Physical activity patterns and clusters in 1001 patients with COPD.

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

Preserved function and reduced angiogenesis potential of the quadriceps in patients with mild COPD.

BACKGROUND: Little is known about limb muscle abnormalities in mild COPD. Inactivity and systemic inflammation could play a role in the development of limb muscle dysfunction in COPD. The objective of the present study was to characterize quadriceps function, enzymatic activities and morphometry, levels of plasma inflammatory markers and physical activity levels in daily life (PAdl) in patients with mild COPD (GOLD 1). METHODS: Mid-thigh muscle cross-sectional area (MTCSA), quadriceps strength, endurance, fiber-type distribution, capillarity, pro-angiogenesis factors (VEGF-A, angiopoietin I and II) and muscle oxidative capacity were assessed in 37 patients with mild COPD and 19 controls. Systemic inflammatory markers (CRP, IL-6, TNF-α, Fibrinogen, SP-D) and PAdl were assessed. RESULTS: MTCSA, quadriceps strength and endurance were not different between COPD and controls. Capillarity and muscle oxidative capacity were all preserved in mild COPD. Reduced pro-angiogenesis factor mRNA expression was seen in COPD. The level of moderately active intensity (>3 METs) was significantly lower in mild COPD and, in multiple regression analyses, the level of physical activity was a determinant of muscle oxidative capacity and capillarization. No between-group differences were found regarding muscle oxidative stress while circulating IL-6 levels were elevated in mild COPD. CONCLUSIONS: The quadriceps muscle function was preserved in mild COPD although a reduced potential for angiogenesis was found. The reduced level of daily activities and evidence of systemic inflammation in these individuals suggest that these factors precede the development of overt limb muscle dysfunction in COPD.

Influences of spinal anesthesia on exercise tolerance in patients with chronic obstructive pulmonary disease.

RATIONALE: Lower limb muscle dysfunction contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We hypothesized that signaling from lower limb muscle group III/IV sensory afferents to the central motor command could be involved in premature cycling exercise termination in COPD. OBJECTIVES: To evaluate the effects of spinal anesthesia, which presumably inhibited central feedback from the lower limb muscle group III/IV sensory afferents on exercise tolerance and cardiorespiratory response during constant work-rate cycling exercise in patients with COPD. METHODS: In a crossover and double-blind randomized design, eight patients with COPD (FEV(1), 67 ± 8% predicted) completed a constant work-rate cycling exercise after sham (NaCl, interspinous L(3)-L(4)) or active (fentanyl 25 µg, intrathecal L(3)-L(4)) spinal anesthesia. MEASUREMENTS AND MAIN RESULTS: When compared with placebo, endurance time was significantly prolonged after spinal anesthesia with fentanyl (639 ± 87 s vs. 423 ± 38 s [mean ± SEM]; P = 0.01). Ventilation and respiratory rate were reduced at isotime points under the fentanyl condition, whereas ventilatory efficiency and dead space ventilation were improved. Patients exhibited less dynamic hyperinflation at isotime points with spinal anesthesia. Consequently, the rise in dyspnea was significantly flatter during the fentanyl condition than with placebo. CONCLUSIONS: Spinal anesthesia enhanced cycling exercise tolerance in patients with COPD, mostly by reducing ventilatory response and dyspnea during exercise; these effects were possibly mediated through the inhibition of group III/IV lower limb sensory muscle afferents.

Distal leg muscle function in patients with COPD.

Quadriceps muscle weakness and increased fatigability are well described in patients with chronic obstructive pulmonary disease (COPD). Whether these functional alterations also exist in distal leg muscles in patients with COPD is uncertain. Fifteen patients with COPD and 15 aged-matched healthy controls performed a 12-minute standardized treadmill exercise during which a fixed total expense of 40 Kcal was reached. The strength of i) dorsiflexors, ii) plantar flexors and iii) quadriceps was assessed at rest and after exercise using maximal voluntary contraction (MVC) and potentiated twitch force (Twpot). Resting MVC and Twpot were significantly lower in patients with COPD when compared with controls respectively for i) dorsiflexors (24.9 ± 8.4 vs. 31.2 ± 8.5 Nm, p < 0.05 and 4.3 ± 1.3 vs. 5.7 ± 1.8 Nm, p < 0.05), ii) plantar flexors (49.5 ± 11.8 vs. 62.1 ± 19.6 Nm, p < 0.05 and 10.8 ± 3.5 vs. 13.4 ± 2.7 Nm, p < 0.05), and iii) quadriceps muscles. There was a greater force loss in the distal leg muscles 15 minutes post-exercise in patients with COPD, while the strength of the quadriceps muscle remained stable in both groups. Patients with COPD had weaker dorsiflexor and plantar flexor muscles when compared to age-matched healthy controls. In addition, when exposed to the same absolute walking task, the fatigability of the distal leg muscles was higher in patients with COPD.

Optimal scaling of random walk Metropolis algorithms using Bayesian large-sample asymptotics.

High-dimensional limit theorems have been shown useful to derive tuning rules for finding the optimal scaling in random walk Metropolis algorithms. The assumptions under which weak convergence results are proved are, however, restrictive: the target density is typically assumed to be of a product form. Users may thus doubt the validity of such tuning rules in practical applications. In this paper, we shed some light on optimal scaling problems from a different perspective, namely a large-sample one. This allows to prove weak convergence results under realistic assumptions and to propose novel parameter-dimension-dependent tuning guidelines. The proposed guidelines are consistent with the previous ones when the target density is close to having a product form, and the results highlight that the correlation structure has to be accounted for to avoid performance deterioration if that is not the case, while justifying the use of a natural (asymptotically exact) approximation to the correlation matrix that can be employed for the very first algorithm run.

An automatic robust Bayesian approach to principal component regression.

Principal component regression uses principal components (PCs) as regressors. It is particularly useful in prediction settings with high-dimensional covariates. The existing literature treating of Bayesian approaches is relatively sparse. We introduce a Bayesian approach that is robust to outliers in both the dependent variable and the covariates. Outliers can be thought of as observations that are not in line with the general trend. The proposed approach automatically penalises these observations so that their impact on the posterior gradually vanishes as they move further and further away from the general trend, corresponding to a concept in Bayesian statistics called whole robustness. The predictions produced are thus consistent with the bulk of the data. The approach also exploits the geometry of PCs to efficiently identify those that are significant. Individual predictions obtained from the resulting models are consolidated according to model-averaging mechanisms to account for model uncertainty. The approach is evaluated on real data and compared to its nonrobust Bayesian counterpart, the traditional frequentist approach and a commonly employed robust frequentist method. Detailed guidelines to automate the entire statistical procedure are provided. All required code is made available, see ArXiv:1711.06341.

Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension.

BACKGROUND: A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite new specific therapies. Whether patients with IPAH exhibit peripheral muscle dysfunction that may contribute to this limitation remains unknown. The hypothesis that the muscles of patients with IPAH are weaker and display morphological changes compared with those of control subjects and that those changes partly correlate with their exercise capacity was tested. OBJECTIVE: To characterise quadriceps function, morphology and the enzymatic profile of patients with IPAH. METHODS: Exercise capacity, limb muscle cross-sectional area by CT scan, quadriceps strength by maximal voluntary contraction and non-volitional magnetic stimulation of the femoral nerve (quadriceps twitch; TWq), and muscle morphology and enzymatic profile by quadriceps biopsy of 10 patients with IPAH were compared with those of 10 matched controls subjects. RESULTS: Patients with IPAH displayed a lower proportion of type I muscle fibres (p=0.05), a lower maximal voluntary contraction (p=0.05) and TWq (p=0.01), and an increased muscular phosphofructokinase/3-hydroxyacyl-CoA-dehydrogenase ratio (p=0.05). They also tended to have lower thigh muscle cross-sectional area (p=0.15). Maximal oxygen uptake correlated with quadriceps strength (R(2)=0.42, p=0.04), and oxygen uptake at anaerobic threshold correlated with muscle oxidative capacity assessed by oxidative enzyme level for citrate synthase (R(2)=0.45, p=0.05) and 3-hydroxyacyl-CoA-dehydrogenase (R(2)=0.86, p<0.01), and type I fibre capillarity (R(2)=0.57, p=0.02). CONCLUSION: Patients with IPAH present significant peripheral muscle changes that partly correlated with their exercise capacity.

Impact of preinduced quadriceps fatigue on exercise response in chronic obstructive pulmonary disease and healthy subjects.

Exercise intolerance in chronic obstructive pulmonary disease (COPD) results from a complex interaction between central (ventilatory) and peripheral (limb muscles) components of exercise limitation. The purpose of this study was to evaluate the influence of quadriceps muscle fatigue on exercise tolerance and ventilatory response during constant-workrate cycling exercise testing (CWT) in patients with COPD and healthy subjects. Fifteen patients with COPD and nine age-matched healthy subjects performed, 7 days apart, two CWTs up to exhaustion at 80% of their predetermined maximal work capacity. In a randomized order, one test was performed with preinduced quadriceps fatigue and the other in a fresh state. Quadriceps fatigue was produced by electrostimulation-induced contractions and quantified by maximal voluntary contraction and potentiated twitch force (TwQ(pot)). Endurance time and ventilatory response during CWT were compared between fatigued and fresh state. Endurance time significantly decreased in the fatigued state compared with the fresh condition in COPD (356 +/- 69 s vs. 294 +/- 45 s, P < 0.05) and controls (450 +/- 74 s vs. 340 +/- 45 s, P < 0.05). Controls showed significantly higher ventilation and end-exercise dyspnea scores in the fatigued condition, whereas, in COPD, fatigue did not influence ventilation or dyspnea during exercise. The degree of ventilatory limitation, as expressed by the Ve/maximum voluntary ventilation ratio, was similar in both conditions in patients with COPD. We conclude that it is possible to induce quadriceps fatigue by local electrostimulation-induced contractions. Our findings demonstrate that peripheral muscle fatigue is an additional important factor, besides intense dyspnea, that limits exercise tolerance in COPD.

Use of facemask and mouthpiece to assess constant-workrate exercise capacity in COPD.

PURPOSE: To compare the response to constant-workrate cycling exercise between the mouthpiece and the facemask in patients with chronic obstructive pulmonary disease (COPD). METHODS: Ten patients with COPD (FEV1: 48 +/- 14% pred, mean +/- SD) performed two symptom-limited constant-workrate cycling exercise tests at 80% of their predetermined peak exercise capacity. One test was performed using a mouthpiece and the other with a facemask, in a random order. The endurance time to constant-workrate exercise was compared between the two interfaces. VO2, VCO2, ventilation (VE), inspiratory capacity, dyspnea Borg score, and heart rate responses during exercise were also compared. RESULTS: Endurance time was similar between the two interfaces (mean difference +/- SD, 30 +/- 74 s, P = 0.23). Except for the end-exercise values, which were lower with the facemask, the VO2, VCO2, and VE responses to submaximal exercise were similar between the two interfaces. Perception of dyspnea, inspiratory capacity, and heart rate kinetics were similar during the two exercise tests. No clear preference about either interface was expressed by the patients. CONCLUSION: The mouthpiece and the facemask can be used with comparable results to determine the endurance time to constant-workrate cycling exercise in patients with COPD. Compared with the mouthpiece, the end-exercise values for VO2, VCO2, and VE were underestimated when a facemask was used. The similar responses in heart rate and symptom perception suggest that this could be due to an air leak at end-exercise with the facemask.

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease.

BACKGROUND: We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category. METHODS: Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups. RESULTS: Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV1/FVC versus clusters I and II COPD patients. CONCLUSIONS: The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients. TRIAL REGISTRATION: www.clinicaltrials.gov. NCT01360788 and NCT01072396.

Tolerance and physiological correlates of neuromuscular electrical stimulation in COPD: a pilot study.

RATIONALE: Neuromuscular electrical stimulation (NMES) of the lower limbs is an emerging training strategy in patients with COPD. The efficacy of this technique is related to the intensity of the stimulation that is applied during the training sessions. However, little is known about tolerance to stimulation current intensity and physiological factors that could determine it. Our goal was to find potential physiological predictors of the tolerance to increasing NMES stimulation intensity in patients with mild to severe COPD. METHODS: 20 patients with COPD (FEV1 = 54±14% pred.) completed 2 supervised NMES sessions followed by 5 self-directed sessions at home and one final supervised session. NMES was applied simultaneously to both quadriceps for 45 minutes, at a stimulation frequency of 50 Hz. Spirometry, body composition, muscle function and aerobic capacity were assessed at baseline. Cardiorespiratory responses, leg discomfort, muscle fatigue and markers of systemic inflammation were assessed during or after the last NMES session. Tolerance to NMES was quantified as the increase in current intensity from the initial to the final NMES session (ΔInt). RESULTS: Mean ΔInt was 12±10 mA. FEV1, fat-free-mass, quadriceps strength, aerobic capacity and leg discomfort during the last NMES session positively correlated with ΔInt (r = 0.42 to 0.64, all p≤0.06) while post/pre NMES IL-6 ratio negatively correlated with ΔInt (r = -0.57, p = 0.001). FEV1, leg discomfort during last NMES session and post/pre IL-6 ratio to NMES were independent factors of variance in ΔInt (r2 = 0.72, p = 0.001). CONCLUSION: Lower tolerance to NMES was associated with increasing airflow obstruction, low tolerance to leg discomfort during NMES and the magnitude of the IL-6 response after NMES. TRIAL REGISTRATION: ClinicalTrials.gov NCT00809120.

Pathogenesis of hyperinflation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease.

Development of therapeutic polymeric nanoparticles for the resolution of inflammation.

Liver X receptors (LXRs) attenuate inflammation by modulating the expression of key inflammatory genes, making LXRs and their ligands particularly attractive candidates for therapeutic intervention in cardiovascular, metabolic, and/or inflammatory diseases. Herein, enhanced proresolving activity of polymeric nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (LXR-NPs) is demonstrated, developed from a combinatorial library of more than 70 formulations with variations in critical physicochemical parameters. In vitro studies on peritoneal macrophages confirm that LXR-NPs are significantly more effective than the free agonist at downregulating pro-inflammatory mediators (MCP-1 and TNFα), as well as inducing the expression of LXR target genes (ABCA1 and SREBP1c). Through a zymosan-induced acute peritonitis in vivo model, LXR-NPs are found to be more efficient than free GW3965 at limiting the recruitment of polymononuclear neutrophils (50% vs 17%), suppressing the gene expression and secretion of pro-inflammatory factors MCP-1 and TNFα in peritoneal macrophages, and decreasing the resolution interval up to 4 h. Furthermore, LXR-NPs suppress the secretion of MCP-1 and TNFα by monocytes and macrophages more efficiently than the commercial drug dexamethasone. Overall, these findings demonstrate that LXR-NPs are capable of promoting resolution of inflammation and highlight the prospect of LXR-based nanotherapeutics for inflammatory diseases.

Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial.

BACKGROUND: The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD. METHODS: Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1). RESULTS: NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001). CONCLUSIONS: In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00874965; URL: www.clinicaltrials.gov.

Walking exercise response to bronchodilation in mild COPD: a randomized trial.

RATIONALE: Patients with mild chronic obstructive pulmonary disease (COPD) present abnormal ventilatory mechanics during exercise and may require bronchodilator therapy. However, bronchodilation does not enhance cycling exercise tolerance in these patients whereas walking may be more sensitive to the effects of bronchodilation. OBJECTIVES: To characterize the impact of bronchodilation on i) exercise tolerance ii) cardiopulmonary response and iii) dynamic hyperinflation following an endurance shuttle walking test in patients with mild COPD. METHODS: In a randomized double-blind cross-over trial, 37 patients with GOLD stage I COPD (FEV(1), 96 ± 2% predicted, mean ± SEM) completed an endurance shuttle walking test up to exhaustion 90 ± 15 min following nebulization of a placebo [NaCl] or of ipratropium bromide/salbutamol sulfate (500 µg/2.5 mg) combination. RESULTS: FEV(1) significantly increased following bronchodilation compared with placebo (0.17 ± 0.02 vs. -0.02 ± 0.01 L, p < 0.0001, mean ± SEM). The difference in walking endurance time between bronchodilation and placebo was not statistically significant (Δ15 ± 12 s, p = 0.21), with the upper and lower boundaries of the 95% confidence interval [-9-40 s, 95% CI] within the proposed minimally important difference for this variable (65 s). The ratio of breathing frequency to tidal volume tended to be decreased with bronchodilation during exercise (p = 0.07), indicating a deeper and slower breathing pattern with bronchodilation. Bronchodilation had a significant effect on dynamic hyperinflation at isotime and at peak exercise. CONCLUSION: Bronchodilation did not improve walking endurance in patients with mild COPD despite small physiological benefits of uncertain clinical relevance.

Quadriceps metabolism during constant workrate cycling exercise in chronic obstructive pulmonary disease.

Impaired resting metabolism in peripheral muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). This study investigated the cytosolic energy metabolism of the quadriceps, from glycogen degradation to lactate accumulation, in exercising patients with COPD, in comparison to healthy controls. We measured, in 12 patients with COPD and 10 control subjects, resting and post-cycling exercise quadriceps levels of 1) energy substrates and end products of glycolysis (glycogen, glucose, pyruvate, and lactate) and intermediate markers of glycolysis (glucose-6-phosphate, glucose-1-phosphate, fructose-6-phosphate) and 2) the activity of key enzymes involved in the regulation of glycolysis (phosphofructokinase, lactate dehydrogenase). Exercise intensity (P < 0.01), duration (P = 0.049), and total work (P < 0.01) were reduced in patients with COPD. The variations in energy substrates and end products of glycolysis after cycling exercise were of similar magnitude in patients with COPD and controls. Glucose-6-phosphate (P = 0.036) and fructose-6-phosphate (P = 0.042) were significantly elevated in patients with COPD after exercise. Phosphofructokinase (P < 0.01) and lactate dehydrogenase (P = 0.02) activities were greater in COPD. Muscle glycogen utilization (P = 0.022) and lactate accumulation (P = 0.025) per unit of work were greater in COPD. We conclude that cycling exercise induced changes in quadriceps metabolism in patients with COPD that were of similar magnitude to those of healthy controls. These intramuscular events required a much lower exercise work load and time to occur in COPD. Our data suggest a greater reliance on glycolysis during exercise in COPD, which may contribute to exercise intolerance in COPD.

Physiological correlates of endurance time variability during constant-workrate cycling exercise in patients with COPD.

RATIONALE: The endurance time (T(end)) during constant-workrate cycling exercise (CET) is highly variable in COPD. We investigated pulmonary and physiological variables that may contribute to these variations in T(end). METHODS: Ninety-two patients with COPD completed a CET performed at 80% of peak workrate capacity (W(peak)). Patients were divided into tertiles of T(end) [Group 1: <4 min; Group 2: 4-6 min; Group 3: >6 min]. Disease severity (FEV(1)), aerobic fitness (W(peak), peak oxygen consumption [VO2(peak)], ventilatory threshold [VO2(VT)]), quadriceps strength (MVC), symptom scores at the end of CET and exercise intensity during CET (heart rate at the end of CET to heart rate at peak incremental exercise ratio [HR(CET)/HR(peak)]) were analyzed as potential variables influencing T(end). RESULTS: W(peak), VO2(peak), VO2(VT), MVC, leg fatigue at end of CET, and HR(CET)/HR(peak) were lower in group 1 than in group 2 or 3 (p≤0.05). VO2(VT) and leg fatigue at end of CET independently predicted T(end) in multiple regression analysis (r = 0.50, p = 0.001). CONCLUSION: T(end) was independently related to the aerobic fitness and to tolerance to leg fatigue at the end of exercise. A large fraction of the variability in T(end) was not explained by the physiological parameters assessed in the present study. Individualization of exercise intensity during CET should help in reducing variations in T(end) among patients with COPD.

Wall-selective probing of double-walled carbon nanotubes using covalent functionalization.

Double-walled carbon nanotubes (DWNTs) present an original coaxial geometry in which the inner wall is naturally protected from the environment by the outer wall. Covalent functionalization is introduced here as an effective approach to investigate DWNT devices. Performed using an aryldiazonium salt, the functionalization is reversible upon thermal annealing and occurs strictly at the surface of the outer wall, leaving the inner wall essentially unaltered by the chemical bonding. Measurements on functionalized DWNT transistors show that the electrical current is carried by the inner wall and provide unambiguous identification of the metallic or semiconducting character of both walls. New insights about current saturation at high bias in DWNTs are also presented as an illustration of new experiments unlocked by the method. The wall-selectivity of the functionalization not only enables selective optical and electrical probing of the DWNTs, but it also paves the way to designing novel electronic devices in which the inner wall is used for electrical transport while the outer wall chemically interacts with the environment.

Effects of a rehabilitation program on skeletal muscle function in idiopathic pulmonary arterial hypertension.

INTRODUCTION: A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite current therapies. Whether a rehabilitation program elicits favorable changes in muscle function which would partly explain improvements in exercise tolerance of IPAH patients remains unknown. We performed this study to assess the effect of a 12-week rehabilitation program on skeletal muscle characteristics and exercise tolerance in patients with IPAH. METHODS: Exercise capacity measured by the 6-minute walk test and by the cycle endurance test (CET), limb muscle cross-sectional area, quadriceps function by maximal voluntary contraction and magnetic stimulation (potentiated twitches), and molecular muscle characteristics by quadriceps biopsy of 5 IPAH patients were assessed before and after a 12-week rehabilitation program. RESULTS: Following training, improvements in all patients were observed for the 6-minute walk test distance, from 441 (75) to 499 (85) m, P = .01, and the CET time, from 429 (239) to 633 (380) seconds, P = .16. Minute ventilation assessed at isotime during CET decreased by 15(11)%, P = .05. This was related to both decreased carbon dioxide output and (Equation is included in full-text article.)E/(Equation is included in full-text article.)co2. These improvements were associated with decreased type IIx fiber proportion, 31(8)% to 23(10)%, P = .05. DISCUSSION: Peripheral muscle characteristic improvements may contribute to the clinical benefit observed following a rehabilitation program in IPAH.