Efficacy of a long-term pulmonary rehabilitation maintenance program for COPD patients in a real-life setting: a 5-year cohort study.

BACKGROUND: Pulmonary rehabilitation (PR) improves exercise capacity, health-related quality of life (HRQoL) and dyspnea in chronic obstructive pulmonary disease (COPD) patients. Maintenance programs can sustain the benefits for 12 to 24 months. Yet, the long-term effects (> 12 months) of pragmatic maintenance programs in real-life settings remain unknown. This prospective cohort study assessed the yearly evolution in the outcomes [6-min walking distance (6MWD), HRQoL, dyspnea] of a supervised self-help PR maintenance program for COPD patients followed for 5 years. The aim was to assess the change in the outcomes and survival probability for 1 to 5 years after PR program discharge in COPD patients following a PR maintenance program supported by supervised self-help associations. METHODS: Data were prospectively collected from 144 COPD patients who followed a pragmatic multidisciplinary PR maintenance program for 1 to 5 years. They were assessed yearly for 6MWD, HRQol (VQ11) and dyspnea (MRC). The 5-year survival probability was compared to that of a control PR group without a maintenance program. A trajectory-based cluster analysis identified the determinants of long-term response. RESULTS: Maintenance program patients showed significant PR benefits at 4 years for 6MWD and VQ11 and 5 years for MRC. The 5-year survival probability was higher than for PR patients without PR maintenance. Two clusters of response to long-term PR were identified, with responders being the less severe COPD patients. CONCLUSIONS: This study provides evidence of the efficacy of a pragmatic PR maintenance program in a real-life setting for more than 3 years. In contrast to short-term PR, long-term PR maintenance appeared more beneficial in less severe COPD patients.

Additional Effects of Nutritional Antioxidant Supplementation on Peripheral Muscle during Pulmonary Rehabilitation in COPD Patients: A Randomized Controlled Trial.

BACKGROUND: Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is not fully reversed by exercise training. Antioxidants are critical for muscle homeostasis and adaptation to training. However, COPD patients experience antioxidant deficits that worsen after training and might impact their muscle response to training. Nutritional antioxidant supplementation in combination with pulmonary rehabilitation (PR) would further improve muscle function, oxidative stress, and PR outcomes in COPD patients. METHODS: Sixty-four COPD patients admitted to inpatient PR were randomized to receive 28 days of oral antioxidant supplementation targeting the previously observed deficits (PR antioxidant group; α-tocopherol: 30 mg/day, ascorbate: 180 mg/day, zinc gluconate: 15 mg/day, selenomethionine: 50 µg/day) or placebo (PR placebo group). PR consisted of 24 sessions of moderate-intensity exercise training. Changes in muscle endurance (primary outcome), oxidative stress, and PR outcomes were assessed. RESULTS: Eighty-one percent of the patients (FEV1 = 58.9 ± 20.0%pred) showed at least one nutritional antioxidant deficit. Training improved muscle endurance in the PR placebo group (+37.4 ± 45.1%, p < 0.001), without additional increase in the PR antioxidant group (-6.6 ± 11.3%; p = 0.56). Nevertheless, supplementation increased the α-tocopherol/γ-tocopherol ratio and selenium (+58 ± 20%, p < 0.001, and +16 ± 5%, p < 0.01, respectively), muscle strength (+11 ± 3%, p < 0.001), and serum total proteins (+7 ± 2%, p < 0.001), and it tended to increase the type I fiber proportion (+32 ± 17%, p = 0.07). The prevalence of muscle weakness decreased in the PR antioxidant group only, from 30.0 to 10.7% (p < 0.05). CONCLUSIONS: While the primary outcome was not significantly improved, COPD patients demonstrate significant improvements of secondary outcomes (muscle strength and other training-refractory outcomes), suggesting a potential "add-on" effect of the nutritional antioxidant supplementation (vitamins C and E, zinc, and selenium) during PR. This trial is registered with NCT01942889.

The self-perception of dyspnoea threshold during the 6-min walk test: a good alternative to estimate the ventilatory threshold in chronic obstructive pulmonary disease.

To determine and/or adjust exercise training intensity for patients when the cardiopulmonary exercise test is not accessible, the determination of dyspnoea threshold (defined as the onset of self-perceived breathing discomfort) during the 6-min walk test (6MWT) could be a good alternative. The aim of this study was to evaluate the feasibility and reproducibility of self-perceived dyspnoea threshold and to determine whether a useful equation to estimate ventilatory threshold from self-perceived dyspnoea threshold could be derived. A total of 82 patients were included and performed two 6MWTs, during which they raised a hand to signal self-perceived dyspnoea threshold. The reproducibility in terms of heart rate (HR) was analysed. On a subsample of patients (n=27), a stepwise regression analysis was carried out to obtain a predictive equation of HR at ventilatory threshold measured during a cardiopulmonary exercise test estimated from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in 1 s. Overall, 80% of patients could identify self-perceived dyspnoea threshold during the 6MWT. Self-perceived dyspnoea threshold was reproducibly expressed in HR (coefficient of variation=2.8%). A stepwise regression analysis enabled estimation of HR at ventilatory threshold from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in 1 s (adjusted r=0.79, r=0.63, and relative standard deviation=9.8 bpm). This study shows that a majority of patients with chronic obstructive pulmonary disease can identify a self-perceived dyspnoea threshold during the 6MWT. This HR at the dyspnoea threshold is highly reproducible and enable estimation of the HR at the ventilatory threshold.

Heterogeneity of Systemic Oxidative Stress Profiles in COPD: A Potential Role of Gender.

Oxidative stress (OS) plays a key role in the muscle impairment and exercise capacity of COPD patients. However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation. This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles. We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP) levels in 54 stable COPD patients referred for a rehabilitation program. The main systemic antioxidant deficits in these patients concerned vitamins and trace elements. Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them. Interestingly, two patient profiles (clusters 3 and 4) had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx. Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity. Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses.

Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients.

The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2 O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models.

Fiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes of different phenotypes in chronic obstructive pulmonary disease patients.

Peripheral muscle dysfunction, associated with reductions in fiber cross-sectional area (CSA) and in type I fibers, is a key outcome in chronic obstructive pulmonary disease (COPD). However, COPD peripheral muscle function and structure show great heterogeneity, overlapping those in sedentary healthy subjects (SHS). While discrepancies in the link between muscle structure and phenotype remain unexplained, we tested whether the fiber CSA and the type I fiber reductions were the attributes of different phenotypes of the disease, using unsupervised clustering method and post hoc validation. Principal component analysis performed on functional and histomorphological parameters in 64 COPD patients {forced expiratory volume in 1 s (FEV1) = 42.0 [30.0-58.5]% predicted} and 27 SHS (FEV1 = 105.0 [95.0-114.0]% predicted) revealed two COPD clusters with distinct peripheral muscle dysfunctions. These two clusters had different type I fiber proportion (26.0 ± 14.0% vs. 39.8 ± 12.6%; P < 0.05), and fiber CSA (3,731 ± 1,233 vs. 5,657 ± 1,098 µm(2); P < 0.05). The "atrophic" cluster showed an increase in muscle protein carbonylation (131.5 [83.6-200.3] vs. 83.0 [68.3-105.1]; P < 0.05). Then, COPD patients underwent pulmonary rehabilitation. If the higher risk of exacerbations in the "atrophic" cluster did not reach statistical significance after adjustment for FEV1 (hazard ratio: 2.43; P = 0.11, n = 54), the improvement of VO2sl after training was greater than in the nonatrophic cluster (+24 ± 16% vs. +6 ± 13%; P < 0.01). Last, their age was similar (60.4 ± 8.8 vs. 60.8 ± 9.0 yr; P = 0.87), suggesting a different time course of the disease. We identified and validated two phenotypes of COPD patients showing different muscle histomorphology and level of oxidative stress. Thus our study demonstrates that the muscle heterogeneity is the translation of different phenotypes of the disease.

A short questionnaire for the assessment of quality of life in patients with chronic obstructive pulmonary disease: psychometric properties of VQ11.

BACKGROUND: There is a need for a validated short instrument that can be used in routine practice to quantify potential short-term change in Health-Related Quality of Life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). Our aim is to determine the validity and reliability of the VQ11 questionnaire dedicated to the routine assessment of HRQoL. METHODS: 181 COPD patients (40-85 yrs, I to IV GOLD stages) completed the VQ11, and several tests. One week later, 49 of these patients completed the VQ11 again. RESULTS: Confirmatory factor analysis supported the two-level hierarchical structure of the VQ11 with 11 items covering three components and HRQoL at a higher level. The VQ11 showed good internal consistency and good reproducibility (r = 0.88). Concurrent validity showed significant correlations between VQ11 total scores and St George's Respiratory Questionnaire-C (r = 0.70), Short Form-36 (r = -0.66 for the physical component and -0.63 for the mental component). We obtained significant correlations with MRC Dyspnea Grades (r = 0.59), the Hospital Anxiety and Depression Scale total score (r = 0.62), and the BODE index (r = 0.53). CONCLUSION: The VQ11 has good measurement properties and provides a valid and reliable measure of COPD-specific HRQoL. It is ready for use in routine practice. CLINICAL REGISTRATION: The study was approved by the University of Montpellier 1 Ethics Committee and the Regional Ethics Committee (authorization number: A00332-53).

Reference values for vastus lateralis fiber size and type in healthy subjects over 40 years old: a systematic review and metaanalysis.

Skeletal muscle atrophy is a major systemic impairment in chronic diseases. Yet its determinants have been hard to identify because a clear research definition has not been agreed upon. The reduction in muscle fiber cross-sectional area (CSA) is a widely acknowledged marker of muscle atrophy, but no reference values for the muscle fiber CSA at the age of the onset of chronic disease have ever been published. Thus, we aimed to systematically review the studies providing data on fiber CSA and fiber type proportion in the vastus lateralis of the quadriceps of healthy subjects (age >40 yr) and then to pool and analyze the data from the selected studies to determine reference values for fiber CSA. We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and identified 19 studies, including 423 subjects that matched the inclusion criteria. On the basis of fiber type and gender, the mean fiber CSA and the lower limits of normal (LLNs) were (%type I*60) + 1,743 µm(2) and (%type I*60) - 718 µm(2), respectively, for men; and (%type I*70) + 139 µm(2) and (%type I*70) - 1,485 µm(2), respectively, for women. There was no significant heterogeneity among subgroups of fiber type and gender. The pooled type I fiber proportion was 50.3% (LLN = 32.9%). In multivariate analysis, fiber CSA was significantly correlated with Vo2 peak (r = 190.92; P = 0.03), and type I fiber proportion was correlated with age (r = -0.024; P = 0.005), body mass index (r = 0.096; P = 0.005), and Vo2 peak (r = -0.053; P = 0.005). Our metaanalysis of a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA according to fiber type and gender. This analysis will be improved by prospective assessment in well-characterized healthy subjects.

Aggravation of pulmonary diffusing capacity in highly trained athletes by 6 weeks of low-volume, low-intensity training.

PURPOSE: Postexercise alveolar-capillary membrane-diffusing capacity (DLco) often decreases in highly trained endurance athletes and seems linked to their training status. To test the hypothesis that training status influences postexercise DLco, 13 male and 2 female triathletes (20.2 ± 4.4 y old, 175.2 ± 6.7 cm tall; weight in a range of 66.6 ± 7.4 kg to 67.4 ± 7.8 kg during the 1-y study) were randomized into experimental (n = 7) and control (n = 8) groups and performed VO(2max) cycle tests and simulated cycle-run successions (CR) of 30 min + 20 min after 3 periods in the competitive season. METHODS: Both groups were tested before (pre- HTP) and after a 30-wk high-training period (HTP) with high training volume, intensity, and frequency. The experimental group was then also tested after a 6-wk low-training period (LTP) with low training volume, intensity, and frequency, while the control group continued training according to the HTP schedule for these 6 wk. Ventilatory data were collected continuously. DLco testing was performed before and 30, 60, and 120 min after the CR trials. RESULTS: Whatever the period or group, DLco was significantly decreased 30 min after CR, with a significantly greater decrease in the experimental group than the control group in LTP (-15.7% and -9.3% of DLco, respectively). CONCLUSIONS: Six weeks of low training volume and intensity were sufficient to reverse the effects of high training volume and intensity on the alveolar-capillary membrane after a CR succession in competitive triathletes.

Blunted muscle angiogenic training-response in COPD patients versus sedentary controls.

The impaired skeletal muscle of chronic obstructive pulmonary disease (COPD) patients reduces exercise capacity. Similar to the oxidative muscle fibres, the angio-adaptation of muscle to training may be blunted in these patients, as in other chronic conditions. We therefore compared muscle functional responses and angio-adaptations after training in COPD patients and sedentary healthy subjects (SHS). 24 COPD patients (forced expiratory volume in 1 s 45.6 ± 17.5% predicted) and 23 SHS (<150 min · week(-1) of moderate-to-vigorous exercise) completed a 6-week rehabilitation programme based on individualised moderate-intensity endurance training. Histomorphological muscle analysis and measurements of pro-angiogenic vascular endothelial growth factor (VEGF)-A and anti-angiogenic thrombospondin (TSP)-1 were conducted before and after training. COPD patients and SHS showed improved symptom-limited oxygen consumption and muscle endurance, although improvements were lower in COPD patients (+0.96 ± 2.4 versus +2.9 ± 2.6 mL · kg(-1) · min(-1), p<0.05, and +65% versus +108%, p = 0.06, respectively). The capillary-to-fibre (C/F) ratio increased less in COPD patients than SHS (+16 ± 10% versus +37 ± 20%, p<0.05) and no fibre type switch occurred in COPD patients. The VEGF-A/TSP-1 ratio increased in COPD patients and SHS (+65% versus +35%, p<0.05). Changes in C/F and symptom-limited oxygen consumption were correlated (r = 0.51, p<0.05). In addition to a lack of fibre switch, COPD patients displayed a blunted angiogenic response to training.

Effect of acute and short-term oral salbutamol treatments on maximal power output in non-asthmatic athletes.

This study aimed to clarify the controversial effects of acute and short-term salbutamol (SAL) intake on sprint performance in healthy athletes. Based on the results of previous studies, an anabolic effect for the short-term treatment and increased glycolysis in both treatments were hypothesized. Eight male recreational athletes completed force-velocity exercise tests after administration of placebo (gelatin), acute oral SAL (6 mg) or short-term oral SAL (12 mg day(-1) for 3 weeks), using a double-blind and randomized protocol. A friction-loaded cycle ergometer fitted with a strain gauge, and an incremental encoder ensured accurate measurement of the force-velocity relationship during sprints. Mechanical data were averaged during each pedal downstroke. Compared with placebo after both acute and 3 weeks of continuous treatment, the force-velocity relationship shifted to the right with power output gains of 14 and 8% (p < 0.001), respectively. This effect was less marked for 3 weeks of continuous treatment compared with acute administration (p < 0.001), suggesting a down-regulation in adrenoceptors. Our first hypothesis thus seems rejected. Significantly higher end-of-exercise and recovery blood lactate concentrations were found under SAL compared with placebo (p < 0.001), supporting our second hypothesis. In conclusion, these data indicate that oral administration of SAL is an effective ergogenic aid for sprint exercise in non-asthmatic athletes. Moreover, an acute treatment seems to be more effective than 3 weeks of continuous treatment.

Evidence of an early physical activity reduction in chronic obstructive pulmonary disease patients.

OBJECTIVE: To compare the lifetime pattern of physical activity (PA) in chronic obstructive pulmonary disease (COPD) patients and sedentary healthy subjects (SHS) using a PA questionnaire with a lifetime period of recall (Quantification de l'Activité Physique [QUANTAP] system), and to compare the pattern of PA reduction in COPD patients with the onset of breathlessness and other relevant clinical events in this disease (diagnosis, first rehabilitation, onset of smoking). DESIGN: Cross-sectional comparative study. SETTINGS: Outpatient university hospital and inpatient pulmonary rehabilitation center. PARTICIPANTS: COPD patients (n=129; mean age ± SD, 61±10y; forced expiratory volume in 1s, 57±23%) and SHS (n=29; mean age ± SD, 61±5y; <150min·wk(-1) of moderate-vigorous PA). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lifetime PA was compared in COPD patients and SHS using the QUANTAP system. The patients with COPD and SHS underwent pulmonary function, exercise, and quadriceps endurance testing. The current PA level was assessed with a triaxial accelerometer and the Voorrips questionnaire. The age at the onset of breathlessness was also recorded. RESULTS: Accelerometry showed no significant difference between patients and SHS (in vector magnitude units, 136±56 vs 135±47; P=.95). Within the past 15 years, the cumulated PA level was not different for each 5-year period. Then, from the period of 16 to 40 years ago, it was systematically higher in patients compared with SHS (in metabolic equivalent/y(-1); median [interquartile range], 6973 [5400-12,207] vs 4248 [3545-5919]; P<.05). The COPD patients reduced their PA earlier than the SHS (45y vs 55y; P<.01), and the PA was dropped before the onset of breathlessness (45y vs 49y; P<.001). CONCLUSIONS: The observation of an early PA reduction, preceding the onset of breathlessness, suggests the implication of prior pathologic mechanisms in the PA reduction of COPD patients.

Systems medicine and integrated care to combat chronic noncommunicable diseases.

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.

Effect of an overground walking training on gait performance in healthy 65- to 80-year-olds.

The aim of this study was to examine the effect of an individualized overground walking interval training on gait performance [i.e., speed and energy cost (C(w))] in healthy elderly individuals. Twenty-two older adults were assigned to either a training group (TG; n=12, 73.4+/-3.9yr) or a non-training control group (CG; n=10, 70.9+/-9.6yr). TG participated in a 7-week individualized walking interval training at intensities progressing from 50 to 100% of ventilatory threshold (T (VE)). Aerobic fitness [maximal oxygen uptake (V O(2max)) and T (VE)], preferred walking speed (PWS), gross and net C(w) (GC(w) and NC(w), respectively) and relative effort (%V O(2max)) at PWS measured before training (PWS(1)) were assessed prior and following the intervention. All outcomes were measured on a treadmill. Significant improvements in GC(w) (-8%; P=0.007), NC(w) (-12%; P=0.003), relative effort (%V O(2max): -12%; P<0.001) and PWS (+12%; P<0.001) were observed in TG but not in CG (P>0.71). V O(2max) and T (VE) remained unchanged in both groups (P>0.57). Changes in GC(w) at PWS(1) (difference between GC(w) at PWS(1) measured pre and post intervention) were inversely correlated with changes in PWS (difference between pre and post PWS; r=-0.67; P=0.02). The decreased C(w) at PWS(1), with no concomitant improvement in aerobic fitness, represents the main contributing factor for the reduction of the relative effort at this speed. This also allows elderly people to increase their PWS post training. Therefore, the present walking training may be an effective way to improve walking performance and delay mobility impairment in older adults.

Reference equation for 6-min walk distance in healthy North African children 6-16 years old.

RATIONALE: To assess the need for a 6-min walk distance (6-MWD) reference equation for healthy North African children 6-16 years old. METHODS: Prospective cross-sectional study. Anthropometric data and 6-MWD were measured in 200 healthy Tunisian children (100 girls) from 6 to 16 years old. RESULTS: Published reference equations did not reliably predict measured 6-MWD in North African children. The 6-MWD was significantly correlated with age, height, and weight (P < 0.001, each). The combination of these parameters explained 60% of the 6-MWD variability in the equation: 6-MWD (m) = 4.63 x height (cm) - 3.53 x weight (kg) + 10.42 x age (years) + 56.32. In an additional group of 41 children prospectively studied to validate the equation, the agreement between measured and predicted 6-MWD was satisfactory. CONCLUSION: This reliable 6-MWD reference equation enriches the World Bank and provides a useful reference for the care of pediatric patients.

6-minute walk distance in healthy North Africans older than 40 years: influence of parity.

The need for a 6-min walk distance (6-MWD) reference equation for healthy North African adults older than 40 years was assessed in a prospective cross-sectional study. Anthropometric data and 6-MWD were measured in 229 healthy Tunisian adults (125 women) over 40 years old. Two subgroups of 38 women were identified according to the parity (lowor=6). The published reference equations did not reliably predict measured 6-MWD. The 6-MWD was significantly correlated with gender, age, weight and height (p<0.001). The combination of these parameters explained 77% of the 6-MWD variability in the equation: 6-MWD (m)=-160.27 x gender (0: men; 1: women) - 5.14 x age (yr) - 2.23 x weight (kg)+2.72 x height (cm)+720.50. Parity accelerated the 6-MWD decline (r=-0.39, p<0.05) and women distinguished only by parity (or=6) showed different 6-MWD (589+/-60 m vs. 555+/-57 m, p<0.05). In an additional group of 30 adults prospectively studied to validate the equation, the agreement between the measured and equation-predicted 6-MWD was satisfactory. In conclusion, this reliable 6-MWD reference equation enriches the World Bank and provides an important element of interpretation for women with high parity.

Implication of xanthine oxidase in muscle oxidative stress in COPD patients.

OBJECTIVE: The aim of this study was to determine the implication of xanthine oxidase (XO) in the exercise-induced muscle oxidative stress and muscle dysfunction of these patients. METHODS: A randomized, crossover and double-blind study was conducted in nine severe COPD patients, who performed a localized quadriceps endurance test after oral treatment with allopurinol, a XO inhibitor or placebo. Redox status was studied in arterial and venous femoral blood before and after the endurance test. RESULTS: In placebo condition, muscle exercise resulted in a significant increase in AOPP and isoprostanes, with a significant increase in the venoarterial difference (v-a) in isoprostanes after exercise as compared with before (p<0.05). In contrast, allopurinol treatment prevented the elevation in AOPP levels and v-a isoprostanes after exercise. However, no significant improvement in quadriceps muscle endurance was observed, but allopurinol treatment seemed to preserve muscle strength properties. CONCLUSION: This study demonstrates that XO is implicated in the exercise-induced muscle oxidative stress of COPD patients. Allopurinol administration seemed to improve only some muscle properties. Therefore other sources of muscle oxidative stress should be implicated in muscle dysfunction observed in these patients.

Does correction of exercise-induced desaturation by O(2) always improve exercise tolerance in COPD? A preliminary study.

BACKGROUND: This study sought to investigate whether correction of exercise-induced desaturation by oxygen supply (O(2)) systematically improves exercise tolerance and cardiorespiratory adaptations in COPD patients. METHODOLOGY: Twenty-five COPD patients [FEV(1)=52+/-2.5% pred] exhibiting exercise-induced desaturation performed cyclo-ergometer endurance exercise at 60%of their maximal workload in two randomized conditions: air vs. O(2). O(2) was adjusted to ensure 90 < or = SpO(2) < or = 95%. Endurance time (Tlim), dyspnoea, ventilation (V (E)), breathing frequency (fb), tidal volume (V(T)), cardiac output (CO), heart rate (HR) and arterio-venous difference in oxygen (AVD) were compared between conditions. RESULTS: The comparison of whole group performance between conditions revealed no differences, but individual analysis showed that O(2) increased Tlim for 14 patients [+68%; p<0.01; (positive responders)], decreased it for seven [-36%; p<0.05; (negative responders)] and induced no change for four (non-responders). For positive responders, improved performance was supported by reduced dyspnoea, V (E), fb, HR and CO and increased AVD. For negative responders, hyperoxia resulted in increased dyspnoea and fb without change in V (E) or cardiovascular parameters. CONCLUSION: For comparable correction of exercise desaturation, O(2) does not induce similar effects on exercise responses in all patients. These results were confirmed in complementary study with 11 consecutives patients at higher exercise intensity. For R+, we recorded the classic and expected O(2) effects on cardiorespiratory adaptations (i.e. reduced ventilatory demand and cardiac output). In the other group, exercise breathing frequency and dyspnoea were paradoxically increased despite desaturation correction. However, this study must be considered as pilot study, which will need to be confirmed in future studies conducted on a larger case series.