RESUMO
The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation.
Assuntos
Galanina , Neurônios , Área Pré-Óptica , Privação do Sono , Animais , Galanina/metabolismo , Galanina/genética , Neurônios/metabolismo , Área Pré-Óptica/metabolismo , Camundongos , Privação do Sono/metabolismo , Privação do Sono/genética , Masculino , RNA-Seq , Camundongos Endogâmicos C57BL , Sono/genética , Sono/fisiologia , Análise de Célula ÚnicaRESUMO
AIM: To assess respiratory symptoms and nocturnal gastro-oesophageal reflux (nGER) among untreated obstructive sleep apnoea (OSA) patients, compared with the general population. Also, if nGER associates differently with respiratory symptoms among OSA patients. METHODS: 2 study cohorts were included: 822 newly diagnosed subjects with moderate-severe OSA and 738 Icelandic general population study participants. All participants answered the same questionnaires. Those reporting nGER symptoms at least once per week were defined as 'with nGER'; those without nGER symptoms and without nGER medication were defined as 'no nGER'; and other participants were defined as having 'possible nGER'. Propensity score-based weights were used to minimise confounding and selection bias and facilitate causal interpretations. RESULTS: The prevalence of nGER among OSA patients was 14.1%, compared with 5.8% in the general population. This increased prevalence in OSA was not explained by differences in age, gender, body mass index, smoking, hypertension and diabetes (adjusted OR (95% CI)=3.79 (2.24 to 6.43)). OSA patients 'with nGER' and with 'possible nGER' reported more wheezing (44% and 44% vs 25%, respectively) and productive cough (47% and 42% vs 29%, respectively), compared with OSA patients with 'no nGER'. The same pattern was seen in the general population, although with a generally lower prevalence. The effect of nGER on respiratory symptoms was similar between the two cohorts. CONCLUSION: nGER was more often reported among untreated moderate-severe OSA patients than in the general population. Participants with nGER had more wheezing and productive cough, both among untreated OSA patients and in the general population.
Assuntos
Refluxo Gastroesofágico , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Sons Respiratórios , Síndromes da Apneia do Sono/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico , TosseRESUMO
STUDY OBJECTIVES: Sleep is an important biological process that is perturbed in numerous diseases, and assessment of its substages currently requires implantation of electrodes to carry out electroencephalogram/electromyogram (EEG/EMG) analysis. Although accurate, this method comes at a high cost of invasive surgery and experts trained to score EEG/EMG data. Here, we leverage modern computer vision methods to directly classify sleep substages from video data. This bypasses the need for surgery and expert scoring, provides a path to high-throughput studies of sleep in mice. METHODS: We collected synchronized high-resolution video and EEG/EMG data in 16 male C57BL/6J mice. We extracted features from the video that are time and frequency-based and used the human expert-scored EEG/EMG data to train a visual classifier. We investigated several classifiers and data augmentation methods. RESULTS: Our visual sleep classifier proved to be highly accurate in classifying wake, non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) states, and achieves an overall accuracy of 0.92 ± 0.05 (mean ± SD). We discover and genetically validate video features that correlate with breathing rates, and show low and high variability in NREM and REM sleep, respectively. Finally, we apply our methods to noninvasively detect that sleep stage disturbances induced by amphetamine administration. CONCLUSIONS: We conclude that machine learning-based visual classification of sleep is a viable alternative to EEG/EMG based scoring. Our results will enable noninvasive high-throughput sleep studies and will greatly reduce the barrier to screening mutant mice for abnormalities in sleep.
Assuntos
Fases do Sono , Vigília , Animais , Eletroencefalografia , Eletromiografia , Aprendizado de Máquina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sono , Sono REMRESUMO
OBJECTIVE: Continuous positive airway pressure (CPAP) therapy reduces circulating intercellular adhesion molecule 1 (ICAM-1) in adults with obstructive sleep apnea (OSA). ICAM-1 levels may affect the daytime sleepiness and elevated blood pressure associated with OSA. We evaluated the association of changes from baseline in ICAM-1 with changes of objective and subjective measures of sleepiness, as well as 24-h ambulatory blood pressure monitoring (ABPM) measures, following 4 months of CPAP treatment. METHODS: The study sample included adults with newly diagnosed OSA. Plasma ICAM-1, 24-h ABPM, Epworth Sleepiness Scale (ESS), and psychomotor vigilance task (PVT) were obtained at baseline and following adequate CPAP treatment. The associations between changes in natural log ICAM-1 and changes in the number of lapses on PVT, ESS score, and 24-h mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, anti-hypertensive medications, AHI, and daily hours of CPAP use. RESULTS: Among 140 adults (83% men), mean (± SD) body mass index (BMI) was 31.5 ± 4.2 kg/m2, and apnea-hyopnea index (AHI) was 36.8 ± 15.3 events/h. Sleepiness measures, although not ICAM-1 or ABPM measures, improved significantly following CPAP treatment. We observed no statistically significant associations between the change in ICAM-1 and changes in sleepiness, MAP, or other ABPM measures. CONCLUSION: Changes in ICAM-1 levels were not related to changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Future work should explore whether or not other biomarkers may have a role in mediating these treatment outcomes in adults with OSA.
Assuntos
Pressão Sanguínea/fisiologia , Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Molécula 1 de Adesão Intercelular/metabolismo , Apneia Obstrutiva do Sono/terapia , Sonolência/fisiologia , Adulto , Idoso , Monitorização Ambulatorial da Pressão Arterial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do TratamentoRESUMO
Physical inactivity is a leading determinant of noncommunicable diseases. Yet, many adults remain physically inactive. Physical activity guidelines do not account for the multidimensionality of physical activity, such as the type or variety of physical activity behaviors. This study identified patterns of physical activity across multiple dimensions (e.g., frequency, duration, and variety) using a nationally representative sample of adults. Sociodemographic characteristics, health behaviors, and clinical characteristics associated with each physical activity pattern were defined. Multivariate finite mixture modeling was used to identify patterns of physical activity among 2003-2004 and 2005-2006 adult National Health and Nutrition Examination Survey participants. Chi-square tests were used to identify sociodemographic differences within each physical activity cluster and test associations between the physical activity clusters with health behaviors and clinical characteristics. Five clusters of physical activity patterns were identified: (a) low frequency, short duration (n = 730, 13%); (b) low frequency, long duration (n = 392, 7%); (c) daily frequency, short duration (n = 3,011, 55%); (d) daily frequency, long duration (n = 373, 7%); and (e) high frequency, average duration (n = 964, 18%). Walking was the most common form of activity; highly active adults engaged in more varied types of activity. High-activity clusters were comprised of a greater proportion of younger, White, nonsmoking adult men reporting moderate alcohol use without mobility problems or chronic health conditions. Active females engaged in frequent short bouts of activity. Data-driven approaches are useful for identifying clusters of physical activity that encompass multiple dimensions of activity. These activity clusters vary across sociodemographic and clinical subgroups.
Assuntos
Exercício Físico , Comportamentos Relacionados com a Saúde , Adulto , Feminino , Humanos , Masculino , Atividade Motora , Inquéritos Nutricionais , Comportamento SedentárioRESUMO
Rationale: Obesity is the primary risk factor for obstructive sleep apnea (OSA). Tongue fat is increased in obese persons with OSA, and may explain the relationship between obesity and OSA. Weight loss improves OSA, but the mechanism is unknown.Objectives: To determine the effect of weight loss on upper airway anatomy in subjects with obesity and OSA. We hypothesized that weight loss would decrease soft tissue volumes and tongue fat, and that these changes would correlate with reductions in apnea-hypopnea index (AHI).Methods: A total of 67 individuals with obesity and OSA (AHI ≥ 10 events/h) underwent a sleep study and upper airway and abdominal magnetic resonance imaging before and after a weight loss intervention (intensive lifestyle modification or bariatric surgery). Airway sizes and soft tissue, tongue fat, and abdominal fat volumes were quantified. Associations between weight loss and changes in these structures, and relationships to AHI changes, were examined.Measurements and Main Results: Weight loss was significantly associated with reductions in tongue fat and pterygoid and total lateral wall volumes. Reductions in tongue fat were strongly correlated with reductions in AHI (Pearson's rho = 0.62, P < 0.0001); results remained after controlling for weight loss (Pearson's rho = 0.36, P = 0.014). Reduction in tongue fat volume was the primary upper airway mediator of the relationship between weight loss and AHI improvement.Conclusions: Weight loss reduced volumes of several upper airway soft tissues in subjects with obesity and OSA. Improved AHI with weight loss was mediated by reductions in tongue fat. New treatments that reduce tongue fat should be considered for patients with OSA.
Assuntos
Obesidade/complicações , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Língua/anatomia & histologia , Língua/fisiologia , Redução de Peso/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estados Unidos/epidemiologiaRESUMO
We hypothesized that positive airway pressure treatment would induce nasal obstruction and decrease nasal cavity due to mucosal swelling. We further hypothesized that subjective and objective nasal obstruction at baseline would negatively affect positive airway pressure adherence. A total of 728 patients with sleep apnea were investigated in the Icelandic Sleep Apnea Cohort at baseline and 2â years after starting positive airway pressure. Patients underwent home sleep apnea testing at baseline. Questionnaires were answered and acoustic rhinometry was completed at baseline and follow-up. The proportion of patients reporting subjective nocturnal nasal obstruction was reduced (baseline: 35% versus follow-up: 24%; p < 0.001). Small interior nasal dimensions increased (pâ <â 0.001) independent of adherence to treatment. Small nasal volume at baseline was a determinant for becoming a non-user of positive airway pressure treatment (odds ratio 2.22, confidence interval 95% 1.35-3.67, pâ =â 0.002). Subjective nasal obstruction decreased 2â years after initiating positive airway treatment in sleep apnea, and objectively small nasal dimensions increased. Small nasal volume at baseline was a negative predictor for positive airway pressure treatment adherence. Maybe most importantly, positive airway pressure treatment did not cause long-term objective or subjective nasal obstruction.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Obstrução Nasal/terapia , Rinometria Acústica/métodos , Apneia Obstrutiva do Sono/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Sleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D). METHODS: Adults (N = 918) from the general population who were a part of the São Paulo Epidemiologic Sleep Study (EPISONO) in São Paulo, Brazil, were genotyped using Human Omni Express BeadChip array. The average age was 42 ± 14.5 years, subjects had a mean body mass index (BMI) of 26.9 ± 5.4 kg/m2, and 44% were male. Based on the Epworth Sleepiness Scale (ESS), subjects were classified as having sleepiness (ESS ≥ 10) or no sleepiness (ESS < 10). Logistic regression models were used to examine the associations with SNPs within candidate genes and sleepiness, adjusting for age, gender, BMI, Apnea-Hypopnea Index (AHI), total sleep time, and ancestry informative principal components (PCs). Complementary analyses using linear regression to assess the relationship between SNPs and continuous ESS were performed. RESULTS: We observed a novel association between the C allele of the rs12522161 SNP on PDE4D and a decreased likelihood of sleepiness, controlling for covariates and ancestry [OR (95% CI) = 0.64 (0.50, 0.81); p = 0.0002]. CONCLUSION: We present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.
Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Epidemiologia Molecular , Sonolência , Adulto , Alelos , Índice de Massa Corporal , Brasil , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Polissonografia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk. METHODS: An exploratory case-control sample of 36 subjects, categorized based on the Epworth Sleepiness Scale (ESS) questionnaire as sleepy (ESS ≥ 10) or non-sleepy (ESS < 10), was recruited among subjects undergoing an overnight sleep study for suspected sleep apnea at the University of Pennsylvania Sleep Center. The average age was 42.4 ± 10.5 years, the mean body mass index (BMI) was 40.0 ± 9.36 kg/m2, median Apnea Hypopnea Index (AHI) was 8.2 (IQR: 2.5-26.5), and 52% were male. Fasting morning blood plasma samples were collected after an overnight sleep study. Biomarkers were explored in subjects with sleepiness versus those without using the multiple linear regression adjusting for age, BMI, smoking, Apnea Hypopnea Index (sleep apnea severity), study cohort, and hypertension. RESULTS: The level of choline is significantly lower (P = 0.003) in sleepy subjects (N = 18; mean plasma choline concentration of 8.19 ± 2.62 µmol/L) compared with non-sleepy subjects (N = 18; mean plasma choline concentration of 9.14 ± 2.25 µmol/L). Other markers with suggestive differences (P < 0.1) include isovalerylcarnitine, Alpha-Amino apidipic acid, Spingosine 1 Phosphate, Aspartic Acid, Propionylcarnitine, and Ceramides (fatty acids; C14-C16 and C-18). CONCLUSION: This pilot study is the first to show that lower levels of plasma choline metabolites are associated with sleepiness. Further exploration of choline and other noted metabolites and their associations with sleepiness will guide targeted symptom management.
Assuntos
Colina/sangue , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Sonolência , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Polissonografia , Fatores de RiscoRESUMO
Study Objective: To validate that the symptomless Multi-Variable Apnea Prediction index (sMVAP) is associated with Obstructive Sleep Apnea (OSA) diagnosis and assess the relationship between sMVAP and adverse outcomes in patients having elective surgery. We also compare associations between Bariatric surgery, where preoperative screening for OSA risk is mandatory, and non-Bariatric surgery groups who are not screened routinely for OSA. Methods: Using data from 40 432 elective inpatient surgeries, we used logistic regression to determine the relationship between sMVAP and previous OSA, current hypertension, and postoperative complications: extended length of stay (ELOS), intensive-care-unit-stay (ICU-stay), and respiratory complications (pulmonary embolism, acute respiratory distress syndrome, and/or aspiration pneumonia). Results: Higher sMVAP was associated with increased likelihood of previous OSA, hypertension and all postoperative complications (p < .0001). The top sMVAP quintile had increased odds of postoperative complications compared to the bottom quintile. For ELOS, ICU-stay, and respiratory complications, respective odds ratios (95% CI) were: 1.83 (1.62, 2.07), 1.44 (1.32, 1.58), and 1.85 (1.37, 2.49). Compared against age-, gender- and BMI-matched patients having Bariatric surgery, sMVAP was more strongly associated with postoperative complications in non-Bariatric surgical groups, including: (1) ELOS (Orthopedics [p < .0001], Gastrointestinal [p = .024], Neurosurgery [p = .016], Spine [p = .016]); (2) ICU-stay (Orthopedics [p = .0004], Gastrointestinal [p < .0001], and Otorhinolaryngology [p = .0102]); and (3) respiratory complications (Orthopedics [p =.037] and Otorhinolaryngology [p =.011]). Conclusions: OSA risk measured by sMVAP correlates with higher risk for select postoperative complications. Associations are stronger for non-Bariatric surgeries, where preoperative screening for OSA is not routinely performed. Thus, preoperative screening may reduce OSA-related risk for adverse postoperative outcomes.
Assuntos
Procedimentos Cirúrgicos Eletivos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Síndromes da Apneia do Sono/diagnóstico , Apneia Obstrutiva do Sono/complicações , Adulto , Cirurgia Bariátrica/efeitos adversos , Feminino , Humanos , Hipertensão/complicações , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Razão de Chances , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Fatores de Risco , Síndromes da Apneia do Sono/complicações , Apneia Obstrutiva do Sono/diagnósticoRESUMO
Sleep is found widely in the animal kingdom. Despite this, few conserved molecular pathways that govern sleep across phyla have been described. The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. However, the role of FABP7 in regulating sleep remains poorly understood. We found that the missense mutation FABP7.T61M is associated with fragmented sleep in humans. This phenotype was recapitulated in mice and fruitflies bearing similar mutations: Fabp7-deficient mice and transgenic flies that express the FABP7.T61M missense mutation in astrocytes also show fragmented sleep. These results provide novel evidence for a distinct molecular pathway linking lipid-signaling cascades within astrocytes in sleep regulation among phylogenetically disparate species.
Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Proteína 7 de Ligação a Ácidos Graxos/biossíntese , Transdução de Sinais/fisiologia , Sono/fisiologia , Proteínas Supressoras de Tumor/biossíntese , Animais , Astrócitos/citologia , Relógios Biológicos/fisiologia , Encéfalo/citologia , Drosophila melanogaster , Proteína 7 de Ligação a Ácidos Graxos/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto , Proteínas Supressoras de Tumor/genéticaRESUMO
Obstructive sleep apnea (OSA) is a worldwide disease whose prevalence is increasing as obesity rates increase. The link between obesity and OSA is likely to be the deposition of fat in the tongue, compromising upper airway size. The role of obesity varies in different ethnic groups, with Chinese being particularly sensitive to increases in weight. OSA lends itself to a personalized approach to diagnosis and therapy. For example, different clinical OSA subtypes likely benefit from therapy in different ways. Hypoglossal nerve stimulation is a useful second-line therapy in patients who cannot tolerate continous positive airway pressure (CPAP) machines or intraoral devices. Technological advances allow patients to participate in their own care, and doing so improves CPAP compliance. We are entering a future where we can focus efforts to predict and prevent OSA on an individual level.
Assuntos
Neoplasias/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Disfunção Cognitiva/epidemiologia , Pressão Positiva Contínua nas Vias Aéreas , Demência/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Terapia por Estimulação Elétrica , Humanos , Nervo Hipoglosso , Incidência , Medicina de Precisão , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/terapia , Distúrbios do Início e da Manutenção do Sono/etiologiaRESUMO
Recent studies have shown an association between obstructive sleep apnea (OSA) and cognitive impairment. This study was done to investigate whether varied levels of cyclical intermittent hypoxia (CIH) differentially affect the microvasculature in the hippocampus, operating as a mechanistic link between OSA and cognitive impairment. We exposed C57BL/6 mice to sham [continuous air, arterial O2 saturation (SaO2 ) 97%], severe CIH to inspired O2 fraction (FiO2 ) = 0.10 (CIH10; SaO2 nadir of 61%), or very severe CIH to FiO2 = 0.05 (CIH5; SaO2 nadir of 37%) for 12 h/day for 2 wk. We quantified capillary length using neurostereology techniques in the dorsal hippocampus and utilized quantitative PCR methods to measure changes in sets of genes related to angiogenesis and to metabolism. Next, we employed immunohistochemistry semiquantification algorithms to quantitate GLUT1 protein on endothelial cells within hippocampal capillaries. Capillary length differed among CIH severity groups (P = 0.013) and demonstrated a linear relationship with CIH severity (P = 0.002). There was a strong association between CIH severity and changes in mRNA for VEGFA (P < 0.0001). Less strong, but nominally significant associations with CIH severity were also observed for ANGPT2 (PANOVA = 0.065, PTREND = 0.040), VEGFR2 (PANOVA = 0.032, PTREND = 0.429), and TIE-2 (PANOVA = 0.006, PTREND = 0.010). We found that the CIH5 group had increased GLUT1 protein relative to sham (P = 0.006) and CIH10 (P = 0.001). There was variation in GLUT1 protein along the microvasculature in different hippocampal subregions. An effect of CIH5 on GLUT1 mRNA was seen (PANOVA = 0.042, PTREND = 0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity.
Assuntos
Capilares/fisiopatologia , Hipocampo/fisiopatologia , Hipóxia/fisiopatologia , Microvasos/fisiopatologia , Angiopoietina-2/metabolismo , Animais , Capilares/metabolismo , Modelos Animais de Doenças , Transportador de Glucose Tipo 1/metabolismo , Hipocampo/metabolismo , Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/metabolismo , RNA Mensageiro/metabolismo , Receptor TIE-2/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. METHODS: Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. RESULTS: The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m(2) . On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. CONCLUSIONS: OSA severity and its accompanying hypoxia are associated with the severity of NAFLD.
Assuntos
Hipóxia/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade Mórbida/complicações , Apneia Obstrutiva do Sono/complicações , Adulto , Cirurgia Bariátrica , Estudos de Coortes , Feminino , Humanos , Hipóxia/etiologia , Inflamação , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Polissonografia , Índice de Gravidade de DoençaRESUMO
Obstructive sleep apnea leads to recurrent arousals from sleep, oxygen desaturations, daytime sleepiness and fatigue. This can have an adverse impact on quality of life. The aims of this study were to compare: (i) quality of life between the general population and untreated patients with obstructive sleep apnea; and (ii) changes of quality of life among patients with obstructive sleep apnea after 2 years of positive airway pressure treatment between adherent patients and non-users. Propensity score methodologies were used in order to minimize selection bias and strengthen causal inferences. The enrolled obstructive sleep apnea subjects (n = 822) were newly diagnosed with moderate to severe obstructive sleep apnea who were starting positive airway pressure treatment, and the general population subjects (n = 742) were randomly selected Icelanders. The Short Form 12 was used to measure quality of life. Untreated patients with obstructive sleep apnea had a worse quality of life when compared with the general population. This effect remained significant after using propensity scores to select samples, balanced with regard to age, body mass index, gender, smoking, diabetes, hypertension and cardiovascular disease. We did not find significant overall differences between full and non-users of positive airway pressure in improvement of quality of life from baseline to follow-up. However, there was a trend towards more improvement in physical quality of life for positive airway pressure-adherent patients, and the most obese subjects improved their physical quality of life more. The results suggest that co-morbidities of obstructive sleep apnea, such as obesity, insomnia and daytime sleepiness, have a great effect on life qualities and need to be taken into account and addressed with additional interventions.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Qualidade de Vida , Apneia Obstrutiva do Sono/psicologia , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Fadiga/epidemiologia , Fadiga/psicologia , Feminino , Humanos , Islândia/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/psicologia , Cooperação do Paciente , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologiaRESUMO
The aim of this study was to evaluate changes in interleukin (IL)-6 and soluble IL-6 receptor levels in obstructive sleep apnea patients and assess the role of positive airway pressure treatment and obesity on these changes. A total of 309 newly diagnosed subjects with sleep apnea from the Icelandic Sleep Apnea Cohort were referred for treatment and reassessed at a 2-year follow-up. Full treatment was defined objectively as use ≥ 4 h day(-1) and ≥ 20 days month(-1). At the 2-year follow-up, there were 177 full users, 44 partial users and 88 non-users. The mean change in biomarker levels from baseline to the 2-year follow-up was assessed in a primary model that included adjustment for baseline biomarker levels, baseline body mass index and change in body mass index, as well as after adjustment for numerous relevant covariates. No significant overall difference in IL-6 level change was found among full, partial and non-users. However, in severely obese patients (body mass index ≥ 35), a significant increase in IL-6 levels during the 2-year period was found in partial and non-users, compared to no change in full users. Results were attenuated in a smaller propensity score matched subsample, although similar trends were observed. No differences were found in soluble IL-6 receptor levels between full users and non-users, after adjustment for confounders. In conclusion, among untreated obese sleep apnea patients, IL-6 levels increase substantially during 2 years, while adherence to positive airway pressure treatment may prevent further increases in this inflammatory biomarker.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Interleucina-6/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Biomarcadores/análise , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Islândia , Interleucina-6/análise , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Receptores de Interleucina-6/análise , Receptores de Interleucina-6/metabolismo , Apneia Obstrutiva do Sono/metabolismoRESUMO
STUDY OBJECTIVES: To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait. DESIGN: Prospective, observational cohort study. SETTING: Academic medical center. PARTICIPANTS: There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram. INTERVENTIONS: Thirty-eight hr of monitored, continuous sleep deprivation. MEASUREMENTS AND RESULTS: Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h(2)) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P < 0.0001) of twin variance was attributed to combined additive and dominance genetic effects. CONCLUSION: Genetic factors explain a large fraction of interindividual variance among rates of performance deficit accumulations on PVT during sleep deprivation.
Assuntos
Adenosina Desaminase/genética , Proteínas Circadianas Period/genética , Desempenho Psicomotor , Tempo de Reação/genética , Privação do Sono/genética , Doença Aguda , Adulto , Análise de Variância , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genéticaRESUMO
STUDY OBJECTIVES: To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels. DESIGN: Cross-sectional cohort. SETTING: The Icelandic Sleep Apnea Cohort. PARTICIPANTS: 454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO2) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m²). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO2 only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women. CONCLUSIONS: OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients.
Assuntos
Proteína C-Reativa/análise , Interleucina-6/sangue , Obesidade/complicações , Apneia Obstrutiva do Sono/complicações , Gordura Abdominal/anatomia & histologia , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Apneia Obstrutiva do Sono/sangueRESUMO
BACKGROUND: The prevalence of obstructive sleep apnea syndrome (OSAS) is higher in children with sickle cell disease (SCD) as compared with the general pediatric population. It has been speculated that overgrowth of the adenoid and tonsils is an important contributor. METHODS: The current study used MRI to evaluate such an association. We studied 36 subjects with SCD (aged 6.9 ± 4.3 years) and 36 control subjects (aged 6.6 ± 3.4 years). RESULTS: Compared with control subjects, children with SCD had a significantly smaller upper airway (2.8 ± 1.2 cm(3) vs 3.7 ± 1.6 cm(3), P < .01), and significantly larger adenoid (8.4 ± 4.1 cm(3) vs 6.0 ± 2.2 cm(3), P < .01), tonsils (7.0 ± 4.3 cm(3) vs 5.1 ± 1.9 cm(3), P < .01), retropharyngeal nodes (3.0 ± 1.9 cm(3) vs 2.2 ± 0.9 cm(3), P < .05), and deep cervical nodes (15.7 ± 5.7 cm(3) vs 12.7 ± 4.0 cm(3), P < .05). Polysomnography showed that 19.4% (seven of 36) of children with SCD had OSAS compared with 0% (zero of 20) of control subjects (P < .05) and that in children with SCD the apnea-hypopnea index correlated positively with upper airway lymphoid tissues size (r = 0.57, P < 001). In addition, children with SCD had lower arterial oxygen saturation nadir (84.3% ± 12.3% vs 91.2% ± 4.2%, P < .05), increased peak end-tidal CO(2) (53.4 ± 8.5 mm Hg vs 42.3 ± 5.3 mm Hg, P < .001), and increased arousals (13.7 ± 4.7 events/h vs 10.8 ± 3.8 events/h, P < .05). CONCLUSIONS: Children with SCD have reduced upper airway size due to overgrowth of the surrounding lymphoid tissues, which may explain their predisposition to OSAS.