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Abstract Craniofacial modification by orthodontic techniques is increasingly incorporated into the multidisciplinary management of sleep-disordered breathing in children and adolescents. With increasing application of orthodontics to this clinical population it is important for healthcare providers, families, and patients to understand the wide range of available treatments. Orthodontists can guide craniofacial growth depending on age; therefore, it is important to work with other providers for a team-based approach to sleep-disordered breathing. From infancy to adulthood the dentition and craniofacial complex change with growth patterns that can be intercepted and targeted at critical time points. This article proposes a clinical guideline for application of multidisciplinary care with emphasis on dentofacial interventions that target variable growth patterns. We also highlight how these guidelines serve as a roadmap for the key questions that will influence future research directions. Ultimately the appropriate application of these orthodontic techniques will not only provide an important therapeutic option for children and adolescents with symptomatic sleep-disordered breathing but may help also mitigate or prevent its onset. Graphical abstract Graphical Abstract

Objectives To investigate whether the OSA‐18 questionnaire and a postoperative patient‐reported outcome measure (PROM) question correlated with polysomnography (PSG) data. Methods A prospective study of otherwise healthy young children with moderate to severe obstructive sleep apnea (OSA) to investigate if the obstructive apnea–hypopnea index (OAHI) before and 6–12 months after adenotonsil surgery correlated with the OSA‐18 total symptom score (TSS) and the sleep disturbance subscale (SDS), as well as a PROM question on symptom improvement with responses on a 4‐grade Likert scale. Results Of 201 children, 173 (86%) had complete data of OAHI and OSA‐18 pre‐ and postoperatively. The mean age was 3.2 years (SD 1.0) and the mean OAHI was 15.9 (11.3). Significant correlations between changes in the OAHI and OSA‐18 were found, both TSS (r = 0.29, p < .001) and SDS (r = 0.53, p < .001). A total of 136 (68%) patients responded to the PROM question, the majority of whose symptoms had disappeared (n = 102) or almost disappeared (n = 30). Four patients had unchanged symptoms, and none had worsening symptoms. A correlation was found between the PROM question and a change in the OAHI (r = 0.36, p < .001), as well as a change in the OSA‐18 TSS (r = 0.24, p = .006) and the SDS (r = 0.34, p < .001). The specificity of the PROM question for prediction of a postoperative OAHI < 2 was 82%, and the sensitivity was 38%. Conclusion Changes in the OAHI significantly correlated with changes in the OSA‐18, especially with the sleep disturbance scale, which could be an alternative for evaluation at follow‐ups. Level of Evidence 3 The correlation between objective and subjective outcomes after adenotonsillar surgery in young children with moderate to severe obstructive sleep apnea showed a moderate correlation between polysomnographic changes and a sleep disturbance subscale change in the OSA‐18.

Abstract 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.

Abstract 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.

Abstract Study Objectives To examine the association between maternal sleep disordered breathing (SDB) and glucose metabolism in early gestation. Methods Women with body mass index (BMI) ≥27 kg/m2 and singleton pregnancies underwent in-home sleep study (HSAT) and homeostatic model assessment (HOMA) in early pregnancy. Insulin resistance (HOMA-IR) and β-cell function (HOMA %B) were derived. Exclusion criteria included pregestational diabetes, use of continuous positive airway pressure and chronic steroid therapy. We performed linear regression analyses to evaluate the association between continuous measures of SDB (respiratory event index (REI), and oxygen desaturation index (ODI)) and glucose metabolism parameters (HOMA-IR and HOMA %B). Analyses were adjusted for a set of a priori selected variables which included gestational age, maternal age, BMI, ethnicity, race, and parity. Results One hundred and ninety-two pregnant women with median (interquartile range) BMI of 35.14 (8.30) kg/m2 underwent HSAT and HOMA assessment at 11.14 (3) and 15.35 (4.14) gestational weeks, respectively. REI and ODI, as continuous values, were associated with HOMA-IR after adjusting for covariates. OSA (obstructive sleep apnea) diagnosis (REI > 5 events per hour) was not associated with HOMA-IR after adjusting for BMI (p ≥ 0.05). None of the parameters were associated with HOMA %B (p > 0.07). Conclusions SDB and insulin resistance are associated in early pregnancy, with a dose response association between respiratory event index severity and insulin resistance. Further studies are needed to establish if pregnant women with overweight and obesity may benefit from early SDB screening to improve glucose metabolic outcome. Clinical trials: NCT02412696, Positive Airway Pressure, Sleep Apnea, and the Placenta (PAP-SAP) https://clinicaltrials.gov/ct2/show/NCT02412696?term=Bourjeily&draw=2&rank=2 and NCT02917876, Predictors of De-novo Development of Obstructive Sleep Apnea in Pregnancy (Predictors) https://clinicaltrials.gov/ct2/show/NCT02917876?term=Bourjeily&draw=2&rank=1

Abstract 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. Graphical Abstract Graphical Abstract

Background Brachycephalic dogs display sleep‐disordered breathing (SDB). The risk factors for SDB remain unknown. Objectives To identify risk factors for SDB. We hypothesized that brachycephaly, increasing severity of brachycephalic obstructive airway syndrome (BOAS), excess weight, and aging predispose to SDB. Animals Sixty‐three privately owned pet dogs were prospectively recruited: 28 brachycephalic and 35 normocephalic (mesaticephalic or dolicocephalic) dogs. Methods Prospective observational cross‐sectional study with convenience sampling. Recording with the neckband was done over 1 night at each dog's home. The primary outcome measure was the obstructive respiratory event index (OREI). Body condition score (BCS) was assessed, and BOAS severity was graded for brachycephalic dogs. Results Brachycephaly was a significant risk factor for high OREI value (ratio of the geometric means 5.6, 95% confidence interval [CI] 3.2‐9.9; P < .001) but aging was not (1.1, 95% CI 1.0‐1.2; P = .2). Excess weight, defined as a BCS of over 5/9, (3.5, 95% CI 1.8‐6.7; P < .001) was a significant risk factor. In brachycephalic dogs, BOAS‐positive class (moderate or severe BOAS signs) was a significant risk factor (2.5, 95% CI 1.1‐5.6; P = .03). Conclusions and Clinical Importance Brachycephaly decreases welfare in a multitude of ways, including disrupting sleep. Brachycephaly, increasing severity of BOAS and excess weight are risk factors for obstructive SDB.

Abstract 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 Graphical Abstract Graphical Abstract

Sleep problems and inadequate physical activity (PA) are associated with numerous adverse health outcomes. Most studies explored the influence of PA on sleep, but how sleep affects engagement in PA across adulthood remains less well investigated. This study examined the association between sleep traits and PA reported the following year in 51,247 Swedish women and men (55–93 years), who completed questionnaires regarding their sleep, PA, and other characteristics. Health status was assessed with data from the Swedish National Patient Registry. Odds ratios and 95% confidence intervals were estimated by binary logistic regression. In multivariable analysis, long sleep duration (≥ 9 h/night), sleep disturbance, and symptoms of sleep-disordered breathing (SDB) were associated with lower odds of engaging in walking or cycling, and exercising the following year. In addition, short sleep duration (< 7 h/night), sleep disturbance, and symptoms of SDB were linked to sedentary behavior (time spent on reading or watching TV). Several sex- and age-specific associations were observed. In addition to previous evidence of a positive effect of PA on sleep, our findings indicate that poor sleep may contribute to lower engagement in PA and a higher level of sedentary behavior, highlighting the bidirectional nature of the relationship between PA and sleep.

A negative intrathoracic pressure threshold is one commonly proposed mechanism for triggering respiratory-induced arousals in obstructive sleep apnea (OSA). If so, they should occur during inspiration, shortly after maximal negative pressure swings. Alternatively, respiratory-induced arousals may occur throughout the respiratory cycle if other mechanisms also contribute. However, arousal timing has been minimally investigated. This study aimed to (1) determine the temporal relationship between respiratory-induced arousals and breathing phase and (2) characterize neuromuscular and load compensation responses prior to arousal. Fifty-one CPAP-treated OSA patients underwent a sleep physiology study with genioglossus and tensor palatini EMG, nasal mask/pneumotachograph, and epiglottic pressure. Transient CPAP reductions were delivered to induce respiratory-related arousals. Of 354 arousals, 65(60-70)%[mean(CI)] occurred during inspiration, 35(30-40)% during expiration. Nadir epiglottic pressure occurred 68(66-69)% into inspiration while inspiratory arousals had a uniform distribution throughout inspiration. Expiratory arousals occurred predominantly in early expiration. CPAP reductions initially reduced minute ventilation by ~2.5 liter/min, which was restored immediately prior to expiratory but not inspiratory arousals. Duty cycle just prior to arousal was greater for inspiratory versus expiratory arousals [0.20(0.18-0.21) vs. 0.13(0.11-0.15)Δbaseline, p = 0.001]. Peak tensor palatini EMG was higher for expiratory versus inspiratory arousals during prearousal breaths [7.6(5.8-9.6) vs. 3.7(3.0-4.5)%Δbaseline, p = 0.001], whereas genioglossus and tonic tensor palatini EMG were similar between arousal types. Over one third of respiratory-induced arousals occur during expiration. These findings highlight the importance of nonpressure threshold mechanisms of respiratory-induced arousals in OSA and suggest that expiratory arousals may be a novel marker of enhanced tensor palatini neuromuscular compensation.