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BACKGROUND: Differences in the pharyngeal site of collapse influence efficacy of non-continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site of collapse using overnight polysomnography. METHODS: 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, n=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (n=22) versus absence (n=128) of CCCp (partial collapse and concurrent tongue base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue base or epiglottis collapse. External validation was performed on a separate dataset (ntotal=466). RESULTS: CCCp was characterised by greater scoopiness (ß=1.5±0.6 per 2sd, multivariable estimate±se) and skewness (ß=11.4±2.4) compared with non-CCCp. The odds ratio for CCCp in predicted positive versus negative subgroups was 5.0 (95% CI 1.9-13.1). The same characteristics provided significant cross-validated prediction of lateral wall (OR 6.3, 95% CI 2.4-16.5), tongue base (OR 3.2, 95% CI 1.4-7.3) and epiglottis (OR 4.4, 95% CI 1.5-12.4) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue base and epiglottis collapse characteristics. External validation confirmed model prediction. CONCLUSIONS: The current study provides a means to recognise patients with likely CCCp or other DISE-based site of collapse categories using routine polysomnography. Since site of collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.
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Endoscopía , Polisomnografía , Apnea Obstructiva del Sueño , Humanos , Masculino , Femenino , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/terapia , Persona de Mediana Edad , Adulto , Modelos Logísticos , Sueño , Anciano , Lengua/fisiopatología , Faringe/fisiopatología , Nervio Hipogloso , Análisis Multivariante , Hueso Paladar , Epiglotis/fisiopatología , Presión de las Vías Aéreas Positiva ContínuaRESUMEN
BACKGROUND: Pharyngeal flow limitation during pregnancy may be a risk factor for adverse pregnancy outcomes but was previously challenging to quantify. Our objective was to determine whether a novel objective measure of flow limitation identifies an increased risk of pre-eclampsia (primary outcome) and other adverse outcomes in a prospective cohort: Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b). METHODS: Flow limitation severity scores (0%=fully obstructed, 100%=open airway), quantified from breath-by-breath airflow shape, were obtained from home sleep tests during early (6-15â weeks) and mid (22-31â weeks) pregnancy. Multivariable logistic regression quantified associations between flow limitation (median overnight severity, both time-points averaged) and pre-eclampsia, adjusting for maternal age, body mass index (BMI), race, ethnicity, chronic hypertension and flow limitation during wakefulness. Secondary outcomes were hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM) and infant birthweight. RESULTS: Of 1939 participants with flow limitation data at both time-points (mean±sd age 27.0±5.4â years and BMI 27.7±6.1â kg·m-2), 5.8% developed pre-eclampsia, 12.7% developed HDP and 4.5% developed GDM. Greater flow limitation was associated with increased pre-eclampsia risk: adjusted OR 2.49 (95% CI 1.69-3.69) per 2sd increase in severity. Findings persisted in women without sleep apnoea (apnoea-hypopnoea index <5â events·h-1). Flow limitation was associated with HDP (OR 1.77 (95% CI 1.33-2.38)) and reduced infant birthweight (83.7 (95% CI 31.8-135.6)â g), but not GDM. CONCLUSIONS: Greater flow limitation is associated with increased risk of pre-eclampsia, HDP and lower infant birthweight. Flow limitation may provide an early target for mitigating the consequences of sleep disordered breathing during pregnancy.
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Preeclampsia , Resultado del Embarazo , Humanos , Embarazo , Femenino , Adulto , Preeclampsia/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Adulto Joven , Modelos Logísticos , Diabetes Gestacional/fisiopatología , Sueño/fisiología , Peso al Nacer , Análisis Multivariante , Paridad , Polisomnografía , Índice de Masa Corporal , Faringe/fisiopatología , Hipertensión Inducida en el Embarazo/fisiopatología , Recién NacidoRESUMEN
BACKGROUND: In the classic model of obstructive sleep apnoea (OSA), respiratory events occur with sleep-related dilator muscle hypotonia, precipitating increased neural ventilatory 'drive'. By contrast, a drive-dependent model has been proposed, whereby falling drive promotes dilator muscle hypotonia to precipitate respiratory events. Here we determine the extent to which the classic versus drive-dependent models of OSA are best supported by direct physiological measurements. METHODS: In 50 OSA patients (5-91 events/hour), we recorded ventilation ('flow', oronasal mask and pneumotach) and ventilatory drive (calibrated intraoesophageal diaphragm electromyography, EMG) overnight. Flow and drive during events were ensemble averaged; patients were classified as drive dependent if flow fell/rose simultaneously with drive. Overnight effects of lower drive on flow, genioglossus muscle activity (EMGgg) and event risk were quantified (mixed models). RESULTS: On average, ventilatory drive fell (rather than rose) during events (-20 (-42 to 3)%baseline, median (IQR)) and was strongly correlated with flow (R=0.78 (0.24 to 0.94)). Most patients (30/50, 60%) were classified as exhibiting drive-dependent event pathophysiology. Lower drive during sleep was associated with lower flow (-17 (-20 to -14)%/drive) and EMGgg (-3.5 (-3.8 to -3.3)%max/drive) and greater event risk (OR: 2.2 (1.8 to 2.5) per drive reduction of 100%eupnoea); associations were concentrated in patients with drive-dependent OSA (ie, flow: -37 (-40 to -34)%/drive, OR: 6.8 (5.3 to 8.7)). Oesophageal pressure-without tidal volume correction-falsely suggested rising drive during events (classic model). CONCLUSIONS: In contrast to the prevailing view, patients with OSA predominantly exhibit drive-dependent event pathophysiology, whereby flow is lowest at nadir drive, and lower drive raises event risk. Preventing ventilatory drive decline is therefore considered a target for OSA intervention.
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Hipotonía Muscular , Apnea Obstructiva del Sueño , Diafragma , Humanos , Hipotonía Muscular/complicaciones , Polisomnografía , Respiración , Sueño , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypothesize that deleterious cardiovascular outcomes are concentrated in a subgroup of patients with a heightened pulse-rate response to apneas and hypopneas (ΔHR). Methods: We measured the ΔHR in the MESA (Multi-Ethnic Study of Atherosclerosis) (N = 1,395) and the SHHS (Sleep Heart Health Study) (N = 4,575). MESA data were used to determine the functional form of the association between the ΔHR and subclinical cardiovascular biomarkers, whereas primary analyses tested the association of the ΔHR with nonfatal or fatal cardiovascular disease (CVD) and all-cause mortality in longitudinal data from the SHHS. Measurements and Main Results: In the MESA, U-shaped relationships were observed between subclinical CVD biomarkers (coronary artery calcium, NT-proBNP [N-terminal prohormone BNP], and Framingham risk score) and the ΔHR; notably, a high ΔHR (upper quartile) was associated with elevated biomarker scores compared with a midrange ΔHR (25th-75th centiles). In the SHHS, individuals with a high ΔHR compared with a midrange ΔHR were at increased risk of nonfatal or fatal CVD and all-cause mortality (nonfatal adjusted hazard ratio [95% confidence interval (CI)], 1.60 [1.28-2.00]; fatal adjusted hazard ratio [95% CI], 1.68 [1.22-2.30]; all-cause adjusted hazard ratio [95% CI], 1.29 [1.07-1.55]). The risk associated with a high ΔHR was particularly high in those with a substantial hypoxic burden (nonfatal, 1.93 [1.36-2.73]; fatal, 3.50 [2.15-5.71]; all-cause, 1.84 [1.40-2.40]) and was exclusively observed in nonsleepy individuals. Conclusions: Individuals with OSA who demonstrate an elevated ΔHR are at increased risk of cardiovascular morbidity and mortality. This study identifies a prognostic biomarker for OSA that appears useful for risk stratification and patient selection for future clinical trials.
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Biomarcadores , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Frecuencia Cardíaca , Pronóstico , Medición de Riesgo/métodos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , MorbilidadRESUMEN
KEY POINTS: Repeated daily mild intermittent hypoxia has been endorsed as a therapy to promote the recovery of respiratory and limb motor dysfunction. One possible side-effect of this therapy is an increase in apnoeic event number and duration, which is particularly relevant to participants with motor disorders coupled with an increased incidence of sleep apnoea. In this study, we report that increases in apnoeic event number and duration, following exposure to daily intermittent hypoxia, are the result of an increase in respiratory loop gain and the arousal threshold, in participants with obstructive sleep apnoea. Daily exposure to mild intermittent hypoxia also led to an increase in the ventilatory response to arousal. Accordingly, individuals with motor disorders receiving mild intermittent hypoxia as a therapy should be screened for the presence of sleep apnoea, and if present, administration of intermittent hypoxia during hours of wakefulness should be combined with continuous positive airway pressure treatment during sleep. ABSTRACT: We determined if exposure to mild intermittent hypoxia (MIH) causes an increase in loop gain (LG) and the arousal threshold (AT) during non-rapid eye movement (NREM) sleep. Male participants with obstructive sleep apnoea (apnoea-hypopnoea index > 5 events/h), matched for age, body mass index and race were divided into two groups (n = 13 in each group). Following a baseline sleep study, one group was exposed to twelve 4-min episodes of hypoxia each day for 10 days and the other group to a sham protocol (SP). On Days 1 and 10, a sleep study was completed following exposure to MIH or the SP. For each sleep study, LG and the AT were measured during NREM sleep, using a model-based approach, and expressed as a fraction of baseline measures. LG increased after exposure to MIH (Day 1: 1.11 ± 0.03, P = 0.002, Day 10: 1.17 ± 0.05, P = 0.001), but not after the SP (Day 1: 1.03 ± 0.04, P = 1.0, Day 10: 1.0 ± 0.02, P = 1.0). AT also increased after exposure to MIH (Day 1: 1.13 ± 0.05, P = 0.01, Day 10: 1.19 ± 0.08, P = 0.05) but not after the SP (Day 1: 1.04 ± 0.05, P = 0.6, Day 10: 0.96 ± 0.04, P = 1.0). Our results might account for increases in apnoea frequency and duration previously observed during NREM sleep following exposure to MIH. Our results also have implications for the use of MIH as a therapeutic modality.
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Nivel de Alerta/fisiología , Hipoxia/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Sueño/fisiología , Adulto , Índice de Masa Corporal , Presión de las Vías Aéreas Positiva Contínua/métodos , HumanosRESUMEN
STUDY OBJECTIVES: Opioid medications are commonly used and are known to impact both breathing and sleep, and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing pathogenesis are not established. METHODS: Patients who underwent clinically-indicated polysomnography confirming sleep-disordered breathing (SDB) (AHI≥5/hr) were included. Each patient using opioids was matched by sex, age, and BMI to three control individuals not using opioids. Physiology known to influence SDB pathogenesis were determined from validated polysomnography-based signal analysis. PSG and physiology paramters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics. RESULTS: 178 individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs 1.7 events/hr; p=0.001) and worsened hypoxemia (5 vs 3% sleep with SpO2<88%; p=0.013), with similar overall AHI. Use of opioids was associated with higher loop gain, a lower respiratory rate and higher respiratory rate variability. Higher loop gain and increased respiratory rate variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia. CONCLUSIONS: Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate deleterious respiratory consequences of chronic opioid use.
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Rationale: The physiological factors modulating the severity of snoring have not been adequately described. Airway collapse or obstruction is generally the leading determinant of snore sound generation; however, we suspect that ventilatory drive is of equal importance. Objective: To determine the relationship between airway obstruction and ventilatory drive on snore loudness. Methods: In 40 patients with suspected or diagnosed obstructive sleep apnea (1-98 events/hr), airflow was recorded via a pneumotachometer attached to an oronasal mask, ventilatory drive was recorded using calibrated intraesophageal diaphragm electromyography, and snore loudness was recorded using a calibrated microphone attached over the trachea. "Obstruction" was taken as the ratio of ventilation to ventilatory drive and termed flow:drive, i.e., actual ventilation as a percentage of intended ventilation. Lower values reflect increased flow resistance. Using 165,063 breaths, mixed model analysis (quadratic regression) quantified snore loudness as a function of obstruction, ventilatory drive, and the presence of extreme obstruction (i.e., apneic occlusion). Results: In the presence of obstruction (flow:drive = 50%, i.e., doubled resistance), snore loudness increased markedly with increased drive (+3.4 [95% confidence interval, 3.3-3.5] dB per standard deviation [SD] change in ventilatory drive). However, the effect of drive was profoundly attenuated without obstruction (at flow:drive = 100%: +0.23 [0.08-0.39] dB per SD change in drive). Similarly, snore loudness increased with increasing obstruction exclusively in the presence of increased drive (at drive = 200% of eupnea: +2.1 [2.0-2.2] dB per SD change in obstruction; at eupneic drive: +0.14 [-0.08 to 0.28] dB per SD change). Further, snore loudness decreased substantially with extreme obstruction, defined as flow:drive <20% (-9.9 [-3.3 to -6.6] dB vs. unobstructed eupneic breathing). Conclusions: This study highlights that ventilatory drive, and not simply pharyngeal obstruction, modulates snore loudness. This new framework for characterizing the severity of snoring helps better understand the physiology of snoring and is important for the development of technologies that use snore sounds to characterize sleep-disordered breathing.
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Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Humanos , Ronquido/diagnóstico , Polisomnografía/métodos , SonidoRESUMEN
Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], -2 [8] and 1 [8] mm Hg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mm Hg per 1-standard-deviation increase in loop gain; P ⩽ 0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT01086800).
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Apnea Obstructiva del Sueño , Humanos , Presión Sanguínea , Apnea Obstructiva del Sueño/complicaciones , Polisomnografía , Presión de las Vías Aéreas Positiva Contínua , Hipoxia/complicaciones , Oxígeno , BiomarcadoresRESUMEN
There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development has not been fully described. Thus we sought to evaluate how obesity leads to OSA and assess how these mechanisms differ between men and women. The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the University of California, San Diego, sleep clinic between January 2017 and December 2019. Using routine polysomnography signals, we determined OSA endotypes. We then performed mediation analyses stratified by sex to determine how BMI influenced the apnea-hypopnea index (AHI) using OSA pathophysiological traits as mediators, adjusting for age, race, and ethnicity. We included 2,146 patients of whom 919 (43%) were women and 1,227 (57%) were obese [body mass index (BMI) > 30 kg/m2]. BMI was significantly associated with AHI in both women and men. In men, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (ßstandardized = 0.124), a reduction in circulatory delay (ßstandardized = 0.063), and an increase in arousal threshold (ßstandardized = 0.029; Pboot-strapped,all < 0.05). In women, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (ßstandardized = 0.05) and circulatory delay (ßstandardized = 0.037; Pboot-strapped,all < 0.05). BMI-related OSA pathogenesis differs by sex. An increase in upper airway collapsibility is consistent with prior studies. A reduction in circulatory delay may lead to shorter and thus more events per hour (higher AHI), while the relationship between arousal threshold and OSA is likely complex.NEW & NOTEWORTHY Our data provide important insights into obesity-related obstructive sleep apnea (OSA) pathogenesis, thereby validating, and extending, prior research findings. This is the largest sample size study to examine the relationships between obesity and gender on OSA pathogenesis. The influence of obesity on sleep apnea severity is mediated by different mechanistic traits (endotypes).
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Índice de Masa Corporal , Obesidad , Polisomnografía , Apnea Obstructiva del Sueño , Humanos , Masculino , Femenino , Obesidad/fisiopatología , Persona de Mediana Edad , Apnea Obstructiva del Sueño/fisiopatología , Polisomnografía/métodos , Adulto , Estudios Retrospectivos , Análisis de Mediación , Factores Sexuales , Factores de Riesgo , Estudios de Cohortes , AncianoRESUMEN
Obstructive sleep apnea (OSA) pathologically stresses the cardiovascular system. Apneic events cause significant oscillatory surges in nocturnal blood pressure (BP). Trajectories of these surges vary widely. This variability challenges the quantification, characterization, and mathematical modeling of BP surge dynamics. We present a method of aggregating trajectories of apnea-induced BP surges using a sample-by-sample averaging of continuously recorded BP. We applied the method to recordings of overnight BP (average total sleep time: 4.77 ± 1.64 h) for 10 OSA patients (mean AHI: 63.5 events/h; range: 18.3-105.4). We studied surges in blood pressure due to obstructive respiratory events separated from other such events by at least 30 s (274 total events). These events increased systolic (SBP) and diastolic (DBP) BP by 19 ± 7.1 mmHg (14.8%) and 11 ± 5.6 mmHg (15.5%), respectively, relative to mean values during wakefulness. Further, aggregated SBP and DBP peaks occurred on average 9 s and 9.5 s after apnea events, respectively. Interestingly, the amplitude of the SBP and DBP peaks varied across sleep stages, with mean peak ranging from 128.8 ± 12.4 to 166.1 ± 15.5 mmHg for SBP and from 63.1 ± 8.2 to 84.2 ± 9.4 mmHg for DBP. The aggregation method provides a high level of granularity in quantifying BP oscillations from OSA events and may be useful in modeling autonomic nervous system responses to OSA-induced stresses.
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Rationale: Central sleep apnea (CSA) is pervasive during sleep at high altitude, disproportionately impacting men and associated with increased peripheral chemosensitivity. Objectives: We aimed to assess whether biological sex affects loop gain (LGn) and CSA severity during sleep over 9-10 days of acclimatization to 3,800 m. We hypothesized that CSA severity would worsen with acclimatization in men but not in women because of greater increases in LGn in men. Methods: Sleep studies were collected from 20 (12 male) healthy participants at low altitude (1,130 m, baseline) and after ascent to (nights 2/3, acute) and residence at high altitude (nights 9/10, prolonged). CSA severity was quantified as the respiratory event index (REI) as a surrogate of the apnea-hypopnea index. LGn, a measure of ventilatory control instability, was quantified using a ventilatory control model fit to nasal flow. Linear mixed models evaluated effects of time at altitude and sex on respiratory event index and LGn. Data are presented as contrast means with 95% confidence intervals. Results: REI was comparable between men and women at acute altitude (4.1 [-9.3, 17.5] events/h; P = 0.54) but significantly greater in men at prolonged altitude (23.7 [10.3, 37.1] events/h; P = 0.0008). Men had greater LGn than did women for acute (0.08 [0.001, 0.15]; P = 0.047) and prolonged (0.17 [0.10, 0.25]; P < 0.0001) altitude. The change in REI per change in LGn was significantly greater in men than in women (107 ± 46 events/h/LGn; P = 0.02). Conclusions: The LGn response to high altitude differed between sexes and contributed to worsening of CSA over time in men but not in women. This sex difference in acclimatization appears to protect females from high altitude-related CSA. These data provide fundamental sex-specific physiological insight into high-altitude acclimatization in healthy individuals and may help to inform sex differences in sleep-disordered breathing pathogenesis in patients with cardiorespiratory disease.
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Altitud , Apnea Central del Sueño , Humanos , Masculino , Femenino , Caracteres Sexuales , Sueño/fisiología , Polisomnografía , Apnea Central del Sueño/etiologíaRESUMEN
Rationale: Sleep apnea is the manifestation of key endotypic traits, including greater pharyngeal collapsibility, reduced dilator muscle compensation, and elevated chemoreflex loop gain. Objectives: We investigated how endotypic traits vary with obesity, age, sex, and race/ethnicity to influence sleep apnea disease severity (apnea-hypopnea index [AHI]). Methods: Endotypic traits were estimated from polysomnography in a diverse community-based cohort study (Multi-Ethnic Study of Atherosclerosis, N = 1,971; age range, 54-93 yr). Regression models assessed associations between each exposure (continuous variables per 2 standard deviations [SDs]) and endotypic traits (per SD) or AHI (events/h), independent of other exposures. Generalizability was assessed in two independent cohorts. Results: Greater AHI was associated with obesity (+19 events/h per 11 kg/m2 [2 SD]), male sex (+13 events/h vs. female), older age (+7 events/h per 20 yr), and Chinese ancestry (+5 events/h vs. White, obesity adjusted). Obesity-related increase in AHI was best explained by elevated collapsibility (+0.40 SD) and greater loop gain (+0.38 SD; percentage mediated, 26% [95% confidence interval (CI), 20-32%]). Male-related increase in AHI was explained by elevated collapsibility (+0.86 SD) and reduced compensation (-0.40 SD; percentage mediated, 57% [95% CI, 50-66%]). Age-related AHI increase was explained by elevated collapsibility (+0.37 SD) and greater loop gain (+0.15 SD; percentage mediated, 48% [95% CI, 34-63%]). Increased AHI with Chinese ancestry was explained by collapsibility (+0.57 SD; percentage mediated, 87% [95% CI, 57-100]). Black race was associated with reduced collapsibility (-0.30 SD) and elevated loop gain (+0.29 SD). Similar patterns were observed in the other cohorts. Conclusions: Different subgroups exhibit different underlying pathophysiological pathways to sleep apnea, highlighting the variability in mechanisms that could be targeted for intervention.
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Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Obesidad , EtnicidadRESUMEN
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by multiple "endotypic traits," including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here, we examined (1) within-night repeatability, (2) long-term consistency, and (3) influences of body position and sleep state, of endotypic traits estimated from in-home polysomnography in mild-to-severe OSA (apnea-hypopnea index, AHI > 5 events/h). METHODS: Within-night repeatability was assessed using Multi-Ethnic Study of Atherosclerosis (MESA): Traits derived separately from "odd" and "even" 30-min periods were correlated and regression (error vs. N windows available) provided a recommended amount of data for acceptable repeatability (Rthreshold = 0.7). Long-term consistency was assessed using the Osteoporotic Fractures in Men Study (MrOS) at two time points 6.5 ± 0.7 years apart, before and after accounting for across-year body position and sleep state differences. Within-night dependence of traits on position and state (MESA plus MrOS data) was estimated using bootstrapping. RESULTS: Within-night repeatability for traits ranged from R = 0.62-0.79 and improved to R = 0.69-0.83 when recommended amounts of data were available (20-35 7-min windows, available in 94%-98% of participants); repeatability was similar for collapsibility, loop gain, and arousal threshold (R = 0.79-0.83), but lower for compensation (R = 0.69). Long-term consistency was modest (R = 0.30-0.61) and improved (R = 0.36-0.63) after accounting for position and state differences. Position/state analysis revealed reduced loop gain in REM and reduced collapsibility in N3. CONCLUSIONS: Endotypic traits can be obtained with acceptable repeatability. Long-term consistency was modest but improved after accounting for position and state changes. These data support the use of endotypic assessments in large-scale epidemiological studies. CLINICAL TRIAL INFORMATION: The data used in the manuscript are from observational cohort studies and are not a part of the clinical trial.
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Aterosclerosis/complicaciones , Fracturas Osteoporóticas/complicaciones , Apnea Obstructiva del Sueño/etiología , Aterosclerosis/etnología , Humanos , Masculino , Fracturas Osteoporóticas/etnología , Posicionamiento del Paciente , Faringe , Polisomnografía , Recurrencia , Apnea Obstructiva del Sueño/etnologíaRESUMEN
BACKGROUND: Conventional metrics to evaluate sleep-disordered breathing (SDB) have many limitations, including their inability to identify subclinical markers of cardiovascular (CV) dysfunction. RESEARCH QUESTION: Does sleep study-derived circulation time (Ct) predict mortality, independent of CV risks and SDB severity? STUDY DESIGN AND METHODS: We derived average lung to finger Ct (LFCt) from sleep studies in older men enrolled in the multicenter Osteoporotic Fractures in Men (MrOS) Sleep study. LFCt was defined as the average time between end of scored respiratory events and nadir oxygen desaturations associated with those events. We calculated the hazard ratio (HRs) for the CV and all-cause mortality by LFCt quartiles, adjusting for the demographic characteristics, body habitus, baseline CV risk, and CV disease (CVD). Additional models included apnea-hypopnea index (AHI), time with oxygen saturation as measured by pulse oximetry (SpO2) < 90% (T90), and hypoxic burden. We also repeated analyses after excluding those with CVD at baseline. RESULTS: A total of 2,631 men (mean ± SD age, 76.4 ± 5.5 years) were included in this study. LFCt median (interquartile range) was 18 (15-22) s. During an average ± SD follow-up of 9.9 ± 3.5 years, 427 men (16%) and 1,205 men (46%) experienced CV death and all-cause death, respectively. In multivariate analysis, men in the fourth quartile of LFCt (22-52 s) had an HR of 1.36 (95% CI, 1.02-1.81) and 1.35 (95% CI, 1.14-1.60) for CV and all-cause mortality, respectively, when compared with men in the first quartile (4-15 s). The results were similar when additionally adjusting for AHI, T90, or hypoxic burden. Results were stronger among men with no history of CVD at baseline. INTERPRETATION: LFCt is associated with both CV and all-cause mortality in older men, independent of baseline CV burden and SDB metrics. LFCt may be a novel physiologic marker for subclinical CVD and adverse outcomes in patients with SDB.
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Circulación Sanguínea/fisiología , Enfermedades Cardiovasculares/fisiopatología , Síndromes de la Apnea del Sueño/mortalidad , Síndromes de la Apnea del Sueño/fisiopatología , Anciano , Humanos , Masculino , Oximetría , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
We present an approach to quantifying nocturnal blood pressure (BP) variations that are elicited by sleep disordered breathing (SDB). A sample-by-sample aggregation of the dynamic BP variations during normal breathing and BP oscillations prompted by apnea episodes is performed. This approach facilitates visualization and analysis of BP oscillations. Preliminary results from analysis of a full night study of 7 SDB subjects (5 Male 2 Female, 52±5.6 yrs., Body Mass Index 36.4±7.4 kg/m2, Apnea-Hypopnea Index 69.1±26.8) are presented. Aggregate trajectory and quantitative values for changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) concomitant with obstructive apnea episodes are presented. The results show 19.4 mmHg (15.3%) surge in SBP and 9.4 mmHg (13.6%) surge in DBP compared to their respective values during normal breathing (p<0.05). Further, the peak of the surge in SBP and DBP occurred about 9s and 7s, respectively, post the end of apnea events. The return of SBP and DBP to baseline values displays a decaying oscillatory pattern.
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Hipertensión , Síndromes de la Apnea del Sueño , Presión Sanguínea , Determinación de la Presión Sanguínea , Femenino , Humanos , Hipertensión/diagnóstico , Masculino , Polisomnografía , Síndromes de la Apnea del Sueño/diagnósticoRESUMEN
Monitoring apnea-induced cerebral blood flow oscillations is of importance for assessing apnea patient brain health. Using an autoregressive moving average model, peak and trough values of cerebral blood flow were estimated from a concurrently recorded forehead photoplethysmography signal. Preliminary testing of the method in 7 subjects (4 F, 32±4 yrs., BMI 24.57±3.87 kg/m2) using a breath hold paradigm for simulating apnea shows that maximum mean and standard deviation of the prediction error is -1.10±8.49 cm/s and the maximum root mean squared of the error is 8.92 cm/s.
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Apnea , Circulación Cerebrovascular , Fotopletismografía , Encéfalo , Contencion de la Respiración , Humanos , Fotopletismografía/métodosRESUMEN
Monitoring apnea-induced cerebral blood flow (CBF) oscillations is of importance for assessing apnea patient brain health. Blood pressure (BP) oscillations during apnea can induce oscillations in CBF. Preliminary results of testing an Auto Regressive Moving Average model relating nocturnal CBP oscillations to nocturnal BP variations in 8 obstructive sleep apnea subjects (3 F, 55±8 yrs., BMI 34.2±7.85 kg/m2) showed that largest mean and standard deviation of the CBF estimation errors was 4.49±7.57 cm/s and maximum root mean squared of the errors was 8.80 cm/s. Hence, reasonable accuracy in estimating CBF from BP during sleep apnea events was observed.
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Presión Sanguínea , Circulación Cerebrovascular , Síndromes de la Apnea del Sueño/diagnóstico , Determinación de la Presión Sanguínea , HumanosRESUMEN
PURPOSE: We determined if oxidative stress prior to sleep onset is correlated to loop gain (LG) and the arousal threshold (AT) during non-rapid eye movement (NREM) sleep. We also explored if LG and AT are correlated with apnea severity and indices of upper airway collapsibility during NREM sleep. METHODS: Thirteen male participants with obstructive sleep apnea (apnea-hypopnea index > 5 events/hr) were administered an antioxidant or placebo cocktail while exposed to mild intermittent hypoxia in the awake state. Thereafter, loop gain and measures of arousal, apnea severity and upper airway collapsibility were ascertained during NREM sleep. RESULTS: Modification in oxidative stress (i.e., 8-hydroxy-2-deoxyguanosine) prior to sleep onset was correlated to LG (r = 0.8, P = 0.003), the number (r = 0.71, P = 0.01) and duration (r = 0.63, P = 0.04) of apneic events and the percentage of time breathing was stable (r = -0.66, P = 0.03) during sleep. Using a forward stepwise regression analysis, our results showed that LG, AT, the ventilatory response to arousal and nadir end-tidal carbon dioxide were determinants of the apnea-hypopnea index (P value range = 0.04-0.001). In addition, the AT was a predictor of measures of upper airway collapsibility, including the hypopnea/apnea + hypopnea ratio and the degree of flow reduction that accompanied hypopneic events (P < 0.001). CONCLUSION: Modifications in oxidative stress following exposure to intermittent hypoxia during wakefulness are positively associated with loop gain and apnea severity during NREM sleep. Moreover, an increase in the arousal threshold is a predictor of increased upper airway collapsibility.
RESUMEN
The effect of untreated Obstructive Sleep Apnoea (OSA) on cerebral haemodynamics and CA impairment is an active field of research interest. A breath-hold challenge is usually used in clinical and research settings to simulate cardiovascular and cerebrovascular changes that mimic OSA events. This work utilises temporal arterial oxygen saturation (SpO2) and photoplethysmography (PPG) signals to estimate the temporal cerebral blood flow velocity (CBFv) waveform. Measurements of CBFv, SpO2, and PPG, were acquired concurrently from volunteers performing two different protocols of breath-hold challenge in the supine position. Past values of the SpO2 and PPG signals were used to estimate the current values of CBFv using different permutations and topologies of supervised learning with shallow artificial neural networks (ANNs). The measurements from one protocol were used to train the ANNs and find the optimum topologies, which in turn were tested using the other protocol. Data collected from 10 normotensive, healthy subjects (four females, age 28.5⯱â¯6.1 years, Body Mass Index (BMI) 24.0⯱â¯4.7â¯kg/m2) were used in this study. The results show that different subjects have different optimum topologies for ANNs, thus indicating the effects of inter-subject variability on ANNs. Successfully reconstructed blind waveforms for the same subject group in the second protocol showed a reasonable accuracy of 60-80% estimation compared to the measured waveforms. HYPOTHESIS: Temporal waveforms for SpO2 and PPG contain adequate information to estimate the temporal CBFv waveform using ANNs. METHODOLOGY: Concurrent measurements of SpO2 and PPG using pulse oximetry from the forehead and CBFv from the middle cerebral artery (MCA) using transcranial Doppler (TCD) were recorded from healthy, normotensive subjects performing a breath-hold challenge. The breath-hold challenge mimicked the cerebrovascular response to apnoea, and was recorded by measuring CBFv in MCA. Two protocols were used, each consisting of five breath-holding manoeuvres and differing in terms of the time between the five successive breath-holds. Using data from one protocol, several permutations of the temporal values of SpO2 and PPG signals were used as inputs to different ANN topologies, in order to train and find the optimum model. The optimum model was evaluated using the data from the other protocol as a blind dataset. RESULTS: Using the first protocol for training, optimum ANN configurations were found to be different for each subject, and accuracy of 75-87% was achieved. When these optimum ANN models were tested using the second protocol as a blind dataset, the accuracy achieved was around 60-80%. CONCLUSIONS: A novel approach employing temporal records of SpO2 and PPG can be used to estimate the CBFv waveform using ANNs with acceptable accuracy. Increases in the size and diversity of the population dataset and the use of features extracted from SpO2 and PPG signals are needed for generalisation of the method and potential future clinical applications.