Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea.

In some individuals with obstructive sleep apnoea (OSA), the palate prolapses into the velopharynx during expiration, limiting airflow through the nose or shunting it out of the mouth. We hypothesised that this phenomenon causes expiratory flow limitation (EFL) and is associated with inspiratory "isolated" palatal collapse. We also wanted to provide a robust noninvasive means to identify this mechanism of obstruction.Using natural sleep endoscopy, 1211 breaths from 22 OSA patients were scored as having or not having palatal prolapse. The patient-level site of collapse (tongue-related, isolated palate, pharyngeal lateral walls and epiglottis) was also characterised. EFL was quantified using expiratory resistance at maximal epiglottic pressure. A noninvasive EFL index (EFLI) was developed to detect the presence of palatal prolapse and EFL using the flow signal alone. In addition, the validity of using nasal pressure was assessed.A cut-off value of EFLI >0.8 detected the presence of palatal prolapse and EFL with an accuracy of >95% and 82%, respectively. The proportion of breaths with palatal prolapse predicted isolated inspiratory palatal collapse with 90% accuracy.This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse.

Upper-Airway Collapsibility and Loop Gain Predict the Response to Oral Appliance Therapy in Patients with Obstructive Sleep Apnea.

RATIONALE: Oral appliances (OAs) are commonly used as an alternative treatment to continuous positive airway pressure for patients with obstructive sleep apnea (OSA). However, OAs have variable success at reducing the apnea-hypopnea index (AHI), and predicting responders is challenging. Understanding this variability may lie with the recognition that OSA is a multifactorial disorder and that OAs may affect more than just upper-airway anatomy/collapsibility. OBJECTIVES: The objectives of this study were to determine how OA alters AHI and four phenotypic traits (upper-airway anatomy/collapsibility and muscle function, loop gain, and arousal threshold), and baseline predictors of which patients gain the greatest benefit from therapy. METHODS: In a randomized crossover study, 14 patients with OSA attended two sleep studies with and without their OA. Under each condition, AHI and the phenotypic traits were assessed. Multiple linear regression was used to determine independent predictors of the reduction in AHI. MEASUREMENTS AND MAIN RESULTS: OA therapy reduced the AHI (30 ± 5 vs. 11 ± 2 events/h; P < 0.05), which was driven by improvements in upper-airway anatomy/collapsibility under passive (1.9 ± 0.7 vs. 4.7 ± 0.6 L/min; P < 0.005) and active conditions (2.4 ± 0.9 vs. 6.2 ± 0.4 L/min; P < 0.001). No changes were seen in muscle function, loop gain, or the arousal threshold. Using multivariate analysis, baseline passive upper-airway collapsibility and loop gain were independent predictors of the reduction in AHI (r2 = 0.70; P = 0.001). CONCLUSIONS: Our findings suggest that OA therapy improves the upper-airway collapsibility under passive and active conditions. Importantly, a greater response to therapy occurred in those patients with a mild anatomic compromise and a lower loop gain.

Mouth Closure and Airflow in Patients With Obstructive Sleep Apnea: A Nonrandomized Clinical Trial.

Importance: Mouth breathing is associated with increased airway resistance, pharyngeal collapsibility, and obstructive sleep apnea (OSA) severity. The common belief is that closing the mouth can mitigate the negative effects of mouth breathing during sleep. However, mouth breathing may serve as an essential route to bypassing obstruction along the nasal route (eg, the velopharynx). Objective: To investigate the role of mouth breathing as an essential route in some patients with OSA and its association with upper airway anatomical factors. Design, Setting, and Participants: This nonrandomized clinical trial included participants diagnosed with OSA who underwent drug-induced sleep endoscopy. Patients were stratified into 3 quantiles based on oral-breathing level (quantile 1: oral airflow < 0.05 L/min; quantile 2: oral airflow 0.05-2.2 L/min; quantile 3: oral airflow > 2.2 L/min). Interventions: Closing the mouth during sleep during alternating breaths by applying pressure to the mentum until teeth are in occlusion. Main Outcomes and Measures: The primary outcome was total inspiratory flow defined as the change in airflow in the transition from mouth relaxed to mouth closed, analyzed overall and by 3 oral-breathing quantiles. The association of velopharyngeal obstruction on the change in total inspiratory airflow was also investigated. Results: Of 66 enrolled patients with OSA, 12 were excluded due to insufficient baseline airflow. The analytic cohort consisted of 54 patients (39 [72%] male; median [IQR] age, 55 [46-64] years; apnea-hypopnea index, 26.9 [17.6-39.9] events/h; and body mass index calculated as weight in kilograms divided by height in meters squared, 28.9 [27.1-31.6]). Mouth closure increased total inspiratory flow by 27.8 percentage points overall (ß, 1.0 [95% CI, 0.4-1.9] L/min). However, outcomes varied based on the degree of baseline oral breathing. No association was found for 10 patients with near-zero mouth breathing (0.9 [95% CI, -0.2 to 2.1] L/min). Airflow improved with mouth closure in 32 patients with moderate levels of mouth breathing (2.0 [95% CI, 1.3-2.7] L/min), whereas it worsened in patients with high levels of mouth breathing (-1.9 [95% CI, -3.1 to -0.6] L/min). Velopharyngeal obstruction was associated with increased mouth breathing (0.6 [95% CI, 0.1-3.0] L/min) and reduced airflow with mouth closure (-1.9 [95% CI, -3.1 to -0.7] L/min). Conclusion and Relevance: Although mouth closure increased inspiratory airflow in the overall cohort of this nonrandomized clinical trial, the outcomes were heterogeneous. In patients who breathe primarily through their mouth during sleep and have velopharyngeal obstruction, airflow worsens with mouth closure. Hence, personalized approaches to treating mouth breathing should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT06547658.

Head rotation improves airway obstruction, especially in patients with less severe obstructive sleep apnea without oropharyngeal collapse.

PURPOSE: Head rotation is thought to have an effect on obstructive sleep apnea (OSA) severity. However, keeping the head rotated fully during sleep is difficult to maintain, and the effect of head rotation is not the same in all OSA patients. Thus, this study aimed to identify whether less head rotation has an effect on airway patency and determine the responder characteristics to the head rotation maneuver (HRM). METHODS: We recruited 221 patients who underwent overnight polysomnography and drug-induced sleep endoscopy (DISE) in a tertiary hospital from June 2019 to July 2020. Airway patency and the site of airway collapse were determined in the supine position with the head at 0, 30, and 60 degrees of rotation (HRM0°, HRM30°, and HRM60°, respectively) during DISE. The site of collapse was determined using the VOTE classification system: the velum (palate), oropharyngeal lateral walls, tongue base, and epiglottis. Each structure was labeled as 0, 1, or 2 (patent, partially obstructed, and completely obstructed, respectively). Airway response to the HRM30° and 60° and the clinical characteristics associated with airway opening were analyzed. RESULTS: The study population had a median age of 52 (25-61) years, a body mass index of 26.7(24.6-29.4) kg/m2, and the apnea-hypopnea index (AHI) of 28.2(13.7-71.9) events/h. HRM influenced airway patency positively not only with HRM60° (p<0.001) but also following limited rotation (HRM30°, p<0.001). Patients with tongue base (40.0% with HRM 60°) and epiglottic (52.6% with HRM 60°) collapse responded particularly well to HRM. Multivariate analysis revealed that lower AHI (p<0.001) and an absence of oropharyngeal lateral walls collapse (p = 0.011) were significant predictors of responders to HRM. CONCLUSION: Head rotation improved airway obstruction in OSA patients, even with a small degree of rotation, and should be further explored as a potential form of therapy in appropriately selected patients.

Mouth Closing to Improve the Efficacy of Mandibular Advancement Devices in Sleep Apnea.

Rationale: Mouth breathing increases upper airway collapsibility, leading to decreased efficacy of obstructive sleep apnea (OSA) treatments. We hypothesized that the use of mandibular advancement devices (MAD) increases mouth breathing, and thus, using an adhesive mouthpiece (AMT) to prevent mouth breathing in combination with MAD can improve the treatment efficacy. Objectives: To evaluate the efficacy of MAD + AMT in comparison with MAD alone. Methods: A prospective crossover pilot study was designed to test this hypothesis. Briefly, adult participants with an apnea-hypopnea index (AHI) between 10 and 50 events/h at the screening visit were randomized to no treatment (baseline), MAD treatment, AMT treatment, and MAD + AMT treatment. As a primary analysis, absolute AHI was compared between MAD and MAD + AMT arms. Secondary analyses included quantifying the percent change in AHI, percentage of complete (AHI < 5 events/h) and incomplete (5-10 events/h) responders, and the efficacy of AMT alone in comparison with other treatment arms. Results: A total of 21 participants were included (baseline AHI = 24.3 ± 9.9 events/h). The median AHI (interquartile range) in the MAD and MAD + AMT arms were 10.5 (5.4-19.6) events/h and 5.6 (2.2-11.7) events/h (P = 0.02), respectively. A total of 76% of individuals achieved an AHI of <10 events/h in the MAD + AMT arm versus 43% in the MAD arm (P < 0.01). Finally, the observed effect was similar in moderate to severe OSA (AHI ⩾ 15 events/h) in terms of absolute reduction and treatment responders, and AMT alone did not significantly reduce the AHI compared with baseline. Conclusions: A combination of an adhesive mouthpiece and MAD is a more effective therapy than MAD alone. These findings may help improve clinical decision making in sleep apnea.

Predicting sleep apnea responses to oral appliance therapy using polysomnographic airflow.

STUDY OBJECTIVES: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. METHODS: Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. RESULTS: In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). CONCLUSIONS: A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.

Effect of Sleeping Position on Upper Airway Patency in Obstructive Sleep Apnea Is Determined by the Pharyngeal Structure Causing Collapse.

Objectives: In some patients, obstructive sleep apnea (OSA) can be resolved with improvement in pharyngeal patency by sleeping lateral rather than supine, possibly as gravitational effects on the tongue are relieved. Here we tested the hypothesis that the improvement in pharyngeal patency depends on the anatomical structure causing collapse, with patients with tongue-related obstruction and epiglottic collapse exhibiting preferential improvements. Methods: Twenty-four OSA patients underwent upper airway endoscopy during natural sleep to determine the pharyngeal structure associated with obstruction, with simultaneous recordings of airflow and pharyngeal pressure. Patients were grouped into three categories based on supine endoscopy: Tongue-related obstruction (posteriorly located tongue, N = 10), non-tongue related obstruction (collapse due to the palate or lateral walls, N = 8), and epiglottic collapse (N = 6). Improvement in pharyngeal obstruction was quantified using the change in peak inspiratory airflow and minute ventilation lateral versus supine. Results: Contrary to our hypothesis, patients with tongue-related obstruction showed no improvement in airflow, and the tongue remained posteriorly located while lateral. Patients without tongue involvement showed modest improvement in airflow (peak flow increased 0.07 L/s and ventilation increased 1.5 L/min). Epiglottic collapse was virtually abolished with lateral positioning and ventilation increased by 45% compared to supine position. Conclusions: Improvement in pharyngeal patency with sleeping position is structure specific, with profound improvements seen in patients with epiglottic collapse, modest effects in those without tongue involvement and-unexpectedly-no effect in those with tongue-related obstruction. Our data refute the notion that the tongue falls back into the airway during sleep via gravitational influences.

Airflow Shape Is Associated With the Pharyngeal Structure Causing OSA.

BACKGROUND: OSA results from the collapse of different pharyngeal structures (soft palate, tongue, lateral walls, and epiglottis). The structure involved in collapse has been shown to impact non-CPAP OSA treatment. Different inspiratory airflow shapes are also observed among patients with OSA. We hypothesized that inspiratory flow shape reflects the underlying pharyngeal structure involved in airway collapse. METHODS: Subjects with OSA were studied with a pediatric endoscope and simultaneous nasal flow and pharyngeal pressure recordings during natural sleep. The mechanism causing collapse was classified as tongue-related, isolated palatal, lateral walls, or epiglottis. Flow shape was classified according to the degree of negative effort dependence (NED), defined as the percent reduction in inspiratory flow from peak to plateau. RESULTS: Thirty-one subjects with OSA (mean apnea-hypopnea index score ± SD, 54 ± 27 events/h) who were 50 ± 9 years of age were studied. NED was associated with the structure causing collapse (P < .001). Tongue-related obstruction (n = 13) was associated with a small amount of NED (median, 19; interquartile range [IQR], 14%-25%). Moderate NED was found among subjects with isolated palatal collapse (median, 45; IQR, 39%-52%; n = 8) and lateral wall collapse (median, 50; IQR, 44%-64%; n = 8). The epiglottis was associated with severe NED (median, 89; IQR, 78%-91%) and abrupt discontinuities in inspiratory flow (n = 9). CONCLUSIONS: Inspiratory flow shape is influenced by the pharyngeal structure causing collapse. Flow shape analysis may be used as a noninvasive tool to help determine the pharyngeal structure causing collapse.

The impact of anatomic manipulations on pharyngeal collapse: results from a computational model of the normal human upper airway.

Obstructive sleep apnea (OSA) is a common disease with important neurocognitive and cardiovascular sequelae. Existing therapies are unsatisfactory, leading investigators to seek alternative forms of anatomic manipulation to influence pharyngeal mechanics. We have developed a two-dimensional computational model of the normal human upper airway based on signal averaging of MRI. Using the finite element method, we can perform various anatomic perturbations on the structure in order to assess the impact of these manipulations on pharyngeal mechanics and collapse. By design, the normal sleeping upper airway model collapses at -13 cm H2O. This closing pressure becomes more negative (ie, less collapsible) when we perform mandibular advancement (-21 cm H2O), palatal resection (-18 cm H2O), or palatal stiffening (-17 cm H2O). Where clinical data are available in the literature, the results of our model correspond reasonably well. Furthermore, our model provides information regarding the site of obstruction and provides hypotheses for clinical studies that can be undertaken in the future (eg, combination therapies). We believe that, in the future, finite element modeling will provide a useful tool to help advance our understanding of OSA and its response to various therapies.

Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a meta-analysis.

STUDY OBJECTIVE: To compare the effectiveness of auto-titrating continuous positive airway pressure (APAP) versus conventional continuous positive airway pressure (CPAP) in reducing the apnea-hypopnea index (AHI), reducing the mean airway pressure, improving subjective sleepiness, and improving treatment adherence in patients with obstructive sleep apnea (OSA). DESIGN: Meta-analysis and metaregression of published randomized trials comparing APAP to CPAP. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: We identified 9 randomized trials studying a total of 282 patients. Compared to CPAP, there was no significant advantage of APAP in reducing AHI or sleepiness (pooled APAP-CPAP posttreatment AHI and Epworth Sleepiness Scale score = -0.20 events per hour, 95% confidence interval:[-0.74,0.35], and -0.56 [-1.4,0.3] respectively). The use of APAP reduced the mean applied pressure across the night by 2.2 cm water [1.9,2.5] compared to CPAP. Adherence with therapy was not substantially improved with APAP; pooled estimate of improvement was 0.20 hours per night ([-0.16,0.57], P = .28) using a random-effects model. CONCLUSIONS: Compared to standard CPAP, APAP is associated with a reduction in mean pressure. However, APAP and standard CPAP were similar in adherence and their ability to eliminate respiratory events and to improve subjective sleepiness. Given that APAP is more costly than standard CPAP, APAP should not be considered first-line chronic therapy in all patients with OSA. However, APAP may be useful in other situations (eg, home titrations, detection of mouth leak) or in certain subgroups of patients with OSA. Identifying circumstances in which APAP is a definite improvement over CPAP in terms of costs or effects should be the focus of future studies.

Mandibular advancement device vs. CPAP in the treatment of obstructive sleep apnea: are they equally effective in Short term health outcomes?

QUESTION: Is the treatment of obstructive sleep apnea (OSA) with mandibular advancement device (MAD) similar in health outcomes to continuous positive airway pressure (CPAP) in the short term (one month health outcomes)? DESIGN: Randomized, open labeled, cross over, non-inferiority trial; Clinical trial registered with https://www.anzctr.org.au (ACTRN 12607000289415). ALLOCATION: Patients randomized to both the treatment acclimatization and treatment arm orders, resulting in 4 randomized sequences for MAD (M) and CPAP (C): MCMC, MCCM, CMMC and CMCM. Each sequence was generated by a computer program using random permuted blocks. The acclimatization periods for each treatment were generally between 4-6 weeks. Treatment periods were for 1 month each. BLINDING: The investigators and participants were not blinded to study arm assignment. FOLLOW-UP PERIOD: 1 month. SETTING: The study was conducted at three sleep centers in Sydney, Australia. SUBJECTS: 126 adults, mean age 49.5 years, 81% male, mean AHI 25.6 events/h, were randomized. INCLUSION CRITERIA: patients with newly diagnosed OSA, AHI > 10 events/h, age ≥ 20 years, ≥ 2 symptoms of OSA (snoring, fragmented sleep, witnessed apneas, or daytime sleepiness), and a willingness to use both treatments. EXCLUSION CRITERIA: previous OSA treatment or a need for immediate treatment, central sleep apnea, a coexisting sleep disorder, regular use of sedatives or narcotics, preexisting lung or psychiatric disease, and any contraindication for oral appliance therapy (e.g., periodontal disease or insufficient dentition). INTERVENTION: Patients meeting eligibility criteria were randomized to a 4-6 week each, acclimatization to CPAP and MAD. A 2 week wash out period was then followed by initial assignment to CPAP or MAD treatment and subsequent cross over. During each of the 4-6 weeks of acclimatization with each device, all patients were asked to use their device for as long as they could tolerate it on a nightly basis. OUTCOMES: The primary outcome was the difference in 24-hour mean arterial pressure (24MAP) between CPAP and MAD determined by 24-hour ambulatory blood pressure (BP) monitoring. Secondary outcome measures were central BP and arterial stiffness measurements, neurobehavioral function, and quality of life (QOL) using the Functional Outcomes of Sleep Questionnaire (FOSQ), the Short Form-36 (SF-36), the Epworth Sleepiness Score (ESS), and the AusEd driving simulator. Daily diaries were also used to monitor treatment side effects and determine subjective compliance. The sample size was calculated to show the non-inferiority of MAD relative to CPAP in the 24MAP after 1 month of therapy, using an a priori determined non-inferiority margin of 1.6 mmHg, assuming 90% power and a true difference between treatment means of zero. The primary hypothesis was tested by comparing the upper limit of the 95% confidence interval for the MAD-CPAP difference in 24MAP with the a priori non-inferiority margin using the paired t-test. PATIENT FOLLOW-UP: 18 patients (14%) withdrew after randomization, leaving 108 (86%) who completed the study. Two patients withdrew because of treatment intolerance (one CPAP and one both CPAP and MAD). Analyses were limited to the 108 subjects who completed the trial, regardless of compliance with their assigned treatment. MAIN RESULTS: There was no statistically significant difference between the groups in the primary outcome. MAD was non-inferior to CPAP with a CPAP-MAD 24MAP difference, 0.2 mmHg (95% confidence interval, -0.7 to 1.1 mmHg). However, ultimately neither treatment lowered BP from baseline in the entire group, after 1 month of therapy. In the subgroup of patients with baseline hypertension (n = 45), there were consistent treatment-related 24MAP improvements (p < 0.05) of 2.5 mmHg (CPAP) and 2.2 mmHg (MAD), with neither treatment having a superior effect. There were no differences in secondary outcome measures between groups, except MAD performed better than CPAP in improving four of eight SF-36 general QOL domains, and the overall mental component score (p < 0.05). Subjective reports of nightly compliance were less for CPAP compared with MAD (mean compliance 5.2 ± 2.0 vs. 6.5 ± 1.3 h/night, p < 0.0001).Treatment preference results showed that 55 patients (51%) preferred MAD, 25 (23%) preferred CPAP, 23 (21%) preferred either, and 5 (4.6%) preferred neither. CONCLUSION: In adults with predominately moderate to severe OSA, the short term (one month) use of an adjustable MAD was not inferior to CPAP in its impact on 24 hour mean ambulatory blood pressure, daytime sleepiness, disease specific and general quality of life. SOURCES OF FUNDING: The study was supported by Project Grant 457557, Practitioner Fellowship 202916 (R.R.G.), Health Professional Fellowship 571179, and CIRUS Postdoctoral Fellowship (C.L.P.) from the Australian National Health and Medical Research Council. ResMed Inc. donated all continuous positive airway pressure equipment for the trial. SomnoMed Ltd. donated all oral appliances for the trial and an unrestricted grant of A$60,000 to support the study.

Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The magnitude of the post-apnea/hypopnea ventilatory overshoot following arousal may perpetuate subsequent respiratory events in obstructive sleep apnea (OSA) patients, potentially contributing to the disorder's severity. As acetazolamide can reduce apnea severity in some patients, we examined the effect of acetazolamide on the ventilatory response to spontaneous arousals in CPAP-treated OSA patients. DESIGN: We assessed the ventilatory response to arousal in OSA patients on therapeutic CPAP before and after administration of acetazolamide for 7 days. SETTING: Sleep research laboratory. PARTICIPANTS: 12 (7M/5F) CPAP-treated OSA patients. INTERVENTIONS: Sustained-release acetazolamide 500 mg by mouth twice daily for one week. MEASUREMENTS AND RESULTS: A blinded investigator identified spontaneous arousals (3-15 s) during NREM sleep. Breath-by-breath measurements of minute ventilation, end-tidal CO(2), tidal volume, expiratory/inspiratory-time, and total breath duration were determined (4-s intervals) 32 s prior and 60 s following each arousal. Acetazolamide significantly increased resting ventilation (7.3 ± 0.2 L/min versus 8.2 ± 0.4 L/min; P < 0.05) and attenuated the percent increase in ventilation following arousal by ~2.5 fold (122.0% ± 4.4% versus 108.7% ± 3.5% pre-arousal level; P < 0.05). There was a positive correlation between the mean increase in ventilatory response to arousal and mean AHI (r(2) = 0.44, P = 0.01). However, absolute peak levels of ventilation following arousal remained unchanged between conditions (8.8 ± 0.4 L/min versus 8.9 ± 0.1 L/min). CONCLUSIONS: Acetazolamide substantially attenuates the increase in ventilation following spontaneous arousal from sleep in OSA patients. This study suggests an additional mechanism by which acetazolamide may contribute to the improvement in ventilatory instability and OSA severity. The data also provide support for reinforcing the importance of ventilatory control in OSA pathogenesis.

Sleep apnea.

Obstructive sleep apnea is a common disorder characterized by repetitive collapse of the pharyngeal airway during sleep. The disorder results primarily from an anatomically small upper airway in conjunction with pharyngeal dilator muscles that can compensate for the anatomic deficiency awake, but not asleep. Ventilatory control instability and a low arousal threshold may contribute to the disorder as well. The consequences of sleep apnea fall into two domains: (1) neurocognitive dysfunction (sleepiness and decreased quality of life) resulting from sleep fragmentation and (2) cardiovascular disease (hypertension, stroke, myocardial infarction, and heart failure) likely resulting from the intermittent hypoxia. The disorder is generally diagnosed in the sleep laboratory over the course of a night, although alternative approaches in the home are also utilized. A number of treatment options are available. Continuous positive airway pressure remains the most consistently effective approach, although oral appliances (generally mandibular-advancing devices) and a number of surgical procedures have some demonstrated efficacy. Thus, therapy must be individualized to the patient's desires and the severity of the apnea.