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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.

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

To determine the effect of continuous positive airway pressure (CPAP), the gold standard treatment for obstructive sleep apnea syndrome (OSAS), on gait control in severe OSAS patients. We conducted a randomized, double-blind, parallel-group, sham-controlled monocentric study in Grenoble Alpes University Hospital, France. Gait parameters were recorded under single and dual-task conditions using a visuo-verbal cognitive task (Stroop test), before and after the 8-week intervention period. Stride-time variability, a marker of gait control, was the primary study endpoint. Changes in the determinants of gait control were the main secondary outcomes. ClinicalTrials.gov Identifier: (NCT02345694). 24 patients [median (Q1; Q3)]: age: 59.5 (46.3; 66.8) years, 87.5% male, body mass index: 28.2 (24.7; 29.8) kg. m−2, apnea–hypopnea index: 51.6 (35.0; 61.4) events/h were randomized to be treated by effective CPAP (n = 12) or by sham-CPAP (n = 12). A complete case analysis was performed, using a mixed linear regression model. CPAP elicited no significant improvement in stride-time variability compared to sham-CPAP. No difference was found regarding the determinants of gait control. This study is the first RCT to investigate the effects of CPAP on gait control. Eight weeks of CPAP treatment did not improve gait control in severe non-obese OSAS patients. These results substantiate the complex OSAS-neurocognitive function relationship.

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.

ObjectiveTo understand the disability of adults with arthrogryposis multiplex congenita (AMC), a rare disease spectrum characterized by at least 2 joint contractures at birth in different body areas.MethodsThis is a retrospective analysis of data for unselected persons with AMC referred to the French center for adults with AMC from 2010 to 2016. All underwent a pluriprofessional systematic and comprehensive investigation of deficits, activity limitation, and participation restriction according to the International Classification of Functioning, Disability and Health and genetic analysis when indicated. Participants were divided by amyoplasia and other AMC types.ResultsMean (SD) age of the 43 participants (27 female) was 33.2 (13.4) years; 28 had amyoplasia and 15 other types of AMC. Beyond joint stiffness, deformities, and muscle weakness, the well-known core symptoms that we quantified and for which first-line treatment involved technical aids, other less visible disorders that could contribute to severe participation restriction were particularly pain and psychological problems including anxiety, fatigue, difficulty in sexual life, altered self-esteem, and feelings of solitude. Severe respiratory disorders were infrequent and were linked toPIEZO2mutations. Gait disorders were not due to respiratory impairment but to skeletal problems and were always associated with amyoplasia when severe. Functional independence was worse but respiratory and swallowing capacities were better with amyoplasia than other AMC types.ConclusionThis study describes disability patterns of a cohort of adults with AMC by genotype. The disability of adults with AMC is influenced by genotype, with important invisible disability.

BackgroundObstructive sleep apnoea (OSA) and obesity are interdependent chronic diseases sharing reduced exercise tolerance and high cardiovascular risk.InterventionA 3-month intervention with innovative training modalities would further improve functional capacity and cardiovascular health than usual cycle exercise training in already continuous positive airway pressure (CPAP)-treated obese patients with OSA.MethodsFifty three patients (352) were randomly allocated to exercise training on a cycle ergometer, either alone (ERGO) or with respiratory muscle training (ERGO+RMT) or non-invasive ventilation (ERGO+NIV). Changes in 6 min walking distance (primary outcome), aerobic capacity (VO2peak), cardiovascular parameters, body composition and sleep quality were evaluated.Measurements and main resultsAll training modalities increased 6 min walking distance without differences between groups (P=0.97). ERGO+NIV and ERGO+RMT led to significantly higher improvement in VO2peak compared with ERGO (3.1 (95% CI 1.6 to 4.6) vs 2.3 (0.8 to 3.7) vs 0.5(−1.0 to 1.9) mL/min/kg, respectively, P=0.04) and ERGO+NIV significantly reduced self-measured blood pressure compared with ERGO+RMT and ERGO (systolic: −9.5 (95% CI −14.1 to −4.9) vs −13 (−5.8 to 3.1) vs −0.7 (−5.1 to 3.8) mm Hg, respectively, P=0.01). Waist and neck circumferences were reduced after ERGO+NIV compared with ERGO+RMT and ERGO (P=0.01).ConclusionsCombining RMT or NIV with cycling exercise training failed to provide further improvement in functional capacity as compared with cycling exercise training alone. However, the combination of NIV and exercise training demonstrated superiority for improving cardiometabolic risk factors in obese CPAP-treated patients with OAS.TRIAL REGISTRATION NUMBERResults, NCT01155271.

Sleep-related breathing disturbances are exacerbated at altitude in patients with Obstructive Sleep Apnea (OSA). The objective of this case report was to determine if a portable auto-CPAP device effectively treated sleep apnea across different altitudes. We report the severity of sleep apnea from 60 to 12,000 feet high in a man with severe OSA (Apnea Hypopnea Index at diagnosis = 60 events/hour) during the 2017 Dakar rally over the Andes mountains. The man was equipped with a lightweight portable auto-CPAP device with a narrow window [6-8 cmH2O]. Pressures delivered and corresponding residual events were assessed at different altitudes. The 95th percentile pressure reached the maximal set pressure at the highest altitudes, and residual AHI increased from 5 events/hour to 45 events/hour at the highest altitudes. Potential mechanisms behind the development of central apnea, and optimal clinical management at altitude are discussed in the light of the findings.

Prolonged cycling exercise performance in normoxia is limited because of both peripheral and central neuromuscular impairments. It has been reported that cerebral perturbations are greater during short-duration exercise in hypoxia compared with normoxia. The purpose of this study was to test the hypothesis that central deficits are accentuated in hypoxia compared with normoxia during prolonged (three bouts of 80 min separated by 25 min) whole-body exercise at the same relative intensity.Ten subjects performed two sessions consisting of three 80-min cycling bouts at 45% of their relative maximal aerobic power in normoxia and hypoxia (FiO2 = 0.12). Before exercise and after each bout, maximal voluntary force, voluntary activation assessed with nerve stimulation and transcranial magnetic stimulation, corticospinal excitability (motor evoked potential), intracortical inhibition (cortical silent period), and electrical (M-wave) and contractile (twitch and doublet peak forces) properties of the knee extensors were measured. Prefrontal and motor cortical oxygenation was also recorded during each cycling bout in both conditions.A significant but similar force reduction (≈-22%) was observed at the end of exercise in normoxia and hypoxia. The modifications of voluntary activation assessed with transcranial magnetic stimulation and nerve stimulation, motor evoked potential, cortical silent period, and M-wave were also similar in both conditions. However, cerebral oxygenation was reduced in hypoxia compared with normoxia.These findings show that when performed at the same relative low intensity, prolonged exercise does not induce greater supraspinal fatigue in hypoxia compared with normoxia. Despite lower absolute exercise intensities in hypoxia, reduced brain O2 availability might contribute to similar amounts of central fatigue compared with normoxia.

Objective and background Impaired cerebral blood flow and cerebrovascular reactivity to hypercapnia during wakefulness at rest as well as reduced exercise tolerance have been reported in severe obstructive sleep apnea (OSA) patients. Impaired cerebral oxygenation and hemodynamics can contribute to reduced exercise performance. We hypothesized that (i) OSA patients show impaired cerebrovascular response both during exercise and in response to hypercapnia together with reduced exercise tolerance and (ii) continuous positive airway pressure (CPAP) treatment improves these alterations in cerebral oxygenation. Methods Fifteen OSA patients and 12 healthy matched controls performed a hypercapnic response test and a maximal cardiopulmonary exercise test before and after eight weeks of CPAP treatment or control period. Prefrontal cortex and muscle oxygenation were assessed by near-infrared spectroscopy (NIRS) during both tests. Results Cerebrovascular reactivity to hypercapnia was impaired in OSA patients (lower increase in oxyhemoglobin [0.29 ± 0.19 vs 0.44 ± 0.14 μmol mmHg−1] and total hemoglobin [0.14 ± 0.15 vs 0.26 ± 0.09 μmol mmHg−1]) compared to controls. Reduced prefrontal cortex oxygen extraction and total blood volume (ie, lower increase in deoxyhemoglobin [1.76 ± 1.57 vs 3.43 ± 2.08 μmol] and total hemoglobin [5.36 ± 7.08 vs 8.55 ± 5.13 μmol at exhaustion], respectively) during exercise together with a reduced exercise tolerance (ie, lower peak oxygen consumption) were observed in OSA patients compared to controls. CPAP treatment did not induce any improvement in cerebrovascular response during hypercapnic response test and exercise. Conlusions This study demonstrates that cerebrovascular response to exercise is altered in OSA and may contribute to exercise intolerance in these patients. Prefrontal cortex oxygenation and exercise tolerance are not significantly improved following eight weeks of CPAP treatment. Clinical trial registration NCT02854280 .

In their comment on our article,1 Drs. Sawatzky and Hall discuss how to positively or negatively describe a handicap, in terms of either ability or disability, and how to inform patients. We refer to the International Classification of Functioning, Disability and Health,2 edited with the aim to provide a unified and standard language for describing health and health-related states. Medical writing is also subject to international recommendations to ensure clear, ethical, and unbiased reporting of scientific findings,3 and this is also true for rare diseases. We followed these recommendations and reject any allegation of a negative attitude in our article.1

ObjectivesHome-based rehabilitation programmes (H-RPs) could facilitate the implementation of pulmonary rehabilitation prior to resection for non-small cell lung cancer (NSCLC), but their feasibility has not been evaluated. The aim of this study was to identify determinants of non-completion of an H-RP and the factors associated with medical events occurring 30 days after hospital discharge.DesignA prospective observational study.InterventionAll patients with confirmed or suspected NSCLC were enrolled in a four-component H-RP prior to surgery: (i) smoking cessation, (ii) nutritional support, (iii) physiotherapy (at least one session/week) and (iv) home cycle-ergometry (at least three times/week).OutcomesThe H-RP was defined as ‘completed’ if the four components were performed before surgery.ResultsOut of 50 patients included, 42 underwent surgery (80% men; median age: 69 (IQR 25%–75%; 60–74) years; 64% Chronic Obstructive Pulmonary Disease (COPD); 29% type 2 diabetes). Twenty patients (48%) completed 100% of the programme. The median (IQR) duration of the H-RP was 32 (19; 46) days. Multivariate analysis showed polypharmacy (n=24) OR=12.2 (95% CI 2.0 to 74.2), living alone (n=8) (single vs couple) OR=21.5 (95% CI 1.4 to >100) and a long delay before starting the H-RP (n=18) OR=6.24 (95% CI 1.1 to 36.6) were independently associated with a risk of non-completion. In univariate analyses, factors associated with medical events at 30 days were H-RP non-completion, diabetes, polypharmacy, social precariousness and female sex.ConclusionFacing multiple comorbidities, living alone and a long delay before starting the rehabilitation increase the risk of not completing preoperative H-RP.Trial registration numberNCT03530059.

This study aimed to compare quadriceps function (i.e. strength, endurance, central, and peripheral fatigue) of young (Young-UnTr) and middle-aged (MidAge-UnTr) untrained men and young endurance-trained men (Young-Tr). Twenty-four male subjects (eight Young-UnTr (26 ± 4 yr), eight Young-Tr (29 ± 3 yr), and eight MidAge-UnTr (56 ± 4 yr) performed a maximal cycling test to assess their fitness level. On a separate visit, subjects performed sets of 10 intermittent (5-s on/5-s off) isometric contractions starting at 10% maximum voluntary contraction (MVC), with 10% MVC increments from one set to another until exhaustion. Electrophysiological and mechanical (e.g. twitch) evoked responses elicited with magnetic femoral nerve stimulation in the relaxed muscle and during MVC (i.e . estimation of voluntary activation using the interpolated twitch technique) were measured at baseline and after each set to assess peripheral and central fatigue, respectively. Endurance (= total number of contractions) was also evaluated. Young-UnTr exhibited larger reductions in evoked quadriceps mechanical responses than MidAge-UnTr and Young-Tr after identical standardized muscle loading (e.g. after the 50% MVC set, reduction in single potentiated twitch was −36 ± 9%, −21±16%, and −2 ± 4%, respectively). At both 50% MVC set and exhaustion, MidAge-UnTr exhibited similar reduction in maximal voluntary activation and displayed similar endurance compared to Young-UnTr. Young-Tr exhibited greater endurance than Young-UnTr without significant changes in maximal voluntary activation throughout the test. This study provides robust comparative data regarding the influence of chronic exposure to endurance training and middle-aged on central and peripheral quadriceps fatigability and endurance. Endurance-trained subjects showed smaller level of peripheral fatigue and displayed no significant central fatigue, even at exhaustion and despite greater endurance performance. Our findings also demonstrate that men in the sixth decade exhibit significant alterations in quadriceps function typically observed in much older subjects. These data emphasize the need for developing normative data for both central and peripheral quadriceps fatigability.

Aim:To examine the role of ventilatory constraint on cardiorespiratory fitness in obese adolescents.Methods:Thirty obese adolescents performed a maximal incremental cycling exercise and were divided into 2 groups based on maximal oxygen uptake (VO2peak): those presenting low (L; n = 15; VO2peak: 72.9 ± 8.6% predicted) or normal (N; n = 15; VO2peak: 113.6 ± 19.2% predicted) cardiorespiratory fitness. Both were compared with a group of healthy controls (C; n = 20; VO2peak: 103.1 ± 11.2% predicted). Ventilatory responses were explored using the flow volume loop method.Results:Cardiorespiratory fitness (VO2peak, in % predicted) was lower in L compared with C and N and was moderately associated with the percent predicted forced vital capacity (FVC) (r = .52; p < .05) in L. At peak exercise, end inspiratory point was lower in L compared with N and C (77.4 ± 8.1, 86.4 ± 7.7, and 89.9 ± 7.6% FVC in L, N, and C, respectively; p < .05), suggesting an increased risk of ventilatory constraint in L, although at peak exercise this difference could be attributed to the lower maximal ventilation in L.Conclusion:Forced vital capacity and ventilatory strategy to incremental exercise slightly differed between N and L. These results suggest a modest participation of ventilatory factors to exercise intolerance.

Background: Recent discovery of cystic fibrosis transmembrane conductance regulator expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities potentially leading to functional impairments. The aim of the present study was to determine whether CF patients with mild to moderate lung disease have altered skeletal muscle contractility and greater muscle fatigability compared to healthy controls. Methods: Thirty adults (15 CF and 15 controls) performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations. Electromyographic and mechanical parameters during voluntary and magnetically-evoked contractions were recorded at rest, during and after a fatiguing isometric task. Quadriceps cross-sectional area was determined by magnetic resonance imaging. Results: Someindexesofmusclecontractilitytendedtobereducedatrest inCFcomparedtocontrols(e.g.,mechanicalresponsetodoubletsstimulation at 100 Hz: 74 ± 30 Nm vs 97 ± 28 Nm, P = 0.06) but all tendencies disappeared when expressed relative to quadriceps cross-sectional area (P N 0.5 for all parameters). CF and controls had similar alterations in muscle contractility with fatigue, similar endurance and post exercise recovery. Conclusions: We found similar skeletal muscle endurance and fatigability in CF adults and controls and only trends for reduced muscle strength in CF which disappeared when normalized to muscle cross-sectional area. These results indicate small quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF with mild to moderate lung disease.

The central nervous system can play a critical role in limiting exercise performance during hypoxic conditions. Hypocapnia, which is associated with hypoxia-induced hyperventilation, may affect cerebral perfusion. We hypothesized that CO2 clamping during hypoxic isometric knee extensions would improve cerebral oxygenation and reduce central fatigue.Fifteen healthy men (mean ± SD: age, 25 ± 8 yr; body mass, 72 ± 11 kg; height, 179 ± 7 cm) performed intermittent isometric knee extensions at ∼50% of maximal voluntary contraction to task failure in normoxia, hypoxia with CO2 clamping (arterial O2 saturation, 80% ± 2%; end-tidal CO2 partial pressure, 40 ± 2 mm Hg), and hypoxia without CO2 clamping (arterial O2 saturation, 80% ± 3%). Transcranial magnetic stimulation and femoral nerve electrical stimulation were used to assess central and peripheral determinants of fatigue. Prefrontal cortex and quadriceps femoris oxygenation were monitored by multichannel near-infrared spectroscopy.Exercise duration was reduced to a similar extent in hypoxia with CO2 clamping (997 ± 460 s) or hypoxia without CO2 clamping (929 ± 412 s) compared to normoxia (1473 ± 876 s; P0.001). Prefrontal cortex and quadriceps oxygenation were increased (+5.3 ± 8.6 and +2.6 ± 3.0 μmol·cm at task failure, respectively; P0.01) during hypoxia with CO2 clamping compared to hypoxia without CO2 clamping. Transcranial magnetic stimulation maximal voluntary activation decreased to a greater extent at task failure in hypoxia without CO2 clamping (-18% ± 8%) compared to hypoxia with CO2 clamping (-9% ± 9%; P0.01) and normoxia (-10% ± 7%; P0.05). Conversely, exercise-induced peripheral fatigue was larger in hypoxia with CO2 clamping than in hypoxia without CO2 clamping (e.g., Db10-to-Db100 ratio of 0.54 ± 0.12 and 0.63 ± 0.11 at task failure, respectively; P0.05).The results demonstrate that CO2 clamping can alter central and peripheral mechanisms that contribute to neuromuscular fatigue during hypoxic isometric knee extensions in men. Hypocapnia impairs cerebral oxygenation and central drive but exerts a protective effect against fatigability in muscles.

International audience; Bronchial challenge with the direct bronchoconstrictor agent methacholine is commonly used for the diagnosis of asthma. The “Lung Function” thematic group of the French Pulmonology Society (SPLF) elaborated a series of guidelines for the performance and the interpretation of methacholine challenge testing, based on French clinical guideline methodology. Specifically, guidelines are provided with regard to the choice of judgment criteria, the management of deep inspirations, and the role of methacholine bronchial challenge in the care of asthma, exercise-induced asthma, and professional asthma.; Le test de provocation bronchique à la méthacholine est couramment utilisé pour la prise en charge de l’asthme. Le groupe de travail « Fonction Respiratoire » de la SPLF propose ici une série de recommandations concernant la réalisation et l’interprétation de ce test, élaborées dans l’esprit de la méthodologie proposée par la Haute Autorité de santé. Les thèmes abordés sont le choix des critères de jugement, la gestion des inspirations profondes, ainsi que la place du test dans la prise en charge de l’asthme, de l’asthme induit par l’exercice et de l’asthme professionnel.

Objectif La force et l’endurance musculaire semblent etre reduites chez le patient atteint de syndrome d’apnee obstructive du sommeil (SAOS) severe. Cette etude visait a evaluer les mecanismes neuromusculaires de la fatigue induite par l’exercice chez le patient SAOS avant et apres 8 semaines de traitement par pression positive continue (PPC). Methodes Douze patients SAOS (âge 59 ± 7 ans ; IMC 27 ± 3kg/m2 ; IAH 46 ± 13) et 11 controles apparies ont ete inclus. La force maximale volontaire (FMV), les niveaux d’activation volontaire (NAV) par stimulation du nerf femoral (FNS) et stimulation magnetique transcrânienne (TMS) et l’inhibition intracorticale ont ete mesures lors d’une tâche fatigante (TF : extensions du genou) jusqu’a epuisement. Resultats Le temps d’effort etait inferieur chez les patients SAOS compares aux controles (991 ± 461 vs 1375 ± 583s, p = 0,017). FMV (138 ± 49 vs 157 ± 49 N/m, p = 0,004), NAVFNS (86 ± 10 vs 89 ± 8 %, p = 0,022) et NAVTMS (86 ± 16 vs 91 ± 7 %, p = 0,049) etaient inferieurs chez les patients SAOS avant et pendant TF. La periode de silence (225 ± 54 vs 194 ± 47 ms, p Conclusion Cette etude demontre que les patients SAOS severes ont une dysfonction du quadriceps probablement liee a un deficit d’activation centrale et une inhibition intracorticale accrue. Un traitement de 8 semaines par PPC n’inverse pas ces alterations neuromusculaires.

Study aim Severe obstructive sleep apnoea (OSA) can lead to neurocognitive alterations, including gait impairments. The beneficial effects of continuous positive airway pressure (CPAP) on improving excessive daytime sleepiness and daily functioning have been documented. However, a demonstration of CPAP treatment efficacy on gait control is still lacking. This study aims to test the hypothesis that CPAP improves gait control in severe OSA patients. Material and methods In this prospective controlled study, twelve severe OSA patients (age = 57.2±8.9 years, body mass index = 27.4±3.1 kg·m-2, apnoea-hypopnoea index = 46.3±11.7 events·h-1) and 10 healthy matched subjects were included. Overground gait parameters were recorded at spontaneous speed and stride time variability, a clinical marker of gait control, was calculated. To assess the role of executive functions in gait and postural control, a dual-task paradigm was applied using a Stroop test as secondary cognitive task. All assessments were performed before and after 8 weeks of CPAP treatment. Results Before CPAP treatment, OSA patients had significantly larger stride time variability (3.1±1.1% vs 2.1±0.5%) and lower cognitive performances under dual task compared to controls. After CPAP treatment, stride time variability was significantly improved and no longer different compared to controls. Cognitive performance under dual task also improved after CPAP treatment. Conclusion Eight weeks of CPAP treatment improves gait control of severe OSA patients, suggesting morphological and functional cerebral improvements. Our data provide a rationale for further mechanistic studies and the use of gait as a biomarker of OSA brain consequences.

Lower muscle strength and endurance have been reported in severe obstructive sleep apnea (OSA). Increased intracortical inhibition previously reported at rest in OSA suggests central neuromuscular impairments in these patients. We hypothesized that (i) OSA patients demonstrate reduced knee extensor strength and endurance due to central impairments and (ii) continuous positive airway pressure (CPAP) treatment improves neuromuscular function in these patients.Twelve OSA patients and 11 healthy controls performed intermittent knee extensions until task failure before and after 8 wk of CPAP treatment or control period. Maximal voluntary contraction, voluntary activation and corticospinal excitability and inhibition assessed by single- and paired-pulse transcranial magnetic stimulation were measured before and during the fatiguing task.Time to exhaustion was lower in OSA (before CPAP treatment: 1008 ± 549 s; after CPAP treatment: 975 ± 378 s) compared with controls (before control period: 1476 ± 633 s; after control period: 1274 ± 506 s; P = 0.017). Obstructive sleep apnea patients had reduced maximal voluntary contraction and VATMS compared with controls throughout the fatiguing task as well as increased intracortical inhibition (all P0.05). Continuous positive airway pressure treatment did not induce any changes in neuromuscular function (P0.05 for all parameters).This study demonstrates that severe OSA patients have cortical impairments which are likely contributing to their reduced knee extensors strength and endurance. Both cortical impairments and neuromuscular function are not improved after 8 wk of CPAP treatment.

SummaryBackground Decreased sleep duration and altered sleep quality are risk factors for obesity in youth. Structured exercise training has been shown to increase sleep duration and improve sleep quality. Objectives This study aimed at evaluating the impact of exercise training for improving sleep duration, sleep quality and physical activity in obese adolescents (OB). Methods Twenty OB (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m−2) and 20 healthy-weight adolescents (HW) completed an overnight polysomnography and wore an accelerometer (SenseWear Bodymedia) for 7 days. OB participated in a 12-week supervised exercise-training programme consisting of 180 min of exercise weekly. Exercise training was a combination of aerobic exercise and resistance training. Results Sleep duration was greater in HW compared with OB (P

Lower muscle strength and endurance have been reported in severe obstructive sleep apnea syndrome (OSAS) patients. Increased intracortical inhibition previously reported at rest in OSAS suggests central neuromuscular impairments in these patients. This study investigated the neuromuscular mechanisms of exercise-induced fatigue in severe OSAS patients before and after an 8-week continuous positive airway pressure (CPAP) treatment. Twelve OSAS patients (age 59±7 yrs; BMI 27±3 kg·m−2; AHI 46±13 events·h−1) and 11 matched controls were included. Maximal voluntary contraction (MVC), voluntary activation (VA) levels assessed by femoral nerve electrical stimulation (FNES) and transcranial magnetic stimulation (TMS) and intracortical inhibition parameters were measured before and during a fatiguing task (FT: repeated isometric knee extensions) until exhaustion. Time to exhaustion was lower in OSAS patients compared to controls (991±461 vs 1375±583s, p=0.017). MVC (138±49 vs 157±49 N·m, p=0.004), VAFNES (86±10 vs 89±8%, p=0.022) and VATMS (86±16 vs 91±7%, p=0.049) were lower in OSAS patients before and during FT. Cortical silent period duration (quadriceps muscles: 225±54 vs 194±47ms at 35%MVC, p This study demonstrates that severe OSAS patients have reduced knee extensors strength and endurance possibly due to central activation deficit and increased intracortical inhibition. An 8-week CPAP treatment did not reverse these neuromuscular impairments.

PURPOSE Losses of peripheral muscle mass and ectopic fat accumulation have been associated with cardiometabolic morbidity in COPD. We aimed at identifying the relationship between quadriceps muscle fat infiltration and cardiovascular risk. MATERIALS AND METHODS From 2009 to 2014, 78 COPD patients (64 ± 8 years; 80% male) were prospectively included after having given written consent (ethical committee approval number: 2006-A00491-50). The cohort was divided into three groups (tertiles) according to body mass index (BMI), low [15

Obstructive sleep apnea (OSA) is now widely seen as a major public health issue with many widespread societal consequences. In addition to an increased stroke risk, OSA leads to neurocognitive alterations. In two recent uncontrolled studies, OSA has been associated with gait impairments, which seemed to be improved after 8 weeks of continuous positive airway pressure (CPAP) treatment. The present controlled study tests the hypothesis that CPAP treatment will improve gait control in severe OSA patients. Prospective controlled study. 12 OSA (age=57.2±8.9 years, BMI=27.4±3.1 kg.m −2 , AHI=46.3±11.7, Epworth sleepiness scale=10±5) and 10 healthy matched subjects were included. Gait spatio-temporal parameters were recorded. Primary study endpoint, stride time variability (STV), a clinical marker of gait control linked with cognitive performance and cerebral integrity was calculated. The role of cognition in gait and postural control was assessed using a dual-task paradigm. Assessments were performed before and after 8 weeks of CPAP treatment. Before CPAP treatment, higher STV (3.1±1.1% vs 2.1±0.5%, p=0.02) and higher mean surface of center of pressure under single task condition (131.2±79.8mm 2 vs 66.9±21.9mm 2 , p=0.02) were measured in OSAS patients compared to controls. After CPAP treatment, STV was improved (2.4±0.5%, p=0.005) and no longer different compared to controls (p=0.32). Cognitive performance of OSA patients under dual task was impaired at baseline and improved under CPAP. CPAP treatment improve gait control of severe non-obese OSA patients suggesting morphological and functional cerebral improvements.

Objective. Obesity and obstructive sleep apnea (OSA) are closely interconnected conditions both leading to high cardiovascular risk. Inactivity is frequent and physical activity programs remain difficult in these patients. We investigated the acute feasibility of two neuromuscular electrical stimulation (NMES) modalities in extremely inactive obese patients with OSA.Design. A randomized cross-over study, with two experimental sessions (one per condition: multipath NMES versus conventional NMES).Setting. Outpatient research hospital.Subjects. Twelve patients with obesity, already treated for OSA.Interventions. No intervention.Measures. Feasibility outcomes included NMES current intensity, knee extension force evoked by NMES, and self-reported discomfort.Results. We found higher current intensity, a trend to significantly higher evoked force and lower discomfort during multipath NMES versus conventional NMES, suggesting better tolerance to the former NMES modality. However, patients were rapidly limited in the potential of increasing current intensity of multipath NMES.Conclusion. Both NMES modalities were feasible and relatively well tolerated by obese patients with OSA, even if multipath NMES showed a better muscle response/discomfort ratio than conventional NMES. There is an urgent need for a proof-of-concept study and interventional randomized controlled trials comparing NMES therapy versus current care to justify its utilization in obese and apneic patients with low physical activity levels.

Background Specific alterations in skeletal muscle related to genetic defects may be present in adults with cystic fibrosis (CF). Limb muscle dysfunction may contribute to physical impairment in CF. Aims and objectives We hypothesized that adults with CF would have altered calf muscle metabolism during exercise. Methods Fifteen adults with CF and fifteen healthy controls matched for age, gender and physical activity performed a maximal cycling test and an evaluation of calf muscle energetics by 31 P magnetic resonance spectroscopy before, during and after plantar flexions to exhaustion. Results Maximal cycling test revealed lower exercise capacities in CF (VO 2peak 2.44±0.11 vs. 3.44±0.23L·Min −1 , P =0.03). At rest, calf muscle phosphorus metabolites and pHi were similar in CF and controls ( P >0.05). Maximal power output during plantar flexions was significantly lower in CF compared to controls (7.8±1.2 vs. 6.6±2.4W; P =0.013). At exhaustion, PCr concentration was similarly reduced in both groups (CF −33±7%, controls −34±6%, P =0.44), while PCr degradation at identical absolute workload was greater in CF patients ( P =0.04). These differences disappeared when power output was normalized for differences in calf size (maximal power output: 0.10±0.02 vs. 0.10±0.03W/cm 2 ; P =0.87). Pi/PCr ratio and pHi during exercise as well as PCr recovery after exercise were similar between groups. Conclusion Similar metabolic calf muscle responses during exercise and recovery were found in CF adults and controls. Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF.

a Inserm U1042, laboratoire HP2, pole locomotion, reeducation et physiologie, clinique physiologie, sommeil et exercice, CHU de Grenoble, universite de Grenoble, 38000 Grenoble, France b Centre de pneumo-allergologie, les acacias, 05107 Briancon, France c Inserm U1046, departement de physiologie, service physiologie clinique, hopital Arnaud de Villeneuve, CHU de Montpellier, 34295 Montpellier, France d Service d’explorations fonctionnelles respiratoires et clinique des maladies respiratoires, hopital Calmette, CHRU de Lille, 59037 Lille, France e Inserm U1087, institut du thorax, CHU de Nantes, 44093 Nantes, France

The potential ergogenic effects of oral salbutamol intake were demonstrated for decades but the underlying mechanisms remain to elucidate. We hypothesized that improved exercise performance after acute oral salbutamol administration is associated with changes in muscle metabolism. Twelve healthy, nonasthmatic, moderately trained, male subjects were recruited to compare in a double-blind crossover randomized study, an oral dose of salbutamol (4 mg) and a placebo. After treatment administration, subjects performed repetitive plantar flexions to exhaustion in a 3T magnet. Continuous (31) P nuclear magnetic resonance spectroscopy assessment of the calf muscles was performed at rest, during exercise, and during recovery. No significant difference between treatments was detected in metabolite concentration at rest (P > 0.05). Creatine phosphate and inorganic phosphate changes during and immediately after exercise were similar between treatments (P > 0.05). Intramuscular pH (pHi) was significantly higher at rest, at submaximal exercise but not at exhaustion with salbutamol (pHi at 50% of exercise duration, 6.8 ± 0.1/6.9 ± 0.1 for placebo and salbutamol, respectively, P < 0.05). The maximal power (28 ± 7 W/23 ± 7 W; P = 0.001) and total work (1702 ± 442 J/1381 ± 432 J; P = 0.003) performed during plantar flexions were significantly increased with salbutamol. Salbutamol induced significant improvement in calf muscle endurance with similar metabolic responses during exercise, except slight differences in pHi. Other mechanisms than changes in muscle metabolism may be responsible for the ergogenic effect of salbutamol administration.

The present study assessed the isolated and synergetic effects of hypoxic exposure and prolonged exercise on cerebral volume and subedema and symptoms of acute mountain sickness (AMS). Twelve healthy males performed three semirandomized blinded 11- hour sessions with (1) an inspiratory oxygen fraction (FiO2) of 12% and 4-hour cycling, (2) FiO2 = 21% and 4-hour cycling, and (3) FiO2 = 8.5% to 12% at rest (matching arterial oxygen saturation measured during the first hypoxic session). Volumetric, apparent diffusion coefficient (ADC), and arterial spin labelling 3T magnetic resonance imaging sequences were performed after 30 minutes and 10 hours in each session. Thirty minutes of hypoxia at rest induced a significant increase in white-matter volume (+0.8 ± 1.0% compared with normoxia) that was exacerbated after 10 hours of hypoxia at rest (+1.5 ± 1.1%) or with cycling (+1.6 ± 1.1%). Total brain parenchyma volume increased significantly after 10 hours of hypoxia with cycling only (+1.3 ± 1.1%). Apparent diffusion coefficient was significantly reduced after 10 hours of hypoxia at rest or with cycling. No significant change in cerebral blood flow was observed. These results demonstrate changes in white-matter volume as early as after 30 minutes of hypoxia that worsen after 10 hours, probably due to cytotoxic edema. Exercise accentuates the effect of hypoxia by increasing total brain volume. These changes do not however correlate with AMS symptoms.

BACKGROUND Exercise training has been shown to improve cardiometabolic health in obese adolescents. OBJECTIVES Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. METHODS We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 age- and gender-matched normal-weight adolescents (NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. RESULTS OB presented lower peak aerobic capacity (24.2 ± 5.9 vs. 39.8 ± 8.3 mL kg(-1) min(-1) , P

Une hypoventilation alveolaire peut donc survenir dans deux grandes situations :• une reduction de la ventilation externe due a une dimi-nution de l’activite des centres respiratoires congenitale ou acquise ; ou a une dysfonction neuromusculaire glo-bale comme dans les maladies neuromusculaires ou des muscles respiratoires qui sont incompetents pour faire face a une charge mecanique augmentee comme dans le syndrome obesite- hypoventilation ou les deformations thoraciques ;• une ventilation externe preservee mais une augmentation de l’espace mort physiologique (augmentation du VD/VT).Si, pour certaines pathologies, comme les maladies neuromusculaires rapidement progressives (exemple : la sclerose laterale amyotrophique), la physiopathologie de l’hypoventilation alveolaire est aisement identiA able, pour d’autres pathologies, l’origine de l’hypoventilation est multifactorielle (ex : le syndrome obesite- hypoventilation). Par ailleurs, l’atteinte musculaire peripherique est un des elements essentiels expliquant la dyspnee des patients en insufA sance respiratoire chronique.Au cours de cet article de synthese, nous envisagerons :• l’importance respective de l’atteinte des muscles respira-toires par rapport aux autres mecanismes dans les grandes etiologies d’insufA sance respiratoire chronique ;• les methodes d’exploration des muscles respiratoires ;• les implications pour la mise en œuvre de la ventilation non invasive et la prescription d’un programme de reha-bilitation respiratoire.

Le lipoxmax correspond a l’intensite d’exercice pour laquelle l’oxydation des lipides est maximale. Cet indice metabolique est determine par calorimetrie lors d’une epreuve d’effort progressive. Le lipoxmax peut etre utilise comme cible d’entrainement dans differentes pathologies, dont l’obesite et le diabete. L’objectif de cette revue de question est d’enoncer les aspects methodologiques de la mesure du lipoxmax en portant une attention particuliere a la validite des echanges gazeux, les particularites du protocole de determination et les facteurs de variabilite et de fiabilite. Dans un deuxieme temps, l’interet et la faisabilite des activites physiques adaptees ciblant le lipoxmax chez les personnes presentant des troubles metaboliques seront explores.

Introduction De nombreuses etudes ont evalue les benefices de programmes de reentrainement a l’effort chez des adultes atteints de mucoviscidose mais ces travaux ont ete realises essentiellement dans un cadre medical [1] ou non supervise a domicile [2] . L’objectif de cette etude est donc d’evaluer les effets d’un accompagnement en APA supervise a domicile, en presentiel ou en visioconference, sur le niveau d’activite physique (AP), les capacites physiques, l’estime de soi et la qualite de vie chez ce public. Methode Dix-huit adultes du CRCM de Grenoble (30 ± 8,13 ans ; VEMS : 2,09 ± 0,72 L) ont beneficie d’un suivi individualise en APA de 6 mois. Une moyenne de 20 seances (12 en visioconference) a ete proposee, combinant exercices d’aerobie et de renforcement musculaire. Resultats Tous les parametres evalues augmentent significativement (p Conclusion Chez les patients adultes atteints de mucoviscidose, un programme d’APA supervise a domicile (presentiel et visioconference) ameliore a la fois le niveau d’AP, les capacites physiques, l’estime de soi et la qualite de vie. Compte tenu de la specificite de cette population, et notamment la problematique de contamination croisee entre patients, il serait interessant d’evaluer l’efficacite d’un suivi en APA realise uniquement en visioconference dans le cadre d’un essai controle randomise.

We investigated the effect of neuromuscular electrical stimulation (NMES) training prior to endurance training in patients with cystic fibrosis (CF) and severe pulmonary obstruction.Fourteen patients with CF (FEV(1) = 35% ± 11% predicted) were prospectively randomized to either a 6-week NMES training program (n = 7) or a 6-week control period (n = 7) both followed by ergocycle (ERGO) training (8 weeks) (NMES + ERGO and control + ERGO groups). Measurements were pulmonary function, mid-thigh circumference, quadriceps strength, 6-min walk distance, maximal exercise capacity on a cycloergometer, plasma biomarkers, insulin resistance (homeostasis model assessment indexes), and quality of life (CF questionnaire for adults and teenagers14 years of age [CFQ14 + ], Baseline Dyspnea Index-Transition Dyspnea Index).NMES + ERGO training greatly improved mid-thigh circumference ( + 2.6 ± 0.9 cm vs - 0.4 ± 1.4 cm), quadriceps strength ( + 6 ± 5 kg vs - 2 ± 2 kg), and BMI ( + 0.6 ± 0.6 kg/m(2) vs - 0.5 ± 0.7 kg/m(2) ) compared with control + ERGO training ( P.05). No differences between groups were found in exercise-induced changes in 6-min walk distance and maximal exercise capacity. However, dyspnea after the 6-minute walk test, the fasting glucose/insulin ratio (calculated as an index of insulin resistance), and physical function and health perception domains of the CFQ14 + improved after NMES + ERGO training compared with control + ERGO training ( P.05). Significant correlations were found between changes in mid-thigh circumference and muscle strength, ventilation requirements during exercise, insulin sensibility, and the physical function section of CFQ14 + ( P.05).NMES training performed prior to endurance training is useful for strengthening peripheral muscles, which in turn may augment gains in body weight and quality of life, further reductions in ventilation requirements during exercise, and retard insulin resistance in patients with CF with severe pulmonary obstruction.

Obstructive sleep apnea (OSA) is now widely seen as a major public health issue with many widespread societal consequences including mood, behavioral and cognitive deficits that impair work performance and productivity. In two recent uncontrolled studies, OSA has been associated with gait impairments, which seemed to be improved after an 8-week continuous positive airway pressure (CPAP) treatment. The present controlled study investigated the impact of an 8-week CPAP treatment on single and dual task gait performances and postural control in OSA patients.Twelve OSA patients (age=57.2±8.9 years, BMI=27.4±3.1 kg.m -2 , AHI=46.3±11.7, Epworth sleepiness scale=10±5) and 10 healthy matched subjects were included. Kinetic postural parameters on a stable and moving platform and spatio-temporal gait parameters were recorded under single and dual task conditions using a visuo-verbal cognitive task (Stroop test).Higher stride time variability (STV) (3.1±1.1% vs 2.1±0.5%, p=0.02) and higher mean surface of center of pressure on stable plan under single task condition (131.2±79.8mm² vs 66.9±21.9mm², p=0.02) were measured in OSAS patients compared to controls. After CPAP treatment, STV was improved (2.4±0.5%, p=0.005) and no longer different compared to controls (p=0.32). Cognitive performance of OSA patients under dual task was impaired at baseline and improved under treatment.The present study shows that severe non-obese OSA patients have impaired gait control and suggests their cognitive origin, which are reversed after 8 weeks of CPAP treatment. The cerebral and neuromuscular substrates of these gait control impairments need to be further elucidated.

Background: We investigated the respective effect of different modalities of exercise training programs on exercise capacity and cardiometabolic parameters in obese patients already treated for OSA. Methods: 53 Obese OSA were randomly assigned to a 3-month exercise training (Ergocycle -ERGO- vs. ERGO supported by non-invasive ventilation -ERGONIV- vs. ERGO + respiratory muscle training -ERGORMT). Walking distance, peak aerobic capacity (VO 2Peak ), body composition (fat-free mass index – FFMI), metabolic, inflammatory and cardiovascular parameters were evaluated before and after training. Results: In intention to treat analysis, ERGONIV and ERGORMT led to higher improvement in VO 2peak than ERGO (+13 ± 2% vs. +11 ± 2% vs. 4 ± 3% pred., respectively, p = 0.01). Furthermore, ERGONIV led to higher reduction in systolic blood pressure than ERGORMT and ERGO (-8.6 ± 2.7 vs. -1.3 ± 1.5 vs. -0.7 ± 2.4 mmHg, respectively, p = 0.02) and ERGORMT led to higher improvement in FFMI than ERGONIV and ERGO (+0.9 ± 0.4 vs. -0.2 ± 0.2 vs. -0.1± 0.2 kg/m², respectively, p = 0.02). Conclusion: Our results showed for the first time an improvement in cardiometabolic parameters after training in obese CPAP-treated OSA. Ventilatory support and respiratory muscle training are efficient adjunctive tools to individualize goals of exercise training in these patients.