was calculated as the total number of events with 3% or more decrease in oxygen saturation divided by the total hours of sleep. The percentage of the night with oxygen saturation greater than or equal to 90% was calculated and the nightly minimum oxygen saturation was determined. Sleep architecture measures scored were total sleep time (TST), sleep efficiency (% SE), sleep onset latency (SOL), stage N1 shifts, total stage shifts, awakenings, rapid eye movement (REM) latency, wakefulness after initial sleep onset (WASO), % TST in N1, % TST in N2, % TST in N3, and % TST in REM.

Statistical analysis

All subjects who had an AHI greater than 5 events per hour at baseline night were included in the data analysis. Based on the baseline AHI measurement, subjects were categorized into three OSA severity groups (mild OSA: AHI ≥ 5 and AHI < 15, moderate OSA: AHI ≥ 15 and AHI < 30, and severe OSA: AHI ≥ 30).

All measurements (AHI, oxygenation, and sleep architecture) obtained at baseline and while on treatment were summarized descriptively by the baseline OSA severity. The change from baseline to treatment and percentage change from baseline to treatment for all these measurements were calculated and summarized descriptively by the baseline OSA severity. A paired t test was used for the test of change or percentage change from baseline to treatment within each group. A two-sample t test was used to make comparison of the change or percentage change from baseline to treatment between the two groups with p < 0.05 considered significant. Statistical analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, NC, USA).

Results

Fifty-four men and 21 women were included in the study; however, four subjects, all women, were found to have baseline AHI less than 5 events per hour and were excluded from further analysis. Age ranged from 26 to 75 years with mean ± standard deviation (SD) of 53.2 ± 11.5 years. Body mass index ranged from 19.1 to 65.9 kg/m² with mean ± SD of 30.7 ± 6.9 kg/m². Comorbidities in the evaluable population included hypertension (52.1%), nasal allergies (29.6%), hypercholesterolemia (25.4%), diabetes (18.3%), asthma (8.4%), coronary artery disease (7.0%), thyroid disorder (5.6%), history of head trauma (4.2%), chronic bronchitis/emphysema (2.8%), transient ischemic attack/stroke (2.8%), seizure disorder (2.8%), prostate cancer (1.4%), arthritis (1.4%), and congestive heart failure (1.4%).

Of the 71 evaluable subjects, 45 (63.4%) were CPAP users, 5 (7.0%) had used CPAP in the past but had discontinued the use of CPAP, and 21 (29.6%) were CPAP naïve. CPAP compliance was self-reported, with 31/45 (68.9%) CPAP users reporting use at least five nights per week and at least 4 h per night.

Based upon baseline AHI measurement, 29 (41%) subjects had severe OSA, 17 (24%) subjects had moderate OSA, and 25 (35%) subjects had mild OSA. The percentage time in the supine position was 72.6 ± 28.0 % (mean ± SD) at baseline and was similar at 76.8 ± 30.4 % during treatment (p = 0.16). The median time interval between baseline PSG and treatment PSG studies was 7 days (quartile range 1−28 days).

Apnea–hypopnea index and oxygenation

AHI was significantly reduced by treatment. Baseline AHI was 34.4 ± 28.9 events per hour (mean ± SD) while AHI with treatment was 20.7 ± 23.3 (p < 0.001). Figure 2 shows the effect of OPT on AHI. The reductions in AHI observed in relation to baseline severity of OSA are shown in Figure 3. Treatment produced AHI less than 10 in 48% of the subjects. AHI was reduced by at least 50% with treatment compared with baseline in 48% of the subjects. Treatment produced the combined effect of AHI less than 10 events per hour and reduction in AHI of at least 50% from baseline in 37% of the subjects. The alternate combined criteria of treatment AHI less than 20 events per hour and reduction in AHI of at least 50% from baseline has been suggested by a panel of advisors to the FDA [FDA, 2004] and was observed in 42% of subjects as follows: nine of 25 subjects (36%) with mild OSA, 12 of 17 (71%) with moderate OSA, and nine of 29 (31%) with severe OSA. Comparing the severity of OSA in the study population at baseline with the results seen with treatment, improvement in the severity of OSA in the group was seen as shown in Figure 4.

Figure 2.

Apnea–hypopnea index (AHI) at baseline and with treatment. Horizontal lines depict median and first and third quartile results for the 71 subjects.

Figure 3.

Apnea–hypopnea index (AHI) in relation to baseline obstructive sleep apnea (OSA) severity. (a) AHI is shown at baseline and with treatment by baseline OSA severity. (b) Reduction of AHI with treatment by baseline severity. Values shown are mean and standard error of the mean; *p < 0.001.

Figure 4.

Severity of obstructive sleep apnea (OSA). Based on apnea–hypopnea index (AHI) measurements at baseline and with treatment, OSA severity was identified for each subject and the portion of the 71-subject population at each severity level is shown. Treatment was effective in reducing the severity of OSA in the population.

ODI was reduced by treatment from 24.8 ± 21.4 events per hour at baseline to 15.7 ± 18.2 per hour with treatment (p < 0.001). The percentage of the night with oxygen saturation of 90% or greater increased with treatment from 87.3% ± 18.5% to 90.2% ± 15.4% (p < 0.05). Minimum recorded oxygen saturation was not significantly altered by treatment (78.5% ± 9.5% at baseline versus 79.6% ±10.5% with treatment). AHI, ODI, and oxygen saturation data are shown by baseline OSA severity in Table 1.

Table 1.

Sleep-disordered breathing measures by baseline OSA severity.

	Mild OSA (n = 25)		Moderate OSA (n = 17)		Severe OSA (n = 29)
	Baseline	Treatment	Baseline	Treatment	Baseline	Treatment
AHI (/h)*	9.7 ± 2.8	7.6 ± 6.2	22.7 ± 4.3	11.2 ± 7.7^†	62.7 ± 24.8	37.6 ± 28.0^†
ODI (/h)*	6.6 ± 3.3	5.4 ± 5.1	18.1 ± 4.8	8.7 ± 6.3^†	44.5 ± 19.9	28.7 ± 22.0^†
Minimum SpO₂ (%)	83.4 ± 5.7	83.6 ± 6.8	78.3 ± 9.6	82.9 ± 8.0^†	74.4 ± 10.3	74.1 ± 12.1
% TST SpO₂ ≥ 90%*	98.3 ± 2.0	97.7 ± 4.7	90.2 ± 14.6	93.5 ± 12.0^†	76.1 ± 22.1	81.9 ± 19.0

Values shown are mean ± standard deviation.

p < 0.05 paired t test of treatment versus baseline in the total population (n = 71).

†

p < 0.05 paired t test of treatment versus baseline in the severity group.

AHI, apnea–hypopnea index; ODI, oxygen desaturation index; OSA, obstructive sleep apnea; SpO₂, oxygen saturation; TST, total sleep time.

Sleep architecture

In the 71 subjects analyzed, there was a significant reduction in TST on the initial night of treatment from 353.6 ± 64.6 min to 333.4 ± 80.4 min. SOL was not significantly altered with treatment. Stage N1 shifts were significantly reduced with treatment from 76.1 ± 38.3 to 58.2 ± 32.1 (p < 0.001). Similarly, stage shifts were reduced with treatment from 196.1 ± 78.1 to 163.4 ± 72.1 (p < 0.001). Awakenings were significantly reduced with treatment from 46.7 ± 28.8 to 36.9 ± 19.9 (p = 0.002) and REM latency was also significantly reduced with treatment from 159.5 ± 88.6 min to 136.5 ± 82.9 min (p = 0.029). Wakefulness after sleep onset was significantly increased with treatment from 65.7 ± 47.0 min to 76.7 ± 53.3 min (p = 0.041). Regarding sleep stage, % TST in N1 was significantly reduced with treatment from 33.3% ± 24.5% to 25.4% ± 17.9% (p < 0.001) while % TST in N2, N3, and REM were significantly increased with treatment (N2: from 50.5% ± 19.4 % to 54.9% ± 13.9% (p = 0.016); N3: from 4.4% ± 5.3% to 6.1% ± 7.0% (p = 0.009); REM: from 11.8% ± 6.2% to 13.6% ± 6.9% (p = 0.003)). Sleep architecture results are shown by baseline OSA severity in Table 2.

Table 2.

Sleep architecture measures by baseline OSA severity.

	Mild OSA (n = 25)		Moderate OSA (n = 17)		Severe OSA (n = 29)
	Baseline	Treatment	Baseline	Treatment	Baseline	Treatment
TST (min)*	360.4 ± 48.3	332.8 ± 59.9^†	372.1 ± 54.9	347.9 ± 86.4	336.9 ± 78.6	325.4 ± 93.0
SE (%)*	84.2 ± 11.7	78.4 ± 11.7^†	83.5 ± 10.6	80.5 ± 14.8	76.1 ± 15.6	75.6 ± 15.9
SOL (min)	18.8 ± 17.2	19.1 ± 20.9	12.8 ± 14.5	12.3 ± 11.5	19.3 ± 28.8	18.8 ± 30.4
N1 shifts*	51.9 ± 20.4	48.8 ± 19.9	66.8 ± 16.5	50.4 ± 22.3^†	102.5 ± 43.1	71.0 ± 40.7^†
Stage shifts*	154.3 ± 39.7	144.2 ± 42.7	179.1 ± 35.6	147.2 ± 51.2^†	242.2 ± 96.0	189.6 ± 93.5^†
Awakenings*	30.6 ± 18.3	31.2 ± 16.4	39.8 ± 14.1	33.5 ± 16.0	64.5 ± 32.9	43.9 ± 23.0^†
REM latency (min)*	142.8 ± 85.3	131.8 ± 71.5	152.3 ± 68.6	141.9 ± 102.4	179.5 ± 101.6	137.2 ± 81.9^†
WASO (min)*	51.2 ± 49.2	73.2 ± 41.2^†	61.4 ± 43.0	69.9 ± 62.0	80.7 ± 44.3	83.6 ± 58.0
% TST in N1*	20.9 ± 15.1	21.1 ± 13.5	22.8 ± 12.4	17.9 ± 13.4	50.2 ± 26.7	33.3 ± 20.7^†
% TST in N2*	58.1 ± 12.0	57.4 ± 10.3	61.0 ± 10.3	60.8 ± 12.3	37.8 ± 21.7	49.3 ± 15.7^†
% TST in N3*	7.5 ± 6.3	6.6 ± 5.8	3.2 ± 4.4	7.0 ± 8.4^†	2.4 ± 3.5	5.1 ± 7.2^†
% TST in REM*	13.5 ± 5.9	14.7 ± 6.0	12.9 ± 5.9	14.3 ± 7.6	9.7 ± 6.2	12.3 ± 7.2^†

Values shown are mean ± standard deviation.

p < 0.05 paired t test of treatment versus baseline in the total population (n = 71).

†

p < 0.05 paired t test of treatment versus baseline in the severity group.

REM, rapid eye movement; SE, sleep efficiency; SOL, sleep onset latency; TST, total sleep time; WASO, wakefulness after initial sleep onset.

Safety

Adverse events were recorded and categorized in accordance with Good Clinical Practice regulations. There were no serious adverse events in the 75 subjects who used the device during PSG. Device-related adverse events were reported by 32% of subjects and 92% of these events were mild, 8% were moderate, and none were severe. The most common adverse event, noted by 19 subjects, was oral tissue discomfort, typically of the palate or throat. Oral tissue irritation, categorized as either abrasion or erythema, was noted in 12% of subjects. No device-related adverse events required medical treatment, other than one subject taking over-the-counter analgesics for mild oral tissue discomfort.

Discussion

In this study, OPT improved measures of sleep-related breathing disturbance in subjects with mild to severe OSA, with improvement in mean AHI from 34.4 ± 28.9 (mean ± SD) at baseline to 20.7 ± 23.3 with treatment (p < 0.001). Clinically relevant improvements were observed in some subjects who were readily identified by comparison of baseline and treatment PSG results; thus, this study suggests that treatment with this noninvasive therapy could potentially be useful for individuals identified as having an appropriate response. While not all subjects responded to OPT, it is important to note that a vigorous response was achieved in some subjects. OPT, in individuals identified as having an appropriate response, can yield similar results to CPAP, with AHI reduction with OPT exceeding 73% in the top quartile in this study compared with reductions ranging from 65% to 90% reported in controlled trials of CPAP [Engleman et al. 2002; Becker et al. 2003; Chakravorty et al. 2002; Kaneko et al. 2003; Monasterio et al. 2001; Pepperell et al. 2002]. Improvements with OPT were notable across the range of disease severity from mild to severe. No significant safety issues were identified in this study. These results suggest that while OPT would not be appropriate for treating all patients, a subset of strong responders can be identified with PSG. Such evaluation can be performed without safety concerns and without precluding other therapeutic options for those who do not have a sufficient response for clinical treatment. Additionally, substantial work evaluating the impact of CPAP on clinically relevant efficacy measures has identified an average use duration dose–response effect on obstructive respiratory events, sleep parameters, excessive daytime sleepiness, quality of life, and long-term health consequences, including cardiovascular disease [Antic et al. 2011; Stepnowsky and Dimsdale, 2002; Peker et al. 2002]. Based on this information, it is possible that among patients who are unable to use CPAP, those with only partial response (e.g. AHI reduction > 50%) to OPT may derive some clinical benefit from such treatment.

Commensurate with improvement in AHI, measures of sleep continuity, consolidation, and depth were improved in a manner consistent with improvements observed in controlled CPAP trials [Chakravorty et al. 2002; Kaneko et al. 2003; Barnes et al. 2004; Brillante et al. 2012; O’Donoghue et al. 2012]. OPT was associated with significant increases in N2, N3, and REM sleep, and significant reductions in stage shifts, awakenings, and REM latency. CPAP treatment commonly ameliorates sleep disturbance produced by obstructive respiratory events, and has been reported to reduce sleep-stage shifts, awakenings, arousal activity, and percentage time spent in N1 sleep, as well as increasing relative time spend in REM sleep and deep sleep. Clinically relevant treatment of OSA is expected to show improvement in measures of sleep disturbance. Therefore, in patients whose OSA is improved with OPT, treatment is expected to yield improvements in sleep measures.

There are several limitations of this study that merit consideration in evaluating these results and in contemplating potential future investigations. This study considered data from a single night of treatment per subject and further investigation will be necessary to document the durability of treatment over time. Chronic effectiveness may be anticipated given that the mechanism of action should be reproducible on a nightly basis. Furthermore, improvements with chronic therapy in symptoms such as daytime sleepiness can be anticipated in view of the PSG results but should be confirmed directly in future investigations. In each subject, the baseline night study was completed before the study night with the device; hence, a bias may have been introduced into the results based upon the sequence of these nights; however, order of PSG evaluation is unlikely to have an effect on respiratory parameters. While concern about a potential ‘first-night effect’ has been raised historically, substantial research over the past decade has uniformly identified no first-night effect on respiratory parameters, including AHI and oxygen desaturation across a variety of sleep-related-breathing-disorder patient types, and diagnostic settings [Ma et al. 2011; Gouveris et al. 2010; Hutchison et al. 2008; Selwa et al. 2008]. Nonetheless, in future studies, a randomized sequence of these study nights may be considered. Each subject served as his own control and the subjects were not blinded with regard to treatment condition; however, blinding of subjects to treatment condition or use of a sham condition appears difficult to achieve due to the distinctive oral sensation that OPT produces.

This feasibility study was conducted at a single center and future investigations reproducing these results at additional centers with varied patient populations would extend these results. The extent of relief of OSA was limited for some subjects and substantial for other subjects in this feasibility study; thus, future studies might evaluate what factors should be used as predictors of response with this technology. Factors that merit consideration include elements of the subject’s history and physical examination, as well as results of the baseline PSG since such data are typically readily available. Mechanisms for lack of response may include inadequate lip seal on the mouthpiece, opening of the mouth, disruption of vacuum delivery to the oral cavity, or inadequate tissue movement with the tested device configuration. With the feasibility of OPT demonstrated in this study, further design improvements might lead to enhanced performance. There are multiple anatomic and physiologic clinical factors that are important in OSA [Riha, 2010]. Imaging studies are being conducted using quantitative methods to help clarify how the device works, how it might be improved, and what patient anatomic configurations are most likely to be responsive to OPT [Schwab et al. 2012]. Adequate nasal airflow is necessary for device use and future investigations may consider quantitative methods to delineate minimum requirements in this regard.

The most common adverse event was mild oral tissue discomfort. Optimization of mouthpiece design and the applied pressure might also impact effectiveness and comfort in the future. Further improvements in comfort have the potential to enhance sleep architecture during OPT. An acclimation period in the future might also facilitate comfort and tolerability. Adherence was not evaluated in this single night comparison study and it will be important to characterize the adherence and the compliance that is achievable with OPT with regular use [Ravesloot and De Vries, 2011; Sawyer et al. 2001; Weaver and Grunstein, 2008].

The safety results suggest that OPT may be a feasible approach for treatment of OSA. Following the demonstration of feasibility in this study, design improvements may be considered to make OPT easily applied in clinical practice. A set of soft polymer mouthpieces manufactured in fixed sizes with appropriate selection for each patient might be preferred to the creation of the custom thermoformed polymer mouthpiece for each patient individually. Such a change could potentially simplify clinical practice and improve patient adaptation to the mouthpiece.

The extent to which patients who reject consideration of therapy with CPAP are amenable to treatment with OPT may be evaluated in future studies. The promising results demonstrated in this feasibility study suggest a potential role for OPT in clinical practice and will likely drive exploration of all of these questions and more.

OPT is a novel mechanism for relieving airway obstruction. The tolerability observed in this study can be anticipated from the low applied pressure. Unlike CPAP, OPT does not apply pressure directly to the airway. Rather, negative pressure is applied to the oral cavity which closes to the airway when the soft palate seals against the tongue. By comparison, the magnitude of negative intraoral pressure produced by the system is less than the negative pressure associated with breastfeeding [McClellan et al. 2008; Geddes et al. 2008, 2012], pediatric training cups [Scarborough et al. 2010], and denture seals [Grossman and Forbes, 1990].

PSG provides a rapid means for identifying individuals with a clinically meaningful response to therapy; thus, patients could be evaluated for treatment with this noninvasive therapy without precluding other treatment options in the future. Given the range of therapeutic options for OSA that exist today and the large population that suffers without adequate treatment, OPT may offer promise as a new noninvasive treatment for selected patients. Future evaluations will facilitate greater understanding of the role for OPT in the treatment of OSA.

Footnotes

Funding

This study was sponsored by ApniCure, Inc.

Conflict of interest statement

Dr Farid-Moayer received grant support in order to execute this study. Dr Siegel is employed part-time by ApniCure. Dr Black serves as a consultant to ApniCure.

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A feasibility evaluation of oral pressure therapy for the treatment of obstructive sleep apnea

Abstract

Objective:

Methods:

Results:

Conclusion:

Keywords

Introduction

Methods

Participants

Protocol design and study sequence

Device description

Polysomnography

Statistical analysis

Results

Apnea–hypopnea index and oxygenation

Sleep architecture

Safety

Discussion

Footnotes

Funding

Conflict of interest statement

References