Project description:Obstructive sleep apnea (OSA) is a common disorder characterized by the reduction or complete cessation in airflow resulting from an obstruction of the upper airway. Several studies have observed an increased risk for cardiovascular morbidity and mortality among OSA patients. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors characterized by the presence of insulin resistance, is often found in patients with OSA, but the complex interplay between these two syndromes is not well understood. In this study, we present the results of a genetic association analysis of 373 candidate SNPs for MetS selected in a previous genome wide association analysis (GWAS). The 384 selected SNPs were genotyped using the Illumina VeraCode Technology in 387 subjects retrospectively assessed at the Internal Medicine Unit of the "Virgen de Valme" University Hospital (Seville, Spain). In order to increase the power of this study and to validate our findings in an independent population, we used data from the Framingham Sleep Study which comprises 368 individuals. Only the rs11211631 polymorphism was associated with OSA in both populations, with an estimated OR=0.57 (0.42-0.79) in the joint analysis (p=7.21×10(-4)). This SNP was selected in the previous GWAS for MetS components using a digenic approach, but was not significant in the monogenic study. We have also identified two SNPs (rs2687855 and rs4299396) with a protective effect from OSA only in the subpopulation with abdominal obesity. As a whole, our study does not support the idea that OSA and MetS share major genetic determinants, although both syndromes share common epidemiological and clinical features.
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
Project description:BackgroundObstructive sleep apnea (OSA) is a common sleep disorder associated with several adverse health outcomes. Given the close association between OSA and obesity, lifestyle and dietary interventions are commonly recommended to patients, but the evidence for their impact on OSA has not been systematically examined.ObjectivesTo conduct a systematic review and meta-analysis to assess the impact of weight loss through diet and physical activity on measures of OSA: apnea-hypopnea index (AHI) and oxygen desaturation index of 4% (ODI4).MethodsA systematic search was performed to identify publications using Medline (1948-2011 week 40), EMBASE (from 1988-2011 week 40), and CINAHL (from 1982-2011 week 40). The inverse variance method was used to weight studies and the random effects model was used to analyze data.ResultsSeven randomized controlled trials (519 participants) showed that weight reduction programs were associated with a decrease in AHI (-6.04 events/h [95% confidence interval -11.18, -0.90]) with substantial heterogeneity between studies (I(2) = 86%). Nine uncontrolled before-after studies (250 participants) showed a significant decrease in AHI (-12.26 events/h [95% confidence interval -18.51, -6.02]). Four uncontrolled before-after studies (97 participants) with ODI4 as outcome also showed a significant decrease in ODI4 (-18.91 episodes/h [95% confidence interval -23.40, -14.43]).ConclusionsPublished evidence suggests that weight loss through lifestyle and dietary interventions results in improvements in obstructive sleep apnea parameters, but is insufficient to normalize them. The changes in obstructive sleep apnea parameters could, however, be clinically relevant in some patients by reducing obstructive sleep apnea severity. These promising preliminary results need confirmation through larger randomized studies including more intensive weight loss approaches.
Project description:ObjectiveOur aim was to assess the efficacy and safety of acupuncture for OSA patients with various severities of the disorder.MethodsEight databases including PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and Chinese Biomedical Literature Database (CBM) were comprehensively searched till July 2019. Randomized controlled trials (RCTs) testing acupuncture in the treatment of OSA were eligible for inclusion. Studies were selected for inclusion, and data were extracted by two authors independently. The Cochrane Collaboration's Risk of Bias Assessment Tool and RevMan software (version 5.3) were used to evaluate the quality of studies and conduct statistical analysis.ResultsNine RCTs with 584 participants were included. The trials covered acupuncture and electropuncture. Acupuncture caused clinically significant reductions in AHI (MD: -6.18; 95% CI: -9.58 to -2.78; Z = 3.56, P = 0.0004) as well as in ESS (MD: -2.84; 95% CI: -4.80 to -0.16, Z = 2.09, P = 0.04). AHI was reduced more in the subgroup analysis of moderate OSA patients (MD: -9.44; 95% CI: -12.44 to -6.45; Z = 6.18, P < 0.00001) and severe OSA patients (MD: -10.09; 95% CI: -12.47 to -7.71; Z = 8.31, P < 0.00001). ESS was also reduced more in the subgroup analysis of moderate OSA patients (MD: -2.40; 95% CI: -3.63 to -1.17; Z = 3.83, P = 0.0001) and severe OSA patients (MD: -4.64; 95% CI: -5.35 to -3.92; Z = 12.72, P < 0.00001). Besides, acupuncture had a beneficial effect on LSaO2 (MD: 5.29; 95% CI: 2.61 to 7.97; Z = 3.86, P = 0.0001). The outcome of AHI and LSaO2 yielded consistent results after sensitivity analysis, but the direction of the outcome of ESS was reversed. And the quality of evidence was mainly low to very low.ConclusionsAcupuncture therapy is effective for OSA patients in reducing AHI and ESS and in improving the LSaO2 of various severities, especially in moderate and severe OSA patients. High-quality trials are urgently needed.
Project description:BackgroundObstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder which could impair someone's quality of life and is also associated with poor outcomes from many diseases. Currently, the evidence regarding the link between OSA and coronavirus disease 2019 (COVID-19) is still conflicting. This study aims to analyze the relationship between OSA and poor outcomes of COVID-19.Materials and methodsWe systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 10th, 2020. All articles published on COVID-19 and OSA were retrieved. The quality of the study was assessed using the Newcastle-Ottawa Scale (NOS) tool for observational studies. Statistical analysis was done using Review Manager 5.4 software.ResultsA total of 21 studies with 54,276 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that OSA was associated with composite poor outcome [OR 1.72 (95% CI 1.55-1.91), p < 0.00001, I2 = 36%, random-effect modeling] and its subgroup which comprised of severe COVID-19 [OR 1.70 (95% CI 1.18-2.45), p = 0.005], ICU admissions [OR 1.76 (95% CI 1.51-2.05), p < 0.00001], the need for mechanical ventilation [OR 1.67 (95% CI 1.48-1.88), p < 0.00001], and mortality [OR 1.74 (95% CI 1.39-2.19), p < 0.00001].ConclusionsExtra care and close monitoring should be provided to patients with OSA to minimize the risk of infections. Simple questionnaires such as STOP-Bang questionnaire can be used for screening patients who may be at risk for severe adverse outcomes.
Project description:Background: Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first line treatment for OSA. However, the molecular and cellular mechanisms underlying OSA-induced morbidities and their response to PAP treatment remain unclear. Methods And Results: DNA methylation profiles were examined in blood monocytes of OSA patients before and after PAP treatment. We identified 1,847 regions showing significant differential DNA methylation (p<0.001 and MAT score >4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions (DMRs) were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPAR). Single locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR responsive elements (PPAREs) of 8 genes in the post-treatment samples, suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPARG complex and downstream gene expression. Conclusions: Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in OSA patients that are responsive to PAP treatment. We postulate that differentially methylated regions in blood monocytes may serve as potential biomarkers in clinical practice.
Project description:BackgroundObstructive sleep apnea (OSA) is a risk factor for several diseases and is correlated with other non-medical consequences that increase the disease's clinical and economic burden. However, OSA's impact is highly underestimated, also due to substantial diagnosis gaps.ObjectiveThis study aims at assessing the economic burden of OSA in the adult population in Italy by performing a cost-of-illness analysis with a societal perspective. In particular, we aimed at estimating the magnitude of the burden caused by conditions for which OSA is a proven risk factor.MethodsA systematic literature review on systematic reviews and meta-analyses, integrated by expert opinion, was performed to identify all clinical and non-clinical conditions significantly influenced by OSA. Using the Population Attributable Fraction methodology, a portion of their prevalence and costs was attributed to OSA. The total economic burden of OSA for the society was estimated by summing the costs of each condition influenced by the disease, the costs due to OSA's diagnosis and treatment and the economic value of quality of life lost due to OSA's undertreatment.ResultsTwenty-six clinical (e.g., diabetes) and non-clinical (e.g., car accidents) conditions were found to be significantly influenced by OSA, contributing to an economic burden ranging from €10.7 to €32.0 billion/year in Italy. The cost of impaired quality of life due to OSA undertreatment is between €2.8 and €9.0 billion/year. These costs are substantially higher than those currently borne to diagnose and treat OSA (€234 million/year).ConclusionsThis study demonstrates that the economic burden due to OSA is substantial, also due to low diagnosis and treatment rates. Providing reliable estimates of the economic impact of OSA at a societal level may increase awareness of the disease burden and help to guide evidence-based policies and prioritisation for healthcare, ultimately ensuring appropriate diagnostic and therapeutic pathways for patients.
Project description:ObjectiveTo determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection.MethodsWe conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p-values < 0.05 were considered statistically significant and statistical analyses were performed using R software.ResultsA total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04-504) risk of neurocognitive impairment.DiscussionAmong patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase.