Comparison of mechanical ventilatory constraints between continuous and intermittent exercises in healthy prepubescent children.

International audienceBBackground: The aim of this study was to evaluate the occurrence and severity of mechanical ventilatory constraints in healthy prepubescent children during continuous and intermittent exercise. Methods: Twelve prepubescent children (7 - 11 years old) performed 7 exercises on a treadmill: one graded test for the determination of maximal aerobic speed (MAS), three continuous exercises (CE) at 60, 70 and 80% of MAS and three intermittent exercises (IE), alternating 15s of exercise with 15s of passive recovery, at 90, 100 and 110% of MAS. During each CE and IE, tidal flow/volume loops were plotted within a maximal flow/volume loop (MFVL) measured at rest before each exercise. Expiratory flow limitation (expFL expressed in %Vt) was defined as the part of exercise tidal volume (Vt) meeting the boundary of MFVL. Breathing strategy was estimated by measuring inspiratory capacity relative to forced vital capacity and tidal volume relative to inspiratory capacity. Other breathing pattern parameters (ventilation VE, Vt, respiratory frequency f) were continuously recorded during exercise. Results: An "intensity" effect was found for during CE (p<0.001) but not during IE (p=0.08). The increase in was predominantly assumed by an increase in f for both exercise modalities. During each exercise, several children heterogeneously experienced expFL ranging between 10 - 90%Vt. For all exercises, Vt was predominantly regulated by an increase in Vt/IC with no change in IC/FVC from rest to exercise. Finally, no significant "modality" effect was found for mechanical ventilatory constraint parameters (expFL, VT/IC and IV/FVC). Discussion: We could conclude that neither of the modalities studied induced more mechanical ventilatory constraints than the other, but that exercise intensities specific to each modality might be greater sources of exacerbation for mechanical ventilatory constraints

PABPN1 gene therapy for oculopharyngeal muscular dystrophy

International audienceOculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment

Etudes des réponses et stratégies ventilatoires en fonction de la modalité d'exercice chez des enfants prépubères sains et des enfants prépubères atteints de mucoviscidose.

Exercise flow/volume loops allow one to study the ventilatory response of a subject and could bring information on the origin and the severity of mechanical ventilatory constraints potentially observed during exercise. Few studies have focused on the effect of an exercise on the adaptation of ventilatory response in prepubescent children with exercise flow/volume loop methodology. However, the characteristics of the children's pulmonary system could induce a specific adaptation of ventilatory response during exercise in prepubescent children in comparison with the adult. Moreover, the exposition to a chronic respiratory disease like cystic fibrosis could accentuate the specificity of ventilatory response during exercise in prepubescent children. The first aim of this work was to study the adaptation of the ventilatory response during an incremental exercise in healthy children and children with cystic fibrosis. Our results have confirmed the existence of a specific ventilatory response in prepubescent children and the occurrence of mechanical ventilatory constraints during incremental exercise. Cystic fibrosis seems to have no effect on the adaptation of the ventilatory response during incremental exercise. However, incremental exercise was not representative of the physical activity frequently performed by children. The second aim of this work was to determine the effect of the exercise modality: continuous vs. intermittent, on the adaptation of the ventilatory response. Firstly, a search of correspondences between continuous and intermittent exercise intensities was performed in order to propose exercise intensities which induce similar cardio-respiratory responses between the two exercise modalities. Secondly, our results have shown the existence of mechanical ventilatory constraints for both exercise modalities, whatever the exercise intensity. However, the occurrence of mechanical ventilatory constraints does not induce respiratory muscles fatigue. Moreover, the exercise modality seems to have no effect on the severity of the mechanical ventilatory constraints. Finally, as for incremental exercise, mild chronic respiratory disease does not influence the adaptation of the ventilatory response during continuous and intermittent exercises. Children with cystic fibrosis showed similar ventilation regulation whatever the exercise modality, which is predominantly made possible by an increase of breathing frequency.L'étude des courbes débit/volume d'exercice permet d'étudier la réponse ventilatoire d'un sujet et d'apporter des informations sur l'origine et la sévérité des contraintes mécaniques ventilatoires potentiellement observées au cours de l'exercice. Très peu d'études se sont focalisées sur l'effet d'un exercice sur l'adaptation de la réponse ventilatoire chez l'enfant prépubère à l'aide de cette méthodologie. Or, les caractéristiques du système pulmonaire de l'enfant pourraient induire une adaptation de la réponse ventilatoire à l'exercice spécifique chez l'enfant prépubère par rapport à l'adulte. De plus, l'exposition à une pathologie respiratoire chronique telle que la mucoviscidose pourrait accentuer la spécificité de la réponse ventilatoire à l'exercice chez l'enfant prépubère. Le premier objectif de ce travail de thèse a été d'étudier l'adaptation de la réponse ventilatoire lors d'un exercice incrémental chez des enfants sains et des enfants atteints de mucoviscidose. Nos résultats ont confirmé l'existence d'une spécificité de la réponse ventilatoire chez l'enfant prépubère et l'apparition de contraintes mécaniques ventilatoires lors de l'exercice incrémental, la mucoviscidose n'ayant pas d'effets sur l'adaptation de la réponse ventilatoire à ce type d'exercice. Toutefois, l'exercice incrémental n'est pas représentatif du type d'activité physique réalisé quotidiennement par les enfants. Aussi, le second objectif de ce travail était d'analyser l'effet de la modalité d'exercice: continue vs. intermittente, sur l'adaptation de la réponse ventilatoire. Ceci s'est traduit dans un premier temps par la recherche de correspondances entre les intensités d'exercices continus et intermittents afin de proposer des intensités d'exercices induisant des réponses cardiorespiratoires similaires entre les deux modalités d'exercice. Dans un second temps, nos résultats ont montré l'existence de contraintes mécaniques ventilatoires pour les deux modalités d'exercice, quelque soit l'intensité d'exercice, sans toutefois induire de fatigue des muscles respiratoires. Toutefois, la modalité d'exercice n'aurait aucune influence sur la sévérité de ces contraintes. De plus, comme pour l'exercice incrémental, la présence d'une pathologie respiratoire chronique légère n'influencerait pas l'adaptation de la réponse ventilatoire lors d'exercices continus et intermittents. Les enfants sains ou atteints de mucoviscidose présentent une régulation de la ventilation réalisée de manière prédominante par une augmentation de la fréquence respiratoire

Intensity level and on-court role of wheelchair rugby players during competition.

International audienceBACKGROUND:This study aims at quantifying the level of physical activity of wheelchair rugby players during matches in order to compare defensives players (DP) and offensives players (OP) profiles. Our hypothesis is that OP would present a higher energy expenditure and intensity level values during matches than DP, due to specific actions according to the on- court role.METHODS:Fifty-two players, including 24 DP and 28 OP (mean age of 34 ± 9 years), from eight French teams involved in the national elite championship and in the French national cup, participated. The seven wheelchair rugby players' classes were differentiated from 0.5 points (most severe deficiencies) to 3.5 points (less severe deficiencies). DP and OP were regrouped from 0.5 to 1.5 points and from 2 to 3.5 points, respectively. Energy expenditure (in Kcal), intensity level (in metabolic equivalent of task) and physical activity time (in minutes) of wheelchair rugby players during competition were evaluated.RESULTS:Statistical analysis between DP and OP showed a significant difference in vigorous activity time with a higher vigorous activity time for OP than DP; p < 0.007), associated with higher mean intensity level for OP vs. DP (4.3±1.0 METs vs. 3.8±0.9 METs respectively; p=0.049). No significant differences between DP and OP were found for active energy expenditure (385 ± 158 Kcal vs. 446 ± 199 Kcal, for DP and OP respectively) during matches.CONCLUSIONS:This study highlighted significantly different wheelchair rugby player profiles between competing DP and OP for the time spent in high intensity and intensity level. Offensive players were more explosive during a match than DP; therefore, training should be adapted accordingly to their roles

Exercise-based games interventions at home in individuals with a neurological disease: A systematic review and meta-analysis

International audienceThe objective of this review was to summarize the current best evidence for the effectiveness, feasibility, user compliance and safety of exercise-based games (EBGs), including virtual reality and interactive video game interventions, for the rehabilitation of individuals with neurological disorders at home

Time to exhaustion and time spent at a high percentage of VO2max in severe intensity domain in children and adults.

International audienceThe aim of the study was to compare time spent at a high percentage of VO2max (>90% of VO2max) (ts90%), time to achieve 90% of VO2max (ta90%), and time to exhaustion (TTE) for exercise in the severe intensity domain in children and adults. Fifteen prepubertal boys (10.3 ± 0.9 years) and 15 men (23.5 ± 3.6 years) performed a maximal graded exercise to determine VO2max, maximal aerobic power (MAP) and power at ventilatory threshold (PVTh). Then, they performed 4 constant load exercises in a random order at PVTh plus 50 and 75% of the difference between MAP and PVTh (PΔ50 and PΔ75) and 100 and 110% of MAP (P100 and P110). VO2max was continuously monitored. The P110 test was used to determine maximal accumulated oxygen deficit (MAOD). No significant difference was found in ta90% between children and adults. ts90% and TTE were not significantly different between children and adults for the exercises at PΔ50 and PΔ75. However, ts90% and TTE during P100 (p < 0.05 and p < 0.01, respectively) and P110 (p < 0.001) exercises were significantly shorter in children. Children had a significantly lower MAOD than adults (34.3 ± 9.4 ml · kg vs. 53.6 ± 11.1 ml · kg). A positive relationship (p < 0.05) was obtained between MAOD and TTE values during the P100 test in children. This study showed that only for intensities at, or higher than MAP, lower ts90% in children was linked to a reduced TTE, compared to adults. Shorter TTE in children can partly be explained by a lower anaerobic capacity (MAOD). These results give precious information about exercise intensity ranges that could be used in children's training sessions. Moreover, they highlight the implication of both aerobic and anaerobic processes in endurance performances in both populations