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.

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.

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.

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).

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.

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.

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.

Daily functioning of dyspnea, self-esteem and physical self in patients with moderate COPD before, during and after a first inpatient rehabilitation program.

PURPOSE: Inpatient rehabilitation improves dyspnea and increases self-esteem between admission and discharge in patients with moderate chronic obstructive pulmonary disease (COPD). Some researchers nevertheless argue that the changes may be due to nursing effects and thus that scores will decrease quickly at home after discharge. This study assessed the change in dyspnea, self-esteem and physical self mean scores and stability in patients with moderate COPD during three consecutive four-week periods: at home, during an inpatient rehabilitation program, and again at home post-discharge. METHODS: Twenty-three consecutive patients [63.9 years (SD 6.6)] with moderate COPD [FEV1 = 55.8% (SD 13.2)] were included. The participants responded to the Physical Self Inventory and rated dyspnea using a visual analogue scale twice a day. Exercise tolerance was assessed with the six-minute walk test (6MWT) at admission and discharge. RESULTS: 6MWT performance improved between admission and discharge [452.3 m. (SD 74.0) vs. 503.3 m. (SD 80.4), p < 0.001]. Dyspnea ratings improved (p < 0.001), as did the self-esteem and physical self scores between the two home periods (p < 0.001). The group showed less instability (SD and range) in their assessments of physical self-worth at home post-discharge compared to pre-admission (p < 0.01). Before rehabilitation, the correlation coefficients between dyspnea, and self-esteem, the perceptions of physical condition and attractive body were all significant. After rehabilitation, the coefficients between dyspnea, and perceived physical condition, physical strength and sport competence were significant (p < 0.05). CONCLUSIONS: The results suggest that a first rehabilitation program increases the mean physical self scores in patients with moderate COPD and decreases their instability; the program also improves dyspnea. However, the impact of rehabilitation was greater on specific perceptions of physical abilities than on the global self-esteem. Randomized controlled trials are needed to confirm these changes, which were probably due to rehabilitation program.

Gender difference in coping strategies among patients enrolled in an inpatient rehabilitation program.

BACKGROUND: Previous research has not addressed gender differences in coping strategies among patients with mild to moderate chronic obstructive pulmonary disease (COPD) who are enrolled in inpatient and multidisciplinary rehabilitation programs. METHODS: The coping strategies of 182 consecutive patients (61 women aged 61.1 years; 121 men aged 62.7 years) with mild to moderate COPD were assessed on admission and then at discharge after 29 days of pulmonary rehabilitation, using the Coping Inventory for Stressful Situations. A one-way analysis of variance for repeated measures was used to test the differences in coping scores. RESULTS: During the rehabilitation program, problem-focused strategies increased (+2.54 [95% confidence interval: 1.41-3.67] with F=23.77, P<.0001), emotion-focused strategies decreased (-2.75 [95% confidence interval: -4.06, -1.45], F=15.37, P<.001), and avoidance strategies were differently (t=2.97, P<.05) influenced in women (+2.43 [95% confidence interval: .66-4.19]) compared with men (-1.30 [95% confidence interval: -2.82-.22]). The prevalence of COPD in women is increasing, and rehabilitation professionals need a greater awareness of how women cope differently than men with this disease.

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.

The effect of respiratory muscle training with CO2 breathing on cellular adaptation of mdx mouse diaphragm.

The aim of our study was to investigate the cellular mechanisms induced by hypercapnic stimulation of ventilation, during 6 weeks/30 min per day, in 10 mdx and 8 C57BL10 mice (10+/-0.2 months old). Ten mdx and eight C57BL10 mice served as control group. This respiratory training increases in vitro maximal tetanic tension of the diaphragm only in mdx mice. Western blot analysis of diaphragm showed: (1) an over-expression of alpha-dystrobrevin in mdx and C57BL10 training group compared to control group (8100+/-710 versus 6100+/-520 and 2800+/-400 versus 2200+/-250 arbitrary units); (2) a decrease in utrophin expression only in mdx training group compared to control group (2100+/-320 versus 3100+/-125 arbitrary units). Daily respiratory muscle training in mdx mice, induces a beneficial effect on diaphragm strength, with an over-expression of alpha-dystrobrevin. Further studies are needed to determine if, in absence of dystrophin, the over-expression of alpha-dystrobrevin could be interpreted as a possible pathway to improve function of dystrophic muscle.

Effects of short vs. prolonged mechanical ventilation on antioxidant systems in piglet diaphragm.

OBJECTIVE: Prolonged controlled mechanical ventilation (MV) is known to induce diaphragmatic oxidative stress that seems to be an important factor reducing force-generating capacity. To better understand the cellular mechanisms involved, this work examined the effect of short vs. prolonged MV on antioxidant defense in the diaphragm. DESIGN AND SETTING: Prospective, randomized, controlled animal study in a university laboratory. METHODS: Eleven piglets (15-20 kg) were assigned to one of two groups: a long-MV group (n=6) ventilated for 3 days or a short-MV group (n=5) ventilated for 3 h. Force frequency curves of the transdiaphragmatic pressure (Pdi) were obtained in vivo by phrenic nerve pacing. Oxidative stress was evaluated by thiobarbituric reactive substance (TBARs) content and the enzymatic antioxidant activity of both superoxide dismutase (SOD) and glutathione peroxidase (GPx) in samples of diaphragm. RESULTS: Pdi decreased in the long-MV group by 30-35% over the 3 days at all frequencies compared to the short-MV group. Diaphragm TBARs content was significantly higher and SOD activity lower in long-MV animals than in short-MV animals after 72 h. GPx activity tended to be lower in diaphragms from long-MV animals, but this difference was not significant. CONCLUSIONS: This study shows that 3 days of MV in piglets is associated with a decrease in antioxidant activity which could emphasize oxidative stress and both contribute to the diaphragm dysfunction caused by MV.

Substrate oxidation during exercise at moderate and hard intensity in middle-aged and young athletes vs sedentary men.

This study investigated the combined effects of endurance training and aging on substrate oxidation during exercise. Thirty-one healthy male subjects in 4 groups (8 middle-aged trained cyclists, 8 young trained cyclists, 7 middle-aged sedentary men, and 8 young sedentary men) performed 2 50-minute cycle ergometer exercise tests, below and above (+/-15%) their individual ventilatory threshold (VT). Substrate oxidation was evaluated by indirect calorimetry during the steady-state tests. Aging decreased carbohydrate (CHO) use (P<.05) in all subjects regardless of fitness status or exercise intensity. However, it declined 2-fold less in the trained men (P<.05) and was associated with a stronger epinephrine response (P<.05). During hard-intensity exercise, endurance training increased by 100% CHO use in the older men (P<.05). In the younger men, training increased fat oxidation but did not change CHO oxidation, resulting in a marked decrease in the ratio between CHO and fat used at high-intensity exercise (-93%; P<.05). These data suggest an age-related decline in the use of CHO as an energy source in exercising men, independent of intensity level. This decline, however, is attenuated in well-trained men for exercise intensities above the VT. In view of these findings, we hypothesize that cycling training performed at a specific exercise intensity (ie, 15% above VT) may improve CHO mobilization and use in middle-aged men.

Changes in respiratory muscle endurance during puberty.

The evaluation of respiratory muscle endurance provides clinically useful information on muscle function, especially in children with respiratory and neuromuscular diseases. However, endurance may be lower in young children than in older children because of the major physical changes of puberty. We thus compared respiratory muscle endurance in 15 healthy pre- and peripubertal children (S1-S2/P1 group) and 14 healthy children near the end of the pubertal process (S4P4 group). All performed a respiratory muscle endurance test threshold load fixed at 50% of the individual maximal inspiratory pressure; (Pi(max)), using a standardized method with a controlled breathing pattern. No significant difference was found between groups for Pi(max). The mean endurance time limit for the S1-S2/P1 group was 138 +/- 20 sec. The S4P4 group was able to breathe with the threshold valve for more than 20 min (1,200 sec) without task failure, except for one girl (385 sec). This study shows that inspiratory muscle endurance is significantly lower in children in early puberty compared to children at the end of the pubertal process. If the underlying mechanisms are not well-known, the present study revealed that if we use the same inspiratory load in prepubertal children as in adults during clinical testing, we are likely to underestimate the susceptibility to task failure of their respiratory muscles. To define a fatigue threshold for the respiratory muscles, as a function of age, thus appears clinically important in further studies, particularly for the management of children with respiratory diseases.

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.

Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy.

The aim of this study was to evaluate the effects of low intensity, home inspiratory muscle training on respiratory muscle endurance in children with Duchenne muscular dystrophy, using a double-blind protocol. The originality aspect of this study is the use of a reproducible method of endurance and of the same method for evaluation and training. We studied eight trained children (mean age 14.7+/-4.5 years) and eight control children (mean age, 12.6+/-1.8 years). For 6 weeks, children breathed twice a day for 10 min through a valve with either 30% (training group) or less than 5% (control group) of their maximum inspiratory pressure (P(imax)). The results showed (1) a 46% improvement in the time limit after training in the training group and no change in the control group and (2) a significant correlation between the total time of respiratory muscle training and the percentage of endurance improvement in the training group. We conclude that specific training improves respiratory muscle endurance in Duchenne muscular dystrophy and the effectiveness of training appears to be dependent on the quantity of training.

6-minute walk testing is more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with COPD.

STUDY OBJECTIVES: Some respiratory patients exhibit oxygen desaturation during rehabilitative walking but not during maximal cardiopulmonary exercise testing (CPET). We evaluated exercise-induced desaturation during 6-min walk testing (6MWT) in comparison with CPET in patients with COPD and determined the reproducibility of the phenomenon. PATIENTS: We tested 80 consecutive patients with COPD (FEV(1), 62.4 +/- 2% predicted) and 10 patients with supplementary COPD (FEV(1), 59.1 +/- 5% predicted) [mean +/- SEM] to determine the reproducibility. MEASUREMENTS AND RESULTS: First, patients with COPD performed cycle CPET (first CPET [CPET-1]). Three days later, they performed two 6MWTs (first 6MWT [6MWT-1] and second 6MWT [6MWT-2]). Pulse oximetric saturation (SpO(2)) was recorded every minute in both tests. Three groups emerged: desaturation at 6MWT not observed at CPET (DND) [n = 23], desaturation in both tests (n = 16), and no desaturation in either test (n = 41). Second, to evaluate reproducibility, 10 additional subjects with COPD who exhibited desaturation during two successive 6MWTs but not in CPET performed a second CPET (CPET-2) and a single-bout 6MWT (6MWT-3) in a supplementary trial. When two CPETs were performed, lack of O(2) desaturation was noted in both. O(2) desaturation was confirmed in 6MWT-2 and 6MWT-3 (7.4 +/- 1% and 7.4 +/- 1.5%, respectively). CONCLUSION: Twenty-eight percent of patients with COPD presented DND. The phenomenon was reproducible and not protocol dependent, emphasizing the clinical interest of the 6MWT.

Effects of controlled mechanical ventilation on respiratory muscle contractile properties in rabbits.

OBJECTIVE: We examined in rabbits the effects of more than 48 h of mechanical ventilation on the contractile properties and fiber type adaptations of the respiratory muscles. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: Nineteen rabbits were randomly allocated to two groups: control (n=10) or mechanically ventilated (MV; n=9) for 51+/-3 h. MEASUREMENTS AND RESULTS: Respiratory muscles contractile properties were analyzed before and after a fatigue protocol using in vivo isometric 1-s tetanic contraction characteristics in both muscles: peak tetanic force, contraction time, relaxation time, and total contraction time. Both muscle fiber type proportions, diameter, and cross-sectional areas were measured using ATPase staining. The MV rabbits showed significant weight loss in both muscles, accompanied by a reduced peak tetanic force (9.96+/-3.2 vs. 7.44+/-2.2 N for diaphragm of control and MV animals respectively), fatigue resistance index, and increased relaxation time (57.5+/-8.7 vs. 85.8+/-9.4 ms for diaphragm of control and MV animals) and contraction time. These impairments in the MV group worsened after the fatigue runs. Both muscle showed a significant atrophy of type IIa and IIb fibers but a stability in type I fibers cross-sectional area. CONCLUSIONS: Mechanical ventilation in rabbits produces alterations in contractile properties of the diaphragm and 5th external intercostal muscle, increases both muscles fatigue, and promotes atrophy of type II fibers.