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

Introduction Unhealthy lifestyles are major factors contributing to chronic conditions. By proposing suitable menu designs and easy recipes, Open Food Service internet app with connected food processors will bring easy solutions to cook and progressively develop healthy dietary habits at home. A randomized controlled trial will test in healthy subjects the ability of connected food processors to modify dietary habits and to improve metabolic homeostasis, assessed with a systems health monitoring, all at home. Methodology and analysis This is a prospective, randomized, single blind and 12 month controlled trial in Grenoble and Aberystwyth. Double consent using Zelen method of randomization is used. Healthy volunteers, 25–50 years old, living in a family, be the main person who prepares meals and be able to use the personal health monitoring devices are recruited, 100 in Grenoble and 60 in Aberystwyth. The principal objective is to evaluate the ability of connected cook devices to modify dietary habits measured by a clinically significant increase of 1 quintile in Alternate Healthy Eating Index-2010. Secondary objectives are a) to demonstrate feasibility to collect data and specimen at home over one year; b) to compare changes at one year in quality of life, body composition, physical activities, sleep duration, gut microbiote; c) to describe urinary metabolomics patterns that are able to report recent dietary habits. Elementary descriptive analysis and integration of all data sets vertically and longitudinally and comparisons between groups will be carried out. The two two studies are conducted separately and analysed in meta-analysis.

International audience; No abstract available

International audience; No abstract available

Background Diuretics have been reported as effective for reducing OSA severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending on the OSA clinical phenotype and comorbidities. To test this hypothesis, we conducted a propensity score-matched cohort analysis of data from the French national sleep apnea registry "Observatoire Sommeil de la Federation de Pneumologie." Research Question Which phenotypic subtypes of OSA may benefit from diuretics? Study Design and Methods A propensity score analysis was used to determine the impact of diuretics on OSA severity. Matching (ratio 1:4) was performed by using a 0.1 collider for the propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI) > 30 events/h, and the usefulness of diuretics was assessed by using a logistic regression model. Results The 69,564 OSA patients studied in the OSFP prospective observational cohort had a median age of 56.9 years (interquartile range: 47.4; 65.6), 67% were men, and the median AHI was 28 (14; 43) events/h. Among them, 9,783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (P = .03) and in patients with hypertension (P Interpretation Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined therapies for hypertensive patients with OSA.

Objective Obstructive sleep apnea (OSA) syndrome is one of the most frequent chronic diseases in the general population. The nocturnal rostral fluid shift is accepted as a key mechanism in OSA pathogenesis in medical conditions associated with fluid overload. The main objective of this study was to assess the prevalence of OSA in patients with lymphedema. Methods A prospective study was conducted in patients with lymphedema hospitalized for complete decongestive therapy between December 2016 and November 2017. A nocturnal respiratory polygraphy, an Epworth sleepiness scale, and lymphedema volume measurements were performed on the first day of decongestive therapy. OSA was diagnosed in patients with an apnea-hypopnea index of five or more events per hour and patients who had been previously diagnosed with OSA and treated by continuous positive airway pressure were identified. Results Forty-three patients completed the study. The prevalence of OSA was 74% and was higher for patients with lymphedema of the lower limbs (85%) vs upper limbs (56%). OSA severity was correlated with a marker of lower limb lymphedema severity (P = .012). The body mass index was higher than in patients with OSA than patients without OSA (median, 31.0 kg/m2 [25th; 75th percentiles, 25.3; 37.0 kg/m2] vs median, 24.2 kg/m2 [25th; 75th percentiles, 22.7; 26.7 kg/m2]; P Conclusions Patients with lymphedema presenting for complete decongestive therapy present a high prevalence rate of OSA, particularly in those with lower limb lymphedema. OSA severity was correlated with a marker of lower limb lymphedema severity. These results suggest that overweight and obese patients with lymphedema should be screened systematically for OSA.

Connected health is a growing field and can be viewed from different perspectives, particularly in sleep apnea syndrome. The purpose of this review is to show how all these aspects of connected health are already used in the management of sleep apnea syndrome (SAS) and its comorbidities. First, it can give patients a better understanding and a better assessment of their health. It also facilitates their healthcare by allowing them a greater role in their care pathway. For healthcare providers, connected health tools make it possible to set up new procedures for diagnosing and monitoring ambulatory patients, and for the making of joint decisions by health professionals and patients. Finally, for researchers, e-health generates massive amounts of data, thus facilitating the acquisition of knowledge in real life situations and the development of new methodologies for clinical studies that are faster, less expensive and just as reliable. All these considerations are already applicable in the field of sleep apnea, both for proposed treatments and for comorbidities management and for the patient's involvement in his/her care pathway.

A particularly high burden of sleep apnoea is reported in patients treated with cardiac implants such as pacemakers and defibrillators. Sleep apnoea diagnosis remains a complex procedure mainly based on sleep and respiratory indices captured by polysomnography (PSG) or respiratory polygraphy (PG).We aimed to evaluate the performance of implantable cardiac devices for sleep apnoea diagnosis compared to reference methods.Systematic structured literature searches were performed in PubMed, Embase and. Cochrane Library was performed to identify relevant studies. Quantitative characteristics of the studies were summarized and a qualitative synthesis was performed by a randomized bivariate meta-analysis and completed by pre-specified sensitivity analyses for different implant types and brands.16 studies involving 999 patients met inclusion criteria and were included in the meta-analysis. The majority of patients were men, of mean age of 64 ± 4.6 years. Sensitivity of cardiac implants for sleep apnoea diagnosis ranged from 60 to 100%, specificity from 50 to 100% with a prevalence of sleep apnoea varying from 22 to 91%. For an apnoea-hypopnoea index threshold ≥30 events/h during polysomnography (corresponding to severe sleep apnoea), the overall performance of the implants was relevant with a sensitivity of 78% and a specificity of 79%. Subgroup analyses on implant type and brand provided no additional information owing to the small number of studies.The respiratory disturbance index provided by cardiac implants is clinically relevant and might improve access to sleep apnoea diagnosis in at-risk cardiovascular populations. PROSPERO Registration number: CRD42020181656.

International audience

Background The management of patients with high cardiovascular risk and OSA must target not only improving adherence to CPAP, but should also include strategies aimed at reducing BP and increasing physical activity. The study aims to evaluate the effectiveness of an integrated intervention using remote patient telemonitoring in reducing BP in high cardiovascular risk patients with OSA. Methods In a multicenter, open, randomized trial, patients with OSA were randomly assigned at CPAP initiation to usual care or multimodal telemonitoring for 6 months. Telemonitoring used electronic equipment collecting information about BP, symptoms, CPAP side effects, and physical activity with home care providers prespecified protocoled actions. The primary effectiveness outcome was assessed using home self-measured BP on 3 consecutive days. Secondary outcomes included CPAP compliance, symptoms, and physical activity. Results Of 306 patients with a median age of 61.3 years [interquartile range, 54.1; 66.1], who were predominantly men, 226 (74%) with a BMI of 32.0 [28.7; 35.6] kg/m2 and an apnea-hypopnea index of 46 [35; 61] events/h, 149 received usual care and 157 received telemonitoring. After 6 months of CPAP, home self-measured BP did not differ significantly between groups. In secondary analyses, there was no significant difference in steps per day, but a significant increase in CPAP adherence and an improvement in daytime sleepiness and quality of life in favor of the multimodal telemonitoring. Conclusions In OSA patients with high cardiovascular risk, multimodal telemonitoring was not superior to usual CPAP care for improving home BP; however, telemonitoring improved adherence and patient-centered outcomes.

International audience; Purpose: In children, the usual indications for continuous positive airway pressure (CPAP) are residual OSA after adenotonsillectomy and/or persistent OSA due to obesity. Data concerning adherence (hours/night) following ambulatory CPAP initiation are scarce.Methods: An observational cohort of 78 children was followed over 2 years. All exhibited sleep-disordered breathing (SDB) symptoms, were assessed by polysomnography, and prescribed CPAP. CPAP was initiated at hospital for 10 children.Results: OSA children, mean age 10.4 ± 3.2 years, were mostly males (75.6%), with a mean body mass index of 21.2 ± 7.3 kg/m2, and mean apnea+hypopnea index of 12.2 ± 10.6 events/hour. Seventy-two children were still on CPAP at 3 months, 63 at 6 months, 55 at 1 year, and 34 at 2 years. CPAP was discontinued thanks to rehabilitation programs, dento-facial orthopedics, and/or weight loss. Mean CPAP adherence at 1, 3, 6, 12, and 24 months was respectively 6.1 ± 2.8, 6.2 ± 2.6, 6.2 ± 2.8, 6.3 ± 2.8, and 7.0 ± 2.7 h/night. There was a trend towards higher CPAP adherence and younger age, primary versus middle/high school attendance, higher baseline apnea+hypopnea index, and neurocognitive disorders.Conclusion: In our population, mean CPAP adherence defined in hours per night was high and did not decrease during the 24-month follow-up. These findings support the feasibility of ambulatory CPAP initiation in non-syndromic OSA. The high CPAP adherence is expected to be associated with improvements in neurocognition, and in metabolic and cardiovascular parameters.

Background One of the major challenges in treating OSA is to achieve adequate CPAP adherence. Telemonitoring has the potential to provide individualized management and early recognition of problems during treatment. Research Question What is the effect of a multimodal telemonitoring intervention on treatment adherence, quality of life, and functional status in symptomatic patients with OSA and low cardiovascular risk? Study Design and Methods In a multicenter, randomized controlled trial, patients newly diagnosed with OSA were randomly assigned to multimodal telemonitoring for 6 months vs usual care (UC). Telemonitoring consisted of built-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks, or persistent residual events. The primary outcome was CPAP adherence (in hours per night). Secondary outcomes included daily symptoms such as fatigue and sleepiness, and quality of life measured by using self-reported questionnaires. Results A total of 206 patients with OSA and a median age of 50.6 years (interquartile range [IQR], 42.1; 58.1 years) were included in the study; they were predominantly male (63%) with a median BMI of 30.6 kg/m2 (IQR, 26.8; 35.1 kg/m2) and a median apnea-hypopnea index of 45.2 events/h (IQR, 34.0; 60.0 events/h). Of these, 102 received UC and 104 received telemonitoring. After 6 months of treatment, CPAP adherence was similar in the two groups when assessed either by mean duration of usage (4.73 ± 2.48 h per night in the telemonitoring group and 5.08 ± 2.44 h per night in the UC group; P = .30) or in percentage of patients adherent to treatment (> 4 h usage per night, > 70% nights; 64% in the telemonitoring group vs 72% in the UC group; P = .24). There was no significant difference between the groups in effect size of improvement in fatigue and sleepiness. Interpretation In patients with severe OSA and low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both the telemonitoring and UC groups, similar improvements in daytime symptoms were achieved. Trial Registry ClinicalTrials.gov; No.: 01796769; URL: www.clinicaltrials.gov

Background: One of the major challenges in treating obstructive sleep apnea (OSA) is to achieve adequate continuous positive airway pressure (CPAP) adherence. We determined the effect of a multimodal telemonitoring intervention on CPAP adherence, quality of life and functional status in symptomatic OSA patients with low cardiovascular risk. Study Design and Methods: In a multicenter, randomized controlled trial, newly diagnosed OSA patients were randomly assigned to multimodal telemonitoring(TM) for 6 months vs usual care (UC). TMconsisted ofbuilt-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks or persistent residual events.The outcomesincluded CPAP adherence, daily symptoms such as fatigue and sleepiness, and quality of life. Results: Of 206 OSA patients aged 50.6 [42.1;58.1] (median [IQR]) years;predominantly male (63%) with body mass index of 30.6 [26.8;35.1] kg/m2and an AHI of 45.2 [34.0;60.0] events/hour) 102 received UC and 104 TM. After 6 months of treatment, CPAPadherence was similar in the two groups when assessed either by mean duration of usage (4.73±2.48 hours/night in the TM group and 5.08±2.44 hours/night in the UC group, p=0.30) or in % of patients adherent to treatment (over 4 hours usage/night, > 70% nights; 64% in TM vs 72% in UC, p=0.24). There was no significant difference between the groups in effect size of improvement in fatigue and sleepiness. Interpretation: In severe OSA patients with low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both TM and UC groups similar improvements in daytime symptoms were achieved.

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.

Rationale Chronic intermittent hypoxia occurring in obstructive sleep apnea (OSA) is independently associated with nonalcoholic fatty liver disease (NAFLD). Chronic obstructive pulmonary disease (COPD) has also been suggested to be linked with liver disease. Objective In this individual participant data meta-analysis, we investigated the association between liver damage and OSA and COPD severity. Methods and measurements Patients suspected of OSA underwent polysomnography (PSG) or home sleep apnea testing (HSAT). Non-invasive tests were used to evaluate liver steatosis (Hepatic Steatosis Index) and fibrosis (Fibrotest or FibroMeter). An individual participant data meta-analysis approach was used to determine if the severity of OSA/COPD affects the type and severity of liver disease. Results were confirmed by multivariate and causal mediation analysis. Sub-group analyses were performed to investigate specific populations. Main results Among 2120 patients, 1584 had steatosis (75%). In multivariable analysis, risk factors for steatosis were an apnea-hypopnea index (AHI) > 5/h, body mass index (BMI) > 26 kg/m2, age, type 2 diabetes (all p-values 26 kg/m2, age, male gender, and type 2 diabetes (all p-values 30/h and COPD stage 1 was associated with an increased risk of steatosis. Conclusion This meta-analysis confirms the strong association between steatosis and the severity of OSA. The relation between OSA and fibrosis is mainly due to BMI as shown by causal mediation analysis.

International audience; We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI20 min with oxygen saturation

One of the major challenges in treating OSA is to achieve adequate CPAP adherence. Telemonitoring has the potential to provide individualized management and early recognition of problems during treatment.What is the effect of a multimodal telemonitoring intervention on treatment adherence, quality of life, and functional status in symptomatic patients with OSA and low cardiovascular risk?In a multicenter, randomized controlled trial, patients newly diagnosed with OSA were randomly assigned to multimodal telemonitoring for 6 months vs usual care (UC). Telemonitoring consisted of built-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks, or persistent residual events. The primary outcome was CPAP adherence (in hours per night). Secondary outcomes included daily symptoms such as fatigue and sleepiness, and quality of life measured by using self-reported questionnaires.A total of 206 patients with OSA and a median age of 50.6 years (interquartile range [IQR], 42.1; 58.1 years) were included in the study; they were predominantly male (63%) with a median BMI of 30.6 kg/mIn patients with severe OSA and low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both the telemonitoring and UC groups, similar improvements in daytime symptoms were achieved.ClinicalTrials.gov; No.: 01796769; URL: www.clinicaltrials.gov.

Background and objective The prevalence of obesity hypoventilation syndrome (OHS) in the unselected obese is unknown. Our objectives were: (i) to determine the prevalence of OHS in ambulatory obese patients not previously referred to a pulmonologist for suspicion of sleep breathing disorders and (ii) to assess whether venous bicarbonate concentration [HCO3 − v] can be used to detect OHS. Methods In this prospective multicentric study, we measured [HCO3 − v] in consenting obese patients attending pathology analysis laboratories. Patients with [HCO3 − v] ≥ 27 mmol/L were referred to a pulmonologist for comprehensive sleep and respiratory evaluations. Those with [HCO3 − v]

Resume Objectif La dysfonction endotheliale (DE) predit la survenue d’evenements cardiovasculaires (CV) tardifs et pourrait etre le lien entre le syndrome d’apnees obstructives du sommeil (SAOS) et les maladies CV. Toutefois, on observe certaines limites methodologiques des meta-analyses anterieures evaluant l’association entre le SAOS et la DE. Methodes Cette meta-analyse sur donnees individuelles portant sur 730 patients sans maladie CV connue issus de 12 etudes a pour objectif d’evaluer une possible association entre la severite du SAOS et la DE. Chaque patient a beneficie d’un enregistrement poly(somno)graphique pour suspicion clinique de SAOS et une evaluation de la fonction endotheliale par plethysmographie digitale. La DE est definie par un indice d’hyperemie reactive transformee en logarithme (Ln-RHI) Resultats Une DE existe respectivement chez 14,9, 18,1 et 26,9 % des patients sans SAOS (indice d’apnee-hypopnee [IAH] 20 min vs Conclusion L’IAH et l’hypoxemie nocturne sont independamment associees a la DE.

Introduction La dysfonction endotheliale (DE) predit la survenue d’evenements cardiovasculaires (CV) tardifs et pourrait etre le lien entre le syndrome d’apnees obstructives du sommeil (SAOS) et les maladies CV. Toutefois, les revues et meta-analyses anterieures evaluant l’association entre le SAOS et la DE presentaient certaines limites methodologiques. Methodes Cette meta-analyse sur donnees individuelles portant sur 730 patients sans maladie CV connue provenant de 12 etudes avait pour objectif de determiner l’existence d’une association entre la severite du SAOS et la DE. Tous les patients ont beneficie d’un enregistrement polygraphique ou polysomnographique pour suspicion clinique de SAOS ainsi qu’une evaluation de la fonction endotheliale par plethysmographie digitale (RH-PAT). La DE a ete definie par un indice d’hyperemie reactive transformee en logarithme (Ln-RHI) Resultats Une DE a ete observee respectivement chez 14,9, 18,1 et 26,9 % des patients sans SAOS (indice d’apnee-hypopnee [IAH] 20 min vs Conclusion La severite du SAOS et l’hypoxemie nocturne sont independamment associees a la DE, facteur predictif des evenements CV tardifs.

Introduction: Connected health is a growing field and can be viewed from different perspectives, particularly in sleep apnea syndrome. Materials and methods: The purpose of this review is to show how all these aspects of connected health are already used in the management of sleep apnea syndrome (SAS) and its comorbidities. Results: First, it can give patients a better understanding and a better assessment of their health. It also facilitates their healthcare by allowing them a greater role in their care pathway. For healthcare providers, connected health tools make it possible to set up new procedures for diagnosing and monitoring ambulatory patients, and for the making of joint decisions by health professionals and patients. Finally, for researchers, e-health generates massive amounts of data, thus facilitating the acquisition of knowledge in real life situations and the development of new methodologies for clinical studies that are faster, less expensive and just as reliable. Discussion: All these considerations are already applicable in the field of sleep apnea, both for proposed treatments and for comorbidities management and for the patient’s involvement in his/her care pathway., Introduction : La santé connectée est en plein essor et peut être envisagée à partir de différentes perspectives notamment dans le syndrome d’apnées du sommeil (SAS). Matériels et méthodes : L’objet de cette revue est de montrer comment toutes ces dimensions de la santé connectée s’appliquent déjà à la prise en charge du SAS et de ses comorbidités. Résultats : Tout d’abord, elle permet au patient une meilleure compréhension et une meilleure évaluation de sa santé. Elle facilite également sa prise en charge en lui permettant de devenir acteur de son parcours de soins. Pour les professionnels de santé, les outils de santé connectée permettent de mettre en place de nouvelles procédures de diagnostic, de suivi des patients ambulatoires et de construire entre professionnels de santé et patients des décisions partagées. Enfin pour les chercheurs, l’e-santé génère des données massives facilitant l’acquisition de connaissances en situation de vie réelle, le développement de nouvelles méthodologies d’études cliniques, plus rapides, moins chères et tout aussi fiables. Discussion : Toutes ces considérations s’appliquent déjà dans le contexte du SAS, que ce soit concernant les traitements proposés comme la gestion des comorbidités associées et l’implication du patient dans son parcours de soins.

Diuretics have been reported as effective for reducing OSA severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending on the OSA clinical phenotype and comorbidities. To test this hypothesis, we conducted a propensity score-matched cohort analysis of data from the French national sleep apnea registry "Observatoire Sommeil de la Fédération de Pneumologie."Which phenotypic subtypes of OSA may benefit from diuretics?A propensity score analysis was used to determine the impact of diuretics on OSA severity. Matching (ratio 1:4) was performed by using a 0.1 collider for the propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI)30 events/h, and the usefulness of diuretics was assessed by using a logistic regression model.The 69,564 OSA patients studied in the OSFP prospective observational cohort had a median age of 56.9 years (interquartile range: 47.4; 65.6), 67% were men, and the median AHI was 28 (14; 43) events/h. Among them, 9,783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (P = .03) and in patients with hypertension (P .01), particularly in patients with hypertension with a BMI between 25 and 35 (P .01). Diuretics had no significant effect on OSA severity in patients with self-reported low physical activity or heart failure.Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined therapies for hypertensive patients with OSA.

International audience; Introduction: Central sleep apnea (CSA) syndrome has gained a considerable interest in the sleep field within the last 10 years. It is overrepresented in particular subpopulations such as patients with stroke or heart failure. Early detection and diagnosis, as well as appropriate treatment of central breathing disturbances during sleep remain challenging. Areas covered: Based on a systematic review of CSA in adults the clinical evidence and polysomnographic patterns useful for discerning central from obstructive events are discussed. Current therapeutic indications of CSA and perspectives are presented, according to the type of respiratory disturbances during sleep, alterations in blood gases and ventilatory control. Expert opinion: The precise identification of central events during polysomnographic recording is mandatory. Therapeutic choices for CSA depend on the typology of respiratory disturbances observed by polysomnography, changes in blood gases and ventilatory control. In CSA with normocapnia and ventilatory instability, adaptive servo-ventilation is recommended. In CSA with hypercapnia and/or rapid-eye movement sleep hypoventilation, non-invasive ventilation is required. Further studies are required as strong evidence is lacking regarding the long-term consequences of CSA and the long-term impact of current treatment strategies.

Introduction & background: Residual events during CPAP contribute to increase treatment drop-outs. Clinical scenarios triggering residual events during CPAP use are poorly described. Aims & objectives: Underlying comorbidities, especially cardiovascular diseases, lifestyle factors, OSA characteristics at baseline and type of mask are suggested as potential contributors. Methods: Patients from the prospective national French sleep apnea registry with apnea-hypopnea index (AHI) = 15/h and CPAP indication were included. A logistic regression analysis was used to identify factors associated with the probability of exhibiting a residual AHI > 5/h whilst on CPAP. Results: 12,285 OSA patients predominantly men (N=8715, 70.9%), middle aged (median [IQR]: 58.2 [49.8;66.1] years) and obese (median body mass index: 31.3 [27.7;35.6] kg/m²) were included. Most had an AHI=5/h (N=9,573, 77.9%) versus 22.1% exhibited an AHI>5/hour. The latter group was significantly less adherent to CPAP (5.75 [4.01;7.00] vs 6.00 [4.53;7.00] h/night). In multivariable analysis, factors associated with a high residual AHI were male gender, age and sedentary lifestyle, OSA severity, cardiovascular comorbidities and interface (orofacial versus nasal mask: OR = 2.15 [CI: 1.95;2.37]). Conclusions: The knowledge of at-risk clinical scenarios predicting more frequent residual events will help in the timely provision of personalized care including type of PAP therapy, attention to comorbidity care and interfacechoice

Introduction & background: Chronic intermittent hypoxia in obstructive sleep apnea (OSA) is associated with Nonalcoholic fatty liver disease (NAFLD). Aims & objectives: In this meta-analysis, we investigate the association between liver injuries, OSA and/or COPD indices of severity. Methods: Patients referred for OSA underwent a polysomnography or overnight respiratory polygraphy. Non-invasive tests were used to evaluate liver steatosis and fibrosis. An individual participant data meta-analysis approach was performed with subgroup analyses to determine if there are some differences between patient subgroups according to OSA or COPD severity. Results: Among 2,402 patients, 1,813 had steatosis (HSI>36). In multivariate analysis, risk factors for steatosis were apnea-hypopnea index (AHI)>30/h (OR: 6.93 [4.92;9.76]), hypertension (OR: 2.37 [1.87;3.01]) and type 2 diabetes (OR: 5.36 [3.32;8.64]). Concerning fibrosis, data were available for 2,526 patients. Among them, 517 patients exhibited liver fibrosis, including 330 (29%) in severe OSA. Risk factors associated with fibrosis were AHI>30/h (OR: 2.38 [1.44; 3.96]), age, male gender (OR: 2.92 [2.22; 3.84], hypertension (OR: 1.53 [1.19; 1.97]) and type 2 diabetes (OR: 4.64 [3.45; 6.24]). Conclusions: This meta-analysis confirms the strong association between OSA and liver diseases and the impact of COPD. Liver diseases should now be included in the list of comorbidities of both COPD and OSA.

Background and objective Continuous positive airway pressure (CPAP) is the first-line therapy for obstructive sleep apnoea (OSA). Residual apnoea and/or hypopnoea events, that is an apnoea-hypopnoea index (AHI) > 5, during CPAP contribute to treatment drop-out. The clinical scenarios triggering residual events during CPAP use are poorly described. Underlying co-morbidities, especially cardiovascular diseases, lifestyle factors, OSA characteristics at diagnosis and type of mask have been suggested as potential contributors. Methods Patients from the prospective French sleep apnoea registry diagnosed with OSA (AHI ≥ 15 events/h) treated with CPAP were included. Logistic regression analysis identified factors associated with a risk of residual AHI > 5 events/h on CPAP. Results The 12 285 OSA patients were predominantly men (n = 8715, 70.9%), middle-aged (58.2 (49.8; 66.1) years) and obese (median body mass index: 31.3 (27.7; 35.6) kg/m2 ). Most had an AHI ≤ 5 events/h (n = 9573, 77.9%) versus 22.1% with AHI > 5/h. The latter were less CPAP adherent (5.75 (4.01; 7.00) vs 6.00 (4.53; 7.00) h/night). In multivariable analysis, factors associated with residual AHI >5/h were male sex, age, sedentary lifestyle, OSA severity, cardiovascular co-morbidities (heart failure and arrhythmia) and type of interface (orofacial mask versus nasal mask: OR = 2.15 (95%CI: 1.95; 2.37)). A subgroup analysis found that patients using pressures above 10 cm H2 O were 1.43 (95% CI: 1.3; 1.57) times more likely to have residual AHI > 5/h. Conclusion Knowing about risk factors for residual apnoeic-hypopnoeic events may assist in the timely provision of personalized care including the type of PAP therapy, attention to co-morbidities and choice of interface.

Introduction & Background: Due to the structural similarity between gabapentin and baclofen, gabapentin was reported to produce ‘baclofen-like’ effects. Baclofen is linked to sleep apnea syndrome (SAS), aggravating sleep-disordered breathing by depressing central ventilatory drive and/or increasing upper airway obstruction. Aims & Objectives: We hypothesized that gabapentinoids might be associated with SAS. Methods: We performed a disproportionality analysis within Vigibase, the large WHO pharmacovigilance database. The relationship between the use of each antiepileptic and the occurrence of adverse drug reaction (i.e. SAS) was assessed by calculating the reported odds ratio (ROR) [95% confidence intervals] in a case-noncase model. Results: Of the 17 519 277 Individual Case Safety Reports reported to Vigibase between December 1970 and July 2018, 8915 (0.05%) were SAS cases; 76 cases of SAS for gabapentin and 123 for pregabalin. The ROR for both drugs were significant: 2.61 [2.08 to 3.27] for gabapentin and 2.42 [2.02 to 2.89] for pregabalin, whereas no other antiepileptic drugs had a ROR with lower boundary > 2. The ROR was also significant for benzodiazepines: 3.07 [2.58 to 3.66] (Figure 1). Conclusions: Rates of gabapentinoids use in the USA tripled between 2002 and 2015, especially in opioid crisis context leading to the emergence of pregabalin and gabapentin misuse and abuse. Physicians need to be aware that sleep apnea might affect patients treated with gabapentinoids.

Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcoholic Fatty Liver Disease (NAFLD) both independently increase cardiovascular risk. We hypothesized that NAFLD might increase the incidence of cardiovascular disease and death in COPD patients. The relationship between NAFLD, incident cardiovascular events, and death was assessed in a prospective cohort of COPD patients with 5-year follow-up. Noninvasive algorithms combining biological parameters (FibroMax®) were used to evaluate steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis. Univariate and multivariate Cox regression models were used to assess the hazard for composite outcome at the endpoint (death or cardiovascular event) for each liver pathology. In 111 COPD patients, 75% exhibited liver damage with a prevalence of steatosis, NASH and fibrosis of 41%, 37% and 61%, respectively. During 5-year follow-up, 31 experienced at least one cardiovascular event and 7 died. In univariate analysis, patients with liver fibrosis had more cardiovascular events and higher mortality (Hazard ratio [95% CI]: 2.75 [1.26; 6.03]) than those with no fibrosis; this remained significant in multivariate analysis (Hazard ratio [95% CI]: 2.94 [1.18; 7.33]). We also found that steatosis and NASH were not associated with increased cardiovascular events or mortality. To conclude, early assessment of liver damage might participate to improve cardiovascular outcomes in COPD patients.

Objectif Evaluation de la performance des implants cardiaques versus polysomnographie pour le diagnostic du SAS. Methodes Une recherche systematique a ete menee pour identifier les etudes repondant a notre objectif. Les performances des implants cardiaques, avec des analyses de sensibilite par fabriquant et types d’implant, ont ete evaluees par une meta-analyse bivariee a effet aleatoire. Le calcul de la sensibilite et la specificite a ete limite au sous-groupe le plus representatif et pour un index d’apnees-hypopnees (IAH)≥ 30/heure. De plus, nous avons effectue des meta-regressions uni et des analyses multivariees pour explorer l’effet des donnees suivantes (âge, IMC, sexe, les prevalences de la fibrillation auriculaire (FA) et du SAS dans la population generale) sur les performances des implants cardiaques. Resultats Cette meta-analyse a porte sur 13 etudes et 647 patients avec donnees valides, en majorite des hommes (> 50 %), d’âge moyen 70,5 ± 4,8 ans. Selon les etudes, la sensibilite variait de 60 a 100 % et la specificite de 50 a 100 % avec une prevalence du SAS de 22 a 91 %. Pour un IAH≥ 30/heure, 6 etudes ont utilise un dispositif de Boston Scientific et 5 etudes ont ete menees avec un stimulateur cardiaque de type pacemaker (PM). La valeur seuil optimale d’evenements respiratoires pour les PMs etait de 31,5/heure avec une sensibilite de 80 % et une specificite de 70 %. Conclusion Le SAS modere a severe, peut etre diagnostique de facon relativement fiable chez le patient porteur d’un implant cardiaque. Ceci devrait participer a l’amelioration du diagnostic de SAS dans les populations a risque cardiovasculaire.

Objectifs La similarite structurelle entre gabapentine, pregabaline et baclofene explique les effets « baclofene-like » des gabapentinoides. Dans une precedente etude a partir des donnees de VigiBase®, le baclofene a ete decrit comme pourvoyeur d’apnees du sommeil, notamment a forte dose dans la prise en charge de l’alcoolodependance [1] . Avec une meme approche, le travail actuel a pour objectif d’identifier si une telle association existe egalement avec les gabapentinoides. Methode Nous avons procede a l’extraction des cas de syndrome d’apnees du sommeil imputables aux antiepileptiques (ATC N03), a partir de la base mondiale de pharmacovigilance de l’OMS (VigiBase®). En juillet 2018, cette base comprenait plus de 17 millions de cas rapportes par pres de 131 pays. Une analyse de disproportionnalite par calcul du odds ratio rapporte (ROR) selon un modele cas-non cas, a ensuite ete realisee pour chaque antiepileptique. On entend par signal de pharmacovigilance, un nombre de notifications de l’effet indesirable d’interet (ici le syndrome d’apnees du sommeil) superieur a celui attendu, c’est-a-dire un taux de notification « disproportionne » associe a un medicament d’interet (ici les gabapentinoides) par rapport au meme effet notifie dans la base pour les autres medicaments. Les benzodiazepines (ATC N03AE) ont ete utilisees comme controle positif, afin de renforcer la robustesse de la methode. Resultats Soixante-seize cas de syndrome d’apnees du sommeil ont ete imputes a la gabapentine (ROR 2,61 [2,08–3,27]). Pour la pregabaline, 123 cas de syndrome d’apnees du sommeil ont ete rapportes (ROR 2,42 [2,02–2,89]). Les ROR etant superieurs au seuil de significativite, nous retenons une association entre gabapentinoides et syndrome d’apnees du sommeil. Aucun signal de disproportionnalite n’a ete retrouve avec les autres antiepileptiques, a l’exception des benzodiazepines (ROR 3,07 [2,58–3,66]). Conclusion Ce signal de pharmacovigilance confirme les resultats precedemment observes avec les agonistes GABAergiques, dont le baclofene. Les professionnels de sante doivent etre avertis que des apnees du sommeil pourraient affecter les patients traites par gabapentine ou pregabaline. Ce d’autant plus que l’utilisation des gabapentinoides est en nette augmentation, souvent associes avec des opioides ou des benzodiazepines [2] . Ils potentialisent ainsi le risque de depression respiratoire, avec des consequences deleteres pouvant aller jusqu’au deces.

Obstructive Sleep Apnea (OSA) is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the OSA-related cardiometabolic alterations. This study aimed at assessing the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and metabolic and inflammatory parameters were assessed such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, NF-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischemia-reperfusion. Circulating lipids, insulin, HOMA-IR, leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver IL-6 and TNF-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in IL-6 but not in TNF- α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and obese rats and increased cardiac endothelin-1 in lean but not obese rats. In conclusion, this study shows that the dyslipidemia and insulin resistance induced by obesity of genetic origin does not enhance the deleterious cardiovascular response to IH and may even partially protect against IH-induced inflammation. This article is protected by copyright. All rights reserved

Resume Les patients atteints d’un syndrome d’apnees obstructives du sommeil (SAOS) presentent des modifications des taux urinaires et sanguins de certains biomarqueurs cardio-metaboliques. Des augmentations des taux de catecholamines, de marqueurs inflammatoires et lipidiques ou encore des modifications des marqueurs du metabolisme glucidique sont frequemment observees au moment du diagnostic du SAOS et peuvent etre attribuees au SAOS ou a ses comorbidites. Chez ces patients SAOS, de nombreuses etudes en ouvert montrent un effet benefique du traitement par pression positive continue (PPC) sur ces biomarqueurs cardio-metaboliques. Cependant, cet effet ne semble pas etre aussi clairement etabli a partir des donnees des essais randomises et controles (PPC versus sham PPC). Une synthese de ces donnees est donc necessaire, afin d’isoler les biomarqueurs a priori sensibles a la PPC pour lesquels un suivi regulier serait informatif pour documenter l’effet de PPC.

Background and objective Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)-associated hypertension are therefore needed. Endothelin-1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24-h diastolic BP (DBP) in patients with OSA never treated by either therapy. Methods In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m2; apnoea–hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2-weeks of washout, the second 4-week period consisted of the alternative treatment (in crossover). The primary outcome was the 24-h mean DBP change after treatment. Results In intention-to-treat analysis, the mean difference in 24-h DBP measurements between treatments was −3.1 (−6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect. Conclusion In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24-h DBP but only reduced office BP suggesting that Endothelin-1 blockade does not play a major role in treatment of OSA-related hypertension.

Background and objective Obstructive sleep apnoea (OSA) could be an independent risk factor for non-alcoholic fatty liver disease (NAFLD) occurrence and progression. The impact of continuous positive airway pressure (CPAP) treatment on non-invasive markers of NAFLD has not been studied. The aim of this study was to evaluate the effect of 6–12 weeks of effective CPAP on the FibroMax test (comprising components including the SteatoTest, NashTest and FibroTest) through three randomized sham controlled studies. Methods The FibroMax test was performed in 103 obstructive sleep apnoea patients (apnoea + hypopnoea index > 15/h) enrolled in a randomized study comparing sham versus effective CPAP. Results At baseline, 40.4% of patients in the sham CPAP group and 45.5% in the CPAP group exhibited liver steatosis. Furthermore, 39.6% of patients in the sham CPAP group and 58.4% in the CPAP group displayed borderline or possible non-alcoholic steatohepatitis (NASH). Six to twelve weeks of effective CPAP did not demonstrate any impact on reducing steatosis, NASH or liver fibrosis even after adjustment for gender, BMI, baseline apnoea + hypopnoea index and severity of liver injury. Conclusion A number of non-invasive markers of liver damage are increased in untreated obstructive sleep apnoea patients, potentially contributing to cardiometabolic risk, but they do not improve after 6–12 weeks of effective CPAP treatment. Clinical trial registration: NCT01196845 (ADISAS), NCT00464659 (MneSAS) and NCT00669695 (StatinflaSAS) at ClinicalTrials.gov.

Acquired central hypoventilation syndrome (CHS) is a rare cause of respiratory failure. We report a case of acquired CHS, diagnosed several years after Listeria monocytogenes (LM) rhombencephalitis. In 1993, a 46-year-old woman presented to our Sleep Clinic with poor sleep, nocturnal choking episodes and daytime fatigue. She denied habitual snoring and hypersomnolence. Her medical history was unremarkable except for severe LM rhombencephalitis in 1977. At that time, the patient had been hospitalised in the intensive care unit following the acute onset of fever, influenza-like symptoms, meningism, facial palsy and nystagmus. Blood and cerebral spinal fluid samples were positive for LM on direct microscopic exam as well cultures. Treatment was initiated but the patient acutely deteriorated, exhibiting tetra paresis, bilateral pontomedullary syndrome, impairment of vigilance, and experienced a cardiac arrest. She was successfully resuscitated and remained in the intensive care unit with gradual and slow recovery. After a lengthy hospital stay, she was eventually discharged from the hospital and resumed a normal life, with few neurological sequelae such as dysphagia and mild facial palsy. To investigate the patient's sleep complaints, an in-laboratory full polysomnography was obtained and revealed central sleep apnoeas and hypopnoeas (Apnoea–Hypopnoea index (AHI)=50 events/hour) with severe nocturnal hypoxaemia. Morning arterial blood gases revealed alveolar hypoventilation with partial pressure of arterial CO2 or PaCO2 of 6.7 kPa and PaO2 of 9.5 kPa. The patient refused further investigations and therapy but agreed to return to clinic for a follow-up in 1 year. In 1994, polysomnography and arterial blood gases showed persistent sleep apnoea and daytime hypoventilation but the patient continued to decline treatment. The patient was then lost to follow-up until 2011, when she presented for the third time to the Sleep Clinic complaining of daytime fatigue, unrefreshing sleep, choking episode during sleep and …