Medline ® Abstracts for References 9-18

The therapeutic effects of weight loss were evaluated in 15 hypersomnolent patients with moderately severe obstructive sleep apnea. As patients decreased their body weight from 106.2 +/- 7.3 kg (mean +/- SE) to 96.6 +/- 5.9 kg, apnea frequency fell from 55.0 +/- 7.5 to 29.2 +/- 7.1 episodes/h (p less than 0.01) in non-rapid-eye-movement sleep with an associated significant decline in the mean oxyhemoglobin saturation during the remaining episodes of sleep apnea from 11.9 +/- 2.4% to 7.9 +/- 1.9% (p less than 0.02). Sleep patterns also improved, with a reduction in stage I sleep from 40.2 +/- 7.3% to 23.5 +/- 4.8% (p less than 0.01), and a rise in stage II sleep from 37.3 +/- 7.0% to 49.4 +/- 4.6% (p less than 0.03). In the 9 patients with the most marked fall in apnea frequency, the tendency toward daytime hypersomnolence was decreased (p less than 0.05). No significant changes in sleep patterns occurred in 8 age- and weight-matched control patients who did not lose weight. Moderate weight loss alone can alleviate sleep apnea, improve sleep architecture, and decrease daytime hypersomnolence.

RATIONALE: Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA.

OBJECTIVES: The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA.

METHODS: Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements.

MEASUREMENTS AND MAIN RESULTS: The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference.

CONCLUSIONS: VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up.

CONTEXT: Obstructive sleep apnea (OSA) is strongly related to obesity. Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA.

OBJECTIVE: To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA.

DESIGN, SETTING, AND PATIENTS: A randomized controlled trial of 60 obese patients (body mass index:>35 and<55) with recently diagnosed (<6 months) OSA and an apnea-hypopnea index (AHI) of 20 events/hour or more. These patients had been prescribed continuous positive airway pressure (CPAP) therapy to manage OSA and were identified via accredited community sleep clinics. The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical researchers in Melbourne, Australia. Patients with obesity hypoventilation syndrome, previous bariatric surgery, contraindications to bariatric surgery, or significant cardiopulmonary, neurological, vascular, gastrointestinal, or neoplastic disease were excluded.

INTERVENTIONS: Patients were randomized to a conventional weight loss program that included regular consultations with a dietitian and physician, and the use of very low-calorie diets as necessary (n = 30) or to bariatric surgery (laparoscopic adjustable gastric banding; n = 30).

MAIN OUTCOME MEASURES: The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to randomization. Secondary outcomes were changes in weight, CPAP adherence, and functional status.

RESULTS: Patients lost a mean of 5.1 kg (95% CI, 0.8 to 9.3 kg) in the conventional weight loss program compared with 27.8 kg (95% CI, 20.9 to 34.7 kg) in the bariatric surgery group (P<.001). The AHI decreased by 14.0 events/hour (95% CI, 3.3 to 24.6 events/hour) in the conventional weight loss group and by 25.5 events/hour (95% CI, 14.2 to 36.7 events/hour) in the bariatric surgery group. The between-group difference was -11.5 events/hour (95% CI, -28.3 to 5.3 events/hour; P = .18). CPAP adherence did not differ between the groups. The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score (mean, 9.3 [95% CI, 0.5 to 18.0]; P = .04).

CONCLUSION: Among a group of obese patients with OSA, the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss.

TRIAL REGISTRATION: anzctr.org Identifier: 12605000161628.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder associated with several adverse health outcomes. Given the close association between OSA and obesity, lifestyle and dietary interventions are commonly recommended to patients, but the evidence for their impact on OSA has not been systematically examined.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the impact of weight loss through diet and physical activity on measures of OSA: apnea-hypopnea index (AHI) and oxygen desaturation index of 4% (ODI4).

METHODS: A systematic search was performed to identify publications using Medline (1948-2011 week 40), EMBASE (from 1988-2011 week 40), and CINAHL (from 1982-2011 week 40). The inverse variance method was used to weight studies and the random effects model was used to analyze data.

RESULTS: Seven randomized controlled trials (519 participants) showed that weight reduction programs were associated with a decrease in AHI (-6.04 events/h [95% confidence interval -11.18, -0.90]) with substantial heterogeneity between studies (I(2) = 86%). Nine uncontrolled before-after studies (250 participants) showed a significant decrease in AHI (-12.26 events/h [95% confidence interval -18.51, -6.02]). Four uncontrolled before-after studies (97 participants) with ODI4 as outcome also showed a significant decrease in ODI4 (-18.91 episodes/h [95% confidence interval -23.40, -14.43]).

CONCLUSIONS: Published evidence suggests that weight loss through lifestyle and dietary interventions results in improvements in obstructive sleep apnea parameters, but is insufficient to normalize them. The changes in obstructive sleep apnea parameters could, however, be clinically relevant in some patients by reducing obstructive sleep apnea severity. These promising preliminary results need confirmation through larger randomized studies including more intensive weight loss approaches.

BACKGROUND: The belief that weight loss improves obstructive sleep apnea (OSA) has limited empirical support. The purpose of this 4-center study was to assess the effects of weight loss on OSA over a 1-year period.

METHODS: The study included 264 participants with type 2 diabetes and a mean (SD) age of 61.2 (6.5) years, weight of 102.4 (18.3) kg, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 36.7 (5.7), and an apnea-hypopnea index (AHI) of 23.2 (16.5) events per hour. The participants were randomly assigned to either a behavioral weight loss program developed specifically for obese patients with type 2 diabetes (intensive lifestyle intervention [ILI]) or 3 group sessions related to effective diabetes management (diabetes support and education [DSE]).

RESULTS: The ILI participants lost more weight at 1 year than did DSE participants (10.8 kg vs0.6 kg; P<.001). Relative to the DSE group, the ILI intervention was associated with an adjusted (SE) decrease in AHI of 9.7 (2.0) events per hour (P<.001). At 1 year, more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among ILI participants was half that of the DSE group. Initial AHI and weight loss were the strongest predictors of changes in AHI at 1 year (P<.01). Participants with a weight loss of 10 kg or more had the greatest reductions in AHI.

CONCLUSIONS: Physicians and their patients can expect that weight loss will result in significant and clinically relevant improvements in OSA among obese patients with type 2 diabetes. Trial Registration clinicaltrials.gov Identifier: NCT00194259.

STUDY OBJECTIVES: To examine whether the initial benefit of weight loss on obstructive sleep apnea (OSA) severity at 1 year is maintained at 4 years.

DESIGN: Randomized controlled trial with follow-up at 1, 2, and 4 years.

SETTING: 4 Look AHEAD clinical centers.

PARTICIPANTS: Two hundred sixty-four obese adults with type 2 diabetes and OSA.

INTERVENTIONS: Intensive lifestyle intervention with a behavioral weight loss program or diabetes support and education.

MEASUREMENTS: Change in apnea-hypopnea index on polysomnogram.

RESULTS: The intensive lifestyle intervention group's mean weight loss was 10.7±0.7 (standard error), 7.4±0.7, and 5.2±0.7 kg at 1, 2, and 4 years respectively, compared to a less than 1-kg weight loss for the control group at each time (P<0.001). Apnea-hypopnea index difference between groups was 9.7±2.0, 8.0±2.0, and 7.7±2.3 events/h at 1, 2 and 4 years respectively (P<0.001). Change in apnea-hypopnea index over time was related to the amount of weight loss (P<0.0001) and intervention, independent of weight loss (P = 0.001). Remission of OSA at 4 years was 5 times more common with intensive lifestyle intervention (20.7%) than diabetes support and education (3.6%).

CONCLUSIONS: Among obese adults with type 2 diabetes and OSA, intensive lifestyle intervention produced greater reductions in weight and apnea-hypopnea index over a 4 year period than did diabetes support and education. Beneficial effects of intensive lifestyle intervention on apneahypopnea index at 1 year persisted at 4 years, despite an almost 50% weight regain. Effect of intensive lifestyle intervention on apnea-hypopnea index was largely, but not entirely, due to weight loss.

BACKGROUND: Excess body weight is a risk factor for obstructive sleep apnoea (OSA). The aim of the systematic review was to establish whether weight loss via lifestyle interventions such as diet and exercise are useful in the treatment of OSA.

METHODS: A literature search was conducted between 1980 and February 2012. Systematic reviews and randomised controlled trials (RCTs) with participants who had OSA, were overweight or obese, and who had undergone lifestyle interventions with the aim of improving sleep apnoea were included. Meta analyses were conducted for a subset of RCTs with appropriate data.

RESULTS: Two systematic reviews and eight RCTs were included. Meta-analyses were conducted for four RCTs comparing intensive lifestyle interventions to a control. The overall weighted mean differences for weight change, change in apnoea -hypopnoea index (AHI) and change in oxygen desaturation index of≥4% were as follows: -13.76 kg (95% confidence interval (CI) -19.21, --8.32), -16.09 (95% CI -25.64, -6.54) and -14.18 (95% CI -24.23, -4.13), respectively. Although high heterogeneity within the meta analyses, all studies favoured the interventions. Long-term follow-up data from three RCTs suggest that improvements in weight and AHI are maintained for up to 60 months.

CONCLUSIONS: Intensive lifestyle interventions are effective in the treatment of OSA, resulting in significant weight loss and a reduction in sleep apnoea severity. Weight loss via intensive lifestyle interventions could be encouraged as a treatment for mild to moderate OSA.

BACKGROUND: Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear.

METHODS: We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure.

RESULTS: Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone.

CONCLUSIONS: In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .).

BACKGROUND: Obesity is an important risk factor for OSA. This study aimed to assess the effect of weight reduction through a lifestyle modification program (LMP) on patients with moderate to severe OSA.

METHODS: This was a parallel group, randomized controlled trial. Altogether, 104 patients with moderate to severe OSA diagnosed on portable home sleep monitoring were randomized to receive a dietician-led LMP or usual care for 12 months. The primary outcome was reduction of apnea-hypopnea index (AHI) at 12 months as assessed by portable home sleep monitoring.

RESULTS: In the intention-to-treat analysis (ITT), LMP (n = 61) was more effective in reducing AHI from baseline (16.9% fewer events in the LMP group vs 0.6% more events in the control group, P = .011). LMP was more effective in reducing BMI (-1.8 kg/m2, 6.0% of the initial BMI; -0.6 kg/m2, 2.0% of the initial BMI in control group; P<.001). The reduction in daytime sleepiness as assessed by Epworth Sleepiness Scale was not significant in ITT but was more in the LMP group (-3.5 in the LMP group vs -1.1 in the control group, P = .004) by treatment per protocol analysis. There was modest improvement in mental health in the ShortForm Health Survey. Eating behavior was improved with increased intake of protein and fiber. These changes were observed 4 months after the initial intensive diet counseling and persisted at 12 months.

CONCLUSIONS: LMP was effective in reducing the severity of OSA and daytime sleepiness. The beneficial effect was sustained in 12 months.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01384760; URL: www.clinicaltrials.gov.

Importance: Many adverse health outcomes are associated with obstructive sleep apnea (OSA).

Objective: To review primary care-relevant evidence on screening adults for OSA, test accuracy, and treatment of OSA, to inform the US Preventive Services Task Force.

Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 2015, references, and experts, with surveillance of the literature through October 5, 2016.

Study Selection: English-language randomized clinical trials (RCTs); studies evaluating accuracy of screening questionnaires or prediction tools, diagnostic accuracy of portable monitors, or association between apnea-hypopnea index (AHI) and health outcomes among community-based participants.

Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles. When multiple similar studies were available, random-effects meta-analyses were conducted.

Main Outcomes and Measures: Sensitivity, specificity, area under the curve (AUC), AHI, Epworth Sleepiness Scale (ESS) scores, blood pressure, mortality, cardiovascular events, motor vehicle crashes, quality of life, and harms.

Results: A total of 110 studies were included (N = 46 188). No RCTs compared screening with no screening. In 2 studies (n = 702), the screening accuracy of the multivariable apnea prediction score followed by home portable monitor testing for detecting severe OSA syndrome (AHI≥30 and ESS score>10) was AUC 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively, but the studies oversampled high-risk participants and those with OSA and OSA syndrome. No studies prospectively evaluated screening tools to report calibration or clinical utility for improving health outcomes. Meta-analysis found that continuous positive airway pressure (CPAP) compared with sham was significantly associated with reduction of AHI (weighted mean difference [WMD], -33.8 [95% CI, -42.0 to -25.6]; 13 trials, 543 participants), excessive sleepiness assessed by ESS score (WMD, -2.0 [95% CI, -2.6 to -1.4]; 22 trials, 2721 participants), diurnal systolic blood pressure (WMD, -2.4 points [95% CI, -3.9 to -0.9]; 15 trials, 1190 participants), and diurnal diastolic blood pressure (WMD, -1.3 points [95% CI, -2.2 to -0.4]; 15 trials, 1190 participants). CPAP was associated with modest improvement in sleep-related quality of life (Cohen d, 0.28 [95% CI, 0.14 to 0.42]; 13 trials, 2325 participants). Mandibularadvancement devices (MADs) and weight loss programs were also associated with reduced AHI and excessive sleepiness. Common adverse effects of CPAP and MADs included oral or nasal dryness, irritation, and pain, among others. In cohort studies, there was a consistent association between AHI and all-cause mortality.

Conclusions and Relevance: There is uncertainty about the accuracy or clinical utility of all potential screening tools. Multiple treatments for OSA reduce AHI, ESS scores, and blood pressure. Trials of CPAP and other treatments have not established whether treatment reduces mortality or improves most other health outcomes, except for modest improvement in sleep-related quality of life.