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Rationale: Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation. Methods: Right atrial appendage biopsies from patients with and without SDB were used to determine HIF-1α, Grp78 and CHOP expressions. Wild-type and HIF-1α+/− mice were exposed to normoxia (N) or IH (21–5% O2, 60 cycles/h, 8 h/day) for 21 days. Expressions of HIF-1α, Grp78 and CHOP, and apoptosis, were measured by Western blot and immunochemistry. In isolated cardiomyocytes, we examined structural integrity of MAM by proximity ligation assay and their function by measuring ER-to-mitochondria Ca2+ transfer by confocal microscopy. Finally, we measured mitochondrial respiration using oxygraphy and calcium retention capacity (CRC) by spectrofluorometry. MAM structure was also investigated in H9C2 cells incubated with 1 mM CoCl2, a potent HIF-1α inducer. Results: In human atrial biopsies and mice, IH induced HIF-1 activation, ER stress and apoptosis. IH disrupted MAM, altered Ca2+ homeostasis, mitochondrial respiration and CRC. Importantly, IH had no effect in HIF-1α+/− mice. Similar to what observed under IH, HIF-1α overexpression was associated with MAM alteration in H9C2. Conclusion: IH-induced ER stress, MAM alterations and mitochondrial dysfunction were mediated by HIF-1; all these intermediate mechanisms ultimately inducing cardiomyocyte apoptosis. This suggests that HIF-1 modulation might limit the deleterious cardiac effects of SDB.

Intermittent hypoxia (IH), the major feature of obstructive sleep apnea syndrome (OSAS), induces atherosclerosis and elastic fiber alterations. VE-cadherin cleavage is increased in OSAS patients and in an IH-cellular model. It is mediated by HIF-1 and Src-tyr-kinases pathways and results in endothelial hyperpermeability. Our aim was to determine whether blocking VE-cadherin cleavage in vivo could be an efficient strategy to inhibit deleterious IH-induced vascular remodeling, elastic fiber defects and atherogenesis. VE-cadherin regulation, aortic remodeling and atherosclerosis were studied in IH-exposed C57Bl/6J or ApoE-/-mice treated or not with Src-tyr-kinases inhibitors (Saracatinib/Pazopanib) or a HIF-1 inhibitor (Acriflavine). Human aortic endothelial cells were exposed to IH and treated with the same inhibitors. LDL and the monocytes transendothelium passage were measured. In vitro, IH increased transendothelium LDL and monocytes passage, and the tested inhibitors prevented these effects. In mice, IH decreased VE-cadherin expression and increased plasmatic sVE level, intima-media thickness, elastic fiber alterations and atherosclerosis, while the inhibitors prevented these in vivo effects. In vivo inhibition of HIF-1 and Src tyr kinase pathways were associated with the prevention of IH-induced elastic fiber/lamella degradation and atherogenesis, which suggests that VE-cadherin could be an important target to limit atherogenesis and progression of arterial stiffness in OSAS.

Abstract Background Intermittent hypoxia (IH) is the major feature of obstructive sleep apnea syndrome, well‐known to induce cardiometabolic complications. We previously demonstrated that IH induces hyperinsulinemia and associated altered insulin signaling in adipose tissue, liver, and skeletal muscle, but impact of IH on cardiac insulin signaling and functional/structural consequences remains unknown. Therefore, the aims of this study were to investigate in both lean and obese mice the effects of chronic IH on the following: (1) cardiac insulin signaling and (2) cardiac remodeling and function. Methods C57BL/6 J male mice were fed low‐fat (LFD) or high‐fat (HFD) diet for 20 weeks, and exposed to IH (21–5% FiO2, 60 s cycle, 8 h/day) or normoxia (N) for the last 6 weeks. Systemic insulin sensitivity was evaluated by an insulin tolerance test. Cardiac remodeling and contractile function were assessed by cardiac ultrasonography. Ultimately, hearts were withdrawn for biochemical and histological analysis. Results In LFD mice, IH‐induced hyperinsulinemia and systemic insulin resistance that were associated with increased phosphorylations of cardiac insulin receptor and Akt on Tyr1150 and Ser473 residues, respectively. In addition, IH significantly increased cardiac interstitial fibrosis and cardiac contractility. In the HFD group, IH did not exert any additional effect, nor on insulin/Akt signaling, nor on cardiac remodeling and function. Conclusion Our study suggests that, despite systemic insulin resistance, IH exposure mediates an adaptive cardiac response in lean but not in obese mice. Further studies are needed to investigate which specific mechanisms are involved and to determine the long‐term evolution of cardiac responses to IH.

Objective The earliest possible detection of individuals with COVID-19 has been essential to curb the spread of infection. Existing digital tools have been scaled up to address this issue. Every night telemonitoring data on continuous positive airway pressure (CPAP) device use, the first-line therapy for obstructive sleep apnoea (OSA), is collected worldwide. We asked whether the changes in CPAP adherence patterns of might constitute an alert for COVID-19. Methods We analysed preliminary results of telemonitoring data, recorded between February 1 and April 30, 2020, on OSA patients followed by our sleep clinics and diagnosed with COVID-19. Results CPAP telemonitoring data from the first 19 patients diagnosed with COVID-19 showed a clear decrease or halt in adherence in the 20 days immediately preceding COVID-19 diagnosis compared to an earlier period (p

BackgroundThe symptomatic response to continuous positive airway pressure (CPAP) therapy in COPD-obstructive sleep apnea overlap syndrome (OVS) compared to OSA syndrome (OSA) alone has not been well studied so far. The aim of this study is to explore main differences in the clinical response to CPAP treatment in OVS compared to OSA alone.Study design and methodsUsing prospective data from the French National Sleep Apnea Registry, we conducted an observational study among 6320 patients with moderate-to-severe OSA, available spirometry, and at least one follow-up visit under CPAP therapy.ResultsCPAP efficacy measured on the residual apnea-hypopnea index and median adherence were similar between OVS and OSA patients. In both groups, the overall burden of symptoms related to sleep apnea improved with CPAP treatment. In a multivariable model adjusted for age, gender, body mass index, adherence to treatment and residual apnea-hypopnea index, OVS was associated with higher odds for persistent morning headaches (OR: 1.37 [95% CI; 1.04; 1.79]; P = 0.02), morning tiredness (OR: 1.33 [95% CI: 1.12; 1.59]; PInterpretationCPAP therapy was effective in normalizing the apnea-hypopnea index and significantly improved OSA-related symptoms, regardless of COPD status. CPAP should be offered to patients with OVS on a trial basis as a significant improvement in OSA-related symptoms can be expected, although the range of response may be less dramatic than in OSA alone.

The progression of chronic obstructive pulmonary disease (COPD) is characterized by episodes of acute exacerbation (AECOPD) of symptoms, decline in respiratory function, and reduction in quality-of-life increasing morbi-mortality and often requiring hospitalization. Exacerbations can be triggered by environmental exposures, changes in lifestyle, and/or physiological and psychological factors to greater or lesser extents depending on the individual’s COPD phenotype. The prediction and early detection of an exacerbation might allow patients and physicians to better manage the acute phase. We summarize the recent scientific data on remote telemonitoring (TM) for the prediction and management of acute exacerbations in COPD patients. We discuss the components of remote monitoring platforms, including the integration of environmental monitoring data; patient reported outcomes collected via interactive Smartphone apps, with data from wearable devices that monitor physical activity, heart rate, etc.; and data from medical devices such as connected non-invasive ventilators. We consider how telemonitoring and the deluge of data it potentially generates could be combined with electronic health records to provide personalized care and multi-disease management for COPD patients.

Background: Noninvasive ventilation (NIV) is accepted as standard of care for chronic hypercapnic respiratory failure (CHRF) and is being increasingly implemented in older subjects. However, little is known regarding the use of NIV on a long-term basis in the very old. The outcomes of this study were: 1/to report the proportion of patients ≥ 75 years old (elderly) among a large group of long-term NIV users and its trend since 2000; 2/to compare this population to a younger population (

Abstract We report the case of a 71‐year‐old obese continuous positive airway pressure (CPAP)‐treated man who developed an acute cardiac failure (ACF) triggered by atrial fibrillation. CPAP data downloaded from the CPAP software (Rescan®) retrospectively demonstrated the progressive development of a high residual central apnoea–hypopnoea index (AHI) with Cheyne–Stokes respiration (CSR). The AHI decreased after cardioversion allowing normalization of cardiac rhythm and function. Raw data extracted from CPAP software showed a gradual decrease in the periodic breathing cycle length related to a simultaneous improvement in left ventricular ejection fraction (LVEF) after cardioversion. During this clinical period of respiratory instability in the presence of cardiac failure, CSR episodes were exacerbated by ventilation overshoots followed by micro‐arousals induced by leaks. This might explain the high night to night variability of CSR occurrence in susceptible patients with impaired cardiac function. Beyond attempts to improve cardiac function, leak reduction might represent an important target for CSR management.

BACKGROUND Sleep‐disordered breathing is associated with a poor prognosis (mortality) in patients with ischemic cardiomyopathy. The understanding of mechanisms linking intermittent hypoxia (IH), the key feature of sleep‐disordered breathing, to ischemic cardiomyopathy progression is crucial for identifying specific actionable therapeutic targets. The aims of the present study were (1) to evaluate the impact of IH on the time course evolution of cardiac remodeling and contractile dysfunction in a rat model of ischemic cardiomyopathy; and (2) to determine the impact of IH on sympathetic activity, hypoxia inducible factor‐1 activation, and endoplasmic reticulum stress in the time course of ischemic cardiomyopathy progression. METHODS AND RESULTS Ischemic cardiomyopathy was induced by a permanent ligature of the left coronary artery in male Wistar rats (rats with myocardial infarction). Rats with myocardial infarction were then exposed to either IH or normoxia for up to 12 weeks. Cardiac remodeling and function were analyzed by Sirius red and wheat germ agglutinin staining, ultrasonography, and cardiac catheterization. Sympathetic activity was evaluated by spectral analysis of blood pressure variability. Hypoxia‐inducible factor‐1α activation and burden of endoplasmic reticulum stress were characterized by Western blots. Long‐term IH exposure precipitated cardiac remodeling (hypertrophy and interstitial fibrosis) and contractile dysfunction during the time course evolution of ischemic cardiomyopathy in rodents. Among associated mechanisms, we identified the early occurrence and persistence of sympathetic activation, associated with sustained hypoxia‐inducible factor‐1α expression and a delayed pro‐apoptotic endoplasmic reticulum stress. CONCLUSIONS Our data provide the demonstration of the deleterious impact of IH on post–myocardial infarction remodeling and contractile dysfunction. Further studies are needed to evaluate whether targeting sympathetic nervous system or HIF‐1 overactivities could limit these effects and improve management of coexisting ischemic cardiomyopathy and sleep‐disordered breathing.

Purpose FACE is a prospective cohort study designed to assess the effect of adding adaptive servoventilation (ASV) to standard care on morbidity and mortality in patients with chronic heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF) or reduced ejection fraction (HFrEF) who have sleep-disordered breathing (SDB) with an indication for ASV. We describe the study design, ongoing data collection and baseline participant characteristics.Participants Consecutive patients with HFpEF, HFmrEF or HFrEF plus SDB with central sleep apnoea (CSA) and indication for ASV were enrolled in the study cohort between November 2009 and December 2018; the ASV group includes those treated with ASV and the control group consists of patients who refused ASV or stopped treatment early. Follow-up is based on standard clinical practice, with visits at inclusion, after 3, 12 and 24 months of follow-up. Primary endpoint is the time to first event: all-cause death or unplanned hospitalisation (or unplanned prolongation of a planned hospitalisation) for worsening of HF, cardiovascular death or unplanned hospitalisation for worsening of HF, and all-cause death or all-cause unplanned hospitalisation.Findings to date 503 patients have been enrolled, mean age of 72 years, 88% male, 31% with HFrEF. HF was commonly of ischaemic origin, and the number of comorbidities was high. SDB was severe (median Apnoea–Hypopnoea Index 42/hour), and CSA was the main indication for ASV (69%). HF was highly symptomatic; most patients were in NYHA class II (38%) or III (29%).Future plans Patient follow-up is ongoing. Given the heterogeneous nature of the enrolled population, a decision was made to use latent class analysis to define homogeneous patient subgroups, and then evaluate outcomes by cluster, and in the ASV and control groups (overall and within patient clusters). First analysis will be performed after 3 months, a second analysis at the 2-year follow-up.Trial registration number NCT01831128; Pre-results.

BackgroundWhile millions of people are living permanently at high altitude (>2,500 m) worldwide, the mechanisms underlying their tolerance to chronic hypoxia and those responsible for the occurrence of chronic mountain sickness (CMS) remain to be elucidated. Excessive erythrocytosis (EE) is thought to be the main mechanism responsible for CMS symptoms and is included in the definition of CMS, but the precise interplay between EE and symptoms of CMS requires further investigations.MethodsThe present study benefits from an exceptional dataset coming from 1,594 dwellers of La Rinconada, the highest city in the world (5,100–5,300 m). Based on individual clinical characteristics, subjects were categorized according to the presence of EE and CMS diagnosis, based on current guidelines.ResultsIn this population of relatively young [32 (23; 39) years] highlanders residing in La Rinconada for only a few years [3 (2; 5) years], the internal prevalence of EE (44%) was high, whereas the internal prevalence of CMS (14%) was similar compared to previous reports in highlander populations living at lower altitude (∼4,000 m) in the Andes. Individuals with EE reported less symptoms compared to individuals with lower hematocrit values. Multivariable analysis revealed that age and sex are the main factors associated with EE, whereas age, hematocrit and number of years living at La Rinconada are factors associated with CMS symptoms.ConclusionIn this specific population of La Rinconada, high hematocrit values were observed but were associated with limited symptoms. These results raise important questions regarding the definition of EE and CMS and their underlying mechanisms in high-altitude populations.

Background: Growth hormone (GH) stimulates the production of insulin-like growth factor 1 (IGF-1) in most tissues and together GH and IGF-1 profoundly impact adipose tissue deposition, glucose metabolism and cardiovascular function. A low serum IGF-I level has been reported as being associated with obstructive sleep apnea (OSA) and might be one of the mechanisms underlying cardio-metabolic risk in OSA patients.Methods: In a multicenter national study, 817 patients consulting for suspicion of OSA (OSA confirmed for 567 patients) underwent serum IGF-1 measurements. We analyzed the association between an IGF-1 level below the median value of the population and variables related to cardio-metabolic risk: body mass index (BMI) and waist circumference, apnea hypopnea index (AHI), cholesterol and triglycerides (expressed as median and divided into quartiles for continuous variables).Results: After adjustment for age and gender, low IGF-1 levels were associated with increased BMI and AHI (Odds ratios (OR) = 2.83; p < 0.0001 and OR = 3.03, p < 0.0001 for Quartile 4 vs. Quartile1, respectively), with elevated cholesterol levels (OR = 1.36, p = 0.0444), and elevated triglyceride levels (OR = 1.36; p = 0.0008).Conclusions: Both adiposity and sleep apnea synergistically predict low levels of IGF-1 and thus could together contribute toward cardio-metabolic risk. Further work are needed to confirm whether IGF-1 levels allow grading severity and predicting response to treatments to aim at a personalized medicine for patients suffering from OSA.

Background: Chronic intermittent hypoxia (IH), the hallmark feature of obstructive sleep apnoea syndrome, contributes to infarct size enhancement after myocardial ischemia–reperfusion (I/R). Curcumin (Curc), the natural pigment of Curcuma longa , has been demonstrated to be beneficial in the context of myocardial injury. In this study, we assessed the effects of Curc on the maladaptive cardiac response to IH, and particularly on IH-induced hypoxia inducible factor-1 (HIF-1) expression, oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis. Methods: Swiss/SV129 mice were exposed to normoxia or IH (21–5% FiO 2 , 60 s cycles, 8 h per day, for 21 days) and treated orally with Curc (100 mg kg −1 day −1 , oral gavage) or its vehicle. Mice were then either euthanised for heart sampling in order to perform biochemical and histological analysis, or subjected to an in vivo ischemia-reperfusion protocol in order to measure infarct size. Results: IH increased nuclear HIF-1α expression and superoxide anion (O 2 .– ) production as well as nuclear factor kappa B (NF-kB) p65, glucose-regulated protein (Grp78) and C/EBP homologous protein (CHOP) expression. IH also induced apoptosis and increased infarct size after I/R . The IH-induced HIF-1 activation, oxidative stress, inflammation, ER stress and apoptosis were abolished by chronic Curc treatment. Curc also significantly decreased infarct size only in mice exposed to IH. Conclusion: Curc prevents IH-induced myocardial cell death signalling. Curc might be used as a combined therapy with continuous positive airway pressure in sleep apnoea patients with high cardiovascular risk.

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.

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.

BackgroundObstructive 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.MethodsIn 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.ResultsSeventy 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.ConclusionPWV 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.

BackgroundMore advanced knowledge is needed on how COPD alters the clinical presentation of obstructive sleep apnea (OSA) and how the association of both diseases, known as 'overlap syndrome' (OVS), impacts on cardiovascular health.ObjectiveTo investigate differences between patients with OVS and those with moderate-to-severe OSA alone.MethodsA cross-sectional study conducted in the French National Sleep Apnea Registry between January 1997 and January 2017. Univariable and multivariable logistic regression models were used to compare OVS versus OSA alone on symptoms and cardiovascular health.Results46,786 patients had moderate-to-severe OSA. Valid spirometry was available for 16,466 patients: 14,368 (87%) had moderate-to-severe OSA alone and 2098 (13%) had OVS. A lower proportion of OVS patients complained of snoring, morning headaches and excessive daytime sleepiness compared to OSA alone (median Epworth Sleepiness Scale score: 9 [interquartile range (IQR) 6-13] versus 10 (IQR 6-13), respectively; P ConclusionsIn adults with moderate-to-severe OSA, OVS was minimally symptomatic, but exhibited higher odds for prevalent coronary heart disease, heart failure and peripheral arteriopathy.

Abstract We introduce a novel interactive framework to handle both instance-level and temporal smoothness constraints for clustering large longitudinal data and for tracking the cluster evolutions over time. It consists of a constrained clustering algorithm, called CVQE+, which optimizes the clustering quality, constraint violation and the historical cost between consecutive data snapshots. At the center of our framework is a simple yet effective active learning technique, named Border, for iteratively selecting the most informative pairs of objects to query users about, and updating the clustering with new constraints. Those constraints are then propagated inside each data snapshot and between snapshots via two schemes, called constraint inheritance and constraint propagation, to further enhance the results. Moreover, a historical constraint is enforced between consecutive snapshots to ensure the consistency of results among them. Experiments show better or comparable clustering results than state-of-the-art techniques as well as high scalability for large datasets. Finally, we apply our algorithm for clustering phenotypes in patients with Obstructive Sleep Apnea as well as for tracking how these clusters evolve over time.

Abstract Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.

The aim of this study was to assess the impact of the nationwide total lockdown (LD) in France on weight loss and body composition modifications in subjects participating in a weight loss program and to evaluate the impact of remote consultations on participants’ adherence to the weight loss program. The CO-RNPC study was a prospective multicentre cohort study including participants undergoing a two to six months program. The rate of weight loss in kg/week was computed before (15 days), during (99 days) and after LD (15 days). In the 1550 completing participants, body weight decreased from 87.1 kg [IQR 77.0; 100.2] to 82.3 kg [72.1; 94.3] resulting in a difference of −4.79 kg [−4.48; −5.10] (p < 0.01), with a corresponding reduction in waist circumference by 4 cm ([0; 9], p < 0.01). The median weight loss was 4.4 kg [0.5; 9.4] in those who used remote consultations, and 1.4 kg [0.8; 5.7] in the no remote consultation group (p < 0.01). In this large prospective cohort, we observed that the rate of weight loss was reduced during LD. This reduction was counterbalanced in participants involved in a remote consultation follow-up with a dose-effect response based on the number of remote consultations.

Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.

Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity (body mass index ≥30 kg·m−2), daytime hypercapnia (arterial carbon dioxide tension ≥45 mmHg) and sleep disordered breathing, after ruling out other disorders that may cause alveolar hypoventilation. OHS prevalence has been estimated to be ∼0.4% of the adult population. OHS is typically diagnosed during an episode of acute-on-chronic hypercapnic respiratory failure or when symptoms lead to pulmonary or sleep consultation in stable conditions. The diagnosis is firmly established after arterial blood gases and a sleep study. The presence of daytime hypercapnia is explained by several co-existing mechanisms such as obesity-related changes in the respiratory system, alterations in respiratory drive and breathing abnormalities during sleep. The most frequent comorbidities are metabolic and cardiovascular, mainly heart failure, coronary disease and pulmonary hypertension. Both continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) improve clinical symptoms, quality of life, gas exchange, and sleep disordered breathing. CPAP is considered the first-line treatment modality for OHS phenotype with concomitant severe obstructive sleep apnoea, whereas NIV is preferred in the minority of OHS patients with hypoventilation during sleep with no or milder forms of obstructive sleep apnoea (approximately

Background and objectivePain, a symptom often present in patients with Chronic Obstructive Pulmonary Disease (COPD), alters quality of life. COPD exacerbation augments several mechanisms that may cause pain (dyspnea, hyperinflation and inflammation) and therefore we hypothesized that pain might be increased during exacerbation.MethodsA prospective cohort study was conducted in patients admitted for acute exacerbations of COPD (AECOPD) in two emergency departments in France and Canada. Patients with cancer-related pain or recent trauma were not included. The Short Form McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI) scale were used to evaluate pain intensity and location. Patients also completed the Borg Dyspnea Scale and Hospital Anxiety and Depression Scale. The questionnaires were completed again during an outpatient assessment in the stable phase. The primary outcome was difference in pain intensity (SF-MPQ) between the exacerbation and stable phases.ResultsFifty patients were included. During exacerbation, 46 patients (92%) reported pain compared to 29 (58%) in the stable phase (pConclusionThe frequency and intensity of pain were higher during AECOPD, with a specific distribution. Pain should therefore be routinely assessed and treated in patients with AECOPD.

ObjectiveMost patients with resistant hypertension (RH) have obstructive sleep apnea (OSA). We aimed to determine the impact of OSA and continuous positive airway pressure (CPAP) treatment on the leptin profile and blood pressure (BP) in patients with RH.MethodsAfter an initial case-control study (RH with and without OSA), we performed a randomized, single blind study in OSA + RH patients receiving either sham CPAP (3 months) followed by active CPAP (6 months) or 6 months of active CPAP. The primary outcome was the comparison of leptin levels between groups of RH patients with or without OSA. Secondary outcomes were the comparison of metabolic parameters, biomarkers of sympathetic activity, and BP indices between the two groups of RH patients with or without OSA. The same outcomes were then evaluated and compared before and after sham and effective CPAP intervention.ResultsSixty-two patients (60 ± 10 years; 77% men) with RH (24-h daytime systolic BP (SBP)/diastolic BP: 145 ± 13/85 ± 10 mmHg, 3.7 antihypertensive drugs) were included. The 37 RH patients exhibiting OSA (60%) were predominantly men (87 vs 64% for non-OSA patients), with a greater prevalence of metabolic syndrome and higher creatininemia. Their leptin concentrations were significantly lower than in non-OSA patients [9 (6; 15) vs 17 (6; 29) ng/mL] but increased after 6 months of CPAP. Three months of effective CPAP significantly decreased night-time SBP by 6.4 mmHg and heart rate (HR) by 6.0 bpm, compared to sham CPAP.ConclusionThe association between OSA and RH corresponds to a specific, predominately male phenotype with a higher burden of metabolic syndrome and higher creatininemia but there was no significant difference between OSA and non-OSA patients regarding BP indices, and the number of antihypertensive drugs used. Active CPAP could be efficient at decreasing night-time BP and HR, but there was no difference between CPAP and sham CPAP groups for all metabolic and SNS markers (NCT00746902 RHOOSAS).

A systematic review of English and French articles using Pubmed/Medline and Embase included studies assessing objective physical activity levels of obstructive sleep apnea (OSA) patients and exploring the effects of exercise training on OSA severity, body mass index (BMI), sleepiness, and cardiorespiratory fitness [peak oxygen consumption (VO2peak)]. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. For objective physical activity levels, eight studies were included. The mean number of steps per day across studies was 5,388 (95% CI: 3,831–6,945; p

Severe obstructive sleep apnoea (OSA) can lead to neurocognitive alterations, including gait impairments. The beneficial effects of continuous positive airway pressure (CPAP) on improving excessive daytime sleepiness and daily functioning have been documented. However, a demonstration of CPAP treatment efficacy on gait control is still lacking. This study aims to test the hypothesis that CPAP improves gait control in severe OSA patients.In this prospective controlled study, twelve severe OSA patients (age = 57.2±8.9 years, body mass index = 27.4±3.1 kg·m-2, apnoea-hypopnoea index = 46.3±11.7 events·h-1) and 10 healthy matched subjects were included. Overground gait parameters were recorded at spontaneous speed and stride time variability, a clinical marker of gait control, was calculated. To assess the role of executive functions in gait and postural control, a dual-task paradigm was applied using a Stroop test as secondary cognitive task. All assessments were performed before and after 8 weeks of CPAP treatment.Before CPAP treatment, OSA patients had significantly larger stride time variability (3.1±1.1% vs 2.1±0.5%) and lower cognitive performances under dual task compared to controls. After CPAP treatment, stride time variability was significantly improved and no longer different compared to controls. Cognitive performance under dual task also improved after CPAP treatment.Eight weeks of CPAP treatment improves gait control of severe OSA patients, suggesting morphological and functional cerebral improvements. Our data provide a rationale for further mechanistic studies and the use of gait as a biomarker of OSA brain consequences.

METHODS:Data from women (n = 305, aged 43 [34; 53] years-old, BMI 44.2 [40.8; 48.2] kg/m2) included in the Severe Obesity Outcome Network (SOON) cohort were analyzed (i) to evaluate collinearity between the different anthropometric markers, (ii) to compare the association of markers with hypertension, type 2 diabetes, obstructive sleep apnea syndrome (OSAS) and other cardiometabolic risks. RESULTS:Hip, waist and neck circumferences correlated with BMI with respectively less collinearity (r = 0.70, r = 0.59 and r = 0.37, respectively, p

RATIONALE:Acute hypercapnic respiratory failure (AHRF) treated with non-invasive ventilation in the ICU is frequently caused by chronic obstructive pulmonary disease (COPD) exacerbations and obesity-hypoventilation syndrome, the latter being most often associated with obstructive sleep apnea. Overlap syndrome (a combination of COPD and obstructive sleep apnea) may represent a major burden in this population, and specific diagnostic pathways are needed to improve its detection early after ICU discharge. OBJECTIVES:To evaluate whether pulmonary function tests can identify a high probability of obstructive sleep apnea in AHRF survivors and outperform common screening questionnaires to identify the disorder. METHODS:Fifty-three patients surviving AHRF (31 males; median age 67 years (interquartile range: 62-74) participated in the study. Anthropometric data were recorded and body plethysmography was performed 15 days after ICU discharge. A sleep study was performed 3 months after ICU discharge. RESULTS:The apnea-hypopnea index was negatively associated with static hyperinflation as measured by the residual volume to total lung capacity ratio in the % of predicted (coefficient = -0.64; standard error 0.17; 95% CI -0.97 to -0.31; p

The classification of obstructive sleep apnea is on the basis of sleep study criteria that may not adequately capture disease heterogeneity. Improved phenotyping may improve prognosis prediction and help select therapeutic strategies.This study used cluster analysis to investigate the clinical clusters of obstructive sleep apnea.An ascending hierarchical cluster analysis was performed on baseline symptoms, physical examination, risk factor exposure and co-morbidities from 18,263 participants in the OSFP (French national registry of sleep apnea). The probability for criteria to be associated with a given cluster was assessed using odds ratios, determined by univariate logistic regression.Six clusters were identified, in which patients varied considerably in age, sex, symptoms, obesity, co-morbidities and environmental risk factors. The main significant differences between clusters were minimally symptomatic versus sleepy obstructive sleep apnea patients, lean versus obese, and among obese patients different combinations of co-morbidities and environmental risk factors.Our cluster analysis identified six distinct clusters of obstructive sleep apnea. Our findings underscore the high degree of heterogeneity that exists within obstructive sleep apnea patients regarding clinical presentation, risk factors and consequences. This may help in both research and clinical practice for validating new prevention programs, in diagnosis and in decisions regarding therapeutic strategies.

Leukotriene B4 (LTB4) production increases in obstructive sleep apnea syndrome (OSA) and is linked to early vascular remodeling, the mechanism of which is unknown. The objective of this study was to to determine the molecular mechanisms of LTB4 pathway activation in polymorphonuclear cells (PMNs) and early vascular remodeling in OSA and the specific contribution of intermittent hypoxia (IH). PMNs were isolated from 120 OSA patients and 33 healthy subjects and used for measurements of LTB4 production, determination of mRNA and protein expression levels, or exposed for four cycles of in vitro IH. PMNs derived from OSA patients exhibited increased LTB4 production, for which apnea-hypopnea index was an independent predictor (P=0.042). 5-Lipoxygenase-activating protein (FLAP) mRNA and protein increased significantly in PMNs from OSA patients versus controls and were associated with carotid luminal diameter and intima-media thickness. LTB4 (10 ng/ml) increased IL-6 (P=0.006) and MCP-1 (P=0.002) production in OSA patient monocytes. In vitro exposure of PMNs from controls to IH enhanced FLAP mRNA levels (P= 0.027) and induced a 2.7-fold increase (P=0.028) in LTB4 secretion compared with PMNs exposed to normoxia. In conclusion, upregulation of FLAP in PMNs in response to IH may participate in early vascular remodeling in OSA patients, suggesting FLAP as a potential therapeutic target for the cardiovascular morbidity associated with OSA.

Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients.The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference.Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist circumference and mean nocturnal SpO2 were inversely correlated (r = -0.43, p = 0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO2, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO2 and not waist circumference was associated with insulin-resistance.Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia.

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.

Sleep-related breathing disturbances are exacerbated at altitude in patients with Obstructive Sleep Apnea (OSA). The objective of this case report was to determine if a portable auto-CPAP device effectively treated sleep apnea across different altitudes. We report the severity of sleep apnea from 60 to 12,000 feet high in a man with severe OSA (Apnea Hypopnea Index at diagnosis = 60 events/hour) during the 2017 Dakar rally over the Andes mountains. The man was equipped with a lightweight portable auto-CPAP device with a narrow window [6-8 cmH2O]. Pressures delivered and corresponding residual events were assessed at different altitudes. The 95th percentile pressure reached the maximal set pressure at the highest altitudes, and residual AHI increased from 5 events/hour to 45 events/hour at the highest altitudes. Potential mechanisms behind the development of central apnea, and optimal clinical management at altitude are discussed in the light of the findings.

Introduction Obstructive sleep apnoea syndrome (OSAS) is one of the most common chronic diseases. It may be associated with symptoms of excessive daytime sleepiness and neurocognitive and cardiovascular complications. First line therapy for OSAS involves home continuous positive airway pressure (CPAP), however, nearly half of patients do not adhere with this treatment over the long term. Cognitive-behavioural interventions that include health professionals and patient and public involvement are increasingly advocated in the fields of education and research. We hypothesise that a peer-driven intervention could help patients with OSAS to resume CPAP use after discontinuation.Methods and analysis We have designed a prospective, multicentre randomised, controlled trial that will be coconducted by health professionals, a home provider of CPAP and patients as experts or peers or participants. The primary aim is to evaluate the impact of a 6-month, peer-driven intervention to promote the resumption of CPAP after discontinuation. We anticipate that 20% of patients in the intervention group will reuse CPAP as compared with 6% in control group, thus, 104 patients must be included in each group. The secondary aims are (1) to evaluate the impact of the peer-driven intervention on adherence to CPAP compared with the control group (mean adherence and percentage of nights with at least 4 hours’ use/night for 70% of nights); (2) to determine factors associated with resumption of CPAP; (3) to assess patient satisfaction with the peer-driven intervention at 6 months; (4) to evaluate the feasibility and the execution of the peer-driven intervention and peer satisfaction. Adult outpatients with an established diagnosis of severe OSA (Apnoea-Hypopnoea Index >30 events/hour) that have stopped using CPAP within 4–12 months after initiation will be recruited. The peers who will perform the intervention will be patients with OSAS treated with CPAP with good adherence (at least 4 hours/night, 70% of nights) and trained in motivational enhancement and cognitive-behavioural therapies. Trained peers will conduct three interviews within 6 months with participants.Ethics and dissemination Ethical approval has been obtained from the French Regional Ethics Committee CPP Ouest II-Angers, (IRB 21.02.25.68606 (2021/2025)). All participants will sign written informed consent. The results will be presented at conferences and published in peer-reviewed journals as well as public media.Trial registration number NCT04538274

Introduction To date, continuous positive airway pressure (CPAP) remains the cornerstone of obstructive sleep apnoea treatment. CPAP data describing residual sleep-disordered breathing events (ie, the CPAP-measured apnoea–hypopnoea indices (AHI-CPAPflow)) is difficult to interpret because it is an entirely different metric than the polysomnography (PSG) measured AHI gold standard (AHI-PSGgold). Moreover, manufacturer definitions for apnoea and hypopnoea are not only different from those recommended for PSG scoring, but also different between manufacturers. In the context of CPAP initiation and widespread telemedicine at home to facilitate sleep apnoea care, there is a need for concrete evidence that AHI-CPAPflow can be used as a surrogate for AHI-PSGgold.Methods and analysis No published systematic review and meta-analysis (SRMA) has compared the accuracy of AHI-CPAPflow against AHI-PSGgold and the primary objective of this study is therefore to do so using published data. The secondary objectives are to similarly evaluate other sleep disordered breathing indices and to perform subgroup analyses focusing on the inclusion/exclusion of central apnoea patients, body mass index levels, CPAP device brands, pressure titration modes, use of a predetermined and fixed pressure level or not, and the impact of a 4% PSG desaturation criteria versus 3% PSG on accuracy. The Preferred Reporting Items for SRMA protocols statement guided study design. Randomised controlled trials and observational studies of adult patients (≥18 years old) treated by a CPAP device will be included. The CPAP intervention and PSG comparator must be performed synchronously. PSGs must be scored manually and follow the American Academy of Sleep Medicine guidelines (2007 AASM criteria or more recent). To assess the risk of bias in each study, the Quality Assessment of Diagnostic Accuracy Studies 2 tool will be used.Ethics and dissemination This protocol received ethics committee approval on 16 July 2020 (IRB_MTP_2020_07_2020000404) and results will be disseminated via peer-reviewed publications.PROSPERO/Trial registration numbers CRD42020159914/NCT04526366; Pre-results

Background: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). Patients and Methods: We measured the silent period (SP) induced by transcranial magnetic stimulation in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could modify it. Results: An increase in the duration of the SP was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the duration did not differ significantly from that of normal subjects. The results of our study show a fragmentation and an enlargement of the SP in the presence of multiple late excitatory potentials (LEPs) in early untreated AD patients. These LEPs were also modulated by donepezil. Conclusions: The results suggest an early functional impairment of cholinergic neurotransmission in AD. The disturbance in acetylcholine output in early AD leads to a decrease in excitability of the motor system.

BACKGROUND: Patients with narcolepsy-cataplexy (NC) mostly exhibit undetectable hypocretin levels. Hypocretin system is one of the key players in the complex interaction between sleep and the cardiovascular system. We tested the hypothesis that hypocretin deficiency affects cardiovascular risk factors by measuring nighttime and daytime ambulatory blood pressure (BP) and the night-to-day BP ratio as well as endothelial dysfunction by the digital pulse amplitude response in drug-free patients with NC compared to controls. METHODOLOGY: Sleep, clinical and biological cardiovascular risk factors, fingertip peripheral arterial tonometry, and 24-hour ambulatory BP monitoring were recorded in 50 drug-free patients with NC and 42 healthy control subjects, except for BP monitoring available in all controls but in 36 patients with NC. PRINCIPAL FINDINGS: More patients than controls were smokers, obese and with dyslipidemia. One-third of patients with NC were "non-dippers" (defined as