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STUDY OBJECTIVE: Treatment of sleep-disordered breathing (SDB) with positive airway pressure (PAP) therapy has unique clinical challenges in individuals living with spinal cord injuries and diseases (spinal cord injury [SCI]/D). Interventions focused on increasing PAP use have not been studied in this population. We aimed to evaluate the benefits of a program to increase PAP use among Veterans with SCI/D and SDB. METHODS: Randomized controlled trial comparing a behavioral Intervention (n = 32) and educational control (n = 31), both including one face-to-face and five telephone sessions over 3 months. The intervention included education about SDB and PAP, goal setting, troubleshooting, and motivational enhancement. The control arm included non-directive sleep education only. RESULTS: Primary outcomes were objective PAP use (nights ≥4 hours used within 90 days) and sleep quality (Pittsburgh Sleep Quality Index [PSQI] at 3 months). These did not differ between intervention and control (main outcome timepoint; mean difference 3.5 [-9.0, 15.9] nights/week for PAP use; p = .578; -1.1 [-2.8, 0.6] points for PSQI; p = .219). Secondary outcomes included fatigue, depression, function, and quality of life. Only fatigue improved significantly more in the intervention versus the control group (p = .025). Across groups, more PAP use was associated with larger improvements in sleep quality, insomnia, sleepiness, fatigue, and depression at some time points. CONCLUSIONS: PAP use in Veterans with SCI/D and SDB is low, and a 3-month supportive/behavioral program did not show significant benefit compared to education alone. Overall, more PAP use was associated with improved symptoms suggesting more intensive support, such as in-home assistance, may be required to increase PAP use in these patients. CLINICAL TRIALS INFORMATION: Title: Treatment of Sleep Disordered Breathing in Patients with SCI. Registration number: NCT02830074. Website: https://clinicaltrials.gov/study/NCT02830074?cond=Sleep%20Apnea&term=badr&rank=5.

Study Objectives: The demand for cost-effective and accessible alternatives to polysomnography (PSG), the conventional diagnostic method for obstructive sleep apnea (OSA), has surged. In this study, we have developed and validated a deep learning model for detecting apnea-hypopnea events using radar data., Methods: We conducted a single-center prospective cohort study, dividing participants with suspected sleep-disordered breathing into development and temporally independent test sets. Utilizing a hybrid CNN-Transformer architecture, we performed fivefold cross-validation on the development set to develop and subsequently validate the model. Evaluation metrics included sensitivity for event detection, mean absolute error (MAE), intraclass correlation coefficient (ICC), and Pearson correlation coefficient (r) for apnea-hypopnea index (AHI) estimation. Linearly weighted kappa statistics (κ) assessed OSA severity., Results: The development set comprised 54 participants (July 2021-May 2022), while the test set included 35 participants (June 2022-June 2023). In the test set, our model achieved an event detection sensitivity of 67.2% (95% CI = 65.8% to 68.5%) and demonstrated a MAE of 7.54 (95% CI = 5.36 to 9.72), indicating good agreement (ICC = 0.889 [95% CI = 0.792 to 0.942]) and a strong correlation (r = 0.892 [95% CI = 0.795 to 0.945]) with the ground truth for AHI estimation. Furthermore, OSA severity estimation showed substantial agreement (κ = 0.780 [95% CI = 0.658 to 0.903])., Conclusions: Our study highlights radar sensors and advanced AI models' potential to improve OSA diagnosis, paving the path for future radar-based diagnostic models in sleep medicine research., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study objectivesThe effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep.DesignPatients were studied on 4 separate nights according to a within-subjects cross-over design.SettingSleep physiology laboratory.PatientsSeven patients with OSA and a low respiratory arousal threshold.InterventionsIn-laboratory polysomnograms were obtained at baseline and after 100 mg of trazodone was administered, followed by detailed overnight physiology experiments under the same conditions. During physiology studies, continuous positive airway pressure was transiently lowered to measure arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle activity (genioglossus and tensor palatini), and upper airway collapsibility (Pcrit).Measurements and resultsTrazodone increased the respiratory arousal threshold by 32 ± 6% (-11.5 ± 1.4 versus -15.3 ± 2.2 cmH2O, P < 0.01) but did not alter the apnea-hypopnea index (39 ± 12 versus 39 ± 11 events/h sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically change with trazodone.ConclusionsTrazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold without major impairment in dilator muscle activity or upper airway collapsibility. However, the magnitude of change in arousal threshold was insufficient to overcome the compromised upper airway anatomy in these patients.

Study Objectives: Sleep disturbances are common in adolescence and associated with a host of negative outcomes. Here, we assess associations between multifaceted sleep disturbances and a broad set of psychological, cognitive, and demographic variables using a data-driven approach, canonical correlation analysis (CCA)., Methods: Baseline data from 9093 participants from the Adolescent Brain Cognitive Development (ABCD) Study were examined using CCA, a multivariate statistical approach that identifies many-to-many associations between two sets of variables by finding combinations for each set of variables that maximize their correlation. We combined CCA with leave-one-site-out cross-validation across ABCD sites to examine the robustness of results and generalizability to new participants. The statistical significance of canonical correlations was determined by non-parametric permutation tests that accounted for twin, family, and site structure. To assess the stability of the associations identified at baseline, CCA was repeated using 2-year follow-up data from 4247 ABCD Study participants., Results: Two significant sets of associations were identified: (1) difficulty initiating and maintaining sleep and excessive daytime somnolence were strongly linked to nearly all domains of psychopathology (r2 = 0.36, p < .0001); (2) sleep breathing disorders were linked to BMI and African American/black race (r2 = 0.08, p < .0001). These associations generalized to unseen participants at all 22 ABCD sites and were replicated using 2-year follow-up data., Conclusions: These findings underscore interwoven links between sleep disturbances in early adolescence and psychological, social, and demographic factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Study Objectives: Subjective recall of supine sleep during pregnancy has been linked to increased risk of stillbirth, but longitudinal, objective data are lacking. We aimed to examine how sleep position and breathing parameters change throughout pregnancy, and investigated associations between maternal supine sleep, assessed objectively in early and late gestation, and fetal growth velocity in high-risk women., Methods: Women with singleton pregnancies and body mass index (BMI) ≥27 kg/m2 underwent level-III sleep apnea testing. Sleep position was assessed by accelerometry. We derived percentiles of estimated fetal weight and birthweight using FetalGPSR software, then calculated growth velocity as change in percentile/week between the second-trimester anatomy scan and birth., Results: In total, 446 women were included, with N = 126 in the longitudinal sleep pattern analysis and N = 83 in the fetal growth analysis. Sleep-onset position and predominant sleep position were significantly correlated in both early (p = 0.001) and late (p < 0.01) pregnancy. However, supine going-to-bed position predicted predominant supine sleep in only 47% of women. Between early and late pregnancy there was a reduction in predominant supine sleepers (51.6% to 30.2%). Percent of sleep spent supine and oxygen desaturation index, in the third trimester, were significantly associated after BMI adjustment (B = 0.018, p = 0.04). Models did not suggest significant effects of early or late pregnancy supine sleep on growth velocity (p > 0.05)., Conclusions: Going-to-bed position predicts predominant supine sleep in less than half of women with overweight and obesity. Time spent supine throughout pregnancy correlates with measures of sleep-disordered breathing. Maternal sleep position patterns did not affect fetal growth velocity in this high-risk population, but the study was not powered to detect differences., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Obesity and male sex are main risk factors for sleep-disordered breathing (SDB). We have shown that male diet-induced obesity (DIO) mice develop hypoventilation, sleep apnea, and sleep fragmentation. The effects of DIO on breathing and sleep architecture in females have not been investigated. We hypothesized that female mice are less susceptible to the detrimental effects of DIO on sleep and SDB compared to males. Female DIO-C57BL/6J and lean C57BL/6J mice underwent 24-hour metabolic studies and were exposed to 8% CO2 to measure the hypercapnic ventilatory response (HCVR), and sleep studies. Ventilatory response to arousals was calculated as ratio of the average and peak minute ventilation (VE) during each arousal relative to the baseline VE. Breathing stability was measured with Poincaré plots of VE. Female obesity was associated with decreased metabolism, indicated by reduced oxygen consumption (VO2) and CO2 production (VCO2). VE in 8% CO2 and HCVR were significantly attenuated during wakefulness. NREM sleep duration was reduced in DIO mice, but REM sleep was preserved. Ventilation during NREM and REM sleep was augmented compared to lean mice. Arousal frequency was similar between groups. Obesity increased the frequency of spontaneous arousals, whereas the apnea index was 4-fold reduced in DIO compared to lean mice. Obesity decreased pre- and post-apnea arousals. Obese mice had more stable breathing with reduced ventilatory response to arousals, compared to lean females. We conclude that obese female mice are protected against SDB, which appears to be related to an attenuated CO2 responsiveness, compared to the lean state., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: To compare overnight declarative memory consolidation and non-rapid eye movement (NREM) sleep electroencephalogram (EEG) oscillations in older adults with obstructive sleep apnea (OSA) to a control group and assess slow-wave activity (SWA) and sleep spindles as correlates of memory consolidation., Methods: Forty-six older adults (24 without OSA and 22 with OSA) completed a word-pair associate's declarative memory task before and after polysomnography. Recall and recognition were expressed as a percentage of the morning relative to evening scores. Power spectral analysis was performed on EEG recorded at frontal (F3-M2, F4-M1) and central (C3-M2, C4-M1) sites. We calculated NREM absolute slow oscillation (0.25-1 Hz) and delta (0.5-4.5 Hz) EEG power, and slow (11-13 Hz) spindle density (number of events per minute of N2 sleep) and fast (13-16 Hz) spindle density., Results: There were no significant differences in overnight recall and recognition between OSA (mean age 58.7 ± 7.1 years, apnea-hypopnea index (AHI) 41.9 ± 29.7 events/hour) and non-OSA (age 61.1 ± 10.3 years, AHI 6.6 ± 4.2 events/hour) groups. The OSA group had lower fast spindle density in the frontal region (p = 0.007). No between-group differences in SWA were observed. In the Control group, overnight recognition positively correlated with slow spindle density in frontal (rho = 0.555, p = 0.020) and central regions (rho = 0.490, p = 0.046). Overnight recall was not related to SWA or spindle measures in either group., Conclusions: Older adults with OSA had deficits in fast sleep spindles but showed preserved overnight declarative memory consolidation. It is possible that compensatory mechanisms are being recruited by OSA patients to preserve declarative memory consolidation despite the presence of sleep spindle deficits., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: To investigate neurocognitive and behavioral outcomes at primary school age in relation to obstructive sleep apnea (OSA) in children with Robin sequence (RS) treated with the Tuebingen palatal plate in infancy and to assess the impact of OSA in these patients., Methods: Forty-two primary school-aged children (n = 21 with RS, n = 21 age- and sex-matched controls) underwent polysomnography, intelligence testing ("Wechsler Intelligence Scale for Children-Fifth Edition" [WISC-V]), and anthropometrics. Families completed a 7-day sleep diary and questionnaires on sleep and behavior (Children's Sleep Habits Questionnaire [CSHQ] and the Child Behavior Checklist [CBCL])., Results: In children with RS (17 non-syndromic, four syndromic; median age 9.7 [8.5-10.8] years), the obstructive apnea-hypopnea index (OAHI) was significantly higher than in controls (1.3 [0.4-2.7]/h vs. 0.4 [0.1-0.6]/h). Two syndromic children with RS were already on nocturnal respiratory support for OSA prior to our study, and one non-syndromic child was diagnosed with severe OSA (OAHI 57/h) despite an unremarkable medical history and questionnaire. The overall intelligence quotient in children with RS was within the normal range and did not differ between children with RS and healthy peers (102 vs. 108, p = .05). However, children with RS had values in the at-risk clinical range for externalizing behavior., Conclusions: These children with RS showed an increased risk of OSA and behavioral problems, suggesting regular screening for OSA throughout childhood. Neurocognitive scores in children with RS were within the normal range after adequate treatment of OSA during infancy., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA) is linked to the emergence and progression of cardiovascular complications including hypertension, stroke, arrhythmias, coronary artery disease, and heart failure. Epidemiological studies have reported that hypertension is associated with respiratory events during REM sleep. We examined the relationship between respiratory events during REM and morning and evening hypertensive blood pressure (BP) levels in a clinical sleep population., Methods: This study included data from in-laboratory diagnostic polysomnographic studies (n = 797) from adults attending for investigation of OSA. Hypertensive BP levels were defined using BP measurements taken in the evening before and morning after polysomnography, and the use of antihypertensive medication. Regression modeling was undertaken to examine the probability of evening and morning hypertensive BP levels according to REM apnea-hypopnea index (AHI), NREM AHI, gender, age, body mass index (BMI), alcohol use, total sleep time (TST), sleep time SpO2 <90%, and smoking status., Results: The probability of morning hypertensive BP levels was significantly independently associated with age (p < .001), BMI (p < .001), and REM AHI (p < .001). No significant effect was found for the male gender, NREM AHI, alcohol use, TST, sleep time SpO2 <90%, or smoking (p > .05 for all). The probability of evening hypertensive BP levels was only significantly associated with age (p < .001), male gender (p = .012), BMI (p < .001), and TST (p = .032)., Conclusions: Respiratory events during REM sleep are significantly associated with morning hypertensive BP levels. Future research is needed to determine whether treatment of these events can prevent or reverse morning hypertensive BP levels., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: This study aimed to examine the craniofacial phenotype of Chinese prepubertal children with and without obstructive sleep apnea (OSA) using a quantitative photographic analysis technique and to develop a prediction model for OSA diagnosis based on the photogrammetric data. Potential ethnic differences in the association between OSA and photogrammetric data between Chinese and Caucasian children were also examined., Methods: This was a cross-sectional study. Chinese children aged 5-12 years old, suspected to have OSA were recruited from our sleep clinic. Frontal and side photos were taken for craniofacial phenotyping by photogrammetry. Polysomnography was performed and participants were divided into three groups: non-OSA (obstructive apnea hypopnea index (OAHI) < 1/h), mild OSA (OAHI between 1/h and 5/h), and moderate-to-severe (MS) OSA (OAHI ≥ 5/h). Prediction models were built from 70% of training data using logistic regression and evaluated on the remaining 30% of test data for receiver operating characteristic (ROC) curve construction., Results: This study included 90 participants (mean age: 8.2 ± 1.6 years, 67 males). Non-OSA, mild OSA, and MS OSA groups included 32, 31, and 27 participants, respectively. There were significant trends for an increasing maxillary-mandibular relationship angle (p = .002) and a decreasing anterior mandibular height to whole face length ratio (p < .001) with increasing OSA severity. A prediction model built with clinical measurements and the two photogrammetric features yielded an area under the ROC curve (AUC) of 0.81 (95% C.I.: 0.64-0.96)., Conclusions: Craniofacial features obtained by photogrammetry are significantly different between OSA groups in prepubertal children. Increased maxillary-mandibular relationship angle is an OSA feature found in both Asian and Caucasian children., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function., Methods: We studied 167 patients with OSA (age 50 ± 13, AHI 35.0 ± 26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline., Results: Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment., Conclusions: Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Study Objectives: Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea., Methods: Children 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis., Results: The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing., Conclusions: Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention., Trial Registration: Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859., (Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2022.)

Study Objectives: To investigate the effect of upper airway fat composition on tongue inspiratory movement and obstructive sleep apnea (OSA)., Methods: Participants without or with untreated OSA underwent a 3T magnetic resonance imaging (MRI) scan. Anatomical measurements were obtained from T2-weighted images. Mid-sagittal inspiratory tongue movements were imaged using tagged MRI during wakefulness. Tissue volumes and percentages of fat were quantified using an mDIXON scan., Results: Forty predominantly overweight participants with OSA were compared to 10 predominantly normal weight controls. After adjusting for age, BMI, and gender, the percentage of fat in the tongue was not different between groups (analysis of covariance [ANCOVA], p = 0.45), but apnoeic patients had a greater tongue volume (ANCOVA, p = 0.025). After adjusting for age, BMI, and gender, higher OSA severity was associated with larger whole tongue volume (r = 0.51, p < 0.001), and greater dilatory motion of the anterior horizontal tongue compartment (r = -0.33, p = 0.023), but not with upper airway fat percentage. Higher tongue fat percentage was associated with higher BMI and older age (Spearman r = 0.43, p = 0.002, and r =0.44, p = 0.001, respectively), but not with inspiratory tongue movements. Greater inspiratory tongue movement was associated with larger tongue volume (e.g. horizontal posterior compartment, r = -0.44, p = 0.002) and smaller nasopharyngeal airway (e.g. oblique compartment, r = 0.29, p = 0.040)., Conclusions: Larger tongue volume and a smaller nasopharynx are associated with increased inspiratory tongue dilation during wakefulness in people with and without OSA. This compensatory response was not influenced by higher tongue fat content. Whether this is also true in more obese patient populations requires further investigation., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Objectives: Infants represent an understudied minority in sleep-disordered breathing (SDB) research and yet the disease can have a significant impact on health over the formative years of neurocognitive development that follow. Herein we report data on SDB in this population using a big data approach., Methods: Data were abstracted using the Cerner Health Facts database. Demographics, sleep diagnoses, comorbid medication conditions, healthcare utilization, and economic outcomes are reported., Results: In a cohort of 68.7 million unique patients, over a 9-year period, there were 9,773 infants and young children with a diagnosis of SDB (obstructive sleep apnea [OSA], nonobstructive sleep apnea, and "other" sleep apnea) who met inclusion criteria, encompassing 17,574 encounters, and a total of 27,290 diagnoses across 62 U.S. health systems, 172 facilities, and 3 patient encounter types (inpatient, clinic, and outpatient). Thirty-nine percent were female. Thirty-nine percent were ≤1 year of age (6,429 infants), 50% were 1-2 years of age, and 11% were 2 years of age. The most common comorbid diagnoses were micrognathia, congenital airway abnormalities, gastroesophageal reflux, chronic tonsillitis/adenoiditis, and anomalies of the respiratory system. Payor mix was dominated by government-funded entities., Conclusions: We have used a novel resource, large-scale aggregate, de-identified EHR data, to examine SDB. In this population, SDB is multifactorial, closely linked to comorbid medical conditions and may contribute to a significant burden of healthcare costs. Further research focusing on infants at highest risk for SDB can help target resources and facilitate personalized management., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: To determine in children with obstructive sleep apnea (OSA) the effect of adenotonsillectomy (AT) on the cyclic alternating pattern (CAP) and the relationship between CAP and behavioral, cognitive, and quality-of-life measures., Methods: CAP parameters were analyzed in 365 overnight polysomnographic recordings of children with mild-to-moderate OSA enrolled in the Childhood Adenotonsillectomy Trial (CHAT), randomized to either early AT (eAT) or watchful waiting with supportive care (WWSC). We also analyzed CAP in a subgroup of 72 children with moderate OSA (apnea-hypopnea index > 10) that were part of the CHAT sample. Causal mediation analysis was performed to determine the independent effect of changes in CAP on selected outcome measures., Results: At baseline, a higher number of A1 phases per hour of sleep was significantly associated with worse behavioral functioning (caregiver Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC): ρ = 0.24, p = 0.042; caregiver Conners' Rating Scale Global Index: ρ = 0.25, p = 0.036) and lower quality of life (OSA-18: ρ = 0.27, p = 0.022; PedsQL: ρ = -0.29, p = 0.015) in the subgroup of children with moderate OSA, but not across the entire sample. At 7-months follow-up, changes in CAP parameters were comparable between the eAT and WWSC arms. CAP changes did not account for significant proportions of variations in behavioral, cognitive, and quality-of-life performance measures at follow-up., Conclusions: We show a significant association between the frequency of slow, high-amplitude waves with behavioral functioning, as well as the quality of life in children with moderate OSA. Early AT in children with mild-to-moderate OSA does not alter the microstructure of nonrapid eye movement sleep compared with watchful waiting after an approximately 7-month period of follow-up., Clinical Trial: The study "A Randomized Controlled Study of Adenotonsillectomy for Children With Obstructive Sleep Apnea Syndrome" was registered at Clinicaltrials.gov (#NCT00560859)., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Machine learning (ML) may provide insights into the underlying sleep stages of accelerometer-assessed sleep duration. We examined associations between ML-sleep patterns and behavior problems among preschool children., Methods: Children from the CHILD Cohort Edmonton site with actigraphy and behavior data at 3-years (n = 330) and 5-years (n = 304) were included. Parent-reported behavior problems were assessed by the Child Behavior Checklist. The Hidden Markov Model (HMM) classification method was used for ML analysis of the accelerometer sleep period. The average time each participant spent in each HMM-derived sleep state was expressed in hours per day. We analyzed associations between sleep and behavior problems stratified by children with and without sleep-disordered breathing (SDB)., Results: Four hidden sleep states were identified at 3 years and six hidden sleep states at 5 years using HMM. The first sleep state identified for both ages (HMM-0) had zero counts (no movement). The remaining hidden states were merged together (HMM-mov). Children spent an average of 8.2 ± 1.2 h/day in HMM-0 and 2.6 ± 0.8 h/day in HMM-mov at 3 years. At age 5, children spent an average of 8.2 ± 0.9 h/day in HMM-0 and 1.9 ± 0.7 h/day in HMM-mov. Among SDB children, each hour in HMM-0 was associated with 0.79-point reduced externalizing behavior problems (95% CI -1.4, -0.12; p < 0.05), and a 1.27-point lower internalizing behavior problems (95% CI -2.02, -0.53; p < 0.01)., Conclusions: ML-sleep states were not associated with behavior problems in the general population of children. Children with SDB who had greater sleep duration without movement had lower behavioral problems. The ML-sleep states require validation with polysomnography., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA) is characterized by recurrent partial to complete upper airway obstructions during sleep, leading to repetitive arousals and oxygen desaturations. Although many OSA biomarkers have been reported individually, only a small subset have been validated through both cross-sectional and intervention studies. We sought to profile serum protein biomarkers in OSA in unbiased high throughput assay., Methods: A highly multiplexed aptamer array (SomaScan) was used to profile 1300 proteins in serum samples from 713 individuals in the Stanford Sleep Cohort, a patient-based registry. Outcome measures derived from overnight polysomnography included Obstructive Apnea Hypopnea Index (OAHI), Central Apnea Index (CAI), 2% Oxygen Desaturation index, mean and minimum oxygen saturation indices during sleep. Additionally, a separate intervention-based cohort of 16 individuals was used to assess proteomic profiles pre- and post-intervention with positive airway pressure., Results: OAHI was associated with 65 proteins, predominantly pathways of complement, coagulation, cytokine signaling, and hemostasis which were upregulated. CAI was associated with two proteins including Roundabout homolog 3 (ROBO3), a protein involved in bilateral synchronization of the pre-Bötzinger complex and cystatin F. Analysis of pre- and post intervention samples revealed IGFBP-3 protein to be increased while LEAP1 (Hepicidin) to be decreased with intervention. An OAHI machine learning classifier (OAHI >=15 vs OAHI<15) trained on SomaScan protein measures alone performed robustly, achieving 76% accuracy in a validation dataset., Conclusions: Multiplex protein assays offer diagnostic potential and provide new insights into the biological basis of sleep disordered breathing., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Up to 5% of adults in Western countries have undiagnosed sleep-disordered breathing (SDB). Studies have shown that electrocardiogram (ECG)-based algorithms can identify SDB and may provide alternative screening. Most studies, however, have limited generalizability as they have been conducted using the apnea-ECG database, a small sample database that lacks complex SDB cases., Methods: Here, we developed a fully automatic, data-driven algorithm that classifies apnea and hypopnea events based on the ECG using almost 10 000 polysomnographic sleep recordings from two large population-based samples, the Sleep Heart Health Study (SHHS) and the Multi-Ethnic Study of Atherosclerosis (MESA), which contain subjects with a broad range of sleep and cardiovascular diseases (CVDs) to ensure heterogeneity., Results: Performances on average were sensitivity(Se)=68.7%, precision (Pr)=69.1%, score (F1)=66.6% per subject, and accuracy of correctly classifying apnea-hypopnea index (AHI) severity score was Acc=84.9%. Target AHI and predicted AHI were highly correlated (R2 = 0.828) across subjects, indicating validity in predicting SDB severity. Our algorithm proved to be statistically robust between databases, between different periodic leg movement index (PLMI) severity groups, and for subjects with previous CVD incidents. Further, our algorithm achieved the state-of-the-art performance of Se=87.8%, Sp=91.1%, Acc=89.9% using independent comparisons and Se=90.7%, Sp=95.7%, Acc=93.8% using a transfer learning comparison on the apnea-ECG database., Conclusions: Our robust and automatic algorithm constitutes a minimally intrusive and inexpensive screening system for the detection of SDB events using the ECG to alleviate the current problems and costs associated with diagnosing SDB cases and to provide a system capable of identifying undiagnosed SDB cases., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: To determine the associations of sleep-disordered breathing (SDB) with subsequent healthcare costs and utilization including inpatient and post-acute care facility stays among community-dwelling older men., Methods: Participants were 1,316 men (mean age 76.1 [SD = 5.7] years) in the Outcomes of Sleep Disorders in Older Men (MrOS sleep) study (from December 2003 to March 2005), who were enrolled in a Medicare Fee-For-Service plan. Primary SDB measures including apnea hypopnea index (AHI) and oxygen desaturation index (ODI) were collected using in-home level 2 polysomnography. Incident healthcare costs and utilization were determined from claims data in the subsequent 3-year period post-MrOS sleep visit., Results: Five hundred and twenty-nine (40.2%) men had at least one hospitalization in the 3-year period. Compared with those without sleep apnea (AHI < 5/hour), men with moderate to severe sleep apnea (AHI ≥ 15/hour) had a higher odds of all-cause hospitalization (odds ratio [OR] adjusted for age and site 1.43, 95% confidence interval [CI]: 1.07-1.90). This association was slightly attenuated after further adjustment for traditional prognostic factors including education, body mass index, comorbid medical conditions, and health status (OR = 1.36; 95% CI: 1.01-1.83). Similar associations were observed for ODI. However, measures of SDB were not related to subsequent healthcare costs (total or outpatient) or odds of post-acute skilled nursing facility stay., Conclusions: Older men with SDB have an increased risk of hospitalization, not entirely explained by the greater prevalence of comorbid conditions, but not higher subsequent total healthcare costs. These findings indicate a need to evaluate the impact of SDB treatment on subsequent healthcare utilization., (Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2019.)

Study Objectives: Early in life impairment of orofacial growth leads to sleep-disordered breathing (SDB). Normal lingual gnosis and praxis are part of this early development related to the normal sensorimotor development of the tongue and surrounding oral musculature. The aim of this retrospective study was to explore if lingual praxia is impaired in both SDB children and adults and if there is an association to craniofacial morphology., Methods: The ability to perform simple tongue maneuvers was investigated in 100 prepubertal SDB children and 150 SDB adults (shown with polysomnography). All individuals had a clinical investigation by specialists to assess any orofacial growth impairment and the elements potentially behind this impairment. In a subgroup of individuals both able and unable to perform the maneuvers, we also performed a blind recognition of forms placed in the mouth., Results: A subgroup of pediatric and adult SDB patients presented evidence not only of orofacial growth impairment, but also apraxia independent of age and severity of OSA., Conclusions: By 3 years of age, children should be able to perform requested tongue maneuvers and have oral form recognition. Abnormal gnosis-praxis was noted, independent of age in SDB children and adults, demonstrating that an abnormal functioning of the tongue in the oral cavity during early development can be detected. Both children and adults with SDB may present similar absences of normal oral development very early in life and a similar presentation of apraxia, suggesting that the distinction of SDB in children versus adults may not be relevant., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Mandibular advancement splint (MAS) therapy is a well-tolerated alternative to continuous positive airway pressure for obstructive sleep apnea (OSA). Other therapies, including nasal expiratory positive airway pressure (EPAP) valves, can also reduce OSA severity. However, >50% of patients have an incomplete or no therapeutic response with either therapy alone and thus remain at risk of adverse health outcomes. Combining these therapies may yield greater efficacy to provide a therapeutic solution for many incomplete/nonresponders to MAS therapy. Thus, this study evaluated the efficacy of combination therapy with MAS plus EPAP in incomplete/nonresponders to MAS alone., Methods: Twenty-two people with OSA (apnea-hypopnea index [AHI] = 22 [13, 42] events/hr), who were incomplete/nonresponders (residual AHI > 5 events/hr) on an initial split-night polysomnography with a novel MAS device containing an oral airway, completed an additional split-night polysomnography with MAS + oral EPAP valve and MAS + oral and nasal EPAP valves (order randomized)., Results: Compared with MAS alone, MAS + oral EPAP significantly reduced the median total AHI, with further reductions with the MAS + oral/nasal EPAP combination (15 [10, 34] vs. 10 [7, 21] vs. 7 [3, 13] events/hr, p < 0.01). Larger reductions occurred in supine nonrapid eye movement AHI with MAS + oral/nasal EPAP combination therapy (ΔAHI = 23 events/hr, p < 0.01). OSA resolved (AHI < 5 events/hr) with MAS + oral/nasal EPAP in nine individuals and 13 had ≥50% reduction in AHI from no MAS. However, sleep efficiency was lower with MAS + oral/nasal EPAP versus MAS alone or MAS + oral EPAP (78 ± 19 vs. 87 ± 10 and 88 ± 10% respectively, p < 0.05)., Conclusions: Combination therapy with a novel MAS device and simple oral or oro-nasal EPAP valves reduces OSA severity to therapeutic levels for a substantial proportion of incomplete/nonresponders to MAS therapy alone., Clinical Trials: Name: Targeted combination therapy: Physiological mechanistic studies to inform treatment for obstructive sleep apnea (OSA)URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372279 Registration: ACTRN12617000492358 (Part C)., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: A collapsible or crowded pharyngeal airway is the main cause of obstructive sleep apnea (OSA). However, quantification of airway collapsibility during sleep (Pcrit) is not clinically feasible. The primary aim of this study was to compare upper airway collapsibility using a simple wakefulness test with Pcrit during sleep., Methods: Participants with OSA were instrumented with a nasal mask, pneumotachograph and two pressure sensors, one at the choanae (PCHO), the other just above the epiglottis (PEPI). Approximately 60 brief (250 ms) pulses of negative airway pressure (~ -12 cmH2O at the mask) were delivered in early inspiration during wakefulness to measure the upper airway collapsibility index (UACI). Transient reductions in the continuous positive airway pressure (CPAP) holding pressure were then performed during sleep to determine Pcrit. In a subset of participants, the optimal number of replicate trials required to calculate the UACI was assessed., Results: The UACI (39 ± 24 mean ± SD; range = 0%-87%) and Pcrit (-0.11 ± 2.5; range: -4 to +5 cmH2O) were quantified in 34 middle-aged people (9 female) with varying OSA severity (apnea-hypopnea index range = 5-92 events/h). The UACI at a mask pressure of approximately -12 cmH2O positively correlated with Pcrit (r = 0.8; p < 0.001) and could be quantified reliably with as few as 10 replicate trials. The UACI performed well at discriminating individuals with subatmospheric Pcrit values [receiver operating characteristic curve analysis area under the curve = 0.9 (0.8-1), p < 0.001]., Conclusions: These findings indicate that a simple wakefulness test may be useful to estimate the extent of upper airway anatomical impairment during sleep in people with OSA to direct targeted non-CPAP therapies for OSA., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA) during pregnancy has been associated with adverse maternal outcomes. However, the effect of maternal OSA on fetal growth is less clear. The placenta is a critical organ for fetal growth and development and the principal determinant of birthweight. We aimed to investigate the effect of maternal OSA on placental growth and function., Methods: Placentas of women recruited to a prospective longitudinal study were consecutively obtained immediately after delivery. Each placenta was measured for length, width, and thickness. Total RNA was isolated for gene expression analysis of VEGF, VEGF receptor, PIGF, and leptin. Histological and morphometric evaluations of the placenta were performed., Results: A total of 53 placentas were investigated. Ten women (19%) had OSA, and the weight of their placentas was significantly higher compared with the placentas of the controls (526.1 ± 83.9 vs. 425.7 ± 95.5 g, p = 0.004). There was a significant positive correlation between placental weight and the log apnea-hypopnea index even after controlling for maternal body mass index (BMI; r = 0.31, p = 0.04). The birthweight/placental weight ratio was significantly lower in women with OSA compared with controls (p = 0.03). Placental weight and newborn triceps adiposity thickness correlated positively after controlling for maternal BMI (r = 0.29, p = 0.04). Leptin expression was 1.8-fold higher in placentas of women with OSA compared with controls (p = 0.02). No histological differences were found between the groups., Conclusions: Maternal OSA is associated with increased placental weight that correlated with OSA severity and neonatal adiposity independently of maternal BMI. Placental leptin overexpression may mediate/underlie the above findings.Trial Registration: Clinical Trials NCT00931099., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Mandibular advancement splints (MAS) are the leading treatment alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). However, not all patients experience clinical benefit and treatment prediction remains challenging. Understanding the effects of mandibular advancement on pharyngeal collapsibility and muscle function may provide valuable information on the mechanisms of MAS, and thereby help to develop novel approaches for patient selection. Thus, we aimed to determine dose-dependent effects of mandibular advancement on pharyngeal collapsibility and muscle function concurrently in OSA patients undergoing MAS therapy., Methods: Twelve (11 male) MAS-naïve patients underwent a detailed physiology sleep study (polysomnography) to quantify pharyngeal collapsibility (PCRIT), pharyngeal muscle responsiveness to negative pharyngeal pressure (via genioglossus intramuscular electromyography and an epiglottic pressure sensor) and effectiveness to restore airflow and minute ventilation (Vi) after 1-minute transient CPAP reductions (induced airflow-limitation) at three mandibular advancement positions: 0% (habitual bite), 50% and 100% of the maximum comfortable mandibular advancement. Standard clinical polysomnography after MAS therapy optimization was performed to determine treatment outcome., Results: Overall, participants were obese with severe OSA (mean ± SD: BMI = 31 ± 4 kg/m2, apnea-hypopnea index [AHI] = 33 ± 14 events/hour). PCRIT decreased with mandibular advancement in a dose-dependent manner (1.8 ± 3.9 vs. -0.9 ± 2.9 vs. -4.0 ± 3.6 cmH2O; p < 0.001). There was no systematic change in genioglossus muscle responsiveness (p = 0.09) or effectiveness to restore peak airflow (p = 0.4) or Vi (p = 0.7) with mandibular advancement., Conclusions: Mandibular advancement reduces pharyngeal collapsibility in a dose-dependent manner without systematically changing genioglossus muscle function in a predominantly obese and severe OSA population. This indicates that the primary mode of action of MAS therapy is via improvement in passive pharyngeal anatomy., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Recent findings indicate that noradrenergic and antimuscarinic processes are crucial for sleep-related reductions in pharyngeal muscle activity. However, there are few human studies. Accordingly, this study aimed to determine if a combined noradrenergic and antimuscarinic intervention increases pharyngeal dilator muscle activity and improves airway function in sleeping humans., Methods: Genioglossus (GG) and tensor palatini electromyography (EMG), pharyngeal pressure, upper airway resistance, and breathing parameters were acquired in 10 healthy adults (5 female) during two overnight sleep studies after 4 mg of reboxetine (REB) plus 20 mg of hyoscine butylbromide (HBB) or placebo using a double-blind, placebo-controlled, randomized, cross-over design., Results: Compared with placebo, peak and tonic GG EMG were lower (Mean ± SD: 83 ± 73 vs. 130 ± 75, p = 0.021 and 102 ± 102 vs. 147 ± 123 % wakefulness, p = 0.021, respectively) but the sleep-related reduction in tensor palatini was less (Median [25th, 75th centiles]: 53[45, 62] vs. 34[28, 38] % wakefulness, p = 0.008) with the drug combination during nonrapid eye movement (non-REM) sleep. These changes were accompanied by improved upper airway function including reduced pharyngeal pressure swings, airway resistance, respiratory load compensation, and increased breathing frequency during N2. REB and HBB significantly reduced rapid eye movement sleep compared with placebo (0.6 ± 1.1 vs. 14.5 ± 6.8 % total sleep time, p < 0.001)., Conclusions: Contrary to our hypothesis, GG muscle activity (% wakefulness) during non-REM sleep was lower with REB and HBB. However, sleep-related reductions in tensor palatini activity were less and upper airway function improved. These findings provide mechanistic insight into the role of noradrenergic and antimuscarinic processes on upper airway function in humans and have therapeutic potential for obstructive sleep apnea., Clinical Trial Registration: Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au, trial ID: ACTRN12616000469415., (© Sleep Research Society 2018. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Mild-to-moderate obstructive sleep apnea (OSA) is highly prevalent in the general population; however, previous studies on its association with incident hypertension are mixed. We examined the association between mild and moderate OSA and incident hypertension in a large random general population sample., Methods: From 1741 adults of the Penn State Cohort, 744 adults without hypertension or severe OSA (i.e. apnea/hypopnea index [AHI] ≥ 30 events/hour) were followed-up after 9.2 years. Mild OSA was defined as an AHI of 5 to 14.9 events/hour (n = 71), while moderate OSA as an AHI of 15 to 29.9 events/hour (n = 32). Incident hypertension was defined by a self-report of receiving antihypertensive medication and/or history of a diagnosis since their baseline study., Results: After adjusting for multiple potential confounders, mild-to-moderate OSA was significantly associated with increased risk of incident hypertension (overall hazard ratio [HR] = 2.94, 95% confidence interval (CI) = 1.96-4.41; HR = 3.24, 95% CI = 2.08-5.03 for mild OSA and HR = 2.23, 95% CI = 1.10-4.50 for moderate OSA). Importantly, this association was modified by age (p-interaction < 0.05); while strong in young and middle-aged adults (HR = 3.62, 95% CI = 2.34-5.60), the association was lost in adults older than 60 years (HR = 1.36 95% CI = 0.50-3.72). Furthermore, the association of mild-to-moderate OSA with components of metabolic syndrome was strongest in young and middle-aged adults., Conclusions: Mild-to-moderate OSA, even when asymptomatic, is associated with increased risk of incident hypertension, but the strength of association significantly decreases with age. Although older participants with asymptomatic mild-to-moderate OSA are not at significant risk of developing hypertension, early detection and intervention, including improving metabolic indices, is especially warranted in young and middle-aged adults., (© Sleep Research Society 2018. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objective: To better understand the inter-individual differences in neurobehavioral impairment in obstructive sleep apnea (OSA) and its treatment with continuous positive airway pressure (CPAP), we examined how changes in sleep electroencephalography (EEG) slow waves were associated with next-day psychomotor vigilance test (PVT) performance., Methods: Data from 28 OSA subjects (Apnea-Hypopnea Index with 3% desaturation and/or with an associated arousal [AHI3A] > 15/hour; AHI3A = sum of all apneas and hypopneas with 3% O2 desaturation and/or an EEG arousal, divided by total sleep time [TST]), who underwent three full in-lab nocturnal polysomnographies (NPSGs: chronic OSA, CPAP-treated OSA, and acute OSA), and 19 healthy sleepers were assessed. Four 20-minute PVTs were performed after each NPSG along with subjective and objective assessment of sleepiness. Three EEG metrics were calculated: K-complex (KC) Density (#/minute of N2 sleep), change in slow-wave activity in 1-second envelopes surrounding KCs (ΔSWAK), and relative frontal slow-wave activity during non-rapid eye movement (NREM) (%SWA)., Results: CPAP treatment of OSA resulted in a decrease in KC Density (chronic: 3.9 ± 2.2 vs. treated: 2.7 ± 1.1; p < 0.01; mean ± SD) and an increase in ΔSWAK (chronic: 2.6 ± 2.3 vs. treated: 4.1 ± 2.4; p < 0.01) and %SWA (chronic: 20.9 ± 8.8 vs. treated: 26.6 ± 8.6; p < 0.001). Cross-sectionally, lower ΔSWAK values were associated with higher PVT Lapses (chronic: rho = -0.55, p < 0.01; acute: rho = -0.46, p = 0.03). Longitudinally, improvement in PVT Lapses with CPAP was associated with an increase in ΔSWAK (chronic to treated: rho = -0.48, p = 0.02; acute to treated: rho = -0.5, p = 0.03). In contrast, OSA severity or global sleep quality metrics such as arousal index, NREM, REM, or TST were inconsistently associated with PVT Lapses., Conclusion: Changes in EEG slow waves, in particular ∆SWAK, explain inter-individual differences in PVT performance better than conventional NPSG metrics, suggesting that ΔSWAK is a night-time correlate of next-day vigilance in OSA., (© Sleep Research Society 2018. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: To examine the association between the age of onset and duration of parent-reported symptoms of sleep-disordered breathing (SDB) and behavioral problems at age 2., Methods: Parent-reported SDB symptoms were assessed quarterly between 3 months and 2 years among 583 Canadian Healthy Infant Longitudinal Development Edmonton-site participants. Parent-reported SDB symptoms were clustered into phenotypes using group-based trajectory analysis based on age of onset and duration of symptoms. Home-based polysomnography (PSG) was completed at 1 year. The Child Behavior Checklist preschool-version (Mean T-score 50, standard deviation 10 points) assessed total, externalizing (attention), and internalizing (anxiety, depression) behaviors at 2 years., Results: Four phenotypes were identified: no SDB (64.7%), early-onset SDB (15.7%, peak symptoms at 9 months), late-onset (14.2%, peak symptoms at 18 months), and persistent SDB symptoms (5.3%, peak symptoms from 3 through 24 months). Persistent SDB (9.5 points, 95% CI 1.7, 17.2; p = .02) predicted the greatest magnitude of effect of total behavior problems, compared with children without SDB. Children with early-onset SDB (3.5 points, 95% CI 1.6, 5.4; p ≤ .001) and late-onset SDB (6.1 points 95% CI 4.0, 8.3; p ≤ .001) had increased total behavioral problems than children without SDB to 2 years. Additional analyses showed that the SDB phenotypes' trajectories were important for internalizing but not for externalizing behavior problems. There were no significant associations between home-PSG and parent-reported behavior problems., Conclusions: Findings suggest that the age of onset and duration of parent-reported SDB symptoms prior to age 2 have adverse consequences for overall behavior problems., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Sleep-disordered breathing (SDB) is prevalent among children and is associated with adverse health outcomes. Worldwide, approximately 250 million individuals reside at altitudes higher than 2000 meters above sea level (masl). The effect of chronic high-altitude exposure on children with SDB is unknown. This study aims to determine the impact of altitude on sleep study outcomes in children with SDB dwelling at high altitude., Methods: A single-center crossover study was performed to compare results of high-altitude home polysomnography (H-PSG) with lower altitude laboratory polysomnography (L-PSG) in school-age children dwelling at high altitude with symptoms consistent with SDB. The primary outcome was apnea-hypopnea index (AHI), with secondary outcomes including obstructive AHI; central AHI; and measures of oxygenation, sleep quality, and pulse rate., Results: Twelve participants were enrolled, with 10 included in the final analysis. Median altitude was 1644 masl on L-PSG and 2531 masl on H-PSG. Median AHI was 2.40 on L-PSG and 10.95 on H-PSG. Both obstructive and central respiratory events accounted for the difference in AHI. Oxygenation and sleep fragmentation were worse and pulse rate higher on H-PSG compared to L-PSG., Conclusions: These findings reveal a clinically substantial impact of altitude on respiratory, sleep, and cardiovascular outcomes in children with SDB who dwell at high altitude. Within this population, L-PSG underestimates obstructive sleep apnea and central sleep apnea compared to H-PSG. Given the shortage of high-altitude pediatric sleep laboratories, these results suggest a role for home sleep apnea testing for children residing at high altitude., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: We tested the hypothesis that estradiol (E2) protects against cardiorespiratory disorders and oxidative stress induced by chronic intermittent hypoxia (CIH) in adult female rats., Methods: Sprague-Dawley female rats (230-250 g) were ovariectomized and implanted with osmotic pumps delivering vehicle or E2 (0.5 mg/kg/d). After 14 days of recovery, the rats were exposed to CIH (21%-10% O2: 8 h/d, 10 cycles per hour) or room air (RA). After 7 days of CIH or RA exposure, we measured arterial pressures (tail cuff), metabolic rate (indirect calorimetry), minute ventilation, the frequency of sighs and apneas at rest, and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). We collected the cerebral cortex, brainstem, and adrenal glands to measure the activity of NADPH and xanthine oxidase (pro-oxidant enzymes), glutathione peroxidase, and the mitochondrial and cytosolic superoxide dismutase (antioxidant enzymes) and measured lipid peroxidation and advanced oxidation protein products (markers of oxidative stress)., Results: CIH increased arterial pressure, the frequency of apnea at rest, and the hypoxic and hypercapnic ventilatory responses and reduced metabolic rate. CIH also increased oxidant enzyme activities and decreased antioxidant activity in the cortex. E2 treatment reduced body weight and prevented the effects of CIH., Conclusions: E2 prevents cardiorespiratory disorders and oxidative stress induced by CIH. These observations may help to better understand the underlying mechanisms linking menopause and occurrence of sleep apnea in women and highlight a potential advantage of hormone therapy., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Our aim was to evaluate the circadian rhythm of distal skin temperature (DST) in sleep-disordered breathing (SDB), its relation to excessive daytime sleepiness and the effect of continuous positive airway pressure (CPAP) on DST., Methods: Eighty SDB patients (53.1 ± 1.2 years old, 27.6% women) and 67 healthy participants (52.3 ± 1.6 years old, 26.9% women) wore a temperature data logger for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test (MWT), Multiple Sleep Latency Test, and Sustained Attention to Response Task protocol to objectively quantify daytime sleepiness. A subset of 21 moderate to severe SDB patients were treated with CPAP during at least 3 months and revaluated with the same procedure. A nonparametric analysis was performed to characterize DST to assess differences between groups and associations among DST, polysomnography, and daytime sleepiness measures., Results: SDB patients showed an unstable, fragmented, flattened, phase-advanced, and less robust DST rhythm as compared to healthy participants. The more severe the SDB, the worse the DST pattern was, as indicated by the correlation coefficient. Sleepiness, according to MWT sleep latencies, was also associated with the higher fragmentation, lower amplitude, and less robustness of the DST rhythm. Treatment with CPAP improved DST pattern regularity and robustness., Conclusion: DST is altered in SDB, exhibiting a direct relationship to the severity of this condition, and improves with CPAP treatment. DST independently correlates with sleepiness, thus, its measurement may contribute to the understanding of the pathophysiology of sleepiness in these patients., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Poor or short sleep and the presence of snoring indicative of sleep-disordered breathing (SDB) have been associated with behavioral problems in school-aged children. We examined the relationship between SDB, sleep duration, obesity risk, and behavioral characteristics in Japanese elementary school students using a large-scale survey., Methods: We conducted a cross-sectional study of children enrolled in all 46 public primary schools in Matsuyama city, Japan. The children's parents or guardians completed a questionnaire that covered sleep habits, presence of SDB risk, and behavioral characteristics., Results: In total, 24 296 responses were received (90% response rate). After excluding incomplete responses, we analyzed complete datasets for 17 769 children. Mean sleep duration decreased with age, as did the prevalence of pediatric SDB. We found an increased risk for the presence of SDB and short sleep among overweight/obese children. With SDB or short sleep, we observed significantly increased odds of restless behaviors, fidgety behaviors, and poor concentration in school., Conclusions: Shorter sleep duration was associated with increased risk of obesity, and in turn, obesity increased SDB risk. Both short sleep duration and SDB risk were significantly associated with behavioral problems in school., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Introduction: Obstructive sleep apnea (OSA) severity is markedly reduced during slow-wave sleep (SWS) even in patients with a severe disease. The reason for this improvement is uncertain but likely relates to non-anatomical factors (i.e. reduced arousability, chemosensitivity, and increased dilator muscle activity). The anticonvulsant tiagabine produces a dose-dependent increase in SWS in subjects without OSA. This study aimed to test the hypothesis that tiagabine would reduce OSA severity by raising the overall arousal threshold during sleep., Aims and Methods: After a baseline physiology night to assess patients' OSA phenotypic traits, a placebo-controlled, double-blind, crossover trial of tiagabine 12 mg administered before sleep was performed in 14 OSA patients. Under each condition, we assessed the effects on sleep and OSA severity using standard clinical polysomnography., Results: Tiagabine increased slow-wave activity (SWA) of the electroencephalogram (1-4 Hz) compared to placebo (1.8 [0.4] vs. 2.0 [0.5] LogμV2, p = .04) but did not reduce OSA severity (apnea-hypopnea index [AHI] 41.5 [20.3] vs. 39.1 [16.5], p > .5). SWS duration (25 [20] vs. 26 [43] mins, p > .5) and arousal threshold (-26.5 [5.0] vs. -27.6 [5.1] cmH2O, p = .26) were also unchanged between nights., Conclusions: Tiagabine modified sleep microstructure (increase in SWA) but did not change the duration of SWS, OSA severity, or arousal threshold in this group of OSA patients. Based on these findings, tiagabine should not be considered as a therapeutic option for OSA treatment., (© Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: Arousals from sleep vary in duration and intensity. Accordingly, the physiological consequences of different types of arousals may also vary. Factors that influence arousal intensity are only partly understood. This study aimed to determine if arousal intensity is mediated by the strength of the preceding respiratory stimulus, and investigate other factors mediating arousal intensity and its role on post-arousal ventilatory and pharyngeal muscle responses., Methods: Data were acquired in 71 adults (17 controls, 54 obstructive sleep apnea patients) instrumented with polysomnography equipment plus genioglossus and tensor palatini electromyography (EMG), a nasal mask and pneumotachograph, and an epiglottic pressure sensor. Transient reductions in CPAP were delivered during sleep to induce respiratory-related arousals. Arousal intensity was measured using a validated 10-point scale., Results: Average arousal intensity was not related to the magnitude of the preceding respiratory stimuli but was positively associated with arousal duration, time to arousal, rate of change in epiglottic pressure and negatively with BMI (R 2 > 0.10, P ≤ 0.006). High (> 5) intensity arousals caused greater ventilatory responses than low (≤ 5) intensity arousals (10.9 [6.8-14.5] vs. 7.8 [4.7-12.9] L/min; P = 0.036) and greater increases in tensor palatini EMG (10 [3-17] vs. 6 [2-11]%max; P = 0.031), with less pronounced increases in genioglossus EMG., Conclusions: Average arousal intensity is independent of the preceding respiratory stimulus. This is consistent with arousal intensity being a distinct trait. Respiratory and pharyngeal muscle responses increase with arousal intensity. Thus, patients with higher arousal intensities may be more prone to respiratory control instability. These findings are important for sleep apnea pathogenesis., (© 2016 Associated Professional Sleep Societies, LLC.)

Study Objectives: To compare polysomnographic parameters in high altitude (HA) native Andean children with low altitude (LA) native peers in order to explain the nocturnal oxyhemoglobin saturation (SpO2) instability reported in HA native children and to study the effect on sleep quality., Methods: Ninety-eight healthy children aged 7-10 y and 13-16 y were recruited at LA (500 m) or HA (3,650 m) above sea level. Physical examination was undertaken and genetic ancestry determined from salivary DNA to determine proportion of European ancestry, a risk factor for poor HA adaptation. Attended polysomnography was carried out over 1 night for 58 children at their resident location., Results: Of 98 children recruited, 85 met inclusion criteria, 58 of 85 (68.2%) completed polysomnography, of which 56 were adequate for analysis: 30 at LA (17 male) and 26 at HA (16 male). There were no altitude differences in genetic ancestry, but a high proportion of European admixture (median 50.6% LA; 44.0% HA). SpO2 was less stable at HA with mean 3% and 4% oxygen desaturation indices greater (both P < 0.001) than at LA. This was not explained by periodic breathing. However, more obstructive hypopnea was observed at HA (P < 0.001), along with a trend toward more central apnea (P = 0.053); neither was explained by clinical findings. There was no difference in sleep quality between altitudes., Conclusions: HA native Andean children have more respiratory events when scoring relies on SpO2 desaturation due to inherent SpO2 instability. Use of American Academy of Sleep Medicine scoring criteria may yield false-positive results for obstructive sleep-disordered breathing at HA., (© 2016 Associated Professional Sleep Societies, LLC.)