RESUMEN
Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.
Asunto(s)
Conducción de Automóvil , Apnea Obstructiva del Sueño , Accidentes de Tránsito/prevención & control , Presión de las Vías Aéreas Positiva Contínua , Humanos , Factores de Riesgo , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , SomnolenciaRESUMEN
PURPOSE: To evaluate the differences in reliability and costs of home respiratory polygraphy (HRP) when installed by the patient and by a nurse, in order to determine the factors affecting and to consider the possible generalization of self-setup procedure. Several HRP devices have been validated for obstructive sleep apnea (OSA) diagnosis but convenience of a nurse intervention in HRP installation has been scarcely studied. METHODS: This is a prospective and interventional study. About 301 participants were assigned to 2 groups: self-setup and nurse intervention. Sleep study, questionnaires, and diagnostic procedures were performed following the clinical practice in 2016. Signals were considered lost above 3 min, and success of the test was established according to guidelines. Costs were calculated according to a previous multicenter study. RESULTS: Both groups (self-setup and nurse intervention) resulted homogeneous in age, gender, BMI, and final diagnosis of OSA. Signal losses during the test were similar in both groups. Slightly higher percentage of unsuccessful tests were obtained in the self-setup procedure (5.3 vs 2.0%, p = 0.121). The costs were similar (107 vs 105 ) in the self-setup group as compared to the nurse setup group. CONCLUSIONS: The setup of HRP by either the patient or nurse had similar costs and data acquisition. Both installation procedures of HRP were similar regarding test reliability and costs. Main findings are that self-installation by the patient could be similarly reliable and economic as installation by a nurse, as far as consensus guidelines are followed. This study demonstrates that self-setup of HRP is a potentially viable option for the diagnosis of OSA.
Asunto(s)
Polisomnografía/economía , Polisomnografía/normas , Evaluación de Procesos, Atención de Salud , Autoevaluación , Apnea Obstructiva del Sueño/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros , Estudios ProspectivosRESUMEN
BACKGROUND: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. METHODS: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. FINDINGS: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. INTERPRETATION: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. FUNDING: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/métodos , Ventilación no Invasiva/métodos , Síndrome de Hipoventilación por Obesidad/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Presión de las Vías Aéreas Positiva Contínua/mortalidad , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Tiempo de Internación/estadística & datos numéricos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Ventilación no Invasiva/mortalidad , Síndrome de Hipoventilación por Obesidad/mortalidad , Síndrome de Hipoventilación por Obesidad/fisiopatología , España/epidemiología , Análisis de Supervivencia , Resultado del Tratamiento , Capacidad Vital/fisiología , Adulto JovenRESUMEN
RATIONALE: Despite a significant association between obesity hypoventilation syndrome (OHS) and cardiac dysfunction, no randomised trials have assessed the impact of non-invasive ventilation (NIV) or CPAP on cardiac structure and function assessed by echocardiography. OBJECTIVES: We performed a secondary analysis of the data from the largest multicentre randomised controlled trial of OHS (Pickwick project, n=221) to determine the comparative efficacy of 2 months of NIV (n=71), CPAP (n=80) and lifestyle modification (control group, n=70) on structural and functional echocardiographic changes. METHODS: Conventional transthoracic two-dimensional and Doppler echocardiograms were obtained at baseline and after 2 months. Echocardiographers at each site were blinded to the treatment arms. Statistical analysis was performed using intention-to-treat analysis. RESULTS: At baseline, 55% of patients had pulmonary hypertension and 51% had evidence of left ventricular hypertrophy. Treatment with NIV, but not CPAP, lowered systolic pulmonary artery pressure (-3.4 mm Hg, 95% CI -5.3 to -1.5; adjusted P=0.025 vs control and P=0.033 vs CPAP). The degree of improvement in systolic pulmonary artery pressure was greater in patients treated with NIV who had pulmonary hypertension at baseline (-6.4 mm Hg, 95% CI -9 to -3.8). Only NIV therapy decreased left ventricular hypertrophy with a significant reduction in left ventricular mass index (-5.7 g/m2; 95% CI -11.0 to -4.4). After adjusted analysis, NIV was superior to control group in improving left ventricular mass index (P=0.015). Only treatment with NIV led to a significant improvement in 6 min walk distance (32 m; 95% CI 19 to 46). CONCLUSION: In patients with OHS, medium-term treatment with NIV is more effective than CPAP and lifestyle modification in improving pulmonary hypertension, left ventricular hypertrophy and functional outcomes. Long-term studies are needed to confirm these results. TRIAL REGISTRATION NUMBER: Pre-results, NCT01405976 (https://clinicaltrials.gov/).
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Ecocardiografía Doppler , Ventilación no Invasiva , Síndrome de Hipoventilación por Obesidad/diagnóstico , Síndrome de Hipoventilación por Obesidad/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Presión de las Vías Aéreas Positiva Contínua/métodos , Ecocardiografía Doppler/métodos , Femenino , Estudios de Seguimiento , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Ventilación no Invasiva/métodos , Síndrome de Hipoventilación por Obesidad/fisiopatología , Polisomnografía/métodos , Calidad de Vida , España , Espirometría , Resultado del TratamientoRESUMEN
OBJECTIVE: Obesity and obstructive sleep apnea in children have been associated with metabolic morbidities. The present study aimed to evaluate the presence of metabolic alterations among obese children recruited from the community, with and without obstructive sleep apnea syndrome (OSAS), and the impact of treatment of OSAS on metabolic profiles. METHODS: A cross-sectional, prospective, multicenter study of Spanish children aged 3-14 years with a body mass index (BMI) ≥95th percentile for age and sex were randomly selected in the first phase. Four groups emerged for follow-up: (1) no treatment; (2) dietary intervention; (3) surgical treatment of OSA; and (4) continuous positive airway pressure (CPAP) treatment of OSA. Fasting blood tests were performed at baseline (T0) and approximately one year after the intervention (T1). RESULTS: A total of 113 obese children with a mean age of 11.3 ± 2.9 years completed T0 and T1 assessments. Their mean BMI z-score at T1 was 1.34 ± 0.59, and mean Respiratory Disturbance Index was 8.6 ± 13.0 at T0 and 3.3 ± 4.0/hour total sleep time at T1. Only glucose fasting levels differed among metabolic parameters in obese children with OSAS and without OSAS at baseline (T0) (p = 0.018). There were statistically significant differences between surgically treated OSAS (p = 0.002), and CPAP-treated OSAS (p = 0.024) versus the non-OSAS group in the glucose levels between baseline (T0) and follow-up (T1) after controlling for age and change in BMI. Significant univariate associations between BMI and C-reactive protein, insulin, and homeostasis model assessment of insulin resistance emerged at both T0 and T1. CONCLUSIONS: Concurrent obesity and OSAS could promote metabolic and inflammatory alterations, and the latter appeared to be sensitive to OSAS treatment outcomes. ClinicalTrials.gov Identifier: NCT01322763.
Asunto(s)
Obesidad/complicaciones , Obesidad/metabolismo , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/terapia , Adolescente , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Presión de las Vías Aéreas Positiva Contínua , Estudios Transversales , Dietoterapia , Femenino , Estudios de Seguimiento , Humanos , Insulina/sangre , Modelos Lineales , Masculino , Obesidad/terapia , Apnea Obstructiva del Sueño/complicaciones , Resultado del TratamientoRESUMEN
RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.
Asunto(s)
Oximetría/métodos , Apnea Obstructiva del Sueño/diagnóstico , Ronquido/diagnóstico , Adolescente , Algoritmos , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Ronquido/complicaciones , Encuestas y CuestionariosRESUMEN
Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA.A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events·h-1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12â weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups.Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (-2.04â mmHg, 95% CI -4.02-â-0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (-1.54â mmHg, 95% CI -4.58-1.51; p=0.32) and mean blood pressure (-1.90â mmHg, 95% CI -4.0-0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed.In women with moderate-to-severe OSA, 12â weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment.
Asunto(s)
Presión Sanguínea , Metaboloma , Apnea Obstructiva del Sueño/terapia , Anciano , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Lípidos/sangre , Persona de Mediana Edad , Apnea Obstructiva del Sueño/metabolismo , EspañaRESUMEN
Study Objectives: Nucleosomes and cell-free double-stranded DNA (dsDNA) have been suggested as promising biomarkers in cell death-related diseases, such as acute coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA) in patients with ACS is unclear. Our aim was to evaluate the relationship between OSA, dsDNA, and nucleosomes and to assess their potential implication in the development of ACS. Methods: Up to 549 patients were included in the study and divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All patients underwent a sleep study, and serum concentrations of dsDNA and nucleosomes were measured. Results: Nucleosome and dsDNA levels were higher in patients with OSA than in controls (nucleosomes: 1.47 ± 0.88 arbitary units [AU] vs. 1.00 ± 0.33 AU; p < .001, dsDNA: 315.6 ± 78.0 ng/mL vs. 282.6 ± 55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients with ACS than in non-ACS, independently of the presence of OSA. Conclusions: Both nucleosomes and dsDNA are increased in patients with OSA and might be related with the high cardiovascular risk seen in these patients. The extensive cell lysis during a myocardial infarction seems to be the major contributor to the high biomarker levels, and OSA does not seem to be implicated in such elevation when this acute event occurs. Clinical trial registration: NCT01335087 (clinicaltrials.gov).
Asunto(s)
Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/patología , Biomarcadores/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/patología , Estudios de Casos y Controles , Muerte Celular , ADN/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/patología , Nucleosomas/metabolismo , Polisomnografía , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de RiesgoRESUMEN
STUDY OBJECTIVES: Nocturnal oximetry has become known as a simple, readily available, and potentially useful diagnostic tool of childhood obstructive sleep apnea (OSA). However, at-home respiratory polygraphy (HRP) remains the preferred alternative to polysomnography (PSG) in unattended settings. The aim of this study was twofold: (1) to design and assess a novel methodology for pediatric OSA screening based on automated analysis of at-home oxyhemoglobin saturation (SpO2), and (2) to compare its diagnostic performance with HRP. METHODS: SpO2 recordings were parameterized by means of time, frequency, and conventional oximetric measures. Logistic regression models were optimized using genetic algorithms (GAs) for three cutoffs for OSA: 1, 3, and 5 events/h. The diagnostic performance of logistic regression models, manual obstructive apnea-hypopnea index (OAHI) from HRP, and the conventional oxygen desaturation index ≥ 3% (ODI3) were assessed. RESULTS: For a cutoff of 1 event/h, the optimal logistic regression model significantly outperformed both conventional HRP-derived ODI3 and OAHI: 85.5% accuracy (HRP 74.6%; ODI3 65.9%) and 0.97 area under the receiver operating characteristics curve (AUC) (HRP 0.78; ODI3 0.75) were reached. For a cutoff of 3 events/h, the logistic regression model achieved 83.4% accuracy (HRP 85.0%; ODI3 74.5%) and 0.96 AUC (HRP 0.93; ODI3 0.85) whereas using a cutoff of 5 events/h, oximetry reached 82.8% accuracy (HRP 85.1%; ODI3 76.7) and 0.97 AUC (HRP 0.95; ODI3 0.84). CONCLUSIONS: Automated analysis of at-home SpO2 recordings provide accurate detection of children with high pretest probability of OSA. Thus, unsupervised nocturnal oximetry may enable a simple and effective alternative to HRP and PSG in unattended settings.
Asunto(s)
Oximetría/métodos , Apnea Obstructiva del Sueño/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Monitoreo Ambulatorio/métodos , Polisomnografía , Reproducibilidad de los ResultadosRESUMEN
Road traffic accidents are one of the main causes of death worldwide and are clearly associated with sleepiness. Individuals with undiagnosed sleep apnea-hypopnea syndrome (SAHS) are among the population with a high risk of experiencing sleepiness at the wheel and, consequently, road traffic accidents. Treatment with continuous positive airway pressure (CPAP) has been shown to reduce the risk of accidents among drivers with SAHS. For this reason, the European Union has included this disease in the psychological and physical criteria for obtaining or renewing a driving license. To comply with this European Directive, Spain has updated its driving laws accordingly. To facilitate the implementation of the new regulations, a group of experts from various medical societies and institutions has prepared these guidelines that include questionnaires to screen for SAHS, diagnostic and therapeutic criteria, and physician's report templates.
Asunto(s)
Conducción de Automóvil/legislación & jurisprudencia , Trastornos de Somnolencia Excesiva/etiología , Concesión de Licencias/normas , Síndromes de la Apnea del Sueño/complicaciones , Accidentes de Tránsito/prevención & control , Presión de las Vías Aéreas Positiva Contínua , Humanos , Concesión de Licencias/legislación & jurisprudencia , Polisomnografía , Desempeño Psicomotor , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapia , España , Encuestas y CuestionariosRESUMEN
STUDY OBJECTIVES: Low flow supplemental oxygen is commonly prescribed to patients with obesity hypoventilation syndrome (OHS). However, there is a paucity of data regarding its efficacy and safety. The objective of this study was to assess the medium-term treatment efficacy of adding supplemental oxygen therapy to commonly prescribed treatment modalities in OHS. METHODS: In this post hoc analysis of a previous randomized controlled trial, we studied 302 sequentially screened OHS patients who were randomly assigned to noninvasive ventilation, continuous positive airway pressure, or lifestyle modification. Outcomes at 2 mo included arterial blood gases, symptoms, quality of life, blood pressure, polysomnography, spirometry, 6-min walk distance, and hospital resource utilization. Statistical analysis comparing patients with and without oxygen therapy in the three treatment groups was performed using an intention-to-treat analysis. RESULTS: In the noninvasive ventilation group, supplemental oxygen reduced systolic blood pressure although this could be also explained by a reduction in body weight experienced in this group. In the continuous positive airway pressure group, supplemental oxygen increased the frequency of morning confusion. In the lifestyle modification group, supplemental oxygen increased compensatory metabolic alkalosis and decreased the apnea-hypopnea index during sleep. Oxygen therapy was not associated with an increase in hospital resource utilization in any of the groups. CONCLUSIONS: After 2 mo of follow-up, chronic oxygen therapy produced marginal changes that were insufficient to consider it, globally, as beneficial or deleterious. Because supplemental oxygen therapy did not increase hospital resource utilization, we recommend prescribing oxygen therapy to patients with OHS who meet criteria with close monitoring. Long-term studies examining outcomes such as incident cardiovascular morbidity and mortality are necessary. CLINICAL TRIALS REGISTRATION: Clinicaltrial.gov, ID: NCT01405976.
Asunto(s)
Síndrome de Hipoventilación por Obesidad/terapia , Terapia por Inhalación de Oxígeno/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de los Gases de la Sangre/estadística & datos numéricos , Presión Sanguínea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía/estadística & datos numéricos , Calidad de Vida , España , Espirometría/estadística & datos numéricos , Resultado del Tratamiento , Caminata/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2â months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2)â mmâ Hg versus -2.8 (95% CI -4.3 to -1.3)â mmâ Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) â mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.
Asunto(s)
Ventilación no Invasiva/métodos , Síndrome de Hipoventilación por Obesidad/terapia , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Dióxido de Carbono/sangre , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Síndrome de Hipoventilación por Obesidad/complicaciones , Síndrome de Hipoventilación por Obesidad/fisiopatología , Presión Parcial , Polisomnografía , Pruebas de Función Respiratoria/métodos , Apnea Obstructiva del Sueño/complicaciones , Resultado del Tratamiento , Capacidad Vital/fisiologíaRESUMEN
RATIONALE: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells. OBJECTIVES: To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status. METHODS: Obese children (body mass index z score >1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cell-substrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays. MEASUREMENTS AND MAIN RESULTS: Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways. CONCLUSIONS: These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.
Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Endotelio Vascular/fisiopatología , MicroARNs/fisiología , Apnea Obstructiva del Sueño/complicaciones , Estudios de Casos y Controles , Niño , Exosomas/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Obesidad Infantil/complicaciones , Obesidad Infantil/fisiopatología , Polisomnografía , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
RATIONALE: Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed. OBJECTIVES: To investigate the effect of CPAP on QoL in women with moderate to severe OSA. METHODS: We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, ≥15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables. MEASUREMENTS AND MAIN RESULTS: The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P < 0.001 for all domains), daytime sleepiness (-2.92; P < 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003). CONCLUSIONS: In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071).
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/métodos , Trastornos de Somnolencia Excesiva/prevención & control , Calidad de Vida/psicología , Apnea Obstructiva del Sueño/psicología , Apnea Obstructiva del Sueño/terapia , Afecto , Ansiedad/prevención & control , Ansiedad/psicología , Depresión/prevención & control , Depresión/psicología , Femenino , Humanos , Persona de Mediana Edad , España , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
STUDY OBJECTIVE: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid ß protein 42 (Aß42) and pre-senilin 1 (PS1). METHODS: Fasting morning plasma samples from otherwise healthy children with a diagnosis of OB, OSA, or both (OSA+OB), and controls, and in a subset of children with OSA after adenotonsillectomy (T&A) were assayed for Aß42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits. RESULTS: 286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar Aß42 (108.3 ± 31.7 pg/mL versus 83.6 ± 14.6 pg/mL) and PS1 levels (0.89 ± 0.44 ng/mL versus 0.80 ± 0.29 pg/mL). However, OSA children (Aß42: 186.2 ± 66.7 pg/mL; P < 0.001; PS1: 3.42 ± 1.46 ng/mL; P < 0.001), and particularly OSA+OB children had significant elevations in both Aß42 (349.4 ± 112.9 pg/mL; P < 0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P < 0.001) circulating concentrations. In a subset of 24 children, T&A resulted in significant reductions of Aß42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P < 0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P < 0.0001). CONCLUSIONS: Thus, OSA, and particularly OSA+OB, are associated with increased plasma levels of AD biomarkers, which decline upon treatment of OSA in a representative, yet not all- encompassing subset of patients, suggesting that OSA may accelerate AD-related processes even in early childhood. However, the cognitive and overall health-related implications of these findings remain to be defined.
Asunto(s)
Adenoidectomía , Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/sangre , Fragmentos de Péptidos/sangre , Presenilina-1/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/terapia , Tonsilectomía , Enfermedad de Alzheimer/complicaciones , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Ayuno , Femenino , Humanos , Masculino , Obesidad/sangre , Obesidad/complicaciones , Obesidad/fisiopatología , Polisomnografía , Estudios Retrospectivos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Delgadez/sangreRESUMEN
BACKGROUND: Obesity hypoventilation syndrome (OHS) is associated with a high burden of cardiovascular morbidity (CVM) and mortality. The majority of patients with OHS have concomitant OSA, but there is a paucity of data on the association between CVM and OSA severity in patients with OHS. The objective of our study was to assess the association between CVM and OSA severity in a large cohort of patients with OHS. METHODS: In a cross-sectional analysis, we examined the association between OSA severity based on tertiles of oxygen desaturation index (ODI) and CVM in 302 patients with OHS. Logistic regression models were constructed to quantify the independent association between OSA severity and prevalent CVM after adjusting for various important confounders. RESULTS: The prevalence of CVM decreased significantly with increasing severity of OSA based on ODI as a continuous variable or ODI tertiles. This inverse relationship between OSA severity and prevalence of CVM was seen in the highest ODI tertile and it persisted despite adjustment for multiple confounders. Chronic heart failure had the strongest negative association with the highest ODI tertile. No significant CVM risk change was observed between the first and second ODI tertiles. Patients in the highest ODI tertile were younger, predominantly male, more obese, more hypersomnolent, had worse nocturnal and daytime gas exchange, lower prevalence of hypertension, better exercise tolerance, and fewer days hospitalized than patients in the lowest ODI tertile. CONCLUSIONS: In patients with OHS, the highest OSA severity phenotype was associated with reduced risk of CVM. This finding should guide the design of future clinical trials assessing the impact of interventions aimed at decreasing cardiovascular morbidity and mortality in patients with OHS. TRIAL REGISTRY: Clinicaltrial.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.
Asunto(s)
Enfermedades Cardiovasculares , Síndrome de Hipoventilación por Obesidad , Anciano , Análisis de los Gases de la Sangre/métodos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Estudios Transversales , Femenino , Humanos , Hipoxia/diagnóstico , Hipoxia/etiología , Masculino , Persona de Mediana Edad , Síndrome de Hipoventilación por Obesidad/sangre , Síndrome de Hipoventilación por Obesidad/complicaciones , Síndrome de Hipoventilación por Obesidad/diagnóstico , Síndrome de Hipoventilación por Obesidad/epidemiología , Polisomnografía/métodos , Prevalencia , Factores Protectores , Índice de Severidad de la Enfermedad , EspañaRESUMEN
OBJECTIVE: Hepatocyte apoptosis and macrophage activation contribute to the disease progression of nonalcoholic fatty liver disease (NAFLD). Obstructive sleep apnea (OSA) in obese children is associated with the severity of NAFLD. The aim of this study was to evaluate plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), cytokeratin 18 (CK18) (markers of apoptosis), and soluble CD163 (sCD163) (marker of macrophage activation) in obese children with and without OSA. METHODS: Consecutive obese children who were evaluated for OSA were recruited. The diagnosis of OSA was made using overnight polysomnography (PSG). Fasting blood samples were used to determine plasma CK18, sFas, sFasL, and sCD163 levels using specific sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty-eight subjects were included in the analysis with a mean age of 8.9 ± 3.2 years and a mean body mass index (BMI) z-score of 2.4 ± 0.49. Circulating sFas and sFasL levels were significantly lower in subjects with mild and severe OSA compared with those without OSA (p < 0.005 for both). In addition, sCD163 levels increased with an increasing severity of OSA (no OSA = 1.6 ± 0.25 mg/L, mild OSA = 2.3 ± 0.45, and severe OSA = 3.0 ± 0.52; p < 0.001), and they correlated with the apnea-hypopnea index (AHI) [rho (95% confidence interval, CI) of 0.71 (0.41, 1.00), p-value <0.001]. In six patients with severe OSA from whom samples were taken before and after tonsillectomy, the sCD163 level decreased significantly after treatment, and there was a trend toward an increase in sFasL. CONCLUSION: Markers of apoptosis and macrophage activation are altered in obese children with OSA, indicating increased apoptotic and inflammatory pressures.
Asunto(s)
Apoptosis/fisiología , Hepatocitos/patología , Obesidad/sangre , Obesidad/patología , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/patología , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Proteína Ligando Fas/sangre , Femenino , Humanos , Queratina-18/sangre , Macrófagos del Hígado/patología , Activación de Macrófagos/fisiología , Masculino , Obesidad/complicaciones , Receptores de Superficie Celular/sangre , Apnea Obstructiva del Sueño/complicaciones , Receptor fas/sangreRESUMEN
The first line of treatment of obstructive sleep apnoea syndrome (OSAS) in children consists of adenotonsillectomy (T&A). The aim of the present study was to evaluate treatment outcomes of OSAS among obese children recruited from the community.A cross-sectional, prospective, multicentre study of Spanish obese children aged 3-14â years, with four groups available for follow-up: group 1: non-OSAS with no treatment; group 2: dietary treatment; group 3: surgical treatment; and group 4: continuous positive airway pressure treatment.117 obese children (60 boys, 57 girls) with a mean age of 11.3±2.9â years completed the initial (T0) and follow-up (T1) assessments. Their mean body mass index (BMI) at T1 was 27.6±4.7â kg·m(-2), corresponding to a BMI Z-score of 1.34±0.59. Mean respiratory disturbance index (RDI) at follow-up was 3.3±3.9â events·h(-1). Among group 1 children, 21.2% had an RDI ≥3â events·h(-1) at T1, the latter being present in 50% of group 2, and 43.5% in group 3. In the binary logistic regression model, age emerged as a significant risk factor for residual OSAS (odds ratio 1.49, 95% confidence interval 1.01-2.23; p<0.05) in obese children surgically treated, and RDI at T0 as well as an increase in BMI emerged as significant risk factors for persistent OSAS in obese children with dietary treatment (OR 1.82, 95% CI 1.09-3.02 (p<0.03) and OR 8.71, 95% CI 1.24-61.17 (p=0.03)).Age, RDI at diagnosis and obesity are risk factors for relatively unfavourable OSAS treatment outcomes at follow-up.