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J Sleep Res ; 29(1): e12889, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31257666


The high prevalence of obstructive sleep apnea has led to increasing interest in ambulatory diagnosis. The SleepMinder™ (SM) is a novel non-contact device that employs radiofrequency wave technology to assess the breathing pattern, and thereby estimate obstructive sleep apnea severity. We assessed the performance of SleepMinder™ in the home diagnosis of obstructive sleep apnea. One-hundred and twenty-two subjects were prospectively recruited in two protocols, one from an unselected sleep clinic cohort (n = 67, mean age 51 years) and a second from a hypertension clinic cohort (n = 55, mean age 58 years). All underwent 7 consecutive nights of home monitoring (SMHOME ) with the SleepMinder™ as well as inpatient-attended polysomnography in the sleep clinic cohort or cardiorespiratory polygraphy in the hypertension clinic cohort with simultaneous SleepMinder™ recordings (SMLAB ). In the sleep clinic cohort, median SMHOME apnea-hypopnea index correlated significantly with polysomnography apnea-hypopnea index (r = .68; p < .001), and in the hypertension clinic cohort with polygraphy apnea-hypopnea index (r = .7; p < .001). The median SMHOME performance against polysomnography in the sleep clinic cohort showed a sensitivity and specificity of 72% and 94% for apnea-hypopnea index ≥ 15. Device performance was inferior in females. In the hypertension clinic cohort, SMHOME showed a 50% sensitivity and 72% specificity for apnea-hypopnea index ≥ 15. SleepMinder™ classified 92% of cases correctly or within one severity class of the polygraphy classification. Night-to-night variability in home testing was relatively high, especially at lower apnea-hypopnea index levels. We conclude that the SleepMinder™ device provides a useful ambulatory screening tool, especially in a population suspected of obstructive sleep apnea, and is most accurate in moderate-severe obstructive sleep apnea.

J Clin Sleep Med ; 15(7): 957-963, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31383232


STUDY OBJECTIVES: Systemic hypertension is highly prevalent in obstructive sleep apnea (OSA) but there are limited data on OSA prevalence in cohorts with hypertension comparing dippers and nondippers. We investigated this relationship in a clinic-based cohort of patients with hypertension who were not screened for any pretest possibility of OSA. METHODS: A total of 100 patients with hypertension aged (mean ± SD) 58 ± 10 years, body mass index 30.5 ± 6.1 kg/m2, and Epworth Sleepiness Scale score 6 ± 4 were included. All underwent overnight attended sleep studies and 24-hour ambulatory blood pressure monitoring. The primary study end-point was OSA prevalence based on the standard criteria of apnea-hypopnea index (AHI) ≥ 15 events/h in patients with dipping and nondipping nocturnal blood pressure. RESULTS: Results showed 10.5% of dippers and 43.5% of nondippers had an AHI ≥ 15 (chi-square P = .001). In univariate analysis, AHI correlated significantly with blood pressure dip (r = -.26, P < .05), as did ESS (r = -.28, P < .05). In linear regression, AHI predicted the magnitude of blood pressure dip (standardised ß = -.288, P = .03), whereas age, body mass index, systolic blood pressure and diastolic blood pressure did not. CONCLUSIONS: Patients with nondipping nocturnal blood pressure are at high risk of OSA, regardless of symptom profile, which supports the recommendation that such patients should be assessed for co-existing OSA.

Eur Respir J ; 49(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28424360


Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort.IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA. Providing mechanistic insight, IH induced a pro-inflammatory phenotype of visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation correlating with the severity of insulin resistance. Complimentary in vitro analysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages. In subjects without comorbidities (n=186), OSA was independently associated with insulin resistance. Furthermore, we found an independent correlation of OSA severity with the M1 macrophage inflammatory marker sCD163.This study provides evidence that IH induces a pro-inflammatory phenotype of the adipose tissue, which may be a crucial link between OSA and the development of insulin resistance.

Hipóxia/metabolismo , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Obesidade/complicações , Apneia Obstrutiva do Sono/metabolismo , Células 3T3-L1 , Adulto , Animais , Humanos , Inflamação/metabolismo , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Modelos Lineares , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Distribuição Aleatória , Apneia Obstrutiva do Sono/fisiopatologia
J Cardiovasc Comput Tomogr ; 11(3): 227-233, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28229911


AIM: To assess the diagnostic accuracy of common carotid artery intima media thickness (CIMT) for coronary artery disease (CAD) detection in patients with obstructive sleep apnoea (OSA). MATERIALS & METHODS: Patients with clinically suspected OSA prospectively underwent polysomnography (PSG), ultrasound CIMT measurement and coronary computed tomography angiography (CTA). An average CIMT of ≥0.9 mm in either common carotid artery designated as a positive test. Coronary CTA was the reference standard for the presence of CAD. Coronary plaque presence, volume, density and type were correlated with CIMT findings. RESULTS: 35 consecutive male patients were enrolled from sleep clinic. Two patients had no evidence of OSA on PSG (apnoea-hypopnea index [AHI]<5/hr), and were excluded. Of the remaining 33, 18 (54%) had mild-moderate OSA (AHI 5-30/hr) and 15 (46%) had severe OSA (AHI >30/hr). Eight (24%) patients had CAD on coronary CTA. Coronary plaques were predominantly non- or partly calcified, and located in proximal coronary artery segments. Sensitivity, specificity, positive and negative predictive and likelihood ratios for a positive CIMT (≥0.9 mm) in diagnosing CAD were 0.5 (95% confidence interval: 0.76-0.12), 0.96 (1-0.89), 80, 85.7, 12.5 and 0.52 respectively. The adjusted odds ratio was 40.8. CONCLUSION: In patients with OSA, CIMT is a highly specific but poorly sensitive test for detecting CAD.

Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Placa Aterosclerótica , Apneia Obstrutiva do Sono/complicações , Adulto , Idoso , Doenças das Artérias Carótidas/complicações , Doença da Artéria Coronariana/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico
Biochem Biophys Res Commun ; 447(4): 660-5, 2014 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-24755071


INTRODUCTION: Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmented inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages. METHODS AND RESULTS: Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-α. IH led to a robust increase in NF-κB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-κB response of adipocytes to both IH and TNF-α was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-κB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-α with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes. CONCLUSION: Human adipocytes demonstrate strong sensitivity to inflammatory gene expression in response to acute IH and hence, adipose tissue may be a key source of inflammatory mediators in OSA.

Adipócitos Brancos/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Mediadores da Inflamação/metabolismo , Fator de Transcrição RelA/metabolismo , Transporte Ativo do Núcleo Celular , Adipocinas/genética , Adipocinas/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Cultivadas , DNA/genética , DNA/metabolismo , Regulação da Expressão Gênica , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/metabolismo , Fator de Transcrição RelA/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
Expert Rev Respir Med ; 8(1): 79-88, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24378218


Sleep may have several negative consequences in patients with chronic obstructive pulmonary disease (COPD). Sleep is typically fragmented with diminished slow wave and rapid-eye-movement sleep, which likely represents an important contributing factor to daytime symptoms such as fatigue and lethargy. Furthermore, normal physiological adaptations during sleep, which result in mild hypoventilation in normal subjects, are more pronounced in COPD, which can result in clinically important nocturnal oxygen desaturation. The co-existence of obstructive sleep apnea and COPD is also common, principally because of the high prevalence of each disorder, and there is little convincing evidence that one disorder predisposes to the other. Nonetheless, this co-existence, termed the overlap syndrome, typically results in more pronounced nocturnal oxygen desaturation and there is a high prevalence of pulmonary hypertension in such patients. Management of sleep disorders in patients with COPD should address both sleep quality and disordered gas exchange. Non-invasive pressure support is beneficial in selected cases, particularly during acute exacerbations associated with respiratory failure, and is particularly helpful in patients with the overlap syndrome. There is limited evidence of benefit from pressure support in the chronic setting in COPD patients without obstructive sleep apnea.

Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Comorbidade , Gerenciamento Clínico , Fadiga/epidemiologia , Fadiga/fisiopatologia , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Hipoventilação/epidemiologia , Hipoventilação/fisiopatologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/terapia , Transtornos do Sono-Vigília/terapia