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Summary: Background: Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA. Methods: In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640. Findings: Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150 mg; effect size [ES] = 0.66 [95% CI: 0.36, 0.96]), pitolisant (20 mg; ES = 0.66 [95% CI: 0.44, 0.88]), and modafinil (200 mg; ES = 0.54: [95% CI: 0.33, 0.74]); 400 mg; ES = 0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200 mg, modafinil 400 mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400 mg and modafinil 200 mg for benefit-risk ratio. Interpretation: Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities. Funding: Bioprojet.

Abstract Monitoring unintentional air leaks in continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) is essential for therapy success. While leaks are often attributed to improperly sealed masks, mouth openings may also cause them, requiring interventions. Recent studies demonstrated distinctive mandibular jaw movement (MJM) signal patterns during sleep related to respiratory events and sleep stages. Analysing MJM during CPAP treatment reveals air leak peaks coinciding with maximal MJM amplitude during obstructive events, and air leak decreases corresponding to arousals. Examining leaks with MJM offers valuable insights into their origins and might open new avenues for CPAP management.

Abstract Background Obstructive sleep apnea (OSA) is a multisystemic chronic disease with disabling symptoms, cardiometabolic comorbidities and reduction in physical activity. Continuous positive airway pressure (CPAP) is the standard treatment for OSA. Only a few studies have characterized trajectories of sleep parameters upon initiation of CPAP and these are limited to one or two nights of polysomnographic recording in a sleep laboratory. This is due to the cost of carrying out these studies and poor tolerance by patients of multiple nights of polysomnographic recordings. No study has characterized sleep over multiple nights before and after CPAP initiation, assessing the multidimensional efficacy of CPAP on patient reported outcomes, objective and subjective sleep quality, oximetry, glucose control and physical activity. New digital technologies enable overnight sleep studies over several nights in the patient’s home, with a reliability of sleep characterization equivalent to polysomnographic recording. The primary aim of this study is to investigate objective slow wave sleep (SWS or N3) quality before CPAP and during the first month of the treatment. Secondary objectives are to assess changes in the following parameters before CPAP and during the first month of the treatment: other objective sleep parameters and sleep stages evolution (W, N1, N2 and REM), nocturnal oxygen desaturations, 24-h blood glucose profile, daily physical activity (the daily steps count), and patient reported outcomes. Methods Seventy patients prescribed CPAP for OSA will be recruited at Grenoble Alpes University Hospital (France) and monitored for 5 weeks using validated innovative wearable connected devices (the Dreem 3 headband, a pedometer, an oximeter, and a continuous glucose sensor) enabling them to track their own sleep and physiological parameters at home before and after CPAP initiation. Discussion By pooling data from the CPAP telemonitoring and other connected devices we should be able to follow the multidimensional trajectories of patients after the initiation of CPAP. This will enable us to determine whether objective changes in sleep parameters in the first few weeks of CPAP treatment are associated with improvements in daytime sleepiness, quality of life, treatment adherence, glucose control and physical activity. The data will provide integrated markers of treatment efficacy and will allow adapted personalized management of OSA in the short and long-term. Trial registration Clinicaltrials (NCT05197855).

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.

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

Summary: 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.

Background Even in countries having nearly universal healthcare provision some individuals forgo or postpone healthcare to which they are entitled. Socioeconomic and geographic inequalities can make access to healthcare difficult for some people, such that they fail to seek it, particularly if they deem the type of care as non-essential. The need to pay at the point of care, the complexity and cost of top-up health insurance, and delays or only partial reimbursement can discourage take-up of care. This can affect the general health of the population.Methods To estimate the rate of forgoing healthcare in the general French population, between 2015 and 2018 we conducted a nationwide cross-sectional survey of individuals visiting French primary healthcare insurance agencies (Caisse Primaire d’Assurance Maladie, CPAM). We asked whether the person had foregone or postponed healthcare in the last 12 months, if so the types of healthcare forgone or put-off, and reasons. Individuals were stratified by the type of complementary (top-up) health insurance they had.Results Out of 164 092 individuals who responded, 158 032 were included in the analysis. Respondents had either private complementary (top-up) insurance (60%), top-up insurance subsidized by the state (29%), or no top-up health insurance (11%). Forgoers (n=40 115; 25.4%) most often lived alone (with or without children), were unemployed, and/ or female. Dental care (54%) and consultations with ophthalmologists, gynaecologists and dermatologists (41%) were most commonly forgone. The reasons were: inability to advance payment and/or to pay the uninsured part (69%), time constraints and difficulty in obtaining appointments (26%).Conclusion We present a snapshot of forgoing healthcare in a developed country, highlighting the need for continuing review by policy-makers of payment regimens, insurance cover, availability and accessibility. While initiatives have already emerged from the results, further reforms are needed to address the problem of people forgoing preventative or perceived non-urgent healthcare, particularly for disadvantaged subgroups.

Social media has become one of the major data sources for social studies through users’ expressions, such as significant moments in their daily life or their feelings and perceptions toward specific discussion topics. In health care, social media is thoroughly used to study people’s discourse on ailments and derive insights into the impact of ailments on patients’ quality of life. Recently, there has been an increasing interest in applying machine learning algorithms to enhance the prediction of ailments through users’ social media data. In this study, nearly 800 million posts were retrieved from Twitter through preprocessing and running the time-aware ailment topic aspect model (T-ATAM) to predict diseases, symptoms, and remedies for two chronic conditions, namely sleep apnea and chronic liver diseases. The study was conducted on English tweets emitted during 2018, most of which were from European countries and the United States. The data were processed using T-ATAM by regions, timestamps, and treatment, namely continuous positive airway pressure (CPAP), to see the differences in the distributions of top diseases along with the top symptoms and remedies in different regions; timestamps; as well as before, during, and after CPAP was introduced. Based on approximately 331,000 tweets related to liver diseases and 1 million tweets on sleep apnea, various visualizations of statistics are displayed, including world maps, word clouds, and histograms. Results of this study indicate that depression and drinking are the leading symptoms of liver diseases; meanwhile, lack of nighttime sleep and overworking are considered the main factors of sleep apnea.

Study objectivesThe prospective Self-Efficacy Measure for Sleep Apnea study (SEMSAS) is investigating thresholds for health literacy, self-efficacy and precariousness at obstructive sleep apnea (OSA) diagnosis to predict CPAP adherence. This paper describes the study protocol and presents baseline data from the ongoing study.MethodsEligible individuals had confirmed OSA and were referred to a homecare provider for continuous positive airway pressure (CPAP) therapy initiation. Data on patient characteristics and comorbidities were collected, along with baseline evaluations of self-efficacy [15-item Self-Efficacy Measure for Sleep Apnea tool (SEMSA-15)], precariousness [Deprivation in Primary Care Questionnaire (DipCareQ)], and health literacy (Health Literacy Questionnaire). CPAP adherence over 12 months of follow-up will be determined using remote monitoring of CPAP device data. The primary objective is to define an optimal SEMSA-15 score threshold to predict CPAP adherence at 3- and 12-month follow-up.ResultsEnrollment of 302 participants (71% male, median age 55 years, median body mass index 31.6 kg/m2) is complete. Low self-efficacy (SEMSA-15 score ≤ 2.78) was found in 93/302 participants (31%), and 38 (12.6%) reported precariousness (DipCareQ score > 1); precariousness did not differ significantly between individuals with a SEMSA-15 score ≤ 2.78 versus >2.78. Health literacy was generally good, but was significantly lower in individuals with versus without precariousness, and with low versus high self-efficacy.ConclusionSEMSAS is the first study using multidimensional baseline assessment of self-efficacy, health literacy and precariousness, plus other characteristics, to determine future adherence to CPAP, including CPAP adherence trajectories. Collection of follow-up data is underway.

Background Obstructive sleep apnea (OSA) is common in heart failure with preserved ejection fraction (HFpEF). However, current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in HFpEF. This study assessed the association between adherence to PAP therapy and health care resource use in patients with OSA and HFpEF. Methods and Results Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to determine associations between PAP adherence and a composite outcome including hospitalizations and emergency room visits. One‐year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 4237 patients (54.0% female, mean age 64.1 years); 40% were considered adherent to PAP therapy (30% intermediate adherent, 30% nonadherent). In the matched cohort, PAP‐adherent patients had fewer health care resource use visits than nonadherent patients, a 57% decrease in hospitalizations, and a 36% decrease in emergency room visits versus the year before PAP initiation. Total health care costs were lower in adherent patients than nonadherent patients ($12 732 versus $15 610, P

Abstract 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

Background/Objectives: Considering the potential greater cardiocirculatory effects of high intensity interval training (HIIT), we hypothesized that a 2-month supervised high volume short interval HIIT would induce greater improvements in CRF and cardiometabolic risk and increase long-term maintenance to physical activity compared to isocaloric moderate intensity continuous training (MICT) in overweight/obesity. Methods: Sixty (19 females) subjects with overweight/obesity were randomized to three training programs (3 times/week for 2 months): MICT (45 min, 50% peak power output-PPO), HIIT (22 × 1-min cycling at 100% PPO/1-min passive recovery) and HIIT-RM (RM: recovery modulation, i.e. subjects adjusted passive recovery duration between 30s and 2 min). After the intervention, participants no longer benefited from supervised physical activity and were instructed to maintain the same exercise modalities on their own. We assessed anthropometrics, body composition, CRF, fat oxidation, lipid profile, glycemic balance, low-grade inflammation, vascular function, spontaneous physical activity and motivation for eating at three time points: baseline (T0), 4 days after the end of the 2-month supervised training program (T2) and 4 months after the end of the training program (T6). Results: HIIT/HIIT-RM induced greater improvement in VO2peak (between +14% and +17%), power output at ventilatory thresholds and at maximal fat oxidation rate (+25%) and waist circumference (−1.53 cm) compared to MICT and tended to decrease insulin resistance. During the four-month follow-up period during which exercise in autonomy was prescribed, HIIT induced a greater preservation of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL. Conclusion: We have shown greater short-term benefits induced by a high volume short interval (1 min) HIIT on cardiorespiratory fitness and cardiometabolic risk over an isocaloric moderate intensity continuous exercise in persons with overweight/obesity. We also showed greater long-term effects (i.e. after 4 months) of this exercise modality on the maintenance of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL.

Background Obstructive sleep apnea (OSA) is a common comorbidity in patients with heart failure, although current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in patients with heart failure. This study assessed the impact of adherence to PAP therapy on health care resource utilization in patients with OSA and heart failure with reduced ejection fraction. Methods and Results Administrative insurance claims data linked with objective PAP therapy use data from patients with OSA and heart failure with reduced ejection fraction were used to determine associations between PAP adherence and a composite outcome of hospitalizations and emergency room visits. One‐year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 3182 patients (69.9% male, mean age 59.7 years); 39% were considered adherent to PAP therapy (29% intermediate adherent, 31% nonadherent). One year after PAP initiation, adherent patients had fewer composite visits than matched nonadherent patients, driven by a 24% reduction in emergency room visits for adherent patients. Composite visit costs were lower in adherent versus nonadherent patients ($3500 versus $5879, P=0.031), although total health care costs were not statistically different ($13 028 versus $14 729, P=0.889). Conclusions PAP therapy adherence in patients with OSA with heart failure with reduced ejection fraction was associated with a reduction in health care resource utilization. This suggests that greater emphasis should be placed on diagnosing and effectively treating OSA with PAP in patients with heart failure with reduced ejection fraction.

Background Obstructive sleep apnea syndrome is a common sleep-breathing disorder associated with adverse health outcomes including excessive daytime sleepiness, impaired quality of life and is well-established as a cardiovascular risk factor. Continuous positive airway pressure is the reference treatment, but its cardiovascular and metabolic benefits are still debated. Combined interventions aiming at improving patient's lifestyle behaviours are recommended in guidelines management of obstructive sleep apnea syndrome but adherence decreases over time and access to rehabilitation programmes is limited. Telerehabilitation is a promising approach to address these issues, but data are scarce on obstructive sleep apnea syndrome. Methods The aim of this study is to assess the potential benefits of a telerehabilitation programme implemented at continuous positive airway pressure initiation, compared to continuous positive airway pressure alone and usual care, on symptoms and cardiometabolic risk factors of obstructive sleep apnea syndrome. This study is a 6-months multicentre randomized, parallel controlled trial during which 180 obese patients with severe obstructive sleep apnea syndrome will be included. We will use a sequential hierarchical criterion for major endpoints including sleepiness, quality of life, nocturnal systolic blood pressure and inflammation biological parameters. Discussion m-Rehab obstructive sleep apnea syndrome is the first multicentre randomized controlled trial to examine the effectiveness of a telerehabilitation lifestyle programme in obstructive sleep apnea syndrome. We hypothesize that a telerehabilitation lifestyle intervention associated with continuous positive airway pressure for 6 months will be more efficient than continuous positive airway pressure alone on symptoms, quality of life and cardiometabolic risk profile. Main secondary outcomes include continuous positive airway pressure adherence, usability and satisfaction with the telerehabilitation platform and medico-economic evaluation. Trial registration Clinicaltrials.gov Identifier: NCT05049928. Registration data: 20 September 2021

Background Although adaptive servo-ventilation (ASV) effectively supresses central sleep apnoea (CSA), little is known about real-world indications of ASV therapy and its effects on quality of life (QoL). Methods This report details the design, baseline characteristics, indications for ASV and symptom burden in patients enrolled in the Registry on the Treatment of Central and Complex Sleep-Disordered Breathing with Adaptive Servo-Ventilation (READ-ASV). This multicentre, European, non-interventional trial enrolled participants prescribed ASV in clinical practice between September 2017 and March 2021. An expert review board assigned participants to ASV indications using a guideline-based semi-automated algorithm. The primary end-point was change in disease-specific QoL based on the Functional Outcomes of Sleep Questionnaire (FOSQ) from baseline to 12-month follow-up. Results The registry population includes 801 participants (age 67±12 years, 14% female). Indications for ASV were treatment-emergent or persistent CSA (56%), CSA in cardiovascular disease (31%), unclassified CSA (2%), coexisting obstructive sleep apnoea and CSA (4%), obstructive sleep apnoea (3%), CSA in stroke (2%) and opioid-induced CSA (1%). Baseline mean apnoea­–hypopnoea index was 48±23 events·h−1 (≥30 events·h−1 in 78%), FOSQ score was 16.7±3.0 (10 in 34%); 62% of patients were symptomatic (FOSQ score 10). Conclusion The most common indications for ASV were treatment-emergent or persistent CSA or CSA in cardiovascular disease (excluding systolic heart failure). Patients using ASV in clinical practice had severe sleep-disordered breathing and were often symptomatic. One-year follow-up will provide data on the effects of ASV on QoL, respiratory parameters and clinical outcomes in these patients.

Abstract MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® is a Good Practice of DG Santé on digitally‐enabled, patient‐centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co‐operation and Development). MASK‐air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK‐air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as‐needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom‐medication score (ARIA‐EAACI‐CSMS) has been validated for clinical practice and trials. The implications of the novel MASK‐air® results should lead to change management in rhinitis and asthma.

Abstract To determine the effect of continuous positive airway pressure (CPAP), the gold standard treatment for obstructive sleep apnea syndrome (OSAS), on gait control in severe OSAS patients. We conducted a randomized, double-blind, parallel-group, sham-controlled monocentric study in Grenoble Alpes University Hospital, France. Gait parameters were recorded under single and dual-task conditions using a visuo-verbal cognitive task (Stroop test), before and after the 8-week intervention period. Stride-time variability, a marker of gait control, was the primary study endpoint. Changes in the determinants of gait control were the main secondary outcomes. ClinicalTrials.gov Identifier: (NCT02345694). 24 patients [median (Q1; Q3)]: age: 59.5 (46.3; 66.8) years, 87.5% male, body mass index: 28.2 (24.7; 29.8) kg. m−2, apnea–hypopnea index: 51.6 (35.0; 61.4) events/h were randomized to be treated by effective CPAP (n = 12) or by sham-CPAP (n = 12). A complete case analysis was performed, using a mixed linear regression model. CPAP elicited no significant improvement in stride-time variability compared to sham-CPAP. No difference was found regarding the determinants of gait control. This study is the first RCT to investigate the effects of CPAP on gait control. Eight weeks of CPAP treatment did not improve gait control in severe non-obese OSAS patients. These results substantiate the complex OSAS-neurocognitive function relationship.

Abstract Background Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. Methods eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI

Abstract In December 2019, a conference entitled “Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health” was held in Helsinki. It was co-organized by the Finnish Institute for Health and Welfare, the Finnish Environment Institute and the European Commission, under the auspices of Finland’s Presidency of the EU. As a side event, a symposium organized as the final POLLAR (Impact of air POLLution on Asthma and Rhinitis) meeting explored the digital transformation of health and care to sustain planetary health in airway diseases. The Finnish Allergy Programme collaborates with MASK (Mobile Airways Sentinel NetworK) and can be considered as a proof-of-concept to impact Planetary Health. The Good Practice of DG Santé (The Directorate-General for Health and Food Safety) on digitally-enabled, patient-centred care pathways is in line with the objectives of the Finnish Allergy Programme. The ARIACARE-Digital network has been deployed in 25 countries. It represents an example of the digital cross-border exchange of real-world data and experience with the aim to improve patient care. The integration of information technology tools for climate, weather, air pollution and aerobiology in mobile Health applications will enable the development of an alert system. Citizens will thus be informed about personal environmental threats, which may also be linked to indicators of Planetary Health and sustainability. The digital transformation of the public health policy was also proposed, following the experience of the Agency for Health Quality and Assessment of Catalonia (AQuAS).

CT registration-derived indices provide data on regional lung functional changes in COPD. However, because unlike spirometry which involves dynamic maximal breathing maneuvers, CT-based functional parameters are assessed between two static breath-holds, it is not clear how regional and global lung function parameters relate to each other. We assessed the relationship between CT-density change (dHU), specific volume change (dsV), and regional lung tissue deformation (J) with global spirometric and plethysmographic parameters, gas exchange, exercise capacity, dyspnoea, and disease stage in a prospective cohort study in 102 COPD patients. There were positive correlations of dHU, dsV, and J with spirometric variables, DLCO and gas exchange, 6-min walking distance, and negative correlations with plethysmographic lung volumes and indices of trapping and lung distension as well as GOLD stage. Stepwise regression identified FEV1/FVC (standardized β = 0.429, p < 0.0001), RV/TLC (β = −0.37, p < 0.0001), and BMI (β = 0.27, p=

Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnoea (OSA), defined as the inability to stay awake during the day. Its clinical descriptors remain elusive, and the pathogenesis is complex, with disorders such as insufficient sleep and depression commonly associated. Subjective EDS can be evaluated using the Epworth Sleepiness Scale, in which the patient reports the probability of dozing in certain situations; however, its reliability has been challenged. Objective tests such as the multiple sleep latency test or the maintenance of wakefulness test are not commonly used in patients with OSA, since they require nocturnal polysomnography, daytime testing and are expensive. Drugs for EDS are available in the United States but were discontinued in Europe some time ago. For European respiratory physicians, treatment of EDS with medication is new and they may lack experience in pharmacological treatment of EDS, while novel wake-promoting drugs have been recently developed and approved for clinical use in OSA patients in the USA and Europe. This review will discuss 1) the potential prognostic significance of EDS in OSA patients at diagnosis, 2) the prevalence and predictors of residual EDS in treated OSA patients, and 3) the evolution of therapy for EDS specifically for Europe.

Aim Intermittent hypoxia (IH) is considered to be a major contributor to obstructive sleep apnoea-related cardiovascular consequences. The present meta-analysis aimed to assess the effects of IH on cardiac remodelling, function and infarct size after myocardial ischaemia across different rodent species and IH severities. Methods and results Relevant articles from PubMed, Embase and Web of Science were screened. We performed a random effect meta-analysis to assess the effect of IH on myocardium in rodents by using standardised mean difference (SMD). Studies using rodents exposed to IH and outcomes related to cardiac remodelling, contractile function and response to myocardial ischaemia–reperfusion were included. 5217 articles were screened and 92 were included, demonstrating that IH exposure induced cardiac remodelling, characterised by cardiomyocyte hypertrophy (cross-sectional area: SMD=2.90, CI (0.82–4.98), I2=94.2%), left ventricular (LV) dilation (LV diameter: SMD=0.64, CI (0.18–1.10), I2=88.04%), interstitial fibrosis (SMD=5.37, CI (3.22–7.53), I2=94.8) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling: SMD=6.70, CI (2.96–10.44), I2=95.9). These structural changes were accompanied by a decrease in LV ejection fraction (SMD=−1.82, CI (−2.52–−1.12), I2=94.22%). Importantly, most of the utilised IH protocols mimicked extremely severe hypoxic disease. Concerning infarct size, meta-regression analyses highlighted an ambivalent role of IH, depending on its severity. Indeed, IH exposure with inspiratory oxygen fraction (FIO2)

BackgroundThe capacity to diagnose obstructive sleep apnoea (OSA) must be expanded to meet an estimated disease burden of nearly one billion people worldwide. Validated alternatives to the gold standard polysomnography (PSG) will improve access to testing and treatment. This study aimed to evaluate the diagnosis of OSA, using measurements of mandibular movement (MM) combined with automated machine learning analysis, compared to in-home PSG.Methods40 suspected OSA patients underwent single overnight in-home sleep testing with PSG (Nox A1, ResMed, Australia) and simultaneous MM monitoring (Sunrise, Sunrise SA, Belgium). PSG recordings were manually analysed by two expert sleep centres (Grenoble and London); MM analysis was automated. The Obstructive Respiratory Disturbance Index calculated from the MM monitoring (MM-ORDI) was compared to the PSG (PSG-ORDI) using intraclass correlation coefficient and Bland-Altman analysis. Receiver operating characteristic curves (ROC) were constructed to optimise the diagnostic performance of the MM monitor at different PSG-ORDI thresholds (5, 15, and 30 events/hour).Results31 patients were included in the analysis (58% men; mean (SD) age: 48 (15) years; BMI: 30.4 (7.6) kg/m2). Good agreement was observed between MM-ORDI and PSG-ORDI (median bias 0.00; 95% CI −23.25 to + 9.73 events/hour). However, for 15 patients with no or mild OSA, MM monitoring overestimated disease severity (PSG-ORDI < 5: MM-ORDI mean overestimation + 5.58 (95% CI + 2.03 to + 7.46) events/hour; PSG-ORDI > 5–15: MM-ORDI overestimation + 3.70 (95% CI −0.53 to + 18.32) events/hour). In 16 patients with moderate-severe OSA (n = 9 with PSG-ORDI 15–30 events/h and n = 7 with a PSG-ORD > 30 events/h), there was an underestimation (PSG-ORDI > 15: MM-ORDI underestimation −8.70 (95% CI −28.46 to + 4.01) events/hour). ROC optimal cut-off values for PSG-ORDI thresholds of 5, 15, 30 events/hour were: 9.53, 12.65 and 24.81 events/hour, respectively. These cut-off values yielded a sensitivity of 88, 100 and 79%, and a specificity of 100, 75, 96%. The positive predictive values were: 100, 80, 95% and the negative predictive values 89, 100, 82%, respectively.ConclusionThe diagnosis of OSA, using MM with machine learning analysis, is comparable to manually scored in-home PSG. Therefore, this novel monitor could be a convenient diagnostic tool that can easily be used in the patients’ own home.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT04262557

Sleep Apnea Syndrome (SAS) is one of the most common chronic diseases, affecting nearly one billion people worldwide. The repetitive occurrence of abnormal respiratory events generates cyclical desaturation-reoxygenation sequences known as intermittent hypoxia (IH). Among SAS metabolic sequelae, it has been established by experimental and clinical studies that SAS is an independent risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). The principal goal of this study was to decrypt the molecular mechanisms at the onset of IH-mediated liver injury. To address this question, we used a unique mouse model of SAS exposed to IH, employed unbiased high-throughput transcriptomics and computed network analysis. This led us to examine hepatic mitochondrial ultrastructure and function using electron microscopy, high-resolution respirometry and flux analysis in isolated mitochondria. Transcriptomics and network analysis revealed that IH reprograms Nuclear Respiratory Factor- (NRF-) dependent gene expression and showed that mitochondria play a central role. We thus demonstrated that IH boosts the oxidative capacity from fatty acids of liver mitochondria. Lastly, the unbalance between oxidative stress and antioxidant defense is tied to an increase in hepatic ROS production and DNA damage during IH. We provide a comprehensive analysis of liver metabolism during IH and reveal the key role of the mitochondria at the origin of development of liver disease. These findings contribute to the understanding of the mechanisms underlying NAFLD development and progression during SAS and provide a rationale for novel therapeutic targets and biomarker discovery.

The primary goal of patient and public involvement (PPI) in healthcare is to improve individual and population health outcomes. This study reports on the successful training of patients to be involved in patient education as peers and clinical research at Grenoble Patients’ School (GPS). GPS was founded by patients as an independent association to train patients to the above objectives tasks. The training team was multi-professional and included expert PPI who were part of the professional team. Medical faculty members and 45 patients, 59% females, 52 ± 6.4 years old, trained between 2016 and 2017, showed high satisfaction at the end of the training courses. Almost all the trained patients were involved as peer educators and 4 were involved in clinical research projects at different stages under the guidance of medical teams. Patient involvement at GPS provided strong benefits to trainees and had some impact on education and obtaining research grants. The outcome of this patient training program resulted in the creation of a Patients’ Department within the Medical and Pharmacy Schools at the Université Grenoble Alpes in 2020, https://medecine.univ-grenoble-alpes.fr/departements/departement-universitaire-des-patients/ .

Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects. Therefore, we tested the impact of citrulline supplementation on IH-induced increase in BP and infarct size. Four groups of rats exposed to normoxia (N) or IH [14 days (d), 8 h/day, 30 s-O2 21%/30 s-O2 5%] and were supplemented or not with citrulline (1 g·kg−1·d−1). After 14 d, BP was measured, and hearts were submitted to global ischemia-reperfusion to measure infarct size. Histological and biochemical analyses were conducted on hearts and aorta to assess oxidative stress. Citrulline significantly reduced BP (–9.92%) and infarct size (–18.22%) under IH only. In the aorta, citrulline supplementation significantly decreased superoxide anion and nitrotyrosine levels under IH and abolished the IH-induced decrease in nitrite. Citrulline supplementation significantly decreased myocardial superoxide anion levels and xanthine oxidase enzyme activity under IH. Citrulline shows a cardioprotective capacity by limiting IH-induced pro-oxidant activity. Our results suggest that citrulline might represent a new pharmacological strategy in OSA patients with high cardiovascular risk.

Background: The effectiveness of positive airway pressure therapies (PAP) is contingent on treatment adherence. We hypothesized that forgoing healthcare may be a determinant of adherence to PAP therapy.Research Question: The objectives were: (i) to assess the impact of forgoing healthcare on adherence to PAP in patients with Chronic Respiratory Failure (CRF) and patients with Obstructive Sleep Apnea Syndrome (OSAS); (ii) to compare forgoing healthcare patterns in these two chronic conditions.Study design and methods: Prospective cohort of patients with OSAS or CRF, treated with PAP therapies at home for at least 12 months. At inclusion, patients were asked to fill-in questionnaires investigating (i) healthcare forgone, (ii) deprivation (EPICES score), (iii) socio-professional and familial status. Characteristics at inclusion were extracted from medical records. PAP adherence was collected from the device's built-in time counters. Multivariable logistic regression models were used to assess the associations between healthcare forgone and the risk of being non-adherent to CPAP treatment.Results: Among 298 patients included (294 analyzed); 33.7% reported forgoing healthcare. Deprivation (EPICES score > 30) was independently associated with the risk of non-adherence (OR = 3.57, 95%CI [1.12; 11.37]). Forgoing healthcare had an additional effect on the risk of non-adherence among deprived patients (OR = 7.74, 95%CI [2.59; 23.12]). OSAS patients mainly forwent healthcare for financial reasons (49% vs. 12.5% in CRF group), whereas CRF patients forwent healthcare due to lack of mobility (25%, vs. 5.9 % in OSAS group).Interpretation: Forgoing healthcare contributes to the risk of PAP non-adherence particularly among deprived patients. Measures tailored to tackle forgoing healthcare may improve the overall quality of care in PAP therapies.Clinical Trial Registration: The study protocol was registered in ClinicalTrials.gov, identifier: NCT03591250.

BackgroundNasal high flow (NHF) is a non-invasive breathing therapy that is based on the delivery via a large-caliber nasal cannula of heated and humidified air at flow rates that exceed peak inspiratory flow. It is thought that positive airway pressure generated by NHF can help reduce gas trapping and improve regional lung ventilation. There are no data to confirm this hypothesis at flow rates applicable in stable chronic obstructive pulmonary disease (COPD) patients.MethodsIn this study, we used non-rigid registration of computed tomography (CT) images acquired at maximal expiration and inspiration to compute regional lung attenuation changes (ΔHU), and lung displacement (LD), indices of regional lung ventilation. Parametric response maps (Galban et al., 2012) were also computed in each experimental condition. Eight COPD patients were assessed at baseline (BL) and after 5 min of NHF and expiratory resistive loading (ERL).ResultsΔHU was: BL (median, IQR): 85 (67.2, 102.8); NHF: 90.7 (57.4, 97.6); ERL: 74.6 (46.4, 89.6) HU (p = 0.531); and LD: 27.8 (22.3, 39.3); 17.6 (15.4, 27.9); and 20.4 (16.6, 23.6) mm (p = 0.120) in the 3 conditions, respectively. No significant difference in trapping was observed. Respiratory rate significantly decreased with both treatments [BL: 17.3 (16.4, 18.9); NHF: 13.7; ERL: 11.4 (9.6, 13.2) bpm; and p < 0.001].ConclusionNeither NHF at 25 L/min nor ERL significantly improved the regional lung ventilation of stable COPD patients with gas trapping, based on functional lung CT imaging. Further study including more subjects is needed to assess the potential effect of NHF on regional lung function at higher flow rates.Clinical Trial Registrationwww.clinicaltrials.gov/under, identifier NCT03821311.

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.