Exercise-induced muscle oxidative stress may be involved in the myopathy associated with chronic obstructive pulmonary disease (COPD). This study was designed to look at whether local exercise induces muscle oxidative stress and whether this oxidative stress may be associated with the reduced muscle endurance in patients with COPD. Quadriceps endurance was measured in 12 patients with COPD (FEV1 = 0.96 +/- 0.14 SEM) and 10 healthy sedentary subjects by repeated knee extensions of the dominant leg. Biopsies of the vastus lateralis muscle were obtained before and 48 hours after exercise. Muscle oxidative stress was measured by lipid peroxidation and oxidized proteins. Muscle antioxidant was evaluated by peroxidase glutathion activity. Quadriceps endurance was significantly reduced in patients with COPD when compared with the healthy control subjects (p < 0.01). Forty-eight hours postexercise, only patients with COPD had a significant increase in muscle lipid peroxidation (p < 0.05) and oxidized proteins (p < 0.05), whereas increased peroxidase glutathion activity was only observed in control subjects (p < 0.05). Both increases in muscle lipid peroxidation and oxidized proteins were significantly and inversely correlated with quadriceps endurance capacity in COPD (p < 0.05). In summary, local exercise induced muscle oxidative stress in patients with COPD, whereas it failed to raise antioxidant activity. In these individuals, muscle oxidative stress was associated with a reduced quadriceps endurance.

This study tested whether the lower economy of walking in healthy elderly subjects is due to greater gait instability. We compared the energy cost of walking and gait instability (assessed by stride to stride changes in the stride time) in octogenarians (G80, n = 10), 65-yr-olds (G65, n = 10), and young controls (G25, n = 10) walking on a treadmill at six different speeds. The energy cost of walking was higher for G80 than for G25 across the different walking speeds (P < 0.05). Stride time variability at preferred walking speed was significantly greater in G80 (2.31 +/- 0.68%) and G65 (1.93 +/- 0.39%) compared with G25 (1.40 +/- 0.30%; P < 0.05). There was no significant correlation between gait instability and energy cost of walking at preferred walking speed. These findings demonstrated greater energy expenditure in healthy elderly subjects while walking and increased gait instability. However, no relationship was noted between these two variables. The increase in energy cost is probably multifactorial, and our results suggest that gait instability is probably not the main contributing factor in this population. We thus concluded that other mechanisms, such as the energy expenditure associated with walking movements and related to mechanical work, or neuromuscular factors, are more likely involved in the higher cost of walking in elderly people.

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The role of exercise-induced oxidative stress in the reduced quadriceps endurance of chronic obstructive pulmonary disease (COPD) patients has never been shown. We conducted a randomized, double-blind, and crossover study in which nine severe patients performed localized dynamic quadriceps endurance tests at 40% of maximal strength after oral treatment with the antioxidant, N-acetylcysteine (NAC), and placebo. Venous blood was sampled before, immediately after exercise, and 6 hours later. Endurance time improved by 25% after NAC treatment compared with placebo (p < 0.05). Superoxide anion (oxidant) release by stimulated phagocytes decreased after treatment (p < 0.05). No change in the antioxidant system was observed. Lipid peroxidation, an index of oxidative stress, was significantly increased 6 hours after exercise in the placebo condition (p < 0.05) but not after treatment. Advanced oxidized protein products, another index of oxidative stress, were also increased 6 hours after exercise by 139 +/- 27% in the placebo condition but only by 54 +/- 19% after treatment (p < 0.05). This study shows that NAC treatment in COPD reduced basal disturbance in the prooxidant system, improved endurance time, and prevented exercise-induced oxidative stress. Oxidative stress thus seems to be implicated in the reduced quadriceps endurance of patients with COPD.

The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease (COPD) is of growing interest, but often requires biopsies, usually with the Bergström technique. The current study was designed to test the validity of a minimally invasive technique: the microbiopsy.In 17 patients with COPD and four normal subjects, two specimens of the vastus lateralis were taken percutaneously under local anaesthesia, one with a 16-gauge needle (microbiopsy) and the other with the Bergström needle. The enzymatic activity of citrate synthase (CS) and phosphofructokinase (PFK), and the myosin heavy chain (MyoHC) composition were measured for both techniques.The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy. The microbiopsy sample weight reached 55¡17 mg. The two techniques showed excellent agreement for CS activity and MyoHC composition. The PFK activity did not differ statistically between the techniques, but the agreement was moderate. The agreement between both biopsy techniques was stable over time. The median (range) fibre number within the microbiopsy specimens was 144 (38-286).In conclusion, the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects, compared with the Bergström technique.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

During exercise, healthy individuals are able to maintain arterial oxygenation, whereas highly-trained endurance athletes may exhibit an exercise-induced arterial hypoxaemia (EIAH) that seems to reflect a gas exchange abnormality. The effects of EIAH are currently debated, and different hypotheses have been proposed to explain its pathophysiology. For moderate exercise, it appears that a relative hypoventilation induced by endurance training is involved. For high-intensity exercise, ventilation/perfusion (V(A)/Q) mismatching and/or diffusion limitation are thought to occur. The causes of this diffusion limitation are still under debate, with hypotheses being capillary blood volume changes and interstitial pulmonary oedema. Moreover, histamine is released during exercise in individuals exhibiting EIAH, and questions persist as to its relationship with EIAH and its contribution to interstitial pulmonary oedema. Further investigations are needed to better understand the mechanisms involved and to determine the long term consequences of repetitive hypoxaemia in highly trained endurance athletes.