Michael Rueschman

Measuring sleep: Accuracy, sensitivity, and specificity of wrist actigraphy compared to polysomnography

OBJECTIVES We validated actigraphy for detecting sleep and wakefulness versus polysomnography (PSG). DESIGN Actigraphy and polysomnography were simultaneously collected during sleep laboratory admissions. All studies involved 8.5 h time in bed, except for sleep restriction studies. Epochs (30-sec; n = 232,849) were characterized for sensitivity (actigraphy = sleep when PSG = sleep), specificity (actigraphy = wake when PSG = wake), and accuracy (total proportion correct); the amount of wakefulness after sleep onset (WASO) was also assessed. A generalized estimating equation (GEE) model included age, gender, insomnia diagnosis, and daytime/nighttime sleep timing factors. SETTING Controlled sleep laboratory conditions. PARTICIPANTS Young and older adults, healthy or chronic primary insomniac (PI) patients, and daytime sleep of 23 night-workers (n = 77, age 35.0 ± 12.5, 30F, mean nights = 3.2). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Overall, sensitivity (0.965) and accuracy (0.863) were high, whereas specificity (0.329) was low; each was only slightly modified by gender, insomnia, day/night sleep timing (magnitude of change < 0.04). Increasing age slightly reduced specificity. Mean WASO/night was 49.1 min by PSG compared to 36.8 min/night by actigraphy (β = 0.81; CI = 0.42, 1.21), unbiased when WASO < 30 min/night, and overestimated when WASO > 30 min/night. CONCLUSIONS This validation quantifies strengths and weaknesses of actigraphy as a tool measuring sleep in clinical and population studies. Overall, the participant-specific accuracy is relatively high, and for most participants, above 80%. We validate this finding across multiple nights and a variety of adults across much of the young to midlife years, in both men and women, in those with and without insomnia, and in 77 participants. We conclude that actigraphy is overall a useful and valid means for estimating total sleep time and wakefulness after sleep onset in field and workplace studies, with some limitations in specificity.

A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: The HomePAP study

STUDY OBJECTIVES To test the utility of an integrated clinical pathway for obstructive sleep apnea (OSA) diagnosis and continuous positive airway pressure (CPAP) treatment using portable monitoring devices. DESIGN Randomized, open-label, parallel group, unblinded, multicenter clinical trial comparing home-based, unattended portable monitoring for diagnosis and autotitrating CPAP (autoPAP) compared with in-laboratory polysomnography (PSG) and CPAP titration. SETTING Seven American Academy of Sleep Medicine (AASM) accredited sleep centers. PARTICIPANTS Consecutive new referrals, age 18 yr or older with high probability of moderate to severe OSA (apnea-hypopnea index [AHI] ≥ 15) identified by clinical algorithm and Epworth Sleepiness Scale (ESS) score ≥ 12. INTERVENTIONS Home-based level 3 testing followed by 1 wk of autoPAP with a fixed pressure CPAP prescription based on the 90% pressure from autotitration of PAP therapy (autoPAP) device (HOME) compared with attended, in-laboratory studies (LAB). MEASUREMENTS CPAP acceptance, time to treatment, adherence at 1 and 3 mo; changes in ESS, and functional outcomes. RESULTS Of 373 participants, approximately one-half in each study arm remained eligible (AHI ≥ 15) to continue in the study. At 3 mo, PAP usage (nightly time at pressure) was 1 hr greater: 4.7 ± 2.1 hr (HOME) compared with 3.7 ± 2.4 hr (LAB). Adherence (percentage of night used ≥ 4 hr) was 12.6% higher: 62.8 ± 29.2% compared with 49.4 ± 36.1% in the HOME versus LAB. Acceptance of PAP therapy, titration pressures, effective titrations, time to treatment, and ESS score change did not differ between arms. CONCLUSIONS A home-based strategy for diagnosis and treatment compared with in-laboratory PSG was not inferior in terms of acceptance, adherence, time to treatment, and functional improvements. TRIAL REGISTRATION http://www.ClinicalTrials.gov; Identifier: NCT: 00642486.

CPAP versus Oxygen in Obstructive Sleep Apnea

BACKGROUND Obstructive sleep apnea is associated with hypertension, inflammation, and increased cardiovascular risk. Continuous positive airway pressure (CPAP) reduces blood pressure, but adherence is often suboptimal, and the benefit beyond management of conventional risk factors is uncertain. Since intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, we evaluated the effects of nocturnal supplemental oxygen and CPAP on markers of cardiovascular risk. METHODS We conducted a randomized, controlled trial in which patients with cardiovascular disease or multiple cardiovascular risk factors were recruited from cardiology practices. Patients were screened for obstructive sleep apnea with the use of the Berlin questionnaire, and home sleep testing was used to establish the diagnosis. Participants with an apnea-hypopnea index of 15 to 50 events per hour were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental oxygen. Cardiovascular risk was assessed at baseline and after 12 weeks of the study treatment. The primary outcome was 24-hour mean arterial pressure. RESULTS Of 318 patients who underwent randomization, 281 (88%) could be evaluated for ambulatory blood pressure at both baseline and follow-up. On average, the 24-hour mean arterial pressure at 12 weeks was lower in the group receiving CPAP than in the control group (-2.4 mm Hg; 95% confidence interval [CI], -4.7 to -0.1; P=0.04) or the group receiving supplemental oxygen (-2.8 mm Hg; 95% CI, -5.1 to -0.5; P=0.02). There was no significant difference in the 24-hour mean arterial pressure between the control group and the group receiving oxygen. A sensitivity analysis performed with the use of multiple imputation approaches to assess the effect of missing data did not change the results of the primary analysis. CONCLUSIONS In patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of obstructive sleep apnea with CPAP, but not nocturnal supplemental oxygen, resulted in a significant reduction in blood pressure. (Funded by the National Heart, Lung, and Blood Institute and others; HeartBEAT ClinicalTrials.gov number, NCT01086800 .).

A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea.

STUDY OBJECTIVES To address whether treatment of sleep apnea improves glucose tolerance. DESIGN Randomized, double-blind crossover study. SETTING Sleep clinic referrals. PATIENTS 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. INTERVENTIONS Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. MEASUREMENTS AND RESULTS The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P < 0.001) improvement in ISI (0,120) and a 28.7% (95%CI: [-46.5%, -10.9%], P = 0.002) reduction in the 2-h insulin level after CPAP compared to sham CPAP. CONCLUSIONS This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical trials information: ClinicalTrials.gov Identifier: NCT01385995.

Sleep disordered breathing is associated with asthma severity in children

OBJECTIVE To examine the relationships among obesity, sleep-disordered breathing (SDB, defined as intermittent nocturnal hypoxia and habitual snoring), and asthma severity in children. We hypothesized that obesity and SDB are associated with severe asthma at a 1- year follow-up. STUDY DESIGN Children aged 4-18 years were recruited sequentially from a specialty asthma clinic and underwent physiological, anthropometric, and biochemical assessment at enrollment. Asthma severity was determined after 1 year of follow-up and guideline-based treatment, using a composite measure of level of controller medication, symptom burden, and health care utilization. Multivariate logistic regression was used to examine adjusted associations of SDB and obesity with asthma severity at 12-month follow-up. RESULTS Among 108 subjects (mean age, 9.1±3.4 years; 45.4% African-American; 67.6% male), obesity and SDB were common, affecting 42.6% and 29.6% of subjects, respectively. After adjusting for obesity, race, and sex, children with SDB had a 3.62-fold increased odds of having severe asthma at follow-up (95% CI, 1.26-10.40). Obesity was not associated with asthma severity. CONCLUSION SDB is a modifiable risk factor for severe asthma after 1 year of specialty asthma care. Further studies are needed to determine whether treating SDB improves asthma morbidity.

Scaling Up Scientific Discovery in Sleep Medicine: The National Sleep Research Resource.

ABSTRACT Professional sleep societies have identified a need for strategic research in multiple areas that may benefit from access to and aggregation of large, multidimensional datasets. Technological advances provide opportunities to extract and analyze physiological signals and other biomedical information from datasets of unprecedented size, heterogeneity, and complexity. The National Institutes of Health has implemented a Big Data to Knowledge (BD2K) initiative that aims to develop and disseminate state of the art big data access tools and analytical methods. The National Sleep Research Resource (NSRR) is a new National Heart, Lung, and Blood Institute resource designed to provide big data resources to the sleep research community. The NSRR is a web-based data portal that aggregates, harmonizes, and organizes sleep and clinical data from thousands of individuals studied as part of cohort studies or clinical trials and provides the user a suite of tools to facilitate data exploration and data visualization. Each deidentified study record minimally includes the summary results of an overnight sleep study; annotation files with scored events; the raw physiological signals from the sleep record; and available clinical and physiological data. NSRR is designed to be interoperable with other public data resources such as the Biologic Specimen and Data Repository Information Coordinating Center Demographics (BioLINCC) data and analyzed with methods provided by the Research Resource for Complex Physiological Signals (PhysioNet). This article reviews the key objectives, challenges and operational solutions to addressing big data opportunities for sleep research in the context of the national sleep research agenda. It provides information to facilitate further interactions of the user community with NSRR, a community resource.

Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use.

RATIONALE We hypothesized that untreated severe obstructive sleep apnea (OSA) is associated with elevated ambulatory blood pressure (BP) in subjects with high cardiovascular disease (CVD) risk despite medical management. METHODS Data from the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a 4-site randomized controlled trial were analyzed. Individuals with moderate-severe OSA (apnea hypopnea index, AHI = 15-50) and cardiovascular risk were recruited from cardiology practices. Those with hypertension were included. Intensive antihypertensive regimen (IAR) was defined as ≥ 3 antihypertensives including a diuretic. Definitions were: controlled BP (BP < 130/80), uncontrolled elevated BP (BP ≥ 130/80 not on IAR) and resistant elevated BP (BP ≥ 130/80 mm Hg despite IAR). Associations of untreated severe OSA (AHI ≥ 30) and uncontrolled and resistant elevated BP were evaluated using logistic regression analyses adjusted for age, sex, race, body mass index, smoking status, diabetes, and CVD. RESULTS Among the 284 participants (mean age 63.1 ± 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants prescribed IAR, resistant elevated BP was more prevalent in those with severe compared to moderate OSA (58.3% vs. 28.6%, p = 0.01). Participants with severe OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI: 1.7-10.2), a finding not reproduced in the absence of IAR use. CONCLUSIONS Among patients with increased cardiovascular risk and moderate to severe OSA, untreated severe compared to moderate OSA was associated with elevated BP despite IAR suggesting untreated severe OSA contributes to poor BP control despite aggressive medication use. COMMENTARY A commentary on this article appears in this issue on page 845.

Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden.

The objective of this study is to examine whether increasing obstructive sleep apnea (OSA) severity is associated with worsening endothelial function. The design is a cross‐sectional examination of the baseline assessment of a multi‐centre randomized controlled clinical trial examining the effects of oxygen, continuous positive airway pressure (CPAP) therapy or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an apnea–hypopnea index (AHI) of 15–50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices [oxygen desaturation index (ODI), AHI and percentage of sleep time below 90% oxygen saturation (total sleep time <90)] and a measure of endothelium‐mediated vasodilatation [Framingham reactive hyperaemia index (F‐RHI) derived from peripheral arterial tonometry (PAT)] were assessed. The sample included 267 individuals with a mean AHI of 25.0 ± 8.5 SD and mean F‐RHI 0.44 ± 0.38. In adjusted models, the slope of the relationship between ODI and F‐RHI differed above and below an ODI of 24.6 (P = 0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% [95% confidence interval (CI): 0%, 5%; P = 0.05], while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: 0%, 27%; P = 0.05) per 5‐unit increase in ODI. A similar pattern was observed between AHI and F‐RHI. No relation was noted with total sleep time <90 and F‐RHI. There was evidence of a graded decline in endothelial function in association with higher levels of intermittent hypoxaemia.

Reproducibility of a Standardized Actigraphy Scoring Algorithm for Sleep in a US Hispanic/Latino Population.

STUDY OBJECTIVES While actigraphy is considered objective, the process of setting rest intervals to calculate sleep variables is subjective. We sought to evaluate the reproducibility of actigraphy-derived measures of sleep using a standardized algorithm for setting rest intervals. DESIGN Observational study. SETTING Community-based. PARTICIPANTS A random sample of 50 adults aged 18-64 years free of severe sleep apnea participating in the Sueño sleep ancillary study to the Hispanic Community Health Study/Study of Latinos. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Participants underwent 7 days of continuous wrist actigraphy and completed daily sleep diaries. Studies were scored twice by each of two scorers. Rest intervals were set using a standardized hierarchical approach based on event marker, diary, light, and activity data. Sleep/wake status was then determined for each 30-sec epoch using a validated algorithm, and this was used to generate 11 variables: mean nightly sleep duration, nap duration, 24-h sleep duration, sleep latency, sleep maintenance efficiency, sleep fragmentation index, sleep onset time, sleep offset time, sleep midpoint time, standard deviation of sleep duration, and standard deviation of sleep midpoint. Intra-scorer intraclass correlation coefficients (ICCs) were high, ranging from 0.911 to 0.995 across all 11 variables. Similarly, inter-scorer ICCs were high, also ranging from 0.911 to 0.995, and mean inter-scorer differences were small. Bland-Altman plots did not reveal any systematic disagreement in scoring. CONCLUSIONS With use of a standardized algorithm to set rest intervals, scoring of actigraphy for the purpose of generating a wide array of sleep variables is highly reproducible.

An Economic Evaluation of Home Versus Laboratory-Based Diagnosis of Obstructive Sleep Apnea.

STUDY OBJECTIVES We conducted an economic analysis of the HomePAP study, a multicenter randomized clinical trial that compared home-based versus laboratory-based testing for the diagnosis and management of obstructive sleep apnea (OSA). DESIGN A cost-minimization analysis from the payer and provider perspectives was performed, given that 3-mo clinical outcomes were equivalent. SETTING Seven academic sleep centers. PARTICIPANTS There were 373 subjects at high risk for moderate to severe OSA. INTERVENTIONS Subjects were randomized to either home-based limited channel portable monitoring followed by unattended autotitration with continuous positive airway pressure (CPAP), versus a traditional pathway of in-laboratory sleep study and CPAP titration. MEASUREMENTS AND RESULTS From the payer perspective, per subject costs for the laboratory-based pathway were