dinoprost and Sleep-Apnea--Obstructive

Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH.. Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02).. COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA.. www.clinicaltrials.gov. Unique identifier: NCT01280006.

Topics: Adult; Blood Pressure; Celecoxib; Cerebrovascular Circulation; Cross-Over Studies; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Double-Blind Method; Epoprostenol; Female; Heart Rate; Humans; Hypoxia; Indomethacin; Male; Middle Aged; Pyrazoles; Sleep Apnea, Obstructive; Sulfonamides; Thromboxane A2

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.. 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-PGF2α 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.. Patients with severe OSAS had higher urinary 8-iso-PGF2α (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-PGF2α (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%).. 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.

Topics: Adult; Biomarkers; Brachial Artery; Continuous Positive Airway Pressure; Dinoprost; Female; Humans; Linear Models; Male; Membrane Glycoproteins; Middle Aged; NADPH Oxidase 2; NADPH Oxidases; Nitrates; Nitrites; Oxidative Stress; Polysomnography; Severity of Illness Index; Sleep Apnea, Obstructive; Treatment Outcome; Ultrasonography; Vasodilation

Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was undertaken to (1) compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle-aged men with OSAS and no other known co-morbidity and healthy controls of the same age, gender and body mass index; and (2) test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy attenuates oxidative stress and nitrate deficiency.. A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities.. Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2-78.2) vs 20.0 (12.5-52.5) pg/ml, p = 0.041, Mann-Whitney test) and lower NOx levels (264 (165-650) vs 590 (251-1465) micromol/l, p = 0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2-58.7) pg/ml at baseline vs 22.5 (16.2-35.3) pg/ml on CPAP, p = 0.0001) and NOx levels increased (280 (177-707) vs 1373 (981-1517) micromol/l, p = 0.0001) after CPAP.. OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.

Topics: Adult; Aged; Blood Pressure; Continuous Positive Airway Pressure; Dinoprost; Double-Blind Method; Humans; Male; Middle Aged; Nitrates; Nitrites; Oxidative Stress; Prospective Studies; Sleep Apnea, Obstructive

Relationships between exhaled breath condensate (EBC) and serum cytokines and apnea-hypopnea index (AHI) in patients with excessive daytime sleepiness and loud snoring were evaluated for their potential to predict the severity of obstructive sleep apnea syndrome (OSAS).. Non-smoking patients with suspected OSAS who had undergone polysomnography (PSG) were selected until 22 non-OSAS, and 22 mild, 22 moderate and 24 severe OSAS cases based on AHI were achieved. Ten healthy smokers served as a smoker control group. Interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and 8-isoprostane were measured in EBC and serum on the morning after PSG and related to OSAS severity using linear discriminant analysis (LDA) and logistic regression (LR).. Biomarker levels, in both EBC and serum, differed significantly across the four groups. Classification by LDA using IL-10 in EBC showed the highest agreement with AHI classification (kappa=0.88). LR distinguished moderate and severe OSAS from mild OSAS and non-OSAS perfectly using IL-6 in EBC and almost perfectly using IL-10 in EBC (area under the ROC curve=0.997). The levels of biomarkers among smokers overlapped with mild to severe OSAS patients.. Among non-smoker OSAS suspects, EBC IL-6 and IL-10 have potential to predict severity of OSAS.

Topics: Adult; Biomarkers; Breath Tests; Cytokines; Dinoprost; Female; Humans; Hypoxia; Interleukin-10; Interleukin-6; Male; Middle Aged; Oxidative Stress; Predictive Value of Tests; Respiratory Function Tests; Severity of Illness Index; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

In the present study, the authors examined the relationship between lipid peroxidation and inflammation in patients with obstructive sleep apnoea (OSA). A total of 40 obese patients with OSA were studied, along with 18 obese and 12 lean subjects without OSA. Overnight excretion of 8-isoprostane in urine and serum levels of high-sensitivity C-reactive protein (hsCRP) were measured. In addition, the effects of 3 months' treatment with nasal continuous positive airway pressure (nCPAP) were studied in 20 obese patients with moderate-to-severe OSA. Overnight urinary excretion of 8-isoprostane and serum levels of hsCRP were significantly higher in patients with moderate-to-severe OSA compared with patients with mild OSA and obese or lean subjects without OSA. Overnight urinary excretion of 8-isoprostane significantly correlated with apnoea-hypopnoea index, duration of hypoxia during sleep, body mass index, and serum levels of hsCRP in patients with OSA. The severity of OSA was an independent factor predicting the urinary excretion of 8-isoprostane. nCPAP significantly decreased urinary excretion of 8-isoprostane and serum levels of hsCRP. In conclusion, these results suggest that both obstructive sleep apnoea severity and obesity can independently contribute to elevations in urinary excretion of 8-isoprostane. Therefore, obstructive sleep apnoea may increase the risks of cardiovascular morbidity in obese patients.

Topics: C-Reactive Protein; Cardiovascular Diseases; Dinoprost; Humans; Inflammation; Lipid Peroxidation; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive

The study was conducted to test the hypothesis that oxidative stress leads to the release of proinflammatory cytokines by activating the Nod-like receptor protein (NLRP)3 inflammasome in patients with obstructive sleep apnoea (OSA).. The study recruited 247 participants who were divided into cases and healthy control groups. OSA patients were subdivided into four subgroups according to sex, blood pressure, body mass index (BMI), and severity of disease. No significant differences were found between cases and controls with respect to age or sex. Peripheral blood samples were collected for analysis after examination, and the serum concentrations of oxidative stress (8-isoprostane), inflammation (interleukin (IL)-18, IL-1β, IL-6, tumour necrosis factor (TNF)-α), and NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) were detected by enzyme-linked immunosorbent assay.. The serum concentrations of both oxidative stress and proinflammatory factors were higher in OSA patients than healthy controls. Subgroup analysis also revealed significant differences according to the apnoea-hypopnea index and BMI. Additionally, correlations were identified between 8-isoprostane and proinflammatory factors (IL-1β, IL-18, and TNF-α). Multiple regression analysis suggested that sleep parameters and BMI affected inflammation. However, no differences were observed in the serum level of NLRP3 inflammasome components between patients and controls. Furthermore, stratified analysis revealed no additional differences.. The current study suggests that oxidative stress leads to inflammation by mechanisms other than activation of the NLRP3 inflammasome in OSA patients. Furthermore, both sleep apnoea and BMI influenced the serum concentration of inflammatory mediators.

Topics: Adult; CARD Signaling Adaptor Proteins; Case-Control Studies; Caspase 1; China; Cytokines; Dinoprost; Female; Humans; Interleukin-1beta; Interleukin-6; Male; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Polysomnography; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Oxidative stress and inflammation are assumed as the main pathological triggers for vascular damage in hypersomnolent obstructive sleep apnoea (OSA) patients, whereas their exact role in less symptomatic population is currently unknown.. To determine whether oxidative stress (urinary 8-isoprostane concentration) and inflammation (plasma resistin levels) are associated with vascular damage in non-hypersomnolent (Epworth Sleep Score <11) OSA patients.. A total of 325 consecutive patients have undergone standard polysomnography, and 256 of them were diagnosed with OSA. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Only 86 patients with ESS <11 participated in the study. The control group was presented by 45 subjects without OSA. Endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation (FMD). Intima-media thickness (IMT) and ankle-brachial index (ABI) were determined by ultrasonography. Urinary 8-isoprostanes (Cayman Chemical, USA) were measured, applying mass spectrometry. Resistin (RayBio_ Human ResistinCat#:ELH-Resistin-001) plasma levels were detected by ELISA.. In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (4·62% ±1·9) and (7·1% ±2·8), respectively (P: 0·013). The prevalence of plaques in a.carotis communis was higher in OSA (16% versus 4%). The same is observed regarding a.tibialis posterior (81% vs. 29%). The average IMT and ABI in OSA and in the control group were, respectively, (IMT - 800 µm versus. 666 µm); (ABI -1·06 versus 1·20). Urinary isoprostanes were higher in OSA patients (0·091 versus 0·078) and correlated negatively to FMD (r: -0·825, P: 0·00), IMT (r: -0·324, P: 0·003) and ABI (r: -0·226, P: 0·043). No association between resistin and the degree of vascular injury was found.. In comparison with the control group, increased prevalence of endothelial dysfunction and vascular damage was established in OSA patients without excessive daytime sleepiness. Urinary 8-isoprostanes (oxidative stress markers) are closely associated with FMD (endothelial dysfunction), IMT and ABI (vascular damage). Resistin plasma levels correlated neither to FMD, nor to IMT or ABI.

Topics: Adult; Aged; Ankle Brachial Index; Biomarkers; Bulgaria; Carotid Intima-Media Thickness; Dinoprost; Endothelium, Vascular; Female; Humans; Inflammation Mediators; Male; Middle Aged; Oxidative Stress; Prevalence; Resistin; Risk Factors; Sleep; Sleep Apnea, Obstructive; Vascular Diseases; Vasodilation

Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown.. To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction.. Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured.. 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio.. While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function.

Topics: Adult; Advanced Oxidation Protein Products; Chemokine CCL2; Cohort Studies; Dinoprost; Endothelium, Vascular; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Smoking

In obstructive sleep apnea-hypopnea syndrome (OSAS), airway collapses and vibrations cause local and systemic inflammatory response and oxidative stress (OS). Our objective was to determine the presence of OS in the airway of patients with OSAS compared with controls without OSAS and determine its relation to treatment with CPAP and other clinical variables.. We performed a prospective observational case-control study with repeated measures. We recruited consecutive patients with SAHS diagnosed using complete polysomnography, and a parallel control group. We collected a sample of exhaled breath condensate (EBC) prior to nasal continuous positive airway pressure (CPAP) treatment and again after 4 months. The marker of OS used was 8-isoprostane (8-IPN). The variables analyzed were age, sex, anthropometric variables, apnea-hypopnea index (AHI), snoring, oxygenation, and polysomnographic variables.. The study included 20 patients and 10 controls. In cases, the initial value of 8-IPN was 6.8 (1.9), and after nasal CPAP, it was 5.3 (1.2) pg/ml (p = 0.02). In controls, the value of 8-IPN was 5.6 (1.1) pg/ml (p = 0.04 compared to initial values). 8-IPN showed significant correlation with snoring, AHI, BMI, nocturnal desaturation index, and non-REM sleep. On multivariate analysis, only snoring was a significant predictor of 8-IPN.. Snoring, and not OSAS severity, could be the phenomenon underlying the presence of local OS measured in the airway of patients with OSAS.

Topics: Adult; Aged; Body Mass Index; Breath Tests; Case-Control Studies; Continuous Positive Airway Pressure; Dinoprost; Female; Humans; Male; Middle Aged; Oxidative Stress; Oxygen; Prospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive; Snoring

To observe the effect of continuous positive airway pressure ventilation on hypersensitive C reaction protein (hsCRP) and 8-isoprostane in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).. A total of 78 OSAHS patients were enrolled and monitored by polysomnography (PSG) in January to March, 2013. Another 40 healthy persons were chosen as controls during the same time. According to apnea hypopnea index (AHI) and oxygen saturation, the patients were divided into mild, moderate and severe groups. Blood and urinary 8-isoprostane and hsCRP levels were detected before and after monitoring. After continuous positive airway pressure treatment for three months, blood and urinary 8-isoprostane and hsCRP were also detected in three groups.. (1) In OSAHS patients, blood 8-isoprostane levels before and after sleep monitoring were (273.80±55.83) ng/L and (337.18±56.28) ng/L urinary 8-isoprostane (35.65±7.08) ng/L and (48.30±14.17) ng/L, hsCRP (7.63±6.10) µg/L and (9.68±8.55)µg/L, respectively. Each parameter reached a significant difference before and after sleep (P<0.05). (2) The levels of blood CRP and urinary 8-isoprostane in the control group before sleep were (4.56±2.43) µg/L, (264.14±33.61) ng/L, (32.77±9.61) ng/L, after sleep were (4.33±2.08) µg/L, (284.27±47.51) ng/L, (31.13±8.24) ng/L. All the levels were less than those of OSAHS group (P<0.05). (3) The levels of blood 8-isoprostane in mild, moderate and severe groups after monitoring were (308.16±53.48) ng/L, (327.36±59.05) ng/L, (340.39±55.31) ng/L respectively, and urinary 8-isoprostane were (35.23±11.28) ng/L, (38.30±10.89) ng/L, (44.57±12.69) ng/L, hsCRP were (5.63±4.26) µg/L, (6.96±4.43) µg/L, (8.92±7.84) µg/L. None of these three parameters showed significant difference between the three groups (P>0.05). However, compared with the control group, blood and urine 8-isoprostane and hsCRP levels of any groups had significant differences (all P values<0.05). (3) There was no significant difference in the levels of hsCRP and 8-isoprostane after sleep between the three groups in OSAHS (P>0.05). (4) Urinary 8-isoprostane level after PSG was positively correlated with hsCRP (r=0.498, P<0.01). Either 8-isoprostane or hsCRP level was correlated with AHI (r=0.479, r=0.550; P<0.01). 8-isoprostane and hsCRP levels were positively correlated with time of blood hemoglobin oxygen saturation below 90% (r=0.413, r=0.502; P<0.01). (5) After continuous positive airway pressure treatment, the levels of 8-isoprostane and hsCRP both in blood or urine were decreased in the three groups of OSAHS patients (P<0.05).. Long term intermittent hypoxia in patients with OSAHS results in enhanced oxidative stress reaction and over-generated inflammatory mediators. There is a positive correlation between oxidative stress and inflammatory mediators, which promotes each other, leading to the organ dysfunction induced by hypoxia.

Topics: C-Reactive Protein; Continuous Positive Airway Pressure; Dinoprost; Humans; Oxidative Stress; Polysomnography; Sleep; Sleep Apnea, Obstructive; Snoring; Tumor Necrosis Factor-alpha

F2-isoprostanes are considered to be a reliable standard biomarker of oxidative stress in vivo because they are not influenced by the intake of lipids in the diet, and they are chemically stable molecules and easily detected. This study aimed to test the hypothesis that 8-isoprostane level is a useful marker to valuate the severity of pediatric obstructive sleep apnea (OSA).. Sixty-five children with sleep-disordered breathing (SDB) (mean age 5.9±2.0 years; 63.1% males) were recruited. The urine sample for the measurement of 8-isoprostane was collected the morning after the polysomnographic recording. Children were divided into two groups according to their apnea-hypopnea index (AHI).. Urinary 8-isoprostane levels positively correlated with the sleep clinical record score (r=0.38, p=0.002) and AHI (r=0.24, p=0.05) and negatively correlated with age (r=-0.36, p=0.003) and body surface area (r=-0.38, p=0.002). Urinary 8-isoprostane levels were significantly higher in the group with AHI of ≥5 events (ev)/h than in the group with AHI of <5 ev/h (p<0.01).. Urinary 8-isoprostane may be used as a specific inflammatory marker to predict the severity of OSA; this method has the advantage of being noninvasive and easy to use in both compliant and noncompliant children.

Topics: Biomarkers; Child; Child, Preschool; Dinoprost; Female; Humans; Male; Oxidative Stress; Polysomnography; Predictive Value of Tests; Reference Values; Sleep Apnea, Obstructive

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent respiratory disorders in the upper airways during sleep. Although continuous positive airway pressure (CPAP) has been accepted to be the most effective treatment for OSAS, its role on inflammation remains debatable. In this study, our aim was to examine the influence of 3 months of CPAP treatment on tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), 8-isoprostane, and peroxynitrite levels in exhaled breathing condensates (EBC) and serum.. Thirty-five patients who were newly diagnosed as moderate or severe OSAS with full night polysomnography and used CPAP therapy regularly for 3 months were included in the study. Polysomnography, spirometric tests, fasting blood samples, and EBC were ascertained on entry into the study and after 3 months of treatment. All patients were assessed monthly for treatment adherence and side effects.. We found that all polysomnographic parameters were normalized after CPAP therapy in the control polysomnogram. Also, all markers in EBC and nitrotyrosine and 8-isoprostane levels in serum were decreased significantly with CPAP treatment. Sedimentation rate, C-reactive protein, IL-6, and TNF-α remained unchanged in serum after treatment. We found that baseline nitrotyrosine levels were significantly correlated with apnea-hypopnea index, oxygen desaturation index, and percent time in SpO2 < 90 % (p < 0.01).. CPAP therapy has primarily a relevant impact on airways, and nitrotyrosine levels correlated well with severity of OSAS. This treatment decreases both inflammation and oxidative stress levels in airways in OSAS patients. Also, this treatment helps to decrease systemic oxidative stress levels in serum.

Topics: Adult; Blood Sedimentation; C-Reactive Protein; Case-Control Studies; Continuous Positive Airway Pressure; Dinoprost; Female; Follow-Up Studies; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Peroxynitrous Acid; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are associated with increased cardiovascular morbidity and mortality. Increased homocysteine is suggested as an independent risk factor for atherosclerosis and cardiovascular disease but remains disputed in OSA. We assessed polysomnography, carotid intima-media thickness (CIMT) and biology in 35 MetS patients, according to the presence (OSA+MetS; n=26) or the absence of OSA (MetS; n=9). In OSA+MetS patients, homocysteine levels were increased compared to MetS subjects (12.8 ± 3.8 vs. 9.5 ± 2.5 μmol/L; P=0.026). In the whole population, homocysteine correlated with apnea-hypopnea index (AHI) (r=0.522; P=0.001) and CIMT (r=0.376; P=0.026). Homocysteine was negatively correlated with plasma thiols (r=-0.406; P=0.017) and positively with urinary 15-F2t-isoprostanes (r=0.347; P=0.044). Multivariate regression analysis revealed that AHI (β=0.559; P<0.001) and urinary 15-F2t-isoprostane (β=0.310; P=0.018) were independently associated with homocysteine level. We conclude that homocysteine level was higher in MetS when associated with OSA and proportional to OSA severity. In this context, vascular remodeling appeared more severe and mediated by oxidative stress.

Topics: Antioxidants; Arousal; Atherosclerosis; Blood Pressure; Carotid Arteries; Carotid Intima-Media Thickness; Chromatography, High Pressure Liquid; Dinoprost; Endothelium, Vascular; Female; Homocysteine; Humans; Isoprostanes; Lipids; Male; Metabolic Syndrome; Middle Aged; Oxidation-Reduction; Oxidative Stress; Polysomnography; Sleep Apnea, Obstructive; Sulfhydryl Compounds; Tandem Mass Spectrometry

Local and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements.. About 45 OSA patients (mean AHI 40+/-25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-alpha and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed.. An increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements.. Increased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity.

Topics: Adult; Biomarkers; Breath Tests; C-Reactive Protein; Case-Control Studies; Dinoprost; Female; Forced Expiratory Volume; Humans; Hydrogen-Ion Concentration; Interleukin-6; Leptin; Linear Models; Lung; Male; Middle Aged; Polysomnography; Sleep Apnea, Obstructive; Smoking; Tumor Necrosis Factor-alpha; Vital Capacity

Adeno-tonsillar hypertrophy is the commonest cause of childhood obstructive sleep apnoea (OSA). Our aim of the study is to correlate the severity of OSA with levels of 8-isoprostane and interleukin-6 (IL-6) and with cardiac diastolic dysfunctions.. Forty children with adenoidal hypertrophy and 20 control children were recruited. The OSA clinical score was evaluated and IL-6 and 8-isoprostane were measured in exhaled breath condensate. The cardiac functions were evaluated by conventional and tissue Doppler echocardiography (TDE).. Higher concentrations of isoprostane-8 and IL-6 were found in group with clinical score >40 (58.595 +/- 2.86 pg/mL and 38 +/- 1.77 pg/mL, respectively) than in control group (34.9 +/- 1.5 pg/mL and 7.02 +/- 0.3 pg/mL, respectively) {p < 0.0001*}. There was positive correlation between level of isoprostane-8 and IL-6 and value of clinical score {p < 0.0001*} and also with the degree of the cardiac dysfunction in those children.. The severity of OSA as indicated by clinical score was positively correlated with degree of elevation of 8-Isoprostane and IL-6 in breath condensate of children with OSA and also with degree of cardiac dysfunction. Echocardiography and tissue Doppler modality are advised to examine these children.

Topics: Adenoids; Biomarkers; Child; Child, Preschool; Diastole; Dinoprost; Female; Humans; Inflammation; Interleukin-6; Male; Oxidative Stress; Pilot Projects; Polysomnography; Pulmonary Artery; Severity of Illness Index; Sleep Apnea, Obstructive; Systole; Ultrasonography; Ventricular Dysfunction

Polysomnography is the standard method for evaluating results of treatments for obstructive sleep apnea syndrome (OSAS), but it is time-consuming and often unavailable.. This study aimed to analyze the correlations between sleepiness, anthropometric parameters, exhaled breath condensate (EBC) and serum cytokine levels with changes in the apnea-hypopnea index (AHI), in order to identify potential measurements that could be an alternative to polysomnography.. Based on AHI results, 22 non-OSAS and 68 OSAS cases were followed up. Among the 68 patients, 5 underwent surgery, 2 were treated with oral appliances, 33 were treated using continuous positive airway pressure and 28 were untreated. AHI, anthropometric parameters, serum and EBC levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and 8-isoprostane were measured at baseline and after a 2-month follow-up. Correlations between the AHI and the other parameters were examined. Akaike's information criterion (AIC) was used to evaluate the fit of logistic regression models, predicting improvements in the severity of the condition from the parameters.. IL-6 and TNF-alpha in EBC and serum gave the highest correlation coefficients (r = 0.62 and r = 0.71 in EBC; r = 0.58 and r = 0.66 in serum, respectively) as well as the lowest AIC values (63.87, 68.97; 62.65, 70.64, respectively). Reductions in waist circumference and weight also correlated with changes in AHI (r = 0.69, AIC = 80.26 and 88.76, respectively).. IL-6 and TNF-alpha measurements may be used in OSAS treatment follow-ups, when polysomnography is not available. Waist circumference and weight could also be used when cytokine laboratory facilities are unavailable.

Topics: Adult; Biomarkers; Body Weight; Case-Control Studies; Cytokines; Dinoprost; Female; Humans; Male; Predictive Value of Tests; Prospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive; Waist Circumference

Excessive daytime sleepiness (EDS) is one of the most frequent symptoms in patients with obstructive sleep apnea syndrome (OSAS). However, not all patients with OSAS manifest EDS. The aim of this study was to assess whether differential circulatory levels of inflammatory mediators would account for differences in somnolence among patients with OSAS. Patients were prospectively recruited from referral patient cohort to the university hospital sleep center. A total of 50 consecutive patients with OSAS undergoing overnight polysomnography with or without EDS and 20 controls were evaluated. EDS was assessed using the Epworth sleepiness scale (ESS) and the multiple sleep latency test after overnight polysomnography. EDS was defined when the ESS was >10 and the mean sleep latency <10 min. Fasting blood was drawn in the morning after polysomnography. Circulating levels of tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), 8-isoprostaglandin F2alpha (8-iso-PGF2alpha), and P-selectin were measured with commercially available high sensitivity kits. Although patients with OSAS have elevated levels of ICAM-1, IL-6, and TNFalpha, there were no statistically significant differences in any of the inflammatory mediators between patients with EDS and without EDS. Emergence of EDS in the context of OSA does not appear to result from the selective increase of any particular somnogenic substance, i.e., TNFalpha, IL-6, ICAM-1, 8-iso-PGF2alpha, and P-selectin in the context of sleep-disordered breathing.

Topics: Cohort Studies; Dinoprost; Disorders of Excessive Somnolence; Female; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Oxidative Stress; Oxygen; P-Selectin; Polysomnography; Prospective Studies; Reference Values; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

HDL is anti-atherogenic and has antioxidant property. HDL dysfunction has been reported in patients with coronary heart disease and we hypothesize that HDL may also be dysfunctional in obstructive sleep apnea (OSA), a condition associated with increased oxidative stress.. 128 OSA patients and 82 controls were recruited. HDL dysfunction was determined by evaluating the ability of HDL to inhibit LDL oxidation ex vivo. Plasma HDL was incubated with native LDL in the presence of dichlorofluorescein which fluoresced upon interaction with lipid oxidation products. Plasma levels of oxidized LDL and 8-isoprostane were measured by ELISA and a specific enzyme immunoassay, respectively.. Plasma total 8-isoprostane levels were elevated in OSA subjects (p<0.01). Despite having similar concentrations of plasma lipids and apolipoproteins as controls, OSA subjects had greater degree of HDL dysfunction (p<0.01) and increased oxidized LDL levels (p<0.05). The apnea-hypopnea index was the main determinant of HDL dysfunction in OSA, accounting for 30% of its variance, with oxidized LDL and apolipoprotein AI contributing to 8% and 5% of its variance respectively (p<0.001).. HDL is dysfunctional in preventing the formation and inactivation of oxidized lipids in OSA subjects and may partly contribute to their increased cardiovascular risk.

Topics: Adult; Atherosclerosis; Biomarkers; Cholesterol, HDL; Dinoprost; Disease Progression; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Oxidative Stress; Prognosis; Retrospective Studies; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients.. The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients.. Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay.. Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001).. These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.

Topics: Breath Tests; Continuous Positive Airway Pressure; Dinoprost; Exhalation; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Oxidative Stress; Sleep Apnea, Obstructive