Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

Study Objectives

1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy.

Design

Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed.

Setting

Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m.

Patients

Study 1: 39 OSAS patients. Study 2: 41 OSAS patients.

Interventions

Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes.

Measurements and Results

An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%).

Conclusions

The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.     

Effect of Continuous Positive Airway Pressure on Adiponectin in Patients with Obstructive Sleep Apnea: A Meta-Analysis

Objective

Obstructive sleep apnea (OSA) has been suggested to be associated with low levels of adiponectin. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; however, previous studies assessing the effect of CPAP on adiponectin in patients with OSA yielded conflicting results. The present meta-analysis was performed to determine whether CPAP therapy could increase adiponectin levels.

Methods

Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before February 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum adiponectin was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy.

Results

Eleven studies involving 240 patients were included in this meta-analysis, including ten observational studies and one randomized controlled study. The meta-analysis showed that there was no change of adiponectin levels before and after CPAP treatment in OSA patients (SMD = 0.059, 95% confidence interval (CI) = −0.250 to 0.368, z = 0.37, p = 0.710). Subgroup analyses indicated that the results were not affected by age, baseline body mass index, severity of OSA, CPAP therapy duration, sample size and racial differences.

Conclusions

This meta-analysis suggested that CPAP therapy has no impact on adiponectin in OSA patients, without significant changes in body weight. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.     

Continuous Positive Airway Pressure Treatment Reduces Mortality in Elderly Patients with Moderate to Severe Obstructive Severe Sleep Apnea: A Cohort Study

Obstructive sleep apnea (OSA) is much more prevalent in older people than in middle-aged or young populations, and has been associated with cardiovascular disease. Continuous positive airway pressure (CPAP) is the first-line therapy for OSA, but its long-term clinical benefit in the elderly is unclear. Here, we carried out a prospective cohort study to explore the survival rate and incidence of cardiovascular events in elderly patients with moderate to severe OSA who did or did not receive CPAP treatment. The study included 130 patients (104 male, 26 female; mean age: 77.8 ± 6.2 years) who were followed up for a mean of 5 ± 2.54 years (range, 1–8 years). Thirty-six patients received CPAP and 88 had no CPAP. The results showed that mortality in the untreated group (21.6%) was significantly higher than in the CPAP group (5.6%). Kaplan–Meier survival analysis showed that the survival rate in the CPAP group was 94.4%, which was markedly higher than the rate of 78.4% in the untreated group. The incidence of cardiovascular events was 13.9% in the CPAP group and 55.7% in the untreated group. The present study provides evidence that CPAP can reduce mortality in older patients with moderate to severe OSA, and lead to a good long-term prognosis. The study also indicates that death in older OSA patients is associated with cardiovascular disease and diabetes.     

Impact of Untreated Obstructive Sleep Apnea on Left and Right Ventricular Myocardial Function and Effects of CPAP Therapy

Background

Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular (LV, RV) function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability.

Methods and Results

82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA (apical RV-Sl: P = 0.0002, BMI: P = 0.02). After CPAP therapy, LV functional parameters (LVEF: P<0.0001, LV performance index: P = 0.03, stroke volume: P = 0.042), and apical RV-Sl (P = 0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA (LVEF: AHI 5–14, 66.4±8.8%, 68.5±10.6% [P = ns]; AHI 15–30∶59.8±7.7%, 68.6±9.3% [P = 0.002]; AHI>30∶54.1±12.4%, 68.2±13.6%[P<0.0001]; apical RV-Sl: AHI 5–14: −17.3±8.7%, −16.0±10.8% [P = ns], AHI 15–30: −9.8±6.0%, −15.4±10.9% [P = 0.028], AHI>30: −6.3±5.7%, −17.9±11.2% [P<0.0001]).

Conclusions

OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function.     

Healthcare Service Utilization by Patients with Obstructive Sleep Apnea: A Population-Based Study

Objective

Although obstructive sleep apnea (OSA) is not a life-threatening disease, very few studies have compared differences in healthcare service utilization between patients with and those without OSA in an Asian population according to different age groups. This study attempted to investigate differences in healthcare service utilization between patients with and those without OSA in different age groups in Taiwan.

Methods

Sampled subjects and data on their health service utilization were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 568 patients with OSA and 2840 subjects without OSA. Each subject was followed for a 1-year period to evaluate their healthcare resource utilization. Wilcoxon-Mann-Whitney tests were performed to compare differences in healthcare utilization between patients with and those without OSA during the 1-year follow-up period.

Results

As to all healthcare service utilization, patients with OSA had significantly more outpatient visits (30.3 vs. 18.6), outpatient costs (US$1231.2 vs. US$764.8), inpatient days (1.8 vs. 1.2), inpatient costs (US$563.6 vs. US$276.7), and total costs (US$1794.8 vs. US$1041.5) than comparison subjects during the 1-year follow-up period. Moreover, patients with OSA aged 40~49 and 50~59 years respectively incurred 2.11- and 2.02-fold higher total costs compared to patients without OSA. However, patients with OSA aged over 70 years did not have higher total costs compared to those without OSA.

Conclusions

This study found that patients with OSA had greater healthcare service utilization than those without OSA. Additionally, patients with OSA in the 40~49- and 50~59-year age groups had about 2-fold higher total costs of healthcare services than those without OSA.     

Relationship between Aldosterone and the Metabolic Syndrome in Patients with Obstructive Sleep Apnea Hypopnea Syndrome: Effect of Continuous Positive Airway Pressure Treatment

Background

Metabolic syndrome (MS) occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS.

Methods

We studied 66 patients with OSAHS (33 with MS and 33 without MS) and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) clinical criteria. Measurements of plasma renin activity (PRA), aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment.

Results

Aldosterone levels were associated with the severity of OSAHS and higher than controls (p = 0.046). Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (p = 0.041). A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (p = 0.012).

Conclusion

This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS.

Trial registration

The study is not a randomized controlled trial and was not registered.

What is the key question?

Are aldosterone levels elevated in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and associated with the presence of metabolic syndrome (MS)?

What is the bottom line?

Current data indicate that OSAHS is highly associated with MS. The underlying mechanistic links between OSAHS and MS are not well delineated to date.There is a close relationship between the Renin-Angiotensin-Aldosterone system and hypertension, and recent evidence involves aldosterone in the pathogenesis of MS.

Why read on?

These findings show that aldosterone levels are elevated in OSAHS in comparison to controls, and continuous positive airway pressure (CPAP) therapy reduces aldosterone levels. They also show that aldosterone levels are associated with the presence of metabolic syndrome, suggesting a potential role of aldosterone excess in the development of metabolic and cardiovascular complications in patients with OSAHS.

What is the bottom line?

Current data indicate that OSAHS is highly associated with MS. The underlying mechanistic links between OSAHS and MS are not well delineated to date.There is a close relationship between the Renin-Angiotensin-Aldosterone system and hypertension, and recent evidence involves aldosterone in the pathogenesis of MS.

Why read on?

These findings show that aldosterone levels are elevated in OSAHS in comparison to controls, and continuous positive airway pressure (CPAP) therapy reduces aldosterone levels. They also show that aldosterone levels are associated with the presence of metabolic syndrome, suggesting a potential role of aldosterone excess in the development of metabolic and cardiovascular complications in patients with OSAHS.     

fMRI颞叶癫痫默认模式网络的研究

许多功能磁共振研究已经发现人脑的一些皮层区域在静息状态下出现共激活,这些区域形成连通的功能网络,称为"默认模式网络"。本文研究颞叶癫痫患者的默认模式网络,运用独立成分分析(Independent component analysis)分离出12例颞叶癫痫患者和12例正常对照的默认模式网络,进行组内分析得到两组被试的统计图,进行组间分析比较两组被试的默认模式网络的差异。结果表明默认模式网络均存在于颞叶癫痫患者和正常对照中,然而,在默认模式包含的网络中,颞叶癫痫患者前扣带回腹侧(ventral anterior cingulated cortex,vACC)、前额中分(medial prefrontal cortex,MPFC)、楔前叶(precuneus)、以及海马旁回区域比正常对照表现出代谢增强。这一结果有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助。     

An Effective Model for Screening Obstructive Sleep Apnea: A Large-Scale Diagnostic Study

Background

Obstructive sleep apnea (OSA) causes high morbidity and mortality and is independently associated with an increased likelihood of multiple complications. The diagnosis of OSA is presently time-consuming, labor-intensive and inaccessible.

Aim

This study sought to develop a simple and efficient model for identifying OSA in Chinese adult population.

Methods

In this study, the efficiency of Epworth Sleepiness Scale (ESS) and a new established prediction model for screening OSA were evaluated in the test cohort (2,032 participants) and confirmed in an independent validation cohort (784 participants).

Results

In the test cohort, a high specificity (82.77%, 95% confidence interval [CI], 77.36–87.35) and a moderate sensitivity (61.65%, 95% CI, 59.35–63.91) were obtained at the threshold of nine for the ESS alone. Notably, sex-stratified analysis revealed different optimum cut-off points: nine for males and six for females. The new generated screening model, including age, waist circumference, ESS score, and minimum oxygen saturation (SaO₂) as independent variables, revealed a higher sensitivity (89.13%, 95% CI, 87.60–90.53) and specificity (90.34%, 95% CI, 85.85–93.77) at the best cut-off point. Through receiver operating characteristics curve analysis, the area under the receiver operating characteristics curve of the model was found significantly larger than that of the ESS alone (0.955 vs. 0.774, P<0.0001). All these results were confirmed in the validation cohort.

Conclusions

A practical screening model comprising minimum SaO₂ and other parameters could efficiently identify undiagnosed OSA from the high-risk patients. Additionally, a sex-specific difference should be considered if the ESS alone is used.     

The Differences in Homocysteine Level between Obstructive Sleep Apnea Patients and Controls: A Meta-Analysis

Background

Studies have reported inconsistent findings regarding the relationship between obstructive sleep apnea (OSA) and homocysteine (HCY) level. This study aimed to assess the difference in plasma HCY level between OSA patients and controls by conducting a meta-analysis of published studies.

Methods

Database of PubMed, SCI, and China National Knowledge Internet (CNKI) were comprehensively searched. Eligible studies regarding plasma HCY level in OSA patients were identified by two independent reviewers. RevMan (version 5.2) and STATA (version 12.0) were employed for data synthesis.

Results

A total of 10 studies involving 432 subjects were included. Meta-analysis showed that plasma HCY levels in OSA group were 3.11 µmol/l higher than that in control group (95% confidence interval: 2.08 to 4.15, P<0.01). Subgroup analysis revealed a more significant differences between OSA patients and controls when average body mass index ≥30 (the total weighted mean difference (WMD) was 3.64), average age<50 (the total WMD was 3.96) and average apnea hypopnea index ≥35 (the total WMD was 4.54).

Conclusions

In this meta-analysis, plasma HCY levels were found to be higher in OSA patients compared to control subjects.     

孟鲁斯特钠对儿童OSAHS治疗效果的初步研究

目的:探讨孟鲁斯特钠对儿童阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)治疗疗效。方法:对经电子鼻咽喉镜检查腺样体III、IV级经多导睡眠监测为OSAHS的儿童96例,分成两组:药物治疗组48例,使用孟鲁斯特钠,连续使用1个月以上;未用药物组48例。对其家长进行相关临床表现的问卷调查。结果:两组患儿在年龄、病程、伴有鼻部疾病情况以及临床问卷分值间均无显著性差异(P0.05)。3个月后随访情况为,药物治疗组经治疗后在"响鼾"、"不安宁的睡眠或频繁醒觉"、"鼻阻塞而张口呼吸"以及"鼻腔很多鼻涕"4个症状的改善有统计学差异(P0.05)。未用药物组随访前、后问卷调查,差异均不具有显著性(P0.05)。结论:孟鲁斯特钠对儿童OSAHS治疗有一定疗效,可先行药物治疗。症状仍无明显改善的再考虑选择手术治疗。     

阻塞性睡眠呼吸暂停综合征临床监测分析

目的:探讨阻塞性睡眠呼吸暂停综合征患者的临床特征及评价疗效。方法:回顾分析70例阻塞性睡眠呼吸暂停综合征患者PSG监测数据。结果:随着呼吸紊乱指数的增加,年龄、体重指数、最长呼吸暂停时间、最低SaO_2%、平均SaO_2%下降等指标在轻度与中、重度SAS之间差异显著;70例患者中伴有高血压52.9%、糖尿病5.7%、冠心病21.4%。结论:OSAS是一种具有潜在危险的疾痛,对OSAS早期诊断治疗是预防发生严重并发症的关键。     

心理干预对阻塞性睡眠呼吸暂停综合征患者的意义

目的:评价在常规手术治疗的基础上联用心理干预措施治疗OSAS的效果.方法:50例OSAS患者随机分为对照组和观察组,对照组采用常规手术治疗,观察组在此基础上,联用心理干预措施.对两组患者的焦虑自评量表(SAS)、抑郁自评量表(SDS)、李克特量问卷调查表评分进行比较.结果:治疗前两组SAS、SDS评分差异不显著,有可比性.治疗后观察组SAS评分为(35.15±6.12)分,明显低于对照组(44.28±7.39)分,具有显著差异(t=4.7576,P＜0.001,见表1);治疗后观察组SDS评分为(37.59±6.34)分,明显低于对照组(42.75±5.69)分,具有显著差异(t=3.0286,P＜0.01,见表1).观察组总满意率为76.00%明显高于对照组的总满意率40.00%,差异显著,具有统计学意义(χ2=6.6502,P＜0.01,见表2).结论:在采用常规手术治疗的基础上联用了心理干预措施治疗OSAS的方式有明显效果,建议临床上进一步推广.     

孟鲁斯特钠对儿童OSAHS治疗效果的初步研究

目的：探讨孟鲁斯特钠对儿童阻塞性睡眠呼吸暂停低通气综合征（obslructivesleepapneahypopneasyndrome,OSAHS）治疗疗效。方法：对经电子鼻咽喉镜检查腺样体Ⅲ、Ⅳ级经多导睡眠监测为OSAHS的儿童96例,分成两组：药物治疗组48例,使用孟鲁斯特钠,连续使用1个月以上;未用药物组48例。对其家长进行相关临床表现的问卷调查。结果：两组患儿在年龄、病程、伴有鼻部疾病情况以及临床问卷分值间均无显著性差异（P〉0．05）。3个月后随访情况为,药物治疗组经治疗后在“响鼾”、“不安宁的睡眠或频繁醒觉”、“鼻阻塞而张口呼吸”以及“鼻腔很多鼻涕”4个症状的改善有统计学差异（P〈0．05）。未用药物组随访前、后问卷调查,差异均不具有显著性（P〉0．05）。结论：孟鲁斯特钠对儿童OSAHS治疗有一定疗效,可先行药物治疗。症状仍无明显改善的再考虑选择手术治疗。     

Risk of Obstructive Sleep Apnea in Adult Patients with Asthma: A Population-Based Cohort Study in Taiwan

Background

There are several publications reported that obstructive sleep apnea (OSA) was associated with asthma. However, large-scaled, population-based cohort study has been limited. We aimed to examine the risk of OSA among adult patients with asthma in an Asian population.

Methods

We conducted a retrospective cohort study using data from the National Health Insurance (NHI) of Taiwan. The asthma cohort included 38,840 newly diagnosed patients between 2000 and 2010. The date of diagnosis was defined as the index date. Each patient was randomly matched with four people without asthma according to gender, age, and the index year as the comparison cohort. The occurrence of OSA was followed up until the end of 2011. The risk of OSA was estimated using the Cox proportional hazard model after adjusting for gender, age, and comorbidities.

Results

The overall incidence of OSA was 2.51-fold greater in the asthma cohort than in the comparison cohort (12.1 versus 4.84 per 1000 person-years). Compared to non-asthma subjects, the adjusted hazard ratio (aHR) of OSA increased to 1.78 for asthma patients with one or less annual emergency room (ER) visit, and 23.8 for those who visited ER more than once per year. In addition, aHR in patients with inhaled steroid treatment compared to those without steroid treatment was 1.33 (95% CI = 1.01–1.76).

Conclusion

Patients with asthma have a significantly higher risk of developing OSA than the general population. The results suggest that the risk of OSA is proportional to asthma control and patients with inhaled steroid treatment have a higher risk for OSA than those without steroid treatment.     

Efficacy of Continuous Positive Airway Pressure on Testosterone in Men with Obstructive Sleep Apnea: A Meta-Analysis

Objective

To evaluate the efficacy of continuous positive airway pressure (CPAP) on serum testosterone in men with obstructive sleep apnea (OSA).

Methods

Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before June 2014. Information on characteristics of subjects, study design, pre- and post-CPAP treatment of serum total testosterone, free testosterone and sexual hormone blinding protein (SHBG) was extracted for analysis.

Results

A total of 7 studies with 9 cohorts that included 232 men were pooled into meta-analysis. There was no change of total testosterone levels before and after CPAP treatment in OSA men (standardized mean difference (SMD) = −0.14, 95%CI: −0.63 to 0.34, z = 0.59, p = 0.558), even subdivided by CPAP therapeutic duration (>3 months). Meanwhile, no significant differences in free testosterone and SHBG were detected after CPAP treatment (SMD =  0.16, 95%CI: −0.09 to 0.40, z = 1.25, p = 0.211 and SMD = −0.58, 95%CI: −1.30 to 0.14, z = 1.59, p = 0.112, respectively).

Conclusion

CPAP has no influence on testosterone levels in men with OSA, further large-scale, well-design interventional investigation is needed.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial

Objective

This study aimed to examine the effects of carbocysteine in OSAS patients.

Methods

A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group.

Results

The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18±4.28 vs. 6.82±3.66; P≤0.01), apnea-hypopnea index (55.34±25.03 vs. 47.56±27.32; P≤0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P≤0.01), and lowest oxygen saturation level (65.88±14.86 vs. 70.41±14.34; P≤0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71±0.15 vs. 0.66±0.15; P≤0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group.

Conclusions

Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02015598","term_id":"NCT02015598"}}NCT02015598