Obese Obstructive Sleep Apnea Research Articles

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in threenonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig.

Obesity is a common finding and a major pathogenetic factor in obstructive sleep apnea (OSA) in adults. To understand the mechanisms behind this, the present study investigated the tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig model. In 4 verified obese/OSA and 3 non-obese/non-OSA control minipigs, MRI fat-weighted images, ultrasound elastography (USE), and sleep video-fluoroscopy (SVF) were performed to quantify the fat composition, tissue stiffness, and respiratory kinematics of the tongue base and soft palate during sedated sleep. The results indicated that the fat composition gradually increased from the rostral to caudal tongue base, particularly in the posterior 1/3 of the tongue base, regardless of the presence of obesity and OSA. However, this trend was not seen in the soft palate and pharyngeal wall. The pharyngeal wall presented the highest fat composition as compared with the tongue base and soft palate. Overall, obese OSA minipigs showed stiffer tongue tissue than the controls, particularly in the rostral region of the tongue in obese Yucatan minipigs. The respiratory moving ranges of the soft palate were greater in both dorsal-ventral and rostral-caudal directions and during both respiratory and expiratory phases in OSA obese than control minipigs, and the largest moving ranges were seen in OSA obese Panepinto minipigs. The moving range of the tongue base was significantly smaller. These results suggest more fat infiltration in the caudal region of the tongue base regardless of the presence of obesity and/or OSA. The greater tissue stiffness of the tongue in obese OSA minipigs may result from altered neuromuscular drive.

Craniofacial features of adult obese obstructive sleep apnoea patients in relation to the obesity onset - A pilot study.

Obesity and craniofacial structures are aetiologies of obstructive sleep apnoea (OSA). The effect of obesity onset on the craniofacial development and growth of obese OSA subjects has been suggested, but supporting data were lacking. This study aimed to assess the craniofacial features of adult obese OSA patients in relation to their obesity onset. A total of 62 adult OSA patients were included in the study, consisting of 12 early-onset (i.e. before puberty), 21 late-onset (i.e. after puberty) and 29 non-obese. All participants underwent a sleep study and cephalometric radiograph. Cephalometric analysis was conducted to measure the craniofacial features among the groups. The early obesity onset group (n = 12) showed a more prognathic mandible, longer lower facial height, protrusive incisors, a more caudal position of the hyoid bone and a wider lower airway. The late-onset group (n = 21) had more proclined and protrusive upper incisors, a shallower overbite, a more inferiorly positioned hyoid bone and an obtuse craniocervical angle. The overall obese group showed a combination of the findings above, plus a shorter soft palate and shorter airway length. There was no significant difference between early and late obesity onset groups. However, the early group showed a tendency for a shallower or decreased mandibular plane angle and deeper overbite. The current pilot study had many limitations but holds important information as a hypothesis generator. Craniofacial features of OSA patients with different obesity onset showed discrepancies and were distinguished from non-obese controls. Adult OSA patients with an early obesity onset showed a tendency for a more hypodivergent growth pattern than those with a late obesity onset.

Association Between Sleep Efficiency and Hypertension in Chinese Obstructive Sleep Apnea Patients.

We aimed to explore the relationship of sleep efficiency (SE) with the prevalence of hypertension in Chinese obstructive sleep apnea (OSA) patients based on polysomnography (PSG) records. We studied 2360 patients with OSA and 764 primary snorers who underwent PSG in our hospital. SE was divided into three grades, including ≥85%, 80%~84.9%, and <80%. Hypertension was defined based either on direct blood pressure measurements, under anti-hypertensive treatments or on physician diagnosis. Multivariate logistic regression models were conducted to investigate the association between SE and hypertension. After adjusting for potential confounding factors, OSA patients with <80% SE and those with 80% to 84.9% SE were significantly associated with the prevalence of hypertension (OR = 1.248, 95% CI 1.018~1.531, P=0.033; OR = 1.380, 95% CI 1.040~1.832, P=0.026). Compared to primary snorers, OSA combined with <85% SE increased the odds of hypertension. In stratified analysis by SE, risk of hypertension only in those with <80% SE was significantly different between OSA and primary snorers. Furthermore, this relationship between reduced SE and hypertension was evident especially in female, younger ages, obese, moderate and severe OSA patients. No significant relationship between reduced SE and hypertension was found in primary snores group. We found that poor SE was correlated with the prevalence of hypertension in Chinese OSA patients, but not in those with primary snoring. Moreover, this relationship was evident especially in female, younger ages, obese, moderate and severe OSA patients.

Evaluation the Possible Role of Interleukin-6 and Tumor Necrosis Factor- Alpha in Pathogenesis of Obstructive Sleep Apnea in Obese Patients: A Case-Control Study:.

According to a mounting body of evidence, recent observations have highlighted considerable association between obstructive sleep apnea (OSA) syndrome and patients' obesity and inflammation, however the exact underlying mechanisms remain to be fully understood. In this study, the relationship between OSA and Interleukin-6 and Tumor necrosis factor- alpha was assessed in obese patients and their serum concentrations were compared to non-OSA obese subjects. This case-control study was conducted on forty-six obese OSA patients (body mass indices, BMI30) and 42 obese but otherwise healthy individuals who were admitted to the pulmonary or obesity clinics of the Hazrat-e Rasool General Hospital (Tehran, Iran) between November 2019 and May 2020 were included. The participants completed the NOSAS, EPWORTH and STOPBANG questionnaires. Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin-6 (IL-6) serum concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) method. Compared to the non-OSA group, OSA patients had higher systolic and diastolic blood pressure, pCO2, bicarbonate (HCO3) and hemoglobin and lower high-density lipoprotein (HDL) values. IL-6 and TNF-α serum levels were not significantly different between both groups. Univariate and multivariate linear regression models showed that BMI, systolic blood pressure, pCO2 and HCO3 can positively affect the serum TNF-α and systolic blood pressure and HCO3 can also positively affect the serum IL-6 values in patients with the OSA. This investigation suggests that among the OSA patients, the heightened inflammatory profile may be influenced by the high BMI. Furthermore, the exclusive relationship between different disease biomarkers and inflammatory agents in OSA patients is intriguing and needs further research.

Combined Airway and Bariatric Surgery (CABS) for Obstructive Sleep Apnea Patients with Morbid Obesity: A Comprehensive Alternative Preliminary Study.

Although continuous positive airway pressure is the gold standard for obstructive sleep apnea (OSA), it does not improve obesity. By contrast, bariatric surgery significantly improves obesity but with sustained OSA in the majority of patients. This study proposes a comprehensive technique-combined airway and bariatric surgery (CABS)-to improve both obesity and OSA. The aims of the study are to evaluate the feasibility, safety and efficacy of CABS in morbidly obese OSA patients. The retrospective study enrolled 20 morbidly obese OSA patients (13 males; median age, 44 years; median apnea-hypopnea index (AHI), 63.2 event/h; median body mass index (BMI), 41.4 kg/m2). The study population was divided into two groups based on patients' volition after shared decision making. The bariatric surgery (BS) group included laparoscopic sleeve gastrectomy (LSG, n = 8) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 2). CABS involved bariatric surgery-LSG (n = 8) and LRYGB (n = 2) in conjunction with airway surgery (concurrent nasal/palatal/lingual surgery [n = 8], concurrent palatal/lingual surgery [n = 2]). Patients received a home sleep apnea test at baseline and one year after surgery. The two patient groups were not different in age, sex, preoperative AHI or preoperative BMI. There was no airway compromise, wound bleeding or infection throughout the postoperative period. One year after surgery, patients in both groups achieved significant improvement in AHI and BMI. Furthermore, the improvement in AHI was significantly higher (p = 0.04) in the CABS group than in the BS group despite the insignificant change in BMI reduction (p = 0.63) between the two groups. In the CABS group, the BMI dropped from 40.4 to 28.4 kg/m2 (p &lt; 0.0001) and the AHI decreased from 75.1 to 4.5 event/h (p = 0.0004). The classic success rate for OSA was 90% and the cure rate was 60% in the CABS group. A perioperative assessment of CABS group patients also revealed a significant improvement in the Epworth sleepiness scale, minimal O2 saturation, snoring index and heart rate. CABS is feasible and safe in treating OSA with morbid obesity. CABS achieves more reduction in AHI than BS alone with high success and cure rates for OSA. CABS can also significantly improve quality of life and general health and offers a comprehensive alternative for morbidly obese OSA patients.

New pharmacologic agents for obstructive sleep apnoea: what do we know and what can we expect?

This review provides a condensed description of pharmacological remedies explored in patients with obstructive sleep apnoea (OSA) as well as projections of what we might expect in terms of clinical performance of these drugs. Conventional drug therapies explored in OSA have generally produced disappointing results and there is a shortage of pharmacological treatment alternatives in this disorder. Recent insights into pathophysiological mechanisms potentially involved in OSA suggest that the condition may be divided into distinct subgroups based on clusters or defined by means of unique functional endotypic criteria. In fact, positive outcomes in clinical trials have now resulted in several drug candidates that show a convincing reduction of sleep disordered breathing in both short and intermediate term. Such drugs may be particularly useful in certain variants of OSA but not in others. These insights have also raised the ambition to create personalized therapies in OSA. Another recent development is the insight that OSA-linked conditions such as obesity, daytime somnolence and various forms of cardiovascular/metabolic disease may provide drug-based targets. For instance, pharmacological obesity therapy may provide not only positive metabolic effects but may also be a way to eliminate the anatomic component in obese OSA patients. Recent insights into the pathophysiology of OSA have opened possibilities to develop personalized therapy. Drugs addressing fundamental aspects of the sleep and breathing disorder provide a particularly promising avenue for development of novel forms of treatment in OSA.

Alterations of cholesterol synthesis and absorption in obstructive sleep apnea: Influence of obesity and disease severity

Background and aimsObstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity. Methods and resultsThis study enrolled 116 OSA patients. Concentrations of non-cholesterol sterols (NCS), measured by LC-MS/MS, were used as markers of cholesterol synthesis and absorption. Apnea-hypopnea index (AHI) and oxygen saturation (SaO2) were utilized as markers of OSA severity. Serum lipid status parameters were determined by routine enzymatic methods. Markers of cholesterol synthesis were increased (P = 0.005), whilst markers of cholesterol absorption decreased (P = 0.001) in obese OSA patients. Cholesterol synthesis/absorption ratio was elevated in obese subjects (P < 0.001). Concentration of cholesterol synthesis marker lathosterol was significantly higher in subjects with severe OSA (P = 0.014) and we observed a trend of decreased cholesterol absorption in these patients. AHI was revealed as an independent determinant of lathosterol concentration (P = 0.022). ConclusionsOur results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.

Joint detection of miR-149-3p and hepcidin predicts the onset of obstructive sleep apnea syndrome in obese patients.

BackgroundObstructive sleep apnea syndrome (OSAS) is a potentially fatal sleep respiratory disorder, and hepcidin has been found to be related with OSAS onset and severity. This study aimed to examine the serum expression of microRNA‐149‐3p (miR‐149‐3p) and hepcidin in OSAS patients, and evaluate the predictive value of miR‐149‐3p and hepcidin for OSAS occurrence in obese population.MethodsThis study analyzed the data from 212 OSAS patients and 120 control individuals. OSAS severity was evaluated by apnea hypopnea index (AHI) from polysomnography. Serum miR‐149‐3p was examined using reverse transcription quantitative PCR, and hepcidin and inflammatory cytokines were measured using ELISA kits. Logistic regression analysis was used to evaluate the predictive value of miR‐142‐3p and hepcidin for OSAS in obese population, and ROC curve was plotted to assess the predictive accuracy.ResultsSerum miR‐149‐3p and hepcidin were increased in OSAS patients, especially in the severe cases, and had diagnostic potential to distinguish OSAS. High miR‐149‐3p and hepcidin were positively correlated with OSAS patients' inflammatory cytokines. Obese OSAS patients had the highest miR‐149‐3p and hepcidin levels, and the two molecules had predictive value of OSAS present in obese population, and the combination of miR‐149‐3p and hepcidin showed the highest predictive accuracy.ConclusionSerum miR‐149‐3p and hepcidin levels were elevated in OSAS patients and correlated with disease severity and systemic inflammation. miR‐149‐3p and hepcidin levels have diagnostic value to distinguish OSAS, exhibited predictive value for OSAS in obese population, and the joint detection of the two molecules showed the highest predictive accuracy.

Analysis of upper airway morphology and laryngopharyngeal reflux in obese patients with OSA

Objective: To investigate the morphological characteristics of upper airway and laryngopharyngeal reflux in obese patients with obstructive sleep apnea (OSA). Methods: A retrospective analysis was performed on the clinical data of 284 adult patients who underwent polysomnography (PSG) from April 2020 to April 2021 in the Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, including 83 males and 201 females, aged (32.70±7.74) years. Patients were divided into obese group (n=234) and non-obese group (n=50) according to body mass index (BMI). Patients were divided into mild OSA group, moderate OSA group, severe OSA group and extremely severe OSA group by PSG.The results of sleepiness and laryngopharyngeal reflux questionnaire, nasolaryngoscopy and polysomnography were compared in each group. SPSS (version 22.0) software was used in data analysis. Results: Compared with the non-obese OSA group, the lymphoid hyperplasia of tongue root was more heavy in the obese OSA group, and Mueller's maneuver showed that the left-right lateral collapse of the velopharyngeal plane was more serious. Meanwhile, the scores of reflux symtom index (RSI) and reflux finding score (RFS) in the obese OSA group were significantly increased, and the scores of RSI and RFS increased with the increase of OSA severity. The main respiratory events in obese patients with OSA were obstructive hypopnea, their apnea-hypopnea indices(AHI) during REM (AHIREM) was significantly higher than non-REM (AHINREM), and they had lower average blood oxygen saturation. Yet, there was no significant difference in the lowest blood oxygen saturation between the two groups. Conclusions: Our study suggests that lateral pharyngeal wall stenosis in velopharyngeal plane and the lymphoid hyperplasia of tongue root in glossopharyngeal plane occurs more frequently in obese patients with OSA. Laryngopharyngeal reflux is significantly increased in obese patients, and OSA increases laryngopharyngeal reflux in obese patients.

Evaluation of left ventricular function in obese patients with obstructive sleep apnea by three-dimensional speckle tracking echocardiography

Both obstructive sleep apnea(OSA) and obesity can cause myocardial remodeling and cardiac insufficiency via corresponding pathophysiological pathways. Therefore, it is speculated that the superposition of OSA and obesity may cause more severe impairment of cardiac function. The objective of our study was to evaluate the early changes of left ventricular systolic function in obese patients with OSA with three-dimensional speckle tracking echocardiography(3D-STE). This study was conducted with 33 obese OSA, 46 non-obese OSA, and 20 healthy subjects. Demographic, biochemical, and Polysomnography(PSG) data were collected, and their relation with the left ventricular strain was measured and analyzed with 3D-STE. The left ventricular strain was significantly worse in the OSA group compared to the control group(P < 0.05). The global longitudinal strain(GLS) was significantly worse obese group compared to non-obese OSA group (P < 0.05). The GLS value positively correlated with body mass index(BMI)(r = 0.406, P < 0.001), apnea-hypopnea index(AHI)(r = 0.610, P < 0.001)and homeostasis model assessment of insulin resistance(HOME-IR)(r = 0.431, P < 0.001) in patients with OSA, as well as high sensitivity C-reactive protein(hs-CRP)(r = 0.394, P < 0.001). Multiple linear regression analysis showed BMI and AHI were predictors of GLS. In OSA patients, the myocardial strain was impaired before the damages in left ventricular ejection fraction, suggesting that the left ventricular systolic function is damaged early. The coexistence of obesity and OSA can lead to severe impairment of cardiac function through mechanisms such as hypoxia and insulin resistance.

Comparison of clinical, biochemical, and polysomnographic parameters between obese and nonobese obstructive sleep apnea.

Background:Obstructive sleep apnea (OSA) occurs in both obese and nonobese individuals. This study was designed to compare clinical, metabolic profile, and polysomnographic parameters among obese and nonobese OSA patients.Material and Methods:This cross-sectional retro-prospective study involved 148 OSA patients. OSA patients were classified as nonobese (body mass index [BMI] <27.5 kg/m2) and obese (BMI ≥27.5 kg/m2) to determine the influence of BMI on its risks, clinical, metabolic, and polysomnographic parameters. For statistical comparisons, continuous variables were analyzed by Student’s t-test and categorical variables by Chi-square.Results:Of 148 patients, 106 patients were of a retrospective group and 42 in the prospective group. 116 patients were obese and 32 were nonobese with a mean BMI of 33.66 ± 5.3 versus. 25.17 ± 2.2 kg/m2 respectively. Female sex (70.7% vs. 43.4%), larger neck circumference (37.99 ± 3.93 vs. 33.67 ± 5.5 cm), loud snoring (94.8% vs. 81.3%), excessive daytime sleepiness (53.4% vs. 9.4%), fatigability (94.8% vs. 75%), high Epworth Sleepiness Scale score (16% vs. 8%), and hypertension (77.6% vs. 46.9%) were significantly (P < 0.05) more common among obese OSA patients while as smoking and sedative use was more prevalent among nonobese OSA group. However, no significant difference in median apnea-hypopnea index and severity of OSA between obese and nonobese group was observed. At the same time, the median oxygen desaturation index was significantly higher in obese patients (26.1 vs. 12.7, P = 0.005).Conclusion:Nonobese OSA patients depicted less severe disease symptoms and thus require high index of suspicion for early identification due to associated cardiovascular risk.

Characteristics of Patients with Obstructive Sleep Apnea at High Risk for Cardiovascular Disease.

Background and Objectives: To evaluate the influence of obstructive sleep apnea (OSA)-related symptoms on prevalent cardiovascular disease (CVD) in a large clinical population of patients. Materials and Methods: A total of 2127 patients (mean age 55 years, 24% women) underwent diagnostic polysomnography and were evaluated using the Epworth sleepiness scale (ESS), the Athens Insomnia Scale (AIS), and the Beck Depression Inventory (BDI). We investigated the predictive value of OSA-associated symptoms for prevalent cardiovascular disease, after adjustment for relevant confounding factors including age, obesity, and co-morbidities. Results: Patients with OSA and CVD were older and had a higher Body Mass Index (BMI); the percentage of obese patients was also higher (83% vs. 70%, p < 0001). They also had greater neck, waist, and hip circumferences and a higher waist-to-hip ratio. Excessive daytime sleepiness (ESS ≥ 10) [odds ratio (95% CI) 1.112 (0.708–1.748), p = 0.64], insomnia symptoms (AIS ≥ 6) [odds ratio (95% CI) 0.748 (0.473–1.184), p = 0.21], frequent awakenings [odds ratio (95% CI) 1.599 (1.019–2.508), p = 0.06], and nocturia [odds ratio (95% CI) 1.359 (0.919–2.009), p = 0.124] were not associated with CVD after adjustment for the previous confounders. On the other hand, depressive symptoms (BDI ≥ 10) independently predicted prevalent CVD [odds ratio (95% CI) 1.476 (1.154–1.887), p = 0.002]. Further analysis in subgroups stratified by age, BMI, and gender demonstrated that depressive symptoms predicted prevalent CVD but only in the subgroup of younger (age group < 60 years), obese (BMI group ≥ 30), and male (OR = 1.959, 95% CI = 1.209–3.175, p = 0.006) OSA patients. Conclusions: OSA patients with CVD were more likely to complain of less typical OSA symptoms and depressive symptoms compared to patients without CVD in this large clinical patient cohort, supportingthecomplexity and heterogeneityof OSA.

Variables predictive of surgical outcomes after hyoid myotomy with suspension to thyroid cartilage

ObjectivesTo evaluate variables predicting improvement in obstructive sleep apnea (OSA) with hyoid suspension to thyroid cartilage 4-suture technique. MethodsSixty adult patients (age range 23–78 years) with OSA underwent hyoid suspension to thyroid cartilage with or without concurrent multi-level surgery over an eight-year period from 2011 to 2019 at a tertiary academic center. All patients had a preoperative apnea hypopnea index (AHI) ≥ 5. Changes in mean AHI, Epworth Sleepiness Scale (ESS), and lowest oxygen saturation (LSAT) were measured with paired Student t-test. Linear and logistic regression models were used to predict change in AHI and surgical success respectively with respect to body mass index (BMI), age, sex, previous sleep surgery, concurrent retrolingual surgery, concurrent palatopharyngoplasty, and preoperative AHI. ResultsThe mean AHI demonstrated a significant improvement from a preoperative AHI of 39.0 ± 25.5 to a postoperative AHI of 31.2 ± 23.4 (p = 0.005). The mean Epworth Sleepiness Score (ESS) significantly improved from 13.1 ± 6.0 to 9.2 ± 5.7 (p = 0.000012). Surgical success, defined as a 50% reduction in preoperative AHI to a postoperative AHI ≤ 20, was obtained in 18/60 (30.0%) patients. Preoperative BMI significantly correlates with variation of change in AHI in multivariable linear regression model (p = 0.003). Preoperative AHI was significant predictor of surgical success in multivariable logistic regression model. ConclusionThe magnitude of improvement in polysomnographic parameters after hyoid suspension to thyroid appears to be more significant in patients with lower BMI. Even patients with an obese BMI and severe OSA achieve significant improvement from this procedure.

Predisposing factors of daytime sleepiness in obese OSA patients.

Excessive daytime sleepiness is a common symptom in obese patients with obstructive sleep apnea. We investigated predisposing factors of excessive daytime sleepiness by comparing obese non-sleepy with sleepy patients with obstructive sleep apnea. Excessive daytime sleepiness was determined by the Epworth Sleepiness Scale in 43 patients (34men and 9 women) with obstructive sleep apnea (apnea-hypopnea index ≥15 events per hr) and obesity (body mass index≥30kg m-2 ). Two subgroups were formed with (Epworth Sleepiness Scale≥11) and without (Epworth Sleepiness Scale<11) excessive daytime sleepiness. The concept of excessive daytime sleepiness was compared with other established daytime performance tests (Stanford Sleepiness Scale, Multiple Sleep Latency Test, Pupillographic Sleepiness Test, Marburger Vigilance test). Associations were calculated between excessive daytime sleepiness and demographic, metabolic and polysomnographic data. We included 19sleepy patients (mean Epworth Sleepiness Scale score 15.2) and 24 non-sleepy patients (mean Epworth Sleepiness Scale score 5.8). Epworth Sleepiness Scale was negatively correlated with age and morning cortisol. Epworth Sleepiness Scale was positively correlated with body mass index, Stanford Sleepiness Scale, Beck's Depression Inventory and Marburger Vigilance test. Sleepy obese patients were significantly younger (mean 49.1years), showed lower morning cortisol level (mean 9.41μg L-1 ) and a trend to higher body mass index (mean 37.5kg m- ²) compared with non-sleepy obese patients (mean: 59.3years, 5.7μg L-1 , 34.6kg m- ², respectively). Many different excessive daytime sleepiness phenotypes are probably enclosed in obese patients with obstructive sleep apnea. Epworth Sleepiness Scale scores were best reflected by the objective Marburger Vigilance test results. The objective test can be particularly useful in cohorts where subjective reports are unreliable and operational readiness is paramount. Sleepy and non-sleepy obese patients with obstructive sleep apnea were similar in all polysomnographic parameters. Sleepy patients were younger, heavier and showed lower morning cortisol levels than non-sleepy patients.

Metabolic syndrome in non-obese patients with OSA: learning points of across-sectional study from atertiary care hospital in Central India.

Study objectivesObesity is often considered mandatory for the diagnosis of Metabolic Syndrome (MS). Data on the prevalence of MS in non-obese patients with Obstructive Sleep Apnea (OSA) is scarce. This study was aimed to determine the prevalence of MS in non-obese patients with OSA.MethodologyAll consecutively diagnosed patients with OSA between October 2018 and November 2019 were screened for metabolic syndrome. Patients with OSA and BMI < 25 kg/m2 (NOOSA) vs BMI > 25 kg/m2 (obese OSA) were compared. Lean waist NOOSA was defined as BMI < 25 kg/m2 and WC < 80 cm (32 in.) for women or < 90 cm (36 in.) for men.ResultsDuring the study period, 502 patients were diagnosed with OSA. MS was observed in 35% of patients with NOOSA compared to obese patients with OSA (79%). In the NOOSA group, hypertension, impaired fasting glucose, diabetes mellitus and dyslipidemia were observed in 65, 48, 14 and 61% respectively and all of these parameters were significantly more common in the obese group (p < 0.001). Parameters of OSA severity (apnea-hypopnea index or AHI, time spent below 90% saturated or T90, and nadir oxygen) were significantly more severe in the obese group with OSA. Approximately 83% of patients in the NOOSA group had at least two metabolic risk factors, compared to the obese OSA group, in which 95% had two or more metabolic risk factors. Sixty-four percent of patients with NOOSA with lean waist had at least two metabolic risk factors. At BMI cut-offs of < 25, < 27 and < 30 kg/m2; 35, 46 and 57% of patients with OSA respectively had metabolic syndrome.ConclusionMetabolic syndrome was observed in approximately one in three patients with OSA and BMI < 25 kg/m2. Approximately two of every three lean waist non-obese patients with OSA had at least two markers of metabolic syndrome. The role of OSA in the development of metabolic syndrome in non-obese individuals needs further exploration.

003 Treatment of Sleep Disordered Breathing with Leptin Loaded Exosomes

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by recurrent periods of upper airway obstruction. The prevalence of OSA exceeds 50% in obese individuals and in 10–20% of obese patients OSA coexists with obesity hypoventilation syndrome (OHS) defined as daytime hypercapnia and hypoventilation during sleep attributed to the depressed control of breathing. There is no effective pharmacotherapy for OSA and OHS. Leptin is a potent respiratory stimulant and a potential therapeutic candidate. However, diet-induced obesity (DIO) results in reduced permeability of the blood-brain barrier (BBB) for leptin. Previous studies have shown that the BBB can be penetrated by exosomes, natural nanoparticles that can be used as drug delivery vehicles. In this study, we aimed to determine if exosomes overcome the BBB and treat OSA and OHS in DIO mice. Methods o examine the ability of exosomes to cross the BBB, male, lean (n=5) and DIO (n=5) C57BL/6J mice were injected with fluorescent exosomes or saline into the lateral tail vein. After 4h fluorescent exosomes biodistribution was evaluated by an in vitro imaging system (IVIS). Saline injected mice images were used for background adjustment. A separate subgroup of male, DIO (n=10) and lean (n=10) mice were headmounted with EEG and nuchal EMG leads. Sleep studies were performed in a plethysmography chamber and mice received saline, empty exosomes, free leptin, or leptin-loaded exosomes in a crossover manner. Results Exosomes were successfully delivered to the brain and the transport across the BBB was more efficient in DIO mice with 2-times greater relative fluorescence units measured in DIO when compared to lean mice (p&amp;lt;0.005). In DIO mice, exosomal leptin induced dramatic 1.7-2.2-fold increases in minute ventilation and 1.5-2.0-fold increases in maximal inspiratory flow during both flow-limited (upper airway/sleep apnea) and non-flow limited breathing (control of breathing) (p&amp;lt;0.05). In contrast, free leptin had no effect. Lean mice did not present significant sleep disordered breathing and no differences were observed between groups. Conclusion We demonstrated that exosomes overcome the BBB and that leptin-loaded exosomes treat OSA and OHS in DIO mice. Support (if any) R01HL 128970, R01HL 138932, R61 HL156240, U18 DA052301, FAPESP 2018/08758-3

The association of obstructive sleep apnea with dyslipidemia in Korean children and adolescents: a single-center, cross-sectional study.

To evaluate whether obstructive sleep apnea (OSA) and its severity are related to dyslipidemia and alanine transaminase elevation as a marker of nonalcoholic fatty liver disease in children. The data collected from polysomnography, laboratory measurements (lipid profile and liver enzyme), and body mass index in children aged 0-18 years who visited the pediatric department between 2012 and 2018 were retrospectively analyzed. There were a total of 273 participants in the study (ages 0-6 years, 7-12 years, and 13-18 years: 61.9%, 26.4%, and 11.7%, respectively). In the ages 7-12 and 13-18 years groups, obesity was strongly associated with OSA severity (Cramer's V = 0.498, P < .001). High-density lipoprotein cholesterol levels were significantly lower in the OSA group than in the non-OSA group, irrespective of the presence of obesity. In addition, high-density lipoprotein cholesterol levels were significantly different between the OSA severity groups after adjusting for body mass index (P = .000). In participants who were obese, moderate and severe OSA were associated with alanine transaminase elevation (P = .023 and P = .045, respectively). This study suggests that OSA may be an independent risk factor for dyslipidemia and that OSA and obesity have a synergistic effect on alanine transaminase elevation. Early diagnosis and treatment of OSA from childhood, especially in obese children, will reduce metabolic complications. Kang EK, Jang MJ, Kim KD, Ahn YM. The association of obstructive sleep apnea with dyslipidemia in Korean children and adolescents: a single-center, cross-sectional study. J Clin Sleep Med. 2021;17(8):1599-1605.

Clinical and Polysomnographic Characteristics of Nonobese and Obese Chinese Patients With Obstructive Sleep Apnea.

Obesity is a risk factor associated with the onset and exacerbation of obstructive sleep apnea (OSA). However, the majority of OSA patients in Asian populations are nonobese. To date, there have been insufficient large-scale studies of the differences in the clinical and polysomnographic features of obese and nonobese OSA patients in this population, and few studies have sought to identify predictors of OSA severity in affected obese and nonobese patients. We conducted a case-matched retrospective study, including 652 consecutive Chinese OSA patients (326 nonobese and 326 obese) to assess differences in demographic, clinical, and polysomnographic data between these two groups. Independent predictors of OSA severity were identified through multivariate linear regression analysis. The age and gender distributions of our obese and nonobese OSA patient cohorts did not differ significantly ( P > 0.05), and rates of comorbidities were comparable in these two patient groups ( P > 0.05). Nonobese patients were more likely to report atypical symptoms of OSA, including insomnia ( P < 0.001), irritability ( P < 0.05), and depressive symptoms ( P < 0.01), whereas obese patients were more likely to report typical symptoms of OSA, such as habitual snoring ( P < 0.001), witnessed apnea ( P < 0.05), and daytime sleepiness ( P < 0.001). Relative to nonobese patients, those who were obese exhibited significantly higher apnea-hypopnea index during total sleep time ( P < 0.001), apnea-hypopnea index during nonrapid eye movement sleep ( P < 0.001), and apnea-hypopnea index during rapid eye movement sleep ( P < 0.001), in addition to lower average oxygen saturation ( P < 0.001), minimal oxygen saturation ( P < 0.001), and a higher oxygen desaturation index ( P < 0.001) and arousal index ( P < 0.001). Total sleep time was, on average, shorter for nonobese patients ( P < 0.05), who also exhibited decreased sleep efficiency and more frequent awakening relative to obese patients ( P < 0.05). A multivariate linear regression analysis revealed that neck circumference and waist circumference were independent predictors of OSA severity in obese patients ( P < 0.05). On average, OSA was typically less severe in nonobese patients, who were also more likely to experience atypical OSA symptoms relative to obese patients. These results also suggest that the differential contributions of body fat accumulation and distribution to OSA severity may offer insights into the pathogenesis, clinical manifestations, and optimal management of this condition in nonobese and obese patient populations. It is vital that clinicians consider these differences to properly diagnose and treat this debilitating condition.

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity.

Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample. 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates. Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009). Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients. A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966.