Severe Obstructive Sleep Apnea Patients Research Articles

Analysis of the myoelectric characteristics of genioglossus in REM sleep and its improvement by CPAP treatment in OSA patients.

To reveal the characteristics of genioglossus (GG) activation in moderate and severe obstructive sleep apnea (OSA) patients during rapid eye movement (REM) sleep compared with non-rapid eye movement (NREM) sleep and to determine whether continuous positive airway pressure (CPAP) could improve GG activation in OSA patients during sleep. All subjects underwent polysomnography (PSG) with synchronous GG electromyography (GGEMG) recording with intra-oral surface electrodes at baseline on the first night. Only those subjects diagnosed with moderate and severe OSA were included and were manually titrated with CPAP to achieve a therapeutic pressure (Pt) with GGEMG recording on the second night. Nine OSA patients and six normal controls were analyzed in this study. The tonic GGEMG was higher in OSA patients during wakefulness (p = 0.003) and NREM sleep (p = 0.015), but it was not higher in REM sleep (p = 0.862). The average phasic activity of OSA patients was significantly higher in all stages, including wakefulness (p = 0.007), NREM sleep (p = 0.005), and REM sleep (p = 0.021). The peak phasic GGEMG was not different in wakefulness compared with normal controls (p = 0.240), but it was higher in OSA patients in NREM sleep (p = 0.001) and REM sleep (p = 0.021), and it was significantly reduced by using CPAP during sleep (NREM sleep: p = 0.027; REM sleep: p = 0.001). Our results demonstrate that GG activation during NREM and REM sleep is associated with component differences. The tonic component of GGEMG exhibited less of a compensatory increase compared with the phasic component in REM sleep, suggesting that it may be one of the pathological mechanisms of UA collapsibility in REM sleep. In addition, treatment with CPAP can normalize GGEMG activity and mostly reduced the peak phasic GGEMG during sleep.

Appropriate BMI Criteria for Indian Population: Does It Help Stratify Obstructive Sleep Apnea (OSA) Patients Better?

Obstructive sleep apnea (OSA) is a common yet unrecognized medical problem with significant morbidity. It is commonly considered an obesity-related problem, although not uncommon in non-obese patients of Indian origin. Currently, the World Health Organization (WHO) Western BMI criteria are widely used to classify obesity levels. Indian population has a different association between body mass index (BMI), percentage of body fat, and health risks compared to the western population. Due to these ethnic variations, applying the appropriate criteria—the WHO recommendation for appropriate BMI for Asian population—would be more suitable for identifying obesity in Indians, and, hence, to identify those at risk for OSA. We aimed to explore the discrepancy that could arise by applying the WHO Western BMI criteria to the Indian population which might misclassify and exclude those who are at risk for obesity-related OSA. This is a retrospective study of patients who presented to Nithra Institute of sleep sciences, Chennai, India, from May 2015 to May 2017. Patients who underwent polysomnography and diagnosed with OSA were included. Data pertaining to demographics, BMI, and severity of OSA were collected and analyzed. Patients were classified into different weight bands based on both the Western and Asian BMI criteria and compared. Stratification based on severity of OSA and its association with both the BMI classification was also analyzed. During the study period, 904 patients were clinically suspected to have OSA, of whom 787 patients underwent polysomnography. Of these, 754 patients were confirmed to have OSA and were included in the study. [626 males (83%)/128 females (16.9%); mean age—50.7 ± 28.6 years]. 735 (97.5%) patients were classified as overweight/obese as per Asian BMI, whereas only 695 (92.2%) patients were classified as overweight/obese as per Western BMI classification. With respect to the association of the BMI categories with the severity of OSA, there were significant differences between the numbers of severe OSA patients in each weight band of Asian BMI when compared to Western BMI. OSA may be underestimated clinically in Indian population when Western BMI criteria is applied. Asian BMI as recommended by WHO is more suitable in reflecting the correlation between obesity and OSA than the western BMI criteria.

Which is more important: the number or duration of respiratory events to determine the severity of obstructive sleep apnea?

Aim: Apnea–hypopnea index (AHI) take account only the number of apnea and hypopnea regardless of their duration and morphology. The aim of this study was to compare the mean obstructive apnea duration (MOAD), mean mixed apnea duration (MMAD), mean central apnea duration (MCAD), mean total apnea duration (MTAD) and mean hypopnea duration (MHD) with the demographic parameters, blood oxygenation and other polysomnographic sleep parameters in patients diagnosed with severe obstructive sleep apnea (OSA).Materials and methods: A retrospective study included 121 patients who had a diagnosis of severe OSA. The correlations between the MOAD, MMAD, MCAD, MTAD, MHD and patient demographic parameters, blood oxygenation and other polysomnographic sleep parameters were analyzed.Results: Severe OSA patients with longer MOAD and MTAD had shorter Stage N3. Longer MOAD, MMAD, MCAD, MTAD, MHD were related to lower mean oxygen saturation. Longer MOAD and MTAD were associated with higher oxygen desaturation index. MOAD, MMAD, MTAD were positively associated with a duration below oxygen saturation 85%.Conclusions: Respiratory events can have different characteristics even though the average number of events per hour would be similar. Novel parameters like MOAD, MMAD, MCAD, MTAD, MHD could enhance the evaluation and classification of OSA in addition to AHI.

Leptin and adiponectin levels in obstructive sleep apnea phenotypes.

Objective: To examine the serum levels of leptin and adiponectin in different obstructive sleep apnea (OSA) phenotypes. Methods: Obese patients who were admitted to our sleep laboratory were included. All patients underwent spirometry, daytime arterial blood gas analysis, polysomnography and transthoracic echocardiography. Serum levels of adiponectin and leptin were recorded. Results: Analysis included 146 OSA patients (81 females, 65 males, age: 49.8±10.7 years, body mass index:40.3±4.9kg/m2, 47.9% severe OSA, 42.5% severe obesity). Females had higher leptin and adiponectin levels (p<0.001;p<0.001, respectively). Leptin levels were higher in patients with severe obesity (p<0.001). Severe OSA patients had lower leptin and adiponectin levels (p=0.023;p=0.035, respectively). Conclusion: Adipokine levels were different especially in OSA patients with severe obesity, female gender and severe OSA.

The role of body fat rate in the evaluation of obstructive sleep apnea

Objective: To investigate the role of body fat ratio in the evaluation of obstructive sleep apnea(OSA). Methods: A retrospective analysis was made on 174 cases (between November, 2017 and April, 2018 showed that) of sleep monitoring in the Department of Otorhinolaryngology in Peking University Third Hospital. The data included the gender, age, body fat rate, body mass index (BMI), neck circumference, and apnea-hypopnea index (AHI). The above data were analyzed by non parametric correlation analysis, receiver operating characterristic (ROC) curve analysis and multiple factor Logistic regression analysis to study the relationship between the gender,age,body fat rate,BMI,neck circumference and other indexes of the patients with AHI. Results: Nonparametric correlation analysis showed that the correlation from strong to weak to AHI among women was BMI (r=0.621, P<0.001),body fat rate (r=0.602, P<0.001), age (r=0.570, P<0.001), neck circumference (r=0.402, P=0.014), respectively. BMI (r=0.599, P<0.001), neck circumference (r=0.493, P<0.001), body fat rate (r=0.318, P<0.001), and age (r=0.256, P=0.003) among men. ROC curve analysis showed that the strong to weak index (area under curve,AUC) of the AHI>15/h among women was the body fat rate (AUC=0.884, P=0.001), BMI(AUC=0.810, P=0.008), neck circumference (AUC=0.759, P=0.027), age (AUC=0.750, P=0.033), and the male was BMI (AUC=0.765,P<0.001), neck circumference (AUC=0.720, P<0.001), age (AUC=0.634, P=0.008), and body fat rate (AUC=0.632, P=0.010), respectively. Multifactor Logistic regression analysis showed that the body fat rate (OR=1.704,95%CI=1.012-2.870) in women was an independent risk factor for AHI greater than 15/h; the age of male (OR=1. 044, 95%CI=1.005-1.085) and BMI (OR=1.285, 95%CI=1.056-1.562) were independent risk factors for AHI greater than 15/h. Conclusion: Body fat rate can be used as a new indicator for predicting the severity of OSA,especially in adult female population. In adult female moderate to severe OSA patients (AHI>15/h), compared with BMI,neck circumference and age,the body fat rate has the greatest correlation with AHI. Compared with BMI,neck circumference and age,the body fat rate has a decisive role in predicting moderate to severe OSA (AHI>15/h).

Formyl peptide receptor 1 up-regulation and formyl peptide receptor 2/3 down-regulation of blood immune cells along with defective lipoxin A4/resolvin D1 production in obstructive sleep apnea patients.

BackgroundThis study aims to investigate the role of FPR 1/2/3 expressions in patients with obstructive sleep apnea (OSA).MethodWe made cross-sectional comparisons of FPR1/2/3 expressions of blood neutrophil, M1/M2a monocyte, and natural killer (NK) cell between 16 healthy subjects (HS), 16 primary snoring (PS) subjects, 46 treatment-naive OSA patients, and 18 severe OSA patients under long-term continuous positive airway pressure treatment (severe OSA on CPAP).ResultsFPR1 expressions on neutrophil were increased in treatment-naive OSA and severe OSA on CPAP groups versus either HS or PS. FPR2 expressions on neutrophil were decreased in treatment-naive OSA versus HS, and returned to normal in severe OSA on CPAP group. FPR1/FPR2 expression ratio on neutrophil was increased in treatment-naive OSA versus either HS or PS. Serum lipoxin A4, resolvin D1 levels, and FPR3 expressions of M1, M2a and NK cells were all decreased in treatment-naive OSA versus HS. OSA patients with hypertension had decreased FPR2 expressions on neutrophil and FPR3 expressions of NK cell. FPR1 expression, FPR1/FPR2 expression ratio on neutrophil, and FPR3 expression of M1 cell were all reversed after > 6-month CPAP treatment in 9 selected patients. In vitro intermittent hypoxia with re-oxygenation treatment in THP-1 cells resulted in increased FPR1/FPR2 expression ratio of M1 cells, and increased FPR1/FPR3 expression ratio of M2a cells.ConclusionsFPR1 over-expression and insufficiency of FPR2 and FPR3 in association with defective lipoxin A4 and resolving D1 production were associated with disease severity of OSA and its adverse consequences.

Effects of somatotropic axis on cognitive dysfunction of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with a variety of neuroendocrine disorders and may lead to many complications, including cognitive dysfunction. The aim of this study was to assess the change of somatotropic axis and to detect the relation between somatotropic axis hormone and cognitive dysfunction. Sixty-six patients with OSA and 16 healthy controls were enrolled in this cross-sectional study. Cognitive function assessment using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and polysomnography were performed on all individuals. Blood samples were taken the next morning following the polysomnography and the level of serum growth hormone-releasing hormone (GHRH) and growth hormone (GH) were analyzed by enzyme-linked immunosorbent assay. Compared with the control group, OSA patients showed significantly lower serum GH level (p < 0.05), whereas no statistical significance of GHRH level was found. In addition, lower MMSE and MoCA scores were found only in the severe OSA patients when compared with the controls. Furthermore, in severe OSA patients with cognitive dysfunction (MMSE score < 27 and MoCA score < 26), serum GHRH and GH levels were significantly lower than those without cognitive dysfunction. Logistic analysis revealed that cognitive dysfunction in severe OSA patients was associated with micro-arousal index and the level of serum GHRH and GH. Decreased serum GH and GHRH levels were found among severe OSA patients with cognitive dysfunction who were overweight, which might promote the occurrence of cognitive dysfunction.

The efficacy of the improved tongue base suspension surgery combined with UPPP in the treatment of severe OSA

Objective:This study was designed to show the preliminary efficacy and safety of the improved tongue base suspension surgery in severe obstructive sleep apnea(OSA) patients classified as Friedman Ⅱand Friedman Ⅲ. Method:The severe OSA patients diagnosed by PSG as Friedman Ⅱ type and Ⅲ type underwent surgery treatment. The tongue base of the patient was implanted with titanium plate and fixed on the chin of mandible. The UPPP surgery was performed with reference to H-UPPP. After surgery, the patients were followed up, PSG was re-examined and the change of various subjective and objective indicators of rehabilitation and adverse reactions were observed and recorded.Result: One hundred and two patients with severe OSA who were not tolerant or unwilling to use CPAP treatment were treated by the above surgical method. All the patients underwent surgery successfully and generally recovered about 1 month after the surgery without obvious tongue base pain, foreign body sensation or other discomfort. Eating and speaking function were as usual, the wound was healed well, and no serious infection or rejection was observed. The main postoperative adverse reactionwas tension line fracture(3 cases). Sixty-seven patients completed follow-up. At 3 to 6 months after surgery, the AHI, ESS sleepiness score and snore index were lower than those before surgery, while LSaO₂and CT 90% were higher than those before surgery(P<0.01). The AHI before surgery was 60.5± 22.4, and the average AHI after surgery was 27.8± 22.4. The effective rate of the surgery was 71.6% and the success rate was 58.2%. The AHI has dropped by an average of 54.0%, and snore improved by 63.9%. Conclusion: After preliminary clinical observation, the study suggests that the improved tongue base suspension with UPPP has satisfactory curative effect and feasibility for the treatment of severe OSA patients classified as Friedman Ⅱ type and Ⅲ type.

Abnormal resting-state functional connectivity of amygdala subregions in patients with obstructive sleep apnea.

Background: The amygdala is one of the core areas of the emotional circuits. Previous neuroimaging studies have revealed that patients with obstructive sleep apnea (OSA) have aberrant structure and function in several brain areas (including the amygdala). However, the resting-state functional connectivity (rs-FC) of amgydala subregions remains uncertain.Objective: To determine whether aberrant rs-FC exists between the amygdala subregions and other brain areas and whether such abnormalities are related to emotional disorders and cognitive impairment in OSA.Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) data of 40 male severe OSA patients and 40 matched healthy controls (HCs) were collected. The rs-FC between the amygdala subregions and other brain areas was compared between the two groups. The correlations between aberrant rs-FC and clinical variables and neuropsychological assessments were evaluated.Results: Compared with the HCs, the OSA patients showed significantly increased rs-FC between the left dorsal amygdala (DA) and the anterior lobe of the cerebellum, among the left ventrolateral amygdala (VA), the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG), and between the right VA and the left IFG. However, significantly decreased rs-FC was observed between the right DA and the right prefrontal cortex (PFC) in OSA patients. No regional differences in rs-FC were found between the OSA patients and HCs in the bilateral medial amygdala (MA).Conclusion: In this study, male severe OSA patients showed complex rs-FC patterns in the amygdala subregions, which may be the result of OSA-related selective damage to the amygdala, and abnormal rs-FC between the amygdala subregions and brain regions associated with emotional, cognitive and executive functions may partly explain the affective deficits and cognitive impairment observed in male severe OSA patients.

Effectiveness of nasal continuous airway pressure therapy in patients with obstructive sleep apnea.

A prospective observational study was carried out with the aim of evaluating the effectiveness of nasal continuous positive airway pressure (nCPAP) therapy on the health-related quality of life (QoL) of patients with obstructive sleep apnea (OSA). The patients included in this study were those recently diagnosed with OSA (AHI>5) and given nCPAP therapy, as well as being referred to a sleep laboratory for an assessment of their sleep disordered breathing. Prior to the start of nCPAP therapy and polysomnography evaluation, patients were asked to complete the validated Quebec sleep questionnaire (QSQ), and their baseline measurements were recorded. Among the study population, 14.41% (n=31) had mild OSA with an apnea and hypopnea index of 5 to 14.9 events/h, while 26.97% (n=58) had moderate OSA and 40% (n=86) had severe OSA. The overall average apnea and hypopnea index of the study population was 30.24±9.73 events/h; mild OSA patients had an average apnea and hypopnea index of 10.09±2.65 events/h, moderate OSA patients had 21.48±4.40 events/h, and severe OSA patients had 59.16±22.14 events/h. A significant difference was observed between the scores before treatment and after 6months of therapy in all domains of the QSQ QoL scores (P<0.0001). Nasal continuous positive airway pressure treatment improved the QoL for patients with mild, moderate, and severe sleep apnea.

Monocytic C-C chemokine receptor 5 expression increases in in vitro intermittent hypoxia condition and in severe obstructive sleep apnea patients

PurposeObstructive sleep apnea (OSA) patients have higher risk of cardiovascular disease. C-C chemokine receptor 5 (CCR5), as an important receptor for monocyte recruitment and the initiation of atherosclerosis, was studied under intermittent hypoxia and in OSA patients.MethodsThe expression and function of CCR5 regulated by intermittent hypoxia in monocytic THP-1 cells were investigated in an in vitro intermittent hypoxia culture system. The expression levels of protein and mRNA were analyzed by western blot and RT/real-time PCR analysis. Cell adhesion assay and transwell filter migration assay were carried out to investigate the adhesion and chemotaxis of monocytes. In addition, the mRNA expression of CCR5 in monocytes isolated from peripheral blood of 72 adults was analyzed.ResultsIntermittent hypoxia upregulated the expression of CCR5 in THP-1 cells and enhanced the adhesion and chemotaxis of monocytes to vascular endothelial cells mediated by RANTES. The CCR5 expression induced by intermittent hypoxia was inhibited by inhibitor for p42/44 MAPK. Besides, the expression of CCR5 in monocytes increased along the AHI value especially in severe OSA patients that was statistically significant compared with mild and moderate OSA groups.ConclusionsThis study demonstrated the increased monocytic CCR5 gene expression in patients with severe OSA. Intermittent hypoxia, the characteristic of OSA, induced monocytic CCR5 gene expression and the enhanced RANTES-mediated chemotaxis and adhesion through p42/44 MAPK signal pathways.

EFFECTS OF LONG-TERM CONTINUOUS POSITIVE AIRWAY PRESSURE THERAPY (CPAP) ON EPICARDIAL FAT THICKNESS AND ARTERIAL STIFFNESS IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA AND HYPERTENSION

Background:obstructive sleep apnea (OSA) is associated with high prevalence of arterial hypertension (AH), obesity, violation of carbohydrate metabolism and dyslipidemia. However, the effects of CPAP therapy to improve epicardial fat thickness of the OSA patient with AH the are poorly understood and poorly studied.Study objective:the aim of the study was to investigate 12-month effects of CPAP therapy with auto-adaptation to inhalation and exhalation of the OSA patient with AH and metabolic disorders (A-Flex therapy) on epicardial fat thickness (EFT).Methods:to the prospective single-center study were included 310 patients with OSA and AH (273 male, 45,3 ± 10,4 yr.) with apnea-hypopnea index (AHI) &gt;5 events /hour. The night polygraphy study (PG) was performed to calculate AHI, oxygen desaturation index (ODI), mean nocturnal saturation (SpO 2 ) by the rules of American Academy of Sleep Medicine (AASM). The calculation of the epicardial fat thickness (EFT), the size and volume of the heart cavities, left ventricular mass index (LVMI) were performed by two-dimensional echocardiography. Endothelial functionof blood vessels determined by finger test was measured according to peripheral arterial tone (PAT). The reactive hyperemia index (RHI) and augmentation index (AI) was calculated. Optimal level of A-Flex therapy was adjusted at home. AHI, the level of air leakage, average pressure and compliance to CPAP treatment were established in accordance with international requirements.Results:after 3 months of A-Flex therapy we found a significant decrease of HOMA-IR -1,09 (95% Cl from -1,74 to -0,96; P=0,021), decrease AI -10.8% (95% Cl from -13,70 to -4.6; P=0,001), decrease EFT -1,26 mm (95% Cl from -2,2 to -0,95; P=0,001) in mild OSA patients. After 6 months of A-Flex therapy we found a significant decrease of HOMAIR -2,81 (95% Cl from -3,74 to -1,46; P=0,001), decrease AI -15.6 % (95% Cl from -17,23 to -11,75; P=0,001), decrease EFT -2,15mm (95% Cl from -3,2 to -1,5; P=0,001) in moderate OSA patients. After 12 months of A-Flex therapy we found a significant decrease of HOMA-IR -4,22 (95% Cl from -5,36 to -2,35; P=0,001), decrease AI -21,05 % (95% Cl from -26,5 to -17,4; P=0,001), decrease EFT -4,0 mm (95% Cl from-5,8 to -2,7; P=0,001) in severe OSA patients.Conclusions:The 12-month A-Flex therapy in moderate and severe OSA patients with AH has a significant therapeutic effect of stabilization systolic and diastolic blood pressure, level of blood lipids and epicardial fat thickness, level of endothelial dysfunction. The 12-month A-Flex therapy has to able to reduce the risks of cardiovascular events in moderate and severe OSA patients with acute metabolic manifestations.

Quality of life, fatigue, anxiety and depression among Egyptian patients with obstructive sleep apnea

Background Sleep disorders have their well-documented deleterious effect on quality of life (QoL). The QoL impairment cannot be detected by polysomnography, which is the gold standard diagnostic tool for diagnosis of obstructive sleep apnea (OSA). Objective This study aimed at the evaluation of QoL, fatigue, depression and anxiety in OSA patients. Relation of QoL to disease severity and sex differences was assessed. Correlation of QoL scores to each other was assessed. Patients and methods We used three disease-specific QoL tools, namely the functional outcome of sleepiness questionnaire-10, the sleep apnea quality of life index, and the OSA patient-oriented severity index. Fatigue, anxiety, and depression were estimated using fatigue severity scale and hospital depression and anxiety scale, respectively. Results A total 170 participants were included; of them, 100 were OSA patients and 70 were non-OSA. OSA patients showed significantly lower QoL and more fatigue, depression, and anxiety symptoms in comparison with the non-OSA group, with more impairment of QoL in severe OSA patients. Female patients with OSA showed more QoL impairment. The highest correlation was observed between the sleep apnea quality of life index and the OSA patient-oriented severity index: r=−0.90, P value less than 0.001. Conclusion This study highlighted the significance of QoL, fatigue, anxiety and depression assessment in OSA patients, especially in those with severe disease.

Are fat oxidation and cardiorespiratory adaptations impaired during exercise in untreated non-obese severe obstructive sleep apnea patients?

Are fat oxidation and cardiorespiratory adaptations impaired during exercise in untreated non-obese severe obstructive sleep apnea patients?

Obstructive sleep apnea is associated with nonsustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is associated with arrhythmias and cardiovascular death. Obstructive sleep apnea (OSA) is highly prevalent and independently associated with atrial fibrillation in patients with HCM. The purpose of this study was to determine the relationship between nonsustained ventricular tachycardia (NSVT) and OSA in hypertrophic obstructive cardiomyopathy (HOCM). One hundred thirty consecutive patients with a confirmed diagnosis of HOCM in Fuwai Hospital between September 2017 and May 2018 were included. Polysomnography and Holter electrocardiography were performed in all patients. Of 130 patients, 72 (55%) were diagnosed with OSA, including 38 with mild, 21 with moderate, and 13 with severe OSA, and 27 patients (21%) had NSVT. The prevalence of NSVT increased with the severity of OSA (none, mild, moderate, and severe: 12%, 16%, 33%, and 54%, respectively; P < .001 for trend). Compared to patients without NSVT, the apnea-hypopnea index was significantly higher in patients with NSVT among the different OSA groups (mild, moderate, and severe: 12 [11-13] vs 7 [6-8], P = .001; 24 [22-28] vs 19 [17-22], P = .01; and 54 [41-62] vs 34 [31-39], P = .008). In multivariate logistic regression analysis, family history of HCM or sudden cardiac death (odds ratio 6; 95% confidence interval 2-22; P = .005) and apnea-hypopnea index (odds ratio 1.07; 95% confidence interval 1.02-1.12; P=.001) were the only factors associated with NSVT after adjustment for age, sex, and body mass index. The presence and severity of OSA in patients with HOCM is independently associated with NSVT, which is a risk factor for sudden cardiac death and cardiovascular death in this population.

Pathophysiology of Obstructive Sleep Apnea (OSA) - Blood Cells' Reactive Oxygen Species and Inflammation Prevent Polycythemia

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia, causes cardiovascular, metabolic, neurocognitive and cancer complications. Hypoxia expands the red cell mass by stimulating erythropoietin (EPO) production; yet in our analysis of 527 OSA patients, <1% had OSA-related polycythemia (Gangaraju et al Blood 2016 128:2444). Typical hypoxia-induced red blood cells (RBCs) mass normalized upon return to normoxia by neocytolysis i.e. preferential destruction of young hypoxia-born RBCs. In an animal model, we demonstrated that neocytolysis is caused by excessive generation of reactive oxygen species (ROS) from increase of mitochondrial retention and accumulation of ROS. ROS increase resulted from decreased antioxidant enzyme catalase mediated by hypoxia-induced miR-21. We hypothesized that polycythemia in OSA was prevented by neocytolysis.It is also well-known that OSA induces systemic inflammation markers including C-reactive protein, IL-6, TNF-α, IL-8, and NF-κb. Inflammation participates in the control of the number of RBCs by inducing hepcidin, the principal regulator of iron metabolism. Increased hepcidin suppresses erythropoiesis by inhibiting iron release from macrophages. Based on this evidence, we also hypothesized that the absence of polycythemia in OSA might be caused by an independent contribution of inflammation-mediated suppression of erythropoiesis.We studied OSA patients before and after treatment with continuous positive airway pressure (CPAP). Increased erythropoiesis was evidenced by increased EPO and reticulocytosis. EPO levels correlated with time spent below sPO2 89 %, indicating that severe OSA patients had more augmented erythropoiesis. However, hematocrit levels were normal. Hemolysis was detected in some but not all OSA patients by end tidal carbon monoxide (a product from heme catabolism). After CPAP treatment, these changes diminished but hematocrits did not change. Conditions favoring neocytolysis were confirmed by increased ROS from expanded reticulocytes' mitochondria which correlated with time spent below sPO2 89 %. Downregulated catalase resulting from increased miR-21 was also detected. Also these changes normalized with CPAP. These results indicate that hemolysis of hypoxia-born RBCs prevents OSA patients from becoming polycythemic. Increased ROS was not only found in reticulocytes but also in leukocytes; these also normalized with CPAP.Expression of inflammatory markers (NFKB1, TNF, and IL6) in granulocytes was higher in OSA compared to controls and normalized by CPAP; these levels correlated with apnea-hypopnea Index (AHI). OSA patients had higher hepcidin levels, correlating with inflammatory marker levels and inversely correlated with EPO. Iron and transferrin saturation levels were lower in OSA compared to controls, inversely correlating with high hepcidin levels. These data indicated that besides neocytolysis, coexistent suppression of erythropoiesis by inflammation contributed to the lack of polycythemia in OSA.In OSA, inflammation mediated increase of ROS in leukocytes is a known causative factor of cardiovascular disease. We now report increase of both ROS and inflammatory markers in leukocytes.We conclude that the absence of polycythemia in OSA is the result of hemolysis via neocytolysis and inflammation-mediated suppression of erythropoiesis. Increased ROS in blood cells and systemic inflammation from OSA-constitute mechanisms likely contributing to the pathophysiology of OSA. DisclosuresGanz:Vifor: Consultancy; Ablynx: Consultancy; Keryx Pharma: Consultancy, Research Funding; Silarus Pharma: Consultancy, Equity Ownership; La Jolla Pharma: Consultancy, Patents & Royalties: Patent licensed to La Jolla Pharma by UCLA; Akebia: Consultancy, Research Funding; Intrinsic LifeScience: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy.

Prevalence of newly established thyroid disorders in patients with moderate-to-severe obstructive sleep apnea syndrome.

Hypothyroidism can directly cause obstructive sleep apnea (OSA) but may also contribute to it through its impact on the metabolic syndrome. The purpose of this study was to establish the prevalence of known and newly diagnosed overt and subclinical hypothyroidism (SCH) among patients with OSA. We prospectively included all consecutive moderate or severe OSA patients referred for CPAP therapy. A fasting blood sample was collected to determine thyroid-stimulating hormone (TSH) and free T4 (FT4) levels. A total of 280 patients were included (70% male). Mean ± SD body mass index (BMI) and apnea-hypopnea index (AHI) were 33 ± 7kg/m2 and 49 ± 25, respectively. Median (range) serum TSH levels and mean ± SD FT4 levels were comparable between severe and moderate OSA (1.7 (1.3-2.6) vs 2.1 (1.2-2.8); p = 0.378 and 15.3 ± 2.3 vs 15.3 ± 2.3; p = 0.981). TSH and FT4 levels were not correlated with AHI (p = 0.297 and p = 0.370, respectively), but TSH was correlated with BMI (p = 0.049).Of all patients, 8.9% had increased serum TSH levels (severe and moderate OSA patients had similar levels (p = 0.711)) and 8.2% were newly diagnosed patients (no differences were observed between severe and moderate OSA (p = 0.450)). A total of 16.4% of patients had some type of thyroid disorder. Thyroid function parameters were associated with BMI but not with the severity of OSA. In our population of moderate or severe OSA, 16% of patients had a thyroid problem and 8% of these were newly diagnosed with SCH.

The association between glycometabolism and nonalcoholic fatty liver disease in patients with obstructive sleep apnea

PurposeGrowing evidence has revealed that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes. This study aimed to assess the association between glycometabolism and NAFLD in patients with obstructive sleep apnea (OSA).MethodsPatients with suspected OSA were enrolled consecutively and then underwent polysomnography, liver ultrasound, and biochemical measurements. Logistic regressions were used to identify factors associated with NAFLD.ResultsIn total, 415 patients were included. The prevalence of NAFLD in the non-OSA, mild OSA, moderate OSA, and severe OSA groups was 37.21%, 69.09%, 68.34%, and 78.08%, respectively. Stepwise logistic regression suggested that percentage of total sleep time spent with oxygen saturation of < 90% (TS90), lowest oxygen saturation (LaSO2), and homeostatic model assessment of insulin resistance (HOMA-IR) were independently associated with NAFLD in all subjects, after adjusting for confounders (odds ratio [OR] = 1.037, p = 0.014; OR = 1.056, p = 0.004; OR = 0.732, p = 0.009; respectively). TS90, LaSO2, and HOMA-IR were also independent predictors for NAFLD in patients with mild and moderate OSA, whereas TS90, LaSO2, and ODI were independent predictors for NAFLD in patients with severe OSA.ConclusionsThere is a relationship between OSA and NAFLD, and the combination of disordered glycometabolism and intermittent hypoxia may act as a “two hit” mechanism to promote the development of NAFLD. Furthermore, intermittent hypoxia alone was an independent predictor for NAFLD in severe OSA patients.

Breathing Irregularity Is Independently Associated With the Severity of Obstructive Sleep Apnea in Patients With Multiple System Atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the combination of cerebellar ataxia, parkinsonism, and autonomic disturbance. Patients with MSA frequently have sleep-disordered breathing. In some patients with MSA, central sleep apnea manifests during the disease's natural course or as a treatment effect. Breathing instability may be involved in the development of obstructive sleep apnea (OSA); therefore, we investigated whether breathing instability affects the severity of OSA in patients with MSA. Patients with MSA and a control group of individuals who were matched for age, body mass index (BMI), and supine apnea-hypopnea index (AHI) were recruited. Breathing instability was evaluated by using polysomnography to determine the irregular pattern with approximate entropy (ApEn) of chest respiratory movements during wakefulness before sleep onset. The ApEn values were compared between the groups. The severity of OSA was evaluated with background parameters and ApEn values by regression analysis. Twenty patients with MSA (9 men; mean age, 61 years; BMI, 24.1 kg/m2; supine AHI, 37.9 events/h) were compared to the control group. The ApEn values were higher in the patients with MSA than those in the control group (1.28 versus 1.11; P < .05). Multiple regression analysis showed that supine AHI was associated with ApEn values but not with BMI in patients with MSA and associated with BMI but not with ApEn values in the individuals in the control group. Patients with MSA had more breathing irregularity. In patients with MSA, breathing instability may be a more influential factor for OSA than BMI. A commentary on this article appears in this issue on page 1641.

A11140 Association of polymorphism of SFTPA Gene and serum SP-A levels with the risk of severe obstructive sleep apnea in Chinese population

Objectives: To investigate the associations of human SFTPA gene polymorphism and serum surfactant proteins A (SP-A) levels with severe obstructive sleep apnea (OSA). Methods: This is a case-control study. 169 subjects with severe OSA and 176 subjects with non-OSA by full night polysomnography were selected as the control and case group. All severe OSA patients and controls were genotyped for four single nucleotide polymorphisms (SNPs) (rs1136451, rs1059225, rs1965708 and rs1059046) of SFTPA gene by Kompetitive Allele Specifc PCR. Serum surfactant proteins A levels were measured by ELISA. Results: The prevalence of severe OSA patients was significantly different between lower serum SP-A levels group and higher serum SP-A levels group (P = 0.015). The lower serum SP-A levels is considered as risk factor for severe OSA after adjustment for covariates (OR: 2.226, 95% confidence interval [CI]: 1.248–3.971, P = 0.007). Moreover, we found that the distribution of additive models (CC 22.2% vs 23.3%, CA 61.1% vs 46.1%, AA 16.7% vs 30.6%, P = 0.039) and recessive models (AA 16.7% vs 30.6%, CA+CC 83.3% vs 69.4%, P = 0.02) of rs1059046 showed significant difference between the higher serum SP-A levels group and lower serum SP-A levels group. The significant difference of the recessive models (AA vs CA+CC) was retained after adjustment for covariates (OR: 2.132, 95% CI: 1.074–4.231, P = 0.03). Conclusion: AA genotype of rs1059046 may be linked with severe OSA by contribute to serum SP-A levels.