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ObjectiveTo determine whether changes in pulmonary vascular resistance (PVR) and changes in pulmonary artery compliance (Cpa) are associated with changes in exercise capacity assessed either by changes in peak oxygen consumption (V′O2) or by changes in 6-min walk distance (6MWD) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA).MethodsInvasive haemodynamic parameters, peakV′O2and 6MWD were measured within 24 h, before and after BPA (interval 3.1±2.4 months) in 34 CTEPH patients without significant cardiac and/or pulmonary comorbidities, of whom 24 received at least one pulmonary hypertension-specific treatment.Cpawas calculated according to the pulse pressure method:Cpa=((SV/PP)/1.76+0.1), where SV is the stroke volume and PP is the pulse pressure. The resistance–compliance (RC)-time of the pulmonary circulation was calculated as the PVR andCpaproduct.ResultsAfter BPA, PVR decreased (562±234versus290±106 dyn·s·cm−5; pCpaincreased (0.90±0.36versus1.63±0.65 mL·mmHg−1; pversus0.321±0.083 s; p=0.75). There were improvements in peakV′O2(1.11±0.35versus1.30±0.33 L·min−1; pversus432±100 m; pV′O2or 6MWD, were significantly associated with changes in PVR, but not with changes inCpa.ConclusionsContrary to what has been reported in CTEPH patients undergoing pulmonary endarterectomy, in CTEPH patients undergoing BPA, changes in exercise capacity were not associated with changes inCpa.

Exercise-induced laryngeal obstruction (EILO) is suspected when dyspnea associated with upper airway symptoms is triggered by exercise. This condition affects mainly adolescent athletes. Visualization of the obstruction, while the patient is experiencing the symptoms during continuous laryngoscopy during exercise (CLE-test) is the gold standard for diagnosing EILO. Our study aims to evaluate the prevalence of EILO in a population presenting exercise-induced inspiratory symptoms (EIIS) or uncontrolled asthma with exertional symptoms. The second objective was to evaluate the diagnostic strength of laryngology consultation (LC) and pulmonary function tests (PFTs).All patients referred to our center for EIIS or uncontrolled asthma with exertional symptoms were included. EILO diagnosis was made if Maat score was 2 for patients with CLE-test or if there were inspiratory anomalies on PFTs and LC. The sensitivity and specificity of LC and PFTs as diagnostic tools were calculated considering CLE-test as the gold standard.Sixty two patients were referred to our center for EIIS or uncontrolled asthma with exertional symptoms. EILO was diagnosed in 28 patients (56%) with associated asthma in 9 patients (18%). The sensibility and specificity of LC for supraglottic anomalies were 75% and 60%, respectively. The sensibility and specificity of PFTs were 61% and 89%, respectively.There was a high prevalence of EILO among patients with EIIS and uncontrolled asthma. Some clinical characteristics might guide the diagnosis. Nevertheless, CLE-test remained the gold standard for EILO diagnosis and identification of the dysfunctional upper airway site to provide specific management.

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.

Background—Adults with Down’s syndrome (DS) present lower physical fitness associated with heightened sedentary behaviors and motor skills impairments. Their etiologies and determinants seem to be heterogeneous. This study aims to evaluate physical fitness in adults with DS and to identify specific physical fitness profiles depending on gender and physical activity levels. Methods—Forty adults with DS (16 women, 24 men, 29.7 ± 7.5 years) performed six tests from the EUROFIT Battery and Motor Assessment Battery for Children (MAB-C). Their maximal aerobic capacity was assessed using an incremental treadmill test to assess (VO2peak). Ecological, physical activity, and sedentary levels were evaluated subjectively (Global Physical Activity Questionnaire) and objectively using an Actigraph GT9X® accelerometer over a seven-day period. Results—VO2peak and isometric strength were significantly lower for women (p < 0.01), whereas men had significantly lower flexibility than women (p < 0.05). Using a principal component analysis and an agglomerative hierarchical analysis, we identified three clusters. Cluster 1 (n = 14; 50% men; Body Mass index = 28.3 ± 4.3) was characterized by significantly poorer physical fitness variables (VO2peak (p < 0.01), strength (p < 0.01) and balance (p < 0.05)) compared to Clusters 2 and 3. Cluster 2 (n = 19; 58% men; Body Mass index = 22.9 ± 2.0) and Cluster 3 (n = 19; 58% men; BMI = 22.9 ± 1.9) were characterized by subjects with comparable physical fitness profiles, except for the balance capacities, which were significantly lower in Cluster 3 (p < 0.05). Conclusions—DS subjects exhibited high heterogeneity in terms of physical fitness, PA, and sedentary levels, with a significant gender effect. The present findings are important to identify subjects at higher risk of sedentary behaviors and impaired motor capacities to develop personalized PA programs.

Resume L’hypoxie hypobare, caracteristique de l’environnement d’altitude, a des consequences physiologiques importantes sur les systemes cardio-vasculaire et respiratoire, qui sont fortement stimules pour maintenir au mieux un apport en oxygene le plus adequat possible. Ce processus dynamique d’acclimatation est influence a la fois par le niveau d’altitude concerne et la vitesse de progression mais est aussi tres individuel avec des reponses et des sensibilites variables. Ce large spectre des reponses est aussi a l’origine de symptomes plus ou moins importants caracterisant des pathologies specifiques que sont le mal aigu des montagnes, l’œdeme cerebral et l’œdeme pulmonaire de haute altitude. Cet article se propose de faire le point sur les connaissances actuelles a la fois sur l’acclimatation mais aussi sur les differentes pathologies specifiques a l’hypoxie d’altitude.

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.

Participation in ultra-endurance running (UER) events continues to grow across ages, including youth athletes. The 50- and 100-km are the most popular distances among youth athletes. Most youth athletes are between 16–18 years; however, some runners younger than 12 years have successfully completed UER events. Parents, athletes, coaches, race directors, and medical professionals often seek advice regarding the safety of youth athletes participating in these events, especially with regard to potential short and long-term health consequences. UER may impact key organ systems during growth and development. We propose a decision-making process, based on current knowledge and the experience of the consensus group that addresses age regulations, medical and psychological well-being, training status and race-specific factors (such as distance, elevation change, remoteness, ambient temperatures, level of medical assistance, and type of provisions provided by the race organizers) to use until evidence of long-term consequences of UER in youth athletes is available. These recommendations are aimed at safe participation in UER events for youth athletes with a proper and individualized assessment.

International audience; No abstract available

It is well established that physical activity reduces all-cause mortality and can prolong life. Ultra-endurance running (UER) is an extreme sport that is becoming increasingly popular, and comprises running races above marathon distance, exceeding 6 h, and/or running fixed distances on multiple days. Serious acute adverse events are rare, but there is mounting evidence that UER may lead to long-term health problems. The purpose of this review is to present the current state of knowledge regarding the potential long-term health problems derived from UER, specifically potential maladaptation in key organ systems, including cardiovascular, respiratory, musculoskeletal, renal, immunological, gastrointestinal, neurological, and integumentary systems. Special consideration is given to youth, masters, and female athletes, all of whom may be more susceptible to certain long-term health issues. We present directions for future research into the pathophysiological mechanisms that underpin athlete susceptibility to long-term issues. Although all body systems can be affected by UER, one of the clearest effects of endurance exercise is on the cardiovascular system, including right ventricular dysfunction and potential increased risk of arrhythmias and hypertension. There is also evidence that rare cases of acute renal injury in UER could lead to progressive renal scarring and chronic kidney disease. There are limited data specific to female athletes, who may be at greater risk of certain UER-related health issues due to interactions between energy availability and sex-hormone concentrations. Indeed, failure to consider sex differences in the design of female-specific UER training programs may have a negative impact on athlete longevity. It is hoped that this review will inform risk stratification and stimulate further research about UER and the implications for long-term health.

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.

Resume Introduction L’insuffisance cardiaque touche pres de 2 % de la population avec une morbi-mortalite elevee malgre les avancees de la prise en charge therapeutique. Le syndrome d’apnee du sommeil (SAS) constitue un facteur de risque et d’aggravation de la dysfonction myocardique. Etat des connaissances Le SAS est retrouve chez 70 % des patients insuffisants cardiaques, 65 % des patients avec hypertension arterielle refractaire, 60 % des patients avec accident vasculaire cerebral et 50 % des patients avec fibrillation atriale. La morbidite cardiovasculaire associee est multipliee par 2 a 3. Les mecanismes physiopathologiques sont l’hypoxie intermittente nocturne, les variations de capnie, les variations de pressions intrathoraciques et les micro-eveils repetes, le tout concourant en une hyperactivation sympathique, une dysfonction endotheliale et une inflammation systemique. Conclusions La prise en charge du SAS chez les patients presentant une dysfonction myocardique doit etre couplee a la prise en charge cardiologique. Il est necessaire de poursuivre les evaluations scientifiques afin de determiner un parcours de soins precis et la place respective de chacune des prises en charge pneumologique et cardiologique.

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.

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.

There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID).The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes.950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR).285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+)The absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503).

Left/right prefrontal cortex (PFC) activation is 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

Aims A unique Andean population lives in the highest city of the world (La Rinconada, 5100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy and CMS highlanders. Methods and results Highlanders living permanently at 3800 m (n = 23) and 5100 m (n = 55) with (n = 38) or without CMS (n = 17) were compared with 18 healthy lowlanders. Rest and exercise echocardiography were performed to describe cardiac remodelling, pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR). Total blood volume (BV) and haemoglobin mass were determined in all people. With the increase in the altitude of residency, the right heart dilated with an impairment in right ventricle systolic function, while the left heart exhibited a progressive concentric remodelling with Grade I diastolic dysfunction but without systolic dysfunction. Those modifications were greater in moderate–severe CMS patients. The mean PAP was higher both at rest and during exercise in healthy highlanders at 5100 m. The moderate–severe CMS subjects had a higher PVR at rest and a larger increase in PAP during exercise. The right heart remodelling was correlated with PAP, total BV, and SpO2. Conclusion Healthy dwellers at 5100 m exhibit both right heart dilatation and left ventricle concentric remodelling with diastolic dysfunction. Those modifications are even more pronounced in moderate–severe CMS subjects and could represent the limit of the heart's adaptability before progression to heart failure.

A study to measure the composition of exhaled air was carried out in subjects living in the highest city in the world: La Rinconada in Peru. People living at high altitude have a strongly disturbed metabolism and have to deal with major physiological disturbances. It is very likely that these subjects develop a disturbance of their redox system. It was therefore undertaken to study their ability to resist oxidative stress by measuring markers in the exhaled air. The traditional biomarkers encountered in this case are the alkanes resulting from the oxidative degradation of unsaturated fatty acids. The breath was collected on carbotrap tubes thanks to the Exp'Air sampling system. The analyses were carried out by GC-MS. In addition to some alkanes, witnesses of the particular conditions of their exposure to the low quantities of oxygen present in the air, it was discovered surprisingly the presence of a compound rarely detected in the exhaled air, limonene. Hypotheses are presented but no certainty exists as to the origin of this compound in the breath. Further studies are underway to determine the conditions and circumstances of occurrence of limonene in the exhaled air of these subjects chronically exposed to hypoxia.

Several brands of water enriched with O2 (O2-waters) are commercially available and are advertised as wellness and fitness waters with claims of physiological and psychological benefits, including improvement in exercise performance. However, these claims are based, at best, on anecdotal evidence or on a limited number of unreliable studies. The purpose of this double-blind randomized study was to compare the effect of two O2-waters (~110 mg O2·L−1) and a placebo (10 mg O2·L−1, i.e., close to the value at sea level, 9–12 mg O2·L−1) on the cardiopulmonary responses and on performance during high-intensity exercise. One of the two O2-waters and the placebo were prepared by injection of O2. The other O2-water was enriched by an electrolytic process. Twenty male subjects were randomly allocated to drink one of the three waters in a crossover study (2 L·day−1 × 2 days and 15 mL·kg−1 90 min before exercise). During each exercise trial, the subjects exercised at 95.9 ± 4.7% of maximal workload to volitional fatigue. Exercise time to exhaustion and the cardiopulmonary responses, arterial lactate concentration and pH were measured. Oxidative damage to proteins, lipids and DNA in blood was assessed at rest before exercise. Time to exhaustion (one-way ANOVA) and the responses to exercise (two-way ANOVA [Time; Waters] with repeated measurements) were not significantly different among the three waters. There was only a trend (p = 0.060) for a reduction in the time constant of the rapid component of VO2 kinetics with the water enriched in O2 by electrolysis. No difference in oxidative damage in blood was observed between the three waters. These results suggest that O2-water does not speed up cardiopulmonary response to exercise, does not increase performance and does not trigger oxidative stress measured at rest.

International audience; Purpose: Both prolonged exercise and acute high-altitude exposure are known to induce cardiac changes. We sought to describe the cardiac responses to speed climbing at high-altitude, including left ventricular (LV) performance assessment using the myocardial work index (MWI), a new index derived from 2D speckle tracking echocardiography (STE).Methods: Eleven elite alpinists (9 males, age: 26 ± 4 years) were evaluated before and immediately after a speed ascent of the Mont-Blanc (4808 m) by echocardiography using conventional measurements as well as STE and MWI computation with derivate parameters as global work efficiency (GWE) or global wasted work (GWW).Results: Athletes performed a long-duration (8 h 58 min ± 60 min) and intense (78 ± 4% of maximal heart rate) ascent under gradual hypoxic conditions (minimal SpO2 at 4808 m: 71 ± 4%). Hypoxic exercise-induced cardiac fatigue was observed post-ascent with a change in right ventricular (RV) and LV systolic function (RV fractional area change: - 20 ± 23%, p = 0.01; LV global longitudinal strain change: - 8 ± 9%, p = 0.02), as well as LV geometry and RV-LV interaction alterations with emergence of a D-shape septum in 5/11 (46%) participants associated with RV pressure overload (mean pulmonary arterial pressure change: + 55 ± 20%, p < 0.001). Both MWI and GWE were reduced post-ascent (- 21 ± 16%, p = 0.004 and - 4 ± 4%, p = 0.007, respectively). Relative decrease in MWI and GWE were inversely correlated with increase in GWW (r = - 0.86, p = 0.003 and r = -0.97, p < 0.001, respectively).Conclusions: Prolonged high-altitude speed climbing in elite climbers is associated with RV and LV function changes with a major interaction alteration. MWI, assessing the myocardial performance, could be a new tool for evaluating LV exercise-induced cardiac fatigue.

Background: Sleep disordered breathing (SDB) is a frequent disorder with serious adverse health consequences in people with Down syndrome (DS). This study aims to evaluate and classify sleep and physical activity (PA) characteristics in adults with DS. Methods: Forty participants with DS wore an accelerometer for seven consecutive days to measure physical activity and sleep–wake patterns. The corresponding data were also obtained by survey and polysomnography. The apnea-hypopnea index (AHI) is calculated from the number of apneas and hypopneas per hour of sleep according to international guidelines. Results: Polysomnography showed SDB based on AHI in 95% of adults: 50% had severe SDB, 22.5% presented moderate and 22.5% mild SDB, predominantly in males. They had poor sleep quality (80.1%) and low PA levels. Using statistical classification methods, we observed three clusters with two opposite profiles. Clusters 2 and 3 showed low PA indices (daily steps: 5719 and 5310, respectively) and severe SDB (AHI = 33.6 and 55.5 events/h), high age and high gonial angle. Cluster 1 showed high PA (mean count of daily steps: 6908) and mild to moderate SDB (AHI = 16.8 events/h), low age and low gonial angle. Conclusions: Our findings suggest that there are different profiles (age, gender, obesity, gonial angle) that are associated with SDB in adults with DS. These results suggest that this may represent important factors to consider when planning health promotion and prevention.

International audience; Champigneulle, Benoit, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V. Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, and Samuel Verges. High-altitude environment and COVID-19: SARS-CoV-2 seropositivity in the highest city in the world. High Alt Med Biol. 22: 000-000, 2021. Background: A reduced coronavirus disease 2019 (COVID-19) diffusion has been suggested in high-altitude areas but remained questionable. Aims of this study were to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity as well as the risk factors associated in La Rinconada, the highest city in the world (5,100-5,300 m), a gold-mining town located in southeastern Peru where >50,000 dwellers live in precarious sanitary conditions. Materials and Methods: We performed a cross-sectional study during a 1-week period in October 2020, using point-of-care lateral flow serological assays allowing detection of antibodies directed against SARS-CoV-2 among voluntary dwellers in La Rinconada. Participants were also questioned about potential occupational and environmental risk factors of COVID-19 occurrence. Results: In a sample of 159 dwellers tested in La Rinconada, 48.4% [95% confidence interval, CI: 40.5-56.4] were seropositive for the SARS-CoV-2. Occurrence of at least one symptom compatible with the COVID-19 over the past 6 months remained the only significant factor associated with SARS-CoV-2 seropositivity (adjusted odds ratio: 3.27; [95% CI: 1.70-6.44]; p < 0.001). Conclusions: The high rate of SARS-CoV-2 seropositivity observed in this small sample of highlanders does not support a protective effect of high-altitude against the COVID-19 spread and demonstrates its large dissemination in vulnerable populations. Clinical Trial Registration number: NCT04604249.

International audience; Increased nitric oxide (NO) bioavailability may improve exercise performance and vascular function. It remains unclear whether older adults who experience a decreased NO bioavailability may benefit from chronic NO precursor supplementation. This randomised, double-blind, trial aims to assess the effect of chronic NO precursor intake on vascular function and exercise performance in older adults (60-70 years old). Twenty-four healthy older adults (12 females) performed vascular function assessment and both local (knee extensions) and whole-body (incremental cycling) exercise tests to exhaustion before and after one month of daily intake of a placebo (PLA) or a nitrate-rich salad and citrulline (N+C, 520mg nitrate and 6g citrulline) drink. Arterial blood pressure (BP) and stiffness, post-ischemic, hypercapnic and hypoxic vascular responses were evaluated. Prefrontal cortex and quadriceps oxygenation was monitored by near-infrared spectroscopy. N+C supplementation reduced mean BP (-3.3mmHg; p=0.047) without altering other parameters of vascular function and oxygenation kinetics. N+C supplementation reduced heart rate and oxygen consumption during submaximal cycling and increased maximal power output by 5.2% (p

Background Excessive ventilation (VE) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. Methods In this longitudinal observational study, symptom-limited cardio-pulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. Results Peak work rate improved by 20% after BPA whilst VE at peak did not change despite improved ventilatory efficiency (lower VE with respect to CO2 output [VCO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), VE and the ideal alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. Conclusions Ventilatory efficiency, physiological VD/VT and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

Participation in ultra-endurance running (UER) events continues to grow across ages, including youth athletes. The 50- and 100-km are the most popular distances among youth athletes. Most youth athletes are between 16-18 years; however, some runners younger than 12 years have successfully completed UER events. Parents, athletes, coaches, race directors, and medical professionals often seek advice regarding the safety of youth athletes participating in these events, especially with regard to potential short and long-term health consequences. UER may impact key organ systems during growth and development. We propose a decision-making process, based on current knowledge and the experience of the consensus group that addresses age regulations, medical and psychological well-being, training status and race-specific factors (such as distance, elevation change, remoteness, ambient temperatures, level of medical assistance, and type of provisions provided by the race organizers) to use until evidence of long-term consequences of UER in youth athletes is available. These recommendations are aimed at safe participation in UER events for youth athletes with a proper and individualized assessment.

International audience; Purpose: A decision tree based on a clinico-physiological score (SHAI score) has been developed to detect subjects susceptible to Severe High Altitude Illness (SHAI). We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ) and to specify the rule for a progressive acclimatization.Methods: Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of SHAI score, ACZ prescription and use and fulfillment of the acclimatization rule.Results: The occurrence of SHAI was 22.6%, similar to what was observed 18 years before (23.7%), while life-threatening forms of SHAI (High Altitude Pulmonary and Cerebral Edema) were less frequent (2.6% to 0.8%, P=0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400 m daily altitude gain were respected (P

Significance: Oxygenation is one of the skin tissue physiological properties to follow for patient care management. Furthermore, long-term monitoring of such parameters is needed at the patient bed as well as outside the hospital. Diffuse reflectance spectroscopy has been widely used for this purpose. Aim: The aim of the study is to propose a low-cost system for the long-term measurement of skin physiological parameters in contact. Approach: We have developed a low-cost, wearable, CMOS-based device. We propose an original method for processing diffuse reflectance data to calculate the tissue oxygen saturation (StO2). Results: We tested the device for the assessment of tissue oxygenation during a first-in-human clinical trial that took place at the Grenoble University Hospital France. Conclusions: The results of this clinical trial show a good accordance between our sensor and commercial devices used a reference.

International audience; Little is known about hemostasis modifications induced by chronic hypoxic exposure in high-altitude residents, especially in those who develop excessive erythrocytosis (EE, i.e. hemoglobin concentration ≥ 21 g·dL-1 in male and ≥ 19 g·dL-1 in female). The aim of this preliminary study was to assess coagulation alterations in highlanders with or without EE using simple hemostatic tests such as bleeding (BT) and clotting (CT) times. Eighty-one male (43 ± 7 years), permanent residents from La Rinconada (Peru), the highest city in the world (5,100-5,300 m), were evaluated. Thirty-six subjects (44 %) presented with EE. EE subjects compared to non-EE subjects had lower BT (3.6 ± 1.2 vs. 7.0 ± 1.9 min, p < 0.001) and CT (11.7 ± 1.7 vs. 15.1 ± 2.3 min, p < 0.001). These results support the notion that highlanders with EE are in a state of hypercoagulability and call for further hemostasis investigations in this population using more detailed hemostatic methods.

In response to chronic hypobaric hypoxia, residents at altitude develop physiological adaptations. Despite these adaptations, chronic mountain sickness (CMS) can be observed in 5-33% of individuals residing at high altitude. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia further amplifies sleep-related disorders so that sleep disturbance is an important feature of CMS. Our aim was to characterize nocturnal hypoxemia and the associated sleep and ambulatory (A) blood pressure (BP) changes in highlanders. Methods: Cardiorespiratory sleep and 24h ABP monitoring studies were performed in highlanders living in Puno (3800m) and La Rinconada (5100m), Peru. Subjects were divided in groups according to CMS severity scale. Results: 77 males were evaluated (age 43 [34-49] yr, BMI 25 [23-27] kg/m2). Subjects with CMS showed higher 24 h and daytime systolic and diastolic BP than those with no CMS. Highlanders with CMS were characterized by a lower nocturnal oxygen saturation (SpO2) mean, nocturnal SpO2 nadir and a higher oxygen desaturation index than those with no CMS. No difference was found in terms of apnea-hypopnea index. Altitude (β -4.3, p=0.02) and CMS class (β -0.5, p=0.01) were significant predictors of a lower nocturnal SpO2. Conclusions: At altitude lower mean nocturnal SpO2 and frequent desaturations might be implicated in CMS pathogenesis. Moreover, CMS subjects showed higher ABP, which might contribute to their reported worse cardiovascular prognosis as compared with no-CMS highlanders. Further pathophysiological and therapeutic intervention studies are needed for a better management of CMS.

International audience; The development of wearable devices for healthcare monitoring is of primary interest, in particular for homecare applications. But it is challenging to develop an evaluation framework to test and optimize such a device by following a non-invasive protocol. As well established reference devices do exist for capnometry, we propose a protocol to evaluate and compare the performance of the transcutaneous carbon dioxide monitoring wristband that we develop. We present here this protocol, the signal processing pipeline and the data analysis based on signal alignment and intercorrelation study, and the first results on a cohort of 13 healthy subjects. This test allows demonstrating the influence of the device response time and of the carbon dioxide content in the ambient air.Clinical Relevance-The protocol described here allows to test and optimize the new device in clinical conditions simulating hypo and hypercapnia variations on a subject at rest, as it would be the case at home to monitor the health status of chronic respiratory patients, and to compare the performances with reference devices. A strong intercorrelation greater than 0.8 has been observed in 5 healthy subjects out of 13 and factors influencing the intercorrelation are suggested.

Background While millions of people are living permanently at high altitude (>2,500 m) worldwide, the mechanisms underlying their tolerance to chronic hypoxia and those responsible for the occurrence of chronic mountain sickness (CMS) remain to be elucidated. Excessive erythrocytosis (EE) is thought to be the main mechanism responsible for CMS symptoms and is included in the definition of CMS, but the precise interplay between EE and symptoms of CMS requires further investigations. Methods The present study benefits from an exceptional dataset coming from 1,594 dwellers of La Rinconada, the highest city in the world (5,100-5,300 m). Based on individual clinical characteristics, subjects were categorized according to the presence of EE and CMS diagnosis, based on current guidelines. Results In this population of relatively young [32 (23; 39) years] highlanders residing in La Rinconada for only a few years [3 (2; 5) years], the internal prevalence of EE (44%) was high, whereas the internal prevalence of CMS (14%) was similar compared to previous reports in highlander populations living at lower altitude (∼4,000 m) in the Andes. Individuals with EE reported less symptoms compared to individuals with lower hematocrit values. Multivariable analysis revealed that age and sex are the main factors associated with EE, whereas age, hematocrit and number of years living at La Rinconada are factors associated with CMS symptoms. Conclusion In this specific population of La Rinconada, high hematocrit values were observed but were associated with limited symptoms. These results raise important questions regarding the definition of EE and CMS and their underlying mechanisms in high-altitude populations.

International audience; Key points: Highlanders develop unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. However, a significant proportion of populations living permanently at high altitude develop maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects of permanent life at high altitude on clinical and haemorheological parameters (blood viscosity and red blood cell aggregation) and to compare clinical and haemorheological parameters of dwellers from the highest city in the world according to CMS severity. Blood viscosity increased with altitude, together with haemoglobin concentration and haematocrit. At 5100 m, highlanders with moderate-to-severe CMS had higher blood viscosity mainly at high shear rate and even at corrected haematocrit (40%), with a lower red blood cell aggregation. Blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.Abstract: Chronic mountain sickness (CMS) is a condition characterised by excessive erythrocytosis (EE). While EE is thought to increase blood viscosity and subsequently to trigger CMS symptoms, the exact relationship between blood viscosity and CMS symptoms remains incompletely understood. We assessed the effect of living at high altitude on haemoglobin, haematocrit and haemorheological parameters (blood viscosity and red blood cell aggregation), and investigated their relationship with CMS in highlanders living in the highest city in the world (La Rinconada, Peru, 5100 m). Ninety-three men participated in this study: 10 Caucasian lowlanders, 13 Andean highlanders living at 3800 m and 70 Andean highlanders living at 5100 m (35 asymptomatic, CMS score ≤5; 15 with mild CMS, CMS score between 6 and 10; 20 with moderate-to-severe CMS, CMS score >10). Blood viscosity was measured at native and corrected haematocrit (40%). Haemoglobin concentration and haematocrit increased with the altitude of residency. Blood viscosity also increased with altitude (at 45 s-1 : 6.7 ± 0.9 mPa s at sea level, 14.0 ± 2.0 mPa s at 3800 m and 27.1 ± 8.8 mPa s at 5100 m; P < 0.001). At 5100 m, blood viscosity at corrected haematocrit was higher in highlanders with moderate-to-severe CMS (at 45 s-1 : 18.9 ± 10.7 mPa s) than in highlanders without CMS (10.2 ± 5.9 mPa s) or with mild CMS (12.1 ± 6.1 mPa s) (P < 0.05). In conclusion, blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.

Moderate-intensity continuous exercise (MICE) improves fat oxidation. High-intensity intermittent exercise (HIIE) is thought to have a greater potential for fat oxidation but it might be too demanding in the long term for patients. We hypothesized that an initial bout of HIIE could maximize fat oxidation during MICE and the following passive recovery. Eighteen healthy participants performed two acute isocaloric exercise sessions at random. MICE consisted of 45-min cycling at 50% of maximal aerobic power (Pmax). COMB began with five 1-min bouts of HIIE at Pmax (interspaced with 1-min recovery periods) followed by 35-min MICE. Gas exchange allowed substrate oxidation rate assessment.Expressed as a % of energy expenditure, fat oxidation (%) increased during in the passive recovery following COMB (Recovery: 36.0 ± 19.4 vs 23.0 ± 20.3%; ES: 0.66; p 0.0001). An initial bout of HIIE preceding a prolonged moderate-intensity exercise may potentiate fat oxidation during the following recovery. This might be relevant for health management of overweight/obese persons.

International audience; Introduction: Combining exercise training with hypoxic exposure has been recently proposed as a new therapeutic strategy to improve health status of obese individuals. Whether hypoxic exercise training (HET) provides greater benefits regarding body composition and cardiometabolic parameters than normoxic exercise training (NET) remains, however, unclear. We hypothesized that HET would induce greater improvement in exercise capacity and health status than NET in overweight and obese individuals.Methods: Twenty-three subjects were randomized into 8-wk HET (11 men and 1 woman; age, 52 ± 12 yr; body mass index, 31.2 ± 2.4 kg·m) or NET (eight men and three women; age, 56 ± 11 yr; body mass index, 31.8 ± 3.2 kg·m) programs (three sessions per week; constant-load cycling at 75% of maximal heart rate; target arterial oxygen saturation for HET 80%, FiO2 ~0.13, i.e., ~3700 m a.s.l.). Before and after the training programs, the following evaluations were performed: incremental maximal and submaximal cycling tests, measurements of pulse-wave velocity, endothelial function, fasting glucose, insulin and lipid profile, blood NO metabolites and oxidative stress, and determination of body composition by magnetic resonance imaging.Results: Peak oxygen consumption and maximal power output increased significantly after HET only (peak oxygen consumption HET + 10% ± 11% vs NET + 1% ± 10% and maximal power output HET + 11% ± 7% vs NET + 3% ± 10%, P < 0.05). Submaximal exercise responses improved similarly after HET and NET. Except diastolic blood pressure which decreased significantly after both HET and NET, no change in vascular function, metabolic status and body composition was observed after training. Hypoxic exercise training only increased nitrite and reduced superoxide dismutase concentrations.Conclusions: Combining exercise training and hypoxic exposure may provide some additional benefits to standard NET for obese individual health status.

International audience; Introduction: Nitric oxide (NO) precursor supplementation has been shown to increase NO bioavailability and can potentially improve vascular function and exercise performance. It remains unclear whether the combination of NO precursor supplementation and exercise training has synergic effects on exercise performance. This study aims to assess the effect of chronic nitrate and citrulline intake on exercise training adaptations in healthy young individuals.Methods: In this randomized, double-bind trial, 24 healthy young (12 females) subjects performed vascular function assessment (blood pressure, pulse wave velocity, postischemia vasodilation, and cerebrovascular reactivity) and both local (submaximal isometric unilateral knee extension) and whole-body (incremental cycling) exercise tests to exhaustion before and after a 2-month exercise training program and daily intake of a placebo or a nitrate-rich salad and citrulline (N + C, 520 mg nitrate and 6 g citrulline) drink. Prefrontal cortex and quadriceps oxygenation was monitored continuously during exercise by near-infrared spectroscopy.Results: N + C supplementation had no effect on vascular function and muscle and cerebral oxygenation during both local and whole-body exercise. N + C supplementation induced a significantly larger increase in maximal knee extensor strength (+5.1 ± 3.5 vs +0.2 ± 5.5 kg, P = 0.008) as well as a trend toward a larger increase in knee extensor endurance (+35.2 ± 26.1 vs +24.0 ± 10.4 contractions, P = 0.092) than placebo, but no effect on exercise training-induced maximal aerobic performance improvement.Conclusion: These results suggest that chronic nitrate and citrulline supplementation enhances the effect of exercise training on quadriceps muscle function in healthy active young individuals, but this does not translate into improved maximal aerobic performances.

Is the stress test still part of the useful examinations in the detection of risk heart disease in sports subjects? Should we continue to use it as a surveillance examination in coronary sports patients? Meta-analysis, considering a ST subshift of more than 1mm as a criterion for positivity, underline the low prevalence of abnormal examinations and a significant rate of false-positives. But for the diagnosis of coronary artery disease, it is mainly the evolution of the ST segment to effort or recovery and the occurrence of stress arrhythmias that detect true positivity. When coronary risk is more important (presence of risk factors, resumption of sport, intense and prolonged efforts), it seems lawful to recommend such a review on a regular basis among men over 40 years of age with two risk factors but Also among veterans taking up sport after a period of prolonged inactivity. For the asymptomatic coronary athlete the stress test remains at the centre of the final decision for the resumption of a sport in competition irrespective of the method of revascularization. Of course the stress test, even inevitable, remains flawed in the detection of coronary artery disease in the asymptomatic athlete. However, it provides additional information on the condition of being maximal, and attaching importance to arrhythmias, the tensional profile and the maximum power developed in addition to the ST segment's only study.

In this study, we hypothesized that adding CO2 to an inhaled hypoxic gas mixture will limit the rise of pulmonary artery pressure (PAP) induced by a moderate exercise. Eight 20-year-old males performed four constant-load exercise tests on cycle at 40% of maximal oxygen consumption in four conditions: ambient air, normobaric hypoxia (12.5% O2), inhaled CO2 (4.5% CO2), and combination of hypoxia and inhaled CO2. Doppler echocardiography was used to measure systolic (s)PAP, cardiac output (CO). Total pulmonary resistance (TPR) was calculated. Arterialized blood pH was 7.40 at exercise in ambient and hypoxia conditions, whereas CO2 inhalation and combined conditions showed acidosis. sPAP increases from rest in ambient air to exercise ranged as follows: ambient + 110%, CO2 inhalation + 135%, combined + 184%, hypoxia + 217% (p