Bethany Staley

Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea.

RATIONALE Home portable monitor testing is increasingly being used to diagnose patients with obstructive sleep apnea (OSA) and to initiate them on continuous positive airway pressure (CPAP) treatment. OBJECTIVES To compare functional outcome and treatment adherence in patients who receive ambulatory versus in-laboratory testing for OSA. METHODS Veterans with suspected OSA were randomized to either home testing or standard in-laboratory testing. Home testing consisted of a type 3 portable monitor recording followed by at least three nights using an automatically adjusting positive airway pressure apparatus. Participants diagnosed with OSA were treated with CPAP for 3 months. MEASUREMENTS AND MAIN RESULTS We measured the change in Functional Outcomes of Sleep Questionnaire score, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured CPAP adherence, with an a priori noninferiority delta of -0.75 hour/day. Of the 296 subjects enrolled, 260 (88%) were diagnosed with OSA, and 213 (75%) were initiated on CPAP. Mean ± SD functional outcome score improved 1.74 ± 2.81 in the home group (P < 0.001) and 1.85 ± 2.46 in the in-laboratory group (P < 0.0001). The lower bound of the one-sided 95% noninferiority confidence interval was -0.54. Mean ± SD hours of daily CPAP adherence were 3.5 ± 2.5 hours/day in the home group and 2.9 ± 2.3 hours/day in the in-laboratory group (P = 0.08). The lower bound of the one-sided 95% noninferiority confidence interval was 0.03. CONCLUSIONS Functional outcome and treatment adherence in patients evaluated according to a home testing algorithm is not clinically inferior to that in patients receiving standard in-laboratory polysomnography.

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.

RATIONALE Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. OBJECTIVES To evaluate the efficacy of continuous positive airway pressure treatment to improve functional status in sleepy patients with mild and moderate obstructive sleep apnea. METHODS Patients with self-reported daytime sleepiness (Epworth Sleepiness Scale score >10) and an apnea-hypopnea index with 3% desaturation and from 5 to 30 events per hour were randomized to 8 weeks of active or sham continuous positive airway pressure treatment. After the 8-week intervention, participants in the sham arm received 8 weeks of active continuous positive airway pressure treatment. MEASUREMENTS AND MAIN RESULTS The Total score on the Functional Outcomes of Sleep Questionnaire was the primary outcome measure. The adjusted mean change in the Total score after the first 8-week intervention was 0.89 for the active group (n = 113) and -0.06 for the placebo group (n = 110) (P = 0.006). The group difference in mean change corresponded to an effect size of 0.41 (95% confidence interval, 0.14-0.67). The mean (SD) improvement in Functional Outcomes of Sleep Questionnaire Total score from the beginning to the end of the crossover phase (n = 91) was 1.73 ± 2.50 (t[90] = 6.59; P < 0.00001) with an effect size of 0.69. CONCLUSIONS Continuous positive airway pressure treatment improves the functional outcome of sleepy patients with mild and moderate obstructive sleep apnea.

Tongue Fat and its Relationship to Obstructive Sleep Apnea

STUDY OBJECTIVES The objective of this study was to determine whether tongue fat is increased in obese sleep apneics compared to obese subjects without sleep apnea. We hypothesized that excess fat is deposited in the tongue in obese patients with sleep apnea. DESIGN Case-control design. SETTING Academic medical center. PATIENTS We examined tongue fat in 31 obese controls (apnea-hypopnea index, 4.1 ± 2.7 events/h) and 90 obese apneics (apnea-hypopnea index, 43.2 ± 27.3 events/h). Analyses were repeated in a subsample of 18 gender-, race-, age-, and BMI-matched case-control pairs. INTERVENTIONS All subjects underwent a MRI with three-point Dixon magnetic resonance imaging. We used sophisticated volumetric reconstruction algorithms to study the size and distribution of upper airway fat deposits in the tongue and masseter muscles within apneics and obese controls. MEASUREMENTS AND RESULTS The data supported our a priori hypotheses that after adjustment for age, BMI, gender, and race, the tongue in apneics was significantly larger (P = 0.001) and had an increased amount of fat (P = 0.002) compared to controls. Similar results were seen in our matched sample. Our data also demonstrate that within the apneic and normal tongue, there are regional differences in fat distribution, with larger fat deposits at the base of the tongue. CONCLUSIONS There is increased tongue volume and deposition of fat at the base of tongue in apneics compared to controls. Increased tongue fat may begin to explain the relationship between obesity and obstructive sleep apnea.

The interaction of obstructive sleep apnea and obesity on the inflammatory markers C-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort.

STUDY OBJECTIVES To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels. DESIGN Cross-sectional cohort. SETTING The Icelandic Sleep Apnea Cohort. PARTICIPANTS 454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO₂) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m²). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO₂ only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women. CONCLUSIONS OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients.

Risk Factors for Excessive Sleepiness in Older Adults

To determine risk factors for excessive daytime sleepiness in older adults.

Heritability of Performance Deficit Accumulation During Acute Sleep Deprivation in Twins

STUDY OBJECTIVES To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait. DESIGN Prospective, observational cohort study. SETTING Academic medical center. PARTICIPANTS There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram. INTERVENTIONS Thirty-eight hr of monitored, continuous sleep deprivation. MEASUREMENTS AND RESULTS Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h(2)) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P < 0.0001) of twin variance was attributed to combined additive and dominance genetic effects. CONCLUSION Genetic factors explain a large fraction of interindividual variance among rates of performance deficit accumulations on PVT during sleep deprivation.

Respiratory event detection by a positive airway pressure device.

STUDY OBJECTIVES Compare automatic event detection (AED) of respiratory events using a positive airway pressure (PAP) device with manual scoring of polysomnography (PSG) during PAP treatment of obstructive sleep apnea (OSA). DESIGN Prospective PSGs of patients using a PAP device. SETTING Six academic and private sleep disorders centers. PATIENTS A total of 148 PSGs from 115 participants with OSA (apnea-hypopnea index [AHI] ≥ 15 events/hr) were analyzed. INTERVENTIONS A signal generated by the PAP device identifying the AED of respiratory events based on airflow was recorded during PSG. MEASUREMENTS AND RESULTS The PSGs were manually scored without visualization of the AED signal and scoring of a hypopnea required a ≥ 4% oxygen desaturation. The apnea index (AI), hypopnea index (HI), and AHI by manual score and PAP AED were compared. A customized computer program compared individual events by manual scoring and AED to determine the true positive, false positive, false negative, or true negative events and found a sensitivity of 0.58 and a specificity of 0.98. The AHI, AI, and HI by the two methods were highly correlated. Bland-Altman analysis showed better agreement for AI than HI. Using a manually scored AHI of ≥ 10 events/hr to denote inadequate treatment, an AED AHI ≥ 10 events/hr had a sensitivity of 0.58 and a specificity of 0.94. CONCLUSIONS An AHI < 10 events/hr by PAP AED is usually associated with good treatment efficacy. Differences between manually scored and AED events were primarily due to different criteria for hypopnea detection.

Performance of an automated polysomnography scoring system versus computer-assisted manual scoring.

STUDY OBJECTIVES Manual scoring of polysomnograms (PSG) is labor intensive and has considerable variance between scorers. Automation of scoring could reduce cost and improve reproducibility. The purpose of this study was to compare a new automated scoring system (YST-Limited, Winnipeg, Canada) with computer-assisted manual scoring. DESIGN Technical assessment. SETTING Five academic medical centers. PARTICIPANTS N/A. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Seventy PSG files were selected at University of Pennsylvania (Penn) and distributed to five US academic sleep centers. Two blinded technologists from each center scored each file. Automatic scoring was performed at Penn by a YST Limited technician using a laptop containing the software. Variables examined were sleep stages, arousals, and apnea-hypopnea index (AHI) using three methods of identifying hypopneas. Automatic scores were not edited and were compared to the average scores of the 10 technologists. Intraclass correlation coefficient (ICC) was obtained for the 70 pairs and compared to across-sites ICCs for manually scored results. ICCs for automatic versus manual scoring were > 0.8 for total sleep time, stage N2, and nonrapid eye movement arousals and > 0.9 for AHI scored by primary and secondary American Academy of Sleep Medicine criteria. ICCs for other variables were not as high but were comparable to the across-site ICCs for manually scored results. CONCLUSION The automatic system yielded results that were similar to those obtained by experienced technologists. Very good ICCs were obtained for many primary PSG outcome measures. This automated scoring software, particularly if supplemented with manual editing, may increase laboratory efficiency and standardize PSG scoring results within and across sleep centers.

Agreement in computer-assisted manual scoring of polysomnograms across sleep centers.

STUDY OBJECTIVES To determine intersite agreement in respiratory event scoring of polysomnograms (PSGs) using different hypopnea definitions. DESIGN Technical assessment. SETTING Five academic medical centers. PARTICIPANTS N/A. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Seventy good-quality PSGs performed in middle-aged women were manually scored by two experienced technologists at each of the five sleep centers using the particular laboratorys own software system. Studies were scored once by each scorer using American Academy of Sleep Medicine (AASM) standards for scoring sleep stages, arousals, and apneas. Hypopneas were then scored using three different AASM criteria: recommended, alternate, and research (Chicago). Means of each PSG variable for the scorers at each site were used to calculate an across-site intraclass correlation coefficient (ICC). Average AHI across the 10 scorers was 7.4 ± 12.3 (standard deviation) events/h using recommended criteria (ICC 0.984; 95% confidence interval [CI] 0.977-0.990), 12.1 ± 13.3 events/h using alternate criteria (ICC 0.947; 95% CI 0.889-0.972), and 15.1 ± 13.9 events/h with Chicago criteria (ICC 0.800; 95% CI 0.768-0.828). ICC across sites was 0.870 (95% CI = 0.847-0.889) for total sleep time, 0.861 (95% CI 0.837-0.881) for number of obstructive apneas and 0.683 (95% CI 0.640-0.722) for number of central apneas. ICCs across sites for hypopneas were very good using recommended criteria (ICC 0.843; 95% CI 0.820-0.870) but decreased when alternate criteria (ICC 0.728; 95% CI 0.689-0.763) and Chicago criteria (ICC 0.535; 95% CI 0.485-0.583) were used. CONCLUSION Experienced scorers at different laboratories have very good agreement in hypopnea and AHI results when good-quality PSGs are scored using AASM-recommended criteria. Substantial degradation of reliability was observed for alternative definitions of hypopneas, particularly that proposed for research.

Metabolic Activity of the Tongue in Obstructive Sleep Apnea. A Novel Application of FDG Positron Emission Tomography Imaging

RATIONALE The metabolic activity of the tongue is unknown in patients with obstructive sleep apnea (OSA). Tongue electromyographic (EMG) activity is increased in patients with OSA. This increase in tongue EMG activity is thought to be related to either increased neuromuscular compensation or denervation with subsequent reinnervation of the muscle fibers. Increased glucose uptake in the tongue would support increased neuromuscular compensation, whereas decreased glucose uptake in the tongue would support denervation with subsequent reinnervation of the muscle fibers. OBJECTIVES To investigate the metabolic activity of the genioglossus and control upper airway muscles in obese patients with sleep apnea compared with obese control subjects. METHODS Obese subjects with and without OSA underwent a standard overnight sleep study to determine an apnea-hypopnea index. Each subject had a positron emission tomography with [(18)F]-2-fluoro-2-deoxy-D-glucose scan in addition to noncontrast computed tomography or magnetic resonance imaging. Glucose uptake was quantified within upper airway tissues with the standardized uptake value. MEASUREMENTS AND MAIN RESULTS We recruited 30 obese control subjects (apnea-hypopnea index, 4.7 ± 3.1 events per hour) and 72 obese patients with sleep apnea (apnea-hypopnea index, 43.5 ± 28.0 events per hour). Independent of age, body mass index, sex, and race, patients with OSA had significantly reduced glucose uptake in the genioglossus (P = 0.03) in comparison with obese normal subjects. No differences in standardized uptake value were found in the control muscles (masseter [P = 0.38] and pterygoid [P = 0.70]) and subcutaneous fat deposits (neck [P = 0.44] and submental [P = 0.95]) between patients with OSA and control subjects. CONCLUSIONS There was significantly reduced glucose uptake in the genioglossus of patients with sleep apnea in comparison with obese normal subjects with [(18)F]-2-fluoro-2-deoxy-D-glucose positron emission tomography imaging. The reduction in glucose uptake was likely secondary to alterations in tongue muscle fiber-type or secondary to chronic denervation. The reduced glucose uptake argues against the neuromuscular compensation hypothesis explaining the increase in tongue EMG activity in obese patients with OSA.