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Abstract Background This study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE). Methods Between 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52). Discussion These observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae.

Abstract Background Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. Methods Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. Results Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p

Introduction Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude.Methods Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude.Results Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= −0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders.Conclusions Lower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies.

Abstract Background Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients. Methods ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process. Discussion An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population. Trial registration ClinicalTrials.gov NCT02377271 . Registered on March 3, 2015.

Aim The impact of obstructive sleep apnoea (OSA)–COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. Study design and methods This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea–hypopnea index at baseline. Results After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (β) −3.0%, 95% CI −4.7 to −1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (β −1.1%, 95% CI −1.5 to −0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal SpO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15–2.67) and systemic hypertension by 1.36 (95% CI 1.07–1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal SpO2 and T90 (increase in time below SpO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Conclusion Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.

IntroductionAcute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission.MethodsIn the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting.ResultsBetween January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders.ConclusionUsing systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear–nose–throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes.

Sleep disorders pose serious cardiovascular threats if not treated effectively. However, adherence to Continuous Positive Airway Pressure (CPAP), the most recommended therapy, is known to be challenging to monitor. Telemonitored CPAP equipment has improved the follow-up of CPAP adherence (hours of use per night) by producing far larger amounts of data collected daily. The analysis of such data have relied on averaging the entire therapeutic history and interpreting it without a proper reference concerning the level of adherence. By contrast, we contribute with an unsupervised machine-learning methodology that (i) translates the adherence data to a scale of discrete numbers that hold correspondence to the most usual 30-day-long patterns as observed in a real-word database; (ii) avoids the loss of information aggregation problem by creating summaries of the time series that capture the dynamic nature of the everyday-use CPAP. Our experiments have detected eight particular adherence behaviors validated with information-oriented statistical criteria; we successfully applied them to the time series of a French hospital to produce summaries that reflect the adherence of any 30 days of interest. Our method can aid physicians in more precisely evaluating the therapy adherence, as well as fostering systems to alert of problems in the treatment automatically.

Aim: To investigate PWV trajectories before and during the lockdown period among Withings Body Cardio bathroom scale users in France, in which a strict total lockdown was imposed, and Germany, in which partial social distancing measures were adopted. Methods: The study population is constituted by Withings BodyCardio Bathroom scale users with at least one recorded weight in the period from week 8 (start 17 February 2020) to week 17 of 2020 (end 26 April 2020) in France (n = 14,131) and Germany (n = 20,104). Subgroup analysis in owner of activity trackers and the blood pressure (BP) oscillometric devices were conducted. Linear growth curve modeling and clustering trajectories analysis were used. Results: French participants experienced during total lockdown a marked reduction in PWV, weight and physical activity, with no change in BP. German participants showed a higher PWV at baseline (difference 0.29 m/s, p < 0.0001), but French participants showed a steeper reduction over time (difference in slope –0.8 cm/s/week, p < 0.0001). Conversely, German participants had a greater weight at baseline than French participants, but also a greater weight reduction during lockdown, with a marginal reduction in PWV. In the French population three clusters were identified: decreasing (24.4%), stable (56.6%) and increasing PWV (19.0%). Decreasing and increasing PWV clusters had similarly higher PWV at baseline than stable PWV cluster, whereas only decreasing PWV cluster showed a significant weight reduction (−500 g). Conclusion: Total lockdown induced a reduction in PWV in a significant proportion of French bathroom scale users, thus representing an opportunity to improve their cardiovascular health.

Background: Use of adaptive servo-ventilation (ASV) has been questioned in patients with central sleep apnea (CSA) and chronic heart failure (CHF). This study aims to detail the present use of ASV in clinical practice.Methods: Descriptive, cross-sectional, multicentric study of patients undergoing long term (≥3 months) ASV in the Cantons of Geneva or Vaud (1,288,378 inhabitants) followed by public or private hospitals, private practitioners and/or home care providers.Results: Patients included (458) were mostly male (392; 85.6%), overweight [BMI (median, IQR): 29 kg/m2 (26; 33)], comorbid, with a median age of 71 years (59–77); 84% had been treated by CPAP before starting ASV. Indications for ASV were: emergent sleep apnea (ESA; 337; 73.6%), central sleep apnea (CSA; 108; 23.6%), obstructive sleep apnea (7; 1.5%), and overlap syndrome (6; 1.3%). Origin of CSA was cardiac (n = 30), neurological (n = 26), idiopathic (n = 28), or drug-related (n = 22). Among CSA cases, 60 (56%) patients had an echocardiography within the preceding 12 months; median left ventricular ejection fraction (LVEF) was 62.5% (54–65); 11 (18%) had a LVEF ≤45%. Average daily use of ASV was [mean (SD)] 368 (140) min; 13% used their device

Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Tumor Necrosis Factor a (TNFα), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1β, and TNFα is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management.

Abstract Background The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with “sharp” large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM patterns. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. Methods In 573 consecutive patients attending an in-laboratory PSG for suspected sleep disordered breathing (SDB), MM signals were acquired using magnetometry and scored manually while blinded from the PSG signal. Data analysis aimed to verify the concordance between the CSB identified by PSG and the presence of LPM or SPM. The data were randomly divided into training and validation sets (985 5-min segments/set) and concordance was evaluated using 2 classification models. Results In PSG, 22 patients (mean age ± SD: 65.9 ± 15.0 with a sex ratio M/F of 17/5) had CSB (mean central apnea hourly indice ± SD: 17.5 ± 6.2) from a total of 573 patients with suspected SDB. When tested on independent subset, the classification of CSB based on LPM and SPM is highly accurate (Balanced-accuracy = 0.922, sensitivity = 0.922, specificity = 0.921 and error-rate = 0.078). Logistic models based odds-ratios for CSB in presence of SPM or LPM were 172.43 (95% CI: 88.23–365.04; p

Central sleep apnoea (CSA) including periodic breathing is prevalent in more than one-third of patients with heart failure and is highly and independently associated with poor outcomes. Optimal treatment is still debated and well-conducted studies regarding efficacy and impact on outcomes of available treatment options are limited, particularly in cardiac failure with preserved ejection fraction. While continuous positive airway pressure and oxygen reduce breathing disturbances by 50%, adaptive servoventilation (ASV) normalises breathing disturbances by to controlling the underlying mechanism of CSA. Results are contradictory regarding impact of ASV on hard outcomes. Cohorts and registry studies show survival improvement under ASV, while secondary analyses of the large SERVE-HF randomised trial showed an excess mortality in cardiac failure with reduced ejection fraction. The current priority is to understand which phenotypes of cardiac failure patients may benefit from treatment guiding individualised and personalised management.

Auto-CPAP may cause sleep fragmentation due to variations in pressure and unintentional leaks. The aim of this study was to compare air leak between fixed-CPAP and auto-CPAP after 4 months of CPAP treatment. This study is an ancillary analysis of a randomized, double-blind, parallel, controlled trial over 4 months, comparing fixed- and auto-CPAP in newly diagnosed patients with OSA. The following data were extracted from the CPAP devices: mean and 90th percentile pressure, residual apnea-hypopnea index, mean CPAP use, and amount of leak. Within each arm, patients were also randomly allocated to use of one of the three different brands of devices. Since the leak was reported differently for each device, median leak value was determined for each brand and leaks were classified as “above the median” or “below the median”. Data from 269 patients were analyzed. The univariate analysis showed that tobacco consumption, CPAP level, and oronasal masks were associated with leaks above the median value but not the type of CPAP. The multivariate analysis showed that only CPAP level and oronasal masks were associated with leaks below the median. There were no differences in the types of mask used between fixed- and auto-CPAP. There was no impact of the type of CPAP on leaks or the type of interface used. We used a method based on the median leak value to standardize comparisons across devices which report leaks with different definitions.

The World Health Organization has estimated that air pollution is a major threat to health, causing approximately nine million premature deaths every year. Each individual has, over their lifetime, a unique exposure to air pollution through their habits, working and living conditions. Medical research requires dedicated tools to assess and understand individual exposure to air pollution in view of investigating its health effects. This paper presents portable sensors produced by the Canarin Project that provides accessible, real time personal exposure data to particulate matter. Our primary results demonstrate the use of portable sensors for the assessment of personal exposure to the different micro-environments attended by individuals, and for inspecting the short-term effects of air pollution through the example of sleep apnea. These findings underscore the necessity of obtaining contextual data in determining environmental exposure and give perspectives for the future of air pollution sensors dedicated to medical research.

BackgroundObstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea–related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases. Thus, in the present study, we hypothesized that nmMLCK plays a key role in the IH‐induced vascular dysfunctions and inflammatory remodeling. Methods and ResultsTwelve‐week‐old nmMLCK+/+ or nmMLCK−/− mice were exposed to 14‐day IH or normoxia. IH was associated with functional alterations characterized by an elevation of arterial blood pressure and stiffness and perturbations of NO signaling. IH caused endothelial barrier dysfunction (ie, reduced transendothelial resistance in vitro) and induced vascular oxidative stress associated with an inflammatory remodeling, characterized by an increased intima‐media thickness and an increased expression and activity of inflammatory markers, such as interferon‐γ and nuclear factor‐κB, in the vascular wall. Interestingly, nmMLCK deletion prevented all IH‐induced functional and structural alterations, including the restoration of NO signaling, correction of endothelial barrier integrity, and reduction of both oxidative stress and associated inflammatory response. ConclusionsnmMLCK is a key mechanism in IH‐induced vascular oxidative stress and inflammation and both functional and structural remodeling.

ContextMandibular movements (MM) are considered as reliable reporters of respiratory effort (RE) during sleep and sleep disordered breathing (SDB), but MM accuracy has never been validated against the gold standard diaphragmatic electromyography (EMG-d).ObjectivesTo assess the degree of agreement between MM and EMG-d signals during different sleep stages and abnormal respiratory events.MethodsTwenty-five consecutive adult patients with SDB were studied by polysomnography (PSG) that also included multipair esophageal diaphragm electromyography and a magnetometer to record MM. EMG-d activity (microvolt) and MM (millimeter) amplitudes were extracted by envelope processing. Agreement between signals amplitudes was evaluated by mixed linear regression and cross-correlation function and in segments of PSG including event-free and SDB periods.ResultsThe average total sleep time was 370 ± 18 min and the apnea hypopnea index was 24.8 ± 5.2 events/h. MM and EMG-d amplitudes were significantly cross-correlated: median r (95% CI): 0.67 (0.23–0.96). A mixed linear model showed that for each 10 µV of increase in EMG-d activity, MM amplitude increased by 0.28 mm. The variations in MM amplitudes (median range: 0.11–0.84 mm) between normal breathing, respiratory effort-related arousal, obstructive, mixed, and central apnea periods closely corresponded to those observed with EMG-d activity (median range: 2.11–8.23 µV).ConclusionMM amplitudes change proportionally to diaphragmatic EMG activity and accurately identify variations of RE during normal sleep and SDB.

Obstructive sleep apnoea (OSA) is a highly prevalent disorder associated with complications such as arterial hypertension, cardiovascular diseases and traffic accidents. The resources allocated for OSA are insufficient and OSA is a significant public health problem. Portable recording devices have been developed for the detection of OSA syndrome and have proved capable of providing an equivalent diagnosis to in-laboratory polysomnography (PSG), at least in patients with a high pre-test probability of OSA syndrome. PSG becomes important in patients who have symptoms and certain comorbidities such as chronic obstructive pulmonary disease or stroke, as well as in patients with a clinical history suggesting a different sleep disorder. Continuous positive airway pressure is the most effective treatment in OSA. Ambulatory monitoring of the therapeutic modalities has been evaluated to enhance the care process and reduce costs compared to the conventional approach, without sacrificing efficiency. This review evaluates the role of portable monitoring devices in the diagnostic process of OSA and the search for alternative strategies based on ambulatory management protocols.

Rationale. Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods. This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. Results. 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m2. In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (−0.29; 0.28), P=0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: −6.34 mmHg (−12.68; −0.01), P=0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion. In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.

BackgroundThe higher mortality rate in untreated patients with obesity-associated hypoventilation is a strong rationale for long-term noninvasive ventilation (NIV). The impacts of comorbidities, medications and NIV compliance on survival of these patients remain largely unexplored.MethodsObservational cohort of hypercapnic obese patients initiated on NIV between March 2003 and July 2008. Survival curves were estimated by the Kaplan-Meier method. Anthropometric measurements, pulmonary function, blood gases, nocturnal SpO(2) indices, comorbidities, medications, conditions of NIV initiation and NIV compliance were used as covariates. Univariate and multivariate Cox models allowed to assess predictive factors of mortality.ResultsOne hundred and seven patients (56% women), in whom NIV was initiated in acute (36%) or chronic conditions, were followed during 43±14 months. The 1, 2, 3 years survival rates were 99%, 94%, and 89%, respectively. In univariate analysis, death was associated with older age (>61 years), low FEV1 (ConclusionCardiovascular comorbidities represent the main factor predicting mortality in patient with obesity-associated hypoventilation treated by NIV. In this population, NIV should be associated with a combination of treatment modalities to reduce cardiovascular risk.

RationaleIn obstructive sleep apnea patients (OSA), continuous positive airway pressure (CPAP) adherence is crucial to improve symptoms and cardiometabolic outcomes. The choice of mask may influence CPAP adherence but this issue has never been addressed properly.ObjectiveTo evaluate the impact of nasal pillows, nasal and oronasal masks on CPAP adherence in a cohort of OSA.MethodsNewly CPAP treated OSA participating in "Observatoire Sommeil de la Fédération de Pneumologie", a French national prospective cohort, were included between March 2009 and December 2011. Anthropometric data, medical history, OSA severity, sleepiness, depressive status, treatment modalities (auto-CPAP versus fixed pressure, pressure level, interface type, use of humidifiers) and CPAP-related side effects were included in multivariate analysis to determine independent variables associated with CPAP adherence.Results2311 OSA (age = 57(12) years, apnea+hypopnea index = 41(21)/h, 29% female) were included. Nasal masks, oronasal masks and nasal pillows were used by 62.4, 26.2 and 11.4% of the patients, respectively. In univariate analysis, oronasal masks and nasal pillows were associated with higher risk of CPAP non-adherence. CPAP non-adherence was also associated with younger age, female gender, mild OSA, gastroesophageal reflux, depression status, low effective pressure and CPAP-related side effects. In multivariate analysis, CPAP non-adherence was associated with the use of oronasal masks (OR = 2.0; 95%CI = 1.6; 2.5), depression, low effective pressure, and side effects.ConclusionAs oronasal masks negatively impact on CPAP adherence, a nasal mask should be preferred as the first option. Patients on oronasal masks should be carefully followed.

Exercise intolerance in COPD seems to combine abnormal ventilatory mechanics, impaired O2 transport and skeletal muscle dysfunction. However their relative contribution and their influence on symptoms reported by patients remain to be clarified. In order to clarify the complex interaction between ventilatory and neuromuscular exercise limiting factors and symptoms, we evaluated respiratory muscles and quadriceps contractile fatigue, dynamic hyperinflation and symptoms induced by exhaustive high-intensity cycling in COPD patients. Fifteen gold II-III COPD patients (age = 67 ± 6 yr; BMI = 26.6 ± 4.2 kg.m(-2)) performed constant-load cycling test at 80% of their peak workload until exhaustion (9.3 ± 2.4 min). Before exercise and at exhaustion, potentiated twitch quadriceps strength (Q(tw)), transdiaphragmatic (P(di,tw)) and gastric (P(ga,tw)) pressures were evoked by femoral nerve, cervical and thoracic magnetic stimulation, respectively. Changes in operational lung volumes during exercise were assessed via repetitive inspiratory capacity (IC) measurements. Dyspnoea and leg discomfort were measured on visual analog scale. At exhaustion, Q(tw) (-33 ± 15%, >15% reduction observed in all patients but two) and Pdi,tw (-20 ± 15%, >15% reduction in 6 patients) were significantly reduced (P15% reduction in 3 patients). Percentage reduction in Q(tw) correlated with the percentage reduction in P(di,tw) (r = 0.66; P

BACKGROUND:Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION:To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY:14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS:OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS:Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION:ClinicalTrials.gov NCT00603096.

Abstract The purpose of this study is to objectively assess by polysomnography total sleep time and sleep macrostructure in glaucomatous versus non-glaucomatous individuals after adjusting for possible confounding factors affecting the quality of sleep. This is an observational, prospective, single-center, case-controlled study using a sleep research database (MARS e-Cohort) collecting clinical data, comorbidities, medications, and sleep studies of glaucomatous and non-glaucomatous individuals. The diagnosis of glaucoma was confirmed with a full comprehensive ophthalmological examination including a visual field test. Total sleep time and the main sleep parameters (time spent in stages 1, 2, 3 and 4, microarousals, apnea–hypopnea index, and indices of hypoxic burden) were compared in glaucomatous and non-glaucomatous individuals after adjusting for age, anthropometric data, and comorbidities. The study included 33 glaucomatous and 66 non-glaucomatous individuals. The median total sleep time was 325 min [273; 398] for the control group and 311 min [244; 349] for the glaucoma group. After adjusting for the potential confounding factors, there was no significant difference in total sleep time (p = 0.3) and other sleep parameters between the control group and the glaucoma group. The sleep macrostructure was comparable in the glaucomatous and non-glaucomatous individuals after careful adjustment for confounders.

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

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