Obstructive Sleep Apnea Subjects Research Articles

Prospective randomised controlled trial to compare fixed pressure CPAP and auto adjusting pressure cpap among symptomatic obstructive sleep apnoea subjects in a tertiary care centre Malaysia

Prospective randomised controlled trial to compare fixed pressure CPAP and auto adjusting pressure cpap among symptomatic obstructive sleep apnoea subjects in a tertiary care centre Malaysia

Normal Hemoglobin Concentrations in Obstructive Sleep Apnea and Associated Neocytolysis-Mediated Hemolysis and Inflammation Mediated Suppression of Expected Elevated Hemoglobin

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) caused by recurrent episodes of upper airway obstruction during sleep. Chronic hypoxia increases red blood cell volume (RBCV) and hemoglobin concentration (Hb) in order to improve tissue oxygen delivery. However, the prevalence of increased Hb in OSA was only 1.7% (9 out of 527 patients) in our prior study (Gangaraju et al Blood 2016 128:2444). The reasons for this relative lack of discernable erythrocytosis is not yet fully understood. Further, the studies of possible changes in RBC and plasma volume in OSA are lacking. We collected blood samples from OSA patients before and after 3 months of continuous positive airway pressure (CPAP) treatment. We estimated erythropoietic activity by measuring erythropoietin (EPO) and reticulocyte count. EPO levels and reticulocytes were higher in OSA patients compared to controls; CPAP treatment normalized these levels. Time spent below sPO2 89% correlated with EPO levels (r=0.3434 and p=0.0403) indicating that episodes of hypoxia augmented erythropoiesis. However, Hb remained normal, leading us to hypothesize that augmented erythropoietic stimulus in OSA is counterbalanced by either 1) increase of hemolysis or 2) erythropoietic resistance to EPO. Hemolysis was detected in some but not all OSA patients by end-tidal carbon monoxide (ETCO), a product of heme catabolism; however, the instrument's limited sensitivity precluded detection of mild hemolysis. We previously showed that hypoxia-increased RBCV is transiently overcorrected upon rapid return to normoxia by preferential destruction of young red cells -neocytolysis. Neocytolysis is caused by excessive accumulation of reactive oxygen species (ROS) from increased retention of mitochondria in reticulocytes and decreased catalase in young RBCs (1). In our OSA subjects, we found that mitochondrial mass and mitochondrial ROS were higher in reticulocytes. Further, ROS were higher in B- cells, T-cells, monocytes, and granulocytes compared to controls. After CPAP treatment, these values normalized and catalase mRNA and enzyme activity also increased. These results support neocytolysis as one of the factors that prevent the increase of Hb in OSA. OSA also induces inflammation, a factor known to inhibit erythropoiesis, in part by induction of hepcidin which inhibits release of iron from macrophages. IL-6 and TNF transcript levels in granulocytes were higher in OSA compared to controls and normalized after CPAP treatment. Hepcidin levels were higher in OSA compared to controls. Hepcidin levels were correlated with inflammatory markers, IL-6 levels were inversely correlated with EPO levels, and iron and transferrin saturation levels were lower in OSA, inversely correlating with elevated hepcidin. The normal Hb does not rule out the presence of polycythemia, as increased RBCV could be offset by concomitant increase in plasma volume resulting in a normal Hb concentration. This was recently demonstrated in Tibetan Sherpas living in hypoxic high altitude who have normal Hb but increased RBCV and plasma volume (PV) (2). One can determine RBCV and PV by inhaling known amount of CO and measuring increments of carboxyhemoglobin together with Hb and hematocrit. We recently obtained the required instrumentation (OpCO, DETALO INSTRUMENTS, Denmark), and are currently correlating our clinical and biochemical measurement with OSA subjects' RBCV and PV to either confirm presence of hypoxia-induced polycythemia or conclusively rule it out. We conclude that the absence of elevated Hb in OSA is attributable not only to neocytolysis but also to the suppression of erythropoiesis by inflammation. 1) Song J, Yoon D, Christensen RD., Horvathova M,Thiagarajan P, and Prchal JT. HIF mediated increased ROS from reduced mitophagy and decreased catalase causes neocytolysis. J Mol. Med., (Berl). 2015 Aug., PMID: 26017143. 2) Stembridge M et all. The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives. Proc Natl Acad Sci U S A.2019 Jul 29. [Epub ahead of print]. Disclosures Lundby: Detalo: Other: CEO and founder. Ganz:Intrinsic LifeSciences: Consultancy, Equity Ownership.

Explorating the Involvement of Plasma Sestrin2 in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) can lead to serious complications such as coronary heart disease and hypertension due to oxidative stress. Sestrin2 expression is upregulated under conditions of oxidative stress. This study aimed to explore whether Sestrin2 was involved in OSA. OSA and healthy control subjects were recruited and matched with age, gender, and body mass index (BMI). Plasma Sestrin2 levels were measured and compared. A multivariate stepwise regression model was used to detect the relationship between Sestrin2 and other variable factors. The Sestrin2 levels were compared between before and after four weeks treatment by nasal continuous positive airway pressure (nCPAP) in severe OSA patients. Fifty-seven subjects were divided into two groups: control group (39.33 ± 9.40 years, n = 21) and OSA group (38.81 ± 7.84 years, n = 36). Plasma Sestrin2 levels increased in the OSA group (control group 2.06 ± 1.76 ng/mL, OSA group 4.16 ± 2.37 ng/mL; P = 0.001). Sestrin2 levels decreased after four-week nCPAP treatment (pre-nCPAP 5.21 ± 2.32 ng/mL, post-nCPAP 4.01 ± 1.54 ng/mL; P = 0.004). Sestrin2 was positively correlated with apnea/hypopnea index (AHI) oxygen desaturation index, while negatively correlated with mean oxygen saturation. Moreover, these correlations remained unchanged after adjusting for gender, age, waist-to-hip ratio, and body mass index. Multiple regression analysis showed that there was an association between Sestrin2 and AHI. Our findings suggest that Sestrin2 is involved in OSA. The increase of plasma Sestrin2 is directly related to the severity of OSA. To some extent, Sestrin2 may be useful for determining the severity of OSA and monitoring the effect of CPAP. In addition, since some complications of OSA such as coronary heart disease and diabetes are usually related with oxidative stress, the role of Sestrin2 in those OSA complications needs further study.

Prevalence of Glaucoma in Patients with Obstructive Sleep Apnea

To determine the prevalence of glaucoma in obstructive sleep apnea (OSA) patients and compare it with that of patients without OSA. Patients investigated for OSA using polysomnography at the sleep center of King Abdulaziz University Hospital were invited to participate in this cross-sectional case series study. American Academy of Sleep Medicine guidelines were used to diagnose OSA. Recruitment of patients with and without OSA was conducted from December 2013 to September 2015. Exclusion criteria included topical and systemic steroid use and presence of other ocular diseases. Two criteria, cup/disc ratio and visual field defects, were necessary for a glaucoma diagnosis. Among 84 adults enrolled, 44 (52%) had a confirmed diagnosis of OSA. Glaucoma prevalence was higher among individuals with OSA (16%) than among non-OSA individuals (8%), a difference that was not statistically significant. A consistent trend, which was not statistically significant after adjusting for cofounders, toward more glaucomatous changes was observed in OSA subjects. Although a trend toward higher glaucoma prevalence was observed in OSA patients, the difference was not statistically significant. As many variables contribute to the development of the two conditions, larger cohorts are needed to evaluate associations between glaucoma and OSA.

Circulating ESM-1 levels are correlated with the presence of coronary artery disease in patients with obstructive sleep apnea

BackgroundEndothelial dysfunction is one of the most important early indicators of atherosclerosis in obstructive sleep apnea (OSA) patients. Endothelial cell specific molecules-1 (ESM-1), which is a novel endothelial dysfunction marker that may be linked to cardiovascular disease. We investigated to assess whether circulating ESM-1 levels are correlated with the presence of coronary artery disease (CAD) in patients with OSA.MethodsWe performed a cross-sectional study in 228 Chinese OSA subjects, including 185 patients with OSA and 43 controls. The Gensini stenosis scoring system was used to assess the severity of CAD. Circulating ESM-1 levels were measured by Human Magnetic Luminex Screening Assay. The associations between circulating ESM-1 levels and CAD were determined by multivariate logistic regression analysis. The association between ESM-1 levels and Gensini scores was determined by multivariate linear regression analysis.ResultsCAD patients had significantly higher circulating ESM-1 levels compared with non-CAD patients (1279.01[918.52–1770.71] pg/ml vs 585.46[423.61–812.56] pg/ml, P < 0.001). After adjusting for confounding factors, we found that circulating ESM-1 levels were an independent risk factor for CAD (OR = 1.633/100 pg ESM-1, 95%CI =1.179–2.262, P = 0.003), while circulating ESM-1 levels have no significant correlation with the Gensini score. Furthermore, circulating ESM-1 showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.910).ConclusionsCirculating ESM-1 might function as a useful biomarker for monitoring the development and progression of CAD in OSA patients.

Urinary EPCR and dermcidin as potential novel biomarkers for severe adult OSA patients

BackgroundDue to low predictive values of obstructive sleep apnea (OSA) screening tools, there is a need for biomarker for screening of OSA patients at an early stage. The aim of the study was to evaluate differentially expressed proteins in blood and urine samples of OSA patients. MethodsIn this study, we used isobaric tagging for relative and absolute quantification (iTRAQ) based proteomics approach to identify differentially expressed proteins, which were subsequently verified and validated using enzyme-linked immunosorbent assay (ELISA) technique in adult OSA patients. ResultsSeventeen differentially expressed proteins were selected from iTRAQ data for verification, based on their clinical significance and reproducibility among different iTRAQ experiment sets. Five of these proteins (plasma = 2; urine = 3) were further validated in plasma (non-OSA- = 42; OSA = 198) and urine samples (non-OSA = 46; OSA = 197). ROC curve analysis for all OSA vs. non-OSA subjects ensured optimal diagnostic utility of two urinary proteins: Endothelial protein c receptor (EPCR) (AUC = 73%, cut-off: 35 pg/ml) and dermcidin (AUC = 74%, cut-off: 4.6 pg/ml). For severe OSA, diagnostic accuracy significantly improved with AUC as 88% and 82% for EPCR (cut-off: 46 pg/ml) and dermcidin (cut-off: 5.2 pg/ml) respectively. Sensitivity and specificity of combined performance of both urinary proteins for severe OSA were 94% and 91% respectively. ConclusionIn this study, urinary EPCR and dermcidin emerged as novel biomarkers for screening severe OSA patients.

Dynamic Estimation of Cerebral Blood Flow Using Blood Pressure Signal in sleep Apnea Patients.

Monitoring apnea-induced cerebral blood flow (CBF) oscillations is of importance for assessing apnea patient brain health. Blood pressure (BP) oscillations during apnea can induce oscillations in CBF. Preliminary results of testing an Auto Regressive Moving Average model relating nocturnal CBP oscillations to nocturnal BP variations in 8 obstructive sleep apnea subjects (3 F, 55±8 yrs., BMI 34.2±7.85 kg/m2) showed that largest mean and standard deviation of the CBF estimation errors was 4.49±7.57 cm/s and maximum root mean squared of the errors was 8.80 cm/s. Hence, reasonable accuracy in estimating CBF from BP during sleep apnea events was observed.

Bone Mineral Density in Obstructive Sleep Apnea and Obesity

BackgroundOsteoporosis, a condition associated with decreased bone density, contributes significantly to morbidity and mortality. Importantly, the incidence and economic burden of osteoporosis is rising partly due to increases in the aging population. Moreover, while the role of obesity on bone health is controversial, studies suggest that obesity alters bone density. Effects of obstructive sleep apnea (OSA), which is more prevalent in ageing and obesity, on any relationship between obesity and BMD are not well known.ObjectiveTo examine the effects of BMI and OSA on total and regional bone density.MethodsA database of all research participants with nocturnal polysomnography and whole body dual energy X‐Ray absorptiometry scan (DEXA) was created. The study population included 72 subjects without OSA (AHI&lt;5, Age: 29.1 ± 7.3 years, BMI: 24.3 ± 3.6 Kg/m2) and 22 subjects with OSA (apnea hypopnea index, AHI&gt;5; 4 females, Age: 43.3 ± 11.2 years, BMI: 30.8 ± 4.1 Kg/m2). We examined the relationship between BMI and BMD in all our subjects. Linear regression models adjusted for age and BMI were used to assess changes in bone density in the presence of OSA. Additional analyses examining the effects of OSA in overweight and obese individuals (BMI&gt;25 kg/m2) and relationship between BMI and BMD in OSA subjects were also undertaken.ResultsTotal body bone density in all our study subjects was positively correlated with BMI (Std Beta = 0.42, 95% CI 0.004 – 0.015, p &lt; 0.001) but not age (Std Beta = 0.04, 95% CI −0.002 −0.003, p = 0.71) or presence of OSA (Std Beta = 0.042, −0.029 − 0.040, p = 0.75). Similarly, bone density in spine was increased with increases in BMI (Std Beta = 0.45, 95% CI 0.006 − 0.019, p = 0.0003) and not affected by age (Std Beta = 0.14, 95% CI −0.001 – 0.005, p = 0.23) or presence of OSA (Std Beta = 0.18, 95% CI −0.011 – 0.065, p = 0.16). Also, increases in BMD in pelvic region were only associated with BMI (Std Beta = 0.30, 0.001 – 0.019, p = 0.024). Age (Std Beta = −0.09, −0.005 – 0.002, p = 0.45) or presence of OSA (Std Beta = 0.19, −0.016 – 0.086, p = 0.17) did not alter BMD in pelvic area. Interestingly, overweight and obese subjects with OSA had a lower pelvic BMD compared to overweight and obese subjects without OSA (1.10 ± 0.12 g/cm3 Vs. 1.19 ± 0.16 g/cm3, p = 0.043), even when OSA subjects had a higher BMI (31.4± 3.7 kg/m2 Vs. 27.8± 3.2 Kg/m2, p = 0.001) and were older (43.4 ± 11.3 years Vs 30.6 ± 8.8 years, p&lt;0.001). Also, the positive relationship between BMI and BMD was not present in OSA subjects in our study population (Total BMD: p = 0.73; Spine BMD: p = 0.94; Pelvic BMD: p=0.77).ConclusionA positive association between bone density and BMI was observed in our study population. However, this relationship was not evident in OSA subjects. Further, our study suggests that OSA may be accompanied by decreased bone density in the pelvic region. Cross‐sectional and longitudinal studies examining the effects of OSA on regional bone density, fractures, and frailty in BMI, age and gender matched populations are warranted.Support or Funding InformationVKS and PS are supported by NIH grant HL65176This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Obstructive Sleep Apnea is Associated with Longitudinal Increases in Amyloid Burden in Elderly Mild Cognitive Impairment Individuals

Cross sectional analysis has shown an association between Obstructive Sleep Apnea (OSA) severity and Aβ burden using amyloid-PET among Mild Cognitive Impairment (MCI) patients. However, whether OSA accelerates longitudinal increases in amyloid beta (Aβ) burden in MCI patients is presently unclear. Study participants included a total of 798 subjects with a diagnosis of MCI and were a subset of the ADNI cohort (adni.loni.usc.edu). OSA was self-reported and participants were labeled either as OSA+ or OSA−. Aβ burden was determined by florbetapir SUVRs. To test whether OSA is associated with the rate of change in Aβ data longitudinally, multilevel mixed effects linear regression was used to fit the models with randomly varying intercepts and slopes allowing dependence on OSA status. The final model was adjusted for age, sex, body mass index, education, CPAP use status, history of respiratory disease, hypertension, diabetes, and history of cardiovascular disease. A significant variation in the change (slope) in Aβ volumes over time was seen (p&lt;.0001). The covariance between the baseline Aβ level and Aβ volume change over time indicated that OSA subjects experienced greater mean change differences in brain Aβ volumes over time (p &lt; .0001). The rate of change in Aβ deposition also varied significantly across OSA groups over the follow-up period. Obstructive Sleep Apnea possibly facilitates longitudinal increases in amyloid burden in elderly Mild Cognitive Impairment individuals. Further research examining mechanisms underlying effects of OSA on the longitudinal increases in Aβ burden is needed.

Beneficial effects of a lifestyle intervention program on C-reactive protein: impact of cardiorespiratory fitness in obese adolescents with sleep disturbances.

The objectives of this study were to assess the relationship between inflammation and obstructive sleep apnea (OSA) and determine whether the lifestyle program's effects on inflammatory markers are associated with changes in anthropometric parameters, cardiorespiratory fitness, sleep duration, and OSA severity in severely obese adolescents. Participants were aged 14.6 (SD 1.2) yr, with a body mass index (BMI) of 40.2 (SD 6.5) kg/m2. Sleep, anthropometric parameters, glucose metabolism, inflammatory profile, and cardiorespiratory fitness [V̇o2peak relative to body weight (V̇o2peakBW) and fat-free mass (V̇o2peakFFM)] were assessed at admission and at the end of a 9-mo lifestyle intervention program (LIP). Associations between C-reactive protein (CRP) concentrations and BMI, sex, oxygen desaturation index (ODI), sleep fragmentation, total sleep time (TST), and V̇o2peak were assessed via ANCOVA. Twenty-three subjects completed the study. OSA subjects ( n = 13) exhibited higher CRP concentrations and a trend for higher BMI than non-OSA subjects ( P = 0.09) at admission. After intervention, OSA was normalized in six subjects, and CRP significantly decreased in the OSA group and in the whole population. In both groups, leptin levels significantly decreased, whereas adiponectin concentrations increased. At admission, BMI adjusted for sex, arousal index, ODI, TST, and V̇o2peakBW was associated with CRP levels (adjusted r2 = 0.32, P < 0.05). The decrease in CRP concentrations postintervention was associated with enhanced V̇o2peakFFM adjusted for sex, weight loss, and changed sleep parameters (adjusted r2 = 0.75, P < 0.05). Despite higher amounts of CRP in OSA subjects, obesity severity outweighs the proinflammatory effects of OSA, short sleep duration, and low cardiorespiratory fitness. However, enhanced cardiorespiratory fitness is associated with the decrease of inflammation after controlling for the same parameters.

Slow-wave activity surrounding stage N2 K-complexes and daytime function measured by psychomotor vigilance test in obstructive sleep apnea.

To better understand the inter-individual differences in neurobehavioral impairment in obstructive sleep apnea (OSA) and its treatment with continuous positive airway pressure (CPAP), we examined how changes in sleep electroencephalography (EEG) slow waves were associated with next-day psychomotor vigilance test (PVT) performance. Data from 28 OSA subjects (Apnea-Hypopnea Index with 3% desaturation and/or with an associated arousal [AHI3A] > 15/hour; AHI3A = sum of all apneas and hypopneas with 3% O2 desaturation and/or an EEG arousal, divided by total sleep time [TST]), who underwent three full in-lab nocturnal polysomnographies (NPSGs: chronic OSA, CPAP-treated OSA, and acute OSA), and 19 healthy sleepers were assessed. Four 20-minute PVTs were performed after each NPSG along with subjective and objective assessment of sleepiness. Three EEG metrics were calculated: K-complex (KC) Density (#/minute of N2 sleep), change in slow-wave activity in 1-second envelopes surrounding KCs (ΔSWAK), and relative frontal slow-wave activity during non-rapid eye movement (NREM) (%SWA). CPAP treatment of OSA resulted in a decrease in KC Density (chronic: 3.9 ± 2.2 vs. treated: 2.7 ± 1.1; p < 0.01; mean ± SD) and an increase in ΔSWAK (chronic: 2.6 ± 2.3 vs. treated: 4.1 ± 2.4; p < 0.01) and %SWA (chronic: 20.9 ± 8.8 vs. treated: 26.6 ± 8.6; p < 0.001). Cross-sectionally, lower ΔSWAK values were associated with higher PVT Lapses (chronic: rho = -0.55, p < 0.01; acute: rho = -0.46, p = 0.03). Longitudinally, improvement in PVT Lapses with CPAP was associated with an increase in ΔSWAK (chronic to treated: rho = -0.48, p = 0.02; acute to treated: rho = -0.5, p = 0.03). In contrast, OSA severity or global sleep quality metrics such as arousal index, NREM, REM, or TST were inconsistently associated with PVT Lapses. Changes in EEG slow waves, in particular ∆SWAK, explain inter-individual differences in PVT performance better than conventional NPSG metrics, suggesting that ΔSWAK is a night-time correlate of next-day vigilance in OSA.

Untreated Obstructive Sleep Apnea Is Associated With Myocardial Injury Independent of Blood Pressure Control in Hypertension.

Obstructive sleep apnea (OSA) and hypertension are independent risk factors of cardiovascular morbidities. This study aims to investigate the relationship between OSA, blood pressure (BP) control, and myocardial injury in patients with difficult-to-control hypertension. Patients with hypertension who required three or more medications were prospectively recruited at a tertiary referral center. In-laboratory polysomnography, followed by blood tests for fasting glucose, glycated hemoglobin, lipids, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), C-reactive protein, and advanced oxidation protein products were performed. After polysomnography, 24-hour ambulatory BP monitoring was arranged. A total of 98 participants were analyzed, with mean age 51 ± 9 years and body mass index 30 ± 5 kg/m2. Previously undiagnosed severe OSA (apneahypopnea index [AHI] ≥ 30 events/h) was present in 51 patients (52%). hsTnI was negatively correlated with nocturnal dip in systolic BP (r = -.205, P = .048). After controlling for confounders, including BP control, AHI and oxygen desaturation index (ODI) were positively correlated with hsTnI (r = .282, P = .009 and r = .279, P = .010, respectively) and C-reactive protein (r = .302, P = .005 and r = .285, P = .008, respectively), but not with BNP or advanced oxidation protein products. Age, ODI, and loss of nocturnal systolic BP dip were significant determinants of hsTnI level (β = .225, P = .022; β = .293, P = .003; and β = -.215, P = .029; R2 = .151). Age, female sex, 24-hour mean diastolic BP, and metabolic syndrome, but not indices of apnea severity, were predictors of BNP level. Unrecognized severe OSA was common in patients with difficult-to-control hypertension, and OSA severity was associated with myocardial injury, independent of BP control with medications. Registry: ClinicalTrials.gov, Title: A Cross-sectional Study of the Occurrence and Effect of Obstructive Sleep Apnea in Subjects With Resistant Hypertension, Identifier: NCT00843583, URL: https://clinicaltrials.gov/ct2/show/NCT00843583.

Modelling mucosal surface roughness in the human velopharynx: a computational fluid dynamics study of healthy and obstructive sleep apnea airways.

We previously published a unique methodology for quantifying human velopharyngeal mucosal surface topography and found increased mucosal surface roughness in patients with obstructive sleep apnea (OSA). In fluid mechanics, surface roughness is associated with increased frictional pressure losses and resistance. This study used computational fluid dynamics (CFD) to analyze the mechanistic effect of different levels of mucosal surface roughness on velopharyngeal airflow. Reconstructed velopharyngeal models from OSA and control subjects were modified, giving each model three levels of roughness, quantified by the curvature-based surface roughness index (CBSRI0.6) (range 24.8-68.6 mm-1). CFD using the k-ω shear stress transport turbulence model was performed (unidirectional, inspiratory, steady-state, 15l/min volumetric flow rate), and the effects of roughness on flow velocity, intraluminal pressure, wall shear stress, and velopharyngeal resistance (Rv) were examined. Across all models, increasing roughness increased maximum flow velocity, wall shear stress, and flow disruption while decreasing intraluminal pressures. Linear mixed effects modeling demonstrated a log-linear relationship between CBSRI0.6 and Rv, with a common slope (log(Rv)/CBSRI0.6) of 0.0079 [95% confidence interval (CI) 0.0015-0.0143; P = 0.019] for all subjects, equating to a 1.9-fold increase in Rv when roughness increased from control to OSA levels. At any fixed CBSRI0.6, the estimated difference in log(Rv) between OSA and control models was 0.9382 (95% CI 0.0032-1.8732; P = 0.049), equating to an 8.7-fold increase in Rv. This study supports the hypothesis that increasing mucosal surface roughness increases velopharyngeal airway resistance, particularly for anatomically narrower OSA airways, and may thus contribute to increased vulnerability to upper airway collapse in patients with OSA.NEW & NOTEWORTHY Increased mucosal surface roughness in the velopharynx of patients with obstructive sleep apnea (OSA) has recently been identified, but its role in OSA pathogenesis is unknown. This is the first study to model the impact of increased roughness on airflow mechanics in the velopharynx. We report that increasing roughness significantly affects airflow, increasing velopharyngeal resistance and potentially increasing the vulnerability to upper airway collapse, particularly in those patients with an already compromised anatomy.

A3937 Genetic Polymorphisms of SP-B and Risk of Obstructive Sleep Apnea

Objectives: To investigate whether polymorphisms of the surfactant protein B (SP-B) gene are associated with or increase the susceptibility to the development of obstructive sleep apnea (OSA). Methods: A total of 345 subjects (169 severe OSA patients, 176 controls) who underwent polysomnography (PSG) were continuously recruited from the Hypertension Center of the People's Hospital of Xinjiang from April to December 2016. Three candidate single nucleotide polymorphisms (SNPs) of the SP-B gene (rs1130866, rs2077079 and rs3024791) were selected and the genotype identification were determined by Kompetitive Allele Specifc PCR genotyping system. Results: The frequencies of rs1130866 genotypes CC, CT and TT were 60.87%, 32.3% and 6.83% in severe OSA group, and 42.35%, 49.41% and 8.24% in the non-OSA group respectively. The genotype distributions of 3 polymorphisms in additive, allele and recessive model showed statistically significant difference between severe OSA and non-OSA group (P < 0.05). After adjustment of age, gender, BMI, smoking and alcohol history, multivariate linear regression showed that genotype CC of rs1130866 contributed as risk factor to OSA (OR = 2.885, 95%CI: 1.657–5.023, P < 0. 001). However, the frequencies of polymorphism of rs2077079 and rs3024791 showed no significant difference between the two groups (P > 0.05). Conclusion: The polymorphism (rs1130866) in SP-B gene potentially involved in the process of the loss of a potential N-linked, amino-terminus glycosylation site of pro-SP-B and may be related to OSA by the surfactant dysfunction in severe OSA subjects.

ASSOCIATION OF OBSTRUCTIVE SLEEP APNEA WITH CENTRAL SEROUS CHORIORETINOPATHY AND CHOROIDAL THICKNESS: A Systematic Review and Meta-Analysis.

Obstructive sleep apnea (OSA) has been associated with an array of ocular disorders. This systematic review aims to investigate the association of OSA with central serous chorioretinopathy (CSCR) and subfoveal choroidal thickness changes on enhanced depth imaging optical coherence tomography. Systematic review and meta-analysis of all articles published up to November 2017 examining rate of OSA in patients with CSCR versus controls or examining subfoveal choroidal thickness measurements on enhanced depth imaging optical coherence tomography in patients with OSA versus controls. Pooled odds ratios and weighted mean difference with 95% confidence intervals (CIs) were calculated. For the CSCR/OSA analysis, 7,238 patients (1,479 with CSCR and 5,759 controls) from 6 studies were eligible. For the choroidal thickness/OSA analysis, 778 eyes of 778 patients (514 with OSA and 264 controls) from 9 studies were eligible. Patients with CSCR had a 1.56 increased odds of having OSA than controls (odds ratio, 1.56; 95% CI, 1.16-2.10). There was no statistically significant difference in choroidal thickness between mild OSA subjects and controls (weighted mean difference = -3.17; 95% CI, -19.10 to 12.76). Patients with moderate OSA (weighted mean difference = -24.14; 95% CI, -42.16 to -6.12) and severe OSA (weighted mean difference = -51.19; 95% CI, -99.30 to -3.08) had thinner choroidal thickness measurements than controls. In summary, our results suggest that patients with CSCR are more likely to have OSA, and that moderate/severe OSA is associated with smaller subfoveal choroidal measurements on enhanced depth imaging optical coherence tomography.

Potential Circulating Biomarkers as Early Diagnosis for Patients with Suspected Obstructive Sleep Apnea and Type 2 Diabetes

Background: Obstructive sleep apnea (OSA) was prevalent in the population worldwide, but the majority of symptomatic OSA remained undiagnosed. Previous evidence suggested the complex relationship between OSA and Type 2 diabetes (T2D). The aim of this study was to explore potential biomarkers to diagnose OSA/T2D in early-stage. Methods: All participants performed polysomnography and fasting plasma glucose for the diagnosis of OSA and T2D. The study population consisted of patients with OSA, T2D and control subjects. Meanwhile, we measured 20 cytokines in plasma using a Luminex platform. Findings: The levels of SELE, SELL and CTSS were significantly increased in patients with OSA and T2D compared to patients with OSA. Further, compared to control subjects, levels of circulating SELE, SELL and CTSS were increased in patients with OSA but not in patients with T2D. In addition, there were strongly and positively correlated with SELE, SELL and CTSS by Pearson correlation analysis. Multiple linear regression analysis demonstrated that SELE, SELL and CTSS were independently associated with the presence of OSA. Furthermore, the optimal cutoff values of circulating SELE, SELL and CTSS for diagnosing OSA were 25.21 ng/mL, 904.43 ng/ml and 4.34 ng/ml, respectively, determined separately via ROC analysis. Interpretation: Circulating SELE, SELL and CTSS may serve as new biomarkers to diagnose subclinical or clinical OSA and contribute to evaluating the early stages of T2D in patients with OSA. Funding: The work was supported by International Science & Technology Cooperation Program of China (2015DFA30160) and Chinese National Natural and Scientific Funding (8167032). Declaration of Interest: The authors declare that they have no anything to disclose regarding competing interests and funding. Ethical Approval: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTR-ROC-17011027). And Ethical approval was granted by the Ethics Committee of Beijing Anzhen Hospital of Capital Medical University according to Helsinki Declaration II. All subjects provided written informed consent to participate.

Catestatin serum levels are increased in male patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a complex sleep disorder associated with autonomic and sympathetic dysregulation. To the contrary, catestatin, an endogenous pleiotropic peptide cleaved from chromogranin A, is known for its inhibitory effects on catecholamine release and sympathetic activity. The aims of the study were to determine catestatin serum levels among male OSA patients compared to healthy control subjects and to explore associations of catestatin with anthropometric, polysomnographic, and lipid profile parameters. Seventy-eight male OSA patients aged 50.3 ± 8.8years and 51 age/sex/BMI-matched control subjects aged 50.4 ± 7.8years were enrolled in the study. Catestatin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA). Catestatin serum levels were significantly higher among OSA patients compared to control subjects (2.9 ± 1.2 vs. 1.5 ± 1.1ng/mL, p < 0.001). Serum catestatin levels significantly correlated with apnea-hypopnea index (AHI) among non-obese OSA subjects (r = 0.466, p = 0.016; β = 0.448, p = 0.026), while in whole OSA population, catestatin levels significantly correlated with neck circumference (r = 0.318, p < 0.001; β = 0.384, p < 0.001) and high-density lipoprotein (HDL) cholesterol (r = - 0.320, p < 0.001; β = - 0.344, p < 0.001). In multivariate-adjusted regression model, serum catestatin was significant and independent predictor of OSA status (OR 4.98, 95% CI 2.17-11.47, p < 0.001). Catestatin serum levels are significantly increased in male OSA population and positively correlate with disease severity in non-obese patients. OSA status is independently predicted by catestatin levels; however, this finding is restricted to patients with moderate-to-severe disease. Further studies are necessary to elucidate the mechanistic role of catestatin in the complex pathophysiology of OSA.

Non-alcoholic fatty liver disease is an independent risk factor for inflammation in obstructive sleep apnea syndrome in obese Asian Indians.

Obstructive sleep apnea (OSA) has been estimated to affect 4-11% of the population and causes systemic inflammation which leads to metabolic syndrome (MS). Non-alcoholic fatty liver disease (NAFLD) is also associated with MS whether NAFLD is an additional risk factor for the systemic inflammation that occurs in OSA is unclear. In this study, we aimed to analyze the association of OSA and NAFLD with MS and systemic inflammation in Asian Indians. Total 240 (132 males and 108 females) overweight/obese subjects [body mass index (BMI > 23kg/m2)] were recruited; of these, 124 subjects had OSA with NAFLD, 47 had OSA without NAFLD, 44 did not have OSA but had NAFLD and 25 had neither OSA nor without NAFLD. Severity of NAFLD was based on abdomen ultrasound and of OSA on overnight polysomnography. Clinical examinations, anthropometry, body composition, metabolic parameters, and inflammatory biomarkers were recorded. Serum levels of leptin, macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6), high sensitive C-reactive protein (Hs-CRP), and tumor necrosis factor alpha (TNF-α) were significantly higher, and adiponectin levels were significantly lower in OSA with NAFLD subjects. Prevalence of MS was significantly increased in OSA and NAFLD subjects (p = 0.001). There was a strong association and correlation between leptin, IL-6, Hs-CRP, MIF, and TNF-α in OSA and NAFLD subjects. Multivariate logistic regression showed that OSA was positively associated with the NAFLD [odds ratio (OR), (95% confidence interval (CL) 3.12 (2.58-7.72), (P = 0.002)]. NAFLD is an additional risk factor in OSA subject which contributes to systemic inflammation in Asian Indians.

Association of inflammatory genes in obstructive sleep apnea and non alcoholic fatty liver disease in Asian Indians residing in north India.

BackgroundPrevious studies have indicated that variants of the high sensitive C-reactive protein (CRP), Interleukin (IL)-6 and leptin receptor (LEPR) genes are associated with the presence of obstructive sleep apnea (OSA) but not in non-alcoholic fatty liver disease (NAFLD) in Asian Indians. The study was conducted to investigate the association of CRP rs1130864 (1444C/T), IL-6 rs1800795 (-174G/C) and LEPR rs1137101 (Q223R) genes with OSA and NAFLD in Asian Indians residing in North India.Methods240 overweight/ obese subjects [body mass index (BMI>23kg/m2)], 124 with OSA and with NAFLD (group 1), 47 with OSA without NAFLD (group 2), 44 without OSA and with NAFLD (group 3) and 25 without OSA and without NAFLD (group 4) were recruited in this study. The severity of NAFLD was based on abdomen liver ultrasound and of OSA on overnight polysomnography. Clinical details, anthropometry profile, body composition, biochemical parameters and inflammatory markers were measured. Polymerase chain reaction and restriction fragment length polymorphism of CRP, IL-6 and LEPR gene was performed. The associations of these polymorphisms with clinical, anthropometric and biochemical profiles were investigated. The genotypes were confirmed by DNA sequencing analysis.ResultsThe C, T and R alleles of IL-6, CRP and LEPR genes was more frequent in OSA and NAFLD subjects and significantly correlated with higher protein levels. The prevalence of variant genotypes C/T of CRP, G/C of IL-6 and Q/R of LEPR genes was significantly higher in OSA subjects as compared to non OSA subjects. Further, C/C genotype of IL-6 (G/C), T/T of CRP (C/T) and RR genotype of LEPR (Q/R) was associated with significantly higher BMI, fat mass (kg), % body fat, waist circumference, serum triglycerides, total cholesterol, alkaline phosphate, aspartate transaminase and fasting insulin levels in OSA and NAFLD subjects. Using a multivariate analysis, the combined effect of three polymorphisms of CRP, IL-6 and LEPR gene variants on OSA and NAFLD risk was evaluated. Odds ratio for OSA and NAFLD with the combination of the three gene polymorphisms increased to 2.84 (95% CI: 1.08–6.54; p = 0.04) even when adjusted for sex, age and BMI.ConclusionPolymorphisms of pro-inflammatory cytokine genes were associated with increased risk of OSA and NAFLD in Asian Indians.

Lung function impairment is not associated with the severity of acute coronary syndrome but is associated with a shorter stay in the coronary care unit.

Previous population-based studies have suggested that lung function impairment (LFI) could be associated with an increase in the mortality of cardiovascular events. We evaluated the association between LFI and the severity and short-term prognosis of acute coronary syndrome (ACS). LFI was established through presence of a forced expiratory volume in one second (FEV1) and/or a forced vital capacity (FVC) less than 80% of predicted. Seventy-one LFI subjects (61.45±10.70 years, 83.10% males) and 247 non-LFI subjects (58.98±11.18 years, 80.57% males) with ACS were included. Subjects with LFI exhibited a higher prevalence of systemic hypertension (57.75% vs. 40.89%, P=0.02) and tobacco exposure (28.50±26.67 vs. 18.21±19.83 pack-years, P=0.007). No significant differences between groups were found regarding the severity of ACS (ejection fraction, Killip class, number of affected vessels, and peak plasma troponin). However, in comparison to non-LFI subjects, a significantly shorter length of stay in the coronary care unit (CCU) was observed in the LFI group (1.83±1.10 vs. 2.24±1.21 days, P=0.01) and this was even shorter in subjects with obstructive LFI (1.62±1.17 days, P=0.009). When considering obstructive sleep apnea (OSA), an interaction with length of stay was found, revealing that OSA subjects with obstructive LFI had the shortest length of stay in the CCU (0.60±0.89 days, P=0.05) also in comparison to non-LFI. This study indicates a possible association between LFI and a shorter length of stay in the CCU but does not show a significant association with ACS severity.