This study was undertaken to test the hypothesis that a reduction in midthigh muscle cross-sectional area obtained by CT scan (MTCSA(CT)) is a better predictor of mortality in chronic obstructive pulmonary disease (COPD) than low body mass index (BMI). We also wished to evaluate whether anthropometric measurements could be used to estimate MTCSA(CT). One hundred forty-two patients with COPD (age = 65 +/- 9 years, mean +/- SD, 26 F, BMI = 26 +/- 6 kg/m(2), FEV(1) = 42 +/- 16% predicted) were recruited from September 1995 to April 2000 with a mean follow-up of 41 +/- 18 months. The primary end-point was all-cause mortality during the study period. A Cox proportional hazards regression model was used to predict mortality using the following independent variables: age, sex, daily use of corticosteroid, FEV(1), DL(CO), BMI, thigh circumference, MTCSA(CT), peak exercise workrate, Pa(O2), and Pa(CO2). Only MTCSA(CT) and FEV(1) were found to be significant predictors of mortality (p = 0.0008 and p = 0.01, respectively). A second analysis was also performed with FEV(1) and MTCSA(CT) dichotomized. Patients were divided into four subgroups based on FEV(1) (< or >or= 50% predicted) and MTCSA(CT) (< or >or= 70 cm(2)). Compared with patients with an FEV(1) >or= 50% predicted and a MTCSA(CT) >or= 70 cm(2), those with an FEV(1) < 50% predicted and a MTCSA(CT) >or= 70 cm(2) had a mortality odds ratio of 3.37 (95% confidence interval, 0.41-28.00), whereas patients with an FEV(1) < 50% predicted and a MTCSA(CT) < 70 cm(2) had a mortality odds ratio of 13.16 (95% confidence interval, 1.74-99.20). MTCSA(CT) could not be estimated with sufficient accuracy from anthropometric measurements. In summary, we found in this cohort of patients with COPD that (1) MTCSA(CT) was a better predictor of mortality than BMI, and (2) MTCSA had a strong impact on mortality in patients with an FEV(1) < 50% predicted. These findings suggest that the assessment of body composition may be useful in the clinical evaluation of these patients.

Peripheral muscle weakness is commonly found in patients with chronic obstructive pulmonary disease (COPD) and may play a role in reducing exercise capacity. The purposes of this study were to evaluate, in patients with COPD: (1) the relationship between muscle strength and cross-sectional area (CSA), (2) the distribution of peripheral muscle weakness, and (3) the relationship between muscle strength and the severity of lung disease. Thirty-four patients with COPD and 16 normal subjects of similar age and body mass index were evaluated. Compared with normal subjects, the strength of three muscle groups (p < 0.05) and the right thigh muscle CSA, evaluated by computed tomography (83.4 +/- 16.4 versus 109.6 +/- 15.6 cm2, p < 0.0001), were reduced in COPD. The quadriceps strength/thigh muscle CSA ratio was similar for the two groups. The reduction in quadriceps strength was proportionally greater than that of the shoulder girdle muscles (p < 0.05). Similar observations were made whether or not patients had been exposed to systemic corticosteroids in the 6-mo period preceding the study, although there was a tendency for the quadriceps strength/thigh muscle CSA ratio to be lower in patients who had received corticosteroids. In COPD, quadriceps strength and muscle CSA correlated positively with the FEV1 expressed in percentage of predicted value (r = 0.55 and r = 0. 66, respectively, p < 0.0005). In summary, the strength/muscle cross-sectional area ratio was not different between the two groups, suggesting that weakness in COPD is due to muscle atrophy. In COPD, the distribution of peripheral muscle weakness and the correlation between quadriceps strength and the degree of airflow obstruction suggests that chronic inactivity and muscle deconditioning are important factors in the loss in muscle mass and strength.

Early lactic acidosis during exercise and abnormal skeletal muscle function have been reported in chronic obstructive pulmonary disease (COPD) but a possible relationship between these two abnormalities has not been evaluated. The purpose of this study was to compare and correlate the increase in arterial lactic acid (La) during exercise and the oxidative capacity of the skeletal muscle in nine COPD patients (age = 62 +/- 5 yr, mean +/- SD, FEV1 40 +/- 9% of predicted) and in nine normal subjects of similar age (54 +/- 3 yr). Following a transcutaneous biopsy of the vastus laterialis, each subject performed a stepwise exercise test on an ergocycle up to his or her maximal capacity during which 5-breath averages of oxygen consumption (Vo2), and serial La concentration measurements were obtained. From the muscle biopsy specimen, the activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase were determined. The La/Vo2 relationship during exercise was fitted by an exponential function in the form La = a + bvo2, where be represents the shape of the relationship. The activity of the oxidative enzymes was significantly lower in COPD than in control subjects (22.8 +/- 3.3 versus 36.8 +/- 8.6 mumol/min/g muscle for CS, and 3.1 +/- 1.1 versus 5.5 +/- 1.4 mumol/min/g for HADH, p < 0.0005) and the increase in lactic acid was steeper in COPD (b = 4.3 +/- 2.0 versus 2.1 +/- 0.2 for normal subjects, p = 0.0005). A significant inverse relationship was found between CS, HADH, and b. No difference was found between the two groups for the glycolytic enzymes. We conclude that in COPD the increase in arterial La during exercise is excessive, the oxidative capacity of the skeletal muscle is reduced, and that these two results are interrelated.

We conclude that in COPD, 1) the vastus lateralis muscle is characterized by a marked decrease in Type I fiber proportion, an increase in Type IIb fiber proportion, a decrease in Type I, IIa, and IIab fiber CSA and by a relatively preserved capillarization; and 2) a 12-wk training program induces a significant increase in Type I and IIa CSA.

The purpose of this study was to evaluate the physiologic responses to endurance training in patients with moderate to severe airflow obstruction by specifically looking at changes in skeletal muscle enzymatic activities. Eleven patients (age = 65 +/- 7 yr, mean +/- SD, FEV1 = 36 +/- 11% of predicted value, range = 24 to 54%) were evaluated before and after an endurance training program. Each evaluation included a percutaneous biopsy of the vastus lateralis and a stepwise exercise test on an ergocycle up to his/her maximal capacity. VE, VO2, VcO2, and serial arterial lactic acid concentration were measured during the exercise test. The activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase was determined. The training consisted of 30-min exercise sessions on a calibrated ergocycle, 3 times a week for 12 wk. The aerobic capacity was severely reduced at baseline (VO2max = 54 +/- 12% of predicted) and increased by 14% after training (p < 0.05). For an identical exercise workload, there was a significant reduction in VE (34.5 +/- 10.0 versus 31.9 +/- 9.0 L/min, p < 0.05) and in arterial lactic acid concentration (3.4 +/- 1.3 versus 2.8 +/- 0.9 mmol/L, p < 0.01) after training. The lactate threshold also increased after training (p < 0.01) while the activity of the three glycolytic enzymes was similar at the two evaluations. In contrast, the activity of CS and HADH increased significantly after training (22.3 +/- 3.5 versus 25.8 +/- 3.8 mumol/min/g muscle for CS, p < 0.05, and 5.5 +/- 2.9 versus 7.7 +/- 2.5 mumol/min/g for HADH, p < 0.01). A significant inverse relationship was found between the percent changes in the activity of CS and HADH, and the percent changes in arterial lactic acid during exercise (p = 0.01). We conclude that endurance training can reduce exercise-induced lactic acidosis and improve skeletal muscle oxidative capacity in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Dyspnea, leg effort (Borg 0 to 10 scale), ventilation, and heart rate (VEmax/VEcap; HRmax/HRcap expressed as a percentage of capacity) were measured at maximal exercise (cycle ergometer) in 97 patients with chronic airflow limitation (CAL) (FEV, 46.6 +/- 14.23% of predicted) and compared with 320 matched control subjects. Patients with CAL achieved a maximum power output of 86 +/- 39.5 W (60 +/- 23.2% of predicted) compared with 140 +/- 37.5 W (98 +/- 14.5% of predicted) in controls (p less than 0.0001), VEmax/VEcap was 72 +/- 19.3% compared with 53 +/- 18.6% (p less than 0.0001), and HRmax/HRcap was 76 +/- 13.5% compared with 82 +/- 13% (p less than 0.001). These findings were expected. The median intensity of dyspnea was 6 (severe to very severe) and leg effort was 7 (very severe) in both groups, and these findings were unexpected. The patients with CAL were handicapped by an increase in both dyspnea and peripheral muscular effort relative to the actual power output. The rating of dyspnea exceeded leg effort in 25 (26%) of CAL versus 69 (22%) control subjects: the rating of leg effort exceeded dyspnea in 42 (43%) CAL and 117 (36%) control subjects; both were rated equally in 30 (31%) CAL and 134 (42%) control subjects, respectively (NS). VEmax/VEcap and HRmax/HRcap were not significantly different in those limited by dyspnea, leg fatigue, or a combination of both. All values are expressed +/- SD.

The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease (COPD). Forty-five patients with moderate to severe COPD were randomized to 12 wk of aerobic training alone (AERO) or combined with strength training (AERO + ST). The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle, and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises. Measurements of peripheral muscle strength, thigh muscle cross-sectional area (MCSA) by computed tomographic scanning, maximal exercise capacity, 6-min walking distance (6MWD), and quality of life with the chronic respiratory questionnaire were obtained at baseline and after training. Thirty-six patients completed the program and constituted the study group. The strength of the quadriceps femoris increased significantly in both groups (p < 0.05), but the improvement was greater in the AERO + ST group (20 +/- 12% versus 8 +/- 10% [mean +/- SD] in the AERO group, p < 0.005). The thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 +/- 13% and 15 +/- 9%, respectively (p < 0.001), but not in the AERO group (3 +/- 6% and 2 +/- 10%, respectively, p > 0.05). These changes were significantly different in the two study groups (p < 0.01). The increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups. The changes in peak exercise work rate, 6MWD, and quality of life were comparable in the two groups. In conclusion, the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass, but does not provide additional improvement in exercise capacity or quality of life.

The applicability of high-intensity training and the possibility of inducing physiologic adaptation to training are still uncertain in patients with severe chronic obstructive pulmonary disease (COPD). The purposes of this study were to evaluate the proportion of patients with moderate to severe COPD in whom high-intensity exercise training (30-min exercise session at 80% of baseline maximal power output [Wmax]) is feasible, and the response to training in these patients. We also sought to evaluate the possible influence of disease severity on the training intensity achieved and on the development of physiologic adaptation following endurance training. Forty-two patients with COPD (age = 66 +/- 7 yr, FEV1 = 38 +/- 13% predicted, [mean +/- SD]) were evaluated at baseline and after a 12-wk endurance training program. Each evaluation included a stepwise exercise test on an ergocycle up to the individual maximal capacity during which minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), and arterial lactic acid concentrations were measured. The training consisted of 25 to 30-min exercise sessions on a calibrated ergocycle three times a week, with a target training intensity at 80% of Wmax. The training intensity was adjusted with the objective of reaching the target intensity, but also to ensure that the cycling exercise could be maintained for the specified duration. The training intensity sustained for the duration of each exercise session averaged 24.5 +/- 12.6, 51.7 +/- 17.4, 63.8 +/- 22.4, and 60.4 +/- 22.7% of Wmax at Weeks 2, 4, 10, and 12, respectively. High-intensity training was achieved in zero, three, five, and five patients at Weeks 2, 4, 10, and 12, respectively. A significant increase in VO2max and Wmax occurred with training (p < 0.0002). This improvement in exercise capacity was accompanied by a 6% and 17% reduction in VE and in arterial lactic acid concentration for a given work rate, respectively (p < 0.0001), suggesting that physiologic adaptation to training occurred. The intensity of training achieved, in % Wmax, was not influenced by the initial VO2max, age, or FEV1. The effects of training were compared in patients with an FEV1 > or = 40% or < 40% predicted. Percent changes in VO2max, Wmax, and VE, were significant and of similar magnitude for both groups, whereas the decrease in arterial lactic acid for a given work rate reached statistical significance only in those patients with an FEV1 > or = 40% predicted. We conclude that although most patients were unable to achieve high-intensity training as defined in this study, significant improvement in their exercise capacity was obtained and physiologic adaptation to endurance training occurred. The training intensity expressed as a percent of the individual maximum exercise capacity, and the relative effectiveness of training, were not influenced by the severity of airflow obstruction.