Day‐Night Variations of Serum Interleukin‐6 in Patients with Severe Obstructive Sleep Apnea Syndrome before and after Continuous Positive Airway Pressure (CPAP)

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin‐6 (IL‐6) is one of the important proinflammatory cytokines. We examined the levels of serum IL‐6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy. Serum IL‐6 levels were significantly reduced after CPAP therapy by 46% (6.2±1.0 vs. 3.3±0.4 pg/ml, p<0.005). No significant 24 h variation of serum IL‐6 in severe OSAS patients was found before CPAP; however, a significant 24 h variation of serum IL‐6 was found after CPAP. Intermittent hypoxia during sleep may contribute to systemic inflammation and result in an elevation of serum IL‐6 in severe OSAS patients.     

Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1.

Obstructive sleep apnea syndrome (OSAS) is one of the most important risk factors of cardiovascular disorders. In the treatment of OSAS, nasal continuous positive airway pressure (nCPAP) has been widely used and found to be effective. In the present study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in untreated OSAS patients compared with an age-matched control group. In addition, we hypothesized that nCPAP may decrease OSAS-induced hypoxic stress and mediators. To examine these hypotheses, we measured circulating ICAM-1 and IL-8 before and after nCPAP therapy in OSAS patients. We observed that nCPAP decreased apnea, desaturation, and the circulating ICAM-1 and IL-8 levels in OSAS patients. The circulating levels of ICAM-1, IL-8, and MCP-1 in untreated OSAS patients were significantly greater than those in the controls. These observations suggest that nCPAP therapy could reduce OSAS-induced hypoxia and generation of inflammatory mediators. Treatment of OSAS using nCPAP can be, therefore, a potential approach to decrease risk of the progression of OSAS-associated disorders.     

The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome

Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may have a direct effect on glucose and lipid metabolism. On the other hand, it is known that IL-6 and TNF-alpha are important pro-inflammatory cytokines in the pathogenesis of atherosclerosis. The goal of present study was to test whether sleep apnea contributes to the previously reported increases of IL-6 and TNF-alpha independent of obesity. Forty-three obese (body mass index, BMI>27 kg/m2) men with newly diagnosed obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index, AHI> or =5) and age- and BMI-matched 22 obese nonapneic male controls (AHI<5) were enrolled in this study. To confirm the diagnosis, all patients underwent standard polysomnography in the sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting. Serum IL-6 and TNF-alpha levels were found significantly higher in OSAS patients than in controls (p=0.002, p=0.03). Serum IL-6 and TNF-alpha levels were significantly correlated with AHI in OSAS patients (r=0.03, p=0.046 and r=0.36, p=0.016). There was no significant correlation between serum IL-6, TNF-alpha levels and AHI in controls. Serum IL-6 and TNF-alpha levels were not correlated with BMI both in OSAS patients and controls. In conclusion, circulating IL-6 and TNF-alpha levels in patients with OSAS, as independent of BMI are significantly higher than levels in controls and there is a positive relationship between previously mentioned cytokines' levels and the severity of OSAS. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating IL-6 and TNF-alpha levels.     

The postoperative stress response and its reflection in cytokine network and leptin plasma levels

The objective of the present report was to clarify the postoperative stress response of some inflammatory markers, namely of proinflammatory cytokines and leptin levels during uncomplicated postoperative periods. The results were compared with the dynamics of these parameters during intraabdominal sepsis. We followed 20 patients after a planned resection of colorectal cancer in stage Ib-IV with uncomplicated healing and 13 obese men after laparoscopic non-adjustable gastric banding. These were compared to 12 patients with proven postoperative sepsis. The control group consisted of 18 healthy men. The observed parameters included serum levels of cytokines, tumor necrosis factor-alpha (TNFalpha), interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1 ra), IL-6, IL-8, soluble receptor of interleukin-2 (sIL-2R) and leptin. It was found that during the first 24 h after resection there was a significant increase in the serum concentration of IL-6 up to 1125+/-240 ng/l, which declined within the next 48-72 h. Serum concentration of TNFalpha was highest 18-24 h after resection (205+/-22 ng/l) and after banding (184+/-77 ng/l). IL-1 beta had a stable serum concentration without significant elevation. Serum concentration of IL-8 after resection rose to 520+/-200 ng/l after 36-48 h. Maximal cytokine levels after gastric banding were quantitatively lower (IL-6 414+/-240 ng/l, TNFalpha 184+/-77 ng/l) than after resection. We found significant elevation of plasma leptin concentration (32+/-10 ng/ml) 24 h after banding compared with preoperative values (18+/-5 ng/ml, p 0.05). Leptin levels 48 and 72 h after banding rapidly returned to the level before operation. During abdominal surgery leptin shows to be an acute phase reactant. Proinflammatory cytokines can be main regulatory factors of leptin during this period. Significant correlation between leptin and TNFalpha (similarly demonstrated by other authors in models of bacterial inflammation) indicates that TNFalpha can be the crucial regulator of leptin generation in the early postoperative period. On the basis of our results we recommend to observe IL-6 and IL-8 at 24-72 h after the surgery in patients with a high risk of early postoperative septic complications.     

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.     

Weight and metabolic effects of CPAP in obstructive sleep apnea patients with obesity

Background

Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.

Methods

In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.

Results

CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.

Conclusions

Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.     

Long-term facilitation in obstructive sleep apnea patients during NREM sleep.

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 +/- 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4-6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O(2) fraction (FI(O(2))) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing (n = 11), and supraglottic pressure (n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 +/- 8% of control), despite decreased Rua to 58 +/- 24% of control (P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.     

Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) may be one of the most important risk factors of cardiovascular disorders, although the exact mechanism remains to be elucidated. In the present study, we hypothesized that OSAS-induced hypoxic stress might be involved in the etiology of cardiovascular disorders by activating adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and L-selectin. To examine this hypothesis, we measured circulating ICAM-1, VCAM-1, and L-selectin levels before and after sleep in OSAS patients and age-matched controls. The circulating ICAM-1, VCAM-1, and L-selectin levels increased in the OSAS patients before sleep compared with the normal subjects (ICAM-1: 392.9 +/- 48.5 vs. 201.2 +/- 55.0 ng/ml, P < 0.05; VCAM-1: 811.0 +/- 87.8 vs. 574.2 +/- 42.7 ng/ml, P < 0.05; L-selectin: 1,386.6 +/- 77.9 vs. 1,038.8 +/- 78.6 ng/ml, P < 0.01, respectively). After sleep, significantly greater levels of ICAM-1 and L-selectin, but not VCAM-1, were observed in the OSAS group. These observations suggest that OSAS-induced hypoxia activates adhesion molecules, resulting in the important risk factor of cardiovascular disorders. Treatment of OSAS can be, therefore, a potential approach to prevention of cardiovascular events.     

A model of sleep-disordered breathing in the C57BL/6J mouse.

To investigate the pathophysiological sequelae of sleep-disordered breathing (SDB), we have developed a mouse model in which hypoxia was induced during periods of sleep and was removed in response to arousal or wakefulness. An on-line sleep-wake detection system, based on the frequency and amplitude of electroencephalograph and electromyograph recordings, served to trigger intermittent hypoxia during periods of sleep. In adult male C57BL/6J mice (n = 5), the sleep-wake detection system accurately assessed wakefulness (97.2 +/- 1.1%), non-rapid eye movement (NREM) sleep (96.0 +/- 0.9%) and rapid eye movement (REM) sleep (85.6 +/- 5.0%). After 5 consecutive days of SDB, 554 +/- 29 (SE) hypoxic events were recorded over a 24-h period at a rate of 63.6 +/- 2.6 events/h of sleep and with a duration of 28.2 +/- 0.7 s. The mean nadir of fraction of inspired O(2) (FI(O(2))) on day 5 was 13.2 +/- 0.1%, and 137.1 +/- 13.2 of the events had a nadir FI(O(2)) <10% O(2). Arterial blood gases confirmed that hypoxia of this magnitude lead to a significant degree of hypoxemia. Furthermore, 5 days of SDB were associated with decreases in both NREM and REM sleep during the light phase compared with the 24-h postintervention period. We conclude that our murine model of SDB mimics the rate and magnitude of sleep-induced hypoxia, sleep fragmentation, and reduction in total sleep time found in patients with moderate to severe SDB in the clinical setting.     

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.     

A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

Background

Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.

Methods

We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6?months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2?? and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.

Results

Patients with severe OSAS had higher urinary 8-iso-PGF2?? (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2?? (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).

Conclusions

The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.     

Restoring the Salivary Cortisol Awakening Response Through Nasal Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea

Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.     

The Effects of CPAP Treatment on Task Positive and Default Mode Networks in Obstructive Sleep Apnea Patients: An fMRI Study

Introduction

Functional magnetic resonance imaging studies enable the investigation of neural correlates underlying behavioral performance. We investigate the effect of active and sham Continuous Positive Airway Pressure (CPAP) treatment on working memory function of patients with Obstructive Sleep Apnea Syndrome (OSAS) considering Task Positive and Default Mode networks (TPN and DMN).

Methods

An experiment with 4 levels of visuospatial n-back task was used to investigate the pattern of cortical activation in 17 men with moderate or severe OSAS before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment.

Results

Patients with untreated OSAS had significantly less deactivation in the temporal regions of the DMN as compared to healthy controls, but activation within TPN regions was comparatively relatively preserved. After 2 months of treatment, active and sham CPAP groups exhibited opposite trends of cerebral activation and deactivation. After treatment, the active CPAP group demonstrated an increase of cerebral activation in the TPN at all task levels and of task-related cerebral deactivation in the anterior midline and medial temporal regions of the DMN at the 3-back level, associated with a significant improvement of behavioral performance, whereas the sham CPAP group exhibited less deactivation in the temporal regions of Default Mode Network and less Task Positive Network activation associated to longer response times at the 3-back.

Conclusion

OSAS has a significant negative impact primarily on task-related DMN deactivation, particularly in the medial temporal regions, possibly due to nocturnal hypoxemia, as well as TPN activation, particularly in the right ventral fronto-parietal network. After 2 months of active nasal CPAP treatment a positive response was noted in both TPN and DMN but without compete recovery of existing behavioral and neuronal deficits. Initiation of CPAP treatment early in the course of the disease may prevent or slow down the occurrence of irreversible impairment.     

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     

Auto-CPAP therapy based on the forced oscillation technique.

Autoadjusting CPAP devices (APAP) are designed to continuously adjust the positive pressure to the required levels, and thus increase treatment quality and patient compliance. The results of APAP treatment strongly depend on the control mechanism of the respective APAP device. In agreement with other working groups, we have recently shown that the forced oscillation technique (FOT) is capable of detecting incipient upper airway obstruction prior to physiological reactions such as the onset of increasing esophageal pressure swings or microarousals. Therefore we studied efficacy and acceptance of a novel APAP device controlled exclusively by FOT. 100 consecutive patients with OSAS confirmed by polysomnography (mean AHI 47.9 +/- 22.6) and daytime sleepiness (Epworth sleepiness scale, ESS 12.6 +/- 3.9) were randomized to either APAP treatment (n = 50) or conventional CPAP treatment (n = 50). Polysomnographies were performed at the second treatment night and subjective sleepiness (modified ESS) was established in the morning. The respiratory disturbance was largely normalized in both treatment groups in the second treatment night (AHI 4.7 +/- 5.3 vs. 3.7 +/- 3.4; n.s.). Both groups showed largely improved sleep profiles and had markedly reduced ESS-scores (6.6 +/- 3.6 vs. 7.0 +/- 3.4; n.s.). The mean treatment pressure during APAP was significantly lower than during CPAP treatment (6.0 +/- 2.0 vs. 9.0 +/- 1.8 mbar; p < 0.001). There were no significant differences between APAP and CPAP treatment in any parameter of efficacy or acceptance. APAP treatment with this device controlled exclusively by FOT is well accepted by the patients and permits an adequate treatment of OSAS without the need for invidiual CPAP titration.     

Serum leptin is not a diagnostic marker for familial Mediterranean fever attacks

The aim of our study is to determine whether there is a relationship between familial Mediterranean fever (FMF) attacks and serum leptin levels. We enrolled 25 patients (22 males and 3 females) and 25 healthy controls (21 males and 4 females) with a mean age of 24.42 +/- 1.22 (Mean +/- SEM) years and 24.30 +/- 1.19 years (Mean +/- SEM), respectively. We investigated serum levels of leptin, interleukin-6 (IL-6) erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),fibrinogen, and leukocyte counts before the attack and 8-12 hours after the attack started. The same parameters have been investigated in the control subjects. The mean serum leptin levels before the attacks were 6.45 +/- 1.05 (Mean +/- SEM) and during the attacks were 7.59 +/- 1.3 (Mean +/- SEM) in FMF group,respectively. There was a slight increase in serum leptin levels during the attacks but it was not statistically significant (P > .05). The mean serum leptin levels were 16.12 +/- 2.81 in the control group which were not different from the mean serum leptin levels before and during the attack periods in the study group (P > .05). However, there were statistical differences in the serum levels of IL-6, ESR, CRP, fibrinogen, and leukocyte counts before and during the attack periods (P > .05). No correlation was found between serum leptin levels and IL-6, ESR, CRP, fibrinogen, and leukocyte counts (P > .05). Serum leptin levels do not increase during FMF attacks and therefore it is not useful for diagnostic purposes and follow-up during treatment.     

连续肾脏替代治疗对脓毒症患者血清中TNF-alpha、IL-6 和IL-8 表达的影响

目的：探讨连续肾脏替代治疗（CRRT）对脓毒症患者血清中肿瘤坏死因子alpha（TNF-alpha）、白介素-6（IL-6）和白介素-8（IL-8）的 影响。方法：将我院2013 年1 月-2014 年6 月间收治的80 例脓毒症患者随机分为观察组与对照组各40 例,两组患者均给予脓毒 症常规治疗,观察组另给予CRRT 治疗。观察比较两组患者治疗前1 天,治疗后24 h,72 h空腹静脉血TNF-alpha、IL-6、IL-8 水平。结 果：观察组治愈率为85.0%（34/40）,明显高于对照组的55.0%（22/40）,差异有统计学意义（P<0.05）;治疗24h、72h 后两组患者 TNF-alpha、IL-6和IL-8 水平均明显下降,其中观察组下降更显著,差异均有统计学意义（P<0.05）。结论：CRRT 能有效降低脓毒症患 者血清中TNF-alpha、IL-6 和IL-8 水平,有助于对炎症反应的正向调节。     

Factors associated with severity of daytime sleepiness and indications for initiating treatment in patients with periodic limb movements during sleep

Obstructive sleep apnea syndrome (OSAS) is closely associated with hypertension. Activity of angiotensin II (Ang II) and non-dipping nocturnal blood pressure (BP) variability are implicated in hypertension-related target organ damage. We examined the correlation between OSAS with serum Ang II levels and evaluated the risk of non-dipping BP variability in 180 patients with essential hypertension (EHT). Eligible patients were divided into three subgroups based on their apnea-hypopnea index (AHI) evaluated by polysomnography. EHT alone, EHT with mild OSAS, and EHT with moderate/severe OSAS. Ambulatory BP monitoring was used to calculate mean BP over 24 h, as well as diurnal and nocturnal BP variability. Serum Ang II was determined with enzyme-linked immun-osorbent assay. EHT patients with OSAS had significantly higher systolic BP calculated either over 24 h, or by diurnal or nocturnal monitoring (P < 0.05). More EHT patients with OSAS showed non-dipping BP profiles than did EHT patients alone (P < 0.05). The number of patients with non-dipping BP increased with increasing OSAS severity. Surgical treatment alleviated OSAS and reduced AHI (P < 0.05). Preoperative serum Ang II in EHT patients with OSAS was significantly higher than that in those without OSAS (P < 0.05), and showed a rising trend with OSAS severity (P < 0.05). Postoperative serum Ang II, BP and the incidence of non-dipping BP were reduced by surgery to levels lower than preoperative values in patients with OSAS. We therefore conclude that OSAS leads to increased serum Ang II and increased risk of non-dipping BP in patients with EHT.

     

Changes in the heart rate variability in patients with obstructive sleep apnea and its response to acute CPAP treatment

Introduction

Obstructive Sleep Apnea (OSA) is a major risk factor for cardiovascular disease. The goal of this study was to demonstrate whether the use of CPAP produces significant changes in the heart rate or in the heart rate variability of patients with OSA in the first night of treatment and whether gender and obesity play a role in these differences.

Methods

Single-center transversal study including patients with severe OSA corrected with CPAP. Only patients with total correction after CPAP were included. Patients underwent two sleep studies on consecutive nights: the first night a basal study, and the second with CPAP. We also analyzed the heart rate changes and their relationship with CPAP treatment, sleep stages, sex and body mass index. Twenty-minute segments of the ECG were selected from the sleep periods of REM, no-REM and awake. Heart rate (HR) and heart rate variability (HRV) were studied by comparing the R-R interval in the different conditions. We also compared samples from the basal study and CPAP nights.

Results

39 patients (15 females, 24 males) were studied. The mean age was 50.67 years old, the mean AHI was 48.54, and mean body mass index was 33.41 kg/m² (31.83 males, 35.95 females). Our results showed that HRV (SDNN) decreased after the use of CPAP during the first night of treatment, especially in non-REM sleep. Gender and obesity did not have any influence on our results.

Conclusions

These findings support that cardiac variability improves as an acute effect, independently of gender or weight, in the first night of CPAP use in severe OSA patients, supporting the idea of continuous use and emphasizing that noncompliance of CPAP treatment should be avoided even if it is just once.