An approach for determining the reliability of manual and digital scoring of sleep stages.

STUDY OBJECTIVES: Inter-scorer variability in sleep staging is largely due to equivocal epochs that contain features of more than one stage. We propose an approach that recognizes the existence of equivocal epochs and evaluates scorers accordingly. METHODS: Epoch-by-epoch staging was performed on 70 polysomnograms by six qualified technologists and by a digital system (Michele Sleep Scoring [MSS]). Probability that epochs assigned the same stage by only two of the six technologists (minority score) resulted from random occurrence of two errors was calculated and found to be <5%, thereby indicating that the stage assigned is an acceptable variant for the epoch. Acceptable stages were identified in each epoch as stages assigned by at least two technologists. Percent agreement between each technologist and the other five technologists, acting as judges, was determined. Agreement was considered to exist if the stage assigned by the tested scorer was one of the acceptable stages for the epoch. Stage assigned by MSS was likewise considered in agreement if included in the acceptable stages made by the technologists. RESULTS: Agreement of technologists tested against five qualified judges increased from 80.8% (range 70.5%-86.4% among technologists) when using the majority rule, to 96.1 (89.8%-98.5%) by the proposed approach. Agreement between unedited MSS and same judges was 90.0% and increased to 92.1% after brief editing. CONCLUSIONS: Accounting for equivocal epochs provides a more accurate estimate of a scorer's (human or digital) competence in scoring sleep stages and reduces inter-scorer disagreements. The proposed approach can be implemented in sleep-scoring training and accreditation programs.

Effect of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Cardiac Remodeling as Assessed by Cardiac Biomarker and Magnetic Resonance Imaging in Nonobese and Obese Adults.

It is unknown whether obesity modifies the effect of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy on cardiac remodeling and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. We compared NT-proBNP and cardiac magnetic resonance imaging in adults without OSA (n=56) and nonobese (n=73; body mass index <30 kg/m2) and obese (n=136; body mass index ≥30 kg/m2) adults with OSA. We also investigated these traits in nonobese (n=45) and obese (n=78) participants with OSA adherent to 4 months of PAP treatment. At baseline, left ventricular mass to end-diastolic volume ratio, a measure of left ventricular concentricity, was greater in both nonobese and obese participants with OSA compared with those without OSA. Participants with OSA and obesity exhibited reduced phasic right atrial function. No significant differences in baseline NT-proBNP were observed across groups. The effect of PAP treatment on NT-proBNP and left atrial volume index was significantly modified by obesity. In nonobese participants, PAP therapy was associated with a decrease in NT-proBNP (P<0.0001) without a change in left atrial volume index, whereas in obese participants, PAP was associated with an increase in left atrial volume index (P=0.006) without a change in NT-proBNP. OSA was associated with left ventricular concentric remodeling independent of obesity and right atrial dysfunction in participants who were obese. PAP treatment was associated with reduced NT-proBNP in nonobese participants with OSA, but left atrial enlargement in obese participants with OSA, suggesting that PAP-induced reduction in BNP release (which is known to occur during obstructive apnea episodes) may lead to volume retention in obese participants with OSA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01578031.

Objective adherence to dental device versus positive airway pressure treatment in adults with obstructive sleep apnea.

Although mandibular advancement device (MAD) treatment of adults with obstructive sleep apnea (OSA) is generally less efficacious than positive airway pressure (PAP), the two treatments are associated, with similar clinical outcomes. As a sub-analysis of a randomized trial comparing the effect of MAD versus PAP on blood pressure, this study compared objectively measured adherence to MAD versus PAP treatment in adults with OSA. Adults with OSA (age 54.1 ± 11.2 [standard deviation] years, 71.1% male, apnea-hypopnea index 31.6 ± 22.7 events/h) were randomized to MAD (n = 89) or PAP (n = 91) treatment for 3-6 months. Objective adherence was assessed with a thermal sensor embedded in the MAD and a pressure sensor in the PAP unit. In a per protocol analysis, no difference was observed in average daily hours of use over all days in participants on MAD (n = 35, 4.4 ± 2.9 h) versus PAP (n = 51, 4.7 ± 1.6 h, p = .597) treatment when days with missing adherence data were included as no use. MAD was used on a lower percentage of days (62.5 ± 36.4% versus 79.9 ± 19.8%, p = .047), but with greater average daily hours of use on days used (6.4 ± 1.9 h versus 5.7 ± 1.2 h, p = .013). Average daily hours of use in the first week were associated with long-term adherence to MAD (p < .0001) and PAP (p = .0009) treatment. Similar results were obtained when excluding days with missing adherence data. In conclusion, no significant difference was observed in objectively measured average daily hours of MAD and PAP adherence in adults with OSA, despite differences in the patterns of use. MAD adherence in the first week predicted long-term use.

Spindles are highly heritable as identified by different spindle detectors.

STUDY OBJECTIVES: Sleep spindles, a defining feature of stage N2 sleep, are maximal at central electrodes and are found in the frequency range of the electroencephalogram (EEG) (sigma 11-16 Hz) that is known to be heritable. However, relatively little is known about the heritability of spindles. Two recent studies investigating the heritability of spindles reported moderate heritability, but with conflicting results depending on scalp location and spindle type. The present study aimed to definitively assess the heritability of sleep spindle characteristics. METHODS: We utilized the polysomnography data of 58 monozygotic and 40 dizygotic same-sex twin pairs to identify heritable characteristics of spindles at C3/C4 in stage N2 sleep including density, duration, peak-to-peak amplitude, and oscillation frequency. We implemented and tested a variety of spindle detection algorithms and used two complementary methods of estimating trait heritability. RESULTS: We found robust evidence to support strong heritability of spindles regardless of detector method (h2 > 0.8). However not all spindle characteristics were equally heritable, and each spindle detection method produced a different pattern of results. CONCLUSIONS: The sleep spindle in stage N2 sleep is highly heritable, but the heritability differs for individual spindle characteristics and depends on the spindle detector used for analysis.

Effect of Weight Loss on Upper Airway Anatomy and the Apnea-Hypopnea Index. The Importance of Tongue Fat.

Rationale: Obesity is the primary risk factor for obstructive sleep apnea (OSA). Tongue fat is increased in obese persons with OSA, and may explain the relationship between obesity and OSA. Weight loss improves OSA, but the mechanism is unknown.Objectives: To determine the effect of weight loss on upper airway anatomy in subjects with obesity and OSA. We hypothesized that weight loss would decrease soft tissue volumes and tongue fat, and that these changes would correlate with reductions in apnea-hypopnea index (AHI).Methods: A total of 67 individuals with obesity and OSA (AHI ≥ 10 events/h) underwent a sleep study and upper airway and abdominal magnetic resonance imaging before and after a weight loss intervention (intensive lifestyle modification or bariatric surgery). Airway sizes and soft tissue, tongue fat, and abdominal fat volumes were quantified. Associations between weight loss and changes in these structures, and relationships to AHI changes, were examined.Measurements and Main Results: Weight loss was significantly associated with reductions in tongue fat and pterygoid and total lateral wall volumes. Reductions in tongue fat were strongly correlated with reductions in AHI (Pearson's rho = 0.62, P < 0.0001); results remained after controlling for weight loss (Pearson's rho = 0.36, P = 0.014). Reduction in tongue fat volume was the primary upper airway mediator of the relationship between weight loss and AHI improvement.Conclusions: Weight loss reduced volumes of several upper airway soft tissues in subjects with obesity and OSA. Improved AHI with weight loss was mediated by reductions in tongue fat. New treatments that reduce tongue fat should be considered for patients with OSA.

Differences in three-dimensional upper airway anatomy between Asian and European patients with obstructive sleep apnea.

STUDY OBJECTIVES: This study evaluated differences in upper airway, soft tissues and craniofacial structures between Asians from China and Europeans from Iceland with OSA using three-dimensional magnetic resonance imaging (MRI). METHODS: Airway sizes, soft tissue volumes, and craniofacial dimensions were compared between Icelandic (N = 108) and Chinese (N = 57) patients with oxygen desaturation index (ODI) ≥ 10 events/h matched for age, gender, and ODI. Mixed effects models adjusting for height or BMI and residual differences in age and ODI were utilized. RESULTS: In our matched sample, compared to Icelandic OSA patients, Chinese patients had smaller BMI (p < 0.0001) and neck circumference (p = 0.011). In covariate adjusted analyses, Chinese showed smaller retropalatal airway size (p ≤ 0.002), and smaller combined soft tissues, tongue, fat pads, and pterygoid (all p ≤ 0.0001), but male Chinese demonstrated a larger soft palate volume (p ≤ 0.001). For craniofacial dimensions, Chinese demonstrated bigger ANB angle (p ≤ 0.0196), differently shaped mandibles, including shorter corpus length (p < 0.0001) but longer ramus length (p < 0.0001), and a wider (p < 0.0001) and shallower (p ≤ 0.0001) maxilla. CONCLUSIONS: Compared to Icelandic patients of similar age, gender and ODI, Chinese patients had smaller retropalatal airway and combined soft tissue, but bigger soft palate volume (in males), and differently shaped mandible and maxilla with more bony restrictions. Results support an ethnic difference in upper airway anatomy related to OSA, which may inform targeted therapies.

Physical Activity Following Positive Airway Pressure Treatment in Adults With and Without Obesity and With Moderate-Severe Obstructive Sleep Apnea.

STUDY OBJECTIVES: To examine the level of physical activity (PA) before and following positive airway pressure (PAP) treatment in adults who have obstructive sleep apnea (OSA) with obesity versus without obesity. METHODS: Simultaneous waist accelerometer and wrist actigraphy recordings were obtained in 129 adults with obesity and 69 adults without obesity and who had OSA prior to and following 4 months of PAP therapy and in 52 patients in a control group. Primary PA measurements were average steps per day on waist accelerometry and average counts per minute (CPM) per day on wrist actigraphy. RESULTS: At baseline, participants with obesity and OSA exhibited fewer steps per day on waist accelerometer and fewer CPM per day on wrist actigraphy compared to participants without obesity and with OSA (despite similar apnea-hypopnea index between groups). Following PAP treatment, participants with OSA had modestly increased CPM per day on wrist actigraphy (17.69 [95% confidence interval (CI), 5.67-29.71], P = .005) and increased light PA time (0.26 [95% CI, 0.07-0.44] hours, P = .008) on waist accelerometer. Participants without obesity and with OSA had greater improvements in PA measures on average compared to participants with obesity and OSA, although the differences were not statistically significant. Weight increased following PAP treatment in the participants with obesity and OSA (1.71 [95% CI, 0.41-3.02] kg, P = .010) but was unchanged in the group without obesity (0.93 [95% CI, -0.89 to 2.76] kg, P = .311). CONCLUSIONS: Compared to study participants without obesity and with OSA, participants with obesity and OSA had reduced PA at baseline. PA increased significantly in participants without obesity, with OSA, and who were adherent to PAP treatment. Results indicate that treatment of OSA is unlikely to be associated with a change in PA in adults with obesity and OSA and help explain the absence of weight loss following PAP treatment in adults with OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, title: The Effects of Treating Obese and Lean Patients With Sleep Apnea (PISA), identifier: NCT01578031, URL: https://clinicaltrials.gov/ct2/show/NCT01578031.

Determinants of sleepiness in obstructive sleep apnea.

STUDY OBJECTIVES: Significant interindividual variability in sleepiness is observed in clinical populations with obstructive sleep apnea (OSA). This phenomenon is only partially explained by the apnea-hypopnea index (AHI). Understanding factors that lead to sleepiness is critical to effective management of patients with OSA. We examined demographic and other factors associated with sleepiness in OSA. METHODS: Prospective study of 283 patients with newly diagnosed OSA by polysomnography (AHI ≥ 5 per hour). Subjective sleepiness (Epworth Sleep Scale [ESS] ≥ 11) and objective sleepiness (psychomotor vigilance task [PVT] mean lapse ≥ 2) were assessed. RESULTS: Participants were classified into four groups (1: sleepy by ESS and PVT, 2: sleepy by PVT only, 3: sleepy by ESS only, and 4: nonsleepy reference group) and compared by generalized logit model. Shorter daily sleep duration by actigraphy and less morningness were associated with higher risk of sleepiness (Odds ratio [OR] = 0.52, 95% confidence interval [CI] 0.33-0.82 and OR = 0.89, CI 0.80-0.98, respectively). African-American race was associated with sleepiness (group 1, OR = 8.8, CI 2.8-27.3; group 2, OR = 16.6, CI 3.3-83.6; and group 3, OR = 3.3, CI 1.0-10.1). IL-6 level was higher in groups 1 and 3 (OR = 1.9, CI 1.0-3.4 and OR 2.0, CI 1.1-3.7, respectively). CONCLUSIONS: African-American race, short sleep duration, chronotype, and increased proinflammatory cytokine IL-6 level were associated with sleepiness in OSA. These findings will inform future investigations determining mechanisms of sleepiness in OSA.

Reliability of the American Academy of Sleep Medicine Rules for Assessing Sleep Depth in Clinical Practice.

STUDY OBJECTIVES: The American Academy of Sleep Medicine has published manuals for scoring polysomnograms that recommend time spent in non-rapid eye movement sleep stages (stage N1, N2, and N3 sleep) be reported. Given the well-established large interrater variability in scoring stage N1 and N3 sleep, we determined the range of time in stage N1 and N3 sleep scored by a large number of technologists when compared to reasonably estimated true values. METHODS: Polysomnograms of 70 females were scored by 10 highly trained sleep technologists, two each from five different academic sleep laboratories. Range and confidence interval (CI = difference between the 5th and 95th percentiles) of the 10 times spent in stage N1 and N3 sleep assigned in each polysomnogram were determined. Average values of times spent in stage N1 and N3 sleep generated by the 10 technologists in each polysomnogram were considered representative of the true values for the individual polysomnogram. Accuracy of different technologists in estimating delta wave duration was determined by comparing their scores to digitally determined durations. RESULTS: The CI range of the ten N1 scores was 4 to 39 percent of total sleep time (% TST) in different polysomnograms (mean CI ± standard deviation = 11.1 ± 7.1 % TST). Corresponding range for N3 was 1 to 28 % TST (14.4 ± 6.1 % TST). For stage N1 and N3 sleep, very low or very high values were reported for virtually all polysomnograms by different technologists. Technologists varied widely in their assignment of stage N3 sleep, scoring that stage when the digitally determined time of delta waves ranged from 3 to 17 seconds. CONCLUSIONS: Manual scoring of non-rapid eye movement sleep stages is highly unreliable among highly trained, experienced technologists. Measures of sleep continuity and depth that are reliable and clinically relevant should be a focus of clinical research.

Carotid Artery Wall Thickness in Obese and Nonobese Adults With Obstructive Sleep Apnea Before and Following Positive Airway Pressure Treatment.

Study objectives: Debate persists as to whether obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. The purpose of this study was to compare carotid intima-media thickness (IMT), an early sign of atherosclerosis, in obese and nonobese adults with OSA before and following positive airway pressure (PAP) treatment. Methods: A total of 206 adults newly diagnosed with OSA with an apnea-hypopnea index (AHI) of 15-75 events/hour and 53 controls with AHI <10 were studied. Waist circumference was used to classify participants as obese and nonobese. Bilateral common carotid artery B-mode ultrasound was performed at baseline to assess IMT, arterial diameter, arterial-wall mass, and circumferential wall stress. Measurements were repeated in 118 participants with OSA who completed a 4-month PAP treatment and had an average daily use over that period of ≥4 hours/day. Results: No significant differences in carotid IMT, diameter, or arterial-wall mass were present at baseline between participants with OSA and controls stratified by waist circumference, after adjusting for other cardiovascular risk factors. In participants with OSA, who had adequate PAP adherence over the 4-month treatment, carotid artery diameter significantly increased (mean change [95% confidence interval] = 0.13 [0.06, 0.20] mm; p = .0004), but no significant changes in carotid IMT, arterial-wall mass, and circumferential stress were observed in obese and nonobese participants. Conclusions: Regardless of obesity status, carotid IMT is not increased in adults with moderate to severe OSA versus controls and does not change following 4 months of PAP treatment.

Heritability of Heart Rate Response to Arousals in Twins.

Objectives: To determine if the large and highly reproducible interindividual differences in arousal intensity and heart rate response to arousal (ΔHR) during non-REM sleep are heritable. Methods: Polysomnograms of 55 monozygotic (14 male and 41 female pairs) and 36 dizygotic (15 male and 21 female pairs) same-sex twin pairs were analyzed. Arousals were scored using the 2012 American Academy of Sleep Medicine criteria. Arousal intensity was scaled (between 0 and 9) using an automatic algorithm based on the change in electroencephalogram time and frequency characteristics. The ΔHR was determined at each arousal. We calculated average arousal duration, average arousal intensity, average overall ΔHR, average ΔHR at a given arousal intensity, slope of ΔHR per arousal intensity, and arousal intensity threshold of ΔHR. Results: The intraclass correlations among monozygotic and dizygotic twin pairs were 0.663 and 0.146, respectively, for average arousal intensity, and 0.449 and 0, respectively, for arousal intensity threshold of ΔHR controlling for age, sex, and race. These values imply large broad sense heritability (H2) for these traits. This evidence was confirmed by a robust maximum likelihood-based variance components estimation approach, with an additive genetic heritability of 0.64 (95% confidence interval: 0.48 to 0.80) for average arousal intensity and a combined additive and dominance genetic heritability and of 0.46 (0.25 to 0.68) for arousal intensity threshold of ΔHR. Results also suggested significant additive genetic effects for average arousal duration, ΔHR at arousal intensity scale 4 and the overall average ΔHR. Conclusion: Genetic factors explain a significant fraction of the phenotypic variability for average arousal intensity and arousal intensity threshold of ΔHR. Results suggest that the duration of arousals and specific average ΔHR values may also be heritable traits. Clinical trial registration: NCT02827461.

An Examination of Methodological Paradigms for Calculating Upper Airway Critical Pressures during Sleep.

STUDY OBJECTIVES: The goal of this study was to examine different paradigms for determining critical closing pressures (Pcrit). Methods of determining Pcrit were compared, including direct observation of occluded (no flow) breaths versus inferring Pcrit from extrapolated data, and Pcrit generated by aggregating pressure-flow data from multiple runs versus Pcrit averaged across individual pressure-flow runs. The relationship between Pcrit and obstructive sleep apnea (OSA) was examined. METHODS: A total of 351 participants with and without OSA underwent overnight polysomnography with pressure-flow measurements to determine Pcrit. A series of filters were applied to raw data to provide consistent, objective criteria for determining which data to include in Pcrit calculations. Observed Pcrit values were computed as the mean nasal pressure level at which a subject had at least two breaths with peak inspiratory flow < 50 mL/sec. Extrapolated Pcrit was calculated in two ways: (1) separately for each individual run and then averaged; and (2) using all valid data from individual runs combined into one plot. RESULTS: Observed Pcrit was calculated in 67% to 69% of participants, a similar or higher proportion of study subjects compared to extrapolated Pcrit values using a ± 3 cm H2O filter. Although raw (unfiltered) extrapolated Pcrit measures were able to be calculated among a greater proportion of participants than filtered, extrapolated Pcrit values, and thus had fewer missing values, they had larger variability. Both extrapolated and observed Pcrit were higher among individuals with OSA compared to those without OSA. CONCLUSIONS: Observed Pcrit provides a reliable descriptor of hypotonic upper airway collapsibility. Different methods for determining Pcrit were able to distinguish subjects with and without OSA.

Short-Term Variability in Apnea-Hypopnea Index during Extended Home Portable Monitoring.

STUDY OBJECTIVES: Apnea-hypopnea index (AHI) is the primary measure used to confirm a diagnosis of obstructive sleep apnea (OSA). However, there may be significant night-to-night variability (NNV) in AHI, limiting the value of AHI in clinical decision-making related to OSA management. We examined short-term NNV in AHI and its predictors during home portable monitoring (PM). METHODS: Single center prospective observational study of patients (n = 84) with newly diagnosed OSA by polysomnography (PSG) AHI ≥ 5/h. All participants underwent 2 to 8 consecutive nights of PM. RESULTS: Participants (n = 84) were middle-aged (47 ± 8.3 y, mean ± standard deviation; SD), including 28 women, with mean AHI on baseline PSG (AHIPSG) of 30.1 ± 31.8. Mean AHI on PM (AHIPM) was 27.4 ± 23.7. Intraclass correlation coefficient (ICC) for AHIPM in the entire sample was 0.73 (95% CI 0.66-0.8), indicating that 27% of the variability in AHIPM was due to intra-individual factors. Mild severity of OSA, defined by AHIPSG 5-15/h, was associated with higher NNV (likelihood ratio, -0.4 ± 0.14; p = 0.006) and absence of comorbidity showed a trend towards higher NNV (-0.54 ± 0.27, p = 0.05) on AHIPM. CONCLUSIONS: The intraindividual short-term NNV in AHIPM is higher in mild versus moderately severe OSA, even in the home setting, where first-night effect is not expected. Larger studies of NNV focused on patients with mild OSA are needed to identify characteristics that predict need and timing for repeated diagnostic testing and treatment. COMMENTARY: A commentary on this article appears in this issue on page 787.

Arousal Responses during Overnight Polysomnography and their Reproducibility in Healthy Young Adults.

STUDY OBJECTIVES: Arousal intensity and heart rate (HR) response to arousal during polysomnography (PSG) vary considerably between patients with sleep disorders. Our objective was to determine the range of these arousal characteristics in healthy young adults and whether they are consistent on repeated testing. DESIGN: Post hoc analysis of 56 preexisting PSG files recorded from 28 healthy adults on 2 consecutive nights. SETTING: Academic medical center and Research and Development Laboratory (YRT Limited, Winnipeg, Manitoba, Canada). PARTICIPANTS: Twenty-eight healthy young adults. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Arousals were identified using an automatic system followed by manual editing. The intensity of arousals was scaled (between 0 and 9) using an automatic algorithm based on the change in the electroencephalography (EEG) signals' wavelet characteristics. 4,751 arousals in 28 pairs of PSGs (night 1 and night 2) were scaled. HR responses (ΔHR) to all arousals were determined and averaged at each arousal scale per file. Overall average arousal intensity ranged 3.0-7.1 in different subjects, and average ΔHR ranged 1.9-18.3 beats.min(-1). Heart rate response at a given arousal intensity, expressed as ΔHR at a moderate arousal scale of 5.0 (ΔHR5), ranged 4.1-18.1 beats.min(-1). There was a strong correlation between arousal intensity and ΔHR within each subject. More importantly, there were excellent intraclass correlations (ICC) between night 1 and night 2 results for all three variables (ICC = 0.72 for average intensity, 0.92 for average ΔHR4, and 0.91 for ΔHR5). CONCLUSIONS: Average arousal intensity and heart rate response to arousal are highly variable among healthy young adults and stable within individuals.

Detection of upper airway status and respiratory events by a current generation positive airway pressure device.

STUDY OBJECTIVES: To compare a positive airway pressure (PAP) device's detection of respiratory events and airway status during device-detected apneas with events scored on simultaneous polysomnography (PSG). DESIGN: Prospective PSGs of patients with sleep apnea using a new-generation PAP device. SETTINGS: Four clinical and academic sleep centers. PATIENTS: Forty-five patients with obstructive sleep apnea (OSA) and complex sleep apnea (Comp SA) performed a PSG on PAP levels adjusted to induce respiratory events. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PAP device data identifying the type of respiratory event and whether the airway during a device-detected apnea was open or obstructed were compared to time-synced, manually scored respiratory events on simultaneous PSG recording. Intraclass correlation coefficients between device-detected and PSG scored events were 0.854 for apnea-hypopnea index (AHI), 0.783 for apnea index, 0.252 for hypopnea index, and 0.098 for respiratory event-related arousals index. At a device AHI (AHIFlow) of 10 events/h, area under the receiver operating characteristic curve was 0.98, with sensitivity 0.92 and specificity 0.84. AHIFlow tended to overestimate AHI on PSG at values less than 10 events/h. The device detected that the airway was obstructed in 87.4% of manually scored obstructive apneas. Of the device-detected apneas with clear airway, a minority (15.8%) were manually scored as obstructive apneas. CONCLUSIONS: A device-detected apnea-hypopnea index (AHIFlow) < 10 events/h on a positive airway pressure device is strong evidence of good treatment efficacy. Device-detected airway status agrees closely with the presumed airway status during polysomnography scored events, but should not be equated with a specific type of respiratory event.

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.

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.

Screening for severe obstructive sleep apnea syndrome in hypertensive outpatients.

The authors attempted to validate a 2-stage strategy to screen for severe obstructive sleep apnea syndrome (s-OSAS) among hypertensive outpatients, with polysomnography (PSG) as the gold standard. Using a prospective design, outpatients with hypertension were recruited from medical outpatient clinics. Interventions included (1) assessment of clinical data; (2) home sleep testing (HST); and (3) 12-channnel, in-laboratory PSG. The authors developed models using clinical or HST data alone (single-stage models) or clinical data in tandem with HST (2-stage models) to predict s-OSAS. For each model, area under receiver operating characteristic curves (AUCs), sensitivity, specificity, negative likelihood ratio, and negative post-test probability (NPTP) were computed. Models were then rank-ordered based on AUC values and NPTP. HST used alone had limited accuracy (AUC=0.727, NPTP=2.9%). However, models that used clinical data in tandem with HST were more accurate in identifying s-OSAS, with lower NPTP: (1) facial morphometrics (AUC=0.816, NPTP=0.6%); (2) neck circumference (AUC=0.803, NPTP=1.7%); and Multivariable Apnea Prediction Score (AUC=0.799, NPTP=1.5%) where sensitivity, specificity, and NPTP were evaluated at optimal thresholds. Therefore, HST combined with clinical data can be useful in identifying s-OSAS in hypertensive outpatients, without incurring greater cost and patient burden associated with in-laboratory PSG. These models were less useful in identifying obstructive sleep apnea syndrome of any severity.

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 laboratory's 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.