Serum C-reactive protein level and sleep characteristics in obstructive sleep apnea syndrome comorbid with panic disorder: a preliminary study.

OBJECTIVE: Investigate the sleep characteristics of patients with obstructive sleep apnea syndrome (OSAS) comorbidity with panic disorder (PD), exploring its potential association with serum C-reactive protein (CRP) levels. PATIENTS AND METHODS: Fifty-four patients (25 OSAS patients with PD and 29 without PD) and 25 healthy controls (HCs) were included. The Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI) were used to assess the mood and sleep quality of the subjects. All patients had circulating CRP levels and polysomnography was performed. RESULTS: OSAS with PD had higher SAS, SDS, PSQI than the OSAS without PD. Compared to OSAS without PD, OSAS with PD had higher percentage of non- rapid eye movement sleep 1 and 2 (N1 and N2%), sleep latency, and a lower percentage of rapid eye movement sleep (REM%). Respiratory-related microarousal index, AHI, and time below 90% oxygen saturation (T90) were low, and the lowest oxygen saturation (LO2) was high. Serum CRP levels in OSAS patients with PD were lower than that in OSAS patients without PD, but higher than that in HCs. In OSAS patients with PD, serum CRP levels were negatively correlated with wake time after sleep onset and SAS scores but positively correlated with sleep efficiency and N2%. Serum CRP levels were positively correlated with T90 and negatively correlated with LO2. CONCLUSION: OSAS patients with PD had worse sleep quality, less severe OSAS, and low serum CRP levels. Serum CRP levels in OSAS patients with PD were associated with poorer sleep quality and duration of hypoxia rather than AHI.

[Activity of the telomerase complex before and after CPAP therapy in patients with obstructive sleep apnea syndrome]. / Aktivnost' telomeraznogo kompleksa na fone SIPAP-terapii u patsientov s sindromom obstruktivnogo apnoe sna.

OBJECTIVE: To evaluate changes in the activity of the telomerase complex in patients with obstructive sleep apnea (OSA) before and after continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: In accordance with the objectives of the stages of the study of telomers-telomerase relationships, we maintained the unified design of the study described earlier. The main group 1 (MG1), n=35, consisted of men, aged 53.4 [45.5-60.1] years with characteristic complaints indicating of OSA. The main group 2 (MG2) included the same patients before and after 6 months of CPAP therapy. Blood sampling was performed after the first diagnostic polysomnography (PSG) and after 6 months of CPAP in the morning after the second PSG. The control group (CG) consisted of 26 men, comparable in age and the presence of chronic diseases. Questionnaire, PSG and blood sampling were conducted in CG as well. All participants signed an informed consent. RESULTS: As a result of the STOP-BANG questionnaire conducted before PSG, all patients in the MG1 had scores from 5 to 8. The scores on the Epworth scale were more than 5 points. In the MG2 apnea-hypopnea index decreased from 20.1 to 6.4 ev/hour, the desaturation index decreased from 15.6 to 7.1 ev/hour after 6 months of CPAP. Statistically significant differences in changes in the activity of the telomerase complex were revealed, which after treatment significantly exceed the values of these indicators before treatment. So, telomerase reverse transcriptase value was 0.04 (0.009; 0.06) in the MG1, after treatment it was 0.07 (0.06; 0.09) in the MG2 and 0.134 (0.009; 0.18) in the CG. Telomerase RNA subunit TER1 values were 0.06 (0.03; 0.09), 0.07 (0.05; 0.09) and 0.136 (0.04; 0.17), respectively. However, despite the activation of the telomerase complex during CPAP therapy in patients with OSA, in the CG its activity is significantly higher in comparison with the MG1 and MG2. CONCLUSION: In OSA accompanied by intermittent hypoxia, a decrease in the activity of the telomerase complex was shown. Elimination of nocturnal hypoxia and improvement of breathing during sleep is accompanied by an increase in the activity of the components of the telomerase complex.

Serum Urotensin II Levels Are Elevated in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4-55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.

The relationship between obstructive sleep apnea and circulating tau levels: A meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory, thinking, language, and, eventually, the ability to carry out the simplest of tasks. Tau protein, the major component of neurofibrillary tangles, is considered a key mediator of AD pathogenesis. The association between obstructive sleep apnea (OSA) and circulating tau remains unclear. The aim of the present meta-analysis was to evaluate the relationship between OSA and circulating tau via quantitative analysis. METHODS: A systematic search of Pubmed, Embase, and Web of Science were performed. The mean values of circulating total tau (T-tau) and phosphorylated tau (P-tau) in OSA and control groups were extracted. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using a random-effect model or fixed-effect model. RESULTS: A total of seven studies comprising 233 controls and 306 OSA patients were included in this study. The meta-analysis showed that the circulating T-tau level was significantly higher in OSA patients than those in the control group (SMD = 1.319, 95% CI = 0.594 to 2.044, z = 3.56, p < .001). OSA patients also had significantly higher circulating P-tau level than control group (SMD = 0.343, 95% CI = 0.122 to 0.564, z = 3.04, p = .002). CONCLUSIONS: The present meta-analysis demonstrated that both circulating T-tau and P-tau levels were significantly increased in OSA subjects when compared with non-OSA subjects. Larger sample-size studies on the association between OSA and circulating tau are still required to further validate our results.

Homocysteine Levels in Severe OSA Patients Before and After TORS-OSA Surgery.

OBJECTIVE: The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. METHODS: Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery. RESULTS: Two hundred sixty-one patients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9 to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012). CONCLUSION: TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.

Evaluation of mandibular advancement device placement based on levels of TNF-alpha in participants with obstructive sleep apnea: A clinical study.

STATEMENT OF PROBLEM: Objective assessments of the effect of mandibular advancement device on patients with obstructive sleep apnea are lacking. PURPOSE: The purpose of this clinical study was to compare levels of serum tumor necrosis factor alpha (TNF-alpha), Epworth Sleepiness Scale score, and Berlin Questionnaire score in patients with mild to moderate obstructive sleep apnea before and after treatment with a mandibular advancement device. MATERIAL AND METHODS: Twenty participants diagnosed with mild to moderate obstructive sleep apnea based on polysomnography testing were enrolled. A custom nonadjustable mandibular advancement device with 70% mandibular protrusion was provided for each participant for management of the obstructive sleep apnea. Evaluation of TNF-alpha levels was performed before treatment (baseline) and 3 and 6 months after starting mandibular advancement device therapy by using a Human TNF-alpha enzyme-linked immunoassay (ELISA) sandwich kit. The Epworth Sleepiness Scale and Berlin Questionnaire were also filled out by the participants at the same time intervals (α=.05). RESULTS: A statistically significant decline in the levels of TNF-alpha was observed at 3 and 6 months compared with baseline (P<.001). The Epworth Sleepiness Scale scores showed a statistically significant reduction at 3 and 6 months compared with baseline (P<.001). The risk of obstructive sleep apnea assessed by using the Berlin Questionnaire was found to be significantly reduced at 6 months compared with baseline (P=.001). CONCLUSIONS: Patients with mild to moderate obstructive sleep apnea showed reduced levels of TNF-alpha and Epworth Sleepiness Scale and Berlin Questionnaire scores when treated with a mandibular advancement device.

Later sleep timing and social jetlag are related to increased inflammation in a population with a high proportion of OSA: findings from the Cleveland Family Study.

STUDY OBJECTIVES: To examine the association between sleep midpoint and inflammation in a population with a large proportion of individuals diagnosed with obstructive sleep apnea syndrome (OSAS), a group that is already prone to increased inflammation. METHODS: Subjects from the Cleveland Family Study underwent overnight polysomnography and completed surveys on sleep habits. Morning and evening blood samples were collected and assayed for proinflammatory biomarkers interleukin (IL)-1, IL-6, and tumor necrosis factor α (TNF-α). Linear regression models were used, adjusting for potential confounders and sleep duration. RESULTS: The study population included 587 adults (52.3% with OSAS). Mean ± standard deviation weekday sleep midpoint was 3.52 ± 2.09 (3:31 am) and weekend sleep midpoint was 4.46 ± 1.69 (4:28 am). The Mean difference between weekday and weekend sleep midpoint (social jetlag) was 0.94 ± 2.08 hours. After adjusting for OSA severity, greater social jetlag was associated with higher levels of the inflammatory cytokine IL-1 (beta: 0.435 pg/mL, 95% confidence interval [CI]: 0.091 to 0.779). Additionally, later timing of sleep during both the weekdays and the weekends was associated with increased levels of IL-6 (weekday beta: 0.182 pg/mL; 95% CI: 0.013 to 0.350; and weekend beta: 0.188 pg/mL; 95% CI: 0.004 to 0.373). No trends were observed with TNF-α and any sleep exposure. CONCLUSIONS: Later sleep timing was associated with elevated levels of IL-6 while increased social jetlag was associated with elevated levels of IL-1. Our results indicate that later sleep schedules and increased social jetlag may lead to higher inflammation, even after controlling for OSA severity. CITATION: Girtman KL, Baylin A, O'Brien LM, Jansen EC. Later sleep timing and social jetlag are related to increased inflammation in a population with a high proportion of OSA: findings from the Cleveland Family Study. J Clin Sleep Med. 2022;18(9):2179-2187.

Association between obstructive sleep apnea and Alzheimer's disease-related blood and cerebrospinal fluid biomarkers: A meta-analysis.

INTRODUCTION: Recent studies indicate that Alzheimer's disease- (AD) related biomarkers, including amyloid ß (Aß40 and Aß42) and tau proteins (P-tau and T-tau), in blood and cerebrospinal fluid (CSF) are associated with obstructive sleep apnea (OSA). However, the results have been inconsistent. Therefore, the primary purpose of this meta-analysis was to determine the relationship between blood and CSF AD-related biomarkers and OSA. METHODS: We searched the Embase, PubMed, Scopus, and Cochrane Library databases for relevant articles till February 2022. RESULTS: Eight articles were finally included after the literature screening, including 446 patients with OSA and 286 controls. Pooled analysis showed that CSF Aß42 (SMD = -0.220, P = 0.136), T-tau (SMD = 0.012, P = 0.89), and P-tau (SMD = 0.099, P = 0.274) levels were not different between patients with OSA and controls. In patients with moderate to severe OSA, CSF Aß42 (SMD = -0.482, P = 0.031) were significantly lower than in controls. Blood T-tau (SMD = 0.560, P = 0.026), P-tau (SMD = 0.621, P < 0.001), and Aß40 (SMD = 0.656, P < 0.001) levels were significantly higher in patients with OSA than in controls. Blood Aß42 (SMD = 0.241, P = 0.232) were not different between patients with OSA and controls. CONCLUSION: OSA is associated with changes in AD-related markers. Higher OSA severity may be associated with the development of AD. AD-related biomarkers, especially in the blood, are clinically efficient, less invasively assessed and monitored, and may be useful for detecting OSA and related cognitive impairments. Further studies are needed to confirm these results.

Effect of positive airway pressure therapy of obstructive sleep apnea on circulating Angiopoietin-2.

BACKGROUND: Obstructive sleep apnea (OSA) has been identified as a possible contributor to interstitial lung disease. While positive airway pressure (PAP) is effective therapy for OSA, it causes large increases in lung volumes during the night that are potentially deleterious, analogous to ventilator-induced lung injury, although this has not been previously studied. The goal of this study was to assess the impact of PAP therapy on four biomarkers of alveolar epithelial and endothelial injury and extracellular matrix remodeling in patients with OSA. METHODS: In 82 patients with moderate to severe OSA who were adherent to PAP therapy, surfactant protein D, osteopontin, angiopoietin-2, and matrix metalloprotease-7 were measured by ELISA in serum samples collected before and 3- to 6-months after initiation of PAP therapy. RESULTS: An increase in angiopoietin-2 level of 0.28 ng/mL following PAP therapy was observed (p = 0.007). This finding was replicated in an independent sample of OSA patients. No significant change was detected in surfactant protein D, osteopontin, or matrix metalloprotease-7. CONCLUSIONS: This finding raises concern for a possible adverse impact of PAP therapy on vascular endothelium.

Endogenous controls and microRNA profile in female patients with obstructive sleep apnea.

Recent studies have evaluated the potential of circulating microRNAs (miRNAs) as valuable biomarkers for characterizing obstructive sleep apnea (OSA) in males. The potential use of miRNAs as clinical indicators in females is unknown. The objective is to identify a set of miRNAs to be used as endogenous controls (ECs) in female patients with OSA. Then, to analyze differences in the miRNA expression profile between patients with and without OSA. This observational, longitudinal study included 85 females with suspected OSA who underwent a polysomnography. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The study population was stratified into 50 OSA patients and 38 non-OSA patients. Exploratory expression profiling of 188 miRNAs consistent and reliable in plasma was performed in a discovery cohort of 21 patients by TaqMan-Low-Density-Array (TLDA). The best ECs were identified by mean centre + standard deviation normalization and concordance correlation restricted normalization. Differentially expressed candidate miRNAs were selected for RT-qPCR validation in a validation cohort of 64 patients. Three circulating miRNAs (miR-30a-5p, miR-93-3p and miR-532-5p) were identified as most stable for use as ECs. Twenty-seven miRNA candidates were identified as potential biomarkers for OSA screening (p value < 0.025) in the TLDA cohort. However, validation cohort showed no differences in the circulating miRNA profile in female patients with and without OSA. We identified a set of ECs in females with OSA that may contribute to result homogeneity in determining circulating miRNAs. Exploratory analysis did not identify a significantly miRNA profile between female patients with and without OSA.

Effect of obstructive sleep apnea on glucose metabolism.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, ß-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown. DESIGN AND METHODS: We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA. RESULTS: OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into both skeletal muscles and adipose tissue, whereas there was no significant difference between the OSA and control groups in insulin action on endogenous glucose production, basal insulin secretion, and glucose-stimulated insulin secretion during both intravenous and oral glucose tolerance tests. CONCLUSIONS: These data demonstrate that OSA is a key determinant of insulin sensitivity in people with obesity and underscore the importance of taking OSA status into account when evaluating metabolic function in people with obesity. These findings may also have important clinical implications because disease progression and the risk of diabetes-related complications vary by T2D subtype (i.e. severe insulin resistance vs insulin deficiency). People with OSA may benefit most from the targeted treatment of peripheral insulin resistance and early screening for complications associated with peripheral insulin resistance.

Upregulated heme biosynthesis increases obstructive sleep apnea severity: a pathway-based Mendelian randomization study.

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Iron and heme metabolism, implicated in ventilatory control and OSA comorbidities, was associated with OSA phenotypes in recent admixture mapping and gene enrichment analyses. However, its causal contribution was unclear. In this study, we performed pathway-level transcriptional Mendelian randomization (MR) analysis to investigate the causal relationships between iron and heme related pathways and OSA. In primary analysis, we examined the expression level of four iron/heme Reactome pathways as exposures and four OSA traits as outcomes using cross-tissue cis-eQTLs from the Genotype-Tissue Expression portal and published genome-wide summary statistics of OSA. We identify a significant putative causal association between up-regulated heme biosynthesis pathway with higher sleep time percentage of hypoxemia (p = 6.14 × 10-3). This association is supported by consistency of point estimates in one-sample MR in the Multi-Ethnic Study of Atherosclerosis using high coverage DNA and RNA sequencing data generated by the Trans-Omics for Precision Medicine project. Secondary analysis for 37 additional iron/heme Gene Ontology pathways did not reveal any significant causal associations. This study suggests a causal association between increased heme biosynthesis and OSA severity.

Evidence of plasma biomarkers indicating high risk of dementia in cognitively normal subjects.

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aß1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aß1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aß1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aß1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.

Plasma profiling reveals a blood-based metabolic fingerprint of obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition. OBJECTIVE: We examined the plasma metabolome and lipidome of patients with suspected OSA, aiming to identify potential diagnosis biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Additionally, we evaluated the impact of continuous positive airway pressure (CPAP) treatment on the circulating metabolomic and lipidomic profile. MATERIAL AND METHODS: Observational-prospective-longitudinal study including 206 consecutive subjects referred to the sleep unit. OSA was defined as an apnea-hypopnoea index ≥ 15 events/h after polysomnography (PSG). Patients treated with CPAP were followed-up for 6 months. Untargeted plasma metabolomic and lipidomic profiling was performed using liquid chromatography coulpled to massspectrometry. RESULTS: A plasma profile composed of 33 metabolites (mainly glycerophospholipids and bile acids) was identified in OSA vs. non-OSA patients. This profile correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses disclosed a 4-metabolites-signature that provided an accuracy (95% CI) of 0.98 (0.95-0.99) for OSA detection. CPAP treatment was associated with changes in 5 plasma metabolites previously altered by OSA. CONCLUSIONS: This analysis of the circulating metabolome and lipidome reveals a molecular fingerprint of OSA, which was modulated after effective CPAP treatment. Our results suggest blood-based biomarker candidates with potential application in the personalized management of OSA and suggest the activation of adaptive mechanisms in response to OSA-derived hypoxia.

Association between Interleukin-6 and vitamin D serum levels in patients with obstructive sleep apnea syndrome and impact of long-term continuous positive airway pressure therapy on biomarker levels.

OBJECTIVE: Hypoxia induces interleukin-6 (IL-6) production in obstructive sleep apnea syndrome (OSAS). Low serum 25 hydroxyvitamin D (25(OH)D) levels have been linked to OSAS susceptibility. Serum 25(OH)D levels have been negatively correlated with serum IL-6 levels in patients with chronic inflammation. No data exist to assess whether there is a correlation between 25(OH)D and IL-6 serum levels in OSAS, while the impact of continuous positive airway pressure (CPAP) therapy on IL-6 or 25(OH)D levels needs further investigation. We aimed to compare the serum 25(OH)D and IL-6 levels between OSAS patients and controls, examine a possible correlation between 25(OH)D and IL-6 levels and the changes of their concentrations after twelve months of CPAP therapy in OSAS patients. METHODS: 15 newly-diagnosed OSAS patients and 15 non-apneic controls were recruited. Serum IL-6 and 25(OH)D levels were measured in the study population at baseline and twelve months after CPAP initiation in OSAS patients. RESULTS: IL-6 levels were elevated in OSAS patients than controls and were positively and negatively correlated with body mass index (BMI) and minimum oxyhemoglobin saturation (minSpO2), respectively. Diabetes mellitus, BMI and minSpO2 independently predicted IL-6 levels. No difference was found in 25(OH)D levels between groups. No correlation between IL-6 and 25(OH)D levels was detected. Effective CPAP therapy did not impact IL-6 or 25(OH)D levels after one year in OSAS patients. CONCLUSIONS: No correlation between IL-6 and 25(OH)D levels was found. IL-6 levels were significantly elevated in OSAS patients than the controls and positively correlated with BMI, diabetes mellitus, and nocturnal hypoxemia.

Endothelial dysfunction in obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. METHODS: NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. RESULTS: Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S' ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. CONCLUSION: Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.

C-reactive protein in children with obstructive sleep apnea and effects of adenotonsillectomy.

OBJECTIVE: C-reactive protein (CRP) is an important serum marker of inflammation associated with cardiovascular outcomes. This study aims to evaluate the association between CRP and childhood obstructive sleep apnea (OSA) and clarify the effects of adenotonsillectomy on serum CRP levels in children with OSA. METHODS: Children with symptoms suggestive of OSA who underwent an overnight polysomnography were recruited from a tertiary medical center. Their serum CRP levels were measured. For children who underwent adenotonsillectomy for OSA treatment, polysomnography and serum high-sensitivity CRP (hs-CRP) level measurement were conducted after surgery. RESULTS: This study included 326 children (mean age: 7.2 ±â€¯3.0 years; boys: 67%). Children with apnea-hypopnea index (AHI) > 5 events/h had significantly higher hs-CRP levels than children with AHI of 1-5 events/h and AHI < 1 event/h [median (interquartile range): 0.08 (0.03-0.25) vs 0.03 (0.02-0.14) vs 0.04 (0.01-0.10), P < 0.001]. Log-transformed hs-CRP levels were positively associated with log AHI values (r = 0.2, P < 0.001). In multiple linear regression analysis, hs-CRP levels were independently associated with AHI; 101 children with OSA (ie, AHI > 1) underwent adenotonsillectomy. In children with OSA in the study cohort, a significant reduction of hs-CRP levels did not occur after surgery [from 0.07 (0.02-0.22) to 0.08 (0.03-0.17), P = 0.716]. In children with OSA having abnormal hs-CRP levels (ie, CRP > 1 mg/dL), hs-CRP levels significantly decreased after surgery [from 1.87 (1.11-2.78) to 0.20 (0.07-1.04), P = 0.043]. CONCLUSION: Children with OSA had increased hs-CRP levels. Children with OSA and abnormal hs-CRP levels exhibited significantly reduced hs-CRP levels following adenotonsillectomy.

Reboxetine Plus Oxybutynin for OSA Treatment: A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

BACKGROUND: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. RESEARCH QUESTION: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? STUDY DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. RESULTS: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P < .001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P < .001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P < .001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. INTERPRETATION: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.