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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.

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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.

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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

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]

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.

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

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 …

Introduction Diuretics have been reported as effective for reducing obstructive sleep apnea (OSA) severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending upon the OSA clinical phenotype and comorbidities. Objective 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” (OSFP). Method 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 propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI) > 30 events/h and the usefulness of diuretics was assessed 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 (IQR): 47.4; 65.6], 67% were men, and the median AHI was 28 [14; 43] events/h. Among them, 9783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (P = 0.03) and in patients with hypertension (P Conclusion Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. Diuretics might be prioritized in combined therapies for hypertensive patients with OSA.

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

Background: Ticagrelor is a P2Y12-receptor antagonist frequently used for dual antiplatelet therapy in coronary artery disease. Cheyne–Stokes respiration with central sleep apnea has been previously reported in 4 patients following ticagrelor introduction. Objective: To analyze in VigiBase, the reported cases of sleep apnea syndrome (SAS) among ticagrelor users compared to other antiplatelet agents. Methods: All cases of SAS and dyspnea associated to ticagrelor were extracted from VigiBase. A disproportionality analysis was performed by calculating the reporting odds ratio (ROR) in a case-noncase study to confirm the relationship between the use of ticagrelor and SAS or dyspnea compared to other drugs. A ROR>2 with a number of cases ≥5 is considered significant. Results: 28 cases of SAS and 2 665 of dyspnea were reported with ticagrelor. The RORs for ticagrelor were significant for SAS (ROR [95%CI] = 4.16 [2.87-6.03]) and for dyspnea (8.26 [7.92-8.62]). This relationship was not found for the other antiplatelet agents: clopidogrel, prasugrel or aspirin. Conclusion: The P2Y12 receptor is expressed in the central nervous system including in the respiratory centers. Ticagrelor by P2Y12 antagonism induces respiratory drive deregulations that might explain the occurrence of dyspnea and SAS. Further studies should investigate the exact incidence, the sustainability and consequences of ticagrelor-induced central sleep apnea.

Serum bicarbonate dosage is sensitive to pharmacological interferences. However, elevated bicarbonate concentration reflects chronic hypoventilation and has been proposed as a simple marker for screening patients with Obesity Hypoventilation Syndrome (OHS), a currently underdiagnosed multimorbid and high mortality disease. We provide a practical overview of the different drugs acting on the acid-base equilibrium to aid clinicians to interpret bicarbonate concentration readings. Little is known about the chronic impact of the usual doses of these drugs on serum bicarbonate concentration and further studies are needed. It is essential to take into account drugs that could interfere with this parameter to avoid misinterpretation of serum bicarbonate levels.

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Ticagrelor is a P2Y12 receptor antagonist used in first-line dual-antiplatelet therapy in coronary artery disease [(1)][1]. Cheyne-Stokes respiration with central sleep apnea was reported in 4 patients after ticagrelor therapy was initiated and disappeared after ticagrelor withdrawal and switch to

BackgroundArterial stiffness, measured by pulse wave velocity (PWV), is a strong independent predictor of late cardiovascular events and mortality. It is recognised that obstructive sleep apnoea (OSA) is associated with cardiovascular comorbidities and mortality. Although previous meta-analyses concluded that PWV is elevated in OSA, we feel that an individual patient data analysis from nine relatively homogeneous studies could help answer: to what extent does OSA drive arterial stiffness?MethodsIndividual data from well-characterised patients referred for suspicion of OSA, included in nine studies in which carotid–femoral PWV was measured using a Complior device, were merged for an individual patient data meta-analysis.Results893 subjects were included (age: 56±11 (mean±SD), 72% men, 84% with confirmed OSA). Body Mass Index varied from 15 to 81 kg/m2 (30±7 kg/m2). PWV ranged from 5.3 to 20.5 m/s (10.4±2.3 m/s). In univariate analysis, log(PWV) was strongly related to age, gender, systolic blood pressure, presence of type 2 diabetes (all pConclusionOur individual patient meta-analysis showed that elevated arterial stiffness in patients with OSA is driven by conventional cardiovascular risk factors rather than apnoea parameters.

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Background: Most of patients suffering from resistant hypertension (RH) have obstructive sleep apnea (OSA). However, little is known about the metabolic profile of these patients as well as the efficacy of continuous positive airway pressure (CPAP) in RH. Methods: We performed a multicentre, comparative (presence or not of OSA), randomized, simple blind study in 62 patients (60 ± 10 years; 77% of men, body mass index, 29.6 ± 3.9 kg/m2) with essential RH (24-hour daytime systolic BP (SBP) / diastolic BP (DBP): 145 ± 13 / 85 ± 10 mmHg, 3.7 antihypertensive drugs). OSA patients (AHI: 37.6 [25.4 ; 51.8] /h, n=37) were randomized to receive either sham CPAP (3-months, n=18) followed by active CPAP (6 months) or only 6 months of active CPAP (n=19). The primary endpoint was the influence of OSA on blood leptin level in patients with RH. The influence of OSA on BP and the impact of CPAP treatment were also studied. Results: The 37 OSA patients with RH (60% of the 62 included patients) were predominantly men, with metabolic syndrome (84 vs 60%, p=0.036). Their blood leptin level was significantly lower than in non-OSA patients (9 [6 ; 15] vs 17 [6 ; 29] ng/mL, p=0.041). In intention to treat analysis, 3 months of CPAP decreased significantly nighttime SBP by 6.4 mmHg (p=0.033) and HR by 6.0 mmHg (p=0.010), compared to sham CPAP effect. Six months under effective CPAP also decreased nighttime BP and improved dipper profile. Conclusion: It is important to investigate OSA in RH and to stat CPAP treatement since besides its interest on sleepiness, CPAP is efficient to decrease nighttime BP in apneic patients suffering from RH. NCT00746902.

Obstructive sleep apnoea (OSA) is characterized by repeated episodes of apnoea and hypopnoea during sleep. Little is known about the potential impact of therapy drugs on the underlying respiratory disorder. Any influence should be taken into account and appropriate action taken, including drug withdrawal if necessary. Here, we review drugs in terms of their possible impact on OSA; drugs which (1) may worsen OSA; (2) are unlikely to have an impact on OSA; (3) those for which data are scarce or contradictory; and (4) drugs with a potentially improving effect. The level of evidence is ranked according to three grades: A - randomized controlled trials (RCTs) with high statistical power; B - RCTs with lower power, non-randomized comparative studies and observational studies; C - retrospective studies and case reports. Our review enabled us to propose clinical recommendations. Briefly, agents worsening OSA or inducing weight gain, that must be avoided, are clearly identified. Drugs such as 'Z drugs' and sodium oxybate should be used with caution as the literature contains conflicting results. Finally, larger trials are needed to clarify the potential positive impact of certain drugs on OSA. In the meantime, some, such as diuretics or other antihypertensive medications, are helpful in reducing OSA-associated cardiovascular morbidity.

Objective Most of patients suffering from resistant hypertension (RH) have obstructive sleep apnea (OSA). However, little is known about the metabolic profile of these patients as well as the efficacy of continuous positive airway pressure (CPAP) in RH. Methods We performed a multicentre, comparative (presence or not of OSA), randomized, simple blind study in 62 patients with essential RH (24-hour daytime systolic BP (SBP) / diastolic BP (DBP): 145±13 / 85±10 mmHg, 3.7 antihypertensive drugs).OSA patients (AHI:37.6 [25.4; 51.8]/h(median [25 th ; 75 th percentiles]), n=37) were randomized to receive either sham CPAP (3-months,n=18)followed by active CPAP (6 months) or only 6 months of active CPAP (n=19). The primary endpoint was the influence of OSA on blood leptin level in patients with RH. The influence of OSA on BP and the impact of CPAP treatment were also studied. Results The 37 OSA patients with RH (60% of the 62 included patients) were predominantly men (87 vs 64% in non-OSA patients, p=0.038), with metabolic syndrome (84 vs 60%, p=0.036). Their blood leptin level was significantly lower than in non-OSA patients (9 [6; 15] vs 17 [6; 29] ng/mL, p =0.041).In intention to treat analysis, 3 months of CPAP decreased significantly nighttime SBP by 6.4 mmHg (p=0.033) and HR by 6.0 mmHg (p=0.010), compared to sham CPAP effect. Six months under effective CPAP also decreased nighttime BP and improved dipper profile. Conclusions It is important to investigate OSA in RH and to start CPAP treatment since besides its interest on sleepiness, CPAP is efficient to decrease nighttime BP in apneic patients suffering from RH.

Obstructive sleep apnoea (OSA) is characterized by repeated episodes of apnoea and hypopnoea during sleep. Little is known about the potential impact of therapy drugs on the underlying respiratory disorder. Any influence should be taken into account and appropriate action taken, including drug withdrawal if necessary. Here, we review drugs in terms of their possible impact on OSA; drugs which (1) may worsen OSA; (2) are unlikely to have an impact on OSA; (3) those for which data are scarce or contradictory; and (4) drugs with a potentially improving effect. The level of evidence is ranked according to three grades: A - randomized controlled trials (RCTs) with high statistical power; B - RCTs with lower power, non-randomized comparative studies and observational studies; C - retrospective studies and case reports. Our review enabled us to propose clinical recommendations. Briefly, agents worsening OSA or inducing weight gain, that must be avoided, are clearly identified. Drugs such as 'Z drugs' and sodium oxybate should be used with caution as the literature contains conflicting results. Finally, larger trials are needed to clarify the potential positive impact of certain drugs on OSA. In the meantime, some, such as diuretics or other antihypertensive medications, are helpful in reducing OSA-associated cardiovascular morbidity.

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing health concernassociated with obesity and type 2 diabetes, and is prevalent in upto 25% of the general population. Current evidencedemonstrates a robust association between NAFLD and cardiovascular morbidity and mortality. Low grade inflammation, oxidative stress, reduced physical activity and metabolic syndrome that are common feature in COPD might participate to NAFLD occurrence but this has been poorly investigated. Methods: Noninvasive blood tests (SteatoTest, NashTest, and FibroTest) were used to evaluate steatosis, nonalcoholic steatohepatitis (NASH), and liver fibrosis in a prospective cohort of COPD patients. Results: Among the 111 COPD included (men, 77.5%; median age, 64 years; median BMI, 25.6 kg/m 2 ;Gold 1-2:74.8%; Gold 3-4:25.2%), the prevalence of steatosis (stages ≥S2), NASH (stages N1 or N2) and fibrosis (stages ≥F1) were respectively 41.4%, 36.9% and 61.3%. In univariate analysis, the different severities of NAFLD were significantly associated with: age, male gender, glycemic control, untreated sleep apnea (Steatosis and fibrosis); body mass index and dyslipidemia (Steatosis and NASH); diabetes and hypertension (Fibrosis) and COPD severity (Steatosis). Conclusion: NALFD is highly prevalent in COPD and might participate to cardiovascular and metabolic co-morbidities.

Background: Available data on the prevalence of OHS has mainly been obtained from cohorts of patients referred to sleep clinics but it remains unknown in unselected obese patients. Aims : i) To determine the prevalence of OHS in a population of ambulatory obese patients, without previous pulmonologist follow-up; ii) to determine independent parameters influencing [HCO3 - v ], a biomarker proposed for identifying potential OHS. Methods: This was a prospective multicentric study in obese patients attending a medical laboratory for routine blood analysis. [HCO3 - v ]was measured and patients with ≥ 27 mMol.L -1 were referred to a pulmonologist for a comprehensive sleep and respiratory evaluation. Patients with [HCO3 - v ] -1 were randomized for either referral to a pulmonologist or ended the study. The patients who had a previous pulmonologist follow-up ended the study, regardless. Results: 1004 patients were included: 24.6% with [HCO3 - v ] ≥ 27mMol.L -1 , 45.9% with -1 ,and 29.5% had previous pulmonologist follow-up. 241 patients comprised the final population of obese patients without previous pulmonologist follow-up who underwent sleep and respiratory assessments. Assuming this sample to be representative of the whole included population, the prevalence of OHS was 1.10; 95% CI=[0.51;2.27]. In multivariate analysis, PaCO 2 , FEV 1 , AHI, BMI, the use of at least three antihypertensive drugs, antidiabetics, proton pump inhibitors or paracetamol were related to [HCO3 - v ]. Conclusion: The prevalence of OHS determined is much lower than previous estimations based on cohorts from sleep clinics. Apart from hypercapnia, increased [HCO3 - v ] may also reflect multimorbidity and polypharmacy.

Introduction: Patients with obstructive sleep apnea (OSA) exhibit cognitive dysfunctions such as significant memory impairment affecting the 3 episodic, procedural, and working memory systems. The objective of this study was to investigate the change in memory processes after continuous positive airway pressure (CPAP) treatment in OSA patients. Design and methods: In this randomized, double blinded, parallel groups and sham-controlled trial, 36 patients with OSA (AHI > 15/h) and naive of CPAP treatment were randomized to receive either CPAP (n=18) or sham-CPAP (n=18) for 6-week. Three separate memory systems (verbal episodic, procedural and working memories) were evaluated for all patients, before and after treatment. Results: Key demographics for the study population were: age 55 ± 11 years, 72.2% male, BMI: 29.5 ± 4.1 kg/m 2 , AHI: 37.1 ± 16.3 /h. Prior to treatment, memory performances of OSA patients were altered. In intention to treat analysis, mnesic deficit were not different after 6 weeks of CPAP or sham CPAP treatment: verbal episodic, procedural and working memory scores were comparable between both groups. Conclusions: While 6 weeks of CPAP was an effective treatment for OSA in terms of reducing breathing disruption during sleep, it did not improve memory processes of OSA patientsin terms of verbal episodic memory, visual-motor and reading procedural memory, auditory and spatialworking memory, which are known to be altered in this context. These results suggest that OSA-neurocognitive relationship is complex and further investigations with longer CPAP exposures (at least 2 months) or on selective population (such as severe OSA patients) would be of interest.

Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage.

Objective The aim of this study was to investigate the changes in a large panel of memory processes after six weeks of continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) patients. This randomized controlled trial compared the influence of effective CPAP to sham CPAP over six weeks on different memory processes in OSA patients. Methods The study took place in a sleep laboratory and outpatient sleep clinic in a French tertiary-care university hospital. A total of 36 patients with OSA were randomized to receive either CPAP ( n = 18) or sham CPAP ( n = 18) for six weeks. Interventions were either effective CPAP or non-effective sham CPAP, for six weeks. All patients underwent an extensive battery of tasks evaluating three separate memory systems, before and after treatment. Verbal episodic memory was tested after forced encoding, procedural memory was tested using simplified versions of mirror drawing and reading tests, and working memory was examined with validated paradigms based on a theoretical model. Results The study subjects were 55 ± 11 years of age and 72.2% were male. The mean body mass index was 29.5 ± 4.1 kg/m 2 and the apnea–hypopnea index was 37.1 ± 16.3/h. Prior to treatment, memory performances of OSA patients were altered. In an intention-to-treat analysis, memory deficits were not significantly improved after six weeks of effective CPAP compared to sham CPAP treatment. Verbal episodic, procedural, and working memory scores were comparable between both groups. Conclusion Using cautious methodology in comparing effective CPAP to sham CPAP and a well-defined set of memory assessments, we did not find improvement in memory performance after six weeks of treatment.