Obstructive Sleep Apnea in Adults: Screening
November 15, 2022
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
|Table of Contents|
By Cynthia Feltner, MD, MPH; Ina F. Wallace, PhD; Shannon Aymes, MD, MPH; Jennifer Cook Middleton, PhD; Kelli L. Hicks, MD, MPH; Manny Schwimmer, MPH; Claire Baker; Casey P. Balio, PhD; Daniel Moore, MPH; Christiane E. Voisin, MSLS; Daniel E. Jonas, MD, MPH
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was published online in JAMA on November 15, 2022 (JAMA. 2022;328(19):1951-1971. doi:10.1001/jama.2022.18357).
Importance: Obstructive sleep apnea (OSA) is associated with adverse health outcomes.
Objective: To review the evidence on screening for OSA in asymptomatic adults or those with unrecognized OSA symptoms to inform the US Preventive Services Task Force.
Data Sources: PubMed/MEDLINE, Cochrane Library, Embase, and trial registries through August 23, 2021; surveillance through September 23, 2022.
Study Selection: English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or treatment of OSA reporting health outcomes or harms, and systematic reviews of treatment reporting changes in blood pressure and apnea-hypopnea index (AHI) scores.
Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. Meta-analysis of intervention trials.
Main Outcomes and Measures: Test accuracy, excessive daytime sleepiness, sleep-related and general health–related quality of life (QOL), and harms.
Results: Eighty-six studies were included (N = 11,051). No study directly compared screening with no screening. Screening accuracy of the Multivariable Apnea Prediction score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI > 30 and Epworth Sleepiness Scale [ESS] score > 10) measured as the area under the curve in 2 studies (n = 702) was 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90). Five studies assessing the accuracy of other screening tools were heterogeneous and results were inconsistent. Compared with inactive control, positive airway pressure was associated with a significant improvement in ESS score from baseline (pooled mean difference, −2.33 [95% CI, −2.75 to −1.90]; 47 trials; n = 7024), sleep-related QOL (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 17 trials; n = 3083), and general health–related QOL measured by the 36-Item Short Form Health Survey (SF-36) mental health component summary score change (pooled mean difference, 2.20 [95% CI, 0.95 to 3.44]; 15 trials; n = 2345) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials; n = 2031). Use of mandibular advancement devices was also associated with a significantly larger ESS score change compared with controls (pooled mean difference, −1.67 [95% CI, 2.09 to −1.25]; 10 trials; n = 1540). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with treatment on mortality, cardiovascular events, or motor vehicle crashes. In 3 systematic reviews, positive airway pressure was significantly associated with reduced blood pressure; however, the difference was relatively small (2-3 mm Hg).
Conclusions and Relevance: The accuracy and clinical utility of OSA screening tools that could be used in primary care settings were uncertain. Positive airway pressure and mandibular advancement devices reduced ESS score. Trials of positive airway pressure found modest improvement in sleep-related and general health–related QOL but have not established whether treatment reduces mortality or improves most other health outcomes.
Obstructive sleep apnea (OSA) is a sleep disorder marked by episodes of narrowing and obstruction of the upper airway during sleep, resulting in reduction or cessation in breathing.1 OSA is defined as more than 5 events per hour of partial (hypopnea) or total (apnea) upper airway obstruction despite efforts to breathe.2 Apnea is defined as total airway obstruction (>90%) for more than 10 seconds, and hypopnea as a partial airway obstruction (>30%) sufficient to cause at least a 3% reduction in blood oxygen saturation or sleep arousals.3 The apnea-hypopnea index (AHI) is used to define the severity of OSA: mild (5-15 events per hour), moderate (16-30 events per hour), and severe (>30 events per hour). Standardized prevalence estimates using the 2012 American Academy of Sleep Medicine (AASM) scoring criteria were 33.2% for any OSA (AHI ≥ 5) and 14.5% for moderate to severe OSA (AHI ≥ 15).4 Risk factors for OSA include male sex,5 postmenopausal status,6 increasing age (40-70 years),7,8 and higher body mass index (BMI).5 A variety of adverse health outcomes are associated with untreated OSA, including cardiovascular disease events, coronary heart disease, heart failure, atrial fibrillation, and stroke. Severe OSA (AHI ≥ 30) is associated with increased all-cause mortality.9,10
In 2017, the US Preventive Services Task Force (USPSTF) concluded that the evidence was insufficient to assess the balance of benefits and harms of screening for OSA in asymptomatic adults (I statement).11 This updated review assessed the current evidence on OSA screening in individuals and settings relevant to US primary care and was used to update the USPSTF recommendation.
Scope of Review
Figure 1 shows the analytic framework and key questions (KQs) that guided the review. Detailed methods are available in the full evidence review.13 In addition to the KQs, this review looked for evidence related to 2 contextual questions that focused on barriers to undergoing diagnostic testing for OSA and the association between AHI and health outcomes (eContextual Questions in the JAMA Supplement).
Data Sources and Searches
PubMed/MEDLINE, the Cochrane Library, and Embase were searched for English-language articles published through August 23, 2021 (eMethods in the JAMA Supplement). ClinicalTrials.gov was searched for unpublished studies. The searches were supplemented by reviewing reference lists of pertinent articles, studies suggested by peer reviewers, and comments received during public commenting periods. From August 23, 2021, through September 23, 2022, ongoing surveillance was conducted through article alerts and targeted searches of journals to identify major studies published in the interim that may affect the conclusions or understanding of the evidence and the related USPSTF recommendation.
Two investigators independently reviewed titles, abstracts, and full-text articles using prespecified eligibility criteria (eTable 1 in the JAMA Supplement). Disagreements were resolved by consensus. For all KQs, English-language studies of adults 18 years or older conducted in countries categorized as “very high” on the Human Development Index14 and rated as fair or good quality were included.
For KQ1 and KQ3 (direct evidence of benefits and harms of screening) and KQ2 (accuracy of screening tools), studies of asymptomatic adults with OSA or persons with unrecognized OSA symptoms were included. For KQ1 and KQ3, randomized clinical trials (RCTs) comparing screened groups with nonscreened groups and reporting on health outcomes were eligible. For KQ2, prospective cohort studies and cross-sectional studies assessing the accuracy of screening questionnaires or clinical prediction tools (alone or followed by an unattended home sleep test) compared with polysomnography conducted in a sleep laboratory were eligible. For KQ2, studies limited to persons referred to sleep laboratories for suspected OSA were excluded. For KQ3 (harms of screening), studies eligible for KQ1 or KQ2 that reported harms of screening or diagnostic tests (eg, false-positive results leading to unnecessary treatment, anxiety, distress, or stigma) were eligible.
For KQs 4 through 6 (benefits and harms of treatment), studies were limited to those of interventions considered first-line treatment for persons diagnosed with OSA (positive airway pressure or mandibular advancement devices [MADs]) compared with inactive control; other interventions (eg, weight loss interventions, oral surgical procedures) were excluded. For KQ4 (benefit of treatment for improving intermediate outcomes), good-quality, recent (within 5 years) systematic reviews comparing positive airway pressure or MADs with an inactive control and reporting on changes in blood pressure or AHI were included. For KQs on the benefits of treatment for improving health outcomes (KQ5) and on the harms of treatment (KQ6), RCTs of adults with a confirmed diagnosis of OSA were eligible.
Data Extraction and Quality Assessment
For each study, 1 investigator extracted information about populations, tests or interventions, comparators, outcomes, settings, and designs, and a second investigator reviewed the information for completeness and accuracy. Two investigators independently assessed the quality of included studies using criteria defined by the USPSTF adapted for this topic supplemented with criteria from the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)15 and from A Measurement Tool to Assess Systematic Reviews (AMSTAR)16 (eTables 2-8 in the JAMA Supplement). Each study was assigned a final quality rating of good, fair, or poor; disagreements were resolved by discussion and consensus.
Data Synthesis and Analysis
Findings for each KQ were summarized in tables, figures, and narrative format. To determine whether meta-analyses were appropriate, the clinical and methodological heterogeneity of the studies were assessed following established guidance.17 For KQ5, random effects restricted maximum likelihood models were conducted on continuous measures of sleepiness, general health–related quality of life (QOL), and sleep-related QOL associated with positive airway pressure and MAD use when at least 3 similar studies were available, analyzing the mean difference in change from the baseline score or the standardized mean difference (SMD). The meta command in Stata version 16 was used to conduct all quantitative analyses.18 The I2 statistic was used to assess the statistical heterogeneity in effects between studies.19-21 Statistical significance was assumed when 95% CIs of pooled results did not cross the null. All testing was 2-sided.
A total of 86 studies (reported in 101 articles; N = 11,051) were included (Figure 2) in the review. Individual study quality ratings are reported in eTables 2 through 8 in the JAMA Supplement.
Benefits of Screening
Key Question 1. Does screening for OSA in adults improve health outcomes, including for specific subgroups of interest?
No eligible studies addressed this question.
Accuracy of Screening
Key Question 2. What is the accuracy of screening questionnaires, clinical prediction tools, and multistep screening approaches (eg, using a questionnaire followed by home-based oximetry/testing) in identifying persons in the general population who are more or less likely to have OSA, including for specific subgroups of interest?
Seven fair-quality studies (n = 2589)22-28 assessing clinical prediction tools or screening questionnaires compared with facility-based polysomnography were included, 4 of which were new to this review (Table 1).25-28 Two evaluated the Berlin Questionnaire,22,25 4 evaluated the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, gender) questionnaire,25-28 and 2 evaluated the Multivariable Apnea Prediction (MVAP) score—alone and when followed by an unattended home sleep test.23,24
The Berlin Questionnaire includes 10 questions about snoring, tiredness, and blood pressure and gathers information on age, sex, height, and weight to classify OSA risk.29 Two included studies of the Berlin Questionnaire enrolled different populations. One sampled Norwegians from the National Population Register.22 Of those who responded, 24% were classified as high risk on the Berlin Questionnaire. The final sample enrolled a population with a mean age of 48 years, 45% were women, the mean BMI was 28 (calculated as weight in kilograms divided by height in meters squared), and the median AHI was 6.4. Although the group receiving polysomnography oversampled high-risk participants (70% were high risk), the authors’ analyses adjusted for bias in the sampling procedure to report estimated screening properties for the general population. In contrast, the second study assessing the Berlin Questionnaire25 included a small (n = 43) but unselected sample of adults with type 2 diabetes recruited from a US general internal medicine clinic. A majority (53%) were female, the mean BMI was 38.3, and the mean AHI was 31.2.
The study enrolling Norwegian participants22 found suboptimal screening accuracy for AHI 5 or greater (sensitivity, 37%; specificity, 84%) and for AHI 15 or greater (sensitivity, 43%; specificity, 80%) (Table 2). The study enrolling US participants with type 2 diabetes from a general internal medicine clinic assessed accuracy for mild (AHI 5-14), moderate (AHI 15-29), and severe (AHI ≥ 30) OSA.25 Specificity of the Berlin Questionnaire was suboptimal for all categories of OSA severity (mild, 0%; moderate, 31%; severe, 26%). Sensitivity was higher for moderate OSA (89%) and for severe OSA (93%) but was lower for mild OSA (80%).
The STOP-BANG questionnaire includes 8 dichotomous items (snoring, tiredness, observed apnea, blood pressure, BMI, age, neck circumference, and gender).30,31 The 4 studies assessing the accuracy of the STOP-BANG questionnaire enrolled diverse populations and used different scoring criteria and additional variables to determine a positive screen result.25-28 Detailed characteristics of each study are reported in Table 1.
The heterogeneity of studies and scoring approaches limits the ability to assess consistency of results. Overall, estimates varied, and no study found both high sensitivity and high specificity (Table 2). One study enrolling US adults with type 2 diabetes found good sensitivity for detecting mild (87%), moderate (93%), and severe (94%) OSA but very low specificity for the same subgroups (mild, 0%; moderate, 19%; severe, 15%).25 In contrast, the study enrolling Spanish adults with Alzheimer disease found modest sensitivity (61%) and somewhat better specificity (76%) for severe OSA.26 The study of Korean adults found moderate sensitivity (62%) and specificity (64%)for detecting mild through severe OSA.27 The study of adults receiving opioids for chronic pain provided accuracy data for the STOP-BANG questionnaire alone as well as for the STOP-BANG questionnaire plus resting daytime SpO2 (first stage). Results for various cutoffs are reported in Table 2; across all screening approaches, sensitivity for the STOP-BANG to detect moderate to severe OSA was very good, but specificity was limited.
The MVAP score combines symptoms of snoring, choking, and witnessed apnea events with BMI, age, and sex.32 It rates apnea risk between 0 and 1, with 0 representing the lowest risk and 1 representing the highest risk. The 2 included studies assessing the MVAP were conducted by the same research group from Philadelphia.23,24 One study evaluated Medicare recipients (n = 452) from the city’s greater metropolitan area, most of whom (74%) had daytime sleepiness.23 The percentage with OSA was not reported, but 27% had OSA syndrome (OSAS) defined as AHI ≥ 5 or greater and Epworth Sleepiness Scale [ESS] score greater than 10. The second study evaluated patients with hypertension from internal medicine practices at a Veterans Affairs medical center and a university-based hypertension clinic (n = 250).24 Eighty percent of participants had OSA (AHI5); of those, 22% had moderate OSA and 25% had severe OSA. Twenty-five percent of all participants had OSAS. The mean ages of participants were 71 years23 and 53 years,24 60% to 64% were non-White, and the mean BMIs were 30 to 32. The study of Medicare recipients included 70% women;23 the other study included 20% women.24 Key quality limitations included concern for attrition bias24 and moderate concern for selection bias or spectrum bias (with high prevalence of OSA, OSAS, and/or sleepiness among those receiving polysomnography) (eTables 2 and 3 in the JAMA Supplement).23,24
Both studies reported operating characteristics of MVAP to predict severe OSAS (AHI ≥ 30 and ESS score >10) using MVAP cutoff scores of 0.48 to 0.49 (Table 2). Sensitivity was 90%23 and 92%,24 with specificity of 64% and 44%, respectively (95% CIs not reported). The study of Medicare recipients reported reasonable discrimination (area under the curve [AUC], 0.78 [95% CI, 0.71-0.85]), whereas the other study found inadequate discrimination (AUC, 0.68 [95% CI, 0.67-0.70]). An AUC less than 0.70 is thought to indicate inadequate discrimination.33,34 Calibration, which is often assessed by plotting the predicted risk vs the observed rate,33 was not reported.
The study of patients with hypertension24 also reported operating characteristics of MVAP to predict any OSAS (AHI ≥5 and ESS score >10) using an MVAP cutoff score of 0.559. That study reported a sensitivity of 69.4%, a specificity of 56.5%, and an AUC of 0.61.
MVAP Score Followed by Home Sleep Test
The same 2 studies described in the previous section also reported measures of discrimination for the MVAP score followed by an unattended home sleep test compared with in-laboratory polysomnography (Table 1).23,24 Both reported characteristics to predict severe OSAS (AHI ≥ 30 and ESS score >10) using different home sleep test AHI cutoffs: 1 used 15,23 and the other used 18.24 Both studies found better operating characteristics with MVAP followed by a home sleep test than with MVAP alone (sensitivity, 88%-91%; specificity, 72%-76%; AUC, 0.80-0.83).
The study of patients with hypertension also reported operating characteristics of MVAP to predict any OSAS (AHI ≥ 5 and ESS score >10) using a home sleep test AHI cutoff of 13.5. It reported a sensitivity of 81%, a specificity of 54%, and an AUC of 0.67.
Harms of Screening
Key Question 3. What are the harms associated with screening or subsequent diagnostic testing for OSA, including for specific subgroups of interest?
No eligible study addressed this question.
Benefits of Treatment
Key Question 4. How effective is treatment with positive airway pressure or MADs for improving intermediate outcomes (ie, the AHI or blood pressure) in persons with OSA, including for specific subgroups of interest?
Four systematic reviews comparing positive airway pressure or MADs with inactive control for reducing AHI or blood pressure were included (eTable 9 in the JAMA Supplement).35-38 For blood pressure outcomes, 1 review of MADs found benefit associated with treatment compared with inactive control (by 1-2 mm Hg); however, differences between groups were imprecise and not statistically significant (eTable 9 in the JAMA Supplement).35 For positive airway pressure, pooled estimates from 1 review found benefit associated with positive airway pressure compared with control for reducing mean 24-hour blood pressure (−2.63 mm Hg [95% CI, −3.86 to −1.39]; 8 trials; n = 994); pooled results for measures of daytime systolic blood pressure and diastolic blood pressure were also significantly lower with positive airway pressure vs control, ranging from −2.76 to −1.98 mm Hg, respectively (eTable 9 in the JAMA Supplement). Results from 2 additional reviews focused on specific populations, including participants with treatment-resistant hypertension, are reported in eTable 9 in the JAMA Supplement.
Two reviews of positive airway pressure reported on the difference between groups in change from baseline AHI.37,38 One found a greater reduction in AHI associated with positive airway pressure than with controls (pooled mean difference, −23.41 events per hour [95% CI, −28.51 to −18.30]; 11 trials; n = 832).37 The second review—which limited inclusion to studies of asymptomatic adults with OSA or studies of minimally symptomatic, nonsleepy adults—found consistent but imprecise pooled estimates (eTable 9 in the JAMA Supplement).38
Effectiveness of Treatment
Key Question 5. How effective is treatment with positive airway pressure or MADs for improving health outcomes in persons with OSA, including for specific subgroups of interest?
This review included 73 good- or fair-quality RCTs (reported in 87 articles) that reported at least 1 eligible health outcome among groups treated with positive airway pressure or a MADs compared with inactive control.
Positive Airway Pressure
Sixty-three RCTs (74 articles) comparing positive airway pressure with sham positive airway pressure (29 RCTs, 33 articles)39-71 or another inactive control (34 RCTs, 41 articles)72-112 reported at least 1 eligible health outcome. Most trials identified participants from sleep clinics or referrals, and none focused on persons who were screen detected in primary care settings. Detailed characteristics are reported in eTables 10 and 11 in the JAMA Supplement.
Most trials (53) followed up participants for 12 weeks or less; 10 trials followed up participants over a longer duration (16 to 24 weeks [5 trials],53,78,87,105,111 52 weeks [3 trials],74,96,108 a median of 4 years [1 trial],75 and a median of 4.7 years [1 trial]).97 The mean age of enrolled populations ranged from 44 to 78 years, and most trials enrolled populations with a mean age of 40 to 59 years; 7 enrolled populations with a mean age of 65 years or older.43,61,79,93,96,97,100 The majority of participants in most trials were men; 1 trial limited enrollment to women,77 and 3 enrolled a majority of women.104,109,113 Most trials did not describe the race and ethnicity of enrolled populations, and those that did (14 trials) used heterogeneous categories and varying levels of detail (eTables 10 and 11 in the JAMA Supplement). The mean BMI in most trials was 30 to 36 (range, 25-47). The mean or median baseline AHI (or similar measure) for most trials was in the severe OSA range (AHI ≥ 30); 13 trials reported mean baseline AHI in the moderate OSA range (AHI 16-30),43,58,61,66,76,80,89, 96,97, 105, 108, 109, 111 and 6 reported a mean baseline AHI in the mild OSA range (AHI 5-15).69,78,81,83,101,107 The severity of OSA for participants enrolled in trials most frequently ranged from moderate to severe (29 trials) or from mild to severe (16 trials). Seventeen trials limited participants to more narrow ranges: mild only,83,107 mild to moderate or moderate only,58,69,76,97,100,101,105 or severe only.40,59,79,91-94,104 One trial did not report sufficient data to determine the range of OSA severity of participants.78 The mean or median baseline ESS score was 10 or greater in most trials, indicating excessive daytime sleepiness (EDS). Eighteen trials reported a mean baseline ESS score of less than 10,40,43,46,66,73-75,78,79,85,87,92,97,100,104,108,109,111 and 6 trials did not report a baseline ESS score.
Mortality. Thirty-one RCTs reported on the number of deaths during the study period (eTable 12 in the JAMA Supplement). The majority (28 RCTs) reported mortality rates at 24 weeks or less, and most of these (25 RCTs) reported no deaths in any study group (eTable 12 in the JAMA Supplement). Two reported on mortality over a median duration of 4 to 5 years; 1 (n = 723) reported 8 deaths in the positive airway pressure group and 3 in the control group (incidence density ratio, 2.6 [95% CI, 0.70-11.8]; P = .16),75 and the second (n = 364) found a similar number of deaths among the positive airway pressure and control groups (8% vs 7%, respectively).97
General Health–Related QOL. Twenty RCTs reported on QOL using the 36-Item Short Form Health Survey (SF-36);40,46,50,59,60,67-69,76,78,83,86,89,94,96,105,107,108,111,112 most trials reported changes on the SF-36 physical component summary score and the mental component summary score. Pooled estimates in change from baseline SF-36 mental component summary score found a significantly greater improvement associated with positive airway pressure compared with inactive control (2.20 [95% CI, 0.95-3.44]; 15 trials; n = 2345).40,46,50,60,67-69,78,86,94,105,107,108,111,112 Similarly, pooled estimates for change in SF-36 physical component summary score from baseline found significantly greater improvement associated with positive airway pressure than with control (1.53 [95% CI, 0.29-2.77]; 13 trials; n = 2031 participants) (Table 3; eFigure 1 in the JAMA Supplement).40,46,50,60,67-69,86,94,107,108,111,112 The pooled estimates for change from baseline SF-36 mental component summary score and SF-36 physical component summary score associated with positive airway pressure were smaller than the range considered a minimal clinically important difference (MCID), which is 4 to 7 for both SF-36 component summary scores.116,117 Few RCTs reported on other measures of QOL. Few studies reported on other QOL measures; overall, results were mixed (eTable 12 in the JAMA Supplement).
Sleep-Related QOL. Seventeen RCTs assessed sleep-related QOL: 6 using the Sleep Apnea Quality of Life Index (SAQLI),54,67,70,78,89,96 10 using the Functional Outcomes of Sleep Questionnaire (FOSQ),40,58-60,65,69,76,84,94,107,111 and 1 using the Quebec Sleep Questionnaire.79 The meta-analysis (combining all measures) found that positive airway pressure was associated with a small but statistically significant improvement in sleep-related QOL compared with controls (SMD, 0.30 [95% CI, 0.19-0.42]; 17 trials; n = 3083) (eFigure 2 in the JAMA Supplement). The subgroup analysis by mean baseline ESS score found a similar but slightly larger effect size in trials with a mean ESS score of 10 or greater (SMD, 0.35 [95% CI, 0.22-0.49]; 11 trials, n = 2228). In studies with a mean baseline ESS score of less than 10, the effect size was smaller and the pooled estimate was not statistically significant (eFigure 4 in the JAMA Supplement). Results shown as a mean difference in scores for each sleep-related QOL measure are provided in eFigure 3 in the JAMA Supplement and summarized in Table 3. For both the SAQLI and FOSQ, the pooled mean difference falls below the range considered an MCID.
ESS Score. Forty-seven trials reported sufficient ESS data to include in meta-analyses. Most were 12 weeks or less in duration; 7 followed up participants for 24 weeks,53,105,111 48 to 52 weeks,74,96,108 or longer.75 The meta-analyses found that positive airway pressure reduced mean ESS scores more than controls (pooled mean difference, −2.33 [95% CI, −2.75 to −1.90]; 47 trials; n = 7024) (Figure 3). The pooled mean difference is within the range considered an MCID for the ESS (−2 to −3).114,115 These analyses found substantial statistical heterogeneity that may be due to variation in positive airway pressure devices, participant characteristics (eg, baseline ESS score), treatment adherence, study duration, or chance; however, no clear explanation was found. As shown in Figure 3, heterogeneity is lower in subgroups defined by narrow ranges of OSA severity (severe only and mild only or mild to moderate vs mild to severe) (Figure 3). However, the meta-analyses by OSA severity subgroup (4 categories: mild to severe, mild only and mild to moderate, moderate only and moderate to severe, and severe only) did not find a clear difference by OSA severity. Differences in mean score change were −2.61 for mild to severe, −1.91 for mild only and mild to moderate, −2.21 for moderate only and moderate to severe, and −3.08 for severe only, and CIs overlapped; the analysis still found considerable statistical heterogeneity within the mild to severe group and the moderate only or moderate to severe group (Figure 3).
Other Health Outcomes. Fewer studies reported on other health outcomes (eTable 12 in the JAMA Supplement). Three RCTs reported on the incidence of motor vehicle crashes over 12 to 52 weeks, and none found a statistically significant difference between groups.53,85,96 Ten reported on the incidence of 1 or more heterogeneous cardiovascular outcomes.46,53,58,70,75,78,85,96,97,111 Six RCTs (1773 total participants) reported on the incidence of myocardial infarction; in 4 of these, a total of 1 myocardial infarction occurred (combined) in either group over 3 weeks to 1 year.58,78,85,96 Two RCTs reported on outcomes over a median of 4 to 5 years; 1 (n = 723) reported 2 myocardial infarctions in the positive airway pressure group and 8 in the control group,75 and the second (n = 244) found a similar number of myocardial infarctions in the positive airway pressure and control groups (9% vs 7%, respectively).97
RCTs reporting on other health outcomes (eg, angina, transient ischemic attacks, measures of cognitive impairment) are shown in eTable 12 in the JAMA Supplement. Overall, too few events occurred to draw conclusions.
Mandibular Advancement Devices
Twelve RCTs (15 articles) evaluated the benefit of MADs for improving health outcomes (eTable 13 in the JAMA Supplement).76,89,120-132 Four studies compared MADs with sham devices that did not advance the mandible,120,121,130-132 1 compared a MAD with a placebo tablet,76 2 compared MADs with no treatment,123,129 and 1 compared a MAD with conservative management of OSA with weight loss.89 All studies recruited participants with known or suspected OSA from specialty clinics, such as sleep medicine or otolaryngology. Treatment durations ranged from 4 to 12 weeks for most studies; however, 1 lasted for only 1 week123 and 1 for 24 weeks.120,121 The mean age of enrolled participants ranged from 46 to 58 years. In 11 trials reporting on sex, the majority of participants were men. No study reported the percentage of minority participants. Almost all studies included participants with mild to moderate OSA, and 6 also included participants with severe OSA.89,122,123,125,128,132
Mortality. Four trials reported on deaths in each group over 1 to 12 weeks of follow-up,76,123,129,132 3 reported no participant deaths, and 1 reported a single death in the control group.132
General Health–Related and Sleep-Related QOL. Six RCTs reported on at least 1 QOL measure.76,89,120,121,129,131,132 Overall, results were mixed, with some studies finding no significant improvement in QOL from using MADs,89,120,121,131 some reporting possible benefits for some measures or subscales but not for others,76,132 and some reporting benefits for some overall QOL scores.129 Further details and specific data are provided in eTable 14 in the JAMA Supplement. Because of inconsistency, imprecision, and heterogeneity of reporting, findings are insufficient to make conclusions about the potential benefits of using MADs for improving QOL.
ESS Score. Ten RCTs of MADs provided sufficient data on change from ESS scores from baseline to be included in pooled estimates;76,89,122-125,128-130,132 MADs were associated with significantly greater reduction from baseline ESS scores than controls (−1.67 [95% CI, −2.09 to −1.25]; 10 trials; n = 1540 participants) (eFigure 5 in the JAMA Supplement). The pooled mean difference, however, falls below the range considered an MCID for the ESS.114,115
Other Health Outcomes. This review included 1 trial assessing each of the following outcomes for participants using MADs over 6 to 12 weeks: cognitive impairment,76 motor vehicle crashes,129 cardiovascular events,129 and headaches.131 Specific data are provided in eTable 14 in the JAMA Supplement. Because of unknown consistency, imprecision, and very small numbers of events, findings were insufficient to make conclusions about the potential benefits of MADs for these outcomes.
Harms of Treatment
Key Question 6. What are the harms associated with treatment of OSA using positive airway pressure or MADs, including for specific subgroups of interest?
Reporting of harms in the included RCTs was sparse, and most did not report information on harms. Nineteen RCTs (reported in 24 articles) reported on harms associated with treatment of OSA, including 9 trials of positive airway pressure,49,53,54,68,69,83,89,101,105,113,133,134 9 of MADs,89,120,121,123-132 and 1 of positive airway pressure and MADs.89 Characteristics and detailed results of all 19 studies reporting harms are provided in eTables 10, 11, 13, 15, and 16 in the JAMA Supplement.
Positive Airway Pressure
Of the 10 included RCTs of positive airway pressure, 6 compared positive airway pressure with a sham device,49,53,54,68,69,113,133,134 and 4 compared positive airway pressure with another control (eg, oral placebo, usual care).83,89,101,105 Most enrolled fewer than 100 persons; 1 trial, the Apnea Positive Pressure Long-term Efficacy Study,53,54 enrolled more than 1000 participants. The majority of participants were men, the mean age ranged from 42 to 62 years, and most participants were overweight or obese (mean BMI, 27-39). Most of the studies followed up patients for 8 to 12 weeks, and 2 lasted 24 weeks.53,54,105
Outcomes reported were heterogeneous, and detailed results are reported in eTable 15 in the JAMA Supplement. In general, harms related to positive airway pressure treatment were likely short-lived and could have been alleviated by discontinuing treatment with positive airway pressure or by supplementing positive airway pressure with additional interventions. Overall, 1% to 47% of participants in trials of positive airway pressure reporting any harms had specific adverse events while using positive airway pressure, including claustrophobia, oral or nasal dryness, eye or skin irritation, rash, nosebleeds, and pain.
Mandibular Advancement Devices
Ten RCTs reported harms related to MAD use.89,120,121,123-132 Most RCTs (6) lasted 4 to 8 weeks, 1 lasted a single week,123 1 lasted 10 weeks,89 1 lasted 12 weeks,124 and 1 lasted 24 weeks.120,121 Across 3 studies that reported any discontinuation of treatment because of adverse events, 7% of patients in the active MAD group discontinued MAD use because of harms compared with 1% of patients in the control group.89,129,132 In 4 RCTs, rates of oral dryness ranged from 5% to 33% in the active MAD group compared with 0% to 3% in the control group.89,120,121,124,129 Six studies reported rates of excess salivation.89,120,121,124-127,129,131 Four trials reported significantly higher rates of excessive salivation associated with MAD use than with sham MAD or no treatment,89,120,121,129 In 7 studies, adverse oral mucosal, dental, or jaw symptoms ranged from 17% to 74% in MAD groups compared with 0% to 17% in the sham group, no-treatment group, or conservative management group. Two studies reported that there was a statistically significant difference only in the percentage who experienced jaw discomfort and tooth tenderness in the MAD group compared with that in the sham group.125-127,131
This systematic review synthesized evidence relevant to screening for OSA in adults. Table 4 summarizes findings, including an assessment of the strength of evidence for each KQ. To date, there is no direct evidence from trials on the benefits and harms of screening for OSA vs no screening. Potential harms of routine screening include overdiagnosis and overtreatment for asymptomatic persons with OSA (AHI ≥ 5) who never had symptoms of OSA or adverse health outcomes from OSA. Other potential harms include costs associated with referrals and additional testing (eg, future polysomnography for follow-up care).
This review identified few eligible studies evaluating the accuracy of questionnaires or prediction tools for distinguishing persons in the general population who are more or less likely to have OSA. No included screening approach was assessed by more than 2 included studies, which limits the ability to draw conclusions about the accuracy of screening tools in primary care. The screening approach evaluated by 2 studies, the MVAP score followed by an unattended home sleep test for detecting severe OSAS (AHI ≥ 30 and ESS score >10), may have promise for screening, but the evidence was limited by potential spectrum bias135-139 due to oversampling of high-risk participants and of those with OSA and OSAS, which may substantially overestimate the accuracy of using the MVAP score to screen for OSA in the general population. The included studies evaluating MVAP enrolled populations with a high prevalence of OSAS (≥ 25%),23,24 OSA (AHI ≥ 5 for 80% of participants),24 and sleepiness (74%).23
This review included fewer studies evaluating questionnaires or clinical prediction tools than some previously published reviews and guidelines,9,140,141 primarily because of the requirement to include studies that enrolled asymptomatic adults or adults with unrecognized symptoms of OSA; referral populations (eg, to sleep clinics) were not eligible. Previous reviews and guidelines focused generally on diagnostic testing (of adults with symptoms suggestive of disordered sleep) rather than on screening (of asymptomatic persons with OSA or those with unrecognized symptoms of OSA). Nevertheless, these reviews and guidelines generally reported low overall quality and strength of evidence for questionnaires and prediction tools.
This review found consistent evidence from good- and fair-quality RCTs that positive airway pressure reduces excessive daytime sleepiness and may improve general health–related and sleep-related QOL. However, benefit associated with positive airway pressure for both general health–related and sleep-related QOL measures falls short of the range considered an MCID (Table 3), and the clinical significance of the 2-point mean reduction on the ESS is somewhat uncertain. For excessive sleepiness, the data suggest a clinically significant reduction in most included trials because 85% of the trials in the meta-analysis for ESS with mean baseline ESS scores of 10 or greater (indicating excessive daytime sleepiness) reported mean end point ESS scores in the normal range of less than 10142,143 for the positive airway pressure groups (mean end point ESS score < 8). However, the threshold for a clinically significant change in ESS score is somewhat uncertain. Although recent systematic reviews noted that experts consider a 1-point change in ESS score clinically significant,9 other sources suggest that a 2- to 3-point change114,115 or a 3- to 4-point change should be the clinically significant threshold for its sample size calculations or interpretation of findings.144-146 Also, the American College of Chest Physicians’ outcome experts evaluating the ESS informally stated that a clinically significant change in the ESS score probably is at least 3 points and cited a specific example that a reduction of 1 point (eg, from 3 [high] to 2 [moderate]) on 2 of 7 ESS domains was unlikely to be clinically relevant (Jon-Erik C. Holty, MD, MS, Stanford University, email, October 2015). Regardless of the clinically significant threshold level, the subjective nature of the ESS creates potential bias in trials of treatment (eg, overreporting of improvements in sleepiness after receiving treatment), and some authors have raised concerns about its construct validity (ie, authors have expressed uncertainty regarding whether it is an accurate measure of sleepiness).147-149
For blood pressure reduction (KQ4), recent systematic reviews found that MAD and positive airway pressure are associated with a reduction in blood pressure of 2 to 3 mm Hg, and 1 review limited to populations with resistant hypertension found a slightly higher mean reduction (5 mm Hg). Some experts suggest that a difference of more than 9 mm Hg systolic/10 mm Hg diastolic is clinically meaningful for patients.150-152 However, guidelines have suggested that across a population, a smaller reduction in systolic blood pressure (2-3 mm Hg) could result in a clinically significant reduction in cardiovascular mortality (4%-5% for coronary heart disease and 6%-8% for stroke).153 Even though MADs and positive airway pressure have been shown to reduce mean blood pressure, no trial to date has shown a significant reduction in mortality or cardiovascular disease.
Evidence on most health outcomes was limited (ie, too few RCTs reported on outcomes or too few events occurred to evaluate the effectiveness of positive airway pressure for reducing mortality or motor vehicle crashes). As summarized in the eContextual Questions in the JAMA Supplement, a relatively large body of observational evidence supports an association between severe OSA and increased risk of many adverse health outcomes, including cardiovascular events, mortality, and cognitive impairment. Some observational studies suggest that the risk of such outcomes increases with each level of OSA severity, which may indicate a dose-response effect; however, this finding is not consistent across all studies or outcomes. In addition, findings of increased risk associated with severe OSA are the strongest among male populations; however, it is difficult to assess whether these relationships do not hold for female populations or reflect sparse evidence on female populations compared with male populations. Observational studies focused on this association are limited, however, primarily owing to potential confounding.
Reporting of harms from treatment in the included studies was sparse. In general, the adverse events related to positive airway pressure treatment were likely short-lived and could have been alleviated by discontinuing treatment with positive airway pressure or by supplementing positive airway pressure with additional interventions. Common adverse events included oral or nasal dryness, eye or skin irritation, and rash. Common adverse effects from MADs included oral or nasal dryness, excessive salivation, and jaw discomfort.
Evidence included in the current review suggests several important research needs. To better understand the potential effectiveness of screening for OSA, RCTs of asymptomatic persons (or those with unrecognized symptoms of OSA) that directly compare screening with no screening and assess health outcomes are needed. To better determine the accuracy of screening questionnaires and clinical prediction tools when used in the general population (related to KQ2), additional studies are needed; such studies should aim to include a representative community population, to avoid spectrum bias, and to further evaluate promising screening approaches (eg, MVAP followed by an unattended home sleep test) as well as other approaches assessed in similar populations for which there were few studies, such as the Berlin Questionnaire and STOPBANG questionnaire. Trials of treatment (positive airway pressure and MAD) that enroll participants who are screen-detected in primary care settings are needed; results of trials that enroll participants referred for OSA symptoms and other sleep issues may not be applicable to populations who are screen-detected.
This review has several limitations. First, studies of screening accuracy were required to have used in-laboratory polysomnography as the reference standard. This is similar to the approach used in previous systematic reviews. Second, studies that focused on the benefits and harms of treatment were limited to studies of interventions considered first-line treatment for persons with newly detected OSA (positive airway pressure and MAD); studies of interventions primarily offered to persons who do not benefit from or tolerate positive airway pressure or MAD were excluded. Third, some of the meta-analyses of RCTs evaluating the benefits of positive airway pressure (KQ5) found substantial statistical heterogeneity. Although a clear explanation for all statistical heterogeneity was not found, possible explanations include variation in enrolled populations, positive airway pressure devices (eg, machines, masks, humidifiers, filters, cushions), apnea and hypopnea definitions, adherence, study duration, study methods, or chance.
The accuracy and clinical utility of OSA screening tools that could be used in primary care settings were uncertain. Positive airway pressure and mandibular advancement devices reduced ESS score. Trials of positive airway pressure found modest improvement in sleep-related and general health–related QOL but have not established whether treatment reduces mortality or improves most other health outcomes.
Source: This article was published online in JAMA on November 15, 2022 (JAMA. 2022;328(19):1951-1971. doi:10.1001/jama.2022.18357).
Conflict of Interest Disclosures: Dr Aymes reported receiving a Health Resources and Services Administration Preventive Medicine Training Grant. No other disclosures were reported.
Funding/Support: This research was funded under contract HHSA-75Q80120D00007, Task Order 01, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).
Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the evidence review to ensure that the analysis met methodological standards, and distributed the draft for public comment and review by federal partners. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.
Additional Information: A draft version of the full evidence review underwent external peer review from 3 content experts (Sean M. Caples, DO, MS, Mayo Clinic; Jon-Erik C. Holty, MD, MS, Stanford University; Paul E. Peppard, PhD, MS, University of Wisconsin-Madison) and 5 federal partner reviewers (Centers for Disease Control and Prevention; National Institute of Dental and Craniofacial Research; National Heart, Lung, and Blood Institute; National Institute on Minority Health and Health Disparities; and National Institutes of Health Office of Research on Women’s Health). Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review. USPSTF members and peer reviewers did not receive financial compensation for their contributions.
1. Osman AM, Carter SG, Carberry JC, Eckert DJ. Obstructive sleep apnea: current perspectives. Nat Sci Sleep. 2018;10:21-34. doi:10.2147/NSS.S124657
2. Faber J, Faber C, Faber AP. Obstructive sleep apnea in adults. Dental Press J Orthod. 2019;24(3):99-109. doi:10.1590/2177-6709.24.3.099-109.sar
3. Veasey SC, Rosen IM. Obstructive sleep apnea in adults. N Engl J Med. 2019;380(15):1442-1449. doi:10.1056/NEJMcp1816152
4. Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7(8):687-698. doi:10.1016/S2213-2600(19)30198-5
5. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006-1014. doi:10.1093/aje/kws342
6. Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med. 2001;163(3 Pt 1):608-613. doi:10.1164/ajrccm.163.3.9911064
7. Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men, I: prevalence and severity. Am J Respir Crit Care Med. 1998;157(1):144-148. doi:10.1164/ajrccm.157.1.9706079
8. Young T, Shahar E, Nieto FJ, et al; Sleep Heart Health Study Research Group. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med. 2002;162(8):893-900. doi:10.1001/archinte.162.8.893
9. Balk EM, Moorthy D, Obadan NO, et al. Diagnosis and Treatment of Obstructive Sleep Apnea in Adults. Agency for Healthcare Research and Quality; 2011.
10. Knauert M, Naik S, Gillespie MB, Kryger M. Clinical consequences and economic costs of untreated obstructive sleep apnea syndrome. World J Otorhinolaryngol Head Neck Surg. 2015;1(1):17-27. doi:10.1016/j.wjorl.2015.08.001
11. Bibbins-Domingo K, Grossman DC, Curry SJ, et al; US Preventive Services Task Force. Screening for obstructive sleep apnea in adults: US Preventive Services Task Force recommendation statement. JAMA. 2017;317(4):407-414. doi:10.1001/jama.2016.20325
12. US Preventive Services Task Force. US Preventive Services Task Force Procedure Manual. Updated May 2021. Accessed October 11, 2022. https://www.uspreventiveservicestaskforce.org/uspstf/procedure-manual
13. Feltner C, Jonas DE, Wallace I, Aymes S, Hicks K, Cook Middleton J. Screening for Obstructive Sleep Apnea in Adults: an Evidence Review for the US Preventive Services Task Force. Evidence Synthesis No. 220. Agency for Healthcare Research and Quality; 2022. AHRQ publication 22-05292-EF-1.
14. Human Development Report 2020: The Next Frontier: Human Development and the Anthropocene. United Nations Development Program; 2020.
15. Whiting PF, Rutjes AW, Westwood ME, et al; QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529-536. doi:10.7326/0003-4819-155-8-201110180-00009
16. Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10. doi:10.1186/1471-2288-7-10
17. West SL, Gartlehner G, Mansfield AJ, et al. Comparative Effectiveness Review Methods: Clinical Heterogeneity. Report 10-EHC070-EF. Agency for Healthcare Research and Quality. Published 2010. Accessed October 11, 2022. https://pubmed.ncbi.nlm.nih.gov/21433337/
18. StataCorp. StataCorp LP; 2019.
19. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558. doi:10.1002/sim.1186
20. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-560. doi:10.1136/bmj.327.7414.557
21. Higgins J, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.3. Cochrane. Published 2022. Accessed October 11, 2022. https://training.cochrane.org/handbook
22. Hrubos-Strøm H, Randby A, Namtvedt SK, et al. A Norwegian population-based study on the risk and prevalence of obstructive sleep apnea: the Akershus Sleep Apnea Project (ASAP). J Sleep Res. 2011;20(1, pt 2):162-170. doi:10.1111/j.1365-2869.2010.00861.x
23. Morales CR, Hurley S, Wick LC, et al. In-home, self-assembled sleep studies are useful in diagnosing sleep apnea in the elderly. Sleep. 2012;35(11):1491-1501. doi:10.5665/sleep.2196
24. Gurubhagavatula I, Fields BG, Morales CR, et al. Screening for severe obstructive sleep apnea syndrome in hypertensive outpatients. J Clin Hypertens (Greenwich). 2013;15(4):279-288. doi:10.1111/jch.12073
25. Edmonds PJ, Gunasekaran K, Edmonds LC. Neck grasp predicts obstructive sleep apnea in type 2 diabetes mellitus. Sleep Disord. 2019;2019:3184382. doi:10.1155/2019/3184382
26. Jorge C, Benítez I, Torres G, et al. The STOP-Bang and Berlin questionnaires to identify obstructive sleep apnoea in Alzheimer’s disease patients. Sleep Med. 2019;57:15-20. doi:10.1016/j.sleep.2019.01.033
27. Shin C, Baik I. Evaluation of a modified STOP-BANG questionnaire for sleep apnea in adults from the Korean general population. Sleep Med Res. 2021;12(1):28-35. doi:10.17241/smr.2020.00808
28. Selvanathan J, Waseem R, Peng P, Wong J, Ryan CM, Chung F. Simple screening model for identifying the risk of sleep apnea in patients on opioids for chronic pain. Reg Anesth Pain Med. 2021;46(10):886-891. doi:10.1136/rapm-2020-102388
29. Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131(7):485-491. doi:10.7326/0003-4819-131-7-199910050-00002
30. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008;108(5):812-821. doi:10.1097/ALN.0b013e31816d83e4
31. Farney RJ,Walker BS, Farney RM, Snow GL, Walker JM. The STOP-Bang equivalent model and prediction of severity of obstructive sleep apnea: relation to polysomnographic measurements of the apnea/hypopnea index. J Clin Sleep Med. 2011;7(5):459-65B. doi:10.5664/JCSM.1306
32. Maislin G, Pack AI, Kribbs NB, et al. A survey screen for prediction of apnea. Sleep. 1995;18(3):158-166. doi:10.1093/sleep/18.3.158
33. Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation. 2010;121(15):1768-1777. doi:10.1161/CIRCULATIONAHA.109.849166
34. Hosmer DW, Lemeshow S. Applied Logistic Regression. John Wiley & Sons; 2000. doi:10.1002/0471722146
35. de Vries GE, Wijkstra PJ, Houwerzijl EJ, Kerstjens HAM, Hoekema A. Cardiovascular effects of oral appliance therapy in obstructive sleep apnea: a systematic review and meta-analysis. Sleep Med Rev. 2018;40:55-68. doi:10.1016/j.smrv.2017.10.004
36. Labarca G, Schmidt A, Dreyse J, et al. Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): systematic review and meta-analysis. Sleep Med Rev. 2021;58:101446. doi:10.1016/j.smrv.2021.101446
37. Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG. Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2019;15(2):301-334. doi:10.5664/jcsm.7638
38. Zhang D, Luo J, Qiao Y, Xiao Y. Continuous positive airway pressure therapy in non-sleepy patients with obstructive sleep apnea: results of a meta-analysis. J Thorac Dis. 2016;8(10):2738-2747. doi:10.21037/jtd.2016.09.40
39. Arias MA, García-Río F, Alonso-Fernández A, Mediano O, Martínez I, Villamor J. Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men. Circulation. 2005;112(3):375-383. doi:10.1161/CIRCULATIONAHA.104.501841
40. Barbé F, Mayoralas LR, Duran J, et al. Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness: a randomized, controlled trial. Ann Intern Med. 2001;134(11):1015-1023. doi:10.7326/0003-4819-134-11-200106050-00007
41. Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, et al. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest. 2006;129(6):1459-1467. doi:10.1378/chest.129.6.1459
42. Chasens ER, Korytkowski M, Sereika SM, Burke LE, Drumheller OJ, Strollo PJ Jr. Improving activity in adults with diabetes and coexisting obstructive sleep apnea. West J Nurs Res. 2014;36(3):294-311. doi:10.1177/0193945913500567
43. Chong MS, Ayalon L, Marler M, et al. Continuous positive airway pressure reduces subjective daytime sleepiness in patients with mild to moderate Alzheimer’s disease with sleep disordered breathing. J Am Geriatr Soc. 2006;54(5):777-781. doi:10.1111/j.1532-5415.2006.00694.x
44. Coughlin SR, Mawdsley L, Mugarza JA, Wilding JP, Calverley PM. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J. 2007;29(4):720-727. doi:10.1183/09031936.00043306
45. Durán-Cantolla J, Aizpuru F, Montserrat JM, et al; Spanish Sleep and Breathing Group. Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial. BMJ. 2010;341:c5991. doi:10.1136/bmj.c5991
46. Egea CJ, Aizpuru F, Pinto JA, et al; Spanish Group of Sleep Breathing Disorders. Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study. Sleep Med. 2008;9(6):660-666. doi:10.1016/j.sleep.2007.06.018
47. Haensel A, Norman D, Natarajan L, Bardwell WA, Ancoli-Israel S, Dimsdale JE. Effect of a 2 week CPAP treatment on mood states in patients with obstructive sleep apnea: a double-blind trial. Sleep Breath. 2007;11(4):239-244. doi:10.1007/s11325-007-0115-0
48. Hoyos CM, Killick R, Yee BJ, Phillips CL, Grunstein RR, Liu PY. Cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: a randomised sham-controlled study. Thorax. 2012;67(12):1081-1089. doi:10.1136/thoraxjnl-2011-201420
49. Hui DS, To KW, Ko FW, et al. Nasal CPAP reduces systemic blood pressure in patients with obstructive sleep apnoea and mild sleepiness. Thorax. 2006;61(12):1083-1090. doi:10.1136/thx.2006.064063
50. Jenkinson C, Davies RJ, Mullins R, Stradling JR. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet. 1999;353(9170):2100-2105. doi:10.1016/S0140-6736(98)10532-9
51. Hack M, Davies RJ, Mullins R, et al. Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea. Thorax. 2000;55(3):224-231. doi:10.1136/thorax.55.3.224
52. Jones A, Vennelle M, Connell M, et al. The effect of continuous positive airway pressure therapy on arterial stiffness and endothelial function in obstructive sleep apnea: a randomized controlled trial in patients without cardiovascular disease. Sleep Med. 2013;14(12):1260-1265. doi:10.1016/j.sleep.2013.08.786
53. Kushida CA, Nichols DA, Holmes TH, et al. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep. 2012;35(12):1593-1602. doi:10.5665/sleep.2226
54. Batool-Anwar S, Goodwin JL, Kushida CA, et al. Impact of continuous positive airway pressure (CPAP) on quality of life in patients with obstructive sleep apnea (OSA). J Sleep Res. 2016;25(6):731-738. doi:10.1111/jsr.12430
55. Lam JC, Lam B, Yao TJ, et al. A randomised controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea. Eur Respir J. 2010;35(1):138-145. doi:10.1183/09031936.00047709
56. Lee IS, Bardwell WA, Kamat R, et al. A model for studying neuropsychological effects of sleep intervention: the effect of 3-week continuous positive airway pressure treatment. Drug Discov Today Dis Models. 2011;8(4):147-154. doi:10.1016/j.ddmod.2011.10.001
57. Loredo JS, Ancoli-Israel S, Kim EJ, Lim WJ, Dimsdale JE. Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a placebo-CPAP-controlled study. Sleep. 2006;29(4):564-571. doi:10.1093/sleep/29.4.564
58. Marshall NS, Neill AM, Campbell AJ, Sheppard DS. Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea. Thorax. 2005;60(5):427-432. doi:10.1136/thx.2004.032078
59. Melehan KL, Hoyos CM, Hamilton GS, et al. Randomized trial of CPAP and vardenafil on erectile and arterial function in men with obstructive sleep apnea and erectile dysfunction. J Clin Endocrinol Metab. 2018;103(4):1601-1611. doi:10.1210/jc.2017-02389
60. Montserrat JM, Ferrer M, Hernandez L, et al. Effectiveness of CPAP treatment in daytime function in sleep apnea syndrome: a randomized controlled study with an optimized placebo. Am J Respir Crit Care Med. 2001;164(4):608-613. doi:10.1164/ajrccm.164.4.2006034
61. Neikrug AB, Liu L, Avanzino JA, et al. Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea. Sleep. 2014;37(1):177-185. doi:10.5665/sleep.3332
62. Nguyen PK, Katikireddy CK, McConnell MV, Kushida C, Yang PC. Nasal continuous positive airway pressure improvesmyocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea. J Cardiovasc Magn Reson. 2010;12:50. doi:10.1186/1532-429X-12-50
63. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002;359(9302):204-210. doi:10.1016/S0140-6736(02)07445-7
64. Kohler M, Pepperell JC, Casadei B, et al. CPAP and measures of cardiovascular risk in males with OSAS. Eur Respir J. 2008;32(6):1488-1496. doi:10.1183/09031936.00026608
65. Phillips CL, Yee BJ, Marshall NS, Liu PY, Sullivan DR, Grunstein RR. Continuous positive airway pressure reduces postprandial lipidemia in obstructive sleep apnea: a randomized, placebo-controlled crossover trial. Am J Respir Crit Care Med. 2011;184(3):355-361. doi:10.1164/rccm.201102-0316OC
66. Robinson GV, Smith DM, Langford BA, Davies RJ, Stradling JR. Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients. Eur Respir J. 2006;27(6):1229-1235. doi:10.1183/09031936.06.00062805
67. Siccoli MM, Pepperell JC, Kohler M, Craig SE, Davies RJ, Stradling JR. Effects of continuous positive airway pressure on quality of life in patients with moderate to severe obstructive sleep apnea: data from a randomized controlled trial. Sleep. 2008;31(11):1551-1558. doi:10.1093/sleep/31.11.1551
68. Smith LA, Vennelle M, Gardner RS, et al. Auto-titrating continuous positive airway pressure therapy in patients with chronic heart failure and obstructive sleep apnoea: a randomized placebo-controlled trial. Eur Heart J. 2007;28(10):1221-1227. doi:10.1093/eurheartj/ehm131
69. Weaver TE, Mancini C, Maislin G, et al. Continuous positive airway pressure treatment of sleepy patients with milder obstructive sleep apnea: results of the CPAP Apnea Trial North American Program (CATNAP) randomized clinical trial. Am J Respir Crit Care Med. 2012;186(7):677-683. doi:10.1164/rccm.201202-0200OC
70. West SD, Nicoll DJ, Wallace TM, Matthews DR, Stradling JR. Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes. Thorax. 2007;62(11):969-974. doi:10.1136/thx.2006.074351
71. West SD, Kohler M, Nicoll DJ, Stradling JR. The effect of continuous positive airway pressure treatment on physical activity in patients with obstructive sleep apnoea: a randomised controlled trial. Sleep Med. 2009;10(9):1056-1058. doi:10.1016/j.sleep.2008.11.007
72. Ballester E, Badia JR, Hernández L, et al. Evidence of the effectiveness of continuous positive airway pressure in the treatment of sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 1999;159(2):495-501. doi:10.1164/ajrccm.159.2.9804061
73. Banghøj AM, Krogager C, Kristensen PL, et al. Effect of 12-week continuous positive airway pressure therapy on glucose levels assessed by continuous glucose monitoring in people with type 2 diabetes and obstructive sleep apnoea: a randomized controlled trial. Endocrinol Diabetes Metab. 2020;4(2):e00148. doi:10.1002/edm2.148
74. Barbé F, Durán-Cantolla J, Capote F, et al; Spanish Sleep and Breathing Group. Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010;181(7):718-726. doi:10.1164/rccm.200901-0050OC
75. Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, et al; Spanish Sleep and Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;307(20):2161-2168. doi:10.1001/jama.2012.4366
76. Barnes M, McEvoy RD, Banks S, et al. Efficacy of positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea. Am J Respir Crit Care Med. 2004;170(6):656-664. doi:10.1164/rccm.200311-1571OC
77. Campos-Rodriguez F, Queipo-Corona C, Carmona-Bernal C, et al; Spanish Sleep Network. Continuous positive airway pressure improves quality of life in women with obstructive sleep apnea: a randomized controlled trial. Am J Respir Crit Care Med. 2016;194(10):1286-1294. doi:10.1164/rccm.201602-0265OC
78. Craig SE, Kohler M, Nicoll D, et al. Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial. Thorax. 2012;67(12):1090-1096. doi:10.1136/thoraxjnl-2012-202178
79. Dalmases M, Solé-Padullés C, Torres M, et al. Effect of CPAP on cognition, brain function, and structure among elderly patients with OSA: a randomized pilot study. Chest. 2015;148(5):1214-1223. doi:10.1378/chest.15-0171
80. Engleman HM, Martin SE, Deary IJ, Douglas NJ. Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome. Lancet. 1994;343(8897):572-575. doi:10.1016/S0140-6736(94)91522-9
81. Engleman HM, Martin SE, Deary IJ, Douglas NJ. Effect of CPAP therapy on daytime function in patients with mild sleep apnoea/hypopnoea syndrome. Thorax. 1997;52(2):114-119. doi:10.1136/thx.52.2.114
82. Engleman HM, Martin SE, Kingshott RN, Mackay TW, Deary IJ, Douglas NJ. Randomised placebo controlled trial of daytime function after continuous positive airway pressure (CPAP) therapy for the sleep apnoea/hypopnoea syndrome. Thorax. 1998;53(5):341-345. doi:10.1136/thx.53.5.341
83. Engleman HM, Kingshott RN, Wraith PK, Mackay TW, Deary IJ, Douglas NJ. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 1999;159(2):461-467. doi:10.1164/ajrccm.159.2.9803121
84. Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001;163(2):344-348. doi:10.1164/ajrccm.163.2.2005037
85. Gottlieb DJ, Punjabi NM, Mehra R, et al. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med. 2014;370(24):2276-2285. doi:10.1056/NEJMoa1306766
86. Lewis EF, Wang R, Punjabi N, et al. Impact of continuous positive airway pressure and oxygen on health status in patients with coronary heart disease, cardiovascular risk factors, and obstructive sleep apnea: a Heart Biomarker Evaluation in Apnea Treatment (HEARTBEAT) analysis. Am Heart J. 2017;189:59-67. doi:10.1016/j.ahj.2017.03.001
87. Jackson ML, Tolson J, Schembri R, et al. Does continuous positive airways pressure treatment improve clinical depression in obstructive sleep apnea? a randomized wait-list controlled study. Depress Anxiety. 2021;38(5):498-507. doi:10.1002/da.23131
88. Jackson ML, Tolson J, Bartlett D, Berlowitz DJ, Varma P, Barnes M. Clinical depression in untreated obstructive sleep apnea: examining predictors and a meta-analysis of prevalence rates. Sleep Med. 2019;62:22-28. doi:10.1016/j.sleep.2019.03.011
89. Lam B, Sam K, Mok WY, et al. Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea. Thorax. 2007;62(4):354-359. doi:10.1136/thx.2006.063644
90. Lim W, Bardwell WA, Loredo JS, et al. Neuropsychological effects of 2-week continuous positive airway pressure treatment and supplemental oxygen in patients with obstructive sleep apnea: a randomized placebo-controlled study. J Clin Sleep Med. 2007;3(4):380-386. doi:10.5664/jcsm.26860
91. Lui MMS, Mak JCW, Chong PWC, Lam DCL, Ip MSM. Circulating adipocyte fatty acid-binding protein is reduced by continuous positive airway pressure treatment for obstructive sleep apnea—a randomized controlled study. Sleep Breath. 2020;24(3):817-824. doi:10.1007/s11325-019-01893-5
92. Martínez-García MA, Capote F, Campos-Rodríguez F, et al; Spanish Sleep Network. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013;310(22):2407-2415. doi:10.1001/jama.2013.281250
93. Martínez-García MÁ, Chiner E, Hernández L, et al; Spanish Sleep Network. Obstructive sleep apnoea in the elderly: role of continuous positive airway pressure treatment. Eur Respir J. 2015;46(1):142-151. doi:10.1183/09031936.00064214
94. Masa JF, Corral J, Alonso ML, et al; Spanish Sleep Network. Efficacy of different treatment alternatives for obesity hypoventilation syndrome: Pickwick Study. Am J Respir Crit Care Med. 2015;192(1):86-95. doi:10.1164/rccm.201410-1900OC
95. McArdle N, Douglas NJ. Effect of continuous positive airway pressure on sleep architecture in the sleep apnea-hypopnea syndrome: a randomized controlled trial. Am J Respir Crit Care Med. 2001;164(8 Pt 1):1459-1463. doi:10.1164/ajrccm.164.8.2008146
96. McMillan A, Bratton DJ, Faria R, et al; PREDICT Investigators. Continuous positive airway pressure in older people with obstructive sleep apnoea syndrome (PREDICT): a 12-month, multicentre, randomised trial. Lancet Respir Med. 2014;2(10):804-812. doi:10.1016/S2213-2600(14)70172-9
97. Peker Y, Glantz H, Eulenburg C, Wegscheider K, Herlitz J, Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea: the RICCADSA randomized controlled trial. Am J Respir Crit Care Med. 2016;194(5):613-620. doi:10.1164/rccm.201601-0088OC
98. Balcan B, Thunström E, Strollo PJ Jr, Peker Y. Continuous positive airway pressure treatment and depression in adults with coronary artery disease and nonsleepy obstructive sleep apnea: a secondary analysis of the RICCADSA Trial. Ann Am Thorac Soc. 2019;16(1):62-70. doi:10.1513/AnnalsATS.201803-174OC
99. Celik Y, Thunström E, Strollo PJ Jr, Peker Y. Continuous positive airway pressure treatment and anxiety in adults with coronary artery disease and nonsleepy obstructive sleep apnea in the RICCADSA trial. Sleep Med. 2021;77:96-103. doi:10.1016/j.sleep.2020.11.034
100. Ponce S, Pastor E, Orosa B, et al; Sleep Respiratory Disorders Group of the Sociedad Valenciana de Neumología. The role of CPAP treatment in elderly patients with moderate obstructive sleep apnoea: a multicentre randomised controlled trial. Eur Respir J. 2019;54(2):1900518. doi:10.1183/13993003.00518-2019
101. Redline S, Adams N, Strauss ME, Roebuck T, Winters M, Rosenberg C. Improvement of mild sleep-disordered breathing with CPAP compared with conservative therapy. Am J Respir Crit Care Med. 1998;157(3, pt 1):858-865. doi:10.1164/ajrccm.157.3.9709042
102. Ruttanaumpawan P, Gilman MP, Usui K, Floras JS, Bradley TD. Sustained effect of continuous positive airway pressure on baroreflex sensitivity in congestive heart failure patients with obstructive sleep apnea. J Hypertens. 2008;26(6):1163-1168. doi:10.1097/HJH.0b013e3282fb81ed
103. Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2003;348(13):1233-1241. doi:10.1056/NEJMoa022479
104. Salord N, Fortuna AM, Monasterio C, et al. A randomized controlled trial of continuous positive airway pressure on glucose tolerance in obese patients with obstructive sleep apnea. Sleep. 2016;39(1):35-41. doi:10.5665/sleep.5312
105. Shaw JE, Punjabi NM, Naughton MT, et al. The effect of treatment of obstructive sleep apnea on glycemic control in type 2 diabetes. Am J Respir Crit Care Med. 2016;194(4):486-492. doi:10.1164/rccm.201511-2260OC
106. Tomfohr LM, Ancoli-Israel S, Loredo JS, Dimsdale JE. Effects of continuous positive airway pressure on fatigue and sleepiness in patients with obstructive sleep apnea: data from a randomized controlled trial. Sleep. 2011;34(1):121-126. doi:10.1093/sleep/34.1.121
107. Wimms AJ, Kelly JL, Turnbull CD, et al; MERGE Trial Investigators. Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(4):349-358. doi:10.1016/S2213-2600(19)30402-3
108. Zhao YY, Wang R, Gleason KJ, et al; BestAIR Investigators. Effect of continuous positive airway pressure treatment on health-related quality of life and sleepiness in high cardiovascular risk individuals with sleep apnea: Best Apnea Interventions for Research (BestAIR) trial. Sleep. 2017;40(4):zsx040. doi:10.1093/sleep/zsx040
109. Ng SSS, Chan TO, To KW, et al. Continuous positive airway pressure for obstructive sleep apnoea does not improve asthma control. Respirology. 2018;23(11):1055-1062. doi:10.1111/resp.13363
110. Celik Y, Yapici-Eser H, Balcan B, Peker Y. Association of excessive daytime sleepiness with the Zung self-rated depression subscales in adults with coronary artery disease and obstructive sleep apnea. Diagnostics (Basel). 2021;11(7):1176. doi:10.3390/diagnostics11071176
111. Traaen GM, Aakerøy L, Hunt TE, et al. Effect of continuous positive airway pressure on arrhythmia in atrial fibrillation and sleep apnea: a randomized controlled trial. Am J Respir Crit Care Med. 2021;204(5):573-582. doi:10.1164/rccm.202011-4133OC
112. Wallström S, Balcan B, Thunström E, Wolf A, Peker Y. CPAP and health-related quality of life in adults with coronary artery disease and nonsleepy obstructive sleep apnea in the RICCADSA trial. J Clin Sleep Med. 2019;15(9):1311-1320. doi:10.5664/jcsm.7926
113. Weinstock TG, Wang X, Rueschman M, et al. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. Sleep. 2012;35(5):617-625B. doi:10.5665/sleep.1816
114. Patel S, Kon SSC, Nolan CM, et al. The Epworth Sleepiness Scale: minimum clinically important difference in obstructive sleep apnea. Am J Respir Crit Care Med. 2018;197(7):961-963. doi:10.1164/rccm.201704-0672LE
115. Crook S, Sievi NA, Bloch KE, et al. Minimum important difference of the Epworth Sleepiness Scale in obstructive sleep apnoea: estimation from three randomised controlled trials. Thorax. 2019;74(4):390-396. doi:10.1136/thoraxjnl-2018-211959
116. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36), I: conceptual framework and item selection. Med Care. 1992;30(6):473-483. doi:10.1097/00005650-199206000-00002
117. Wyrwich KW, Tierney WM, Babu AN, Kroenke K, Wolinsky FD. A comparison of clinically important differences in health-related quality of life for patients with chronic lung disease, asthma, or heart disease. Health Serv Res. 2005;40(2):577-591. doi:10.1111/j.1475-6773.2005.0l374.x
118. Weaver TE, Crosby RD, Bron M, Menno D, Mathias SD. Using multiple anchor-based and distribution-based estimates to determine the Minimal Important Difference (MID) for the FOSQ-10. Sleep. 2018;41(suppl 1):A227. doi:10.1093/sleep/zsy061.611
119. Flemons WW, Reimer MA. Development of a disease-specific health-related quality of life questionnaire for sleep apnea. Am J Respir Crit Care Med. 1998;158(2):494-503. doi:10.1164/ajrccm.158.2.9712036
120. Aarab G, Lobbezoo F, Hamburger HL, Naeije M. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial. Respiration. 2011;81(5):411-419. doi:10.1159/000319595
121. Nikolopoulou M, Aarab G, Ahlberg J, Hamburger HL, de Lange J, Lobbezoo F. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial on temporomandibular side-effects. Clin Exp Dent Res. 2020;6(4):400-406. doi:10.1002/cre2.288
122. Andrén A, Hedberg P, Walker-Engström ML, Wahlén P, Tegelberg A. Effects of treatment with oral appliance on 24-h blood pressure in patients with obstructive sleep apnea and hypertension: a randomized clinical trial. Sleep Breath. 2013;17(2):705-712. doi:10.1007/s11325-012-0746-7
123. Bloch KE, Iseli A, Zhang JN, et al. A randomized, controlled crossover trial of two oral appliances for sleep apnea treatment. Am J Respir Crit Care Med. 2000;162(1):246-251. doi:10.1164/ajrccm.162.1.9908112
124. Durán-Cantolla J, Crovetto-Martínez R, Alkhraisat MH, et al. Efficacy of mandibular advancement device in the treatment of obstructive sleep apnea syndrome: a randomized controlled crossover clinical trial. Med Oral Patol Oral Cir Bucal. 2015;20(5):e605-e615. doi:10.4317/medoral.20649
125. Naismith SL, Winter VR, Hickie IB, Cistulli PA. Effect of oral appliance therapy on neurobehavioral functioning in obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med. 2005;1(4):374-380. doi:10.5664/jcsm.26365
126. Gotsopoulos H, Chen C, Qian J, Cistulli PA. Oral appliance therapy improves symptoms in obstructive sleep apnea: a randomized, controlled trial. Am J Respir Crit Care Med. 2002;166(5):743-748. doi:10.1164/rccm.200203-208OC
127. Gotsopoulos H, Kelly JJ, Cistulli PA. Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial. Sleep. 2004;27(5):934-941. doi:10.1093/sleep/27.5.934
128. Johnston CD, Gleadhill IC, Cinnamond MJ, Gabbey J, Burden DJ. Mandibular advancement appliances and obstructive sleep apnoea: a randomized clinical trial. Eur J Orthod. 2002;24(3):251-262. doi:10.1093/ejo/24.3.251
129. Quinnell TG, Bennett M, Jordan J, et al. A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO). Thorax. 2014;69(10):938-945. doi:10.1136/thoraxjnl-2014-205464
130. Gagnadoux F, Pépin JL, Vielle B, et al. Impact of mandibular advancement therapy on endothelial function in severe obstructive sleep apnea. Am J Respir Crit Care Med. 2017;195(9):1244-1252. doi:10. 1164/rccm.201609-1817OC
131. Marklund M, Carlberg B, Forsgren L, Olsson T, Stenlund H, Franklin KA. Oral appliance therapy inpatients with daytime sleepiness and snoring or mild to moderate sleep apnea: a randomized clinical trial. JAMA Intern Med. 2015;175(8):1278-1285. doi:10.1001/jamainternmed.2015.2051
132. Petri N, Svanholt P, Solow B, Wildschiødtz G, Winkel P. Mandibular advancement appliance for obstructive sleep apnoea: results of a randomised placebo controlled trial using parallel group design. J Sleep Res. 2008;17(2):221-229. doi:10.1111/j.1365-2869.2008.00645.x
133. Malow BA, Foldvary-Schaefer N, Vaughn BV, et al. Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot trial. Neurology. 2008;71(8):572-577. doi:10.1212/01.wnl.0000323927.13250.54
134. Redline S. Effects of treatment of sleep apnea on metabolic syndrome. [NCT01385995]. 2014. Accessed October 11, 2022. https://www.clinicaltrials.gov/show/NCT01385995
135. Goehring C, Perrier A, Morabia A. Spectrum bias: a quantitative and graphical analysis of the variability of medical diagnostic test performance. Stat Med. 2004;23(1):125-135. doi:10.1002/sim.1591
136. Mulherin SA, Miller WC. Spectrum bias or spectrum effect? subgroup variation in diagnostic test evaluation. Ann Intern Med. 2002;137(7):598-602. doi:10.7326/0003-4819-137-7-200210010-00011
137. Jelinek M. Spectrum bias: why generalists and specialists do not connect. Evid Based Med. 2008;13(5):132-133. doi:10.1136/ebm.13.5.132
138. Lachs MS, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Ann Intern Med. 1992;117(2):135-140. doi:10.7326/0003-4819-117-2-135
139. Willis BH. Spectrum bias—why clinicians need to be cautious when applying diagnostic test studies. Fam Pract. 2008;25(5):390-396. doi:10.1093/fampra/cmn051
140. Myers KA, Mrkobrada M, Simel DL. Does this patient have obstructive sleep apnea? the Rational Clinical Examination systematic review. JAMA. 2013;310(7):731-741. doi:10.1001/jama.2013.276185
141. Qaseem A, Dallas P, Owens DK, Starkey M, Holty JE, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161(3):210-220. doi:10.7326/M12-3187
142. Johns M, Hocking B. Daytime sleepiness and sleep habits of Australian workers. Sleep. 1997;20(10):844-849. doi:10.1093/sleep/20.10.844
143. Johns MW. Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the Epworth Sleepiness Scale: failure of the MSLT as a gold standard. J Sleep Res. 2000;9(1):5-11. doi:10.1046/j.1365-2869.2000.00177.x
144. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol. 1998;43(1):88-97. doi:10.1002/ana.410430115
145. Kingshott RN, Vennelle M, Coleman EL, Engleman HM, Mackay TW, Douglas NJ. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 2001;163(4):918-923. doi:10.1164/ajrccm.163.4.2005036
146. Puhan MA, Suarez A, Lo Cascio C, Zahn A, Heitz M, Braendli O. Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial. BMJ. 2006;332(7536):266-270. doi:10.1136/bmj.38705.470590.55
147. Medical Advisory Secretariat. Oral appliances for obstructive sleep apnea: an evidence-based analysis. Ont Health Technol Assess Ser. 2009;9(5):1-51.
148. Miletin MS, Hanly PJ. Measurement properties of the Epworth Sleepiness Scale. Sleep Med. 2003;4(3):195-199. doi:10.1016/S1389-9457(03)00031-5
149. Smith SS, Oei TP, Douglas JA, Brown I, Jorgensen G, Andrews J. Confirmatory factor analysis of the Epworth Sleepiness Scale (ESS) in patients with obstructive sleep apnoea. Sleep Med. 2008;9(7):739-744. doi:10.1016/j.sleep.2007.08.004
150. Vongpatanasin W. Resistant hypertension: a review of diagnosis and management. JAMA. 2014;311(21):2216-2224. doi:10.1001/jama.2014.5180
151. Bisognano JD, Bakris G, Nadim MK, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58(7):765-773. doi:10.1016/j.jacc.2011.06.008
152. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M; Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomised controlled trial. Lancet. 2010;376(9756):1903-1909. doi:10.1016/S0140-6736(10)62039-9
153. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572. doi:10.1001/jama.289.19.256
Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes.
A dashed line depicts a health outcome that follows an intermediate outcome. For additional information, see the USPSTF Procedure Manual.12
AHI indicates apnea/hypopnea index; MAD, mandibular advancement device; OSA, obstructive sleep apnea; PAP, positive airway pressure.
The sum of the number of studies per key question (KQ) exceeds the total number of studies because some studies were applicable to multiple KQs.
USPSTF indicates US Preventive Services Task Force.
ESS indicates Epworth Sleepiness Scale; OSA, obstructive sleep apnea; PAP, positive airway pressure.
|Source, country||Study design (quality)||Participants||Name of
|Age, mean (SD), y||Women, %||Race and ethnicity, %||BMI, mean (SD)||AHI, mean (SD)||Hypertension, %||OSA, %|
|Hrubos-Strom et al,22 2011
|Cross-sectional (fair)||Participants (n = 518) randomly drawn from Norwegian National Population Registera||Berlin Questionnaire (Norwegian translation)||48 (11.2)||45||NR||28 (4.8)||Median, 6.4 (NR)b||27||NR|
|Morales et al,23 2012
|Cross-sectional (fair)||Medicare recipients (n = 452) from greater Philadelphia metro region, most with some daytime sleepinessc||MVAP score; MVAP score + AHI from unattended HST||71 (5.4)||70||Black, 61
|30 (6.2)||NR||NR||Any OSA, NR
Any OSAS (AHI ≥5 and ESS >10), 27e
|Gurubhagavatula et al,24 2013
|Cross-sectional (fair)||US adults (n = 250) with hypertension from internal medicine practices and a hypertension clinicf||MVAP score; MVAP score + AHI from unattended HST||53 (7.7)||20||Black, 59
|32.1 (7.4)||22.5 (22.9)||100||Of the 79% who had in-laboratory polysomnography:
Any OSA, 80g
|Edmonds et al,25 2019
|Cross-sectional (fair)||US adults (n = 43) with type 2 diabetes from a general internal medicine clinic||STOP-BANG, Berlin Questionnaire||NR||53||NR||38 (7.7)||31.2 (28.1)||NR||Mild (AHI 5-14), 28
Moderate (AHI 15-29), 26
Severe (AHI ≥30), 37
|Jorge et al,26 2019
|Cross-sectional (fair)||Spanish adults (n = 91) with a recent diagnosis of mild to moderate Alzheimer disease||Modified STOP-BANGi||Median, 76 (IQR, 73-80)||64||NR||Median, 28 (IQR, 25.2-30.2)||20.7 (10.6-40.3)||57||Mild (AHI 5-14), 26.4
Moderate (AHI 15-30), 25.3
Severe (AHI >30), 37.4
|Shin and Baik,27
|Cross-sectional (fair)||Korean adults (n=1033) enrolled in a population-based cohort studyj||Modified STOP-BANGk||59 (7.9)||48||Asian, 100||25 (3.0)||7.3 (8.9)||38||Mild (AHI 5-14), 32.4
Moderate (AHI 15-29), 10.1
Severe (AHI ≥30), 3.1
et al,28 2021l
|Cross-sectional (fair)||Adults (n = 202 and 199m) receiving opioids for chronic pain||STOP-BANG; STOP-BANG + resting daytime SpO2||53 (12.8)||58||NR||29 (6.4)||Median, 6.5 (IQR, 2.3-19.4)||33||NR|
Abbreviations: AHI, apnea-hypopnea index; BMI, body mass index; ESS, Epworth Sleepiness Scale; HST, home sleep test; KQ, key question; MVAP, Multivariable Apnea Prediction; NR, not reported; OSA, obstructive sleep apnea; OSAS, obstructive sleep apnea syndrome; SpO2, oxygen saturation by pulse oximetry; STOP-BANG, snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, gender.
a Data in this row describe the 518 participants who underwent polysomnography. The 518 were a subset of the larger study population of 16,302 who completed the Berlin Questionnaire. The mean age of the larger study population was 48 years, 53% were women, the mean BMI was 26 (SD, 4.3), and 14% had hypertension.
b Standard deviation was not reported, but 25th and 75th percentiles were 1.7 and 18.3, respectively.
c Seventy-four percent met their definition of daytime sleepiness (frequency of sleepiness, based on whether they had a problem staying awake, every day or several [≥ 3] days per week); 32% had ESS scores greater than 10 (Indira Gurubhagavatula, MD, MPH, University of Pennsylvania, email, July 2015).
d Caucasian is the term used in the publication.
e Mild (AHI 5-15 and ESS >10), 9%; at least moderate (AHI ≥ 15 and ESS > 10), 17%; moderate (AHI 15-30 and ESS>10), 8%; severe (AHI >30 and ESS >10), 8%.
f Required to have blood pressure 140/90 mm Hg or greater or to be taking antihypertensive medications.
g Mild, 34%; moderate, 22%; severe, 25%.
h At least mild (AHI ≥ 5 and ESS > 10): 25%; severe (AHI ≥ 30 and ESS >10): 7.6%.
i Modified STOP-BANG (age >70 years, BMI >26; neck circumference >26.5 cm).
j Validation sample only.
k Modified STOP-BANG (age 5-64 years 1 point, 65 years or older 2 points; and waist circumference >85, snoring, observed apnea; high blood pressure, BMI >25; each 1 point).
l Although this is a 2-stage study, only the findings from the first stage in which all patients were included are reported.
m The n of 202 represents those who received the STOP-BANG and polysomnography; the n of 199 includes those who received STOP-BANG, polysomnography, and resting daytime SpO2.
|Source||Cutoff value of screening questionnaire(s)/tool(s)||Reference standard definition of OSA diagnosis||Sensitivity (95% CI)||Specificity (95% CI)||AUROC (95% CI)||Calibration||Other accuracy measures
|Hrubos-Strom et al,22 2011||Berlin Questionnaire, ≥2 positive categories||AHI ≥5a||37.2 (36.0-38.4)||84.0 (83.2-84.7)||NR||NR||PPV, 61.3 (59.7-62.9)
NPV, 66.2 (65.3-67.1)
PLR, 2.3 (2.2-2.5)
NLR, 0.8 (0.7-0.8)
|AHI ≥15a||43.0 (41.2-44.8)||79.7 (79.0-80.5)||NR||NR||PPV, 33.5 (32.0-35.0)
NPV, 85.5 (84.8-86.1)
PLR, 2.1 (2.0-2.3)
NLR, 0.7 (0.7-0.7)
|Morales et al,23 2012||MVAP, 0.49||Severe OSAS (AHI ≥30 and ESS >10)||90.0 (NR)||64.4 (NR)||0.78 (0.71-0.85)||NR||NLR, 0.141 (NR)
NPTP, 1.1 (NR)
|MVAP + HSTb, uAHI 15b||Severe OSAS (AHI ≥30 and ESS >10)||90.0 (NR)||75.7 (NR)||0.83 (0.77-0.90)||NR||NLR, 0.120 (NR)
NPTP, 0.01 (NR)
|Gurubhagavatula et al,24 2013||MVAP, 0.483||Severe OSAS (AHI ≥30 and ESS >10)||91.5 (NR)||43.9 (NR)||0.68 (0.67-0.70)||NR||NLR, 19.0 (NR)
NPTP, 0.015 (NR)
|MVAP, 0.559||Any OSAS (AHI ≥5 and ESS >10)||69.4 (NR)||56.5 (NR)||0.61 (NR)||NR||NLR, 0.524 (NR)
NPTP, 14.8 (NR)
|MVAP + HST, uAHI 18b||Severe OSAS (AHI ≥30 and ESS >10)||88.2 (NR)||71.6 (NR)||0.80 (0.78-0.82)||NR||NLR, 0.162 (NR)
NPTP, 0.015 (NR)
|MVAP + HST, uAHI 13.5b||Any OSAS (AHI ≥5 and ESS >10)||80.5 (NR)||54.0 (NR)||0.67 (NR)||NR||NLR, 0.349 (NR)
NPTP, 0.104 (NR)
|Edmonds et al,25 2019||STOP-BANG ≥3||Mild (AHI 5-14)||87.2 (NR)||0||NR||NR||PPV, 89.5 (NR)
NPV, 0 (NR)
|Moderate (AHI 15-29)||92.6 (NR)||18.8 (NR)||NR||NR||PPV, 65.8 (NR)
NPV, 60.0 (NR)
|Severe (AHI ≥30)||93.8 (NR)||14.8 (NR)||NR||NR||PPV, 39.5 (NR)
NPV, 80.0 (NR)
|Berlin Questionnaire, ≥2 positive categories||Mild (AHI 5-14)||79.5 (NR)||0 (NR)||NR||NR||PPV, 88.6 (NR)
NPV, 0 (NR)
|Moderate (AHI 15-29)||88.9 (NR)||31.3 (NR)||NR||NR||PPV, 68.6 (NR)
NPV, 62.5 (NR)
|Severe (AHI ≥30)||93.8 (NR)||25.9 (NR)||NR||NR||PPV, 42.9 (NR)
NPV, 87.5 (NR)
|Jorge et al,26 2019||Modified STOP-BANG (age older than 70 y; BMI >26; neck circumference >26.5 cm) ≥2 positive categories||Severe (AHI >30)||61.0 (47-74)||76.0 (59-89)||0.72 (0.61-0.83)||NR||PPV, 81.0 (66-91)
NPV, 54.0 (39-69)
|Shin and Baik,27 2021||Modified STOP-BANG ≥3 (snoring; observed apnea; high blood pressure; BMI >25; age 5-64 y, 1 point; ≥65 y, 2 points; waist circumference>85 cm; diabetes; male)||All (AHI ≥5)||62.3 (60.5-64.2)||64.5 (62.9-66)||0.73 (0.70-0.76)||NR||PPV, 64 (63.4-64.4)
NPV, 71.8 (71.1-72.5)
|Mild to moderate (5 < AHI < 30)||62.0 (60.1-63.9)||63.8 (62.2-65.4)||0.72 (0.69-0.75)||NR||PPV, 61.6 (61.0-62.3)
NPV, 72.6 (71.9-73.3)
|Severe (AHI ≥30)||79.1 (77.3-80.9)||53.3 (51.6-54.9)||0.78 (0.72-0.84)||NR||PPV, 6.03 (6.89-6.17)
NPV, 99.2 (99.1-99.2)
|Selvanathan et al,28 2021||STOP-BANG ≥3c||Moderate to severe (AHI ≥15)||89.2 (80.1-95.0)||38.0 (33.6-40.7)||NR||NR||NR|
|STOP-BANG ≥3 or resting daytime SpO2 ≤95%c||All (AHI ≥5)||92.9 (87.8-96.0)||31.6 (24.5-37.0)||NR||NR||PPV, 67.3 (63.9-69.8)
NPV, 73.5 (57.0-86.0)
PLR, 1.4 (1.2-1.5)
NLR, 0.2 (0.1-0.5)
|Mild to moderate (5 < AHI < 30)||95.4 (87.7-98.8)||23.1 (19.4-24.8)||NR||NR||PPV, 37.6 (34.6-38.9)
NPV, 91.2 (76.5-97.7)
PLR, 1.24 (1.0-1.3)
NLR, 0.2 (0.05-0.6)
|Severe (AHI ≥30)||100.0 (89.4-100)||21.0 (18.6-21.0)||NR||NR||PPV, 22.4 (20.0-22.4)
NPV, 100 (88.4-100)
PLR, 1.3 (1.1-1.3)
Abbreviations: Abbreviations: AHI, apnea-hypopnea index; AUROC, area under the receiver operating characteristic curve; BMI, body mass index; ESS, Epworth Sleepiness Scale; HST, home sleep test; KQ, key question; MVAP, Multivariable Apnea Prediction; NLR, negative likelihood ratio; NPTP, negative posttest probability; NPV, negative predictive value; NR, not reported; OSA, obstructive sleep apnea; OSAS, obstructive sleep apnea syndrome; PLR, positive likelihood ratio; PPV, positive predictive value; SpO2, oxygen saturation by pulse oximetry; STOP-BANG, snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, gender; uAHI, unattended AHI from home sleep test.
a Estimates were based on a simulated model that adjusted for oversampling of Berlin Questionnaire high-risk participants (not just based on findings for the 518 in the clinical sample).
b Two-stage process using MVAP for everyone, then an unattended HST to estimate AHI for those with an intermediate MVAP score.
c Although this is a 2-stage study, only the findings from the first stage in which all patients were included are reported.
|Outcome measure||No. of trials||No. of participants||Effect size, mean difference (95% CI)||I2||Estimated MCID|
|ESS||47||7024||−2.33 (−2.75 to −1.90)||88||−2 to −3114,115|
|SF-36 PCS||13||2031||1.53 (0.29 to 2.77)||59||4 to 7116,117|
|SF-36 MCS||15||2345||2.20 (0.95 to 3.44)||64||4 to 7|
|All measures||17||3083||SMD, 0.30 (0.19 to 0.42)||55||NAa|
|FOSQ only||10||1425||0.55 (0.05 to 1.06)||70||1.8 to 2.2118|
|SAQLI only||6||1725||0.40 (0.17 to 0.62)||81||1 to 2119|
Abbreviations: ESS, Epworth Sleepiness Scale; FOSQ, Functional Outcomes of Sleep Questionnaire; MCID, minimal clinically important difference; MCS, mental component summary score; NA, not applicable; PCS, physical component summary score; QOL, quality of life; SAQLI, Sleep Apnea Quality of Life Index; SF-36, 36-Item Short Form Health Survey; SMD, standardized mean difference.
a An SMD between 0.2 and 0.4 is considered a small effect size.
prediction tool, test, or intervention
|No. of studies and study design (total sample size) by test or outcome||Summary of findings by test or outcome||Consistency and precision||Reporting bias||Study
|Body of evidence
|Overall strength of evidence||Applicability|
|KQ1: Benefits of screening|
|None||0||No eligible study||NA||NA||NA||Insufficient||NA|
|KQ2: Accuracy of screening questionnaires, clinical prediction tools, and multistep screening approaches|
|Berlin Questionnaire||2 Cross-sectional studies
|Varies by OSA threshold (AHI cut point)
|Unknown consistency: studies used different reference test thresholds
Unknown precision: 1 study reported CIs (precise) and 1 did not report CIs)
|Undetected||Fair||Studies enrolled different populations; 1 with risk of bias due to attrition bias and spectrum bias, and 1 (enrolling US adults with type 2 diabetes) with small sample size and risk of bias due to unclear methods for calculating accuracy of OSA categories||Insufficient||Unclear: 1 study enrolled general population of Norway and 1 enrolled US adults with type 2 diabetes|
|STOP-BANG||2 Cross-sectional studies
|Varies by OSA threshold (AHI cut point)
|Unknown consistency: studies used different reference test thresholds
Unknown precision: 1 study reported CIs (precise) and 1 did not report CIs)
|Undetected||Fair||Studies enrolled different populations: 1 with type 2 diabetes and 1 who used opioids for chronic pain
Both studies had a moderate risk of bias due to lack of clarity related to screening and reference standard interpreted separately; unclear methods for calculating accuracy of OSA categories
|Insufficient||Persons with type 2 diabetes and taking opioids for chronic pain|
|Modified STOP-BANGa||1 Cross-sectional study
Sensitivity, 61% (95% CI, 4% to 74%)
Specificity, 76% (95% CI, 59% to 89%)
|Unknown consistency (single study)
|Undetected||Fair||Single study with risk of bias due to patient selection||Insufficient||Persons with Alzheimer disease|
|Modified STOP-BANGb||1 Cross-sectional study
Sensitivity, 93% (95% CI, 88% to 96%)
Specificity, 32% (95% CI, 24% to 37%)
|Unknown, single study
|Undetected||Fair||Risk of bias due to unclear methods for calculating accuracy by OSA severity category||Insufficient||Persons taking opioids for chronic pain|
|MVAP score (for severe OSAS)||2 Cross-sectional studies
|For severe OSAS (AHI ≥30 and ESS >10) using MVAP cutoff 0.48-0.49:
Sensitivity, 90%-91.5% (95% CI NR)
Specificity, 43.9%-64.4% (95% CI NR)
AUC, 0.68 (95% CI, 0.67 to 0.70) to 0.78 (95% CI, 0.71 to 0.85)
|Inconsistent (1 with inadequate discrimination; 1 with reasonable discrimination)
|Undetected||Fair||Concern for spectrum bias in both studies; risk of attrition bias in 1 study||Insufficient||Populations with high prevalence of OSAS (≥25%); only 1 study reported % with any OSA (80%); studies included Medicare recipients and adults with hypertension|
|MVAP score (for any OSAS)||1 Cross-sectional study
|For any OSAS (AHI ≥5 and ESS >10):
Sensitivity, 69.4% (95% CI NR)
Specificity, 56.5% (95% CI NR)
AUC, 0.614 (95% CI NR)
|Undetected||Fair||Concern for spectrum bias; risk of attrition bias||Insufficient||Populations with high prevalence of OSAS; studies included Medicare recipients and adults with hypertension|
|MVAP score followed by unattended; HST (for severe OSAS)||2 Cross-sectional studies
|For severe OSAS (AHI ≥30 and ESS>10) using home-based AHI of 15 or 18:
Sensitivity, 88.2%-90.9% (95% CI NR)
Specificity, 71.6%-75.7% (95% CI NR)
AUC, 0.799 (95% CI, 0.777 to 0.822) and 0.833 (95% CI, 0.765 to 0.902)
|Undetected||Fair||Concern for spectrum bias in both studies; risk of attrition bias in 1 study||Low||Populations with high prevalence of OSAS; studies included Medicare recipients and adults with hypertension|
|MVAP score followed by unattended HST (for any OSAS)||1 Cross-sectional study
|For any OSAS (AHI ≥5 and ESS >10):
Sensitivity, 80.5% (95% CI NR)
Specificity, 54.0% (95% CI NR)
AUC, 0.672 (95% CI NR)
|Undetected||Fair||Concern for spectrum bias; risk of attrition bias||Insufficient||Populations with high prevalence of OSAS; studies included Medicare recipients and adults with hypertension|
|KQ3: Harms associated with screening or subsequent diagnostic testing|
|None||0||No eligible study||NA||NA||NA||Insufficient||NA|
|KQ4: Efficacy of treatment for improving intermediate outcomes|
|Positive airway pressure||AHI:
2 systematic reviews: 1 focused on any OSA severity (11 RCTs; 832) participants) and 1 limited to nonsleepy populations (3 RCTs; 1541 participants)
|AHI, pooled mean difference:
Any OSA severity, −23.41 (95% CI, −28.51 to −18.30); I2= 93%
Nonsleepy populations, −15.57 (95% CI, −29.32 to −1.82); I2= 87.2%
Daytime blood pressure, pooled mean difference:
|Consistent for AHI and blood pressure
Precise for AHI and blood pressure; imprecise for blood pressure in pooled estimate limited to nonsleepy populations
|Undetected||Goodd||Most trials were ≤12 wk; estimates associated with significant heterogeneity||Moderate for AHI and blood pressure in overall (any) OSA populations and populations with resistant hypertension; low for blood pressure in nonsleepy populations||Referral population with known OSA|
1 systematic review (11 RCTs; 469 participants)
|No statistically significant reduction in daytime, nighttime, or 24-h blood pressure measures||Consistent
|Undetected||Goodd||Variations in blood pressure treatment at baseline and limited follow-up (1-3 mo)||Low||Referral population with known OSA|
|KQ5: Efficacy of treatment for improving health outcomes|
|Positive airway pressuree||Mortality: 31 RCTs (2673)
ESS: 47 RCTs (7024)
SF-36 PCS: 13 RCTs (2031)
SF-36 MCS: 15 RCTs (2345)
Sleep-related QOL (SAQLI, FOSQ, or QSQ): 17 RCTs (3083)
|Mortality: no event (27 RCTs) or 1 event (2 RCTs) at ≤12 wk; no significant difference at 24 wk (1 RCT: 2 vs 2), median of 4 y (1 RCT: 8 vs 3), or median of 5 y
ESS: pooled mean difference, −2.33 (95% CI, −2.75 to −1.90)
SF-36 PCS: positive airway pressure vs any comparator; mean difference, 1.53 (95% CI, 0.29 to 2.77)
SF-36 MCS: positive airway pressure vs any comparator; mean difference, 2.20 (95% CI, 0.95 to 3.44)
SAQLI or FOSQ: positive airway pressure vs any comparator; SMD, 0.30 (95% CI, 0.19 to 0.42)
Cardiovascular events: overall, too few events were observed to draw conclusions
|Mortality and cardiovascular events:
Consistent for RCTs of relatively short duration (≤12-24 wk), unknown for longer duration
SF-36 PCS and MCS:
|Detected for SF-36 outcomes (6 RCTs reported individual SF-36 domains only)
Undetected for all other outcomes
|7 Good; 54 fair||Study duration may be insufficient to determine benefit for many health outcomes; small number of total events observed across studies for some outcomes (eg, mortality, cardiovascular events)||Moderate for sleep-related QOL and ESS, low for general health–related QOL; insufficient for other health outcomes||Referral population with known OSA|
|MADse||Mortality: 4 RCTs (245)
ESS: 10 RCTs (1540)
SF-36 total: 1 RCT (97)
SF-36 PCS: 2 RCTs (183)
SF-36 MCS: 2 RCTs (183)
Sleep-related QOL: 3 RCTs (256)
|ESS: pooled mean difference, −1.67 (95% CI, −2.09 to −1.25); 1 death in no-treatment group in one 4-wk RCT (n = 93)
QOL measures: mixed results
|Undetected for most; suspected for QOL measures||2 Good; 10 fair||Short study durations (1-12 wk), small number of studies reporting the outcomes and too few events (for mortality and motor vehicle crashes)||Moderate for ESS; insufficient for other outcomes||Referral population with known OSA|
|KQ6: Harms associated with treatment|
|Positive airway pressure||10 RCTs (2064)||Overall, 1% to 47% had specific adverse events while using positive airway pressure
Commonly reported harms were oral or nasal dryness, eye or skin irritation, and rash
|Undetected, but sparse reporting of harms||Fair||High heterogeneity in reporting and findings||Low||Referral population with known OSA|
|MADs||10 RCTs (684)||Overall, 17% to 74% had any harms while using MADs
Commonly reported harms were oral or nasal dryness, excess salivation, oral mucosal/dental/jaw symptoms
|Undetected, but sparse reporting of harms||Fair||High amount of heterogeneity in reporting and findings; most trials reported harms over a relatively short duration||Low||Referral population with known OSA|
Abbreviations: AHI, apnea-hypopnea index; AUC, area under the curve; DBP, diastolic blood pressure; ESS, Epworth Sleepiness Scale; FOSQ, Functional Outcomes of Sleep Questionnaire; HST, home sleep test; KQ, key question; MAD, mandibular advancement device; MCS, mental component summary score; MVAP, Multivariable Apnea Prediction; NA, not applicable; NR, not reported; OSA, obstructive sleep apnea; OSAS, obstructive sleep apnea syndrome; PCS, physical component summary score; QOL, quality of life; QSQ, Quebec Sleep Questionnaire; RCT, randomized clinical trial; SAQLI, Sleep Apnea Quality of Life Index; SBP, systolic blood pressure; SF-36, 36-Item Short Form Health Survey; SMD, standardized mean difference; STOP-BANG, snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, gender.
a Modified STOP-BANG (age >70 years; body mass index ≥ 26; neck circumference >26.5 cm).
b Modified STOP-BANG (age 5-64 years, 1 point; age ≥ 65 years, 2 points; and waist circumference >85, snoring; observed apnea; high blood pressure; body mass index >25; each 1 point).
c Pooled estimates were similar for nighttime and 24-hour blood pressure outcomes and for subgroup analyses of populations with hypertension and resistant hypertension.
d Study quality rating refers to quality of the systematic reviews, not the quality of individual trials included by the reviews.
e Selected results for the most commonly reported outcomes are included in this table. Details on additional measures (eg, Nottingham Health Profile) with few studies and insufficient evidence to draw conclusions are provided in the text and appendices.