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PURPOSE: To examine factors accounting for differences in hyoid motion during obstructive breathing events amongst obstructive sleep apnea (OSA) patients. METHODS: This was a prospective cohort study from June 2022 to October 2022. Patients with OSA undergoing evaluation for PAP alternative therapies with drug-induced sleep endoscopy with positive airway pressure titration (DISE-PAP). All patients underwent DISE-PAP and concurrent hyoid-focused ultrasound. DISE-PAP enabled measurement of airway physiology (flow, respiratory effort) and airway collapsibility (pharyngeal opening pressure, PhOP). Hyoid-ultrasound enabled hyoid bone movement during obstructive breathing. Respiratory effort was measured using a retro-epiglottic pressure-sensitive catheter. Hyoid position was measured using a standardized, awake, CT protocol. Regression analyses adjusted for age, race, sex, and BMI were performed to associate indices of respiratory effort and CT data with hyoid motion. RESULTS: On average, the 26 patients in this cohort were older (63.9 ± 10.5 years), male (69%), overweight (29.6 ± 3.99 kg/m2), and with moderate-to-severe OSA (26.8 ± 10.4 events/hour). Greater respiratory effort was associated with increased hyoid motion (ß [95% CI] = 0.034 [0.016,0.052], standardized ß = 0.261,p = 0.0003). Higher hyoid position was associated with greater hyoid displacement (ß [95% CI] = -0.20 [-0.38,-0.01], Standardized ß = -0.57, p = 0.036). CONCLUSION: Our data demonstrate that greater respiratory effort, higher hyoid position, and higher airway collapsibility, but not airflow, are associated with greater hyoid motion during obstructive breathing in DISE. These findings suggest that downward hyoid movement represents a compensatory response to upper airway obstruction. Further studies should investigate the vectors of hyoid motion to better understand its role in sleep-related airway collapse.
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STUDY OBJECTIVES: There is limited knowledge regarding the progression or consistency of symptoms in 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 (AHI<5) were incorporated as a known class at each time point. Multinomial logistic regression assessed the effect of age, sex, body mass index (BMI) and AHI on specific class transitions. RESULTS: The sample consisted of 1,408 women (53.8%) and mean (SD) age 62.4 (10.5) years. We identified four 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 five-year older age was associated with a 50% increase in odds to transit from excessively sleepy to moderately sleepy [OR (95% CI: 1.52 (1.17, 1.97)]. Women had 1.97 times higher odds (95% CI: 1.21, 3.18) to transition from moderately sleepy to minimal symptoms. A 5-unit increase in BMI was associated with 2.39 greater odds (95% CI: 1.30, 4.40) to transition from minimal symptoms to excessively sleepy. Changes in AHI 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.
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OBJECTIVE: There are disparities between Black and White patients in the utilization of positive airway pressure (PAP) alternatives for obstructive sleep apnea (OSA). Given low utilization rates among Black patients, there is limited knowledge of PAP alternative outcomes in this group. Therapeutic PAP levels are clinically accessible measures that have been shown to predict PAP alternative outcomes. Herein, we examined differences in PAP requirements between Black and White patients in a large clinical sample. STUDY DESIGN: Cross-sectional. SETTING: Academic sleep center. METHODS: We included OSA patients prescribed autoadjusting PAP between January 2018 and 2020 with baseline apnea-hypopnea index (AHI) ≥ 10. Mean and 90th percentile PAP levels were compared between White and Black patients who used PAP for ≥1 hour daily using linear regression controlling for age, sex, body mass index (BMI), AHI, oxygen saturation nadir, and mask type. RESULTS: There were 157 Black and 234 White patients who were generally obese (BMI, 37.3 ± 8.7) with severe OSA (AHI, 36.9 ± 25.6). Black patients had a 0.68 cm higher (95% confidence interval [CI]: 0.36, 1.35) mean PAP level and 0.85 cm H2O higher (95% CI: 0.36, 1.35) 90th percentile PAP level than white patients. Although statistically significant, differences were small and not clinically meaningful. CONCLUSION: Black and White OSA patients had clinically insignificant differences in PAP requirements, suggesting comparable upper airway collapsibility. Considering the predictive value of therapeutic PAP levels, our findings suggest Black and White patients may have comparable PAP alternative responses from a collapsibility standpoint. Future studies should explore reasons for low utilization of PAP alternatives among Black patients.
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Background: Autism spectrum disorder (ASD) is a highly heritable and heterogeneous neurodevelopmental disorder characterized by impaired social interactions, repetitive behaviors, and a wide range of comorbidities. Between 44-83% of autistic individuals report sleep disturbances, which may share an underlying neurodevelopmental basis with ASD. Methods: We recruited 382 ASD individuals and 223 of their family members to obtain quantitative ASD-related traits and wearable device-based accelerometer data spanning three consecutive weeks. An unbiased approach identifying traits associated with ASD was achieved by applying the elastic net machine learning algorithm with five-fold cross-validation on 6,878 days of data. The relationship between sleep and physical activity traits was examined through linear mixed-effects regressions using each night of data. Results: This analysis yielded 59 out of 242 actimetry measures associated with ASD status in the training set, which were validated in a test set (AUC: 0.777). For several of these traits (e.g. total light physical activity), the day-to-day variability, in addition to the mean, was associated with ASD. Individuals with ASD were found to have a stronger correlation between physical activity and sleep, where less physical activity decreased their sleep more significantly than that of their non-ASD relatives. Conclusions: The average duration of sleep/physical activity and the variation in the average duration of sleep/physical activity strongly predict ASD status. Physical activity measures were correlated with sleep quality, traits, and regularity, with ASD individuals having stronger correlations. Interventional studies are warranted to investigate whether improvements in both sleep and increased physical activity may improve the core symptoms of ASD.
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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.
Subject(s)
Galanin , Neurons , Preoptic Area , Sleep Deprivation , Animals , Galanin/metabolism , Galanin/genetics , Neurons/metabolism , Preoptic Area/metabolism , Mice , Sleep Deprivation/metabolism , Sleep Deprivation/genetics , Male , RNA-Seq , Mice, Inbred C57BL , Sleep/genetics , Sleep/physiology , Single-Cell AnalysisABSTRACT
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels generate electrical rhythmicity in various tissues although primarily heart, retina and brain. The HCN channel blocker compound, Ivabradine (Corlanor), is approved by the US Food and Drug Administration (FDA) as a medication to lower heart rate by blocking hyperpolarization activated inward current in the sinoatrial node. In addition, a growing body of evidence suggests a role for HCN channels in regulation of sleep/wake behavior. Zebrafish larvae are ideal model organisms for high throughput drug screening, drug repurposing and behavioral phenotyping studies. We leveraged this model system to investigate effects of three HCN channel blockers (Ivabradine, Zatebradine Hydrochloride and ZD7288) at multiple doses on sleep/wake behavior in wild type zebrafish. Results of interest included shorter latency to daytime sleep at 0.1 µM dose of Ivabradine (ANOVA, p: 0.02), moderate reduction in average activity at 30 µM dose of Zatebradine Hydrochloride (ANOVA, p: 0.024) in daytime, and increased nighttime sleep at 4.5 µM dose of ZD7288 (ANOVA, p: 0.036). Taken together, shorter latency to daytime sleep, decrease in daytime activity and increased nighttime sleep indicate that different HCN channel antagonists affected different parameters of sleep and activity.
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OBJECTIVE: Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility. STUDY DESIGN: Cross-sectional analysis from a prospective cohort. SETTING: Academic medical center. METHODS: Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, PcritA) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either PcritA or PhOP. RESULTS: One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m2), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or PcritA, but a larger tongue was associated with more positive PhOP (â´ = 0.20, P = .02), and more positive PcritA (â´ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures. CONCLUSION: After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis.
Subject(s)
Endoscopy , Palate, Soft , Pharynx , Sleep Apnea, Obstructive , Tomography, X-Ray Computed , Tongue , Humans , Male , Female , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/diagnostic imaging , Middle Aged , Cross-Sectional Studies , Prospective Studies , Palate, Soft/diagnostic imaging , Palate, Soft/physiopathology , Pharynx/diagnostic imaging , Pharynx/physiopathology , Tongue/diagnostic imaging , Tongue/physiopathology , Adult , Polysomnography , Continuous Positive Airway Pressure , Airway Obstruction/diagnostic imaging , Airway Obstruction/physiopathologyABSTRACT
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.
Subject(s)
Gastroesophageal Reflux , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Respiratory Sounds , Sleep Apnea Syndromes/diagnosis , Sleep Apnea, Obstructive/diagnosis , CoughSubject(s)
Endoscopy , Maxilla , Sleep Apnea, Obstructive , Humans , Male , Female , Sleep Apnea, Obstructive/diagnosis , Maxilla/abnormalities , Middle Aged , Adult , Airway Obstruction/etiologyABSTRACT
OBJECTIVE: To determine the effect of upper airway surgery on cardiovascular function in patients with obstructive sleep apnea (OSA). STUDY DESIGN: A prospective, self-controlled study from 2018 to 2023. SETTING: Two academic medical centers. METHODS: Seventy-four patients underwent surgery for OSA, including: tonsillectomy, adenoidectomy, epiglottidectomy, modified uvulopalatopharyngoplasty, maxillary expansion, and maxillomandibular advancement. Twenty-four-hour ambulatory blood pressure (BP), peripheral arterial tonometry (PAT)-based home sleep study, and sleep-related patient-reported outcomes (PROs) were captured preoperatively and at 6 months postoperatively. Paired T-tests evaluated changes in outcomes after surgery. RESULTS: Forty-one patients successfully completed preoperative and postoperative assessments. Patients were generally middle-aged (43.8 ± 12.5 years), obese (BMI 33.0 ± 5.8 kg/m2), male (68%), White (71%), and had severe OSA (apnea-hypopnea index [AHI] 33.9 ± 29.5 events/h). The 4% oxygen desaturation index (ODI) decreased from 30.7 ± 27.1 to 12.2 ± 13.6 events/h (P < .01) after surgery. There was no significant difference in 24-h BP following surgery, though clinically meaningful reductions in nocturnal systolic (-1.95 [-5.34, 1.45] mmHg) and nocturnal diastolic (-2.30 [-5.11, 0.52] mmHg) blood pressure were observed. Stratified analysis showed patients undergoing skeletal surgery (n = 17) demonstrated larger average reductions compared to those undergoing soft tissue surgery in nocturnal systolic (-4.12 [-7.72, -0.51] vs -0.10 [-5.78, 5.58] mmHg) and nocturnal diastolic (-3.94 [-7.90, 0.01] vs -0.90 [-5.11, 3.31] mmHg) pressures. No meaningful changes were observed in PAT Autonomic Index (PAI) measurements. CONCLUSION: Surgical therapy for OSA did not demonstrate statistically significant improvements in 24-h BP. However, clinically meaningful reductions in nocturnal BP were observed, particularly in skeletal surgery patients, supporting the need for larger studies of cardiovascular outcomes following OSA surgery.
Subject(s)
Blood Pressure , Manometry , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/surgery , Sleep Apnea, Obstructive/physiopathology , Male , Female , Prospective Studies , Adult , Blood Pressure/physiology , Middle Aged , Treatment Outcome , Patient Reported Outcome MeasuresABSTRACT
Rationale: Apneic individuals have reduced airway caliber during sleep. The biomechanical changes in upper airway anatomy contributing to this airway narrowing are largely unknown. Objectives: We sought to investigate the state-dependent (wake vs. sleep) biomechanical behavior of the upper airway soft-tissue and craniofacial structures. Methods: Upper airway magnetic resonance imaging was performed in 15 sleep-deprived control subjects (apnea-hypopnea index, <5; 0.3 ± 0.5 events per hour) and 12 sleep-deprived apneic subjects (apnea-hypopnea index, ⩾5; 35.2 ± 18.1 events per hour) during wake and sleep and analyzed for airway measures and soft-tissue/mandibular movement. Results: In the retropalatal region, control subjects showed sleep-dependent reductions (P ⩽ 0.037) in average cross-sectional airway area (CSA), minimum CSA, and anteroposterior and lateral dimensions. Apneic subjects showed sleep-dependent reductions (P ⩽ 0.002) in average CSA, minimum CSA, and anteroposterior and lateral dimensions. In the retroglossal region, control subjects had no sleep-dependent airway reductions. However, apneic subjects had sleep-dependent reductions in minimal CSA (P = 0.001) and lateral dimensions (P = 0.014). Control subjects only showed sleep-dependent posterior movement of the anterior-inferior tongue octant (P = 0.039), whereas apneic subjects showed posterior movement of the soft palate (P = 0.006) and all tongue octants (P ⩽ 0.012). Sleep-dependent medial movement of the lateral walls was seen at the retropalatal minimum level (P = 0.013) in control subjects and at the retropalatal and retroglossal minimum levels (P ⩽ 0.017) in apneic subjects. There was posterior movement of the mandible in apneic subjects (P ⩽ 0.017). Conclusions: During sleep, control and apneic subjects showed reductions in retropalatal airway caliber, but only the apneic subjects showed retroglossal airway narrowing. Reductions in anteroposterior and lateral airway dimensions were primarily due to posterior soft palate, tongue and mandibular movement and to medial lateral wall movement. These data provide important initial insights into obstructive sleep apnea pathogenesis.
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Magnetic Resonance Imaging , Oropharynx , Proof of Concept Study , Sleep Apnea, Obstructive , Humans , Male , Female , Oropharynx/diagnostic imaging , Oropharynx/physiopathology , Middle Aged , Biomechanical Phenomena , Adult , Sleep Apnea, Obstructive/physiopathology , Case-Control Studies , Polysomnography , Sleep/physiology , Tongue/diagnostic imaging , Tongue/physiopathology , Palate, Soft/diagnostic imaging , Palate, Soft/physiopathologyABSTRACT
OBJECTIVE: With the recent addition of airflow and respiratory effort channels, our group has observed central and mixed apnea events during drug-induced sleep endoscopy (DISE). We measured the frequency and timing of sentinel central and/or mixed events (SCents), as well as assessed for differences in velum, oropharynx, tongue, and epiglottis (VOTE) classification compared to obstructive events. STUDY DESIGN: Prospective single-cohort study. SETTING: Tertiary Care Academic Medical Center. METHODS: Patients underwent DISE between June 2020 and November 2022. Nasal airflow, thoracoabdominal effort belt signals, and videoendoscopy were simultaneously captured. Demographics, sleep study, and DISE data were compared among patients with and without SCents using Student's T tests or χ2 tests. RESULTS: On average, the cohort (n = 103) was middle-aged (53.5 ± 12.1 years), overweight (body mass index of 29.7 ± 5.3 kg/m2), and had severe obstructive sleep apnea (apnea-hypopnea index of 30.7 ± 18.7 events/h). Forty-seven patients (46%) were found to have at least 1 SCent. Among those with SCent, 45 (95.7%) transitioned to obstructive pathology after an average of 7.91 ± 2.74 minutes, with at least 95% of patients expected to do so within 12.57 minutes. Twenty-nine out of 47 patients (61.2% [95% confidence interval: 46.4.9%, 75.5%]) with SCent had meaningful differences between central/mixed and obstructive VOTE scores. CONCLUSION: Central events were present in almost half of our cohort. At least 95% of patients were expected to transition to obstructive events within 12 to 13 minutes of propofol initiation. In addition, over half of patients demonstrate significantly different VOTE scores between central and obstructive events. These factors should raise awareness of central events and scoring passive apneas during DISE and consider delaying VOTE scoring.
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Endoscopy , Sleep Apnea, Obstructive , Humans , Middle Aged , Male , Female , Prospective Studies , Endoscopy/methods , Sleep Apnea, Obstructive/epidemiology , Prevalence , Polysomnography , Adult , SleepABSTRACT
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 sleepyâ ≥â 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)â ≥â 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 spentâ <â 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.
Subject(s)
Disorders of Excessive Somnolence , Sleep Apnea, Obstructive , Humans , Male , Female , Sleepiness , Sleep Apnea, Obstructive/complications , Wakefulness , PhenotypeABSTRACT
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.