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Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.
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Síndrome de Hipoventilación por Obesidad/diagnóstico , Síndrome de Hipoventilación por Obesidad/terapia , Humanos , Estados UnidosRESUMEN
BACKGROUND: Mild obstructive sleep apnea (OSA) is a highly prevalent disorder in adults; however, whether mild OSA has significant neurocognitive and cardiovascular complications is uncertain. OBJECTIVES: The specific goals of this Research Statement are to appraise the evidence regarding whether long-term adverse neurocognitive and cardiovascular outcomes are attributable to mild OSA in adults, evaluate whether or not treatment of mild OSA is effective at preventing or reducing these adverse neurocognitive and cardiovascular outcomes, delineate the key research gaps, and provide direction for future research agendas. METHODS: Literature searches from multiple reference databases were performed using medical subject headings and text words for OSA in adults as well as by hand searches. Pragmatic systematic reviews of the relevant body of evidence were performed. RESULTS: Studies were incongruent in their definitions of "mild" OSA. Data were inconsistent regarding the relationship between mild OSA and daytime sleepiness. However, treatment of mild OSA may improve sleepiness in patients who are sleepy at baseline and improve quality of life. There is limited or inconsistent evidence pertaining to the impact of therapy of mild OSA on neurocognition, mood, vehicle accidents, cardiovascular events, stroke, and arrhythmias. CONCLUSIONS: There is evidence that treatment of mild OSA in individuals who demonstrate subjective sleepiness may be beneficial. Treatment may also improve quality of life. Future research agendas should focus on clarifying the effect of mild OSA and impact of effective treatment on other neurocognitive and cardiovascular endpoints as detailed in the document.
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Enfermedades Cardiovasculares/complicaciones , Trastornos Neurocognitivos/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Enfermedades Cardiovasculares/fisiopatología , Humanos , Trastornos Neurocognitivos/fisiopatología , Sociedades , Resultado del Tratamiento , Estados UnidosRESUMEN
Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10â events·h(-1), diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp ) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104-0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196-0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.
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Resistencia a la Insulina , Insulina/sangre , Obesidad Mórbida/fisiopatología , Faringe/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Sueño , Adiposidad , Adulto , Antropometría , Cirugía Bariátrica , Glucemia/análisis , Índice de Masa Corporal , Estudios Transversales , Femenino , Homeostasis , Humanos , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Polisomnografía , Presión , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/fisiopatología , Apnea Obstructiva del Sueño/complicacionesRESUMEN
The transition from wake to sleep is accompanied by a host of physiologic changes, which result in major alterations in respiratory control and may result in sleep-related breathing disorders. The central sleep apneas are a group of sleep-related breathing disorders that are characterized by recurrent episodes of airflow reduction or cessation due to a temporary reduction or absence of central respiratory drive. The fundamental hallmark of central sleep apnea (CSA) disorders is the presence of ventilatory control instability; however, additional mechanisms play a role in one or more specific manifestations of CSA. CSA may manifest during conditions of eucapnia/hypocapnia or chronic hypercapnia, which is a useful clinical classification that lends understanding to the underlying pathophysiology and potential therapies. In this review, an overview of normal breathing physiology is provided, followed by a discussion of pathophysiologic mechanisms that promote CSA and the mechanisms that are specific to different manifestations of CSA.
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Apnea Central del Sueño/fisiopatología , Respiración de Cheyne-Stokes/diagnóstico , Respiración de Cheyne-Stokes/fisiopatología , Humanos , Hipercapnia/diagnóstico , Hipercapnia/fisiopatología , Hipocapnia/diagnóstico , Hipocapnia/fisiopatología , Ventilación Pulmonar/fisiología , Centro Respiratorio/fisiopatología , Apnea Central del Sueño/diagnósticoRESUMEN
Exercise improves chronic inflammation and is recommended as a first-line medical or behavioral treatment for OSA with obesity. We examined whether the effects of an exercise program on inflammatory blood markers differed according to severity of OSA among obese adults. Overweight (BMI > 27 kg/m2) adults were evaluated for OSA using overnight polysomnography and subsequently classified as exhibiting no-to-mild OSA (AHI < 15 events/hour) or moderate-to-severe OSA (AHI ≥ 15 events/hour). Cardiorespiratory fitness, body composition assessed by DXA, fasting metabolic parameters and adipokines (i.e., glucose, insulin, leptin and adioponectin), and multiple markers of inflammation (i.e., CRP, IL-4, IL-8 and TNF-α) were measured at baseline (Pre) and following a 6-week (3 days per week) comprehensive exercise program (Post). Ten adults (Age: 48 ± 8 years; W:6; M:4) with no/mild OSA and 12 adults (Age: 54 ± 8 years; W:5; M:7) with moderate/severe OSA completed all aspects of the trial. No significant differences in age, cardiorespiratory fitness, body composition, fasting metabolic parameters and most inflammatory markers were observed between groups at baseline. Exercise training decreased total fat mass (Pre: 41,167 ± 13,315 g; Post: 40,311 ± 12,657 g; p = 0.008), leptin (Pre: 26.7 ± 29.6 pg/ml; Post: 22.7 ± 19.4 pg/ml; p = 0.028) and adiponectin (Pre: 16.6 ± 10.9 µg/ml; Post: 11.0 ± 10.6 µg/ml; p = 0.004) in those with moderate/severe OSA. Among those with no/mild OSA, exercise training resulted in a decrease in total fat mass (Pre = 37,332 ± 20,258 g; Post: 37,068 ± 18,268 g, p = 0.037). These data suggest that while 6 weeks of exercise reduced adipokines in those with moderate-to-severe OSA, it was not sufficient to improve common markers of inflammation among overweight adults with OSA.
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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.
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Calidad de Vida , Apnea Obstructiva del Sueño , Anciano , Humanos , Estados Unidos , Medicare , Apnea Obstructiva del Sueño/terapia , Presión de las Vías Aéreas Positiva Contínua , Evaluación de Resultado en la Atención de Salud , Investigación sobre Servicios de Salud , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
STUDY OBJECTIVES: The aims of this study were to characterize obstructive sleep apnea (OSA) care pathways among commercially insured individuals in the United States and to investigate between-groups differences in population, care delivery, and economic aspects. METHODS: We identified adults with OSA using a large, national administrative claims database (January 1, 2016-February 28, 2020). Inclusion criteria included a diagnostic sleep test on or within ≤ 12 months of OSA diagnosis (index date) and 12 months of continuous enrollment before and after the index date. Exclusion criteria included prior OSA treatment or central sleep apnea. OSA care pathways were identified using sleep testing health care procedural health care common procedure coding system/current procedural terminology codes then selected for analysis if they were experienced by ≥ 3% of the population and assessed for baseline demographic/clinical characteristics that were also used for model adjustment. Primary outcome was positive airway pressure initiation rate; secondary outcomes were time from first sleep test to initiation of positive airway pressure, sleep test costs, and health care resource utilization. Associations between pathway type and time to treatment initiation were assessed using generalized linear models. RESULTS: Of 86,827 adults with OSA, 92.1% received care in 1 of 5 care pathways that met criteria: home sleep apnea testing (HSAT; 30.8%), polysomnography (PSG; 23.6%), PSG-Titration (19.8%), Split-night (14.8%), and HSAT-Titration (3.2%). Pathways had significantly different demographic and clinical characteristics. HSAT-Titration had the highest positive airway pressure initiation rate (84.6%) and PSG the lowest (34.4%). After adjustments, time to treatment initiation was significantly associated with pathway (P < .0001); Split-night had shortest duration (median, 28 days), followed by HSAT (36), PSG (37), PSG-Titration (58), and HSAT-Titration (75). HSAT had the lowest sleep test costs and health care resource utilization. CONCLUSIONS: Distinct OSA care pathways exist and are associated with differences in population, care delivery, and economic aspects. CITATION: Wickwire EM, Zhang X, Munson SH, et al. The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States. J Clin Sleep Med. 2024;20(4):505-514.
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Síndromes de la Apnea del Sueño , Apnea Central del Sueño , Apnea Obstructiva del Sueño , Adulto , Humanos , Estados Unidos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/terapia , Síndromes de la Apnea del Sueño/complicaciones , Sueño , Polisomnografía/métodos , Apnea Central del Sueño/complicacionesRESUMEN
The period of the year from spring to fall, when clocks in most parts of the United States are set one hour ahead of standard time, is called daylight saving time, and its beginning and ending dates and times are set by federal law. The human biological clock is regulated by the timing of light and darkness, which then dictates sleep and wake rhythms. In daily life, the timing of exposure to light is generally linked to the social clock. When the solar clock is misaligned with the social clock, desynchronization occurs between the internal circadian rhythm and the social clock. The yearly change between standard time and daylight saving time introduces this misalignment, which has been associated with risks to physical and mental health and safety, as well as risks to public health. In 2020, the American Academy of Sleep Medicine (AASM) published a position statement advocating for the elimination of seasonal time changes, suggesting that evidence best supports the adoption of year-round standard time. This updated statement cites new evidence and support for permanent standard time. It is the position of the AASM that the United States should eliminate seasonal time changes in favor of permanent standard time, which aligns best with human circadian biology. Evidence supports the distinct benefits of standard time for health and safety, while also underscoring the potential harms that result from seasonal time changes to and from daylight saving time. CITATION: Rishi MA, Cheng JY, Strang AR, et al. Permanent standard time is the optimal choice for health and safety: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2024;20(1):121-125.
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Ritmo Circadiano , Trastornos del Sueño del Ritmo Circadiano , Humanos , Estados Unidos , Sueño , Relojes Biológicos , Estaciones del AñoRESUMEN
The objective of this study is to examine whether increasing obstructive sleep apnea (OSA) severity is associated with worsening endothelial function. The design is a cross-sectional examination of the baseline assessment of a multi-centre randomized controlled clinical trial examining the effects of oxygen, continuous positive airway pressure (CPAP) therapy or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an apnea-hypopnea index (AHI) of 15-50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices [oxygen desaturation index (ODI), AHI and percentage of sleep time below 90% oxygen saturation (total sleep time <90)] and a measure of endothelium-mediated vasodilatation [Framingham reactive hyperaemia index (F-RHI) derived from peripheral arterial tonometry (PAT)] were assessed. The sample included 267 individuals with a mean AHI of 25.0 ± 8.5 SD and mean F-RHI 0.44 ± 0.38. In adjusted models, the slope of the relationship between ODI and F-RHI differed above and below an ODI of 24.6 (P = 0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% [95% confidence interval (CI): 0%, 5%; P = 0.05], while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: 0%, 27%; P = 0.05) per 5-unit increase in ODI. A similar pattern was observed between AHI and F-RHI. No relation was noted with total sleep time <90 and F-RHI. There was evidence of a graded decline in endothelial function in association with higher levels of intermittent hypoxaemia.
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Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/fisiopatología , Endotelio Vascular/fisiopatología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Biomarcadores/análisis , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/patología , Presión de las Vías Aéreas Positiva Contínua , Estudios Transversales , Endotelio Vascular/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Sueño , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/terapia , Factores de Tiempo , VasodilataciónRESUMEN
PURPOSE: Obstructive sleep apnea (OSA) is associated with poorer executive function. This study examined the effects of a comprehensive exercise intervention on executive function in overweight adults with mild and moderate-to-severe OSA. METHODS: Participants aged between 30 and 65 years, with a body mass index (BMI) ranging from 27 to 42 kg/m2, participated in a 6-week exercise program. Standardized polysomnographic recording methods provided total Apnea-Hypopnea Index (AHI) and level of hypoxemia. Executive function was assessed using the NIH Toolbox Flanker Inhibitory Control Test. A submaximal treadmill exercise test evaluated cardiorespiratory fitness. Participants with baseline total AHI between 5 and 14.9 events/h were classified as mild OSA and participants with baseline total AHI 15 ≥ events/h were classified as moderate-to-severe OSA. RESULTS: Fifteen participants completed 18 exercise sessions. Significant differences between OSA categories at baseline were observed for sleep characteristics, but not for fitness or executive function. Wilcoxon Signed Rank Tests showed significant increases in median values for the Flanker Test in the moderate-to-severe category only, z = 2.429, p < .015, η2 = .737. CONCLUSION: Six weeks of exercise improved executive function in overweight individuals with moderate-to-severe OSA, but not in those with mild OSA.
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Background: Mild obstructive sleep apnoea (OSA) is a common disorder associated with daytime sleepiness and impaired quality of life. Given that adherence to positive airway pressure (PAP) therapy in OSA is suboptimal, alternative strategies are needed particularly for patients with mild OSA. Daytime neuromuscular electrical stimulation (NMES) of the tongue is a new therapeutic modality for mild OSA. The objective of this study was to determine if patients with mild OSA adhere to daytime NMES. Methods: A randomised, sham-controlled, double-masked controlled trial was conducted in 40 patients with mild OSA who received either high-intensity (active) or low-intensity (sham) NMES for 6â weeks. The primary end-point was adherence to therapy. Exploratory outcomes included the respiratory event index (REI) and the Epworth Sleepiness Scale (ESS) score. Results: More than 90% of participants in each arm were adherent to NMES. Exploratory analyses revealed a 32.7% (95% CI 15.5-49.9%) drop in the REI with active NMES, with no significant change in the REI with sham NMES. Improvements were larger in the supine than non-supine REI. Both the apnoea index and hypopnoea index improved with active NMES. Finally, the ESS score improved with active but not with sham NMES. Conclusions: Daytime NMES was well accepted, with a majority using it for the recommended period. NMES of the tongue use was associated with improvements in OSA severity and daytime sleepiness. Additional research is needed to define its role in the treatment armamentarium across the spectrum of OSA severity and in patients who are intolerant to PAP therapy.
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Continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA). Although CPAP improves symptoms (e.g., daytime sleepiness), there is a lack of high-quality evidence that CPAP prevents many long-term outcomes, including cognitive impairment, myocardial infarction, and stroke. Observational studies suggest that patients with symptoms may be particularly likely to experience these preventive benefits with CPAP, but ethical and practical concerns limited the participation of such patients in prior long-term randomized trials. As a result, there is uncertainty about the full benefits of CPAP, and resolving this uncertainty is a key priority for the field. This workshop assembled clinicians, researchers, ethicists, and patients to identify strategies to understand the causal effects of CPAP on long-term clinically important outcomes among patients with symptomatic OSA. Quasi-experimental designs can provide valuable information and are less time and resource intensive than trials. Under specific conditions and assumptions, quasi-experimental studies may be able to provide causal estimates of CPAP's effectiveness from generalizable observational cohorts. However, randomized trials represent the most reliable approach to understanding the causal effects of CPAP among patients with symptoms. Randomized trials of CPAP can ethically include patients with symptomatic OSA, as long as there is outcome-specific equipoise, adequate informed consent, and a plan to maximize safety while minimizing harm (e.g., monitoring for pathologic sleepiness). Furthermore, multiple strategies exist to ensure the generalizability and practicality of future randomized trials of CPAP. These strategies include reducing the burden of trial procedures, improving patient-centeredness, and engaging historically excluded and underserved populations.
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Disfunción Cognitiva , Infarto del Miocardio , Apnea Obstructiva del Sueño , Humanos , Presión de las Vías Aéreas Positiva Contínua , Consentimiento Informado , Apnea Obstructiva del Sueño/terapiaRESUMEN
Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity due, in part, to impaired vascular function. Exercise confers cardioprotection by improving vascular health. Yet, whether OSA severity affects the vascular improvements conferred with exercise training is not known. Overweight (body mass index (BMI) >27 kg/m2) adults were evaluated for OSA and enrolled in a six-week exercise intervention. Baseline assessments of brachial artery flow-mediated dilation (BAFMD), central augmentation index (AIx) and pulse wave velocity (PWV) were repeated post training. Fifty-one participants (25 men; 26 women) completed the study. Despite improved aerobic capacity (p=0.0005) and total fat mass (p=0.0005), no change in vascular function was observed. Participants were divided into two severity groups according to their baseline total apnea-hypopnea index (AHI) as either 5 to 14.9 eventsâ¢hr-1 (n= 21; Age=48 ± 7 yrs; BMI=33.7 ± 4.6kgâ¢m-2) or 15 ≥eventsâ¢hr-1 (n=30; Age=56 ± 13 yrs; BMI = 34.3 ± 4.2 kgâ¢m-2). No effect of OSA group was observed for BAFMD (p=0.82), AIx (p=0.37) or PWV (p=0.44), suggesting that OSA severity does not influence the effect of exercise on vascular function. The vascular effects of extended exercise programs of greater intensity in overweight OSA patients should be examined.
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This document summarizes the work of the CPAP and bilevel PAP therapy for OSA Technical Expert Panel working group. For positive airway pressure (PAP) therapy, the most pressing current coverage barriers identified were: an insufficient symptom list describing all potential symptoms in patients with mild OSA; the 4 h per night of PAP usage requirement to keep the device; the additional sleep studies requirement to re-qualify for PAP or supplemental oxygen; and the inability to use telehealth visits for follow-up visits. Critical evidence supports changes to current policies and includes: symptom list inadequate to cover all scenarios based on updated clinical practice guidelines; published evidence that 2 h per night of PAP use can result in benefit to quality of life and other metrics; the costs of another sleep study not justified for all nonadherent patients or for supplemental oxygen due to other types of assessment currently available; and the remarkable success and acceptance of telehealth visits. To achieve optimal access for patients on PAP therapy, we make the following key suggestions: removing symptom criteria for mild OSA; reduce continued coverage criteria to > 2 h per night; eliminate the need for a sleep study to re-qualify if nonadherent or for new Centers for Medicare & Medicaid Services beneficiaries already on and adherent to PAP therapy; allow telehealth visits for documenting benefit and adherence; and allow PAP reports and domiciliary oximetry to qualify for supplemental oxygen with PAP if needed. This paper shares our best vision for bringing the right device to the right patient at the right time.
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Hipoxia , Medicare , Respiración con Presión Positiva/métodos , Calidad de Vida , Apnea Obstructiva del Sueño , Evaluación de Síntomas , Humanos , Hipoxia/diagnóstico , Hipoxia/etiología , Hipoxia/fisiopatología , Hipoxia/terapia , Medicare/organización & administración , Medicare/normas , Cooperación del Paciente , Selección de Paciente , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/psicología , Evaluación de Síntomas/métodos , Evaluación de Síntomas/normas , Telemedicina/organización & administración , Estados UnidosRESUMEN
Obstructive sleep apnea leads to chronic intermittent hypoxia (CIH) and is associated with atherosclerosis. We have previously shown that C57BL/6J mice exposed to CIH and a high-cholesterol diet develop dyslipidemia, atherosclerosis of the aorta, and upregulation of a hepatic enzyme of lipoprotein secretion, stearoyl coenzyme A desaturase 1 (SCD-1). We hypothesized that (1) SCD-1 deficiency will prevent dyslipidemia and atherosclerosis during CIH; and (2) human OSA is associated with dyslipidemia and upregulation of hepatic SCD. C57BL/6J mice were exposed to CIH or normoxia for 10 weeks while being treated with either SCD-1 or control antisense oligonucleotides. Obese human subjects underwent sleep study and bariatric surgery with intraoperative liver biopsy. In mice, hypoxia increased hepatic SCD-1 and plasma very-low-density lipoprotein cholesterol levels and induced atherosclerosis lesions in the ascending aorta (the cross-section area of 156514+/-57408 microm(2)), and descending aorta (7.0+/-1.2% of the total aortic surface). In mice exposed to CIH and treated with SCD-1 antisense oligonucleotides, dyslipidemia and atherosclerosis in the ascending aorta were abolished, whereas lesions in the descending aorta showed 56% reduction. None of the mice exposed to normoxia developed atherosclerosis. In human subjects, hepatic SCD mRNA levels correlated with the degree of nocturnal hypoxemia (r=0.68, P=0.001). Patients exhibiting oxyhemoglobin desaturations at night showed higher plasma triglyceride and low-density lipoprotein cholesterol levels, compared to subjects without hypoxemia. In conclusion, CIH is associated with dyslipidemia and overexpression of hepatic SCD in both humans and mice alike; SCD-1 deficiency attenuates CIH-induced dyslipidemia and atherosclerosis in mice.
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Aterosclerosis/enzimología , Dieta Aterogénica , Dislipidemias/enzimología , Hipoxia/enzimología , Hígado/enzimología , Síndrome de Hipoventilación por Obesidad/enzimología , Oligonucleótidos Antisentido/farmacología , Estearoil-CoA Desaturasa/antagonistas & inhibidores , Estearoil-CoA Desaturasa/biosíntesis , Animales , Aorta/enzimología , Aorta/patología , Aterosclerosis/inducido químicamente , Aterosclerosis/patología , Colesterol/efectos adversos , Colesterol/farmacología , VLDL-Colesterol/sangre , Enfermedad Crónica , Dislipidemias/inducido químicamente , Dislipidemias/patología , Inducción Enzimática/efectos de los fármacos , Humanos , Hipoxia/inducido químicamente , Hipoxia/patología , Hígado/patología , Masculino , Ratones , Síndrome de Hipoventilación por Obesidad/patología , Oxihemoglobinas/metabolismo , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , Triglicéridos/sangre , Regulación hacia Arriba/efectos de los fármacosRESUMEN
RATIONALE: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. OBJECTIVES: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. METHODS: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n = 20) were obtained during bariatric surgery. MEASUREMENTS AND MAIN RESULTS: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 +/- 29 events/hour and the median oxygen desaturation during apneic events was 4.6 +/- 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. CONCLUSIONS: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.
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Hígado Graso/etiología , Resistencia a la Insulina , Obesidad Mórbida/complicaciones , Apnea Obstructiva del Sueño/etiología , Sueño/fisiología , Adulto , Anciano , Biopsia , Glucemia/metabolismo , Índice de Masa Corporal , Ensayo de Inmunoadsorción Enzimática , Hígado Graso/sangre , Hígado Graso/epidemiología , Femenino , Humanos , Insulina/sangre , Hígado/patología , Masculino , Maryland/epidemiología , Persona de Mediana Edad , Obesidad Mórbida/sangre , Obesidad Mórbida/patología , Pronóstico , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología , Adulto JovenRESUMEN
Polysomnography studies are an essential tool for the sleep physician and aid in the diagnosis and treatment of sleep disorders. Polysomnography refers to the recording, analysis, and interpretation of multiple physiologic signals collected simultaneously. Rapid advancements in technology have transformed the field from a time when analog studies were collected on paper to computer-assisted collection of digitally transformed studies. Sleep clinicians, whether physicians, respiratory therapists, or sleep technologists, must therefore have an understanding of a broad array of principles underlying the collection of the various signals. In addition, an understanding of basic technical rules in the evaluation of polysomnography studies is necessary for both the scoring and interpretation of such studies. The American Academy of Sleep Medicine published a new manual for the scoring of sleep and associated events in 2007. These changes included modifications to the visual scoring of sleep, the scoring of sleep-disordered breathing events, and movement disorders during sleep. A few early studies have evaluated the effects of the changes in scoring guidelines to the previous Rechtschaffen and Kales (R&K) rules for sleep and the American Academy of Sleep Medicine rules for respiratory events. Some controversy regarding the scoring of respiratory events continues to exist and requires further studies to be performed.
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Polisomnografía , Trastornos del Sueño-Vigilia/diagnóstico , Diagnóstico Diferencial , Humanos , Polisomnografía/instrumentación , Polisomnografía/métodos , Trastornos del Sueño-Vigilia/fisiopatologíaRESUMEN
BACKGROUND: Portable monitoring is a convenient means for diagnosing sleep apnea. However, data on whether one night of monitoring is sufficiently precise for the diagnosis of sleep apnea are limited. RESEARCH QUESTION: The current study sought to determine the variability and misclassification in disease severity over three consecutive nights in a large sample of patients referred for sleep apnea. METHODS: A sample of 10,340 adults referred for sleep apnea testing was assessed. A self-applied type III monitor was used for three consecutive nights. The apnea-hypopnea index (AHI) was determined for each night, and a reference AHI was computed by using data from all 3 nights. Pairwise correlations and the proportion misclassified regarding disease severity were computed for each of the three AHI values against the reference AHI. RESULTS: Strong correlations were observed between the AHI from each of the 3 nights (r = 0.87-0.89). However, substantial within-patient variability in the AHI and significant misclassification in sleep apnea severity were observed based on any 1 night of monitoring. Approximately 93% of the patients with a normal study on the first night and 87% of those with severe sleep apnea on the first night were correctly classified compared with the reference derived from all three nights. However, approximately 20% of the patients with mild and moderate sleep apnea on the first night were misdiagnosed either as not having sleep apnea or as having mild disease, respectively. CONCLUSIONS: In patients with mild to moderate sleep apnea, one night of portable testing can lead to misclassification of disease severity given the substantial night-to-night variability in the AHI.
Asunto(s)
Síndromes de la Apnea del Sueño/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño/clasificación , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: A high prevalence of sleep disordered breathing (SDB) has been reported in persons with Marfan syndrome (MFS), a single gene disorder of connective tissue resulting in premature death from aortic rupture. The burden of SDB and accompanying hemodynamic stress could warrant broad screening in this population. Our goal was to assess the utility of traditional SDB screening tools in our sample of persons with MFS. METHODS: Participants were recruited during an annual Marfan Foundation meeting and Marfan status confirmed using the Ghent criteria. Screening questionnaires were administered and SDB assessed by home sleep testing. We assessed accuracy of screening tools using receiver-operating characteristic curve analyses. RESULTS: The prevalence of moderate-severe SDB was 32% in our sample of 31 MFS participants. The Stop-Bang questionnaire had the highest positive predictive value (PPV) of 60% and the highest negative predictive value (NPV) of 100% using the high- and moderate-risk cut-offs, respectively, and the Berlin questionnaire had a PPV of 50% and an NPV of 92.3% at the high-risk cut-off. When those with mild SDB were included, the Stop-Bang and the Sleep Apnea Clinical Score (SACS) questionnaires demonstrated useful screening accuracies with PPVs of 94.7% and 92.9%, and NPVs of 63.6% and 47.1%, respectively, at the moderate-risk cut-offs. CONCLUSION: A survey of SDB in a sample of persons with MFS reveals not only a high burden of SDB but also that conventional screening instruments have utility if adapted appropriately. Future studies should validate the utility of these screening tools given concerns that SDB may contribute to progression of aortic pathology in MFS.