Hypoglossal nerve stimulation versus positive airway pressure therapy for obstructive sleep apnea.

PURPOSE: Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea-hypopnea index (AHI), and (3) effectiveness. METHODS: Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated. RESULTS: Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP. CONCLUSION: Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03756805.

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT).

OBJECTIVE: The effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D. METHODS: This randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants' adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use). RESULTS: Baseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP -13.10 [-25.49 to -0.7] vs. sham -7.26 [-20.2 to 5.69]; P = .519) but different in HbA1c (CPAP -0.24 [-0.48 to -0.003] vs sham 0.15 [-0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP -0.26 [-0.53 to 0.002] vs sham -0.24 [-0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012). CONCLUSION: CPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.

Metabolic outcomes in adults with type 2 diabetes and sleep disorders.

PURPOSE: Insomnia is frequently co-morbid with obstructive sleep apnea (OSA); the effect of insomnia or co-morbid insomnia and OSA (OSA + I) on associated metabolic outcomes in adults with type 2 diabetes (T2D) remains unclear. This study in adults with T2D compared metabolic outcomes among persons with OSA, insomnia, or OSA + I. METHODS: This study analyzed baseline data from the Diabetes Sleep Treatment Trial of persons recruited for symptoms of OSA or poor sleep quality. Home sleep studies determined OSA presence and severity. Insomnia was evaluated using the Insomnia Severity Index. Height and weight to calculate body mass index (BMI) and blood for laboratory values were obtained. Multivariate general linear models were used to examine the impact of the type of sleep disorder and sociodemographic, lifestyle, and sleep risk factors on metabolic outcomes. RESULTS: Participants (N = 253) were middle-aged (56.3 ± 10.5 years), white (60.5%), obese (mean BMI of 35.3 ± 7.1 kg/m2), and male (51.4%) with poor glucose control (mean HbA1c of 8.0 ± 1.8%). Most participants had OSA + I (42.7%) or insomnia only (41.0%). HbA1c and BMI differed among the sleep disorder groups. In addition, in the adjusted models, having insomnia only, compared to OSA only, was associated on average with higher HbA1c levels (b = 1.08 ± 0.40, p < 0.007) and lower BMI (b = - 7.03 ± 1.43, p < 0.001). CONCLUSIONS: Findings suggest that insomnia frequently co-exists with OSA, is independently associated with metabolic outcomes in adults with T2D, and should be considered in investigations of the effects of OSA in persons with T2D. TRIAL REGISTRATION: Diabetes-Obstructive Sleep Apnea Treatment Trial (NCT01901055), https: Clinicaltrials.gov/ct2/show/NCT01901055; Registration date: July 17, 2013.

Internet-Based Cognitive-Behavioral Therapy for Insomnia in Adults With Asthma: A Pilot Study.

Background/Objective: Insomnia is common among adults with asthma and is associated with worse asthma control. Cognitive-behavioral therapy for insomnia (CBT-I) is an effective treatment for insomnia with medical comorbidities, but it has not been tested in asthma. The purpose of this study was to assess the feasibility and acceptability of an Internet-based CBT-I intervention, called Sleep Healthy Using the Internet (SHUTi), among adults with asthma and comorbid insomnia, and to gather preliminary efficacy data on changes in insomnia severity, sleep quality, asthma control, and asthma-related quality of life. Methods: A single-group, pretest-posttest design was employed, where all participants completed the SHUTi program. Online questionnaires were completed pre- and postintervention. Individual telephone interviews were conducted after posttreatment data collection to obtain participants' experiences with SHUTi and suggestions for improvement. Results: The sample (N = 23) comprised men and women aged 18-75 years with moderate to severe, not well-controlled asthma, and comorbid insomnia. Nineteen (83%) completed postintervention assessments. Improvements on the Insomnia Severity Index, Pittsburgh Sleep Quality Index, Asthma Control Test, and Asthma Quality of Life Questionnair-Marks were observed at postintervention. Data from the telephone interviews suggest that most participants had a positive experience with SHUTi. Participants suggested incorporating asthma-specific content into future versions of the intervention. Conclusions: Internet-based CBT-I is a potential treatment option for adults with asthma and comorbid insomnia.

Post-approval upper airway stimulation predictors of treatment effectiveness in the ADHERE registry.

Upper airway stimulation (UAS) has been shown to reduce severity of obstructive sleep apnoea. The aim of this study was to identify predictors of UAS therapy response in an international multicentre registry.Patients who underwent UAS implantation in the United States and Germany were enrolled in an observational registry. Data collected included patient characteristics, apnoea/hypopnoea index (AHI), Epworth sleepiness scale (ESS), objective adherence, adverse events and patient satisfaction measures. Post hoc univariate and multiple logistic regression were performed to evaluate factors associated with treatment success.Between October 2016 and January 2018, 508 participants were enrolled from 14 centres. Median AHI was reduced from 34 to 7 events·h-1, median ESS reduced from 12 to 7 from baseline to final visit at 12-month post-implant. In post hoc analyses, for each 1-year increase in age, there was a 4% increase in odds of treatment success. For each 1-unit increase in body mass index (BMI), there was 9% reduced odds of treatment success. In the multivariable model, age persisted in serving as statistically significant predictor of treatment success.In a large multicentre international registry, UAS is an effective treatment option with high patient satisfaction and low adverse events. Increasing age and reduced BMI are predictors of treatment response.

Determinants of depressive mood in coronary artery disease patients with obstructive sleep apnea and response to continuous positive airway pressure treatment in non-sleepy and sleepy phenotypes in the RICCADSA cohort.

We explored determinants of depressive mood in adults with coronary artery disease and obstructive sleep apnea and response to positive airway pressure treatment in sleepy and non-sleepy phenotypes. In this secondary analysis of the RICCADSA trial conducted in Sweden, 493 cardiac patients with obstructive sleep apnea (n = 386) or no obstructive sleep apnea (n = 107) with complete Epworth Sleepiness Scale and Zung Self-rating Depression Scale questionnaires were included. Sleepy (Epworth Sleepiness Scale ≥10) versus non-sleepy (Epworth Sleepiness Scale <10) patients with depressive mood (Zung Self-rating Depression Scale score ≥50) were evaluated after 3 and 12 months of positive airway pressure treatment. In all, 133 patients (27.0%) had depressive mood (29.3% of obstructive sleep apnea versus 18.7% of no obstructive sleep apnea; p = 0.029), with a higher percentage among the sleepy phenotype (36.9% versus 24.5%; p = 0.009). In multivariate analysis, depressive mood was significantly associated with female sex, body mass index and Epworth Sleepiness Scale. Among 97 obstructive sleep apnea patients with depressive mood at baseline, there was a significant reduction in the scores at follow-up both in the sleepy and non-sleepy patients allocated to positive airway pressure treatment, whereas no significant changes were observed in the untreated group (p = 0.033). The device use (hr/night) predicted improvement in mood (odds ratio, 1.33; 95% confidence interval, 1.10-1.61; p = 0.003) adjusted for age, female sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index and delta Epworth Sleepiness Scale score. We conclude that obstructive sleep apnea was associated with depressive mood in adults with coronary artery disease. Treatment with positive airway pressure improved mood in both phenotypes, independent of the confounding factors.

Sleep phenotype in the Townes mouse model of sickle cell disease.

PURPOSE: Patients with sickle cell disease (SCD) regularly experience abnormal sleep, characterized by frequent arousals and reduced total sleep time. However, obstructive sleep apnea syndrome (OSAS) is a common comorbidity of SCD, making it unclear whether the disease per se is impacting sleep, or sleep disruption is secondary to the presence of OSAS. Thus, we assessed sleep, independent of OSAS, using a mouse model of SCD. METHODS: Sleep was compared between 10-to-12-week-old Townes knockout-transgenic mice with the sickle cell phenotype SS (n = 6) and Townes mice with sickle cell trait AS (n = 6; control). The mice underwent chronic polysomnographic electrode implantation (4EEG/2EMG) to assess sleep architecture. RESULTS: The SS mice had significantly lower hemoglobin concentration compared to control AS mice (7.3 ± 1.3 vs. 12.9 ± 1.7 g/dL; p < 0.01), consistent with the expected SCD phenotype. SS mice exhibited significantly decreased total NREM sleep time (45.0 ± 0.7 vs. 53.0 ± 1.3% 24 h sleep time; p < 0.01), but no change in total REM sleep time compared to the AS mice. The SS mice took longer to resume sleep after a wake period compared to the AS mice (3.2 ± 0.3 min vs. 1.9 ± 0.2 min; p < 0.05). Unexpectedly, SS mice experienced fewer arousals compared to AS mice (19.0 ± 0.9 vs. 23.3 ± 2.1 arousals/h of sleep; p = 0.031). CONCLUSIONS: The presence of decreased total NREM sleep associated with reduced arousals, in the absence of OSAS, suggests a distinctive underlying sleep phenotype in a mouse model of SCD.

A Couples-Oriented Intervention for Positive Airway Pressure Therapy Adherence: A Pilot Study of Obstructive Sleep Apnea Patients and Their Partners.

Background: Partner involvement can influence positive airway pressure (PAP) therapy use among patients with obstructive sleep apnea (OSA). This study assessed the feasibility, acceptability, and preliminary efficacy of a couples-oriented education and support (CES) intervention for PAP adherence. Participants: Thirty newly diagnosed OSA patients and their partners were randomly assigned to one of three groups: an education and support intervention directed at both patient and partner (CES), an education and support intervention directed only at the patient (PES), or usual care (UC). Methods: Feasibility and acceptability were assessed through enrollment and posttreatment program evaluations, respectively. Assessments of sleep quality, daytime sleepiness, and daytime function were obtained from both patients and partners at baseline and 3 months after PAP initiation. Objective PAP adherence was assessed at 1 week, 1 month, and 3 months. Results: Recruitment and attrition data suggest adequate feasibility. All patients and partners in the CES group reported that the intervention was helpful. Patients in the CES and PES groups increased their PAP adherence over the first month of treatment, whereas PAP adherence decreased over this period in the UC group. For patients, large to medium effects for sleep quality (d = -1.01), daytime sleepiness (d = -0.51), and daytime function (d = 0.51) were found for the CES group. The PES and UC groups effect sizes were large to small for sleep quality (d = -0.94; d = -0.40), daytime sleepiness (d = -0.42; d = -0.82), and daytime function (d = 0.41; d = 0.57), respectively. For partners, large effects for daytime sleepiness (d = -1.31) and daytime function (d = 1.54) and small to medium effect for sleep quality (d = -0.31) were found for the CES group. Worsening of sleep quality (d = 0.65) and no change in daytime sleepiness or daytime function were found for the PES group. For the UC group, medium to large effects were found for sleep quality (d = -0.77), daytime sleepiness (d = -0.77), and daytime function (d = 0.65). Conclusions: The findings of this pilot study provide support for taking a couples intervention approach to improve PAP adherence.

Association of obstructive sleep apnea with microvascular endothelial dysfunction and subclinical coronary artery disease in a community-based population.

Studies have reported an association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) morbidity and mortality. Proposed mechanisms include endothelial dysfunction and atherosclerosis. We aimed to investigate the associations of OSA with endothelial dysfunction and subclinical atherosclerotic coronary artery disease (CAD), and assess the impact of race on these associations. We used data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a community-based prospective cohort with approximately equal representation of black and white participants. OSA severity was measured in 765 individuals using the apnea-hypopnea index (AHI). Endothelial dysfunction was measured using the Endo-PAT device, expressed as Framingham reactive hyperemia index (F_RHI). Coronary artery calcium (CAC), a marker of subclinical CAD, was quantified by electron beam computed tomography. There were 498 (65%) female participants, 282 (37%) black individuals, and 204 (26%) participants with moderate/severe OSA (AHI ≥15). In univariate models, moderate/severe OSA was associated with lower F_RHI and higher CAC, as well as several traditional CVD risk factors including older age, male sex, hypertension, diabetes, higher body mass index, and lower high-density lipoprotein cholesterol levels. In a multivariable model, individuals with moderate/severe OSA had 10% lower F_RHI and 35% higher CAC, which did not reach statistical significance ( p=0.08 for both comparisons). There was no significant interaction of race on the association of OSA with F_RHI or CAC ( p-value >0.1 for all comparisons). In a community-based cohort comprised of black and white participants, moderate/severe OSA was modestly associated with endothelial dysfunction and subclinical atherosclerotic CAD. These associations did not vary by race.

Obstructive sleep apnea and self-reported functional impairment in revascularized patients with coronary artery disease in the RICCADSA trial.

PURPOSE: Daytime sleepiness, a frequent symptom of obstructive sleep apnea (OSA), can impact functional status. In patients with coronary artery disease (CAD) and concomitant OSA, the distinction between sleep-related functional impairment from underlying CAD versus OSA is unclear. This study evaluated the impact of OSA on sleep-related functional impairment in patients with CAD and compared the effect of 1-year continuous positive airway pressure (CPAP) use on change in impairment between those with and without excessive daytime sleepiness (EDS) and OSA. We hypothesized that sleep-related functional impairment is impacted by EDS independent of OSA in patients with CAD. METHODS: One hundred five CAD patients without OSA and 105 with moderate-to-severe OSA from the RICCADSA trial were matched on disease severity and included in the current substudy. Of those with OSA, 80 were allocated to CPAP. Functional Outcomes of Sleep Questionnaire (FOSQ) score < 17.9 corresponded to sleep-related functional impairment. RESULTS: Following revascularization, CAD patients with and without OSA frequently report sleep-related functional impairment (35% and 27.3%, respectively; p = .29). Moderate-to-severe OSA was not related to baseline FOSQ scores < 17.9 in regression analyses; EDS was (OR 4.82, 95% CI 2.12-11.0; p < .001). CPAP use significantly improved FOSQ scores from baseline to 1-year follow-up in OSA patients with EDS (17.2 ± 2.0 to 18.15 ± 1.7, p = .002) despite suboptimal adherence. CONCLUSIONS: Sleep-related functional impairment may be reflective of persistent EDS, independent of OSA. Diagnosing OSA and initiating treatment are worthwhile in individuals with CAD and EDS, as both are important to guide appropriate therapy in patients with CAD.