Validation of an Overnight Wireless High-Resolution Oximeter plus Cloud-Based Algorithm for the Diagnosis of Obstructive Sleep Apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common but largely underdiagnosed condition. This study aimed to test the hypothesis that the oxygen desaturation index (ODI) obtained using a wireless high-resolution oximeter with a built-in accelerometer linked to a smartphone with automated cloud analysis, Overnight Digital Monitoring (ODM), is a reliable method for the diagnosis of OSA. METHODS: Consecutive patients referred to the sleep laboratory with suspected OSA underwent in-laboratory polysomnography (PSG) and simultaneous ODM. The PSG apnea-hypopnea index (AHI) was analyzed using the criteria recommended and accepted by the American Academy of Sleep Medicine (AASM) for the definition of hypopnea: arousal or ≥3% O2 desaturation (PSG-AHI3%) and ≥4% O2 desaturation (PSG-AHI4%), respectively. The results of PSG and ODM were compared by drawing parallels between the PSG-AHI3% and PSG-AHI4% with ODM-ODI3% and ODM-ODI4%, respectively. Bland-Altman plots, intraclass correlation, receiver operating characteristics (ROC) and area under the curve (AUC) analyses were conducted for statistical evaluation. ClinicalTrial.gov: NCT03526133. RESULTS: This study included 304 participants (men: 55%; age: 55±14 years; body mass index: 30.9±5.7 kg/m2; PSG-AHI3%: 35.3±30.1/h, ODM-ODI3%: 30.3±25.9/h). The variability in the AASM scoring bias (PSG-AHI3% vs PSG-AHI4%) was significantly higher than that for PSG-AHI3% vs ODM-ODI3% (3%) and PSG-AHI4% vs ODM-ODI4% (4%) (9.7, 5.0, and 2.9/h, respectively; p<0.001). The limits of agreement (2±SD, derived from the Bland-Altman plot) of AASM scoring variability were also within the same range for (PSG vs ODM) 3% and 4% variability: 18.9, 21.6, and 16.5/h, respectively. The intraclass correlation/AUC for AASM scoring variability and PSG vs ODM 3% or 4% variability were also within the same range (0.944/0.977 and 0.953/0.955 or 0.971/0.964, respectively). CONCLUSION: Our results showed that ODM is a simple and accurate method for the diagnosis of OSA.

Association between adherence to continuous positive airway pressure treatment and cost among medicare enrollees.

OBJECTIVE: To analyze the cost associated with sleep apnea and effects of continuous positive airway pressure (CPAP) treatment on costs among fee-for-service Medicare beneficiaries. METHODS: Retrospective cohort design using 5% Medicare claims between 2006 and 2010. Medicare beneficiaries with and without sleep apnea diagnosis between 2007 and 2008 were identified and followed retrospectively for 2 years pre-index-date and 2 years post-index-date. We defined CPAP fill as at least one durable medical equipment claim for CPAP in 6-month period. At least three CPAP fills was defined as "full adherence," and one or two CPAP fills was "partial adherence." We used interrupted time series and generalized linear log-link models to study the association between sleep apnea, CPAP treatment, and costs. To minimize bias, we used propensity score and instrumental variables approach. RESULTS: Sleep apnea was associated with higher costs (odds ratio [OR] = 1.60; 95% confidence interval [CI] = 1.58, 1.63) compared to those without sleep apnea. Almost half of those with sleep apnea received CPAP treatment. Interrupted time series analysis indicated post level increase in mean monthly cost for full CPAP adherence group, partial CPAP adherence group and no-CPAP group. However, the increase was smallest for the full CPAP adherence group. Full CPAP adherence was associated with lower change in cost (OR = 0.92; 95% CI = 0.88, 0.97) compared to the no-CPAP group. CONCLUSIONS: Medicare beneficiaries with sleep apnea experience increased cost. Full adherence to CPAP treatment for sleep apnea was associated with lower increase in cost. These findings emphasize the need to effectively identify and treat sleep apnea in Medicare patients.

Validation of an overnight wireless high-resolution oximeter plus cloud-based algorithm for the diagnosis of obstructive sleep apnea

OBJECTIVES: Obstructive sleep apnea (OSA) is a common but largely underdiagnosed condition. This study aimed to test the hypothesis that the oxygen desaturation index (ODI) obtained using a wireless high-resolution oximeter with a built-in accelerometer linked to a smartphone with automated cloud analysis, Overnight Digital Monitoring (ODM), is a reliable method for the diagnosis of OSA. METHODS: Consecutive patients referred to the sleep laboratory with suspected OSA underwent in-laboratory polysomnography (PSG) and simultaneous ODM. The PSG apnea-hypopnea index (AHI) was analyzed using the criteria recommended and accepted by the American Academy of Sleep Medicine (AASM) for the definition of hypopnea: arousal or ≥3% O2 desaturation (PSG-AHI3%) and ≥4% O2 desaturation (PSG-AHI4%), respectively. The results of PSG and ODM were compared by drawing parallels between the PSG-AHI3% and PSG-AHI4% with ODM-ODI3% and ODM-ODI4%, respectively. Bland-Altman plots, intraclass correlation, receiver operating characteristics (ROC) and area under the curve (AUC) analyses were conducted for statistical evaluation. ClinicalTrial.gov: NCT03526133. RESULTS: This study included 304 participants (men: 55%; age: 55±14 years; body mass index: 30.9±5.7 kg/m2; PSG-AHI3%: 35.3±30.1/h, ODM-ODI3%: 30.3±25.9/h). The variability in the AASM scoring bias (PSG-AHI3% vs PSG-AHI4%) was significantly higher than that for PSG-AHI3% vs ODM-ODI3% (3%) and PSG-AHI4% vs ODM-ODI4% (4%) (9.7, 5.0, and 2.9/h, respectively; p<0.001). The limits of agreement (2±SD, derived from the Bland-Altman plot) of AASM scoring variability were also within the same range for (PSG vs ODM) 3% and 4% variability: 18.9, 21.6, and 16.5/h, respectively. The intraclass correlation/AUC for AASM scoring variability and PSG vs ODM 3% or 4% variability were also within the same range (0.944/0.977 and 0.953/0.955 or 0.971/0.964, respectively). CONCLUSION: Our results showed that ODM is a simple and accurate method for the diagnosis of OSA.

Does Kidney Transplantation Affect Sleep and Fatigue in Patients With Kidney Disease?

BACKGROUND: Sleep disorders and fatigue are highly prevalent in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients but there is limited evidence on the effect of kidney transplant (KTx) on these. METHODS: In a prospective cohort study of patients with advanced CKD (estimated glomerular filtration rate<30 mL/min/1.73 m2) or ESKD, polysomnography and patient-reported symptom assessments were conducted. Pre- and post-KTx changes in sleep apnea (SA) severity (measured by apnea hypopnea index [AHI]) were analyzed and compared with patients who did not receive KTx. Regression models were used to examine predictors of SA severity. RESULTS: Among 77 patients (mean age 51 y, BMI 29 kg/m2, 66% males, 23% ESKD), 61% had SA at baseline. Among 39 KTx recipients, 56% had SA, with 39% having moderate-severe SA after 10 ± 5.6 months post-KTx. There was no difference in AHI in either the KTx (median 6 versus 8; P = 0.37) or no-KTx (median 15 versus 16; P = 0.61) groups after an average of 19.9 ± 8.9 months. KTx led to significant clinically meaningful improvements in fatigue and health-related quality of life (adjusted effect size 0.3-0.6). In multivariable regression, baseline AHI was the only significant predictor of SA severity (adjusted ß = 3.6/5 units, 95% confidence interval 2.1, 5.2) after adjusting for KTx status, age, sex, and body mass index. CONCLUSIONS: More than half of the KTx recipients had SA. There was no significant change in SA severity with KTx. Clinically meaningful moderate size improvements in patient-reported fatigue and health-related quality of life may be seen with KTx.

Treating OSA: Current and emerging therapies beyond CPAP.

Continuous positive airway pressure (CPAP) is the standard treatment for moderate-to-severe obstructive sleep apnoea (OSA). However, adherence to CPAP is limited and non-CPAP therapies are frequently explored. Oral appliance (OA) therapy is currently widely used for the treatment of snoring, mild, moderate and severe OSA. The most commonly used and studied OA consists of a maxillary and mandibular splint which hold the lower jaw forward during sleep. The efficacy of OA is inferior to CPAP; however, the effectiveness as measured by sleepiness, quality of life, endothelial function and blood pressure is similar likely due to higher acceptance and subjective adherence. Upper airway stimulation augments neural drive by unilaterally stimulating the hypoglossal nerve. The Stimulation Therapy for Apnea Reduction (STAR) study enrolled 126 patients and demonstrated a 68% reduction in OSA severity. A high upfront cost and variable response are the main limitations. Oropharyngeal exercises consist of a set of isometric and isotonic exercises involving the tongue, soft palate and lateral pharyngeal wall. The collective reported trials (n = 120) showed that oropharyngeal exercises can ameliorate OSA and snoring (~30-40%). Nasal EPAP devices consist of disposable one-way resister valve. A systematic review (n = 345) showed that nasal EPAP reduced OSA severity by 53%. The Winx device consists of a mouthpiece placed inside the oral cavity that is connected by tubing to a console that generates negative pressure. Winx may provide successful therapy for ~30-40% of OSA patients. In conclusion, several non-CPAP therapies to treat OSA are currently available.

Sleep-apnea risk and subclinical atherosclerosis in early-middle-aged retired National Football League players.

PURPOSE: Limited data from former National Football League (NFL) players suggest that obstructive sleep apnea (OSA) may be highly prevalent after retirement. It remains unclear whether the high prevalence of OSA in retired players is comparable to nonathletes. This retrospective analysis compared sleep apnea (SA) risk in retired NFL players to a community cohort (CARDIA Sleep study), and examined associations between SA risk and cardiovascular risk factors, including subclinical atherosclerosis. MATERIALS AND METHODS: Retired NFL players (n=122) were matched to CARDIA Sleep participants by age ±2 years (range 37-55 years), body mass index ±2 kg/m2, race, and male sex. Participants underwent electron-beam computed tomography to measure coronary artery calcium (CAC) and completed the Berlin Questionnaire to determine SA risk. The presence of CAC was defined as an Agatston score >0. RESULTS: Retired NFL players had a greater prevalence of high SA risk than the matched CARDIA Sleep participants (27% vs 11.5%, P=0.002). Compared to the CARDIA Sleep participants, retired players were less likely to smoke, and had higher blood pressure, lower fasting glucose levels, and higher cholesterol levels. However, there was no difference in the prevalence of detectable CAC (30% vs 30%, P=1). In both players and the community cohort, SA risk was not significantly associated with CAC after controlling for age, race, and body mass index. CONCLUSION: Retired NFL players have a greater prevalence of high SA risk but similar prevalence of CAC compared with a well-matched community cohort.

Metabolic Syndrome and the Lung.

A link between metabolic syndrome (MetS) and lung diseases has been observed in several cross-sectional and longitudinal studies. This syndrome has been identified as an independent risk factor for worsening respiratory symptoms, greater lung function impairment, pulmonary hypertension, and asthma. This review will discuss several potential mechanisms to explain these associations, including dietary factors and the effect of adiposity and fat-induced inflammation on the lungs, and the role of other comorbidities that frequently coexist with MetS, such as OSA and obesity. In contrast to the well-known association between asthma and obesity, the recognition that MetS affects the lung is relatively new. Although some controversy remains as to whether MetS is a unique disease entity, its individual components have independently been associated with changes in pulmonary function or lung disease. There is, however, uncertainty as to the relative contribution that each metabolic factor has in adversely affecting the respiratory system; also, it is unclear how much of the MetS-related lung effects occur independently of obesity. In spite of these epidemiological limitations, the proposed mechanistic pathways strongly suggest that this association is likely to be causal. Given the wide prevalence of MetS in the general population, it is imperative that we continue to further understand how this metabolic disorder impacts the lung and how to prevent its complications.

Upper Airway Stimulation for Obstructive Sleep Apnea: Self-Reported Outcomes at 24 Months.

OBJECTIVES: To evaluate the long-term (24-mo) effect of cranial nerve upper airway stimulation (UAS) therapy on patient-centered obstructive sleep apnea (OSA) outcome measures. METHODS: Prospective, multicenter, cohort study of 126 patients with moderate to severe OSA who had difficulty adhering to positive pressure therapy and received the surgically implanted UAS system. Outcomes were measured at baseline and postoperatively at 12 mo and 24 mo, and included self- and bedpartner-report of snoring intensity, Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ). Additional analysis included FOSQ subscales, FOSQ-10, and treatment effect size. RESULTS: Significant improvement in mean FOSQ score was observed from baseline (14.3) to 12 mo (17.3), and the effect was maintained at 24 mo (17.2). Similar improvements and maintenance of effect were seen with all FOSQ subscales and FOSQ-10. Subjective daytime sleepiness, as measured by mean ESS, improved significantly from baseline (11.6) to 12 mo (7.0) and 24 mo (7.1). Self-reported snoring severity showed increased percentage of "no" or "soft" snoring from 22% at baseline to 88% at 12 mo and 91% at 24 mo. UAS demonstrated large effect size (> 0.8) at 12 and 24 mo for overall ESS and FOSQ measures, and the effect size compared favorably to previously published effect size with other sleep apnea treatments. CONCLUSIONS: In a selected group of patients with moderate to severe OSA and body mass index ≤ 32 kg/m2, hypoglossal cranial nerve stimulation therapy can provide significant improvement in important sleep related quality-of-life outcome measures and the effect is maintained across a 2-y follow-up period.

Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months.

OBJECTIVE: To determine the stability of improvement in polysomnographic measures of sleep disordered breathing, patient reported outcomes, the durability of hypoglossal nerve recruitment and safety at 18 months in the Stimulation Treatment for Apnea Reduction (STAR) trial participants. DESIGN: Prospective multicenter single group trial with participants serving as their own controls. SETTING: Twenty-two community and academic sleep medicine and otolaryngology practices. MEASUREMENTS: Primary outcome measures were the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI). Secondary outcome measures were the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation percent time < 90% during sleep. Stimulation level for each participant was collected at three predefined thresholds during awake testing. Procedure- and/or device-related adverse events were reviewed and coded by the Clinical Events Committee. RESULTS: The median AHI was reduced by 67.4% from the baseline of 29.3 to 9.7/h at 18 mo. The median ODI was reduced by 67.5% from 25.4 to 8.6/h at 18 mo. The FOSQ and ESS improved significantly at 18 mo compared to baseline values. The functional threshold was unchanged from baseline at 18 mo. Two participants experienced a serious device-related adverse event requiring neurostimulator repositioning and fixation. No tongue weakness reported at 18 mo. CONCLUSION: Upper airway stimulation via the hypoglossal nerve maintained a durable effect of improving airway stability during sleep and improved patient reported outcomes (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire) without an increase of the stimulation thresholds or tongue injury at 18 mo of follow-up.

African Genetic Ancestry is Associated with Sleep Depth in Older African Americans.

STUDY OBJECTIVES: The mechanisms that underlie differences in sleep characteristics between European Americans (EA) and African Americans (AA) are not fully known. Although social and psychological processes that differ by race are possible mediators, the substantial heritability of sleep characteristics also suggests genetic underpinnings of race differences. We hypothesized that racial differences in sleep phenotypes would show an association with objectively measured individual genetic ancestry in AAs. DESIGN: Cross sectional. SETTING: Community-based study. PARTICIPANTS: Seventy AA adults (mean age 59.5 ± 6.7 y; 62% female) and 101 EAs (mean age 60.5 ± 7 y, 39% female). MEASUREMENTS AND RESULTS: Multivariate tests were used to compare the Pittsburgh Sleep Quality Index (PSQI) and in-home polysomnographic measures of sleep duration, sleep efficiency, apnea-hypopnea index (AHI), and indices of sleep depth including percent visually scored slow wave sleep (SWS) and delta EEG power of EAs and AAs. Sleep duration, efficiency, and sleep depth differed significantly by race. Individual % African ancestry (%AF) was measured in AA subjects using a panel of 1698 ancestry informative genetic markers and ranged from 10% to 88% (mean 67%). Hierarchical linear regression showed that higher %AF was associated with lower percent SWS in AAs (ß (standard error) = -4.6 (1.5); P = 0.002), and explained 11% of the variation in SWS after covariate adjustment. A similar association was observed for delta power. No association was observed for sleep duration and efficiency. CONCLUSION: African genetic ancestry is associated with indices of sleep depth in African Americans. Such an association suggests that part of the racial differences in slow-wave sleep may have genetic underpinnings.

Traditional and nontraditional cardiovascular risk factors in comorbid insomnia and sleep apnea.

OBJECTIVES: Insomnia and sleep apnea frequently co-occur and are independently associated with an increased risk of cardiovascular disease, but little is known about cardiovascular disease risk among individuals with comorbid insomnia and sleep apnea. The current study examined traditional risk factors and a physiologic biomarker of cardiovascular risk in comorbid insomnia and sleep apnea. DESIGN: Community-based participatory research study. PARTICIPANTS: The sample comprised 795 participants without preexisting cardiovascular disease from the Heart Strategies Concentrating On Risk Evaluation (Heart SCORE) study. MEASUREMENTS AND RESULTS: Participants were assessed for symptoms of insomnia and sleep apnea risk, as well as for presence of obesity, smoking, a sedentary lifestyle, hypertension, dyslipidemia, and diabetes. Baseline resting brachial artery diameter was measured by B-mode ultrasonography. A total of 138 participants (17.4%) met criteria for insomnia syndrome alone, 179 (22.5%) were at high risk for sleep apnea alone, 95 (11.9%) reported both insomnia syndrome and high sleep apnea risk, and 383 (48.2%) reported having neither insomnia nor sleep apnea symptoms Both high sleep apnea risk alone and comorbid insomnia and high sleep apnea risk groups had greater frequencies of obesity, sedentary lifestyle, hypertension, and three or more traditional cardiovascular risk factors and significantly larger brachial artery diameters than the insomnia alone group and those without insomnia or sleep apnea symptoms. No differences in traditional cardiovascular risk factors or brachial artery diameter were found between the high sleep apnea risk and comorbid groups. CONCLUSIONS: These findings suggest that sleep apnea is a major contributor to cardiovascular risk and co-occurring insomnia does not appear to add to this risk.

Resistant hypertension and obstructive sleep apnea in the setting of kidney disease.

OBJECTIVES: To explore the relationship between obstructive sleep apnea (OSA) and resistant hypertension in chronic kidney disease (CKD) and end-stage renal disease (ESRD). METHODS: We examined sleep parameters and blood pressure (BP) in 224 community-based, non-CKD participants from the Sleep-SCORE study: 88 nondialysis-dependent CKD and 95 ESRD participants. Unattended home polysomnography with standardized scoring protocols and automated BP monitors were used. Resistant hypertension was defined as a BP of at least 140/90  mmHg despite at least three antihypertensive drugs. RESULTS: Mean SBP of the CKD and ESRD groups were significantly higher than that of the non-CKD group [148.2 (23.8), 144.5 (26.7) vs. 132.2  mmHg (26.7), respectively; P < 0.0001] despite the use of more antihypertensive medications. The CKD and ESRD groups had higher rates of resistant hypertension than the non-CKD group (41.4, 22.6 vs. 6.7%, respectively; P < 0.0001). The severity of sleep apnea was associated with a higher risk of resistant hypertension. Although resistant hypertension was associated with severe sleep apnea in participants with ESRD [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.2-23.2), there was no significant association in the non-CKD (OR 3.5, 95% CI 0.8-15.4) or CKD groups (OR 1.2, 95% CI 0.4-3.7) after accounting for case-mix. CONCLUSION: The association between resistant hypertension and sleep apnea appeared robust in ESRD. OSA may contribute to resistant hypertension or both may be linked to a common underlying process such as volume excess. Future studies in patients with kidney disease should further characterize the resistant hypertension-OSA relationship and determine whether treatment of underlying mechanisms may improve outcomes.