Homocysteine as a predictor of apnea-hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO).

BACKGROUND: Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Homocysteine (Hcy) metabolism, when impaired, can elicit cellular senescence mechanisms that may be shared with OSA. Hence, our objective was to explore the role of Hcy concentrations both as a predictor of AHI values and as a potential risk factor for OSA. METHODS: Involving 1042 volunteers aged 20 to 80 years, the initial study (2007) included polysomnographic evaluations, questionnaires on sleep and general health, as well as biochemical analyses. After an 8-year interval, 715 participants from the initial study were invited for a follow-up assessment in 2015. RESULTS: Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy concentrations ≥ 15 µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] ß = 7.43; 95%CI 2.73 to 12.13) over time, compared to those with plasma concentrations < 10 µmol/L. A similar trend was apparent in those with plasma Hcy concentrations between 10 ≥ and < 15 µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI 1.01 to 5.39) compared to those with plasma Hcy concentrations < 10 µmol/L. CONCLUSIONS: In summary, our study suggests that increased plasma Hcy concentrations could be considered a risk factor for the development of OSA. These findings highlight that elevated plasma Hcy concentrations can predict the severity of OSA, underscoring their correlation with the AHI.

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.

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.

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.

Circulating sTweak is associated with visceral adiposity and severity in patients with obstructive sleep apnea syndrome.

Hypoxia is linked to an inflammatory imbalance in obstructive sleep apnea syndrome (OSAS). Circulating soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a cytokine that regulates inflammation and insulin resistance in adipose tissue. This study first investigated sTWEAK concentrations in patients OSAS and evaluated associations between sTWEAK concentrations and visceral adiposity, metabolic dysfunction, and hypoxia observed in OSAS. Forty age, sex, and body mass index-matched patients with simple habitual snoring (HSS) and 70 patients with OSAS were included. Patients were divided according to OSAS severity: mild-moderate (apnea-hypopnea index, AHI 5-30 events/h) and severe (AHI ≥ 30 events/h). Anthropometric data, glucose metabolism, visceral fat (VF) ratio, and sTWEAK levels were compared. sTWEAK levels were higher in the OSAS group than in the HSS group (931.23 ± 136.48 vs. 735.22 ± 102.84 ng/L, p = 0.001). sTWEAK levels were higher in severe OSAS than in mild-moderate OSAS (1031.83 ± 146.69 vs. 891.01 ± 110.01 ng/L, p = 0.002. When we evaluated the sTWEAK value and AHI, VF ratio, total cholesterol, blood pressure, homeostasis model of assessment-insulin resistance, and high-sensitivity C-reactive protein using multiple regression analysis, a significant correlation was found between sTWEAK levels and AHI (p < 0.001). It was found that sTWEAK levels were not correlated with glucose metabolism and VF ratio. Increased circulating sTWEAK levels were associated with the severity of OSAS. High sTWEAK levels were correlated with increased AHI. sTWEAK concentrations are linked to severe OSAS.

The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells.

Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients, the cell's morphology changes, NF-κB pathway is activated, and their beating rate and viability decreases. These results suggest an important link between OSAS, systemic inflammatory signals and end-organ cardiovascular diseases. In this work, we confirmed and expanded these observations on a new in vitro system of beating human cardiomyocytes (CM) differentiated from human embryonic stem cells (hES). Our results show that incubation with pediatric OSAS sera, in contrast to sera from healthy children, induces over-expression of NF-κB p50 and p65 subunits, marked reduction in CMs beating rate, contraction amplitude and a strong reduction in intracellular calcium signal. The use of human CM cells derived from embryonic stem cells has not been previously reported in OSAS research. The results further support the hypothesis that NF-κB dependent inflammatory pathways play an important role in the evolution of cardiovascular morbidity in OSAS. This study uncovers a new model to investigate molecular and functional aspects of cardiovascular pathology in OSAS.

The Rise of IGFBP4 in People with Obstructive Sleep Apnea and Multilevel Sleep Surgery Recovers Its Basal Levels.

IGFBP4 is the smallest member of the insulin-like growth factor binding protein family (IGFBP). It is a hepatic protein that plays a role in modulating the activity and bioavailability of IGF-I. The expression of IGFBP4 was found to increase under conditions of hypoxia. Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic episodes of intermittent hypoxia and fragmented sleep. Our aim was to quantify levels of circulating IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP7 in fasting plasma samples of 69 Kuwaiti participants and explore its correlation with indices of OSA. The quantification was performed using multiplexing assay. The study involved 28 controls and 41 patients with OSA. Levels of circulating IGFBP4 were significantly higher in people with OSA (289.74 ± 23.30 ng/ml) compared to the control group (217.60 ± 21.74 ng/ml, p = 0.028). The increase in IGFBP4 correlated significantly and positively with AHI (r = .574, p = .01) and AI (r = .794, p = .001) in people with moderate and severe OSA. There was a significant decline in circulating IGFBP4 after 3 months of surgery (225.89 ± 18.16 ng/ml, p = 0.012). This was accompanied by a prominent improvement in OSA (AHI 8.97 ± 2.37 events/h, p = 0.001). In this study, our data showed a significant increase in circulating IGFBP4 in people with OSA. We also report a significant positive correlation between IGFBP4 and indices of OSA at baseline, which suggests IGFBP4 as a potential diagnostic biomarker for OSA. There was a significant improvement in OSA after 3 months of surgical intervention, which concurred with a significant decline in IGFBP4 levels. Altogether, the detected change suggests a potential link between IGFBP4 and OSA or an OSA-related factor, whereby OSA might play a role in triggering the induction of IGFBP4 expression.

Early Atherosclerotic Inflammatory Pathways in Children with Obstructive Sleep Apnea.

OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.

The effects of high-sensitivity C-reactive protein on the clinical outcomes in obstructive sleep apnea patients undergoing off-pump coronary artery bypass grafting.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity and high-sensitivity C-reactive protein (Hs-CRP), and their respective impact on the clinical outcomes in patients undergoing off-pump cardiac artery bypass grafting (OPCABG). METHODS: We enrolled consecutive eligible patients listed for elective OPCABG who underwent cardiorespiratory polygraphy before surgery between January 2019 and December 2019 in this prospective observational single-center study. Baseline, intraoperative, and postoperative clinical data were compared between absent-mild and moderate-severe OSA groups. Regression analysis investigated the relationship between Hs-CRP level and severity of OSA, and further assessed the factors influencing postoperative atrial fibrillation, duration of hospitalization, and hospital cost. RESULTS: Patients with moderate-severe OSA accounted for 42.3% (52/123) of the cohort. Partial pressure of carbon dioxide (PCO2), Hs-CRP, apnea hypopnea index (AHI), mean apnea time, maximum apnea time, and oxygen desaturation index ODI ≥ 3% were significantly higher in the moderate-severe OSA group than in the absent-mild OSA group. Left ventricle ejection fraction (LVEF), lowest arterial oxygen saturation (SaO2), and mean SaO2 were significantly lower in the moderate-severe OSA group. Moderate-severe OSA was associated with elevated Hs-CRP level (OR = 2.356, 95% CI 1.101-5.041, P = 0.027). Hs-CRP was an independent risk factor for post-CABG atrial fibrillation (POAF) (OR = 1.212, P = 0.01). Hs-CRP level independently correlated with duration of hospitalization (B = 0.456, P = 0.001) and hospital cost (B = 1.111, P = 0.044). CONCLUSION: Hs-CRP level was closely related to OSA severity and have potential utility in predicting POAF, duration of hospitalization, and hospital costs in patients undergoing OPCABG.

The effects of vitamin D supplemantation on prognosis in patients with mild obstructive sleep apnea syndrome

Background/aim: The aim of this study was to investigate the effect of vitamin D on the disease prognosis and biochemical parameters in patients with mild obstructive sleep apnea syndrome (OSAS). Materials and methods: Nineteen adult male individuals (18­65 years) who were diagnosed with mild OSAS after polysomnography and had low vitamin D levels were included in the study. Each week, patients took 50.000 IU Vitamin D3 supplementation for 8 weeks. Polysomnography, biochemical parameters FBG (fasting blood glucose), lipid profile (TG, TC, LDL-C, HDL-C, VLDL-C), calcium, phosphorus, parathormone, calcitonin, serum 25(OH)D, insulin, CRP, TNF-α, IL-6, and IL-10 of patients were evaluated at the beginning of study and at the end of the study. All assessments, including polysomnography, were repeated after 8 weeks. Results: Serum vitamin D levels were initially 19.5 ± 5.01 ng/mL and increased to 41.8 ± 10.51 ng/mL (p < 0.001) at the end of the study. FBG, TC and HOMA-IR of the patients were significantly decreased (p < 0.05). CRP, TNF-α, IL-6, and IL-10 levels were also correlated with serum vitamin D levels (p < 0.05). There was a significant decrease in number of obstructive apneas, apneas a nd hypopneas, apnea index, hypopnea index, and apnea hypopnea index of the patients (p < 0.05). Conclusion: As a result, it is thought that vitamin D supplementation may have a positive effect on the disease prognosis of mild OSAS.

A community study of the risk for obstructive sleep apnea and respiratory inflammation in an adult Chinese population.

Objectives: We aimed to investigate the relationship between obstructive sleep apnea (OSA) risk and respiratory inflammation evaluated by the exhaled breath condensate (EBC) interleukin-6 (IL-6) and plasma surfactant protein-D (SP-D), based on the Berlin questionnaire (BQ) screening values in an adult, urban community in Beijing, China.Methods: Volunteers aged >40 years were recruited from the Shichahai community of central Beijing (Registration number: NCT04832711). Their general information and disease history were recorded. OSA risk was assessed using the BQ. IL-6 in EBC and plasma SP-D were d etected by enzyme-linked immunoassay through specimens collected while fasting. The differences in IL-6 and SP-D values between high-risk and low-risk groups for OSA were compared, and the factors affecting their values were analyzed.Results: Among 1,239 participants, 18.8% of participants were in the high-risk group. There were more participants with higher body mass index, chronic hypertension, coronary heart disease, and diabetes in the high-risk group than in the low-risk group (P < 0.05). There were no significant differences in EBC IL-6 and plasma SP-D between the high- and low-OSA risk groups (p > 0.05). After adjustment for age, sex and chronic comorbidities, multivariate logistic regression showed that there was no correlation between risk of OSA and IL-6 in EBC. However, the risk of OSA (odds ratio [OR] [95% CI]: 1.69 [1.15,2.48]; ß = 0.522) and BMI (OR [95%CI]: 0.94 [0.91,0.98]; ß = -0.061) were independently associated with plasma SP-D level (p < 0.05 for both). Stratification analysis showed that OSA risk were independently associated with plasma SP-D levels in participants <65 years, or men, or participants with BMI<25.Conclusion: This study showed that plasma SP-D, an inflammation biomarker, was associated with risk of OSA and BMI in a Chinese central urban community.The relationship between the risk of OSA and respiratory inflammation in community populations needs to be further evaluated.

The influence of obstructive sleep apnea syndrome on anthropometric parameters at 12 months after laparoscopic sleeve gastrectomy.

The aim of this study was to assess the influence of obstructive sleep apnea syndrome (OSAS) on the change in anthropometric parameters and body composition, in patients undergoing laparoscopic sleeve gastrectomy (LSG). This prospective study included patients undergoing LSG who had pre-operative polysomnography data and were also evaluated at six and 12 months after surgery. All patients included also had whole body composition analysis data before surgery and at six and 12 months after surgery. The results are presented in comparison between patients with and without OSAS. We included 73 patients in the analysis with a mean ± SD age and body mass index (BMI) of 40.3 ± 10.9 years and 45.4 ± 6.3 kg/m2, respectively. As compared to the baseline levels, at 6 months there was a significant decrease in BMI, weight, waist circumference, serum glucose and HbA1c. At 12 months there was no further decrease as compared to the 6 months levels, irrespective of OSAS status. We observed a significant decrease at 6 months in percentage of fat, in both types of patients. However, as compared to the 6 months levels, at 12 months the percent fat had a significant decrease only in patients without OSAS (- 4.6%, 95% CI - 7.6 to - 1.7%) and not in those with OSAS (- 2.2%, 95% CI - 4.5 to 0.2%). In our study, patients with OSAS showed a similar decrease in different anthropometric parameters as those without OSAS after LSG. However, at 12 months of follow-up there was a significant decrease in the percent fat only in patients without OSAS.

Interleukin 6 as a marker of depression in women with sleep apnea.

Depression is common in women with obstructive sleep apnea (OSA), but objective markers of depression have not yet been explored in such patients. We hypothesized that inflammation and antioxidant biomarkers may be associated with depression in a cohort of OSA women. We conducted a multicentre, cross-sectional study in 247 women diagnosed with moderate-to-severe OSA. Depression was assessed by the depression subscale of the Hospital Anxiety and Depression Questionnaire (HAD-D) and defined as a score ≥11. Associations between tumour necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF) plasma levels and depression were assessed. The women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index (BMI) of 33.5 (29.0-38.3) Kg/m2 , Epworth Sleepiness Scale (ESS) score of 10 (6-13) and apnea-hypopnea index (AHI) of 33.3 (22.8-49.3). Logistic regression analyses revealed that only IL6 levels were associated with the presence of depression (adjusted odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.34), whereas linear regression further confirmed that IL6 levels were significantly associated with HAD-D scores (ß = .154; 95% CI, 0.03-0.30). Multivariate regression analysis showed that IL6 (OR, 1.22; 95% CI, 1.09-1.36), ESS (OR, 1.10; 95% CI 1.02-1.19) and physical activity <30 min/day (OR, 2.51; 95% CI, 1.25-5.05) were independent predictors of depression. Thus, we conclude that in a cohort of women with moderate-to-severe OSA, IL6 levels are independently associated with the presence of depression and correlate with depression scores. Low physical activity and higher ESS scores are also independent indicators of risk of depression in this population.

Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea.

BACKGROUND: Raftlin is a large, major lipid raft protein of cell membranes. Raftlin levels have not been previously examined in patients with obstructive sleep apnea (OSA). Our study aimed to evaluate the changes in raftlin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) values from the preoperative state to the third month postoperatively in patients undergoing expansion sphincter pharyngoplasty for OSA. METHODS: Of 60 patients, 10 patients had mild OSA (AHI 5-14), 10 moderate (AHI 15-29), 10 severe (AHI ≥ 30), and 30 with AHI < 5 formed a control group. Preoperatively and at 3 months post-operatively, IL-6, IL-8, TNFα, and raftlin values were measured. RESULTS: Preoperatively, mean raftlin levels were 914.4 ± 62.7 pg/mL for controls, 910.0 ± 42.5 pg/mL in mild, 1000.5 ± 63.3 pg/mL in moderate, and 1386.3 ± 101.4 pg/mL in severe groups, with moderate and severe groups significantly elevated compared to controls (p < 0.001). Preoperatively to 3 months post-operatively, raftlin levels decreased significantly in each OSA group (p < 0.05). Levels of IL-6, IL-8 and TNFα followed similar patterns at baseline and after surgical intervention. CONCLUSIONS: Raftlin levels at the third postoperative month decreased significantly compared with preoperative levels in parallel with other markers of inflammation.

Patients with obstructive sleep apnea have suppressed levels of soluble cytokine receptors involved in neurodegenerative disease, but normal levels with airways therapy.

PURPOSE: Obstructive sleep apnea (OSA) results in systemic intermittent hypoxia. By one model, hypoxic stress signaling in OSA patients alters the levels of inflammatory soluble cytokines TNF and IL6, damages the blood brain barrier, and activates microglial targeting of neuronal cell death to increase the risk of neurodegenerative disorders and other diseases. However, it is not yet clear if OSA significantly alters the levels of the soluble isoforms of TNF receptors TNFR1 and TNFR2 and IL6 receptor (IL6R) and co-receptor gp130, which have the potential to modulate TNF and IL6 signaling. METHODS: Picogram per milliliter levels of the soluble isoforms of these four cytokine receptors were estimated in OSA patients, in OSA patients receiving airways therapy, and in healthy control subjects. Triplicate samples were examined using Bio-Plex fluorescent bead microfluidic technology. The statistical significance of cytokine data was estimated using the nonparametric Wilcoxon rank-sum test. The clustering of these high-dimensional data was visualized using t-distributed stochastic neighbor embedding (t-SNE). RESULTS: OSA patients had significant twofold to sevenfold reductions in the soluble serum isoforms of all four cytokine receptors, gp130, IL6R, TNFR1, and TNFR2, as compared with control individuals (p = 1.8 × 10-13 to 4 × 10-8). Relative to untreated OSA patients, airways therapy of OSA patients had significantly higher levels of gp130 (p = 2.8 × 10-13), IL6R (p = 1.1 × 10-9), TNFR1 (p = 2.5 × 10-10), and TNFR2 (p = 5.7 × 10-9), levels indistinguishable from controls (p = 0.29 to 0.95). The data for most airway-treated patients clustered with healthy controls, but the data for a few airway-treated patients clustered with apneic patients. CONCLUSIONS: Patients with OSA have aberrantly low levels of four soluble cytokine receptors associated with neurodegenerative disease, gp130, IL6R, TNFR1, and TNFR2. Most OSA patients receiving airways therapy have receptor levels indistinguishable from healthy controls, suggesting a chronic intermittent hypoxia may be one of the factors contributing to low receptor levels in untreated OSA patients.

Changes in Serum Leptin Level After Multilevel Surgery in Patients with Obstructive Sleep Apnea.

OBJECTIVE: Leptin hormone plays an important role in metabolic control and is elevated in obstructive sleep apnea (OSA). The aim of this study was to assess the hypothesis that surgical treatment will reduce leptin levels in OSA patients. STUDY DESIGN: Prospective study. SUBJECTS AND METHODS: Twenty-three patients with multilevel OSA underwent modified genioglossus muscle advancement with anterolateral advancement pharyngoplasty between April 2018 and September 2019. Serum leptin level was measured preoperatively and 3 months postoperatively for all patients and 18 control subjects. All patients were evaluated before and 3 months after surgery by history taking, clinical examination, polysomnography, cephalometry, and Epworth Sleepiness Scale. RESULTS: Preoperatively, patients with OSA had a higher Leptin level (18.46 ± 4.73 ng/mL) than did control subjects (7.07 ± 1.26 ng/mL) (P < .001). Surgery resulted in a significant reduction in the level of leptin from 18.46 ± 4.73 ng/mL to 8.03 ± 2.22 ng/mL (P < .001). Reductions in leptin level was correlated with changes in apnea hypopnea index (AHI) (r = 0.61, P = .002) and minimum oxygen saturation (SaO2) (r = -0.54, P = .008). CONCLUSION: Effective multilevel surgery in the form of modified genioglossus muscle advancement with anterolateral advancement pharyngoplasty could significantly reduce leptin level in OSA patients and this reduction is correlated with the degree of OSA improvement in term of AHI and SaO2. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E665-E670, 2021.

Serum periostin and TNF-α levels in patients with obstructive sleep apnea-hypopnea syndrome.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may cause pulmonary diseases, and periostin plays an important role on the development of pulmonary diseases. In addition, periostin and pro-inflammatory cytokine TNF-α can regulate each other in vivo. This study aimed to observe the changes of serum periostin and TNF-α levels in patients with OSAHS compared with healthy volunteers and to investigate their correlation. METHODS: A convenience sample of 67 patients with OSAHS in our hospital from December 2018 to December 2019 was selected and categorized into mild, moderate, and severe groups according to apnea-hypopnea index by polysomnography. In addition, 21 healthy volunteers were selected as the control group. Serum levels of periostin and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Results were analyzed using the SPSS software. RESULTS: Both serum periostin and TNF-α levels in all the three OSAHS groups were higher than those of the control group and increased with severity of OSAHS. The severe group had significantly higher serum periostin and TNF-α levels than the mild and moderate groups (p < 0.05). For patients with OSAHS, serum periostin and TNF-α levels positively correlated with the apnea-hypopnea index (AHI) (p < 0.01) and negatively correlated with the lowest saturation oxygen (LSaO2) and mean saturation oxygen (MSaO2) (both p < 0.01). In addition, there was a positive correlation between serum periostin and TNF-α levels in patients with OSAHS (p < 0.001). CONCLUSIONS: Serum periostin and TNF-α levels were significantly increased in patients with OSAHS and may serve as a potential biomarker for severity of OSAHS. These findings suggest that it may be fruitful to study the role of periostin and TNF-α in OSAHS-induced pulmonary diseases.

Transferrin saturation is independently associated with the severity of obstructive sleep apnea syndrome and hypoxia among obese subjects.

INTRODUCTION & AIMS: Obstructive sleep apnea syndrome (OSAS) is a frequent complication of obesity. Intermittent chronic hypoxia which frequently results from OSAS could modulate the systemic control of iron metabolism and alter serum iron parameters, especially among obese patients. AIMS: to evaluate whether serum parameters of iron bioavailability and storage (primary), as well as age, waist circumference, arterial hypertension and tobacco use (secondary) are associated with OSAS severity and/or hypoxia. METHODS: design: a single-center retrospective study with prospective data collection; inclusion criteria: consecutive patients referred for initial assessment for obesity underwent nocturnal respiratory polygraphy and iron status serum assessment within a 3-month period. The adjusted analyzes were performed using ANOVA and reported as adjusted means and 95% confidence interval (95% CI). RESULTS: 13 men and 56 women were included. OSAS prevalence: 72% (n = 50). Ferritin (mean ± SD, 260 ± 276 vs. 111 ± 89 µg/l, p = 0.01) and transferrin saturation (31 ± 10 vs. 24 ± 9%, p = 0.002) were significantly higher in case of moderate/severe OSAS than in absent/mild OSAS, independently from gender and tobacco use. Serum iron (19.4 µg/l [CI95%, 16.5-22.3] vs. 16.2 µg/l ([14.1-18.2], p = 0.056) and transferrin saturation (31.5% [26.3-36.7]) vs. 25.3% [21.6-29.1], p = 0.043) were higher when time under oxygen saturation <90% was >15%. Age (mean ± SD, 51 ± 11 vs. 41 ± 12 yr, p = 0.001), waist circumference (136 ± 18 vs. 123 ± 12 cm, p = 0.003), arterial hypertension (59% (n = 13/22) vs. 23% (n = 11/47), p = 0.004) and tobacco use (64% (n = 14/22) vs. 32% (n = 15/47), p = 0.01) were significantly greater in moderate/severe OSAS than in absent/mild OSAS. CONCLUSIONS: Transferrin saturation was associated with OSAS severity and time under hypoxia. This suggests a relationship between OSAS-induced hypoxia and iron metabolism among obese patients.