Arterial stiffness in patients with COPD: the role of systemic inflammation and the effects of pulmonary rehabilitation.

Clear evidence for an association between systemic inflammation and increased arterial stiffness in patients with chronic obstructive pulmonary disease (COPD) is lacking. Moreover, the effects of pulmonary rehabilitation on arterial stiffness are not well studied. We aimed to 1) confirm increased arterial stiffness in COPD; 2) evaluate its correlates including systemic inflammation; and 3) study whether or not it is influenced by pulmonary rehabilitation. Aortic pulse-wave velocity (APWV) was determined in 168 healthy volunteers, and APWV and inflammatory markers were determined in 162 COPD patients during baseline evaluation of a pulmonary rehabilitation programme. A complete post-pulmonary rehabilitation dataset was collected in 129 patients. It was found that APWV was increased in COPD patients when compared with controls, blood pressure and age predicted baseline APWV, and systemic inflammatory markers were not independently related to APWV. Although baseline APWV was predictive for the change in APWV after pulmonary rehabilitation (r= -0.77), on average APWV did not change (10.7 ± 2.7 versus 10.9 ± 2.5 m·s(-1); p=0.339). Arterial stiffness in COPD is not related to systemic inflammation and does not respond to state-of-the-art pulmonary rehabilitation. These results emphasise the complexity of cardiovascular risk and its management in COPD.

The metabolic response during resistance training and neuromuscular electrical stimulation (NMES) in patients with COPD, a pilot study.

Resistance training and transcutaneous neuromuscular electrical stimulation (NMES) are new modalities in rehabilitation of severely disabled patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to compare the metabolic response during resistance training and during NMES of the quadriceps femoris muscles in patients with COPD entering pulmonary rehabilitation. Pulmonary function, body composition, peak aerobic capacity, the Medical Research Council dyspnoea grade, the one-repetition maximum strength assessment were evaluated in 13 COPD patients. Additionally, peak oxygen uptake, peak minute ventilation and Borg symptom scores were assessed during a resistance training session and a NMES session. The median peak oxygen uptake and median peak minute ventilation during the resistance training session were significantly higher compared to the NMES session. Additionally, these higher metabolic responses were accompanied by higher symptom Borg scores for dyspnoea and leg fatigue. To conclude, the metabolic response was significantly lower during a NMES session compared to a resistance exercise training session in patients with COPD. Nevertheless, both modalities seem to result in an acceptable metabolic response accompanied by a clinically acceptable sensation of dyspnoea and leg fatigue.

The functional, metabolic, and anabolic responses to exercise training in renal transplant and hemodialysis patients.

BACKGROUND: Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients and is related to muscle weakness. Its pathogenesis may vary between these groups leading to a different response to exercise. The aim of the study was to compare intrinsic muscular parameters between HD and RTx patients and controls, and to assess the response to exercise training on exercise capacity and muscular structure and function in these groups. METHODS: Quadriceps function (isokinetic dynamometry), body composition (dual-energy x-ray absorptiometry), and vastus lateralis muscle biopsies were analyzed before and after a 12-week lasting training-program in 35 RTx patients, 16 HD patients, and 21 healthy controls. RESULTS: At baseline, myosin heavy chain (MyHC) isoform composition and enzyme activities were not different between the groups. VO2peak and muscle strength improved significantly and comparably over the training-period in RTx, HD patients and controls (p(time)<0.05). The proportion of MyHC type I isoforms decreased (p(time)<0.001) and type IIa MyHC isoforms increased (p(time)<0.05). The 3-hydroxyacyl-CoA-dehydrogenase activity increased (p(time)=0.052). Intrinsic muscular changes were not significantly different between groups. In the HD group, changes in lean body mass were significantly related to changes in muscle insulin-like growth factor (IGF)-II and IGF binding protein-3. CONCLUSIONS: Abnormalities in metabolic enzyme activities or muscle fiber redistribution do not appear to be involved in muscle dysfunction in RTx and HD patients. Exercise training has comparable beneficial effects on functional and intrinsic muscular parameters in RTx patients, HD patients, and controls. In HD patients, the anabolic response to exercise training is related to changes in the muscle IGF system.

Extra-pulmonary features in COPD patients entering rehabilitation after stratification for MRC dyspnea grade.

Experts have stated that referral for rehabilitation of patients with chronic obstructive pulmonary disease (COPD) becomes appropriate when these patients become aware of their disability (e.g. usually grade 3 to 5 on the Medical Research Council (MRC) dyspnea scale). However, patients with MRC dyspnea grade 1/2 may also suffer from extra-pulmonary features, such as abnormal body composition, exercise intolerance and reduced disease-specific health status. In the present study, we have studied whether and to what extent chronic obstructive pulmonary disease (COPD) patients with MRC dyspnea grade 1/2 have extra-pulmonary features compared to patients with grade 3, 4 or 5? Pulmonary function, body composition, 6-min walking distance, peak exercise capacity, anxiety, depression and disease-specific health status have been assessed in 333 outpatients who had been referred for pulmonary rehabilitation. On average, patients with MRC dyspnea grade 1/2 had a better exercise tolerance and disease-specific health status compared to patients with grade 4 or 5. Nevertheless, grade 1/2 patients had a higher prevalence of muscle mass depletion. In addition, these patients did still have aberrant values in one or more of the aforementioned outcomes. On average, patients with MRC dyspnea grade 1/2 may clearly suffer from extra-pulmonary features, indicating the necessity to refer these patients for rehabilitation. Therefore, MRC dyspnea scale alone does not appear to be a suitable measure to identify most patients with COPD who have to be referred for rehabilitation.

Preliminary study on the assessment of visceral adipose tissue using dual-energy x-ray absorptiometry in chronic obstructive pulmonary disease.

BACKGROUND: Visceral adipose tissue (VAT) was shown to be increased in patients with chronic obstructive pulmonary disease (COPD) compared to control subjects with comparable body mass index (BMI). Our aim was to determine the relation of VAT by dual-energy x-ray absorptiometry (DEXA) in patients with COPD by disease severity, BMI, other indices of body composition and static lung volumes. METHODS: 294 COPD patients admitted for rehabilitation were studied. Lung function, static lung volumes and body composition (i.e. BMI, waist circumference, fat-free mass, fat mass and fat distribution between android and gynoid fat mass) were assessed before entering pulmonary rehabilitation. VAT was estimated within the android region by using DEXA. Patients were stratified for gender, BMI (cut-off of 25 kg/m2) and GOLD stage. To assess the impact of VAT on lung volumes, patients were also stratified for VAT less and above 50th percentile. RESULTS: Both male and female patients with more severe airflow limitation had significantly lower VAT values, but these differences disappeared after stratification for BMI. VAT was significantly and strongly correlated with other body composition parameters (all p < 0.001). Patients with moderate to severe airflow limitation and lower VAT had increased static lung hyperinflation and lower diffusing capacity for carbon monoxide. Nevertheless, multivariate stepwise regression models including for BMI, age, gender and forced expiratory volume in 1 s (FEV1) as confounders did not confirm an independent role for VAT on static lung hyperinflation and diffusion capacity. CONCLUSION: After stratification for BMI, VAT is comparable in moderate to very severe COPD patients. Furthermore, BMI and demographics, but not VAT, were independent predictors of static lung hyperinflation and diffusing capacity in COPD.

Arm mechanical efficiency and arm exercise capacity are relatively preserved in chronic obstructive pulmonary disease.

PURPOSE: Previous studies indicate that energy expenditure related to physical activity is enhanced and that mechanical efficiency of leg exercise is reduced in patients with chronic obstructive pulmonary disease (COPD). However, it is yet unclear whether an inefficient energy expenditure is also present during other activities in COPD. This study was carried out to examine arm efficiency and peak arm exercise performance relative to leg exercise in 33 (23 male) patients with COPD ((mean +/- SEM) age: 61 +/- 2 yr; FEV : 40 +/- 2% of predicted) and 20 sex- and age-matched healthy controls. METHODS: Body composition, pulmonary function, resting energy expenditure (REE), and peak leg and arm exercise performance were determined. To calculate mechanical efficiency, subjects performed submaximal leg and arm ergometry at 50% of achieved peak loads. During exercise testing, metabolic and ventilatory parameters were measured. RESULTS: In contrast to a reduced leg mechanical efficiency in patients compared with controls (15.6 +/- 0.6% and 22.5 +/- 0.6%, respectively; < 0.001), arm mechanical efficiency was comparable in both groups (COPD: 18.3 +/- 0.9%, controls: 21.0 +/- 1.2%; NS). Arm efficiency was not related to leg efficiency, pulmonary function, work of breathing, or REE. Also, arm exercise capacity was relatively preserved in patients with COPD (ratio arm peak work rate/leg peak work rate in patients: 89% vs 53% in controls; < 0.001). CONCLUSION: Mechanical efficiency and exercise capacity of the upper and lower limbs are not homogeneously affected in COPD, with a relative preservation of the upper limbs. This may have implications for screening of exercise tolerance and prescription of training interventions in patients with COPD. Future studies need to elucidate the mechanism behind this observation.

Rehabilitation decreases exercise-induced oxidative stress in chronic obstructive pulmonary disease.

The effect of exercise at different intensities as well as the effect of intensive supervised pulmonary rehabilitation on oxidative stress were studied for chronic obstructive pulmonary disease (COPD). Eleven patients with COPD and 11 healthy age-matched control subjects performed a maximal and submaximal exercise cycle ergometry test at 60% of peak workload. Patients with COPD performed these tests before and after 8 wk of pulmonary rehabilitation. Measurements were done before, immediately after, and 4 h after both exercise tests. At rest, increased oxidative stress was observed in patients compared with control subjects, as measured by urinary malondialdehyde (MDA; p < 0.05) and hydrogen peroxide (H2O2) in breath condensate (p < 0.05). In healthy control subjects, a significant increase in urinary MDA was observed 4 h after both exercise tests (p = 0.05), whereas H2O2 significantly increased immediately after maximal exercise (p < 0.05). In patients with COPD, before rehabilitation, reactive oxygen species-induced DNA damage in peripheral blood mononuclear cells, urinary MDA, and plasma uric acid were significantly increased after both exercise tests (p < 0.05), whereas no significant increase was observed in plasma MDA. In contrast, exhaled H2O2 was only significantly increased after maximal exercise (p < 0.02). Although after rehabilitation peak workload was increased by 24%, a similar oxidative stress response was found. Remarkably, a decrease in reactive oxygen species-induced DNA damage was detected after exercise at submaximal intensity despite increased exercise duration of 73%. In summary, patients with COPD had increased pulmonary and systemic oxidative stress both at rest and induced by exercise. In addition, pulmonary rehabilitation increased exercise capacity and was associated with reduced exercise-induced oxidative stress.

Similarities in skeletal muscle strength and exercise capacity between renal transplant and hemodialysis patients.

Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients. Aim of the study was to assess to what extent exercise capacity and skeletal muscle strength of RTx patients differ from HD patients and healthy controls and to elucidate potential determinants of exercise capacity in RTx patients. Exercise capacity, muscle strength, lean body mass (LBM) and physical activity level (PAL) were measured by cycle-ergometry, isokinetic dynamometry, DEXA and Baecke Questionnaire, respectively, in 35 RTx, 16 HD and 21 controls. VO2peak and muscle strength of the RTx patients were significantly lower compared to controls (p<0.01), but not different compared to HD patients. In RTx patients, strength (p<0.001), PAL (p=0.001) and age (p=0.045) were significant predictors of VO2peak. Muscle strength was related to LBM (p=0.001) and age (p=0.001), whereas gender (p<0.001) and renal function (p=0.01) turned out to be significant predictors of LBM. No effects of corticosteroids were observed. Exercise capacity and muscle strength seem equally reduced in RTx and HD patients compared to controls. In RTx patients, muscle strength and PAL are highly related to exercise capacity. Renal function appears to be a significant predictor of LBM, and through the LBM, of muscle strength and exercise capacity.