Severe OSA Patients Research Articles

The role of obstructive sleep apnea and nocturnal hypoxia as predictors of mortality in cancer patients

BackgroundObstructive sleep apnea (OSA), due to its high prevalence, has been associated with a number of comorbidities, frequently impacting the overall course of these other diseases if left untreated. Recent studies highlight a potential association between OSA and cancer. This study investigates how OSA severity and hypoxia affect cancer prognosis, aiming to elucidate how they interplay. MethodsRetrospective study including patients with a diagnosis of OSA after any cancer type followed up in a tertiary center during a 10-year period. OSA was mainly diagnosed after level III polysomnographic studies. ResultsNocturnal hypoxia was significantly more prevalent in patients presenting lung cancer versus other malignancies and was associated with higher rates of oncologic disease progression. Overall survival was significantly lower in severe OSA patients and also in patients presenting nocturnal hypoxia. A composite hypoxia score considering both OSA severity and significant hypoxia was an independent predictor of mortality regardless of clinical cancer staging and treatment. Shorter time between cancer and OSA diagnosis was also associated with worse prognosis. ConclusionThis study suggests an association between OSA severity and nocturnal hypoxia and increased cancer mortality independently from possible confounding factors such as age, cancer clinical staging at diagnosis, treatment modality and also progression. Neoplastic patients with severe OSA and/or complex hypoxia seem to have lower overall survival rates than those with less severe OSA and nocturnal hypoxia.

DIAGNOSTIC VALUE OF SERUM IRISIN LEVELS IN HYPERTENSIVE PATIENTS WITH SEVERE OBSTRUCTIVE SLEEP APNEA SYNDROME

Objective: To observe the diagnostic value of serum irisin level in patients with hypertension for severe obstructive sleep apnea syndrome. Design and method: A total of 156 hypertensive patients were selected from the Hypertension Center of the People 's Hospital of Xinjiang Uygur Autonomous Region from September 2019 to January 2020. Baseline data, PSG and ABPM were collected and serum irisin levels were measured. According to AHI, the patients were divided into severe OSAS group (n=79 cases) and non-severe OSAS group (n=77 cases). Results: Male patients in severe OSAS group were significantly more than those in non-severe OSAS group, and abdominal circumference and neck circumference in severe OSAS group were greater than those in non-severe OSAS group. Serum irisin concentration in severe OSAS patients was lower than that in non-severe OSAS group, and the difference was statistically significant(14.94 ng/ml vs 42.34 ng/ml, p < 0.001). Serum irisin concentration was negatively correlated with AHI (r=-0.359, p < 0.01). The critical value of serum irisin concentration was 38.07 mg/ml by ROC curve, the AUC is 0.761, the sensitivity was 86.07%, the specificity was 61.07%, the positive predictive value was 69.38%, and the negative predictive value was 81.03%. Conclusions: In hypertensive population, the serum irisin concentration of OSA patients was negatively correlated with the severity of OSAS. Serum irisin level can be used as a diagnostic index for severe OSAS patients.

Small Extracellular Vesicles Harboring PD-L1 in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSA) has been associated with increased cancer incidence and aggressiveness. One hypothesis to support this association is the implication of immune response, particularly the programmed cell death pathway, formed by the receptor PD-1 and its ligand PD-L1. Recent studies have shown dysregulation of this pathway in severe OSA patients. It has also been shown that small extracellular vesicles (sEVs) carrying PD-L1 induce lymphocyte dysfunction. Thus, the aim of our study was to analyze the expression of PD-L1 on sEVs of OSA patients and to evaluate the role of sEVs on lymphocyte activation and cytotoxicity. Circulating sEVs were isolated from OSA patients and the control group. Lymphocytes were isolated from the control group. Circulating sEVs were characterized by western blot, nanotracking analysis, and flow cytometry and were incubated with lymphocytes. Our results show no differences in the quantity and composition of sEVs in OSA patients and no significant effects of sEVs in OSA patients on lymphocyte activation and cytotoxicity. These results suggest that OSA does not modify PD-L1 expression on sEVs, which does not contribute to dysregulation of cytotoxic lymphocytes.

Hematological parameters as predictors of OSA severity

BackgroundObstructive sleep apnea syndrome (OSAS) is a common disease that has a prevalence of 6 to 13% of the adult population. It is characterized by recurrent obstruction partial or total upper airway and subsequent paroxysmal nocturnal hypoxia, leading to intermittent arousals from sleep and excessive daytime sleepiness.This work aimed to evaluate the relationship between the hematological parameters in CBC with differential as a new biomarker showing systemic inflammation and as an indicator of OSAS severity.Patient and methodsThis retrospective cross-sectional analysis included 100 subjects with OSA from those attending Chest departments in Benha University Hospital from 2021 to 2022 and 2022 to 2023 period. All patients were subjected to full history taking and clinical examination, electrocardiogram, chest X-ray posteroanterior view, full night of polysomnography, and complete blood count with differential.ResultsThere was a statistically significant difference between mild; moderate and severe OSA patients regarding platelets to lymphocyte ratio. A statistically significant difference between mild and severe OSA regarding neutrophil to lymphocyte ratio was found. There was a statistically significant positive correlation between OSA severity and platelet level, N/L, and P/L ratio.ConclusionThe hematological indices including neutrophil to lymphocyte ratio and platelet to lymphocyte ratio could be alternatives to expensive time-consuming biochemical markers to evaluate the inflammation and severity in the OSAS population.

O006 Major adverse cardiovascular events in severe Obstructive Sleep Apnoea: Associations with symptom subtypes and symptom burden

Abstract Background Obstructive sleep apnoea (OSA) is a heterogeneous disorder with certain phenotypes at increased risk of major adverse cardiovascular events (MACE). We investigated whether symptom subtypes and/or symptom burden are useful predictors of MACE risk in severe OSA. Method In a longitudinal sleep clinic cohort with apnoea-hypopnoea index ≥30 events/hour (n=1767), we investigated 19 OSA-related symptoms across four symptom domains (upper airway [UA], insomnia and disturbed sleep, morning, and daytime sleepiness) and the Epworth Sleepiness Scale score. Latent class analysis identified five symptom subtypes. A symptom burden score (0–8) was developed by selecting the two symptoms from each domain most strongly associated with MACE. Multivariable-adjusted associations of subtypes and symptom burden with future MACE were investigated using Cox regressions. Results Over a median follow-up of 7 years, 18.7% developed MACE. Relative to the moderately sleepy subtype, the disturbed sleep (adjusted hazard ratio [HR], 1.65; 95%CI, 1.15–2.37) and UA symptoms predominant (HR, 1.57; 95%CI, 1.05–2.34) subtypes showed increased MACE risk. There was a graded increase in MACE risk with increasing symptom burden score (adjusted p for linear trend = 0.003). Compared to patients that reported ≤2 of 8 symptoms, those with ≥7 symptoms showed an independent risk for MACE (HR, 1.77; 95%CI, 1.12–2.77). Discussion Both symptom subtypes and symptom burden may help identify severe OSA patients at increased risk of MACE. However, our novel symptom burden score may have more clinical utility as it is an easily calculated summative measure of OSA-related symptoms that allows objective comparisons across diverse patient populations.

Polysomnographic Phenotypes of Obstructive Sleep Apnea in a Real-Life Cohort: A Pathophysiological Approach

IntroductionObstructive sleep apnea (OSA) is heterogeneous and complex, but its severity is still based on the apnea–hypoapnea index (AHI). The present study explores using cluster analysis (CA), the additional information provided from routine polysomnography (PSG) to optimize OSA categorization. MethodsCross-sectional study of OSA subjects diagnosed by PSG in a tertiary hospital sleep unit during 2016–2020. PSG, demographical, clinical variables, and comorbidities were recorded. Phenotypes were constructed from PSG variables using CA. Results are shown as median (interquartile range). Results981 subjects were studied: 41% females, age 56 years (45–66), overall AHI 23events/h (13–42) and body mass index (BMI) 30kg/m2 (27–34). Three PSG clusters were identified: Cluster 1: “Supine and obstructive apnea predominance” (433 patients, 44%). Cluster 2: “Central, REM and shorter-hypopnea predominance” (374 patients, 38%). Cluster 3: “Severe hypoxemic burden and higher wake after sleep onset” (174 patients, 18%). Based on classical OSA severity classification, subjects are distributed among the PSG clusters as severe OSA patients (AHI≥30events/h): 46% in cluster 1, 17% in cluster 2 and 36% in cluster 3; moderate OSA (15≤AHI<30events/h): 57% in cluster 1, 34% in cluster 2 and 9% in cluster 3; mild OSA (5≤AHI<15events/h): 28% in cluster 1, 68% in cluster 2 and 4% in cluster 3. ConclusionsThe CA identifies three specific PSG phenotypes that do not completely agree with classical OSA severity classification. This emphasized that using a simplistic AHI approach, the OSA severity is assessed by an incorrect or incomplete analysis of the heterogeneity of the disorder.

Prevalence of obstructive sleep apnea in patients with lone atrial fibrillation

Abstract Purpose The aim of this study is to detect the prevalence of obstructive sleep apnea syndrome (OSAS) in patients having lone atrial fibrillation (AF). Patients and methods Fifty patients with lone AF were referred to our sleep unit from the Department of Cardiology at the University Hospital. Lone AF was defined as AF in patients without cardiac structural abnormality and less than 60 years of age. All patients were subjected to a detailed history with stress on the number and date of documented episodes of AF and how it was terminated, OSA symptoms (excessive daytime sleepiness, witnessed apnea, loud habitual snoring, and nocturnal choking), and OSA screening questionnaires. ENT and cardiac examination by a specialist was done. Full-night attended polysomnography was performed on full night. Results The median apnea–hypopnea index in the studied group was 10.8 (range, 0.4–69.4). There were 21 (42.0%) non-OSA patients, while there were 29 (58%) OSA patients. There were eight (27.6%) mild OSA patients. Moderate OSA patients were 10 (34.5%). Severe OSA patients were 11 (37.9%). Median of the frequency of AF episodes in the last 1 year was significantly higher in the OSA group than in the normal group (P=0.01). No significant difference was present between both groups as regards the number of nocturnal arrhythmias not related to respiratory events. The frequency of paroxysmal AF episodes during the last year shows a significant positive correlation with severity of OSA, desaturation index, and total arousal index. Conclusion The results of our study support our hypothesis that OSA is a risk factor for AF. We should investigate patients with lone AF for the possibility of OSA.

Obstructive sleep apnea in type 2 diabetes mellitus patients

Abstract Objective The study aims to identify the prevalence and risk factors for OSA in a group of Egyptian patients with type 2 diabetes. Methods 125 type 2 diabetes mellitus patients visited Mansoura University Hospital (Diabetes Mellitus Outpatient Clinic (OPC) at Specialized Medical Hospital and the Sleep Disordered Breathing Unit of the Chest Department), all of them exposed to history taking, the patients underwent anthropometric measurements (weight, height, body mass index, neck circumference), a test of their tonsillar size, Malampati score, Friedman OSA score, Epworth sleepiness scale (ESS), Berlin questionnaire, STOP BANG questionnaire, full-night polysomnography, fasting, and postprandial blood sugar. Results The study included 125 T2DM Egyptian patients with a mean age of 54.63 ± 9.47 years. Males accounted for 35.2 percent of patients, while females accounted for 64.8%. According to the study of co-morbidity, hypertension constituted 77 (61.1%), ischemic heart disease 28 (22.4%), other cardiac diseases 11 (8.8%), bronchial asthma 6 (4.8%), liver diseases 6 (4.8%), hypothyroidism 3 (2.4%), and renal diseases 3 (2.4%). A total of seven patients (5.6%) had no OSA symptoms, 87 had borderline symptoms, and 31 had positive symptoms. There were 51 (40.8%) normal patients, 12 (9.6%) borderline patients, and 62 (49.6%) sleepy patients on the Epworth scale. According to the Stop-Bang questionnaire, 121 (96.8%) patients answered positively. It was determined that 122 patients (97.6%) were at high risk based on the Berlin questionnaire. There were 17 patients (13.6%) with OSA on polysomnography, of which six were moderate (35.3%) and 11 were severe (64.7%). Among moderate and severe OSA patients, glycosylated hemoglobin levels differed significantly. Multivariate logistic regression analysis for independent predictors of OSA, chronic renal disease patients is the most common associated risk factor (OR = 14.3, CI = 1.2–67) then hypertension (OR = 5.6,CI=1.2–25.5) and heart failure (OR = 4.4). Conclusions OSA affects 13.6% patients with type 2 diabetes patients who are hypertensive are at higher risk of OSA, chronic renal failure is considered another risk factor Furthers studies are needed on a big scale of Egyptian diabetic patients to detect the prevalence of OSA

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea.

Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R=0.603) and smoking (R=0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.

Enhanced pain sensitivity in obese patients with obstructive sleep apnoea syndrome is partially reverted by treatment: An exploratory study.

Obesity is frequently associated with obstructive sleep apnoea syndrome (OSA) and chronic pain. OSA as well as continuous positive airway pressure (CPAP) treatment may modulate the pain perception threshold (PT) in patients with obesity. In this prospective, longitudinal study, all patients admitted for obesity assessment were screened for OSA by nocturnal polygraphy (SOMNOcheck® , IAH ≥10) and performed mechanical (Von Frey electronic device) and electrical (PainMatcher® ) pain tests. Those with severe OSA were retested for PT 1 month after initiation of CPAP therapy. Newly diagnosed patients with severe OSA (hypopnea apnoea index >30) have been offered to start CPAP treatment. Among 85 patients, there were 27 OSA patients, aged between 40 ± 13.2 years with a BMI of 42 ± 7.2kg/m2 . Severe OSA patients (N=11) showed a lower PT than non-OSA patients (N=58) during mechanical (177 ± 120 vs. 328 ± 136 g, p < 0.01) and electrical methods (7.4 ± 6.4 vs. 12.9 ± 6.7 stimulation duration steps; p=0.03). In the severe OSA group (N=7), an increased PT was observed 1month after CPAP treatment during mechanical pain testing (298 ± 69 vs. 259 ± 68 g, p < 0.05), but not during electrical pain testing (11.5 ± 3.0 vs. 12.4 ± 3.8 stimulation duration steps, p=0.50). In patients with obesity, this exploratory study showed that the presence of an OSA is associated with a decreased PT, whereas implantation of a CPAP device tends to normalize pain perception.

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

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

Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study

BackgroundObstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases. MethodsThis post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24–72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE. ResultsWe included 86 patients (median age: 61 years, median BMI: 29.4 kg/m2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71–0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems. ConclusionIn ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management.

An evaluation of the change in serum SCUBE-1 levels with CPAP treatment in patients with severe obstructive sleep apnea

ABSTRACT Objective Signal peptide CUB-EGF domain-containing protein 1 (SCUBE-1) is a cell surface protein, wherein inflammation causes an increase in serum. The aim of this study was to compare serum SCUBE-1 levels in OSA patients and to investigate the serum SCUBE-1 change with CPAP treatment. Methods Blood samples were obtained from 61 severe OSA patients and from 25 control subjects evaluated as simple snorers. The 61 patients with severe OSA were treated with CPAP therapy and were recalled for follow up after 1 year. Evaluation was made after 1 year of CPAP therapy. Results Serum SCUBE-1 values were significantly higher in patients with severe OSA. The SCUBE-1 values significantly decreased after treatment with CPAP. Conclusion Serum SCUBE-1 values in OSA patients showed a significant reduction in SCUBE-1 levels following 1 year of CPAP treatment.

Impact of obstructive sleep apnea on platelet activation and development of silent brain infarctions

BackgroundObstructive sleep apnea (OSA) is a unique potent predictor for stroke compared to other predictors. By aiding in the adherence of leukocytes and platelets, soluble P-selectin (sP-selectin) contributes to the development of ischemic stroke. The objective of this study was to investigate the independent impact of OSA on platelet activation and development of silent brain infarction. Twenty-four OSA patients and 24 controls were studied in a case–control study, who underwent one-night polysomnography, magnetic resonance imaging for evaluation of silent brain infarctions (SBI), measurement of serum (sP-selectin) levels for assessment of increased platelet activation and C-reactive protein (CRP) serum levels.ResultsOut of 24 patients, 5 (20.8%) had mild OSA and 8 (33.3%) had moderate and 11 (45.8%) had severe OSA. Serum levels of sP-selectin were statistically significantly higher in moderate and severe groups (p < 0.001). Eleven (57.9%) patients in moderate and severe OSA had SBI. Fifty percent of patients with moderate OSA had elevated serum sP-selectin and 25.0% of them had SBI and 81.8% of severe OSA patients had elevated serum sP-selectin and 81.8% of them had SBI. Patients with mild OSA and controls had no SBI and normal serum sP-selectin level. CRP was statistically significantly higher in moderate and severe OSA groups (16.6% and 45.8%) than the mild and control groups (4.1% and 0%) (p < 0.001).ConclusionModerate and severe obstructive sleep apnea were associated independently with elevated serum sP-selectin reflecting increased platelet function, elevated inflammatory marker CRP and an increased risk of silent brain infarctions.

P109 Predicting major adverse cardiovascular events using symptom subtypes of severe obstructive sleep apnoea

Abstract Background Obstructive sleep apnoea (OSA) is a complex heterogeneous disorder, and patients with similar disease severity present with different symptom profiles and outcomes. It is unclear whether OSA symptom subtypes independently predict incident major adverse cardiovascular events (MACE). Method Consecutive patients attending a tertiary sleep clinic from 2006 to 2010 were prospectively investigated and linked to administrative health data. Data from 1,767 patients with severe OSA (apnoea-hypopnoea index ≥30 events/hour) were used in latent class analysis to identify symptom subtypes. Associations between symptom subtypes and incident MACE were assessed using Cox proportional hazards models, with adjustment for known cardiovascular risk factors. Results On average, patients were middle-aged (mean± SD 52.5±13.2 years), obese (BMI, 35.4±7.9 kg/m²), and male (71.7%). Four symptom subtypes were identified: high symptom burden: severe sleepiness (26.0%), high symptom burden: sleep onset insomnia (34.8%), moderate symptom burden (18.4%), and minimal symptoms (20.7%). Over a median follow-up of 7 years, 330 (18.7%) patients developed MACE. After adjustment for covariates, the high symptom burden: sleep onset insomnia subtype was associated with increased risk for MACE relative to those with moderate (HR, 1.59; 95%CI, 1.12–2.25; P=0.010) or minimal (HR, 1.47; 95%CI, 1.07–2.03; P=0.018) symptom burden. Discussion Distinct symptom subtypes can be identified among severe OSA patients. In symptomatic patients, those with a high prevalence of sleep onset insomnia were at increased risk of MACE, relative to those with moderate or minimal symptom burden. Our findings suggest that symptom subtypes may be clinically relevant in risk stratification for MACE in severe OSA.

P027 Predictors of CPAP failure in severe obstructive sleep apnoea and obesity hypoventilation syndrome patients

Abstract There are mixed findings regarding predictors of failing continuous positive airway pressure in the obstructive sleep apnoea and obesity hypoventilation population, with duration of time under 90% oxygen saturation independently associated with treatment failure. Our study examined predictors of CPAP failure in severe OSA and OHS patients using baseline characteristics, diagnostic polysomnography, arterial blood gases and TcCO2 oximetry data. An observational review of patients in an accredited sleep laboratory from 2016 to 2021 was performed. Patients with treatment studies demonstrating CPAP failure were compared to patients controlled on CPAP therapy via pressure determination study. Independent t-test compared group characteristics and multivariate logistic regression was performed to assess predictors of CPAP failure. Data is presented as mean unless otherwise stated. Twenty patients who required bilevel support ventilation were compared to thirty-five patients controlled by CPAP. Total sleep time (266vs328minutes, p=0.007) and sleep efficiency (62% vs 75%, p=0.028) was lower in the BSV group. Patients who failed CPAP spent a greater percentage of T&amp;lt;88% on their diagnostic study (T&amp;lt;88%, 46.4%vs9.66%, p=0.001). Percentage of T&amp;lt;88% oxygen saturations were significant in being able to predict CPAP failure (p&amp;lt;0.001) using a model including arterial blood gas PaCO2 and TcCO2 data. TcCO2, blood gases and baseline demographic data were not significant in determining CPAP failure. Our study strengthens the duration of time spent hypoxic or T&amp;lt;88% as a significant predictor of CPAP failure. Surprisingly, TcCO2 data and paired arterial blood gas data was not able to predict who would require bilevel ventilation in our cohort.

Involvement of Galectin-3 in neurocognitive impairment in obstructive sleep apnea via regulating inflammation and oxidative stress through NLRP3

ObjectiveAccumulated studies have revealed that oxidative stress and inflammation play important roles in the development of OSA related cognitive dysfunction. Galectin-3, a member of the galectin family, has been reported to be involved in the neuroinflammatory diseases. However, the relationship between Galectin-3 and cognitive impairment in OSA remains ambiguous. Materials and methods47 new diagnosed OSA patients and 18 age-, gender-, education- and body mass index-matched healthy control subjects were enrolled in the present study. All subjects underwent whole-night in-laboratory polysomnography (PSG). Montreal Cognitive Assessment (MoCA) was used to evaluated the cognitive function of OSA patients. Serum Galectin-3, interleukin (IL)-1β and IL-8 were examined by enzyme-linked immunosorbent assay (ELISA). The levels of malonaldehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were measured to evaluate oxidative stress. Protein level of Galectin-3 and NLRP3 in peripheral blood mononuclear cells (PBMCs) and human microglial clone 3 (HMC3) cells were measured by Western Blot. ResultsSerum Galectin-3 level in severe OSA patients (2.31 ± 0.43 ng/m) was higher than those in mild-moderate OSA patients (1.87 ± 0.32 ng/m, p < 0.001) and those in the healthy controls (1.56 ± 0.22 ng/ml, p < 0.001). Similarly, Galectin-3 level in PBMCs was increased with disease severity (p < 0.01). In addition, OSA patients also showed higher levels of inflammation and oxidative stress (p < 0.01). Patients with OSA scored significantly lower than healthy controls on the MoCA test after controlling for age, gender, education, and BMI. CPAP treatment for 12 weeks effectively reduced the levels of Galectin-3, inflammation and oxidative stress, as well as improved cognitive function of severe OSA patients. Closed correlations were observed between Galectin-3 with sleep respiratory parameters and cognitive dysfunction. In addition, we explored the underlying mechanism of Galectin-3 in neuroinflammation and oxidative stress. We treated HMC3 cells with LPS to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to a dose-dependent increase in Galectin-3 expression, meanwhile induced inflammation and oxidative stress. Inhibiting Galectin-3 with a specific Galectin-3 inhibitor, TD139, significantly ameliorated LPS-induced neuroinflammation and oxidative stress via suppressing NLRP3. ConclusionCurrent findings suggest that increased Galectin-3 might be involved in the cognitive impairment of OSA patients by promoting neuroinflammation and oxidative stress via regulating NLRP3. These results suggested that Galectin-3 inhibition may exert a protective role against the neurocognitive dysfunction associated with OSA.

Improved diagnostic accuracy for pediatric obstructive sleep apnea using an out-of-center sleep test

ObjectivePolysomnography (PSG) is considered the gold standard for diagnosing obstructive sleep apnea syndrome (OSA) in children. However, many hospitals do not carry out PSG evaluations, and use out-of-center sleep test (OCST) devices for diagnosis instead. The aim of this study was to confirm the reliability of OCSTs for the diagnosis of pediatric OSA. We also investigated the factors influencing diagnostic reliability of OCST for the severe OSA patients who should be treated earlier. MethodsThis was a retrospective study using the Ota Memorial Sleep Center database. We analyzed the data of children who underwent Type 4 OCST at home and Type 1 PSG in the sleep lab between April 2006 to April 2015. Cephalometric parameters and anthropometric findings such as enlarged tonsils were also evaluated. We compared the 3% oxygen desaturation index (ODI3%) measured by OCST with the apnea-hypopnea index (AHI) measured by PSG. We used Receiver Operator Curve (ROC) to calculate the optimal OCST- ODI3% value to diagnose PSG-AHI ≥10 per hour. In order to determine which factors increase the accuracy of OCST, we calculated the accuracy, sensitivity and specificity in regard to the predicted values using multiple logistic regression analysis. The Ethics Committee of Ota General Hospital approved the study (approval no. 21018). ResultsA total of 191 children were enrolled in this study. The study included 127 boys and 64 girls, with a mean age of 5.4 years (range: 3-8 years), BMI of 15.7 kg/m² (range: 11.5-35.7 kg/m²), PSG-AHI of 17.4 per hour (range: 0.3-89.8 per hour). The sensitivity, specificity and accuracy with an OCST-ODI cutoff of 6.3 per hour were 64.4%, 70.3% and 67.5%, respectively, to detect PSG-AHI ≥ 10 per hour for children with suspected OSA. Multivariable stepwise regression revealed that increases of sensitivity, specificity and accuracy with an OCST-ODI cutoff of 6.3 per hour were independently predicted by facial axis, which is cephalometric angle of 81° or less, and tonsil hypertrophy, which is Brodsky +3 or +4, showing increases to 73.3%, 71.3%, and 72.3%, respectively, whereas age, gender, body mass index, adenoid size and other cephalometric parameters were not significant predictors. ConclusionThe results of the statistical analyses suggest that it would be useful to add the assessment of tonsil size and facial axis as well as OCST to determine whether the threshold of PSG-AHI ≥ 10 per hour has been crossed.

Event related delta and theta oscillations are reduced in severe obstructive sleep apnea as a possible electrophysiologial evidence of subtle cognitive changes

AbstractBackgroundObstructive Sleep Apnea Syndrome (OSAS) is a common sleep disorder that leads to widespread cognitive impairment when left untreated. OSAS is also reported as a risk factor for developing Alzheimer’s disease. Recent studies report a shared pathophysiology between OSAS and Alzheimer’s disease (Polsek et al., 2018; Baril et al., 2018). Working memory and attention related ERP P300 deficits were previously reported (for a review see, Raggi and Ferri, 2012). This study aims to investigate electrophysiological changes by using time‐frequency analysis to gain a better understanding on cognitive impairment in OSAS.Method56 severe OSAS patients and age, education and gender matched 33 healthy controls were participated to the study. Participants completed a classical auditory oddball task. A complex Morlet with Gabor normalization was applied and total power within four frequency bandwidths, delta (0.5‐3.5 Hz), theta (4‐7 Hz), alpha (8‐13 Hz), and beta (15‐30 Hz), was calculated using Event‐Related Spectral Perturbation (ERSP) analyses.ResultOSAS patients had reduced delta and theta ERPS to target stimuli compared to healthy controls in repeated measures ANOVA yielding a significant main GROUP effect (respectively, [F(1,87)=9.181, p=0.003] and [F(1,87)=5.083, p=0.027]). No differences were found on alpha and beta power.ConclusionWe found reduced delta and theta activity in severe OSAS patients. Delta EROs activity is associated with attention and decision making (Başar ve Stampfer, 1985; Stampfer ve Başar, 1985), whereas theta activity was associated with task induced activation of working memory (Yordanova et al. 2000). Reduced delta and theta EROs activity can be useful indices of subtle cognitive impairment in severe OSAS even before neuropsychological test. These results strengthen our understanding of the cognitive changes in OSAS by means of electrophysiological methodologies. This study was supported by Dokuz Eylul University Scientific Research Projects (Project Number: 2014.KB.SAG.058).

Disturbances of the Gut Microbiota, Sleep Architecture, and mTOR Signaling Pathway in Patients with Severe Obstructive Sleep Apnea-Associated Hypertension

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (n = 27) and with hypertension (n = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria (P < 0.05), and reduced arginine and proline metabolism pathways (P=0.001), compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals (P < 0.05). Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway (P=0.006) was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.