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Naima Laharnar,1,* Sebastian Herberger,1,* Lisa-Kristin Prochnow,1 Ning-Hung Chen,2 Peter A Cistulli,3,4 Allan I Pack,5 Richard Schwab,5 Brendan T Keenan,5 Diego R Mazzotti,5,6 Ingo Fietze,1,7 Thomas Penzel1,8 1Department of Internal Medicine and Dermatology, Interdisciplinary Center of Sleep Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Department of Pulmonary and Critical Care Medicine, Sleep Center, Chang Gung Memorial Hospital, Taipei, Taiwan; 3Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia; 4Department of Respiratory Medicine, Royal North Shore Hospital, Sydney, NSW, Australia; 5Department of Medicine/Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Internal Medicine, Division of Medical Informatics, University of Kansas Medical Center, Kansas City, KS, USA; 7The Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov, First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia; 8Department of Biology, Saratov State University, Saratov, Russia*These authors contributed equally to this workCorrespondence: Naima LaharnarDepartment of Internal Medicine and Dermatology, Interdisciplinary Center of Sleep Medicine, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Chariteplatz 1, Berlin, 10117, GermanyTel +49-30 450 513 120Email naima.laharnar@charite.dePurpose: An early prescreening in suspected obstructive sleep apnea (OSA) patients is desirable to expedite diagnosis and treatment. However, the accuracy and applicability of current prescreening tools is insufficient. We developed and tested an unbiased scoring system based solely on objective variables, which focuses on the diagnosis of severe OSA and exclusion of OSA.Patients and Methods: The OSA prediction score was developed (n = 150) and validated (n = 50) within German sleep center patients that were recruited as part of the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Six objective variables that were easy to assess and highly correlated with the apnea–hypopnea index were chosen for the score, including some known OSA risk factors: body-mass index, neck circumference, waist circumference, tongue position, male gender, and age (for women only). To test the predictive ability of the score and identify score thresholds, the receiver-operating characteristics (ROC) and curve were calculated.Results: A score ≥ 8 for predicting severe OSA resulted in an area under the ROC curve (ROC-AUC) of 90% (95% confidence interval: 84%, 95%), test accuracy of 82% (75%, 88%), sensitivity of 82% (65%, 93%), specificity of 82% (74%, 88%), and positive likelihood ratio of 4.55 (3.00, 6.90). A score ≤ 5 for predicting the absence of OSA resulted in a ROC-AUC of 89% (83%, 94%), test accuracy of 80% (73%, 86%), sensitivity of 72% (55%, 85%), specificity of 83% (75%, 89%), and positive likelihood ratio of 4.20 (2.66, 6.61). Performance characteristics were comparable in the small validation sample.Conclusion: We introduced a novel prescreening tool combining easily obtainable objective measures with predictive power and high general applicability. The proposed tool successfully predicted severe OSA (important due to its high risk of cardiovascular disease) and the exclusion of OSA (rarely a feature of previous screening instruments, but important for better differential diagnosis and treatment).Keywords: obstructive sleep apnea, diagnostic, sensitivity, specificity, screening

Rationale: The effect of obesity on upper airway soft tissue structure and size was examined in the New Zealand Obese (NZO) mouse and in a control lean mouse, the New Zealand White (NZW).Objectives: We hypothesized that the NZO mouse has increased volume of neck fat and upper airway soft tissues and decreased pharyngeal airway caliber.Methods: Pharyngeal airway size, volume of the upper airway soft tissue structures, and distribution of fat in the neck and body were measured using magnetic resonance imaging (MRI). Dynamic MRI was used to examine the differences in upper airway caliber between inspiration and expiration in NZO versus NZW mice.Measurements and Main Results: The data support the hypothesis that, in obese NZO versus lean NZW mice, airway caliber was significantly smaller (P < 0.03), with greater parapharyngeal fat pad volumes (P < 0.0001) and a greater volume of other upper airway soft tissue structures (tongue, P = 0.003; lateral pharyngeal walls, P = 0.01; soft palate, P = 0.02). Dynamic MRI showed that the airway of the obese NZO mouse dilated during inspiration, whereas in the lean NZW mouse, the upper airway was reduced in size during inspiration.Conclusions: In addition to the increased volume of pharyngeal soft tissue structures, direct fat deposits within the tongue may contribute to airway compromise in obesity. Pharyngeal airway dilation during inspiration in NZO mice compared with narrowing in NZW mice suggests that airway compromise in obese mice may lead to muscle activation to defend upper airway patency during inspiration. [ABSTRACT FROM AUTHOR]

Sleepiness plays an important role in major crashes of commercial vehicles. Because determinants are likely to include inadequate sleep and sleep apnea, we evaluated the role of short sleep durations over 1 wk at home and sleep apnea in subjective sleepiness (Epworth Sleepiness Scale), objective sleepiness (reduced sleep latency as determined by the Multiple Sleep Latency Test), and neurobehavioral functioning (lapses in performance, tracking error in Divided Attention Driving Task) in commercial drivers. Studies were conducted in 247 of 551 drivers at higher risk for apnea and in 159 of 778 drivers at lower risk. A multivariate linear association between the sets of outcomes and risk factors was confirmed (p < 0.0001). Increases in subjective sleepiness were associated with shorter sleep durations but not with increases in severity of apnea. Increases in objective sleepiness and performance lapses, as well as poorer lane tracking, were associated with shorter sleep durations. Associations with sleep apnea severity were not as robust and not strictly monotonic. A significant linear association with sleep apnea was demonstrated only for reduced sleep latency. The effects of severe apnea (apnea-hypopnea index, at least 30 episodes/h), which occurred in 4.7%, and of sleep duration less than 5 h/night, which occurred in 13.5%, were similar in terms of their impact on objective sleepiness. Thus, addressing impairment in commercial drivers requires addressing both insufficient sleep and sleep apnea, the former being more common. [ABSTRACT FROM AUTHOR]

Rationale: Sleep apnea is believed to be a genetic disorder. Thus, we hypothesized that anatomic risk factors for sleep apnea would demonstrate family aggregation.Objectives: We used volumetric magnetic resonance imaging in a sib pair "quad" design to study the family aggregation of the size of upper airway soft tissue structures that are associated with increased risk for obstructive sleep apnea.Methods: We examined 55 sleep apnea probands (apnea-hypopnea index [AHI]: 43.2 +/- 26.3 events/h), 55 proband siblings (AHI: 11.8 +/- 16.6 events/h), 55 control subjects (AHI: 2.1 +/- 1.7 events/h), and 55 control siblings (AHI: 4.2 +/- 4.0 events/h). The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for visceral neck fat and craniofacial dimensions.Measurements and Main Results: The data support our a priori hypothesis that the volume of the important upper airway soft tissue structures is heritable. The volume of the lateral pharyngeal walls (h(2) = 36.8%; p = 0.001), tongue (h(2) = 36.5%; p = 0.0001), and total soft tissue (h(2) = 37.5%; p = 0.0001) demonstrated significant levels of heritability after adjusting for sex, ethnicity, age, visceral neck fat, and craniofacial dimensions. In addition, our data indicate that heritability of the upper airway soft tissue structures is found in normal subjects and patients with apnea. Thus, it is not simply a consequence of the prevalence of apnea.Conclusions: This is the first time family aggregation of size of the upper airway soft tissue structures has been demonstrated. [ABSTRACT FROM AUTHOR]

Since the original clarification of the obstructive nature of obstructive sleep apnea (OSA) in 1965, much has been learned about the disorder. It is a condition with a high prevalence with obesity as a major risk factor. It aggregates in families, a relationship that is not simply explained by obesity. Premenopausal women are relatively protected from the disorder because OSA is uncommon in this group. Its prevalence in women rises after menopause. Although OSA is a risk factor for excessive sleepiness, there is developing evidence that it is also a risk factor for hypertension, acute cardiovascular events, and insulin resistance. The first line of therapy is nasal continuous positive airway pressure. Data as to the efficacy of continuous positive airway pressure in severe OSA have come from randomized, placebo-controlled clinical trials with the endpoints being sleepiness, quality of life, and 24-h ambulatory blood pressure. Data are currently less convincing for treatment outcomes in mild to moderate OSA, and new clinical trials to assess outcomes in this group are underway. Thus, even though this field only began toward the end of the first century of the American Thoracic Society, substantial progress has been made, and OSA has increasingly emerged as a major public health concern. [ABSTRACT FROM AUTHOR]

Unlabelled: We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.Methods: Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.Results: We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).Conclusions: Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor. [ABSTRACT FROM AUTHOR]

Excluding the presence of obstructive sleep apnea in commercial drivers is valuable, as the syndrome may increase their risk of sleepiness-related accidents. Using polysomnography as the criterion standard, we prospectively compared accuracies of five strategies in excluding the presence of severe sleep apnea and, secondarily, any sleep apnea among 406 commercial drivers. These strategies were as follows: (1) symptoms; (2) body mass index; (3) symptoms plus body mass index; (4) a two-stage approach with symptoms plus body mass index for everyone, followed by oximetry for a subset; and (5) oximetry for all. For excluding severe apnea, the two-stage strategy was highly successful, with 91% sensitivity and specificity, and a negative likelihood ratio of 0.10. This strategy was comparable in accuracy to oximetry, which had a negative likelihood ratio of 0.12, and was 88% sensitive and 95% specific. If we avoided oximetry altogether, then symptoms together with body mass index were 81% sensitive and 73% specific, with a negative likelihood ratio of 0.26. On the other hand, excluding any apnea could not be done with reasonable accuracy unless oximetry was used. We conclude that two-stage screening is likely to be a viable means of excluding severe sleep apnea among commercial drivers. [ABSTRACT FROM AUTHOR]

We used sophisticated volumetric analysis techniques with magnetic resonance imaging in a case-control design to study the upper airway soft tissue structures in 48 control subjects (apnea-hypopnea index, 2.0 +/- 1.6 events/hour) and 48 patients with sleep apnea (apnea-hypopnea index, 43.8 +/- 25.4 events/hour). Our design used exact matching on sex and ethnicity, frequency matching on age, and statistical control for craniofacial size and visceral neck fat. The data support our a priori hypotheses that the volume of the soft tissue structures surrounding the upper airway is enlarged in patients with sleep apnea and that this enlargement is a significant risk factor for sleep apnea. After covariate adjustments the volume of the lateral pharyngeal walls (p < 0.0001), tongue (p < 0.0001), and total soft tissue (p < 0.0001) was significantly larger in subjects with sleep apnea than in normal subjects. These data also demonstrated, after covariate adjustments, significantly increased risk of sleep apnea the larger the volume of the tongue, lateral pharyngeal walls, and total soft tissue: (1) total lateral pharyngeal wall (odds ratio [OR], 6.01; 95% confidence interval [CI], 2.62-17.14); (2) total tongue (OR, 4.66; 95% CI, 2.31-10.95); and (3) total soft tissue (OR, 6.95; 95% CI, 3.08-19.11). In a multivariable logistic regression analysis the volume of the tongue and lateral walls was shown to independently increase the risk of sleep apnea. [ABSTRACT FROM AUTHOR]

Detailed analysis of the upper airway has not been performed in children with obstructive sleep apnea. We used magnetic resonance imaging and automatic segmentation to delineate the upper airway in 20 children with obstructive sleep apnea and in 20 control subjects (age, 3.7 +/- 1.4 versus 3.9 +/- 1.7 years, respectively). We measured mean and minimal cross-sectional area, length, and volume of: (1) the total airway; (2) regions along the adenoid, tonsils, and where adenoid and tonsils overlap; and (3) 10 segments at 10% increments along the airway. The mean cross-sectional area of the total airway of the obstructive sleep apnea group was significantly smaller in comparison with the control group, 28.1 +/- 12.6 versus 47.1 +/- 18.2 mm2, respectively (p < 0.0005). Minimal cross-sectional area and airway volume were smaller in this group, 4.6 +/- 3.3 versus 15.7 +/- 12.7 mm2 (p < 0.0005), and 1,129 +/- 515 versus 1,794 +/- 846 mm3 (p < 0.005), respectively. Regional analysis suggested that the upper airway in children with obstructive sleep apnea is most restricted where adenoid and tonsils overlap. Segmental analysis demonstrated that the upper airway is restricted throughout the initial two-thirds of its length and that the narrowing is not in a discrete region adjacent to either the adenoid or tonsils, but rather in a continuous fashion along both. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea (OSA) is common in commercial drivers, and associated with increased risk of crashes if untreated, making diagnosis and effective treatment crucial in this population., Study Design and Methods: This is a retrospective summary of a clinical programme based on telemedicine and remote treatment monitoring developed with a national trucking company to screen new hires in the USA for OSA and implement positive airway pressure (PAP) management. New hires were informed of the programme and consented as part of their employment. Drivers who did not comply with the evaluation or with PAP after diagnosis were removed from driving commercial vehicles by the company or did not pursue further employment., Results: A total of 975 drivers were enrolled. Among screened drivers, 35.5% were cleared without a sleep study, 15.0% were cleared following a sleep study (apnoea-hypopnoea index (AHI) <5 events·h -1 ), 22.1% had mild OSA (AHI 5-15) and 27.4% had moderate-severe OSA (AHI ≥15). Those with moderate-severe OSA were more obese (body mass index 36.2±6.3 kg·m -2 ) and had more comorbidities. Of 269 drivers starting PAP, 160 (59.5%) maintained participation in a care management programme, 80 (29.7%) resigned or were terminated, 23 (8.6%) were cleared to discontinue PAP and six (2.2%) were complex cases requiring transfer of care. Illustrating effectiveness, those that maintained participation had excellent PAP adherence (5.27±1.61 h·night -1 ; 88.5±12.9% days used; 79.7±17.7% days used ≥4 h)., Interpretation: Remote assessment of OSA and PAP management in commercial drivers is feasible and effective. This approach has wide-ranging applications, particularly in populations and areas with a lack of sleep medicine providers., Competing Interests: Conflict of interest: The authors have no conflicts of interest., (Copyright ©The authors 2024.)

Study Objectives: There is limited knowledge regarding the progression or consistency of symptoms in obstructive sleep apnea (OSA) over time. Our objective was to examine the changes in symptom subtypes and identify predictors over a span of 5 years., Methods: Data of 2,643 participants of the Sleep Heart Health Study with complete baseline and 5-year follow-up visits were analyzed. Latent class analysis on 14 symptoms at baseline and follow-up determined symptom subtypes. Individuals without OSA (apnea-hypopnea index < 5) were incorporated as a known class at each time point. Multinomial logistic regression assessed the effect of age, sex, body mass index, and apnea-hypopnea index on specific class transitions., Results: The sample consisted of 1,408 females (53.8%) and mean (standard deviation) age 62.4 (10.5) years. We identified 4 OSA symptom subtypes at both baseline and follow-up visits: minimally symptomatic , disturbed sleep , moderately sleepy , and excessively sleepy . Nearly half (44.2%) of the sample transitioned to a different subtype; transitions to moderately sleepy were the most common (77% of all transitions). A 5-year older age was associated with a 50% increase in odds to transit from excessively sleepy to moderately sleepy (odds ratio [95% confidence interval]: 1.52 [1.17, 1.97]). Females had 1.97 times higher odds (95% confidence interval: 1.21, 3.18) to transition from moderately sleepy to minimal symptoms . A 5-unit increase in body mass index was associated with 2.39 greater odds (95% confidence interval: 1.30, 4.40) to transition from minimal symptoms to excessively sleepy . Changes in apnea-hypopnea index did not significantly predict any transitions., Conclusions: The symptoms of OSA may fluctuate or remain stable over time. Knowledge of symptom progression in OSA may support clinicians with treatment decisions., Citation: Morris JL, Scott PW, Magalang U, et al. Symptom subtype progression in obstructive sleep apnea over 5 years. J Clin Sleep Med . 2024;20(11):1773-1783., (© 2024 American Academy of Sleep Medicine.)

Idiopathic hypersomnia (IH) is a poorly-understood sleep disorder characterized by excessive daytime sleepiness despite normal nighttime sleep. Combining human genomics with behavioral and mechanistic studies in fish and flies, we uncover a role for beat-Ia/CADM2 , synaptic adhesion molecules of the immunoglobulin superfamily, in excessive sleepiness. Neuronal knockdown of Drosophila beat-Ia results in sleepy flies and loss of the vertebrate ortholog of beat-Ia , CADM2 , results in sleepy fish. We delineate a developmental function for beat-Ia in synaptic elaboration of neuropeptide F (NPF) neurites projecting to the suboesophageal zone (SEZ) of the fly brain. Brain connectome and experimental evidence demonstrate these NPF outputs synapse onto a subpopulation of SEZ GABAergic neurons to stabilize arousal. NPF is the Drosophila homolog of vertebrate neuropeptide Y (NPY), and an NPY receptor agonist restores sleep to normal levels in zebrafish lacking CADM2 . These findings point towards NPY modulation as a treatment target for human hypersomnia.

Although genome-wide association studies (GWAS) have identified loci for sleep-related traits, they do not directly uncover the underlying causal variants and corresponding effector genes. The majority of such variants reside in non-coding regions and are therefore presumed to impact cis-regulatory elements. Our previously reported 'variant-to-gene mapping' effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in both Drosophila and zebrafish, implicated phosphatidyl inositol glycan (PIG)-Q as a functionally relevant gene at the insomnia "WDR90" GWAS locus. However, importantly that effort did not characterize the corresponding underlying causal variant. Specifically, our previous 3D genomic datasets nominated a shortlist of three neighboring single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium within an intronic enhancer region of WDR90 that contacted the open PIG-Q promoter. We sought to investigate the influence of these SNPs collectively and then individually on PIG-Q modulation to pinpoint the causal "regulatory" variant. Starting with gross level perturbation, deletion of the entire region in NPCs via CRISPR-Cas9 editing and subsequent RNA sequencing revealed expression changes in specific PIG-Q transcripts. Results from individual luciferase reporter assays for each SNP in iPSCs revealed that the region with the rs3752495 risk allele (RA) induced a ~2.5-fold increase in luciferase expression. Importantly, rs3752495 also exhibited an allele-specific effect, with the RA increasing the luciferase expression by ~2-fold versus the non-RA. In conclusion, our variant-to-function approach and in vitro validation implicate rs3752495 as a causal insomnia variant embedded within WDR90 while modulating the expression of the distally located PIG-Q., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sleep is an essential behavior that is still poorly understood. Sleep abnormalities accompany a variety of psychiatric and neurological disorders, and sleep can serve as a modifiable behavior in the treatment of these disorders. Zebrafish ( Danio rerio ) has proven to be a powerful model organism to study sleep and the interplay between sleep and these disorders due to the high conservation of the neuro-modulatory mechanisms that control sleep and wake states between zebrafish and humans. The zebrafish is a diurnal vertebrate with a relatively simple nervous system compared to mammalian models, exhibiting conservation of sleep ontogeny across different life stages. Zebrafish larvae are an established high-throughput model to assess sleep phenotypes and the biological underpinnings of sleep disturbances. To date, sleep measurement in juvenile and adult zebrafish has not been performed in a standardized and reproducible manner because of the relatively low-throughput nature in relation to their larval counterparts. This has left a gap in understanding sleep across later stages of life that are relevant to many psychiatric and neurodegenerative disorders. Several research groups have used homemade systems to address this gap. Here, we report employing commercially available equipment to track activity and sleep/wake patterns in juvenile and adult zebrafish. The equipment allows researchers to perform automated behavior assays in an isolated environment with light/dark and temperature control for multiple days. We first explain the experimental procedure to track the sleep and activity of adult zebrafish and then validate the protocol by measuring the effects of melatonin and DMSO administration. Key features • Allows an isolated and controllable environment to carry out activity and sleep assays in juvenile and adult zebrafish. • Measures activity of zebrafish in life stages later than early development, which requires feeding animals during the assay. • Requires use of a commercially available equipment system and six tanks. • The activity of zebrafish can be tracked for five days including an acclimation step., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Purpose: Previous studies assessed different components of telemedicine management pathway for OSA instead of the whole pathway. This randomized, controlled, and non-inferiority trial aimed to assess whether telemedicine management is clinically inferior to in-person care in China., Methods: Adults suspected of OSA were randomized to telemedicine (web-based questionnaires, self-administered home sleep apnea test [HSAT], automatically adjusting positive airway pressure [APAP], and video-conference visits) or in-person management (paper questionnaires, in-person HSAT set-up, APAP, and face-to-face visits). Participants with an apnea-hypopnea index (AHI) ≥ 15 events/hour received APAP for 3 months. The non-inferiority analysis was based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score and APAP adherence. Cost-effectiveness analysis was performed., Results: In the modified intent-to-treat analysis set (n = 111 telemedicine, 111 in-person), FOSQ scores improved 1.73 (95% confidence interval [CI], 1.31-2.14) points with telemedicine and 2.05 (1.64-2.46) points with in-person care. The lower bound of the one-sided 95% non-inferiority CI for the difference in change between groups of - 0.812 was larger than the non-inferiority threshold of - 1. APAP adherence at 3 months was 243.3 (223.1-263.5) minutes/night for telemedicine and 241.6 (221.3-261.8) minutes/night for in-person care. The lower bound of the one-sided 95% non-inferiority CI of - 22.2 min/night was higher than the non-inferiority delta of - 45 min/night. Telemedicine had lower total costs than in-person management (CNY 1482.7 ± 377.2 vs. 1912.6 ± 681.3; p < 0.0001), driven by patient costs, but no significant difference in QALYs., Conclusions: Functional outcomes and adherence were not clinically inferior in patients managed by a comprehensive telemedicine approach compared to those receiving in-person care in China., Clinical Trial Registration: https://www.chictr.org.cn , Registration number ChiCTR2000030546. Retrospectively registered on March 06, 2020., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation., Competing Interests: Declaration of interests B.C.R. receives funding from Novo Nordisk and Boehringer Ingelheim that was not utilized for this project., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA., Methods: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy ≥ 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy.", Results: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) ≥ 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO2], time spent < 90% SpO2, and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders., Conclusions: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: The objectives of this study were to understand the relative comorbidity burden of obstructive sleep apnea (OSA), determine whether these relationships were modified by sex or age, and identify patient subtypes defined by common comorbidities., Methods: Cases with OSA and noncases (controls) were defined using a validated electronic health record (EHR)-based phenotype and matched for age, sex, and time period of follow-up in the EHR. We compared prevalence of the 20 most common comorbidities between matched cases and controls using conditional logistic regression with and without controlling for body mass index. Latent class analysis was used to identify subtypes of OSA cases defined by combinations of these comorbidities., Results: In total, 60,586 OSA cases were matched to 60,586 controls (from 1,226,755 total controls). Patients with OSA were more likely to have each of the 20 most common comorbidities compared with controls, with odds ratios ranging from 3.1 to 30.8 in the full matched set and 1.3 to 10.2 after body mass index adjustment. Associations between OSA and these comorbidities were generally stronger in females and patients with younger age at diagnosis. We identified 5 distinct subgroups based on EHR-defined comorbidities: High Comorbidity Burden, Low Comorbidity Burden, Cardiovascular Comorbidities, Inflammatory Conditions and Less Obesity, and Inflammatory Conditions and Obesity., Conclusions: Our study demonstrates the power of leveraging the EHR to understand the relative health burden of OSA, as well as heterogeneity in these relationships based on age and sex. In addition to enrichment for comorbidities, we identified 5 novel OSA subtypes defined by combinations of comorbidities in the EHR, which may be informative for understanding disease outcomes and improving prevention and clinical care. Overall, this study adds more evidence that OSA is heterogeneous and requires personalized management., Citation: Te TT, Keenan BT, Veatch OJ, Boland MR, Hubbard RA, Pack AI. Identifying clusters of patient comorbidities associated with obstructive sleep apnea using electronic health records. J Clin Sleep Med . 2024;20(4):521-533., (© 2024 American Academy of Sleep Medicine.)

Aim: To assess respiratory symptoms and nocturnal gastro-oesophageal reflux (nGER) among untreated obstructive sleep apnoea (OSA) patients, compared with the general population. Also, if nGER associates differently with respiratory symptoms among OSA patients., Methods: 2 study cohorts were included: 822 newly diagnosed subjects with moderate-severe OSA and 738 Icelandic general population study participants. All participants answered the same questionnaires. Those reporting nGER symptoms at least once per week were defined as 'with nGER'; those without nGER symptoms and without nGER medication were defined as 'no nGER'; and other participants were defined as having 'possible nGER'. Propensity score-based weights were used to minimise confounding and selection bias and facilitate causal interpretations., Results: The prevalence of nGER among OSA patients was 14.1%, compared with 5.8% in the general population. This increased prevalence in OSA was not explained by differences in age, gender, body mass index, smoking, hypertension and diabetes (adjusted OR (95% CI)=3.79 (2.24 to 6.43)). OSA patients 'with nGER' and with 'possible nGER' reported more wheezing (44% and 44% vs 25%, respectively) and productive cough (47% and 42% vs 29%, respectively), compared with OSA patients with 'no nGER'. The same pattern was seen in the general population, although with a generally lower prevalence. The effect of nGER on respiratory symptoms was similar between the two cohorts., Conclusion: nGER was more often reported among untreated moderate-severe OSA patients than in the general population. Participants with nGER had more wheezing and productive cough, both among untreated OSA patients and in the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objectives: This study aimed to evaluate and compare measurements of standardized craniofacial and intraoral photographs between clinical and general population samples, between groups of individuals with an apnea-hypopnea index (AHI) ≥ 15 and AHI < 15, and their interaction, as well as the relationship with the presence and severity of obstructive sleep apnea (OSA)., Methods: We used data from 929 participants from Sleep Apnea Global Interdisciplinary Consortium, in which 309 patients from a clinical setting and 620 volunteers from a general population., Results: AHI ≥ 15 were observed in 30.3% of the total sample and there were some interactions between facial/intraoral measures with OSA and both samples. Mandibular volume (p < 0.01) and lateral face height (p = 0.04) were higher in the AHI ≥ 15 group in the clinical sample compared to the AHI ≥ 15 group in the general population and AHI < 15 group in the clinical sample. When adjusted for sex and age, greater mandible width (p < 0.01) differed both in the clinical and in the general population samples, reflecting AHI severity and the likelihood of OSA. The measure of smaller tongue curvature (p < 0.01) reflected the severity and probability of OSA in the clinical sample and the higher posterior mandibular height (p = 0.04) showed a relationship with higher AHI and higher risk of OSA in the general population. When adjusted for sex, age, and body mass index, only smaller tongue curvature (p < 0.01) was associated with moderate/severe OSA., Conclusions: Measures of greater tongue and mandible were associated with increased OSA risk in the clinical sample and craniofacial measurement was associated in the general population sample., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This multisociety commentary critically examines the Agency for Healthcare Research and Quality (AHRQ) final report and systematic review on long-term health outcomes in obstructive sleep apnea. The AHRQ report was commissioned by the Centers for Medicare & Medicaid Services and particularly focused on the long-term patient-centered outcomes of continuous positive airway pressure, the variability of sleep-disordered breathing metrics, and the validity of these metrics as surrogate outcomes. This commentary raises concerns regarding the AHRQ report conclusions and their potential implications for policy decisions. A major concern expressed in this commentary is that the AHRQ report inadequately acknowledges the benefits of continuous positive airway pressure for several established, long-term clinically important outcomes including excessive sleepiness, motor vehicle accidents, and blood pressure. While acknowledging the limited evidence for the long-term benefits of continuous positive airway pressure treatment, especially cardiovascular outcomes, as summarized by the AHRQ report, this commentary reviews the limitations of recent randomized controlled trials and nonrandomized controlled studies and the challenges of conducting future randomized controlled trials. A research agenda to address these challenges is proposed including study designs that may include both high quality randomized controlled trials and nonrandomized controlled studies. This commentary concludes by highlighting implications for the safety and quality of life for the millions of people living with obstructive sleep apnea if the AHRQ report alone was used by payers to limit coverage for the treatment of obstructive sleep apnea while not considering the totality of available evidence., Citation: Patil SP, Billings ME, Bourjeily G, et al. Long-term health outcomes for patients with obstructive sleep apnea: placing the Agency for Healthcare Research and Quality report in context-a multisociety commentary. J Clin Sleep Med . 2024;20(1):135-149., (© 2024 American Academy of Sleep Medicine.)

Healthy sleep is essential for physical and mental health, and social wellbeing; however, across the globe, and particularly in developing countries, national public health agendas rarely consider sleep health. Sleep should be promoted as an essential pillar of health, equivalent to nutrition and physical activity. To improve sleep health across the globe, a focus on education and awareness, research, and targeted public health policies are needed. We recommend developing sleep health educational programmes and awareness campaigns; increasing, standardising, and centralising data on sleep quantity and quality in every country across the globe; and developing and implementing sleep health policies across sectors of society. Efforts are needed to ensure equity and inclusivity for all people, particularly those who are most socially and economically vulnerable, and historically excluded., Competing Interests: Declaration of interests DCL serves on the scientific advisory board for Apnimed. CMM has received research grants from Eisai, Idorsia, and Lallemand Health; and is a scientific advisory board member and consultant for Eisai and Idorsia. VKS is a consultant for Jazz, Apnimed, Bayer, Lilly, Zoll, and Huxley; and is a scientific advisory board member for Sleep Number. PCZ is a consultant for Eisai, Idorsia, Harmony Bioscience, Jazz, Sleep Number, and CVS Caremark; and serves as President of the World Sleep Society. PRE is a consultant for Invicta Medical. All other authors declare no competing interests., (Copyright © 2023 Copyright © Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aim: To study the effect of positive airway pressure (PAP) treatment on nocturnal gastro-oesophageal reflux (nGOR) and respiratory symptoms among clinical obstructive sleep apnoea (OSA) patients., Methods: 822 patients newly diagnosed with OSA referred for PAP treatment were recruited. 732 patients had a 2-year follow-up visit with continuous PAP compliance data (366 full PAP users, 366 partial/non-PAP users). They answered questionnaires, including reporting of nGOR, sleep and respiratory symptoms and general health. Patients with nGOR symptoms once a week or more were defined as "with nGOR". Those without nGOR symptoms and nGOR medication were defined as "no nGOR". Others were defined as "possible nGOR"., Results: At 2-year follow-up, PAP treatment among full users resulted in decreased nGOR (adjusted OR 0.58, 95% CI 0.40-0.86) and wheezing (adjusted OR 0.56, 95% CI 0.35-0.88) compared with partial/non-PAP users. Decreased nGOR, among both full and partial/non-users of PAP treatment, was associated with a decrease in productive morning cough (adjusted OR 4.70, 95% CI 2.22-9.99) and a decrease in chronic bronchitis (adjusted OR 3.86, 95% CI 1.74-8.58), but not decreased wheezing (adjusted OR 0.90, 95% CI 0.39-2.08). A mediation analysis found that PAP treatment directly led to a decrease in wheezing, not mediated through nGOR. Conversely, PAP treatment decreased productive cough mediated through a decrease in nGOR., Conclusion: In an unselected group of OSA patients, PAP treatment for 2 years was associated with a decrease in nGOR and respiratory symptoms. The PAP treatment itself was associated with less wheezing. A decrease in nGOR through PAP treatment was associated with a decrease in productive cough., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Sleep apnea is heterogeneous in multiple dimensions. There are different physiological risk factors that may have clinical relevance. However, assessing them is challenging. An approach to ascertain them using a simple model of ventilatory control has been proposed. It is based, however, on untenable assumptions. There are limited validation data and reproducibility is not stellar. There are also different symptom subtypes. They have been found in multiple population-based and clinical cohorts worldwide. Symptomatic benefit from therapy is most marked in the excessively sleepy subtype. This group may also be the group at increased CV risk from obstructive sleep apnea., (Copyright © 2023 Elsevier Inc. All rights reserved.)