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RATIONALE: Three-year continuous positive airway pressure (CPAP) therapy termination rates are up to 50%, and therapy termination is associated with higher all-cause mortality and incident cardiovascular event risk. OBJECTIVE(S): This study investigated the impact of CPAP therapy termination in the first year on long sick leave leading to permanent work disability in patients with obstructive sleep apnea (OSA) based on data from the nAtionwide cLAimS data laKe for sleep Apnoea (ALASKA). METHODS: French national health insurance reimbursement system (SNDS) data were analyzed for all adults with OSA aged ≤62 years who started CPAP therapy in France in 2015/2016. CPAP therapy termination was defined as the cessation of CPAP reimbursements triggered by the respiratory physician/sleep specialist in charge of follow-up. Individuals who terminated therapy were compared with those who continued to use CPAP. The primary outcome was sick leave ultimately leading to permanent work disability. A multivariable Finn and Gray model, adjusted for age, sex, cardiovascular/metabolic comorbidities, depression, and CPAP prescriber clinical specialty was used to assess the risk of long-term sick leave leading to permanent work disability over 3 years' follow-up. RESULTS: The analysis included 174,270 individuals (median age 52.0 years [interquartile range 44.0-57.0], 67.5% male). The 1-year CPAP therapy termination rate was 22.3%. The proportion of individuals with long-term sick leave leading to permanent work disability was significantly higher in the CPAP termination versus continuation group (0.60% vs. 0.52%; p=0.042). In an adjusted multivariable Cox model, CPAP termination was associated with an increased risk of permanent work disability (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41; p=0.01), primarily in the subgroup aged >55 years (HR 1.41, 95% CI 1.06-1.87; p=0.02). CONCLUSIONS: These real-world data from a comprehensive, unbiased database highlight the potential occupational impact of CPAP therapy termination.
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In a prospective cohort of OSA patients without comorbidities at inclusion, age, mean blood pressure, mean oxygen saturation and minimum oxygen saturation were associated with long-term incidence of severe health events https://bit.ly/3VyYEzC.
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INTRODUCTION: Long-term adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea remains suboptimal and low adherence increases healthcare costs. This study investigated relationships between CPAP adherence and the intensity of support provided by homecare providers after implementation of telemonitoring and pay-for-performance reimbursement for CPAP in France. METHODS: Adults who started CPAP in 2018/2019, used telemonitoring, and had ≥1 year of homecare provider data were eligible. The main objective was to determine associations between CPAP adherence at 1 month (low [<2h/night], intermediate [2 to <4h/night], high [≥4h/night]) and the number/type of homecare provider interactions (home visits, phone calls, mask change) during the first year. RESULTS: Eleven thousand, one hundred sixty-six individuals were included (mean age 59.8±12.7 years, 67% male). The number of homecare provider interactions per person increased significantly as 1-month CPAP usage decreased (7.65±4.3, 6.5±4.0, 5.4±3.4 in low, intermediate and high adherence groups; p<0.01). There was marked improvement in device usage over the first 5-6 months of therapy in the low and intermediate adherence subgroups (p<0.05 after adjustment for age, sex, initial CPAP adherence, and number of interactions). After adjustment for age, sex and 1-month adherence, having 3-4 interactions was significantly associated with better 1-year adherence (odds ratio 1.24, 95% confidence interval 1.05-1.46), while having >7 interactions was significantly associated with worse 1-year adherence. CONCLUSIONS: The telemonitoring/reimbursement scheme in France had a positive impact on CPAP adherence and facilitated a more personalised approach to therapy management, focusing resources on patients with low and intermediate adherence.
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INTRODUCTION: Behavioural weight loss programmes are generally accepted as being beneficial in reducing cardiometabolic risk and improving patient-reported outcomes. However, prospective data from large real-world cohorts are scarce concerning the mid-term and long-term impact of such interventions. The objective of this large prospective cohort study (n>10 000 participants) is to demonstrate the effectiveness of the standardised Nutritional and Psycho-Behavioural Rehabilitation programme (RNPC Programme) in reducing the percentage of subjects requiring insulin and/or other diabetes drug therapy, antihypertensive drugs, lipid-lowering therapies and continuous positive airway pressure therapy for obstructive sleep apnoea after the end of the intervention. The rate of remission of hypertension, type 2 diabetes and sleep apnoea will also be prospectively assessed. METHODS: This is a prospective multicentre observational study carried out in 92 RNPC centres in France. Participants will follow the standardised RNPC Programme. The prospective dataset will include clinical, anthropometric and biochemical data, comorbidities, medications, body composition, patient-reported outcome questionnaire responses, sleep study data with objective measurements of sleep apnoea severity and surrogate markers of cardiovascular risk (ie, blood pressure and arterial stiffness). About 10 000 overweight or obese participants will be included over 2 years with a follow-up duration of up to 5 years. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Ethics Committee (Comité de protection des personnes Sud-Est I) of Saint-Etienne University Hospital, France (SI number: 23.00174.000237). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of a future randomised controlled trial in the specific population identified as good responders to the RNPC Programme. TRIAL REGISTRATION NUMBER: NCT05857319.
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Obesity , Weight Loss , Humans , Prospective Studies , Obesity/complications , Obesity/therapy , France , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Hypertension/therapy , Weight Reduction Programs/methods , Sleep Apnea, Obstructive/therapy , Research Design , Female , Observational Studies as Topic , Male , Multicenter Studies as Topic , Cardiovascular Diseases/prevention & controlABSTRACT
Excessive daytime sleepiness (EDS) is frequent among patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and can persist despite the optimal correction of respiratory events (apnea, hypopnea and respiratory efforts), using continuous positive airway pressure (CPAP) or mandibular advancement device. Symptoms like apathy and fatigue may be mistaken for EDS. In addition, EDS has multi-factorial origin, which makes its evaluation complex. The marketing authorization [Autorisation de Mise sur le Marché (AMM)] for two wake-promoting agents (solriamfetol and pitolisant) raises several practical issues for clinicians. This consensus paper presents recommendations of good clinical practice to identify and evaluate EDS in this context, and to manage and follow-up the patients. It was conducted under the mandate of the French Societies for sleep medicine and for pneumology [Société Française de Recherche et de Médecine du Sommeil (SFRMS) and Société de Pneumologie de Langue Française (SPLF)]. A management algorithm is suggested, as well as a list of conditions during which the patient should be referred to a sleep center or a sleep specialist. The benefit/risk balance of a wake-promoting drug in residual EDS in OSAHS patients must be regularly reevaluated, especially in elderly patients with increased cardiovascular and psychiatric disorders risks. This consensus is based on the scientific knowledge at the time of the publication and may be revised according to their evolution.
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Sympathetic overactivity caused by chronic intermittent hypoxia is a hallmark of obstructive sleep apnea. A high sympathetic tone elicits increases in plasma free fatty acid and insulin. Our objective was to assess the impact of 14 nights of chronic intermittent hypoxia exposure on sympathetic activity, glucose control, lipid profile and subcutaneous fat tissue remodelling in non-obese healthy humans. In this prospective, double-blinded crossover study, 12 healthy subjects were randomized, among them only nine underwent the two phases of exposures of 14 nights chronic intermittent hypoxia versus air. Sympathetic activity was measured by peroneal microneurography (muscle sympathetic nerve activity) before and after each exposure. Fasting glucose, insulin, C-peptide and free fatty acid were assessed at rest and during a multisampling oral glucose tolerance test. We assessed histological remodelling, adrenergic receptors, lipolysis and lipogenesis genes expression and functional changes of the adipose tissue. Two weeks of exposure of chronic intermittent hypoxia versus ambient air significantly increased sympathetic activity (p = 0.04). Muscle sympathetic nerve activity increased from 24.5 [18.9; 26.8] before to 21.7 [13.8; 25.7] after ambient air exposure, and from 20.6 [17.4; 23.9] before to 28.0 [24.4; 31.5] bursts per min after exposure to chronic intermittent hypoxia. After chronic intermittent hypoxia, post-oral glucose tolerance test circulating free fatty acid area under the curve increased (p = 0.05) and free fatty acid sensitivity to insulin decreased (p = 0.028). In adipocyte tissue, intermittent hypoxia increased expression of lipolysis genes (adipocyte triglyceride lipase and hormone-sensitive lipase) and lipogenesis genes (fatty acid synthase; p < 0.05). In this unique experimental setting in healthy humans, chronic intermittent hypoxia induced high sympathetic tone, lipolysis and decreased free fatty acid sensitivity to insulin. This might participate in the trajectory to systemic insulin resistance and diabetes for patients with obstructive sleep apnea.
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INTRODUCTION: Monitoring changes in symptoms over time during long-term nocturnal home non-invasive ventilation (NIV) using patient-reported outcome measures is crucial. This study aimed to identify factors associated with changes in the S3-NIV total score, its two domains ("respiratory symptoms" and "sleep and NIV-related side effects") and individual item responses. METHODS: We conducted a retrospective, longitudinal data analysis of a cohort of adults with chronic respiratory failure treated with NIV. Data were obtained from a French homecare provider. Multivariate linear and multinomial ordinal mixed effect models were used to identify factors associated with changes in S3-NIV scores over time. RESULTS: Median follow-up was 2 years for 2135 participants. Each participant completed a median of five S3-NIV questionnaires; totaling 11,359 analyzed questionnaires. Type of respiratory condition, sex, age and time since NIV initiation were associated with change in S3-NIV score over time. NIV adherence was not associated with total S3-NIV score but high adherence was associated with more severe respiratory symptoms and an improvement in sleep and NIV-related side effects during the follow-up. Intensity of pressure support was associated with a lower total S3-NIV score and more side effects. Face masks and supplemental oxygen were associated with a lower S3-NIV total score. CONCLUSION: Changes in S3-NIV scores over time are associated with the individual's characteristics and NIV settings. Analysis of the two domains and individual items of the S3-NIV could increase understanding of the difficulties experienced by people on NIV.
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Home Care Services , Noninvasive Ventilation , Respiratory Insufficiency , Humans , Male , Female , Respiratory Insufficiency/therapy , Retrospective Studies , Aged , Middle Aged , Chronic Disease , Longitudinal Studies , Patient Reported Outcome Measures , Patient Compliance , Time Factors , Aged, 80 and over , Adult , FranceABSTRACT
Obstructive sleep apnea is a common type of sleep-disordered breathing associated with multiple comorbidities. Nearly a billion people are estimated to have obstructive sleep apnea, which carries a substantial economic burden, but under-diagnosis is still a problem. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. Telemedicine-based interventions (TM) have been evaluated to improve access to diagnosis, increase CPAP adherence, and contribute to easing the follow-up process, allowing healthcare facilities to provide patient-centered care. This narrative review summarizes the evidence available regarding the potential future of telemedicine in the management pathway of OSA. The potential of home sleep studies to improve OSA diagnosis and the importance of remote monitoring for tracking treatment adherence and failure and to contribute to developing patient engagement tools will be presented. Further studies are needed to explore the impact of shifting from teleconsultations to collaborative care models where patients are placed at the center of their care.
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OBJECTIVE/BACKGROUND: Chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA) and their comorbid association called Overlap Syndrome (OS) are frequent chronic diseases with high individual and societal burdens. Precise descriptions of the respective symptoms, comorbidities, and medications associated with these three conditions are lacking. We used a multidimensional phenotyping approach to identify relevant phenotypes characterizing these 3 disorders. PATIENTS/METHODS: 308 patients with OSA, COPD and OS were prospectively assessed using a combination of body shape measurements and multidimensional questionnaires evaluating sleep, fatigue, depression and respiratory symptoms. Comorbidities and medications were confirmed by physicians. Patients made home blood pressure self-measurements using a connected wearable device to identify undiagnosed or uncontrolled hypertension. RESULTS: Three distinct relevant phenotypes were identified. OSA patients were round in shape with a balanced waist-to-hip ratio, frequent witnessed apneas, nocturia, daytime sleepiness, depression, and high diastolic blood pressure. COPD patients had a thinner body shape with a high waist-to-hip ratio, complained mainly of fatigue, and exhibited a higher resting heart rate. OS patients were round in shape with a balanced waist-to-hip ratio, reported little sleepiness and depression, but had impaired sleep and the highest rate of cardio-metabolic comorbidities. Diminished fitness-to-drive was most apparent in patients with OSA and OS. Home blood pressure measurements identified undiagnosed hypertension in 80 % of patients and in nearly 80 % of those with hypertension it was uncontrolled by their current medications. CONCLUSIONS: Our systematic multidimensional phenotyping approach identified distinct body shapes, symptoms, and comorbidity profiles among patients with OSA, COPD, and OS.
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Comorbidity , Phenotype , Pulmonary Disease, Chronic Obstructive , Sleep Apnea, Obstructive , Humans , Male , Female , Sleep Apnea, Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Middle Aged , Aged , Surveys and Questionnaires , Prospective Studies , Hypertension/complications , Hypertension/diagnosis , Depression , Waist-Hip Ratio , FatigueABSTRACT
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.
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Atrial Fibrillation , Continuous Positive Airway Pressure , Sleep Apnea, Obstructive , Humans , Female , Atrial Fibrillation/therapy , Atrial Fibrillation/economics , Atrial Fibrillation/epidemiology , Atrial Fibrillation/diagnosis , Male , Middle Aged , Retrospective Studies , Aged , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/economics , Sleep Apnea, Obstructive/epidemiology , Continuous Positive Airway Pressure/economics , United States/epidemiology , Health Resources/statistics & numerical data , Health Resources/economics , Health Care Costs/statistics & numerical data , Hospitalization/economics , Hospitalization/statistics & numerical data , Patient Compliance/statistics & numerical data , Treatment OutcomeABSTRACT
BACKGROUND: The polysomnography (PSG) is the gold-standard for obstructive sleep apnea (OSA) syndrome diagnosis and assessment under positive airway pressure (PAP) therapies in children. Recently, an innovative digital medicine solution, including a mandibular jaw movement (MJM) sensor coupled with automated analysis, has been validated as an alternative to PSG for pediatric application. OBJECTIVE: This study aimed to assess the reliability of MJM automated analysis for the assessment of residual apnea/hypopnea events during sleep in children with OSA treated with noninvasive ventilation (NIV) or continuous PAP (CPAP). METHODS: In this open-label prospective non-randomized multicentric trial, we included children aged from 5 to 18 years with a diagnosis of severe OSA. The children underwent in-laboratory PSG with simultaneous MJM monitoring and at-home recording with MJM monitoring 3 months later. Agreement between PSG and MJM analysis in measuring the residual apnea-hypopnea index (AHI) was evaluated by the Bland-Altman method. The treatment effect on residual AHI was estimated for both PSG and MJM analysis. RESULTS: Fifteen (60% males) children were included with a median age of 12 years [interquartile range 8-15]. Two (17%) were ventilated with NIV and 13 (83%) with CPAP. There was a good agreement between MJM-AHI and PSG-AHI with a median bias of -0.25 (95% CI: -3.40 to +2.04) events/h. The reduction in AHI under treatment was consistently significant across the three measurement methods: in-laboratory PSG and MJM recordings in the laboratory and at home. CONCLUSION: Automated analysis of MJM is a highly reliable alternative method to assess residual events in a small population treated with PAP therapies.
Subject(s)
Continuous Positive Airway Pressure , Mandible , Polysomnography , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/physiopathology , Child , Male , Female , Prospective Studies , Adolescent , Continuous Positive Airway Pressure/methods , Mandible/physiopathology , Child, Preschool , Reproducibility of Results , Noninvasive Ventilation/methodsABSTRACT
Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly (P < 0.01), whereas QTVI decreased (P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified (P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (ß = 0.405, P < 0.01), STVQT (ß = 0.151, P < 0.01), and QTVI (ß = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep.NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.
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Arrhythmias, Cardiac , Sleep Apnea, Obstructive , Male , Humans , Female , Death, Sudden, Cardiac/etiology , Sleep Apnea, Obstructive/complications , Arousal , Electrocardiography/adverse effects , Heart Rate/physiology , Hypoxia/complicationsABSTRACT
PURPOSE: The objective of this study was to analyze the nycthemeral variations in blood pressure (BP) in individuals who presented with non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: BP was recorded for 24â h (ambulatory blood pressure monitoring, ABPM) in 65 patients with acute NAION. Three definitions of nighttime periods were used: definition 1, 1 a.m.-6 a.m.; definition 2, 10 p.m.-7 a.m.; and definition 3, 10 p.m.-8 a.m. For each of these definitions, patients were classified according to the value of nocturnal reduction in BP into dippers (10-20%), mild dippers (0-10%), reverse dippers (< 0%), and extreme dippers (> 20%). RESULTS: The proportions of dippers, mild dippers, reverse dippers, and extreme dippers varied significantly depending on the definition chosen. We found the highest number of patients with extreme dipping (23%) when using the strictest definition of nighttime period (definition 1, 1 a.m.-6 a.m.), as compared with 6.2% and 1.5% for the other definitions, respectively. Overall, 13 of 33 patients without known systemic hypertension (39%) were diagnosed with hypertension after ABPM. No risk factor for NAION was associated with the extreme-dipping profile. Finally, the prevalence of systemic hypertension was high (69%). CONCLUSION: In our population of patients who had an episode of NAION, the proportion of extreme dippers was higher than that usually found in the literature. However, extreme dipping is not a frequent feature of patients with NAION as compared to patients with systemic hypertension. ABPM is recommended for all patients with NAION and unknown history of systemic hypertension.
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INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is a chronic multiorgan pathology that has a negative impact on quality of life. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, CPAP termination rates remain very high, and adherence to therapy is a major issue. To date, studies targeting predictive factors of CPAP adherence by OSAS patients mainly include clinical data. The social, socioeconomic, psychological, and home environment aspects have been far less studied and largely underestimated. This study aims to obtain solid quantitative results examining the relationship between the determinants of refusal, non-adherence, or termination of CPAP treatment, and in particular the pivotal role played by health literacy. METHODS AND ANALYSIS: This is a prospective, multicentre, observational study recruiting patients attending the sleep clinic of the Grenoble Alpes University Hospital, France. Consecutive adults (>18 years) recently diagnosed with OSAS and prescribed CPAP treatment with telemonitoring will be enrolled in the present study. They will benefit from home visits by a CPAP technician or nurse at CPAP initiation. Patients will then be followed up for 6 months through the telemonitoring platform of a home-care provider. The primary objective is to evaluate the impact of health literacy (health literacy, measured by the European Health Literacy Survey questionnaire (HLS-EU-16) on the refusal, non-adherence or termination of CPAP treatment in newly diagnosed OSAS patients, during the first 6 months after diagnosis. The target sample size is 250 participants. ETHICS AND DISSEMINATION: The study protocol, patient information, and the non-opposition form were approved by the French national ethics committee (CPP 2021-92, January 2022). All patients are required to have signed a written informed consent form permitting their anonymised personal and medical data to be used for clinical research purposes. We will publish the results in a peer-reviewed medical journal and on our institutional websites. TRIAL REGISTRATION NUMBER: NCT05385302.
Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Adult , Humans , Continuous Positive Airway Pressure , Prospective Studies , Quality of Life , Sleep Apnea, Obstructive/therapy , Ambulatory Care Facilities , Observational Studies as Topic , Multicenter Studies as TopicABSTRACT
Obstructive sleep apnea (OSA) is characterized by intermittent repeated episodes of hypoxia-reoxygenation. OSA is associated with cerebrovascular consequences. An enhanced blood-brain barrier (BBB) permeability has been proposed as a marker of those disorders. We studied in mice the effects of 1 day and 15 days intermittent hypoxia (IH) exposure on BBB function. We focused on the dorsal part of the hippocampus and attempted to identify the molecular mechanisms by combining in vivo BBB permeability (Evans blue tests) and mRNA expression of several junction proteins (zona occludens (ZO-1,2,3), VE-cadherin, claudins (1,5,12), cingulin) and of aquaporins (1,4,9) on hippocampal brain tissues. After 15 days of IH exposure we observed an increase in BBB permeability, associated with increased mRNA expressions of claudins 1 and 12, aquaporins 1 and 9. IH seemed to increase early for claudin-1 mRNA expression as it doubled with 1 day of exposure and returned near to its base level after 15 days. Claudin-1 overexpression may represent an immediate response to IH exposure. Then, after 15 days of exposure, an increase in functional BBB permeability was associated with enhanced expression of aquaporin. These BBB alterations are possibly associated with a vasogenic oedema that may affect brain functions and accelerate neurodegenerative processes.
Subject(s)
Aquaporins , Sleep Apnea, Obstructive , Mice , Animals , Blood-Brain Barrier/metabolism , Claudin-1/metabolism , Disease Models, Animal , Hypoxia/metabolism , Claudins/metabolism , Sleep Apnea, Obstructive/metabolism , Permeability , Aquaporins/metabolism , RNA, Messenger/metabolism , Claudin-5/metabolismABSTRACT
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a heterogeneous condition covering many clinical phenotypes in terms of the diversity of symptoms. Patient-based OSA screening questionnaires used in routine practice contain significantly varying contents that can impact the reliability and validity of the screening. We investigated to what extent common patient-based OSA screening questionnaires differ or overlap in their item content by conducting a rigorous, methodical, and quantified content overlap analysis. METHODS: We conducted an item content analysis of 11 OSA screening questionnaires validated in adult populations and characterized their overlap using a 4-step approach: (1) selection of OSA screening questionnaires, (2) item extraction and selection, (3) extraction of symptoms from items, and (4) assessment of content overlap with the Jaccard index (from 0, no overlap, to 1, full overlap). RESULTS: We extracted 72 items that provided 25 distinct symptoms from 11 selected OSA questionnaires. The overlap between them was weak (mean Jaccard index: 0.224; ranging from 0.138 to 0.329). All questionnaires contained symptoms of the "OSA symptom" dimension (eg, snoring or witnessed apneas). The STOP-BANG (0.329) and the Berlin (0.280) questionnaires exhibited the highest overlap content. Ten symptoms (40%) were investigated in only 1 questionnaire. CONCLUSIONS: The heterogeneity of content and the low overlap across these questionnaires reflect the challenges of screening OSA. The different OSA questionnaires potentially capture varying aspects of the disorder, with the risk of biased results in studies. Suggestions are made for better OSA screening and refinement of clinical OSA phenotypes. CITATION: Gauld C, Baillieul S, Martin VP, et al. Symptom content analysis of OSA questionnaires: time to identify and improve relevance of diversity of OSA symptoms? J Clin Sleep Med. 2024;20(7):1105-1117.
Subject(s)
Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/diagnosis , Surveys and Questionnaires/standards , Reproducibility of Results , Male , Female , Adult , Middle Aged , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Symptom Assessment/standards , Mass Screening/methodsABSTRACT
Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Using lean mice exposed to long-term IH and a cohort of lean OSA patients (n = 71), we conducted comprehensive hepatic transcriptomics, lipidomics, and targeted serum proteomics. Significantly, we demonstrated that long-term IH alone can induce NASH molecular signatures found in human steatohepatitis transcriptomic data. Biomarkers (PPARs, NRFs, arachidonic acid, IL16, IL20, IFNB, TNF-α) associated with early hepatic and systemic inflammation were identified. This molecular link between IH, sleep apnea, and steatohepatitis merits further exploration in clinical trials, advocating for integrating sleep apnea diagnosis in liver disease phenotyping. Our unique signatures offer potential diagnostic and treatment response markers, highlighting therapeutic targets in the comorbidity of NAFLD and OSA.