Association Between Sleep Apnea Treatment and Health Care Resource Use in Patients With Atrial Fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. METHODS AND RESULTS: Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). CONCLUSIONS: These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.

Healthcare resource utilisation and costs in patients with treated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a highly prevalent yet underdiagnosed disease that creates a large economic burden on the United States healthcare system. In this retrospective study, we tested the hypothesis that adherence to positive airway pressure (PAP) therapy, the 'gold standard' treatment for OSA, is associated with reduced healthcare resource utilisation and costs. We linked de-identified payer-sourced medical claims and objective PAP usage data for patients newly diagnosed with OSA. Inverse probability of treatment weighting was used to create balanced groups of patients who were either adherent, intermediately adherent, or non-adherent to PAP therapy. From a sample of 179,542 patients (average age 52.5 years, 61% male), 37% were adherent, 40% intermediate, and 23% non-adherent. During the first year, PAP adherence was significantly associated with fewer emergency room visits (mean [SD] adherent: 0.39 [1.20] versus intermediate: 0.47 [1.30], p < 0.001; versus non-adherent: 0.54 [1.44], p < 0.001), all-cause hospitalisations (mean [SD] adherent: 0.09 [0.43] versus intermediate: 0.12 [0.51], p < 0.001; versus non-adherent: 0.13 [0.55], p < 0.001), and lower total costs (mean [SD] adherent $5874 [8045] versus intermediate $6523 [9759], p < 0.001; versus non-adherent $6355 [10,517], p < 0.001). Results were similar in the second year of PAP use. These results provide additional evidence from a large, diverse sample to support the diagnosis and treatment of OSA and encourage long-term adherence to PAP therapy.

Intermittent Hypoxia Mediates Cancer Development and Progression Through HIF-1 and miRNA Regulation.

INTRODUCTION: There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs are involved in cancer development and progression with expression being influenced by hypoxia. The aims of this work were (i) to compare miRNAs expression in controls versus patients affected by OSA without or with cancer (ONCO-OSA) and (ii) in colorectal cancer cells exposed to intermittent hypoxia (IH), to evaluate miRNAs impact on tumor progression in vitro. METHODS: We detected miRNAs by qRT-PCR in patients' sera and in CaCo2 cells exposed to 2-32h of IH with or without acriflavine (ACF), a HIF-1 inhibitor. Viability and transwell invasion test were applied to investigate the proliferation and migration of CaCo2 exposed to IH and treated with miRNA inhibitors or acriflavine. HIF-1α activity was evaluated in CaCo2 cells after IH. RESULTS: The levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145 increased in OSA but not ONCO-OSA patients. MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. IH stimulated cell proliferation and migration. This effect was reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1α gene expression. Conversely, acriflavine reduced the expression of these miRNAs. CONCLUSIONS: We identified a signature of miRNAs, induced by the IH environment. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1.

Differential Impact of Intermittent vs. Sustained Hypoxia on HIF-1, VEGF and Proliferation of HepG2 Cells.

Obstructive sleep apnea (OSA) is an emerging risk factor for cancer occurrence and progression, mainly mediated by intermittent hypoxia (IH). Systemic IH, a main landmark of OSA, and local sustained hypoxia (SH), a classical feature at the core of tumors, may act separately or synergistically on tumor cells. Our aim was to compare the respective consequences of intermittent and sustained hypoxia on HIF-1, endothelin-1 and VEGF expression and on cell proliferation and migration in HepG2 liver tumor cells. Wound healing, spheroid expansion, proliferation and migration were evaluated in HepG2 cells following IH or SH exposure. The HIF-1α, endothelin-1 and VEGF protein levels and/or mRNA expression were assessed, as were the effects of HIF-1 (acriflavine), endothelin-1 (macitentan) and VEGF (pazopanib) inhibition. Both SH and IH stimulated wound healing, spheroid expansion and proliferation of HepG2 cells. HIF-1 and VEGF, but not endothelin-1, expression increased with IH exposure but not with SH exposure. Acriflavine prevented the effects of both IH and SH, and pazopanib blocked those of IH but not those of SH. Macitentan had no impact. Thus, IH and SH stimulate hepatic cancer cell proliferation via distinct signaling pathways that may act synergistically in OSA patients with cancer, leading to enhanced tumor progression.

Remote Monitoring of Positive Airway Pressure Data: Challenges, Pitfalls, and Strategies to Consider for Optimal Data Science Applications.

Over recent years, positive airway pressure (PAP) remote monitoring has transformed the management of OSA and produced a large amount of data. Accumulated PAP data provide valuable and objective information regarding patient treatment adherence and efficiency. However, the majority of studies that have analyzed longitudinal PAP remote monitoring have summarized data trajectories in static and simplistic metrics for PAP adherence and the residual apnea-hypopnea index by the use of mean or median values. The aims of this article are to suggest directions for improving data cleaning and processing and to address major concerns for the following data science applications: (1) conditions for residual apnea-hypopnea index reliability, (2) lack of standardization of indicators provided by different PAP models, (3) missing values, and (4) consideration of treatment interruptions. To allow fair comparison among studies and to avoid biases in computation, PAP data processing and management should be conducted rigorously with these points in mind. PAP remote monitoring data contain a wealth of information that currently is underused in the field of sleep research. Improving the quality and standardizing data handling could facilitate data sharing among specialists worldwide and enable artificial intelligence strategies to be applied in the field of sleep apnea.

Chronic intermittent hypoxia, a hallmark of obstructive sleep apnea, promotes 4T1 breast cancer development through endothelin-1 receptors.

The association between obstructive sleep apnea (OSA) and cancer is still debated and data are scarce regarding the link between OSA and breast cancer progression. Since conclusive epidemiological studies require large sample sizes and sufficient duration of exposure before incident cancer occurrence, basic science studies represent the most promising approach to appropriately address the topic. Here we assessed the impact of intermittent hypoxia (IH), the major hallmark of OSA, on the development of breast cancer and explored the specific involvement of the endothelin signaling pathway. Original in vitro and in vivo models were used where 3D-spheroids or cultures of murine 4T1 breast cancer cells were submitted to IH cycles, and nude NMRI mice, orthotopically implanted with 4T1 cells, were submitted to chronic IH exposure before and after implantation. The role of the endothelin-1 in promoting cancer cell development was investigated using the dual endothelin receptor antagonist, macitentan. In vitro exposure to IH significantly increased 4T1 cell proliferation and migration. Meta-analysis of 4 independent in vivo experiments showed that chronic IH exposure promoted tumor growth, assessed by caliper measurement (overall standardized mean difference: 1.00 [0.45-1.55], p < 0.001), bioluminescence imaging (1.65 [0.59-2.71]; p < 0.01) and tumor weight (0.86 [0.31-1.41], p < 0.01), and enhanced metastatic pulmonary expansion (0.77 [0.12-1.42]; p = 0.01). Both in vitro and in vivo tumor-promoting effects of IH were reversed by macitentan. Overall, these findings demonstrate that chronic intermittent hypoxia exposure promotes breast cancer growth and malignancy and that dual endothelin receptor blockade prevents intermittent hypoxia-induced tumor development.

Machine learning and geometric morphometrics to predict obstructive sleep apnea from 3D craniofacial scans.

BACKGROUND: Obstructive sleep apnea (OSA) remains massively underdiagnosed, due to limited access to polysomnography (PSG), the highly complex gold standard for diagnosis. Performance scores in predicting OSA are evaluated for machine learning (ML) analysis applied to 3D maxillofacial shapes. METHODS: The 3D maxillofacial shapes were scanned on 280 Caucasian men with suspected OSA. All participants underwent single night in-home or in-laboratory sleep testing with PSG (Nox A1, Resmed, Australia), with concomitant 3D scanning (Sense v2, 3D systems corporation, USA). Anthropometric data, comorbidities, medication, BERLIN, and NoSAS questionnaires were also collected at baseline. The PSG recordings were manually scored at the reference sleep center. The 3D craniofacial scans were processed by geometric morphometrics, and 13 different supervised algorithms, varying from simple to more advanced, were trained and tested. Results for OSAS recognition by ML models were then compared with scores for specificity and sensitivity obtained using BERLIN and NoSAS questionnaires. RESULTS: All valid scans (n = 267) were included in the analysis (patient mean age: 59 ± 9 years; BMI: 27 ± 4 kg/m2). For PSG-derived AHI≥15 events/h, the 56% specificity obtained for ML analysis of 3D craniofacial shapes was higher than for the questionnaires (Berlin: 50%; NoSAS: 40%). A sensitivity of 80% was obtained using ML analysis, compared to nearly 90% for NoSAS and 61% for the BERLIN questionnaire. The auROC score was further improved when 3D geometric morphometrics were combined with patient anthropometrics (auROC = 0.75). CONCLUSION: The combination of 3D geometric morphometrics with ML is proposed as a rapid, efficient, and inexpensive screening tool for OSA. TRIAL REGISTRATION NUMBER: NCT03632382; Date of registration: 15-08-2018.

AKR1B10, One of the Triggers of Cytokine Storm in SARS-CoV2 Severe Acute Respiratory Syndrome.

Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and Tumor Necrosis Factor a (TNFα), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1ß, and TNFα is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management.

Novel avenues to approach non-CPAP therapy and implement comprehensive obstructive sleep apnoea care.

Recent advances in obstructive sleep apnoea (OSA) pathophysiology and translational research have opened new lines of investigation for OSA treatment and management. Key goals of such investigations are to provide efficacious, alternative treatment and management pathways that are better tailored to individual risk profiles to move beyond the traditional continuous positive airway pressure (CPAP)-focused, "one size fits all" trial-and-error approach, which is too frequently inadequate for many patients. Identification of different clinical manifestations of OSA (clinical phenotypes) and underlying pathophysiological phenotypes (endotypes) that contribute to OSA have provided novel insights into underlying mechanisms and have underpinned these efforts. Indeed, this new knowledge has provided the framework for precision medicine for OSA to improve treatment success rates with existing non-CPAP therapies such as mandibular advancement devices and upper airway surgery, and newly developed therapies such as hypoglossal nerve stimulation and emerging therapies such as pharmacotherapies and combination therapy. Additionally, these concepts have provided insight into potential physiological barriers to CPAP adherence for certain patients. This review summarises the recent advances in OSA pathogenesis, non-CPAP treatment, clinical management approaches and highlights knowledge gaps for future research. OSA endotyping and clinical phenotyping, risk stratification and personalised treatment allocation approaches are rapidly evolving and will further benefit from the support of recent advances in e-health and artificial intelligence.

European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea.

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear-nose-throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes.

Bariatric surgery short-term outcomes in patients with obstructive sleep apnoea: the Severe Obesity Outcome Network prospective cohort.

BACKGROUND/OBJECTIVES: Although the benefits of bariatric surgery have been clearly established, it is not known whether they are as important in patients with obstructive sleep apnoea (OSA). Primary aim: to evaluate whether patients with moderate-to-severe OSA (apnoea-hypopnea index (AHI) ≥ 15 events/h) treated by continuous positive airway pressure/non-invasive ventilation (median [IQR] adherence 6.5 h/night [5; 7.9] at baseline) lose the same amount of body weight 1 year after bariatric surgery as patients with no or mild OSA. Secondary objectives: to compare the evolution of type 2 diabetes and hypertension after bariatric surgery, and surgical complication rates between groups. METHODS/SUBJECTS: Analyses were performed in 371 patients included in a prospective cohort of bariatric surgery, the Severe Obesity Outcome Network cohort. Subjects having moderate-to-severe OSA (n = 210) at baseline were compared with other subjects (n = 161). RESULTS: Excess weight loss (%EWL) at 1 year was lower in patients with moderate-to-severe OSA than in patients without (64.9%EWL [46.9; 79.5] vs. 73.8%EWL [56.6; 89.3], p < 0.01). Multivariable analysis showed that age, initial body mass index and type of surgery, but not OSA status, were associated with 1-year %EWL. Diabetes remitted in 25 (41%) patients with moderate-to-severe OSA and 16 (48%) patients with no or mild OSA (p = 0.48). Hypertension remitted in 28 (32.9%) patients with moderate-to-severe OSA and 9 (40.9%) with no or mild (p = 0.48). Complication rates were 28 (13.3%) in patients with moderate-to-severe OSA and 12 (7.5%) in patients with no or mild OSA (p = 0.07). CONCLUSIONS: Patients with OSA lose less body weight after bariatric surgery. This was related to older age and a higher baseline body mass index. However, the improvements of diabetes and hypertension were similar to that of patients without OSA, and the risk of surgical complications was not higher.

Accelerometry-derived respiratory index estimating apnea-hypopnea index for sleep apnea screening.

BACKGROUND AND OBJECTIVE: Sleep Apnea Syndrome (SAS) is a multimorbid chronic disease with individual and societal deleterious consequences. Polysomnography (PSG) is the multi-parametric reference diagnostic tool that allows a manual quantification of the apnea-hypopnea index (AHI) to assess SAS severity. The burden of SAS is affecting nearly one billion people worldwide explaining that SAS remains largely under-diagnosed and undertreated. The development of an easy to use and automatic solution for early detection and screening of SAS is highly desirable. METHODS: We proposed an Accelerometry-Derived Respiratory index (ADR) solution based on a dual accelerometry system for airflow estimation included in a machine learning process. It calculated the AHI thanks to a RUSBoosted Tree model and used physiological and explanatory specifically developed features. The performances of this method were evaluated against a configuration using gold-standard PSG signals on a database of 28 subjects. RESULTS: The AHI estimation accuracy, specificity and sensitivity of the ADR index were 89%, 100% and 80% respectively. The added value of the specifically developed features was also demonstrated. CONCLUSION: Overnight physiological monitoring with the proposed ADR solution using a machine learning approach provided a clinically relevant estimate of AHI for SAS screening. The physiological component of the solution has a real interest for improving performance and facilitating physician's adhesion to an automatic AHI estimation.

VE-cadherin cleavage in sleep apnoea: new insights into intermittent hypoxia-related endothelial permeability.

BACKGROUND: Obstructive sleep apnoea (OSA) causes intermittent hypoxia that in turn induces endothelial dysfunction and atherosclerosis progression. We hypothesised that VE-cadherin cleavage, detected by its released extracellular fragment solubilised in the blood (sVE), may be an early indicator of emergent abnormal endothelial permeability. Our aim was to assess VE-cadherin cleavage in OSA patients and in in vivo and in vitro intermittent hypoxia models to decipher the cellular mechanisms and consequences. METHODS: Sera from seven healthy volunteers exposed to 14 nights of intermittent hypoxia, 43 OSA patients and 31 healthy control subjects were analysed for their sVE content. Human aortic endothelial cells (HAECs) were exposed to 6 h of intermittent hypoxia in vitro, with or without an antioxidant or inhibitors of hypoxia-inducible factor (HIF)-1, tyrosine kinases or vascular endothelial growth factor (VEGF) pathways. VE-cadherin cleavage and phosphorylation were evaluated, and endothelial permeability was assessed by measuring transendothelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran flux. RESULTS: sVE was significantly elevated in sera from healthy volunteers submitted to intermittent hypoxia and OSA patients before treatment, but conversely decreased in OSA patients after 6 months of continuous positive airway pressure treatment. OSA was the main factor accounting for sVE variations in a multivariate analysis. In in vitro experiments, cleavage and expression of VE-cadherin increased upon HAEC exposure to intermittent hypoxia. TEER decreased and FITC-dextran flux increased. These effects were reversed by all of the pharmacological inhibitors tested. CONCLUSIONS: We suggest that in OSA, intermittent hypoxia increases endothelial permeability in OSA by inducing VE-cadherin cleavage through reactive oxygen species production, and activation of HIF-1, VEGF and tyrosine kinase pathways.

Profile of exposures and lung function in adults with asthma: An exposome approach in the EGEA study.

BACKGROUND: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures. OBJECTIVE: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach. METHODS: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV1) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation<0.70) identified in step 1. RESULTS: The ExWAS identified 21 factors showing suggestive association with FEV1 (none significant when controlling for multiple tests). The sBPR conducted on 15 uncorrelated exposures identified in step 1, revealed 3 clusters composed of 30, 115 and 454 individuals with a mean ± SD FEV1(%pred) of 79% ± 21, 90% ± 19 and 93% ± 16, respectively. Cluster 1 was composed of individuals with heavy smoking, poor diet, higher outdoor humidity and proximity to traffic, while cluster 2 and 3 included individuals with moderate/low levels of exposure to these factors. DISCUSSION: This exposome study identified a specific profile of joint lifestyle and environmental factors, associated with a low FEV1 in adults with asthma. None of the exposures revealed significant association when considered independently.

Management of sleep apnoea syndrome (SAS) in patients with vasovagal syncope (VVS): a protocol for the VVS-SAS cohort study.

INTRODUCTION: Recurrent vasovagal syncope (VVS) is associated with decreased quality-of-life and frequent use of emergency services. The evidence base for causality, diagnostic procedures and potential VVS treatments is poor. Scattered observations in the literature suggest a link between respiratory disturbances during sleep and VVS. Empirical observations lead us to further hypothesise that the appropriate management of sleep apnoea syndrome (SAS) may help resolve comorbid recurrent VVS in certain patients. We therefore designed this pilot study to provide a framework for the observation of changes in outcomes accompanying the deployment of SAS treatments in patients with VVS. METHODS AND ANALYSIS: This is a multicentre, registry-based study whose primary objective is to evaluate the effect of SAS management on the number of syncope/presyncope episodes in a population suffering from both VVS and SAS. To this effect, syncope rates prior to the treatment of SAS will be compared with those occurring after the initiation of the latter. In addition, yearly assessments will collect data for echocardiography, polysomnography, Holter monitoring, table tilt tests, multiple sleep latency tests, SAS management parameters and questionnaires describing fatigue, depression and quality-of-life. Sixty patients will be included with a minimum follow-up period of 12 months. The primary analysis will use comparisons of centrality for paired data to describe the changes in syncope rates before versus after the initiation of SAS management. Longitudinal data will be analysed using mixed models with patients set as a random effect. Subgroup analyses will be performed for SAS-treatment adherence and efficacy. ETHICS AND DISSEMINATION: The VVS-SAS registry was approved by an ethics committee (Comité pour la Protection des Personnes Ile-de-France VI, Reference number CPP/2-18) in accordance with French law. The princeps publication will present before-after SAS management results and longitudinal analyses. TRIAL REGISTRATION NUMBER: NCT04294524. Pre-results.

Preoperative Screening for Obstructive Sleep Apnea Using Alternative Scoring Models of the Sleep Tiredness Observed Pressure-Body Mass Index Age Neck Circumference Gender Questionnaire: An External Validation.

BACKGROUND: The Sleep Tiredness Observed Pressure-Body mass index Age Neck circumference Gender (STOP-Bang) questionnaire is a validated preoperative screening tool for identifying patients with obstructive sleep apnea (OSA). Although it has a high sensitivity at scores ≥3, its specificity is moderate, particularly for scores of 3-4. This study aimed to externally validate the STOP-Bang questionnaire and the alternative scoring models that have been proposed to improve its predictive performance. METHODS: This prospective cohort study included 115 surgical patients with preoperative STOP-Bang scores of 3-8. Type 3 sleep recordings identified moderate-to-severe OSA, reflected by an apnea-hypopnea index (AHI) of >15. Patients were categorized into 2 subgroups: patients with an intermediate (STOP-Bang 3-4) or a high risk of OSA (STOP-Bang 5-8). For patients with scores of 3-4, we tested approaches identified in previous studies: stepwise stratification of the STOP-Bang questionnaire and additional preoperative measurement of serum bicarbonate concentrations. RESULTS: The incidence of moderate-to-severe OSA was significantly higher in patients with STOP-Bang scores of 5-8 than in patients with scores of 3-4: 45 of 58 patients (78%) versus 30 of 57 patients (53%), respectively (P < .01). For patients with STOP-Bang scores of 3-4, we found no differences regarding their OSA diagnosis between patients included in the alternative scoring models and those not included. CONCLUSIONS: The STOP-Bang questionnaire detected moderate-to-severe OSA patients when scores reached 5-8. However, its performance was altered in patients with STOP-Bang scores of 3-4, and alternative scoring models with specific combinations of factors failed to improve the screening of these patients.

Long-term variations of arterial stiffness in patients with obesity and obstructive sleep apnea treated with continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular co-morbidities and mortality. Arterial stiffness is an independent predictor of cardiovascular risk and mortality, and is influenced by the presence of OSA and related comorbidities. There is a paucity of data regarding long-term evolution of arterial stiffness in CPAP-treated OSA patients. We aimed to prospectively study long term PWV variations and determinants of PWV deterioration. METHODS: In a prospective obese OSA cohort, at time of diagnosis and after several years of follow-up we collected arterial stiffness measured by carotid-femoral pulse wave velocity (PWV), clinical and metabolic parameters, and CPAP adherence. Univariate and multivariate analyses were performed in order to determine contributing factors. RESULTS: Seventy two OSA patients (men: 52.8%, median age: 55.8 years and median BMI of 38.5 kg/m2) with a prevalence of hypertension: 58.3%, type 2 diabetes: 20.8%, hypercholesterolemia: 33.3%, current or past smoking: 59.7%, were evaluated after a median follow-up of 7.4 [5.8; 8.3] years. Over the period of follow-up, the median increase in PWV was 1.34 [0.10; 2.37] m/s. In multivariate analysis, the increase in PWV was associated with older age (10 extra years was associated with a 5.24 [1.35; 9.12] % increase in PWV) and hypertension (a significant increase in PWV of 8.24 [1.02; 15.57] %). No impact of CPAP adherence on PWV evolution was found. CONCLUSION: PWV progression in CPAP-treated OSA patients is mainly related to pre-existing cardio-metabolic comorbidities and not influenced by CPAP adherence. In this high cardiovascular risk population, it is crucial to associated weight management and exercise with CPAP treatment.

Chronic toxoplasmosis and sleepiness in obstructive sleep apnea: Is there a link?

INTRODUCTION: Sleepiness is the main clinical expression of obstructive sleep apnea (OSA) syndrome resulting from upper airway collapse. Recent studies have discussed the fact that the presence of T. gondii cysts in the brain and the resulting biochemical and immunological mechanisms could be linked to neurobehavioral disorders. The aim of the present study was to explore the potential impact of chronic toxoplasmosis on sleepiness and on obstructive sleep apnea (OSA) severity in OSA obese patients. MATERIALS AND METHODS: A case control study on obese patients screened for OSA was performed. According to the sleep disorder and matched based on gender, age and body mass index (BMI), two groups of obese patients were selected from our sample collection database. All patients were tested for toxoplasmosis serological status measuring anti-Toxoplasma IgG and IgM levels. Univariable and multivariable logistic regression models were performed to assess the impact of chronic toxoplasmosis on sleepiness and OSA severity. RESULTS: 107 obese patients suffering from OSA were included in the study (median age: 53.3 years Interquartile range (IQR): [41.9-59.9]; median BMI: 39.4 kg/m2 IQR: [35.5-44.1], apnea-hypopnea index = 27.5 events/h [10.7-49.9]). Chronic toxoplasmosis was present in 63.4% and 70.7% of patients with or without sleepiness (p = 0.48), respectively and was not associated either to sleepiness (OR: 0.76, 95% CI: [0.52; 2.33], p = 0.64) or OSA severity (OR = 1.75, 95% CI: [0.51; 5.98] p = 0.37). CONCLUSION: Although chronic Toxoplasma infection in immunocompetent humans has been associated to several behavioral disorders or pathologies in recent literature, we demonstrate here that chronic toxoplasmosis is not associated to sleepiness and to sleep apnea syndrome severity in obese patients suspected of sleep apnea syndrome.

Metabolic profiles among COPD and controls in the CanCOLD population-based cohort.

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations.