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Purpose: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles., Methods: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep., Results: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001)., Conclusion: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk., (© 2024. The Author(s).)

Study Objectives: Recent studies suggest that sleepy patients with obstructive sleep apnea (OSA) are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with OSA using heart rate variability (HRV) analysis. We hypothesized that HRV profiles of sleepy patients would indicate higher cardiovascular risk., Methods: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS ≥ 10) and non-sleepy OSA patients (ESS < 10). HRV parameters were averaged across available ECG signals during N2 sleep., Results: A total of 421 patients were evaluated, with a mean age of 54 (14) years, body mass index of 33 (9) kg/m2, apnea-hypopnea index of 21 (28) events/h, and 66% male. The sleepy group consisted of 119 patients and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p = 0.028), total power (TP, p = 0.031), absolute low frequency (LF, p = 0.045), and high-frequency (HF, p = 0.010) power compared to non-sleepy patients. Sleepy patients with moderate-to-severe OSA exhibited lower HRV values for: (RMSSD, p = 0.045; TP, p = 0.052), absolute LF (p = 0.051), and HF power (p = 0.025). There were no differences in other time and frequency domain HRV markers., Conclusions: This study shows a trend toward parasympathetic withdrawal in sleepy OSA patients, particularly in moderate-to-severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Purpose: This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis., Methods: Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30 s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI)., Results: In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56 ± 11 years, BMI 29.8 ± 5.3 kg/m 2 , and treatment duration was 4.0 ± 3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (β(SE) =  - 2.21 (0.01), t =  - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment., Conclusion: The study findings suggest that successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability., (© 2023. The Author(s).)

Purpose: To compare the anatomical balance and shape of the upper airway in the supine position between adults with positional obstructive sleep apnea (POSA) and adults with non-positional OSA (NPOSA)., Methods: Adults diagnosed with OSA (apnea-hypopnea index (AHI) > 10 events/h) were assessed for eligibility. POSA was defined as the supine AHI more than twice the AHI in non-supine positions; otherwise, patients were classified as NPOSA. Cone beam computed tomography (CBCT) imaging was performed for every participant while awake in the supine position. The anatomical balance was calculated as the ratio of the tongue size to the maxillomandibular enclosure size. The upper airway shape was calculated as the ratio of the anteroposterior dimension to the lateral dimension at the location of the minimal cross-sectional area of the upper airway (CSAmin-shape)., Results: Of 47 participants (28 males, median age [interquartile range] 56 [46 to 63] years, median AHI 27.8 [15.0 to 33.8]), 34 participants were classified as having POSA (72%). The POSA group tended to have a higher proportion of males and a lower AHI than the NPOSA group (P = 0.07 and 0.07, respectively). After controlling for both sex and AHI, the anatomical balance and CSAmin-shape were not significantly different between both groups (P = 0.18 and 0.73, respectively)., Conclusion: Adults with POSA and adults with NPOSA have similar anatomical balance and shape of their upper airway in the supine position., Trial Registration: This study was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR Trial ACTRN12611000409976)., (© 2023. The Author(s).)

Purpose: Obesity is a reversible risk factor for obstructive sleep apnoea (OSA). Weight loss can potentially improve OSA by reducing fat around and within tissues surrounding the upper airway, but imaging studies are limited. Our aim was to study the effects of large amounts of weight loss on the upper airway and volume and fat content of multiple surrounding soft tissues., Methods: Participants undergoing bariatric surgery were recruited. Magnetic resonance imaging (MRI) was performed at baseline and six-months after surgery. Volumetric analysis of the airway space, tongue, pharyngeal lateral walls, and soft palate were performed as well as calculation of intra-tissue fat content from Dixon imaging sequences., Results: Among 18 participants (89% women), the group experienced 27.4 ± 4.7% reduction in body weight. Velopharyngeal airway volume increased (large effect; Cohen's d [95% CI], 0.8 [0.1, 1.4]) and tongue (large effect; Cohen's d [95% CI], - 1.4 [- 2.1, - 0.7]) and pharyngeal lateral wall (Cohen's d [95% CI], - 0.7 [- 1.2, - 0.1]) volumes decreased. Intra-tissue fat decreased following weight loss in the tongue, tongue base, lateral walls, and soft palate. There was a greater effect of weight loss on intra-tissue fat than parapharyngeal fat pad volume (medium effect; Cohen's d [95% CI], - 0.5 [- 1.2, 0.1], p = 0.083)., Conclusion: The study showed an increase in velopharyngeal volume, reduction in tongue volume, and reduced intra-tissue fat in multiple upper airway soft tissues following weight loss in OSA. Further studies are needed to assess the effect of these anatomical changes on upper airway function and its relationship to OSA improvement., (© 2022. The Author(s).)

Polysomnograms (PSGs) contain a wealth of physiological information that is routinely recorded but not utilised in sleep studies. Intermittent hypoxia arising from obstructive sleep apnoea (OSA) events is an important risk in the later development of cardiovascular disease (CVD). Analysis of oximetry patterns from PSG studies may enable early assessment of CVD risk. The aim of this study was to compare associations of different time-domain oximetry patterns with incident CVD in OSA patients. All participants with OSA and no pre-existing CVD at baseline or within the first two years of follow-up, were selected from the Sleep Heart Health Study data and used for analysis (N=2878). We examined oximetry parameters that are calculated from desaturation events and from time series analysis and compared them to incident CVD outcomes using proportional hazards regression models adjusted for age, race, smoking, BMI, and sex. Our results show that were no associations between OSA oximetry parameters and incident CVD for OSA patients.

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA)., Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus., Results: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated., Conclusion: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy., (© 2022 ARS-AAOA, LLC.)

Purpose: The autonomic nervous system may mediate acute apnoea-induced atrial fibrillation (AF). We compared cardiac autonomic function in paroxysmal atrial fibrillation (PAF) patients with and without obstructive sleep apnoea (OSA)., Methods: Case control study of 101 patients with PAF recruited at two tertiary centres. All patients underwent in-laboratory polysomnography. ECG signal demonstrating "steady state" sinus rhythm (i.e. with arrhythmic beats and respiratory events excluded) was included in the analysis. Cardiac autonomic function was assessed via measures of heart rate variability (HRV) and reported by sleep stage (REM vs Non-REM) for patients with and without OSA., Results: Sixty-five (66.3%) of patients were male, mean age 61.5 ± 11.6 years, mean BMI 27.1 ± 4.3 kg/m 2 . Global measures of HRV (triangular index, total power) did not differ between PAF patients with and without OSA in either REM or non-REM sleep. Frequency-domain analysis during non-REM sleep in PAF patients with OSA showed increased cardiac parasympathetic modulation (HF-nu: 39.1 ± 15.7 vs 48.0 ± 14.6, p = 0.008) and reduced cardiac sympathetic modulation (LF-nu 54.1 ± 19.7 vs 43.7 ± 18.0, p = 0.012, LF/HF ratio: 2.1 ± 2.0 vs 1.2 ± 1.0, p = 0.007). Results remained significant after adjusting for age, sex, and BMI (adjusted p values 0.024, 0.045 and 0.018 respectively). There were no differences in HRV parameters during REM sleep., Conclusions: This is the first study of HRV in PAF patients with and without OSA. Our results indicate limited differences in HRV between groups. However, this work suggests a chronic increase in parasympathetic nervous modulation and relative reduction in sympathetic modulation in PAF patients with OSA during steady-state non-REM sleep., (© 2022. Crown.)

Social jetlag is the discrepancy between socially determined sleep timing on workdays and biologically determined sleep timing on days free of social obligation. Poor circadian timing of sleep may worsen sleep quality and increase daytime sleepiness in obstructive sleep apnea (OSA). We analysed de-identified data from 2,061 participants (75.2% male, mean [SD] age 48.6 [13.4] years) who completed Sleep Apnea Global Interdisciplinary Consortium (SAGIC) research questionnaires and underwent polysomnography at 11 international sleep clinic sites. Social jetlag was calculated as the absolute difference in the midpoints of sleep between weekdays and weekends. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Linear regression analyses were performed to estimate the association between social jetlag and daytime sleepiness, with consideration of age, sex, body mass index, ethnicity, insomnia, alcohol consumption, and habitual sleep duration as confounders. Of the participants, 61.5% had <1 h of social jetlag, 27.5% had 1 to <2 h, and 11.1% had ≥2 h. Compared to those with <1 h of social jetlag, those with ≥2 h of social jetlag had 2.07 points higher ESS (95% confidence interval [CI] 0.77-3.38, p = 0.002), and those with 1 to <2 h of social jetlag had 0.80 points higher ESS (95% CI 0.04-1.55, p = 0.04) after adjustment for potential confounding. Interaction with OSA severity was observed; social jetlag appeared to have the greatest effect on daytime sleepiness in mild OSA. As social jetlag exacerbates daytime sleepiness in OSA, improving sleep timing may be a simple but novel therapeutic target for reducing the impact of OSA., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included ( N  = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized β [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P  < 0.001), mandibular width (standardized β [95% CI] = 0.15 [0.10-0.20]; P  < 0.001), and tongue thickness (standardized β [95% CI] = 0.06 [0.02-0.10]; P  = 0.001) and smaller airway width (standardized β [95% CI] = -0.08 [-0.15 to -0.002]; P  = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.

Dental sleep medicine as a discipline was first described about a quarter of a century ago. Snoring, obstructive sleep apnea, sleep bruxism, xerostomia, hypersalivation, gastroesophageal reflux disease, and orofacial pain were identified as dental sleep-related conditions. This scoping review aimed to: i) identify previously unidentified dental sleep-related conditions; and ii) identify the role of oral healthcare providers in the prevention, assessment, and management of dental sleep-related conditions in adults. A systematic literature search was conducted in PubMed, Embase.com, Web of Science, and Cochrane. Studies that reported an actual or likely role of oral healthcare providers in the prevention, assessment, and/or management of sleep-related conditions were included. Of the 273 included studies, 260 were on previously listed dental sleep-related conditions; the other 13 were on burning mouth syndrome. Burning mouth syndrome was therefore added to the list of dental sleep-related conditions for the first aim and categorized into sleep-related orofacial pain. For the second aim, the role of oral healthcare providers was found to be significant in the prevention, assessment, and management of obstructive sleep apnea and sleep bruxism; in the assessment and management of snoring, sleep-related orofacial pain, and oral dryness; and in the assessment of sleep-related gastroesophageal reflux condition., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Objectives: Autonomic function is impaired in obstructive sleep apnea (OSA) and may mediate the association between OSA and cardiovascular risk. We investigated the effect of OSA therapy on autonomic function through a systematic review and meta-analysis of intervention studies., Methods: A systematic search using three databases (Medline, Embase, and Scopus) was performed up to December 9, 2020. Studies of OSA patients ≥ 18 years with autonomic function assessed before and after treatment with positive airway pressure, oral appliance, positional therapy, weight loss, or surgical intervention were included for review. Random effects meta-analysis was carried out for five groups of autonomic function indices. Risk of bias was assessed using the Cochrane Collaboration tool., Results: Forty-three eligible studies were reviewed with 39 included in the meta-analysis. OSA treatment led to large decreases in muscle sympathetic nerve activity (Hedges' g = -1.08; 95% CI -1.50, -0.65, n = 8) and moderate decreases in catecholamines (-0.60; -0.94, -0.27, n = 3) and radio nucleotide imaging (-0.61; -0.99, -0.24, n = 2). OSA therapy had no significant effect on baroreflex function (Hedges' g = 0.15; 95% CI -0.09, 0.39, n = 6) or heart rate variability (0.02; -0.32, 0.36, n = 14). There was a significant risk of bias due to studies being primarily non-randomized trials., Conclusions: OSA therapy selectively improves autonomic function measures. The strongest evidence for the effect of OSA therapy on autonomic function was seen in reduced sympathetic activity as assessed by microneurography, but without increased improvement in parasympathetic function. OSA therapy may reduce the risk of cardiovascular disease in OSA through reduced sympathetic activity., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Study Objectives: Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. The aim of this study was to compare associations of different oximetry patterns with incident CVD in men and women with OSA., Methods: Sleep Heart Health Study data were used for analysis. n = 2878 Participants (51.8% female; mean age 63.5 ± 10.5 years) with OSA (Apnea Hypopnea Index [AHI] ≥ 5 events/h) and no pre-existing CVD at baseline or within the first 2 years of follow-up were included. Four oximetry analysis approaches were applied: desaturation characteristics, time series analysis, power spectral density, and non-linear analysis. Thirty-one resulting oximetry patterns were compared to incident CVD using proportional hazards regression models adjusted for age, race, smoking, BMI, and sex., Results: There were no associations between OSA oximetry patterns and incident CVD in the total sample or in men. In women, there were some associations between incident CVD and time series analysis (e.g. SpO2 distribution standard deviation, HR 0.81, 95% CI 0.68-0.96, p = 0.014) and power spectral density oximetry patterns (e.g. Full frequency band mean HR 0.75; 95% CI 0.59-0.95; p = 0.015)., Conclusions: Comprehensive comparison of baseline oximetry patterns in OSA found none were related to development of CVD. There were no standout individual oximetry patterns that appear to be candidates for CVD risk phenotyping in OSA, but some showed marginal relationships with CVD risk in women. Further work is required to understand whether OSA phenotypes can be used to predict susceptibility to cardiovascular disease., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Context/objective: Obstructive sleep apnoea (OSA) develops soon after cervical spinal cord injury (SCI) at rates higher than the general population, but the mechanisms are not understood. This study aimed to determine whether OSA in SCI is associated with altered pharyngeal muscle dilatory mechanics during quiet breathing, as has been observed in the non-SCI injured with obstructive sleep apnoea. Design: Cross sectional imaging study. Setting: Medical research institute. Participants: Eight cervical SCI patients with OSA were recruited and compared to 13 able-bodied OSA patients and 12 able-bodied healthy controls of similar age and BMI. Interventions and outcome measures: 3T MRI scans of upper airway anatomy and tagged-MRI to characterize airway muscle motion during quiet breathing were collected for analysis. Results: Considerable variation in the patterns of inspiratory airway muscle motion was observed in the SCI group, with some participants exhibiting large inspiratory airway dilatory motions, and others exhibiting counterproductive narrowing during inspiration. These patterns were not dissimilar to those observed in the able-bodied OSA participants. The increase in airway cross-sectional area of able-bodied control participants was proportional to increase in BMI, and a similar, but not significant, relationship was present in all groups. Conclusion: Despite the limited sample size, these data suggest that SCI OSA patients have heterogeneous pharyngeal dilator muscle responses to the negative pressures occurring during inspiration but, as a group, appear to be more similar to able-bodied OSA patients than healthy controls of similar age and BMI. This may reflect altered pharyngeal pressure reflex responses in at least some people with SCI.

Study Objectives: To characterize how mandibular advancement enlarges the upper airway via posterior tongue advancement in people with obstructive sleep apnea (OSA) and whether this is associated with mandibular advancement splint (MAS) treatment outcome., Methods: One-hundred and one untreated people with OSA underwent a 3T magnetic resonance (MRI) scan. Dynamic mid-sagittal posterior tongue and mandible movements during passive jaw advancement were measured with tagged MRI. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of maximum advancement. Treatment outcome was determined after a minimum of 9 weeks of therapy., Results: Seventy-one participants completed the study: 33 were responders (AHI<5 or AHI≤10 events/hr with >50% AHI reduction), 11 were partial responders (>50% AHI reduction but AHI>10 events/hr), and 27 nonresponders (AHI reduction<50% and AHI≥10 events/hr). Responders had the greatest naso- and oropharyngeal tongue anterior movement (0.40 ± 0.08 and 0.47 ± 0.13 mm, respectively) and oropharyngeal cross-sectional area enlargement (6.41 ± 2.12%) per millimeter of mandibular advancement. A multivariate model that included tongue movement and percentage of airway enlargement per millimeter of mandibular advancement along with baseline AHI correctly classified 69.2% (5-fold cross-validated 62.5%, n = 39) of participants in response categories when the jaw was advanced in the range that would usually be regarded as sufficient for clinical efficacy (> 4 mm). In comparison, a model using only baseline AHI correctly classified 50.0% of patients (5-fold cross-validated 52.5%, n = 40)., Conclusions: Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improve treatment response categorization to a satisfactory level (69.2%, 5-fold cross-validated 62.5%)., (© 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.)

Background: Prediction tools without patient-reported symptoms could facilitate widespread identification of OSA., Research Question: What is the diagnostic performance of OSA prediction tools derived from machine learning using readily available data without patient responses to questionnaires? Also, how do they compare with STOP-BANG, an OSA prediction tool, in clinical and community-based samples?, Study Design and Methods: Logistic regression and machine learning techniques, including artificial neural network (ANN), random forests (RF), and kernel support vector machine, were used to determine the ability of age, sex, BMI, and race to predict OSA status. A retrospective cohort of 17,448 subjects from sleep clinics within the international Sleep Apnea Global Interdisciplinary Consortium (SAGIC) were randomly split into training (n = 10,469) and validation (n = 6,979) sets. Model comparisons were performed by using the area under the receiver-operating curve (AUC). Trained models were compared with the STOP-BANG questionnaire in two prospective testing datasets: an independent clinic-based sample from SAGIC (n = 1,613) and a community-based sample from the Sleep Heart Health Study (n = 5,599)., Results: The AUCs (95% CI) of the machine learning models were significantly higher than logistic regression (0.61 [0.60-0.62]) in both the training and validation datasets (ANN, 0.68 [0.66-0.69]; RF, 0.68 [0.67-0.70]; and kernel support vector machine, 0.66 [0.65-0.67]). In the SAGIC testing sample, the ANN (0.70 [0.68-0.72]) and RF (0.70 [0.68-0.73]) models had AUCs similar to those of the STOP-BANG (0.71 [0.68-0.72]). In the Sleep Heart Health Study testing sample, the ANN (0.72 [0.71-0.74]) had AUCs similar to those of STOP-BANG (0.72 [0.70-0.73])., Interpretation: OSA prediction tools using machine learning without patient-reported symptoms provide better diagnostic performance than logistic regression. In clinical and community-based samples, the symptomless ANN tool has diagnostic performance similar to that of a widely used prediction tool that includes patient symptoms. Machine learning-derived algorithms may have utility for widespread identification of OSA., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Mandibular advancement splint (MAS) therapy is the leading alternative to continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnoea. A MAS is an oral appliance which advances the mandible in relation to the maxilla, thus increasing airway calibre and reducing collapsibility. Although it is less effective than CPAP in reducing the apnoea-hypopnoea index (AHI), it has demonstrated equivalence to CPAP in a number of key neurobehavioural and cardiovascular health outcomes, perhaps due to increased tolerability and patient adherence when compared to CPAP. However, response to MAS is variable, and reliable prediction tools for patients who respond best to MAS therapy have thus far been elusive; this is one of the key clinical barriers to wider uptake of MAS therapy. In addition, the most effective MAS devices are custom-made by a dentist specialising in the treatment of sleep disorders, which may present financial or accessibility barriers for some patients. MAS devices are generally well tolerated but may have side effects including temporomandibular joint (TMJ) dysfunction, hypersalivation, tooth pain and migration as well as occlusal changes. A patient-centred approach to treatment from a multidisciplinary team perspective is recommended. Evidence-based clinical practice points and areas of future research are summarised at the conclusion of the chapter., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Study Objectives: The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat)., Methods: This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed., Results: The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04-0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement., Conclusions: This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required., Clinical Trial: This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014., (© 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.)

Obstructive sleep apnea (OSA) is a highly prevalent and underdiagnosed medical condition, which is associated with various cardiovascular and metabolic diseases. The current mainstay of therapy is continuous positive airway pressure (CPAP); however, CPAP is known to be poorly accepted and tolerated by patients. In randomized controlled trials evaluating CPAP in cardiovascular outcomes, the average usage was less than 3.5 hours, which is below the 4 hours per night recommended to achieve a clinical benefit. This low adherence may have resulted in poor effectiveness and failure to show cardiovascular risk reduction. The mandibular advancement device (MAD) is an intraoral device designed to advance the mandible during sleep. It functions primarily through alteration of the jaw and/or tongue position, which results in improved upper airway patency and reduced upper airway collapsibility. The MAD is an approved alternative therapy that has been consistently shown to be the preferred option by patients who are affected by OSA. Although the MAD is less efficacious than CPAP in abolishing apnea and hypopnea events in some patients, its greater usage results in comparable improvements in quality-of-life and cardiovascular measures, including blood pressure reduction. This review summarizes the impact of OSA on cardiovascular health, the limitations of CPAP, and the potential of OSA treatment using MADs in cardiovascular risk reduction., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

A new method for calculation of an overnight oximetry signal metric which is predictive of cardiovascular disease (CVD) outcomes in individuals undergoing an overnight sleep test is presented. The metric - the respiratory event desaturation transient area (REDTA) - quantifies the desaturation associated with respiratory events. Data from the Sleep Heart Health Study, which includes overnight oximetry signals and long-term CVD outcomes, was used to develop and test the parameter. Performance of the REDTA parameter was assessed using Cox proportional hazard ratios and compared to established metrics of hypoxia. Results show that hazard ratios in adjusted Cox analysis for predicting cardiovascular death using REDTA are up to 1.90 (95%CI: 1.22-2.96) which compares with the best of the established metrics. A big advantage of our metric compared to other high performing metrics is its ease of computation.

Objectives: Oral appliance therapy for obstructive sleep apnoea (OSA) reduces blood pressure (BP) but there is little information on relationship to circadian BP pattern (nocturnal BP dipping or non-dipping). The aims of this study were to determine whether nocturnal dipping pattern influences BP changes following oral appliance therapy, and to determine the effect of oral appliance therapy on circadian BP pattern., Methods: Participants in two randomized trials of oral appliance therapy (1-2 months) with 24-h ambulatory BP monitoring (ABPM) data were included (N = 152). Nocturnal BP Dippers (nocturnal/diurnal SBP ratio <0.9) and non-dippers were compared for BP changes following oral appliance therapy and the effect of oral appliance therapy on nocturnal BP dipping was assessed., Results: Of 152 participants, 64.5% were dippers. Dippers were on average younger and less likely to be hypertensive (42 vs. 82.7%, P < 0.001). Nondippers showed greater reduction in nocturnal BP measures, related to higher BP measures at baseline. There was no difference in the relationship between treatment effectiveness and BP changes between groups. Oral appliance therapy converted only 23% of baseline non-dippers to a nocturnal dipping profile., Conclusion: Baseline circadian BP profile influenced the BP response to oral appliance therapy, largely because of higher baseline BP in the non-dipper subgroup. Oral appliance therapy did not convert OSA patients to a more favourable circadian BP profile. Further work is required to understand the effect of oral appliance therapy on circadian BP profile and of the individuals who will receive cardiovascular benefit from oral appliance therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Use of in-laboratory polysomnography (PSG) to diagnose obstructive sleep apnoea (OSA) is cost and resource intensive. Questionnaires, physical measurements and home monitors have been studied as potential simpler alternatives. This study aimed to develop a diagnostic model for OSA for use in primary care., Methods: Primary care practitioners were trained to recognize symptoms of sleep apnoea and recruited patients based on the clinical need to investigate OSA. Assessment was by symptom questionnaires, anthropomorphic measurements, digital facial photography, and a single-channel nasal flow monitor (Flow Wizard©, DiagnoseIT, Sydney, Australia) worn at home for 3 nights. The in-laboratory PSG was the reference test, with OSA defined as apnoea-hypopnoea index (AHI) ≥10 events/h., Results: In the model development phase, 25 primary care practitioners studied 315 patients in whom they suspected OSA, of which 57% had AHI≥10 and 22% had AHI≥30. Published OSA questionnaires provided low to moderate prediction of OSA (area under the curve [AUC] 0.53-0.73). The nasal flow monitor alone yielded high accuracy for predicting OSA with AUC of 0.87. Sensitivity was 0.87 and specificity 0.77 at a threshold respiratory event index (REI) of 18 events/h. A model adding age, gender, symptoms and BMI to the nasal flow monitor REI only modestly improved OSA prediction (AUC 0.89), with similar AUC (0.88) confirmed in the validation population of 114 patients., Conclusion: Sleep apnoea can be diagnosed in the primary care setting with a combination of clinical judgement and portable monitor test outcomes., (© 2021 Asian Pacific Society of Respirology.)

Study Objectives: Oral appliance (OA) therapy usage can be objectively measured through temperature-sensing data chips embedded in the appliance. Initial reports of group data for short-term treatment usage suggest good nightly hours of usage. However, individual variability in treatment usage patterns has not been assessed. We aimed to identify OA treatment usage subtypes in the first 60 days and the earliest predictors of these usage patterns., Methods: OSA patients were recruited for a study of OA therapy with an embedded compliance chip (DentiTrac, Braebon, Canada). Fifty-eight participants with 60 days of downloadable treatment usage data (5-minute readings) were analyzed. A hierarchical cluster analysis was used to group participants with similar usage patterns. A random forest classification model was used to identify the minimum number of days to predict usage subtype., Results: Three user groups were identified and named: "Consistent Users" (48.3%), "Inconsistent Users," (32.8%) and "Non-Users" (19.0%). The first 20 days provided optimal data to predict the treatment usage group a patient would belong to at 60 days (90% accuracy). The strongest predictors of user group were downloaded usage data, average wear time, and number of days missed., Conclusions: Granular analysis of OA usage data suggests the existence of treatment user subtypes (Consistent, Inconsistent, and Non-Users). Our data suggest that 60-day usage patterns can be identified in the first 20 days of treatment using downloaded treatment usage data. Understanding initial treatment usage patterns provide an opportunity for early intervention to improve long-term usage and outcomes., Citation: Sutherland K, Almeida FR, Kim T, et al. Treatment usage patterns of oral appliances for obstructive sleep apnea over the first 60 days: a cluster analysis. J Clin Sleep Med . 2021;17(9):1785-1792., (© 2021 American Academy of Sleep Medicine.)

Obstructive sleep apnea (OSA) is a highly prevalent condition, resulting in recurrent hypoxic events, sleep arousal, and daytime sleepiness. Patients with OSA are at an increased risk of cardiovascular morbidity and mortality. The mechanisms underlying the development of cardiovascular disease in OSA are multifactorial and cause a cascade of events. The primary contributing factor is sympathetic overactivity. Heart rate variability (HRV) can be used to evaluate shifts in the autonomic nervous system, during sleep and in response to treatment in patients with OSA. Newer technologies are aimed at improving HRV analysis to accelerate processing time, improve the diagnosis of OSA, and detection of cardiovascular risk. The present review will present contemporary understandings and uses for HRV, specifically in the realms of physiology, technology, and clinical management., (© 2021 European Sleep Research Society.)

Study Objectives: The impact of therapy with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) has not been directly compared in patients with severe obstructive sleep apnea (OSA). The purpose of this individual participant data meta-analysis was to compare the treatment effects of CPAP and titratable MAD on sleepiness, quality of life, sleep-disordered breathing severity, and sleep structure in patients with severe OSA., Methods: Randomized controlled trials (RCTs) that included severe OSA patients were identified in order to compare the impact of the two treatments. Individual data from severe OSA patients were extracted from the databases and pooled for analysis., Results: Of the seven studies identified, three crossover RCT and one parallel-group RCT corresponding to 151 patients and 249 observations (125 in the CPAP treatment arm and 124 in the MAD treatment arm) were included in the analysis. Titratable MAD had a similar impact to CPAP on major patient-centered outcomes (sleepiness and quality of life). CPAP was more effective in reducing AHI and ODI. However, the two treatments had a similar impact on sleep structure with an increase of N3 and REM sleep. Finally, treatment adherence and preference were largely in favor of MAD., Conclusion: This meta-analysis suggests that MAD represents an effective alternative treatment in severe OSA patients intolerant to CPAP or who prefer alternate therapy., (© 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.)

Obstructive sleep apnea (OSA) is an independent risk factor for hypertension and cardiovascular disease. Effects of OSA on the autonomic nervous system may mediate this association. We performed a systematic literature review to determine the profile of autonomic function associated with OSA. Three electronic databases were searched for studies of OSA patients aged ≥18 years in which autonomic function was assessed. Studies comparing patients with and without OSA, or examining the association of OSA severity with changes in autonomic function were included. Seventy-one studies met the inclusion criteria and autonomic function has been assessed using a range of techniques. The profile of autonomic function found in OSA include increased sympathetic activity, reduced parasympathetic activity and less consistently found low heart rate variability. Altered autonomic function in OSA may explain the pathophysiology of increased cardiovascular risk. Evidence from intervention studies is required to determine if treatment improves autonomic function associated with OSA., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Study Objectives: Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample., Methods: 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates., Results: Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009)., Conclusions: Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients., Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00003966., (© 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: Although obstructive sleep apnea (OSA) is a known risk factor for atrial fibrillation (AF), there is a paucity of data around its diagnosis and management in patients with AF. The objectives of this study were to compare the diagnostic accuracy of commonly used OSA screening tools in an AF population, including a level 3 portable sleep study device, and to examine the epidemiology of OSA in a hospital cohort with AF., Methods: One hundred seven patients with AF recruited from 2 tertiary centers underwent a panel of OSA screening tools and in-laboratory polysomnography in randomized order., Results: Oxygen desaturation index derived from a level 3 portable sleep study device performed best for moderate to severe and severe OSA, with excellent diagnostic accuracy (area under the curve, 0.899; 95% confidence interval, 0.838-0.960 and area under the curve, 0.925; 95% confidence interval, 0.859-0.991, respectively). Sixty-seven patients (62.6%) were newly diagnosed with OSA (31.8% mild, 18.7% moderate, 12.1% severe)., Conclusions: Undiagnosed OSA is highly prevalent in a hospital AF cohort. However, it is characterized by a relative paucity of symptoms, markedly limiting the usefulness of history or screening questionnaires. This is the first study to find that a level 3 home sleep study device shows excellent diagnostic accuracy in patients with AF. This finding may inform AF management guidelines., Clinical Trial Registration: Registry: Australian New Zealand Clinical Trials Registry; Name: The validity and reliability of a portable device for the diagnosis of Obstructive Sleep Apnoea in patients with Atrial Fibrillation; URL:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371024; Identifier: ACTRN12616001016426., (© 2021 American Academy of Sleep Medicine.)

Study Objectives: To investigate whether the presence of tendinous PMR could predict treatment outcome and how it affects lateral wall mechanical properties. Mandibular advancement increases the lateral dimensions of the nasopharyngeal airway via a direct connection from the airway to the ramus of the mandible. The anatomical structure in this region is the pterygomandibular raphe (PMR), but a tendinous component is not always present. Whether tendon presence influences treatment outcome is unknown., Methods: In total, 105 participants with obstructive sleep apnea completed detailed anatomical magnetic resonance imaging with and without mandibular advancement. The study design was case-control. Variables were compared between participants with and without the tendon present., Results: The amount of maximum mandibular advancement decreased when pterygomandibular tendon was present (4.0 ± 1.2 mm present versus 4.6 ± 1.4 mm absent, p = 0.04). PMR tendon-absent participants had a lower posttreatment apnea hypopnea index (16 ± 12 events/hour tendon present versus 9 ± 9 events/hour absent, p = 0.007) and were more likely to have complete response (63% versus 36%, p = 0.02). However, tendon-absent participants were more likely to not complete the study (χ 2 (3) = 10.578, p = 0.014). Tendon-absent participants had a greater increase in midline anteroposterior airway diameter (1.6 ± 1.7 mm versus 0.6 ± 2.3 mm, p = 0.04)., Conclusion: When PMR tendon is absent, treatment response and amount of maximum advancement improve, possibly at the expense of reduced splint tolerability. Tendon presence may help predict a group less likely to respond to mandibular advancement splint therapy., (© 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.)

Background: Obstructive sleep apnoea (OSA) is associated with increased blood pressure variability (BPV) and are risk factors for cardiovascular disease. We aimed to assess the comparative effects of two OSA therapies, continuous positive airway pressure (CPAP) and mandibular advancement splint (MAS), on BPV., Methods: This is a secondary analysis of data collected as part of a previously published randomised crossover trial of one month each of CPAP and MAS therapy. BPV was determined from 24-h-ambulatory blood pressure recordings in 92 patients with moderate to severe OSA at baseline and after one month of optimised treatment with each modality. BPV was assessed by three measures: Standard deviation of the mean (SD), Coefficient of variation (CoV), and the Average Real Variability (ARV) index., Results: Neither CPAP nor MAS therapy improved BPV, with no difference between treatments. BPV did not change in hypertensive OSA patients, however, there was a reduction in ARV of diastolic blood pressure in the effectively treated compared to ineffectively treated CPAP patients, Δ ARV 24-h-DBP (mmHg), -0.72 ± 2.14, 0.34 ± 1.52, P = 0.02, respectively. There was no difference between effective versus ineffective MAS treatment, Δ ARV 24-h-DBP (mmHg), -0.04 ± 2.4, 0.02 ± 1.9, P = 1.00, respectively., Conclusions: One month of optimised CPAP or MAS therapy did not improve short term BPV in patients with moderate to severe OSA. The subgroup of patients on effective CPAP showed some improvement in BPV with CPAP but not MAS. Further work on the effect of OSA therapy on BPV following long-term therapy is needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Study Objectives: Obesity is a common and reversible risk factor for obstructive sleep apnea (OSA). However, there is substantial unexplained variability in the amount of OSA improvement for any given amount of weight loss. Facial photography is a simple, inexpensive, and radiation-free method for craniofacial assessment. Our aims were (1) to determine whether facial measurements can explain OSA changes, beyond weight loss magnitude and (2) whether facial morphology relates to how effective weight loss will be for OSA improvement., Methods: We combined data from three weight loss intervention trials in which participants had standardized pre-intervention facial photography (N = 91; 70.3% male, mean ± SD weight loss 10.4 ± 9.6% with 20.5 ± 51.2% apnea-hypopnea index [AHI] reduction). Three skeletal-type craniofacial measurements (mandibular length, lower face height, and maxilla-mandible relationship angle) were assessed for relationship to AHI change following weight loss intervention., Results: Weight and AHI changes were moderately correlated (rho = 0.3, p = 0.002). In linear regression, an increased maxilla-mandible relationship angle related to AHI improvement (β [95% CI] -1.7 [-2.9, -0.5], p = 0.004). Maxilla-mandible relationship angle explained 10% in the variance in AHI over the amount predicted by weight loss amount (20%). The relationship between weight change and AHI was unaffected by the maxilla-mandible relationship angle (interaction term p > 0.05)., Conclusions: Regardless of facial morphology, weight loss is similarly moderately predictive of OSA improvement. Increased maxilla-mandible relationship angle, suggestive of retrognathia, was weakly predictive of OSA response to weight loss. Although this is unlikely to be clinically useful, exploration in other ethnic groups may be warranted., (© 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 characterize how mandibular advancement splint (MAS) alters inspiratory tongue movement in people with obstructive sleep apnea (OSA) during wakefulness and whether this is associated with MAS treatment outcome., Methods: A total of 87 untreated OSA participants (20 women, apnea-hypopnea index (AHI) 7-102 events/h, aged 19-76 years) underwent a 3T MRI with a MAS in situ. Mid-sagittal tagged images quantified inspiratory tongue movement with the mandible in a neutral position and advanced to 70% of the maximum. Movement was quantified with harmonic phase methods. Treatment outcome was determined after at least 9 weeks of therapy., Results: A total of 72 participants completed the study: 34 were responders (AHI < 5 or AHI ≤ 10events/h with >50% reduction in AHI), 9 were partial responders (>50% reduction in AHI but AHI > 10 events/h), and 29 nonresponders (change in AHI <50% and AHI ≥ 10 events/h). About 62% (45/72) of participants had minimal inspiratory tongue movement (<1 mm) in the neutral position, and this increased to 72% (52/72) after advancing the mandible. Mandibular advancement altered inspiratory tongue movement pattern for 40% (29/72) of participants. When tongue dilatory patterns altered with advancement, 80% (4/5) of those who changed to a counterproductive movement pattern (posterior movement >1 mm) were nonresponders and 71% (5/7) of those who changed to beneficial (anterior movement >1 mm) were partial or complete responders., Conclusions: The mandibular advancement action on upper airway dilator muscles differs between individuals. When mandibular advancement alters inspiratory tongue movement, therapeutic response to MAS therapy was more common among those who convert to a beneficial movement pattern., (© 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.)

Long-term effective therapy is essential for obstructive sleep apnea (OSA) control and preventing comorbidity. OSA patients are often reported to be more receptive to oral appliance therapy over positive airway pressure (PAP). Oral appliance usage can now be objectively recorded by temperature microsensors. Studies using commercially available microsensor chips have reported data out to 1 year, with high rates of adherence (>80%), albeit in small samples. There is opportunity to further use this technology to understand individual adherence factors and patterns and in obtaining objective measures of treatment effectiveness, particularly for longer-term health outcomes and allowing comparison to PAP., Competing Interests: Disclosure K. Sutherland has received in kind support from SomnoMed Australia in the form of donation of oral appliances for investigator-initiated research. P.A. Cistulli holds an endowed academic Chair at the University of Sydney, established through funding from ResMed. P.A. Cistulli has received research support from ResMed, SomnoMed, Zephyr Sleep Technologies, and Bayer. He is a consultant/adviser to Zephyr Sleep Technologies, ResMed, and SomnoMed. He has a pecuniary interest in SomnoMed related to a previous role in R&D (2004). He has received speaker fees from Nox Medical and ResMed. O. Dalci has no conflicts to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Obstructive sleep apnoea (OSA) appears common in pregnancy. Complications of pregnancy such as gestational diabetes and hypertension predispose women to cardiometabolic disease in later life. It is unknown if snoring during pregnancy is a risk marker for later-life OSA., Methods: We analysed data from N = 897 women in the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), which recruited patients attending sleep clinics at 11 sites. There were 577 cases with current OSA and 320 controls. Cases were further categorised into mild, moderate, and severe OSA based on apnoea-hypopnoea index. Retrospective self-report of snoring during pregnancy was the exposure of interest and was reported by 2.9% of cases and 3.4% of controls., Results: Multinomial regression demonstrated that snoring during a previous pregnancy was not significantly associated with mild (OR 0.34, 95% CI 0.09-1.25, p = 0.10), moderate (OR 0.69, 95% CI 0.21-2.19, p = 0.52), or severe OSA (OR 1.86, 95% CI 0.77-4.48, p = 0.17) compared to no snoring during pregnancy. Results were unchanged after adjustment for age, body mass index, and ethnicity. 79% of women reported current snoring but all who snored during pregnancy reported current snoring., Conclusions: Women who snore during pregnancy continue snoring in later-life but do not appear more likely to develop OSA. These findings are limited by self-reported data, recall bias, and small numbers of women who reported snoring during pregnancy. A prospective study with objective measurement of sleep and snoring during pregnancy is needed to examine the links between sleep disorders in pregnancy with health in later life., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Extreme phenotypes of OSA have not been systematically defined., Research Question: This study developed objective definitions of extreme phenotypes of OSA by using a multivariate approach. The utility of these definitions for identifying characteristics that confer predisposition toward or protection against OSA is shown in a new prospective sample., Study Design and Methods: In a large international sample, race-specific liability scores were calculated from a weighted logistic regression that included age, sex, and BMI. Extreme cases were defined as individuals with an apnea-hypopnea index (AHI) ≥ 30 events/hour but low likelihood of OSA based on age, sex, and BMI (liability scores > 90th percentile). Similarly, extreme controls were individuals with an AHI < 5 events/hour but high likelihood of OSA (liability scores < 10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium, and differences in photography-based craniofacial and intraoral phenotypes were evaluated., Results: This study included retrospective data from 81,338 individuals. A total of 4,168 extreme cases and 1,432 extreme controls were identified by using liability scores. Extreme cases were younger (43.1 ± 14.7 years), overweight (28.6 ± 6.8 kg/m 2 ), and predominantly female (71.1%). Extreme controls were older (53.8 ± 14.1 years), obese (34.0 ± 8.1 kg/m 2 ), and predominantly male (65.8%). These objective definitions identified 29 extreme cases and 87 extreme controls among 1,424 Sleep Apnea Global Interdisciplinary Consortium participants with photography-based phenotyping. Comparisons suggest that a greater cervicomental angle increases risk for OSA in the absence of clinical risk factors, and smaller facial widths are protective in the presence of clinical risk factors., Interpretation: This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic, and physiologic pathways to OSA., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

For almost 50 years, sleep laboratories around the world have been collecting massive amounts of polysomnographic (PSG) physiological data to diagnose sleep disorders, the majority of which are not utilized in the clinical setting. Only a small fraction of the information available within these signals is utilized to generate indices. For example, the apnea-hypopnea index (AHI) remains the primary tool for diagnostic and therapeutic decision-making for obstructive sleep apnea (OSA) despite repeated studies showing it to be inadequate in predicting clinical consequences. Today, there are many novel approaches to PSG signals, making it possible to extract more complex metrics and analyses that are potentially more clinically relevant for individual patients. However, the pathway to implement novel PSG metrics/analyses into routine clinical practice is unclear. Our goal with this review is to highlight some of the novel PSG metrics/analyses that are becoming available. We suggest that stronger academic-industry relationships would facilitate the development of state-of-the-art clinical research to establish the value of novel PSG metrics/analyses in clinical sleep medicine. Collectively, as a sleep community, it is time to reinvent how we utilize the polysomnography to move us towards Precision Sleep Medicine., Competing Interests: Conflicts of interest The following authors declare financial interests/personal relationships: Jinyoung Kim has received research support (equipment) from Cerebra. Peter A. Cistulli holds an endowed academic chair at the University of Sydney, established through funding from ResMed and is a consultant/adviser/received research support from ResMed, SomnoMed, Zephyr Sleep Technologies. He has a pecuniary interest in SomnoMed related to a previous role in R&D (2004). He has received speaker fees from Nox Medical and ResMed. Philip de Chazal holds an endowed academic chair at the University of Sydney, established through funding from ResMed and has received research support from ResMed and SpaceLabs. Kate Sutherland has received research support (equipment) from SomnoMed. The following SAGIC members (not authors) declare the following financial interests/personal relationships: Richard Schwab receives grant funding/research support from ResMed, Inspire and CryOSA. þórarinn Gislason and Bryndís Benediktsdóttir have a pecuniary interest in Nox Holding ehf and in Nox Health Inc. Nigel McArdle received research funding support from Oventus Pty Ltd, Nyxoah Pty Ltd and Zelda Therapeutics Pty Ltd., (Published by Elsevier Ltd.)

In this paper, we explored the link between sleep apnoea and cardiovascular disease (CVD) using a time-series statistical measure of sleep apnoea-related oxygen desaturation. We compared the performance of a hypoxic measure derived from the polysomnogram with the Apnoea Hypopnoea Index (AHI) in predicting CVD mortality in patients of the Sleep Heart Health Study.We estimated the relative cumulative time of SpO 2 below 90% (T r 90) using pulse oximetry signals from polysomnogram recordings as the hypoxic measure of desaturation patterns. Then, the survival curves for hypoxia quintiles were evaluated for the prediction of CVD mortality and were compared with the results using AHI for prediction. We also calculated the Cox hazard ratios for T r 90 and AHI. Our results show that the T r 90 was a better predictor of CVD mortality outcomes than AHI.

Obstructive sleep apnea (OSA) is a highly heterogeneous disorder, with diverse pathways to disease, expression of disease, susceptibility to co-morbidities and response to therapy, and is ideally suited to precision medicine approaches. Clinically, the content of the information-rich polysomnogram (PSG) is not currently fully utilized in determining patient management. Novel PSG parameters such as hypoxic burden, pulse transit time, cardiopulmonary coupling and the frequency representations of PSG sensor signals could predict a variety of cardiovascular disease, cancer and neurodegeneration co-morbidities. The PSG can also be used to identify key pathophysiological parameters such as loop gain, arousal threshold and muscle compensation which can enhance understanding of the causes of OSA in an individual, and thereby guide choices on therapy. Machine learning methods performing their own parameter extraction coupled with large PSG data sets offer an exciting opportunity for discovering new links between the PSG variables and disease outcomes. By exploiting existing and emerging analytical methods, the PSG may offer a pathway to personalized management for OSA., (© 2019 Asian Pacific Society of Respirology.)

Introduction : Obstructive sleep apnea (OSA) is a chronic condition which requires a comprehensive chronic disease management model, rather than a device-focused approach, so as to achieve the best possible health outcomes. Oral appliances are the main alternative to continuous positive airway pressure (CPAP) for the treatment of OSA. There has been an expansion of the research evidence to support the use of oral appliances in clinical practice and the clinical use of oral appliances for the treatment of OSA has become a mainstream practice. Areas covered : This review summarizes the evidence base for the use of oral appliances for the treatment of OSA. The types of oral appliances; their mechanism of action and clinical efficacy for the treatment of OSA; adverse effects, and the impact on patient acceptability and treatment adherence; and clinical effectiveness and health outcomes are discussed. Expert opinion : Personalization of treatment is vitally important in OSA and is a pre-requisite for optimizing adherence with treatment which, in turn, is a key determinant of clinical effectiveness. Treatment of OSA with mandibular advancement splints could provide an equivalent health benefit to CPAP despite not achieving a complete normalization of polysomnographic indices, mediated by differences in adherence profiles.

This critical review focuses on obstructive sleep apnea (OSA) and its management from a dental medicine perspective. OSA is characterized by ≥10-s cessation of breathing (apnea) or reduction in airflow (hypopnea) ≥5 times per hour with a drop in oxygen and/or rise in carbon dioxide. It can be associated with sleepiness and fatigue, impaired mood and cognition, cardiometabolic complications, and risk for transportation and work accidents. Although sleep apnea is diagnosed by a sleep physician, its management is interdisciplinary. The dentist's role includes 1) screening patients for OSA risk factors (e.g., retrognathia, high arched palate, enlarged tonsils or tongue, enlarged tori, high Mallampati score, poor sleep, supine sleep position, obesity, hypertension, morning headache or orofacial pain, bruxism); 2) referring to an appropriate health professional as indicated; and 3) providing oral appliance therapy followed by regular dental and sleep medical follow-up. In addition to the device features and provider expertise, anatomic, behavioral, demographic, and neurophysiologic characteristics can influence oral appliance effectiveness in managing OSA. Therefore, OSA treatment should be tailored to each patient individually. This review highlights some of the putative action mechanisms related to oral appliance effectiveness and proposes future research directions.

Purpose: Craniofacial structure is an important risk factor in the development of obstructive sleep apnoea. Most craniofacial imaging methods are not feasible for large-scale studies or the clinic. Craniofacial photography is a high-throughput technique for facial phenotyping; however, derived measurements are a composite of skeletal and soft tissue craniofacial information. Weight change is a paradigm to help determine which facial measurements most relate to regional soft tissue (i.e. change with weight) versus skeletal structure (i.e. stable with weight changes). We aimed to assess the association between weight change and changes in key facial measurements from facial photography., Methods: Calibrated frontal and profile photographs were taken of participants in weight loss studies (N = 106). Univariate linear regression was used to assess whether weight change explained changes in facial dimensions., Results: Patients lost 11.7 ± 10.8 kg body weight and 2.0 ± 2.0 cm of neck circumference. Weight changes influenced face width (r = 0.3, p < 0.001), mandibular width (r = 0.4, p < 0.001) and cervicomental angle (r = 0.3, p = 0.001). Facial angles, facial heights and mandibular length were not influenced by weight change., Conclusions: A weight loss paradigm suggests that face and mandibular width and cervicomental angle most strongly reflect regional adiposity. Facial angles and heights are insensitive to weight change and could be more representative of craniofacial skeletal structure. This study informs the interpretation of facial phenotype assessed by this craniofacial photographic method which can be applied to future studies of craniofacial phenotype in OSA.

Obstructive Sleep Apnoea (OSA) is a highly prevalent disorder across the world and is characterised by repeated obstruction of the pharyngeal airway during sleep, resulting in oxygen desaturation (intermittent hypoxia) and sleep fragmentation. As awareness of the disorder has risen over the last few decades, there is growing recognition that OSA is a highly heterogeneous disorder, and that application of a precision medicine framework to its treatment could significantly enhance patient outcomes by allowing prediction of who has OSA, who needs it treated, who is susceptible to symptoms and comorbidities, which treatment should be used and who will respond to therapy. To achieve this, there is a need to develop an understanding of intermediate OSA phenotypes in terms of their contribution to disease pathogenesis, clinical and physiological expression and treatment responses. Recently, there have been an increasing number of studies using unsupervised (cluster) analytical approaches that have generated new insights, demonstrating the viability of a precision medicine approach in sleep medicine. These advances will undoubtedly influence the emerging field of dental sleep medicine, and dentists need to be aware of these developments., (© 2019 John Wiley & Sons Ltd.)

Rationale: Oral appliance therapy is efficacious in many patients with obstructive sleep apnea (OSA), but prediction of treatment outcome is challenging. Small, detailed physiological studies have identified key OSA endotypic traits (pharyngeal collapsibility and loop gain) as determinants of greater oral appliance efficacy. Objectives: We used a clinically applicable method to estimate OSA traits from routine polysomnography and identify an endotype-based subgroup of patients expected to show superior efficacy. Methods: In 93 patients (baseline apnea-hypopnea index [AHI], ≥20 events/h), we examined whether polysomnography-estimated OSA traits (pharyngeal: collapsibility and muscle compensation; nonpharyngeal: loop gain, arousal threshold, and ventilatory response to arousal) were associated with oral appliance efficacy (percentage reduction in AHI from baseline) and could predict responses to treatment. Multivariable regression (with interactions) defined endotype-based subgroups of "predicted" responders and nonresponders (based on 50% reduction in AHI). Treatment efficacy was compared between the predicted subgroups (with cross-validation). Results: Greater oral appliance efficacy was associated with favorable nonpharyngeal traits (lower loop gain, higher arousal threshold, and lower response to arousal), moderate (nonmild, nonsevere) pharyngeal collapsibility, and weaker muscle compensation (overall R 2  = 0.30; adjusted R 2  = 0.19; P  = 0.003). Predicted responders ( n  = 54), compared with predicted nonresponders ( n  = 39), exhibited a greater reduction in AHI from baseline (mean [95% confidence interval], 73% [66-79] vs. 51% [38-61]; P  < 0.0001) and a lower treatment AHI (8 [6-11] vs. 16 [12-20] events/h; P  = 0.002). Differences persisted after adjusting for clinical covariates (including baseline AHI, body mass index, and neck circumference). Conclusions: Quantifying OSA traits using clinical polysomnography can identify an endotype-based subgroup of patients that is highly responsive to oral appliance therapy. Prospective validation is warranted.

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.)

Aim: The primary aim of this study was to assess the differences in the upper airway morphology between responders and non-responders to mandibular advancement splint (MAS) treatment in obstructive sleep apnoea (OSA) management. The secondary aim was to assess the correlation between the minimum cross-sectional area of the upper airway and the anatomical structures (i.e. mandibular external length, maxillary length, soft palate length, area of the tongue, maxillomandibular enclosure size, and anatomical balance ratio) surrounding the upper airway. The third aim was to assess the differences in the overall skeletal configuration between responders and non-responders to MAS treatment., Methods: Data from 64 patients (23 females and 41 males) diagnosed with OSA by polysomnography (PSG) at baseline and provided with an adjustable MAS were analysed. All patients had NewTom3G cone beam computed tomography (CBCT) scans, performed in the supine position, at baseline. After acclimatization to MAS, follow-up PSG tests were performed to assess the apnoea-hypopnea index (AHI) with the MAS in situ. Responders were defined by a post-treatment AHI less than 10/hour and at least 50 per cent reduction in AHI, and non-responders by a post-treatment AHI at least 10/hour or less than 50 per cent reduction in AHI. Several upper airway and anatomical variables surrounding the upper airway based on CBCT images were measured to determine the differences between responders and non-responders to MAS., Results: There were 36 responders (AHI = 24.8 ± 11.9 at baseline) and 28 non-responders (AHI = 31.2 ± 20.3 at baseline) to MAS. There were no significant differences in the upper airway morphology between responders and non-responders (P = 0.17-0.93) or in the anatomical structure surrounding the upper airway (P = 0.24-0.58)., Conclusion: Within the limitations of this study, it can be concluded that there are no significant differences in upper airway morphology and in anatomical structures surrounding the upper airway between responders and non-responders to MAS treatment. These findings suggest that the craniofacial anatomical structures analyzed in this study cannot explain the response to MAS treatment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA) is a global health issue and is associated with obesity and oropharyngeal crowding. Global data are limited on the effect of ethnicity and sex on these relationships. We compare associations between the apnea-hypopnea index (AHI) and these risk factors across ethnicities and sexes within sleep clinics., Methods: This is a cross-sectional, multicenter study of patients with OSA from eight sleep centers representing the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Four distinct ethnic groups were analyzed, using a structured questionnaire: Caucasians (Australia, Iceland, Germany, United States), African Americans (United States), Asians (Taiwan), and South Americans (Brazil). Regression analyses and interaction tests were used to assess ethnic and sex differences in relationships between AHI and anthropometric measures (body mass index [BMI], neck circumference, waist circumference) or Mallampati score., Results: Analyses included 1,585 individuals from four ethnic groups: Caucasian (60.6%), African American (17.5%), Asian (13.1%), and South American (8.9%). BMI was most strongly associated with AHI in South Americans (7.8% increase in AHI per 1 kg/m 2 increase in BMI; P < .0001) and most weakly in African Americans (1.9% increase in AHI per 1 kg/m 2 increase in BMI; P = .002). In Caucasians and South Americans, associations were stronger in males than females. Mallampati score differed between ethnicities but did not influence AHI differently across groups., Conclusions: We demonstrate ethnic and sex variations in associations between obesity and OSA. For similar BMI increases, South American patients show greatest AHI increases compared to African Americans. Findings highlight the importance of considering ethnicity and sex in clinical assessments of OSA risk., (© 2019 American Academy of Sleep Medicine.)

Purpose: Clinical methods to identify responders to oral appliance (OA) therapy for obstructive sleep apnoea (OSA) are needed. Awake nasopharyngoscopy during mandibular advancement, with image capture and subsequent processing and analysis, may predict treatment response. A qualitative assessment of awake nasopharyngoscopy would be simpler for clinical practice. We aimed to determine if a qualitative classification system of nasopharyngoscopic observations reflects treatment response., Methods: OSA patients were recruited for treatment with a customised two-piece OA. A custom scoring sheet was used to record observations of the pharyngeal airway (velopharynx, oropharynx, hypopharynx) during supine nasopharyngoscopy in response to mandibular advancement and performance of the Müller manoeuvre. Qualitative scores for degree (< 25%, 25-50%, 50-75%, > 75%), collapse pattern (concentric, anteroposterior, lateral) and diameter change (uniform, anteroposterior, lateral) were recorded. Treatment outcome was confirmed by polysomnography after a titration period of 14.6 ± 9.8 weeks. Treatment response was defined as (1) Treatment AHI < 5, (2) Treatment AHI < 10 plus > 50% AHI reduction and (3) > 50% AHI reduction., Results: Eighty OSA patients (53.8% male) underwent nasopharyngoscopy. The most common naspharyngoscopic observation with mandibular advancement was a small (< 50%) increase in velopharyngeal lateral diameter (37.5%). The majority of subjects (72.5%) were recorded as having > 75% velopharyngeal collapse on performance of the Müller manoeuvre. Mandibular advancement reduced the observed level of pharyngeal collapse at all three pharyngeal regions (p < 0.001). None of the nasopharyngoscopic qualitative scores differed between responder and non-responder groups., Conclusion: Qualitative assessment of awake nasopharyngoscopy appears useful for assessing the effect of mandibular advancement on upper airway collapsibility. However, it is not sensitive enough to predict oral appliance treatment outcome.

Study Objectives: An oral appliance (OA) is a validated treatment for obstructive sleep apnea (OSA). However, therapeutic response is not certain in any individual and is a clinical barrier to implementing this form of therapy. Therefore, accurate and clinically applicable prediction methods are needed. The goal of this study was to derive prediction models based on multiple awake assessments capturing different aspects of the pharyngeal response to mandibular advancement. We hypothesized that a multimodal model would provide robust prediction., Methods: Patients with OSA (apnea-hypopnea index [AHI] > 10 events/h) were recruited for treatment with a customized OA (n = 142, 59% male). Participants underwent facial photography (craniofacial structure), spirometry (mid-inspiratory flow at 50% vital capacity [MIF 50 ] and mid-expiratory flow at 50% vital capacity [MEF 50 ] and the ratio MEF 50 /MIF 50 ) and nasopharyngoscopy (velopharyngeal collapse with Mueller maneuver and mandibular advancement). Treatment response was defined by 3 criteria: (1) AHI < 5 events/h plus ≥ 50% reduction, (2) AHI < 10 events/h plus ≥ 50% reduction, (3) ≥ 50% AHI reduction. Multivariable regression models were used to assess predictive utility of phenotypic assessments compared to clinical characteristics alone (age, sex, obesity, baseline AHI)., Results: Craniofacial structure and flow-volume loops predicted treatment response. Accuracy of the prediction models (area under the receiver operating characteristic curve) for each criterion were 0.90 (criterion 1), 0.79 (criterion 2), and 0.78 (criterion 3). However, these prediction models including phenotypic assessments did not provide a statistically significant improvement over clinical predictors only., Conclusions: Multimodal awake phenotyping does not enhance OA treatment outcome prediction. These office-based, awake assessments have limited utility for robust clinical prediction models. Future work should focus on sleep-related assessments., Commentary: A commentary on this article appears in this issue on page 1837., Clinical Trial Registration: Registry: Australian New Zealand Clinical Trials Registry, Title: Multimodal phenotyping for the prediction of oral appliance treatment outcome in obstructive sleep apnoea, Identifier: ACTRN12611000409976, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336663., (© 2018 American Academy of Sleep Medicine.)