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International audience; Objective: In obstructive sleep apnea patients on continuous positive airway pressure (CPAP) treatment there is growing evidence for a significant impact of the type of mask on the residual apnea-hypopnea index (rAHI). Here, we propose a method for automatically classifying the impact of mask changes on rAHI.Methods: From a CPAP telemonitoring database of 3,581 patients, an interrupted time series design was applied to rAHI time series at a patient level to compare the observed rAHI after a mask-change with what would have occurred without the mask-change. rAHI time series before mask changes were modelled using different approaches. Mask changes were classified as: no effect, harmful, beneficial. The best model was chosen based on goodness-of-fit metrics and comparison with blinded classification by an experienced respiratory physician.Results: Bayesian structural time series with synthetic controls was the best approach in terms of agreement with the physician.s classification, with an accuracy of 0.79. Changes from nasal to facial mask were more often harmful than beneficial: 13.4% vs 7.6% (p-value < 0.05), with a clinically relevant increase in average rAHI greater than 8 events/hour in 4.6% of cases. Changes from facial to nasal mask were less often harmful: 6.0% vs 11.4% (p-value < 0.05).Conclusion: We propose an end-to-end method to automatically classify the impact of mask changes over fourteen days after a switchover.Significance: The proposed automated analysis of the impact of changes in health device settings or accessories presents a novel tool to include in remote monitoring platforms for raising alerts after harmful interventions.

International audience; Objectives: The aim of the present study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration.Design: Prospective nonrandomized study.Setting: Patients hospitalized in ICU for COVID-19 infection.Patients: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU.Interventions: None.Measurements and main results: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status.Conclusions: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

BackgroundCurrent guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective.MethodsPatients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP).ResultsBetween May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2and PaCO26.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2(difference −0.27 kPa, 95% CI −0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI −£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference −0.006, 95% CI −0.05 to 0.04). There were no differences in secondary outcomes.DiscussionThere was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference.Trial registration numbersNCT02342899andISRCTN51420481.

International audience; une altération du système glymphatique, une atteinte du système à oréxine et des lésions du système circadien avec des anomalies de sécrétion de mélatonine. La polymédication et les conséquences psychiatriques et douloureuses secondaires au TC sont autant de facteur précipitants les troubles du sommeil. La prise en compte de ces spécificités physiopathologiques et cliniques est indispensable pour appréhender les troubles du sommeil aux différentes étapes du parcours de soin de ces patients. Du fait de la relation bidirectionnelle entre lésion traumatique et troubles du sommeil, un dépistage actif et adapté ainsi qu'une prise en charge multidisciplinaire et personnalisée pourrait permettre d'obtenir des bénéfices spécifiques chez les patients traumatisés crâniens.

International audience; Purpose: In patients with COPD, one of the leading indications for domiciliary non-invasive ventilation (NIV), a major paradigm shift has been observed over the past decade in the method for adjusting NIV settings, with the use of sufficient ventilatory support to achieve a significant reduction in PaCO2. Whether this approach may be relevant to other populations, especially slowly progressive neuromuscular diseases (NMD), is unknown.Methods: This study was conducted as a post hoc analysis from a previously published randomized controlled trial (NCT03458507). Patients with NMD treated with domiciliary NIV were stratified according to the level of ventilatory support: high-level tidal volume (HLVT; mL/kg of predicted body weight [PBW]) or high-level pressure support (HLPS), defined as a value above median value of the whole population (> 6.8 mL/kgPBW or 9.0 cmH2O, respectively). Primary outcome was mean nocturnal transcutaneous CO2 pressure (PtcCO2). Secondary outcomes included adherence to NIV, leaks, and side effects.Results: Of a total of 26 patients, 13 were exposed to HLVT, with significantly lower nocturnal PtcCO2 (respectively 40.5 ± 4.2 vs. 46.3 ± 3.9 mmHg, p = 0.002). A linear correlation between VT (mL/kgPBW) and mean nocturnal PtcCO2 was evidenced (r = - 0.59, 95%CI [- 0.80; - 0.25], p = 0.002). No significant impact of HLVT was found on secondary outcomes.Conclusion: Despite the lack of power of this post hoc analysis, our results suggest that higher levels of ventilatory support are correlated with lower PtcCO2 in patients with NMD. Further studies are desirable to assess the extent to which the level of assistance influences PaCO2 evolution in patients with slowly progressive NMD, as well as in restrictive thoracic disorders.

International audience; Protein kinase inhibitors experienced their advent in the 2000s. Their market introduction made it possible to constitute a class of targeted therapies administered orally. This name was chosen to mark a break with conventional chemotherapy drugs, but it is important to stress that these are multi-target drugs with complex affinity profiles. Adverse effects can be explained by direct interactions with their targets of interest, chosen for their indications (on-target) but also interactions with other targets (off-target). The adverse effect profiles of these drugs are therefore varied and it is possible to identify common profiles related to inhibitions of common targets. Identification of these targets has improved the global understanding of the pathophysiological mechanisms underlying the onset of adverse drug reactions as well as of the related diseases, and makes it possible to predict the adverse effect profile of new protein kinase inhibitors based on their affinities. In this review, we describe the main adverse drug reactions associated with protein kinase inhibitors, their frequency and their plausible mechanisms of action.

International audience; High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH (pHa) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations-where the latter are thought to be fully adapted to high altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders and Andean and Sherpa highlanders at various altitudes (∼3,800, ∼4,300, and ∼5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n = 7) had elevated pHa compared with Sherpas (n = 12; P < 0.01), but not to lowlanders (n = 16; 9 days acclimatized; P = 0.09); 2) at 4,300 m, lowlanders (n = 16; 21 days acclimatized) had elevated pHa compared with Andeans (n = 32) and Sherpas (n = 11; both P < 0.01), and Andeans had elevated pHa compared with Sherpas (P = 0.01); and 3) at 5,000 m, lowlanders (n = 16; 14 days acclimatized) had higher pHa compared with both Andeans (n = 66) and Sherpas (n = 18; P < 0.01, and P = 0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P = 0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.NEW & NOTEWORTHY Lowlander, Andean, and Sherpa arterial blood data were combined across five independent high-altitude expeditions in the United States, Nepal, and Peru to assess acid-base status at ∼3,800, ∼4,300, and ∼5,000 m. The main finding was that Andean and Sherpa highlander populations have more acidic arterial blood, due to elevated arterial carbon dioxide and similar arterial bicarbonate compared with acclimatizing lowlanders at altitudes ≥4,300 m.

International audience; The basal metabolic rate characterizes the energy consumption of the human body at rest. It can be estimated by using respiratory gas exchange analyzers and indirect calorimetry. During cycling this value could vary due to several adaptation processes such as an increase in breathing and blood circulation, controlling body temperature, among others. In this paper we propose to reconstruct the instantaneous value of this basal metabolic rate, referred here as basal power (measured in Watts), by using a robust discrete-time proportional integral (PI) observer. The observer design is based on a solution of linear matrix inequalities and uses an uncertain linear parameter varying model of the gas exchange dynamics. The proposed methodology allows the reconstruction of the basal power while making the respiratory gas exchange estimation robust to bounded uncertainties and disturbances. The PI observer has been validated in simulation.

International audience; The frequency of high-altitude sojourns (for work, leisure, air travel or during car/train journeys) justifies the question of their tolerance, especially in people with pre-existing respiratory disease. Reduced barometric pressure and abrupt variations in temperature and inhaled air density may be responsible for modifications affecting the respiratory system and, in fine, oxygenation. These modifications may compromise altitude tolerance, further worsen respiratory dysfunction and render physical exercise more difficult. In obstructive lung disease, altitude is associated with gas exchange impairment, increased ventilation at rest and during exercise and heightened pulmonary artery pressure through hypoxic vasoconstriction, all of which may worsen dyspnea and increase the risk of altitude intolerance (acute mountain sickness, AMS). The most severe patients require rigorous evaluation, and hypoxic testing can be proposed. People with mild to moderate intermittent asthma can plan high altitude sojourns, provided that they remain under control at night and during exercise, and follow an adequate action plan in case of exacerbation. Respiratory disease patients with pulmonary artery hypertension (PAH) and chemoreflex control abnormalities need to be identified as at risk of altitude intolerance.

Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p

Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA.Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively.Results: The [HCO3-] level was normal in most patients (average 24.0 +/- 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030

International audience; Objectives: We aimed at assessing the efficacy and safety on antibiotics exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in critically ill adult patients with laboratory-confirmed SARS-CoV-2 pneumonia.Methods: This multicentre, parallel-group, open-label, randomised controlled trial enrolled patients admitted to 13 intensive care units (ICU) in France. Patients were assigned (1:1) to the control strategy, where antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first seven days of randomisation to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was > 1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end-point was antibiotic-free days at day 28.Results: Between April 20st and November 23st 2020, 194 patients were randomised, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial coinfection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference -2.0, (95% CI -10.6 to 6.6), P=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups.Conclusion: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.

Study Objectives In-laboratory polysomnography is the current gold standard for objective sleep measurements in clinical trials, but this does not capture night-to-night variability in sleep parameters. This study analyzed variability in sleep parameters recorded over multiple nights of sleep in an ecological setting using a portable sleep monitor and then estimated the minimum sample sizes required to reliably account for inter- and intra-individual variability in sleep parameters. Methods Participants were males who self-reported the absence of sleep disorders, and used a sleep monitoring device (Dreem Headband, Dreem, France) over multiple nights of sleep. Night-to-night variability of sleep parameters was determined over five consecutive weeknights using coefficients of variation (CV), and the minimal number of individuals and nights needed to reliably determine each sleep parameter was assessed. Results Night-to-night variability for the whole group (n = 94; 470 nights) was high (CV 0.44–0.58) for N2, N3, sleep onset and persistent sleep latencies, and wake after sleep onset (WASO), medium (CV 0.22–0.28) for N1 and N3 percentage, awakenings and REM latency, and low (CV 0.04–0.19) for sleep efficiency, N2 and REM percentages, total sleep time (TST) and micro-arousal index. Minimum sample sizes for reliable assessment of TST and WASO were 2 nights with 10 participants and 4 nights with 50 participants, respectively. Conclusions Night-to-night variability of sleep parameters is underestimated and under-recognized. These data on variability in commonly used sleep parameters will facilitate better estimation of sample sizes and number of nights required in clinical trials based on the outcomes of interest.

The general public increasingly adopts smart wearable devices to quantify sleep characteristics and dedicated devices for sleep assessment. The rapid evolution of technology has outpaced the ability to implement validation approaches and demonstrate relevant clinical applicability. There are untapped opportunities to validate and refine consumer devices in partnership with scientists in academic institutions, patients, and the private sector to allow effective integration into clinical management pathways and facilitate trust in adoption once reliability and validity have been demonstrated. We call for the formation of a working group involving stakeholders from academia, clinical care and industry to develop clear professional recommendations to facilitate appropriate and optimized clinical utilization of such technologies.

Objectives: This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (SunosiTM) 37.5 (OSA only), 75, 150, or 300 mg/d. Methods: In two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open -label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy. Results: After 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was-0.84%, compared with 0.54% for placebo, in participants with OSA; and-0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was-1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg,-1.2%; 300 mg,-2.5%).Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of-2.2% and-1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss >= 5% relative to baseline was 25.7% overall and increased in a dose -dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among sub-groups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss >= 5%, respectively. No weight-related treatment-emergent adverse events were serious. Conclusions: Solriamfetol treatment was associated with decreases in body weight in a dose-related manner.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundMechanisms underlying blood pressure changes in obstructive sleep apnoea (OSA) are incompletely understood. Increased respiratory effort is one of the main features of OSA and is associated with sympathetic overactivity, leading to increased vascular wall stiffness and remodelling. This study investigated associations between a new measure of respiratory effort (percentage of total sleep time spent with increased respiratory effort based on measurement of mandibular jaw movements (MJM): REMOV, %TST) and prevalent hypertension in adults referred for evaluation of suspected OSA.MethodsA machine learning model was built to predict hypertension from clinical data, conventional polysomnography (PSG) indices and MJM-derived parameters (including REMOV). The model was evaluated in a training subset and a test subset.ResultsThe analysis included 1127 patients: 901 (80%) in the training subset and 226 (20%) in the test subset. The prevalence of hypertension was 31% and 30%, respectively, in the training and test subsets. A risk stratification model based on 18 input features including REMOV had good accuracy for predicting prevalent hypertension (sensitivity 0.75 and specificity 0.83). Using the Shapley additive explanation method, REMOV was the best predictor of hypertension after clinical risk factors (age, sex, body mass index and neck circumference) and time with oxygen saturation ConclusionThe proportion of sleep time spent with increased respiratory effort automatically derived from MJM was identified as a potential new reliable metric to predict prevalent hypertension in patients with OSA.

Obstructive sleep apnea (OSA) is one of the most frequent chronic diseases, and comorbid obesity occurs in more than 60% of cases. Variations in body weight influence both OSA severity and OSA-related symptoms. We prospectively assessed the impact of a weight-loss program using the Berlin score to reflect OSA risk, and we also used the Epworth Sleepiness Scale (ESS) to assess daytime sleepiness. DietSleep was a prospective multicentric cohort study investigating OSA risk and daytime sleepiness before and after weight-loss intervention. One hundred and twenty-seven patients were included (initial OSA risk 36%), most of whom were women (85.8%) with a median body mass index (BMI) of 29.7 kg/m2, and the interquartile range was (27.6; 34). The diet-based weight-loss program induced a median decrease in BMI of 3.7 kg/m2 (−5; −2.9) (body weight~12.1% (−16.0; −8.8)) over a period of 171 days (114; 269). Changes in anthropometric values were similar regarding OSA risk after adjusting for initial values. Berlin scores significantly improved from 3 (1; 5) to 1 (0; 2), p < 0.01; the proportion of patients with a Berlin score ≥2 decreased from 36% to 7% after the intervention. The proportion of patients with ESS ≥11 decreased from 13% to 2%. These results confirm that a weight-loss program produces clinically relevant weight loss and a significant improvement in both OSA and subjective daytime sleepiness.

International audience; Background: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.Methods: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.Results: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).Conclusions: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

International audience; Elastic fibers, made of elastin (90%) and fibrillin-rich microfibrils (10%), are the key extracellular components, which endow the arteries with elasticity. The alteration of elastic fibers leads to cardiovascular dysfunctions, as observed in elastin haploinsufficiency in mice (Eln+/-) or humans (supravalvular aortic stenosis or Williams–Beuren syndrome). In Eln+/+ and Eln+/- mice, we evaluated (arteriography, histology, qPCR, Western blots and cell cultures) the beneficial impact of treatment with a synthetic elastic protein (SEP), mimicking several domains of tropoelastin, the precursor of elastin, including hydrophobic elasticity-related domains and binding sites for elastin receptors. In the aorta or cultured aortic smooth muscle cells from these animals, SEP treatment induced a synthesis of elastin and fibrillin-1, a thickening of the aortic elastic lamellae, a decrease in wall stiffness and/or a strong trend toward a reduction in the elastic lamella disruptions in Eln+/- mice. SEP also modified collagen conformation and transcript expressions, enhanced the aorta constrictive response to phenylephrine in several animal groups, and, in female Eln+/- mice, it restored the normal vasodilatory response to acetylcholine. SEP should now be considered as a biomimetic molecule with an interesting potential for future treatments of elastin-deficient patients with altered arterial structure/function.

IntroductionThe European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and to investigate the clinical outcome during positive airway pressure (PAP) treatment.MethodProspective OSA patient data were recruited from 35 sleep clinics in 21 European countries. Unsupervised cluster analysis (anthropometrics, clinical variables) was performed in a random sample (n=5000). Subsequently, all patients were assigned to the clusters using a conditional inference tree classifier. Responses to PAP treatment change in apnoea severity and Epworth sleepiness scale (ESS) were assessed in relation to baseline patient clusters and at short- and long-term follow-up.ResultsAt baseline, 20 164 patients were assigned (mean age 54.1±12.2 years, 73% male, median apnoea–hypopnoea index (AHI) 27.3 (interquartile range (IQR) 14.1–49.3) events·h−1, and ESS 9.8±5.3) to seven distinct clusters based on anthropometrics, comorbidities and symptoms. At PAP follow-up (median 210 [IQR 134–465] days), the observed AHI reduction (n=1075) was similar, whereas the ESS response (n=3938) varied: largest reduction in cluster 3 (young healthy symptomatic males) and 6 (symptomatic males with psychiatric disorders, −5.0 and −5.1 units, respectively (all pConclusionOSA patients can be classified into clusters based on clinically identifiable features. Importantly, these clusters may be useful for prediction of both short- and long-term responses to PAP intervention.

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.

International audience; Objectives: The respiratory workload, according to the diaphragm thickening fraction (TF) during sweep gas flow (SGF), decrease during weaning from venoarterial extracorporeal membrane oxygenation (VA ECMO) was evaluated for the present study.Design: Prospective observational study.Setting: Monocentric.Participants: Patients were included if they were suitable for a first VA ECMO weaning trial and were breathing spontaneously.Interventions: SGF was set for 15 minutes when the TF was measured at 4 L/min, 2 L/min, and 1 L/min, with a 10-minute return to baseline between each step. Mechanical ventilation, when required, was set to pressure-support ventilation mode with 7 cmH2O (pressure support) and a positive end-expiratory pressure of 0 cmH2O. Diaphragm ultrasound was used to assess the TF at the end of each step. Demographics, left ventricular ejection fraction (LVEF), and outcome were collected.Measurements and main results: Fifteen patients were included. Ten patients were extubated, and five were ventilated. TF values were 6.3% [0-10] at 4 L/min, 13.3% [10-26] at 2 L/min, and 26.7% [22-44] at 1 L/min (analysis of variance: p < 0.001 between 4 L/min and 2 L/min and p = 0.03 between 2 L/min and 1 L/min). TF did not differ whether patients were or were not ventilated or whether they were or were not weaned successfully from ECMO. TF was correlated with LVEF at 1 L/min SGF (Pearson R 0.67 [0.21-0.88]; p = 0.009) and at 2 L/min (R 0.7 [0.27-0.89]; p = 0.005) but not at 4 L/min. SGF mitigated the relationship between LVEF and TF (analysis of covariance: p < 0.005).Conclusions: Diaphragm TF was related to the SGF of the venoarterial ECMO settings and LVEF at the time of weaning.

Combining moderate-intensity exercise training with hypoxic exposure may induce larger improvement in cardiometabolic risk factors and health status compared with normoxic exercise training in obesity. Considering the greater cardiometabolic effects of high-intensity intermittent training (HIIT), we hypothesized that hypoxic high-volume HIIT (H-HIIT) would induce greater improvement in cardiorespiratory fitness and health status despite a lower absolute training workload than normoxic HIIT (N-HIIT) in overweight/obesity. Thirty-one subjects were randomized to an 8-week H-HIIT [10 male and 6 female; age: 51.0 ± 8.3 years; body mass index (BMI): 31.5 ± 4 kg·m−2] or N-HIIT (13 male and 2 female; age: 52.0 ± 7.5 years; BMI: 32.4 ± 4.8 kg·m−2) program (3 sessions/week; cycling at 80% or 100% of maximal workload for H-HIIT and N-HIIT, respectively; target arterial oxygen saturation for H-HIIT 80%, [Formula: see text] ∼0.12, i.e., ∼4,200 meters above sea level). Before and after training, the following evaluations were performed: incremental maximal and submaximal cycling tests, pulse-wave velocity, endothelial function, fasting glucose, insulin, lipid profile, and body composition. Maximal exercise (V̇o2peak: H-HIIT +14.2% ± 8.3% vs. N-HIIT +12.1 ± 8.8%) and submaximal (ventilatory thresholds) capacity and exercise metabolic responses (power output at the crossover point and at maximal fat oxidation rate) increased significantly in both groups, with no significant difference between groups and without other cardiometabolic changes. H-HIIT induced a greater peak ventilatory response (ANOVA group × time interaction F = 7.4, P = 0.016) compared with N-HIIT. In overweight/obesity, the combination of normobaric hypoxia and HIIT was not superior for improving cardiorespiratory fitness improvement compared with HIIT in normoxia, although HIIT in hypoxia was performed at a lower absolute training workload.

International audience; No abstract available

The association between obstructive sleep apnea (OSA) and cancer is still debated and data are scarce regarding the link between OSA and breast cancer progression. Since conclusive epidemiological studies require large sample sizes and sufficient duration of exposure before incident cancer occurrence, basic science studies represent the most promising approach to appropriately address the topic. Here we assessed the impact of intermittent hypoxia (IH), the major hallmark of OSA, on the development of breast cancer and explored the specific involvement of the endothelin signaling pathway. Original in vitro and in vivo models were used where 3D-spheroids or cultures of murine 4T1 breast cancer cells were submitted to IH cycles, and nude NMRI mice, orthotopically implanted with 4T1 cells, were submitted to chronic IH exposure before and after implantation. The role of the endothelin-1 in promoting cancer cell development was investigated using the dual endothelin receptor antagonist, macitentan. In vitro exposure to IH significantly increased 4T1 cell proliferation and migration. Meta-analysis of 4 independent in vivo experiments showed that chronic IH exposure promoted tumor growth, assessed by caliper measurement (overall standardized mean difference: 1.00 [0.45–1.55], p

International audience; Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.

International audience; No abstract available

STUDY OBJECTIVES: Minimal focus has been placed on variations in health care delivery for obstructive sleep apnea (OSA). This study compared positive airway pressure usage in developing countries (Brazil and Mexico) vs. a developed country (United States) and investigated the impact of a patient engagement tool (myAir; ResMed, San Diego, CA) on adherence. METHODS: Deidentified data from the AirView database (ResMed) for patients receiving positive airway pressure therapy with wirelessly connected Air10 (AirSense and AirCurve) devices in Brazil, Mexico, and the United States were analyzed. Adherence was defined using US Center for Medicare and Medicaid Services (CMS) criteria (usage ≥ 4 h/night on ≥ 70% of nights in the first 90 days). RESULTS: The analysis included 4,181,490 patients (Brazil: 31,672; Mexico 16,934; United States: 4,132,884). CMS adherence over 90 days was slightly lower in Latin America vs. the United States (Brazil: 71.7%; Mexico: 66.4%; United States: 74.0%). Significantly fewer patients were using the patient engagement tool in Brazil (8.1%) and Mexico (2.8%) vs. the United States (26%; both P < .001). Patients registered to use an engagement tool had a higher rate of CMS adherence and were twice as likely to achieve CMS adherence. Average daily usage and days with usage > 4 hours in the first week were the strongest predictors of CMS adherence. Across all countries, > 80% of patients meeting CMS criteria at 3 months were still using positive airway pressure therapy at 1 year, with 1-year adherences rates of > 75%. CONCLUSIONS: Short-term and long-term positive airway pressure adherence rates in Brazil and Mexico were similar to those achieved in the United States. Patients who registered to use an engagement tool consistently had better adherence than those who did not. CITATION: Drager LF, Malhotra A, Yan Y, et al. Adherence with positive airway pressure therapy for obstructive sleep apnea in developing vs developed countries: a big data study. J Clin Sleep Med. 2021;17(4):703–709.

International audience; No abstract available

International audience; Background and AimsTOTUM-63, a fibre and polyphenol rich plant-based composition, has been demonstrated to significantly improve body weight and glucose homeostasis in animal models of obesity. Our study aimed at exploring whether the mechanisms include modulation of gut (glucose-dependent insulinotropic peptide (GIP), glucagon-like petide-1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY)) and pancreatic (insulin, glucagon) hormones, all important regulators of glucose control, appetite and body weight.Methods and ResultsMale C57BL/6JRJ mice were assigned to either standard chow (CON), high fat diet (HF, 60% energy from fat) or HF-TOTUM-63 (HF diet 60% supplemented with TOTUM-63 2.7%) for 10 weeks. In vivo glucose homeostasis (oral glucose tolerance test (OGTT), intraperitoneal pyruvate tolerance test (ipPTT)), glucose-induced portal vein hormone concentration, gut hormone gene expression and protein content as well as enteroendocrine cell contents were assessed at the end of the dietary intervention. The present study evidenced that TOTUM-63 reduced food intake, limited weight gain and improved glucose and pyruvate tolerance of HF-fed animals. This was associated with an increase in PYY content in the colon, an altered pattern of PYY secretion between fasted and glucose-stimulated states, and with a significant improvement in the portal vein concentration of GLP-1, insulin and glucagon, but not GIP and CCK, in response to glucose stimulation.ConclusionOverall, these data suggest that TOTUM-63 might have a specific impact on gut L-cells and on the expression and secretion of GLP-1 and PYY incretins, potentially contributing to the reduced food intake, body weight gain and improved glucose homeostasis.

International audience; Introduction: Exercise limitation in chronic obstructive pulmonary disease (COPD) is multi-factorial; however, growing evidence indicates that muscle dysfunction may contribute in some patients.Areas covered: This work outlines current evidence for and against increased peripheral muscle fatigability in COPD through a comprehensive review of relevant literature available on PubMed/MEDLINE until May 2020. The authors first discuss key methodological issues relative to muscle fatigue assessment by non-volitional techniques, particularly magnetic stimulation. The authors then provide a detailed discussion of critical studies to have objectively measured skeletal muscle fatigue in individuals with COPD.Expert opinion: Current evidence indicates that localized (knee extension) and cycling exercise are associated with increased quadriceps fatigability in most COPD patients. Increased fatigability, however, has not been consistently found in response to walking, likely reflecting the tendency of 'central' respiratory constraints to overshadow potential functional impairments in the appendicular muscles in this form of exercise. Thus, addressing skeletal muscle abnormalities may be critical to translate improvements in lung mechanics (e.g., due to bronchodilator therapy) into better exercise tolerance. The positive effects of pulmonary rehabilitation on muscle fatigability are particularly encouraging and suggest a role for these measurements to test the efficacy of emerging adjunct training strategies focused on the peripheral muscles.

National audience

International audience; Purpose: Ultramarathon running includes two main types of events: single-stage race (SSR) and multistage races (MSR). Direct comparison of neuromuscular fatigue and recovery after SSR versus MSR race of comparable distance and elevation has never been performed. The aim of this study was to assess neuromuscular fatigue and recovery after two ultramarathons of equal distance performed either (i) in a single stage or (ii) in four successive days.Methods: Thirty-one runners participated in the study: 17 ran 169 km in a single-stage race and 14 performed around 40 km·d over 4 d. The two races were performed on the same course. Neuromuscular function was tested before (PRE), after (POST), and 2 (D + 2), 5 (D + 5) and 10 (D + 10) days after the races. Neuromuscular function was evaluated on both knee extensors (KE) and plantar flexors (PF) with voluntary and evoked contractions using electrical (femoral and tibial, respectively) nerve stimulation.Results: Reduction of voluntary activation measured in the KE was greater (i.e., central fatigue) for SSR than MSR directly after the race (-23% vs -7%), P < 0.01). Reductions in evoked mechanical KE and PF responses on relaxed muscle (i.e., peripheral fatigue) of both KE and PF took longer to recover in MSR than in SSR.Conclusions: Performing prolonged running exercise over several days, each separated by rest, elicits more prolonged impairments in contractile function compared with single-stage ultramarathon, whereas single-stage mountain ultramarathon ran on the same course is associated with greater central fatigue.

Exercise intolerance is characteristically multi-factorial in patients with chronic obstructive pulmonary disease (COPD) [1]. At least in symptomatic patients with moderate-to-severe airflow limitation, higher operating lung volumes assume a relevant role in decreasing patients’ tolerance to sustain “prolonged” exercise. As a consequence of the dynamic increase in the end-expiratory lung volume, tidal volume (VT) occurs close to total lung capacity (TLC), thereby reducing the room for further lung–chest wall expansion. The combination of low dynamic lung compliance and a severely reduced inspiratory reserve volume causes a mismatch between a growing respiratory neural drive and the resulting lung–chest wall displacement [2]. It has been postulated that such critical inspiratory constraints (CIC) lead to a plateau in VT, and a concomitant increase in dyspnoea as a function of ventilation (V′E) [3]. Accordingly, patients change their perception of the uncomfortable respiratory sensations from “laboured breathing” to “insufficient inspiration”, prompting early exercise termination [4]., The concept of critical inspiratory constraints is key to the modern understanding of exercise pathophysiology in patients with moderate-to-severe COPD https://bit.ly/2A6bCxD

According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance., D’après les dernières analyses de cas notamment en Chine et en Italie, le diabète semble être un facteur de risque d’aggravation de l’état clinique d’un patient atteint par le COVID-19 mais est-il un facteur de susceptibilité ? Une analyse de la littérature à la date du 6 mai 2020 tente de répondre à la question. Les données concernant le type de traitement antidiabétique à utiliser dans ces circonstances et son impact éventuel sur l’état clinique d’un patient infecté par le COVID-19 sont très rares. La dipeptidylpeptidase 4 (DPP-4), glycoprotéine membranaire ubiquitaire présente à la surface de nombreuses cellules et existant aussi sous forme soluble, est impliquée dans les réponses immunitaires inflammatoires en modifiant la production de plusieurs cytokines. La DPP-4 est impliquée dans l'infection des cellules par certains virus. Nous abordons la question de l’utilisation des inhibiteurs des DPP-4 chez les patients diabétiques et il n’y a pas à ce jour de données qui indiquent que l’état clinique des patients dépend de leur utilisation. De la même façon, l’utilisation de la metformine, des sulfamides hypoglycémiants, des analogues du GLP1 comme de l’insuline n’ont pas fait l’objet d’études dans ce contexte. Il nous parait prudent en phase aigüe de la maladie, en particulier chez les patients nécessitant un séjour en unités de soins intensifs de privilégier l’insuline chez eux. A la lumière d’une revue des recommandations sur la prise en charge des diabétiques,l’optimisation du contrôle glycémique est à privilégier et plusieurs messages clefs délivrés par les Sociétés savantes concluent ce travail.

Since December 2019, the COVID-19 pandemic has become a major public health problem. To date, there is no evidence of a higher incidence of COVID in patients with autoimmune rheumatic diseases and we support the approach of maintaining chronic rheumatological treatments. However, once infected there is a small but significant increased risk of mortality. Among the different treatments, NSAIDs are associated with higher rates of complications, but data for other drugs are conflicting or incomplete. The use of certain drugs for autoimmune inflammatory rheumatisms appears to be a potentially interesting options for the treatment. The rationale for their use is based on the immune system runaway and the secretion of pro-inflammatory cytokines (Il1, IL6, TNFα) in severe forms of the disease. Notably, patients on chloroquine or hydroxychloroquine as a treatment for their autoimmune rheumatic disease are not protected from COVID-19., Depuis décembre 2019, la pandémie de COVID-19 est devenue un problème majeur de santé publique. À ce jour, il n’y a aucune preuve d’une incidence plus élevée de COVID chez les patients atteints de maladies rhumatismales auto-immunes et nous soutenons l’approche consistant à maintenir les traitements rhumatologiques chroniques. Cependant, une fois infecté, il y a un risque accru de mortalité faible mais significatif. Parmi les différents traitements, les AINS sont associés à des taux plus élevés de complications, mais les données pour d’autres médicaments sont contradictoires ou incomplètes. L’utilisation de certains médicaments pour les rhumatismes inflammatoires auto-immuns semble être une option potentiellement intéressante pour le traitement. La raison de leur utilisation est basée sur l’emballement du système immunitaire et la sécrétion de cytokines pro-inflammatoires (Il1, IL6, TNFα) dans les formes graves de la maladie. Notamment, les patients sous chloroquine ou hydroxychloroquine comme traitement de leur maladie rhumatismale auto-immune ne sont pas protégés contre la COVID-19.

International audience; Bruxism is a heterogeneous condition related to various underlying mechanisms, including the presence of OSA. This case report illustrates that sleep mandibular movement monitoring and analysis could provide a useful opportunity for detection of both sleep bruxism and respiratory effort. The current case suggests that tracking of respiratory effort could enable evaluation of bruxism and its potential interactions. Successful treatment of sleep-related respiratory effort may lead to improved or resolution of bruxism in cases where such a causal relationship does exist.

Summary Background Positive airway pressure (PAP) has become a prominent treatment for children with sleep-disordered breathing. However, there are no large-scale studies to clarify whether PAP is well tolerated in children, and which factors are associated with better adherence to PAP therapy. In this study, we aimed to clarify adherence patterns of PAP therapy in a large paediatric population. Methods We did a cross-sectional big-data analysis in children from Oct 1, 2014, to Aug 1, 2018, using existing data derived from PAP devices uploaded nightly in the AirView cloud database. The AirView database is a usage tracking system available to all patients who are assigned PAP therapy, which requires consent from the patient or parent or guardian. All patients older than 4 years and younger than 18 years who used continuous or automated PAP devices were evaluated. Only patients living in the USA and enrolled with a single insurance company were included. If patients were participating in an engagement programme, programme onset must have been within 7 days of therapy onset. Our primary outcome was the proportion of patients who used PAP continuously over 90 days. The primary outcome was assessed in all patients who met the age inclusion criterion and had reliable age data available. Data on missing PAP use were imputed as zero, but data on other metrics were not imputed and excluded from analysis. Findings We used data recorded from Oct 1, 2014, to Aug 1, 2018. Of 40 140 children screened, 36 058 (89·8%) were US residents and 20 553 (90·1%) of them met the eligibility criteria and had accessible data (mean age 13·0 years [SD 3·7]). On the basis of 90 days of monitoring data, 12 699 (61·8%) patients continuously used PAP. Factors significantly associated with adherence included age group, residual apnoea–hypopnoea index, use and onset of patient engagement programmes, PAP pressure, and nightly median PAP mask leak, all over the 90-day study period. Interpretation To our knowledge, our study represents the largest analysis of children using PAP therapy to date. The findings suggest that adherence to PAP therapy is lower than in previous reports from adults. However, numerous actionable factors were associated with improvements in adherence and should be used strategically in clinical decision making to improve PAP adherence in children. Funding ResMed.

International audience; High altitude exposes humans to hypobaric hypoxia, which induces various physiological and molecular changes. Recent studies point toward interaction between circadian rhythms and the hypoxic response, yet their human relevance is lacking. Here, we examine the effect of different high altitudes in conjunction with time of day on human whole-blood transcriptome upon an expedition to the highest city in the world, La Rinconada, Peru, which is 5,100 m above sea level. We find that high altitude vastly affects the blood transcriptome and, unexpectedly, does not necessarily follow a monotonic response to altitude elevation. Importantly, we observe daily variance in gene expression, especially immune-related genes, which is largely altitude dependent. Moreover, using a digital cytometry approach, we estimate relative changes in abundance of different cell types and find that the response of several immune cell types is time- and altitude dependent. Taken together, our data provide evidence for interaction between the transcriptional response to hypoxia and the time of day in humans.

Background Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported. Methods With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software. Results 8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25–75: 61–77], 25.6% 95% 8.75–10.75) min/day, p 95% 4.00–6.00) min/day, p Conclusion During the first and second lockdowns, the COVID-19 pandemic had a clinically irrelevant effect on PAP adherence for the study population. Future studies are needed to describe COVID-19 pandemic impact on PAP adherence not only for long-term PAP-treated SA patients but also for incident cases. Trial registration The COVADENE study was registered on March 1st, 2021 on ClinicalTrials.gov (Identifier: NCT04775966)

International audience; Purpose: The combined effects of acute hypoxia and exercise on cognition remain to be clarified. We investigated the effect of speed climbing to high altitude on reactivity and inhibitory control in elite climbers.Methods: Eleven elite climbers performed a speed ascent of the Mont-Blanc (4810 m) and were evaluated pre- (at 1000 m) and immediately post-ascent (at 3835 m). In both conditions, a Simon task was done at rest (single-task session, ST) and during a low-intensity exercise (dual-task session, DT). Prefrontal cortex (PFC) oxygenation and middle cerebral artery velocity (MCAv) were monitored using near-infrared spectroscopy and transcranial Doppler, respectively, during the cognitive task. Self-perceived mental fatigue and difficulty to perform the cognitive tests were estimated using a visual analog scale. Heart rate and pulse oxygenation (SpO2) were monitored during the speed ascent.Results: Elite climbers performed an intense (~ 50% of the time ≥ 80% of maximal heart rate) and prolonged (8h58 ± 6 min) exercise in hypoxia (minimal SpO2 at 4810 m: 78 ± 4%). Reaction time and accuracy during the Simon task were similar pre- and post-ascent (374 ± 28 ms vs. 385 ± 39 ms and 6 ± 4% vs. 5 ± 4%, respectively; p > 0.05), despite a reported higher mental fatigue and difficulty to perform the Simon task post-ascent (all p < 0.05). The magnitude of the Simon effect was unaltered (p > 0.05), suggesting a preserved cognitive control post-ascent. Pattern of PFC oxygenation and MCAv differed between pre- and post-ascent as well as between ST and DT conditions.Conclusions: Cognitive control is not altered in elite climbers after a speed ascent to high-altitude despite substantial cerebral deoxygenation and fatigue perception.

BackgroundAdaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA.MethodsHFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea–hypopnoea index (AHI) ≥15 events·h−1with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed.Results40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h−1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min−1at baseline to 44.6±11.2 bursts·min−1; ASV group: 43.0±9.0 bursts·min−1at baseline to 42.74±9.45 bursts·min−1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective.ConclusionsSuppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

International audience; Background: Long-term noninvasive ventilation (LTNIV) is widely used in patients with chronic hypercapnic respiratory failure (CHRF) related to COPD. Prognosis of these patients is however poor and heterogenous. Research Question: In COPD patients under LTNIV for CHRF, is it possible to identify specific phenotypes which are predictive of probability of pursuing NIV and survival? Study Design and Methods: A latent class analysis was performed in a COPD population under LTNIV included in a comprehensive database of patients in the Geneva Lake area, to determine clinically relevant phenotypes. The observation period of this subgroup of COPD was extended to allow assessment of survival and/or pursuit of NIV for at least 2 years after inclusion. A logistic regression was conducted to generate an equation accurately attributing an individual patient to a defined phenotype. The identified phenotypes were compared on a series of relevant variables, as well as for probability of pursuing NIV or survival. A competitive risk analysis allowed to distinguish death from other causes of cessation of NIV. Results: Two phenotypes were identified: a “respiratory COPD” profile with very severe airway obstruction, a low or normal body mass index, and a low prevalence of comorbidities and a “systemic COPD” profile of obese COPDs with moderate airway obstruction and a high rate of cardiovascular and metabolic comorbidities. The logistic regression correctly classified 95.7% of patients studied. Probability of pursuing NIV and survival were significantly related to these phenotypes, with a poorer prognosis for “respiratory COPD.” Probability of death 5 years after implementing NIV was 22.3% (95% CI: 15.4–32.2) for “systemic COPD” versus 47.2% (37.4–59.6) for “respiratory COPD” (p = 0.001). Conclusion: The two distinct phenotypes of COPD under LTNIV for CHRF identified appear to be strongly related to prognosis and require further validation in other cohort studies.

International audience; Background and objective: Case reports have suggested that continuous positive airway pressure (CPAP) telemonitoring can detect the onset of acute cardiac events such as decompensated heart failure (HF) or atrial fibrillation through an increase in the apnoea-hypopnoea index (AHI) and onset of Cheyne-Stokes Respiration (CSR). This study addressed whether long-term remote CPAP treatment telemonitoring revealing CSR can help detect serious cardiac events (SCEs) in obstructive sleep apnoea (OSA) patients.Methods: This monocentric prospective cohort study included adults receiving CPAP therapy for OSA with daily telemonitoring. Any sudden increase in AHI generated an alert for the home healthcare provider to download CPAP data to identify CSR. A medical consultation was scheduled if CSR was detected.Results: We included 555 adults (412 men; 57% with known cardiovascular comorbidities). During the 1-year follow-up, 78 CSR episodes were detected in 74 patients (CSR+). The main conditions associated with incident CSR were HF (24 patients [30.8%]), ventilatory instability (21, 26.9%), leaks (13, 16.7%), medications inducing central apnoeas (baclofen, ticagrelor, opioids) (7, 9.0%), arrhythmias (6, 7.7%) and renal failure (2, 2.6%). Fifteen (20.3%) CSR+ patients had a confirmed SCE. In univariable analysis, a CSR episode increased the risk of an SCE by 13.8-fold (5.7-35.6) (p < 0.0001), with an adjusted OR of 5.7 (2.0-16.8) in multivariable analysis.Conclusion: Long-term telemonitoring of patients on CPAP treatment can alert CSR episodes and allows early detection of SCEs in patients with or without known cardiac comorbidities.

CT registration-derived indices provide data on regional lung functional changes in COPD. However, because unlike spirometry which involves dynamic maximal breathing maneuvers, CT-based functional parameters are assessed between two static breath-holds, it is not clear how regional and global lung function parameters relate to each other. We assessed the relationship between CT-density change (dHU), specific volume change (dsV), and regional lung tissue deformation (J) with global spirometric and plethysmographic parameters, gas exchange, exercise capacity, dyspnoea, and disease stage in a prospective cohort study in 102 COPD patients. There were positive correlations of dHU, dsV, and J with spirometric variables, DLCO and gas exchange, 6-min walking distance, and negative correlations with plethysmographic lung volumes and indices of trapping and lung distension as well as GOLD stage. Stepwise regression identified FEV1/FVC (standardized β = 0.429, p < 0.0001), RV/TLC (β = −0.37, p < 0.0001), and BMI (β = 0.27, p=β = 0.32, p=β = −0.48, p=

“Exercise starts and ends in the brain”: this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of exercise termination. In fact, there has been a growing interest relative to the “brain” response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the “brain” as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the “brain” contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research.

International audience; No abstract available

Objective: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time.Methods: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice.Results: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). Conclusion: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

International audience; Over recent years positive airway pressure (PAP) remote monitoring has transformed the management of obstructive sleep apnea and produced a large amount of data. Accumulated PAP data provide valuable and objective information regarding patient treatment adherence and efficiency. However, the majority of studies analyzing longitudinal PAP remote monitoring summarize data trajectories in static and simplistic metrics for PAP adherence and the residual apnea-hypopnea index (AHI) by using mean or median values. The aims of this article are to suggest directions for improving data cleaning and processing and to address major concerns for data science applications including: 1) conditions for rAHI reliability, 2) lack of standardization of indicators provided by different PAP models, 3) missing values and 4) consideration of treatment interruptions. To allow fair comparison between studies and to avoid biases in computation, PAP data processing and management should be conducted rigorously with these points in mind. PAP remote monitoring data contain a wealth of information that is currently underused in the field of sleep research. Improving the quality and standardizing data handling could facilitate data sharing among specialists worldwide and enable artificial intelligence strategies to be applied in the field of sleep apnea.

International audience; Left/right prefrontal cortex (PFC) activation are linked to positive/negative affects, respectively. Besides, larger left PFC oxygenation during exercise relates to higher cardiorespiratory fitness (CRF). High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) in improving CRF. The influence of training on PFC oxygenation and affects during exercise in individuals with obesity is, however, currently unknown. Twenty participants with obesity (14 males, 48±8 years, body-mass index= 35±6 kg•m-2) were randomized to MICT [50% peak work rate (WRpeak)] or HIIT (1min bouts 100% WRpeak; 3 sessions/week, 8 weeks). Before/after training, participants completed an incremental ergocycle test. Near-infrared spectroscopy and the Feeling Scale assessed PFC oxygenation and affects during exercise, respectively. Improvements in CRF (e.g. WRpeak: 32±14 vs 20±13W) were greater after HIIT vs MICT (p