Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease.

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator. In a randomised double-blind crossover study, 23 patients with COPD (mean +/- SEM forced expiratory volume in one second 42 +/- 3% of the predicted value) inhaled salmeterol 50 microg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate. After salmeterol versus placebo at rest, volume-corrected maximal expiratory flow rates increased by 175 +/- 52%, inspiratory capacity (IC) increased by 11 +/- 2% pred and functional residual capacity decreased by 11 +/- 3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (VO2) and carbon dioxide output. Salmeterol increased peak exercise endurance, VO2 and ventilation by 58 +/- 19, 8 +/- 3 and 12 +/- 3%, respectively. Improvements in peak VO2 correlated best with increases in peak VT; increases in peak VT and resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increased VT. Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance.     

Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease

Patients with severe chronic obstructive pulmonary disease (COPD) develop dynamic lung hyperinflation (DH) during symptom-limited incremental and constant work exercise with cycle ergometer and treadmill. The increase in end-expiratory lung volume seems to be the best predictor of dyspnea. Quantification of DH is based on the relatively complex use of on-line measurement of inspiratory capacity (IC) from flow volume loops. We reasoned that DH could occur during daily activities such as walking, and that it could be simply measured using the spirometrically determined IC. We studied 72 men with COPD (FEV(1) = 45 +/- 13.3% predicted). IC was measured at rest and after a 6-min walk test. Exertional dyspnea was evaluated using the Borg scale and dyspnea during daily activities with the modified Medical Research Council (MRC) scale. IC decreased significantly from 28.9 +/- 6.7% TLC at rest to 24.1 +/- 6.8% TLC after exercise (p < 0.001). Exertional dyspnea correlated with DeltaIC (r = -0.49, p < 0.00001) and baseline MRC (r = 0.59, p < 0.00001). In many patients with COPD, walking leads to DH that can be easily determined with simple spirometric testing. DH helps explain exercise capacity limitation and breathlessness during simple daily activities.     

Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation

In severe chronic obstructive pulmonary disease (COPD), carbon dioxide retention during exercise is highly variable and is poorly predicted by resting pulmonary function and arterial blood gases or by tests of ventilatory control. We reasoned that in patients with compromised gas exchange capabilities, exercise hypercapnia could be explained, in part, by the restrictive consequences of dynamic lung hyperinflation. We studied 20 stable patients with COPD (FEV(1) = 34 +/- 3 percent predicted; mean +/- SEM) with varying gas exchange abnormalities (Pa(O(2)) range, 35 to 84 mm Hg; Pa(CO(2)) range, 31 to 64 mm Hg). During symptom-limited maximum cycle exercise breathing room air, Pa(CO(2)) increased 7 +/- 1 mm Hg (p < 0.05) from rest to peak exercise (range, -6 to 25 mm Hg). We measured the change in Pa(CO(2)) after hyperoxic breathing at rest as an indirect test of ventilation-perfusion abnormalities. The change in Pa(CO(2)) from rest to peak exercise correlated best with the acute change in Pa(CO(2)) during hyperoxia at rest (r(2) = 0.62, p < 0.0005) and with resting arterial oxygen saturation (r(2) = 0.30, p = 0.011). During exercise, the strongest correlates of serial changes in Pa(CO(2)) from rest included concurrent changes in end-expiratory lung volume expressed as a percentage of total lung capacity (partial correlation coefficient [r] = 0.562, p < 0.0005) and oxygen saturation (partial r = 0.816, p < 0.0005). In severe COPD, the propensity to develop carbon dioxide retention during exercise reflects marked ventilatory constraints as a result of lung hyperinflation as well as reduced gas exchange capabilities.     

Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest.

Expiratory flow limitation (FL) at rest is frequently present in chronic obstructive pulmonary disease (COPD) patients. It promotes dynamic hyperinflation with a consequent decrease in inspiratory capacity (IC). Since in COPD resting IC is strongly correlated with exercise tolerance, this study hypothesized that this is due to limitation of the maximal tidal volume (VT,max) during exercise by the reduced IC. The present study investigated the role of tidal FL at rest on: 1) the relationship of resting IC to VT,max; and 2) on gas exchange during peak exercise in COPD patients. Fifty-two stable COPD patients were studied at rest, using the negative expiratory pressure technique to assess the presence of FL, and during incremental symptom-limited cycling exercise to evaluate exercise performance. At rest, FL was present in 29 patients. In the 52 patients, a close relationship of VT,max to IC was found using non-normalized values (r=0.77; p < 0.0001), and stepwise regression analysis selected IC as the only significant predictor of VT,max. Subgroup analysis showed that this was also the case for patients both with and without FL (r=0.70 and 0.76, respectively). In addition, in FL patients there was an increase (p < 0.002) in arterial carbon dioxide partial pressure at peak exercise, mainly due to a relatively low VT,max and consequent increase in the physiological dead space (VD)/VT ratio. The arterial oxygen partial pressure also decreased at peak exercise in the FL patients (p < 0.05). In conclusion, in chronic obstructive pulmonary disease patients the maximal tidal volume, and hence maximal oxygen consumption, are closely related to the reduced inspiratory capacity. The flow limited patients also exhibit a significant increase in arterial carbon dioxide partial pressure and a decrease in arterial oxygen partial pressure during peak exercise.     

Prediction of maximum exercise tolerance in patients with COPD

Exercise tolerance in patients with COPD is difficult to predict from measurements of lung function. We examined multiple physiologic and psychosocial variables in an attempt to predict exercise performance in a group of patients with COPD enrolled in a clinical trial of pulmonary rehabilitation. A total of 119 patients (FEV1 = 1.41 +/- 0.64 L) were divided randomly into either a study group (group A, n = 58) or validation group (group B, n = 61). Stepwise multiple regression in group A revealed that peak oxygen uptake (peak VO2) was predicted best by the following equation: Peak VO2 (L/min) = (0.0327 x DCO) + (0.0040 x MVV)-(0.0156 x peak-exercise VD/VT) + (0.0259 x resting VE) + 0.848; r = 0.90; SE = 0.233 L/min. This equation was then cross-validated in group B. It demonstrated excellent validity: measured peak VO2 (L/min) = (1.13 x predicted peak VO2)-0.0891; r = 0.90; SE = 0.239 L/min. We conclude that exercise tolerance was predicted reasonably well from measurements of lung function and gas exchange in this group of patients with COPD. However, the variability of the prediction would limit its usefulness in individual patients.     

Accuracy of pulmonary function tests in predicted exercise capacity in COPD patients

PURPOSE: The purpose of this study was to examine exercise tolerance in patients with COPD from measurements of resting pulmonary function parameters. METHODS: A total of 57 COPD patients were administered the pulmonary function test (PFT) and cardiopulmonary exercise test. The results were analyzed and essentially linear relationships emerged when each subject's VO2 peak was plotted against his individual PFT parameters. Those significant contributors were then introduced in a stepwise multiple regression analysis to determine the best predictor of the VO2 peak. RESULTS: Stepwise multiple regressions in variables revealed that peak oxygen consumption (VO2 peak) was predicted best by the following equation: VO2 peak=(maximum voluntary ventilation x 0.024)+(forced mid-expiratory flow x 0.47)+(body surface area x 0.988)-0.913 (r=0.90; r2=0.81 SE=0.29 L/min). CONCLUSION: We conclude that exercise capacity was predicted from measurements of resting pulmonary function parameters with excellent accuracy in the COPD patient.     

Diffusing Capacity for Carbon Monoxide is Linked to Ventilatory Demand in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (VD/VT) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P_CO2 allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43–80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological VD/VT ratios (r = ?0.55, p = 0.0015 and r = ?0.40, p = 0.032; respectively). The peak physiological VD/VT ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted V˙O2) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological VD/VT at peak exercise, respectively. The non-invasive measurement of transcutaneous P_CO2 both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO₂ measurement.     

Exhaled nitric oxide and exercise in stable COPD patients

STUDY OBJECTIVE: To evaluate exhaled nitric oxide (eNO) during exercise in patients with stable COPD. SETTING: Outpatient evaluation in a rehabilitation center. PATIENTS: Eleven consecutive male patients with stable COPD (age, 65 +/- 6 years; FEV(1), 56 +/- 10% predicted). Eight healthy (six men; age, 51 +/- 16 years) nonsmoking, nonatopic volunteers served as control subjects. METHODS: In each subject, a symptom-limited cycle ergometry test was performed by monitoring eNO with the tidal-breath method to assess eNO concentration (FENO) and output (VNO) at rest, peak exercise, and recovery time. RESULTS: Resting FENO (9.8 +/- 5.1 and 14.1 +/- 6.3 parts per billion, respectively) and VNO (4.2 +/- 2.0 and 5.9 +/- 3.4 nmol/min, respectively) were lower, although not significantly, in COPD patients than in control subjects. In both groups, FENO significantly decreased whereas VNO significantly increased during exercise. Both variables returned to baseline during the recovery time. Peak exercise VNO, but not FENO, was significantly lower in COPD patients than in control subjects (7.9 +/- 5.4 and 12.7 +/- 6.0 nmol/min, respectively, p < 0.05). The rise in VNO was weakly correlated to oxygen consumption VO(2)) both in control subjects (r = 0.31, p = 0. 002) and in COPD patients (r = 0.22, p = 0.03). FENO showed an inverse correlation to VO(2) in both groups (r = -0.53, p = 0.000; r = -0.31, p = 0.003 in control subjects and COPD patients, respectively). CONCLUSIONS: In patients with mild and moderate COPD, eNO during exercise parallels that observed in normal control subjects. VNO, but not FENO, is significantly reduced at peak exercise in COPD patients as compared with control subjects. The long-term effects of exercise training on eNO has to be evaluated by further studies.     

Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease.

We wished to determine which resting spirometric parameters best reflect improvements in exercise tolerance and exertional dyspnea in response to acute high-dose anticholinergic therapy in advanced COPD. We studied 29 patients with stable COPD (FEV(1) = 40 +/- 2% predicted [%pred]; mean +/- SEM) and moderate to severe chronic dyspnea. In a double-blind placebo-controlled cross-over study, patients performed spirometry and symptom-limited constant-load cycle exercise before and 1 h after receiving 500 micrograms of nebulized ipratropium bromide (IB) or saline placebo. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo. In response to IB (n = 58): FEV(1), FVC, and inspiratory capacity (IC) increased by 7 +/- 1%pred, 10 +/- 1%pred, and 14 +/- 2%pred, respectively (p < 0.001), with no change in the FEV(1)/FVC ratio. After receiving IB, exercise endurance time (Tlim) increased by 32 +/- 9% (p < 0.001) and slopes of Borg dyspnea ratings over time decreased by 11 +/- 6% (p < 0.05). Percent change (%Delta) in Tlim correlated best with DeltaIC%pred (p = 0.020) and change in inspiratory reserve volume (DeltaTLC%pred) (p = 0.014), but not with DeltaFVC%pred, DeltaPEFR%pred, or DeltaFEV(1)%pred. Change in Borg dyspnea ratings at isotime near end exercise also correlated with DeltaIC%pred (p = 0.04), but not with any other resting parameter. Changes in spirometric measurements are generally poor predictors of clinical improvement in response to bronchodilators in COPD. Of the available parameters, increased IC, which is an index of reduced resting lung hyperinflation, best reflected the improvements in exercise endurance and dyspnea after IB. IC should be used in conjunction with FEV(1) when evaluating therapeutic responses in COPD.     

Effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in COPD

There is increasing evidence that dynamic hyperinflation (DH) have negative effects on exercise performance and quality of life in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in patients with COPD. 72 clinically stable patients with moderate to severe COPD and 30 healthy age-matched control subjects were included in this study. Pulmonary function tests including lung volumes and maximal respiratory muscle forces, arterial blood gas analyses, evaluation of exertional dyspnea with the Borg scale, and The Saint George Respiratory Questionnaire (SGRQ, Turkish version) were performed at rest and after a 6-min walk test. We measured the change in inspiratory capacity (AlphaIC) after exercise to reflect DH. 80% of patients with COPD significantly decreased IC after exercise (DH). AlphaIC were -0.27 +/- 0.26 L in COPD and 0.8 +/- 0.17 L in controls (p= 0.001). A stepwise multiple regression analysis showed that to be a patient with COPD, Basal Dyspnea Index (BDI) and AlphaIC were the best predictors of 6 MWD (r(2)= 0.53, p< 0.001). FEV1 added an additinal 9% to the variance in 6 MWD. Exertional dyspnea (AlphaBorg) correlated with AlphaIC (r= -0.44, p= 0.0001) and BDI (r= 0.34, p= 0.02). AlphaIC significantly correlated with symptom (r= -0.36, p= 0.008), activity (r= -0.31, p= 0.03) and total scores (r= -0.30, p= 0.04) of SGRQ. Dynamic hyperinflation can often occur during exersice in patients with COPD. Extent of dynamic hyperinflation could able to explain exercise capacity limitation, exercise dyspnea, and poor quality of life in patients with COPD.     

Tiotropium and simplified detection of dynamic hyperinflation

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.     

Prediction of PaO2 during treadmill walking in patients with COPD

We studied the possibility of predicting PaO2 during exercise of a given oxygen uptake (VO2) from resting pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD). The three-minute incremental treadmill exercise was performed with serial measurements of PaO2 via intra-arterial catheter in 46 patients (mean FEV1 = 1.09 +/- 0.49L, mean FEV1/FVC = 44 +/- 15 percent). In most of the patients, the changes of PaO2 were quite linear in relation to the oxygen uptake, so a slope (PaO2/VO2) could be obtained from the regression equation in each patient. The mean value of the slope (SL) was -23.0 +/- 16.6 mm Hg/L VO2/min. Correlation between SL and all parameters of resting PFTs were computed. Because of the high correlation coefficient between SL and %DCO (SL = -59.3 + 0.501 X %DCO, r = 0.851, p less than 0.001), it was possible to predict PaO2 at a given VO2 using the following equation: PaO2 predicted = PaO2 rest + SL X (VO2 -0.25), where SL was derived from measured %DCO and resting VO2 was assumed 0.25 L/min. There was a high correlation between the predicted PaO2 at VO2 of 1.0 L/min and the estimated PaO2 obtained from individual PaO2 regression with an r value = 0.898 and SEE = +/- 5.8 mm Hg. A prospective study in 12 patients with COPD was then carried out. There was a high correlation (r = 0.857) between the predicted PaO2 obtained from the present equation and the estimated PaO2 at VO2 = 1.0 L/min. It was concluded that PaO2 during treadmill walking with a given oxygen uptake is predictable from a resting PaO2 and a diffusing capacity. This predicted value may be useful in the management of patients with COPD.     

Limitation of exercise tolerance in chronic heart failure: distinct effects of left bundle-branch block and coronary artery disease

OBJECTIVES: The aim of this study was to identify resting measurements of left ventricular (LV) function that predict exercise capacity in dilated cardiomyopathy (DCM); in particular, the effects of left bundle branch block (LBBB), coronary artery disease (CAD), and total isovolumic time (t-IVT). BACKGROUND: The t-IVT is a major determinant of cardiac output during dobutamine stress in DCM, and is itself determined by the presence or absence of LBBB and CAD. METHODS: A total of 111 patients with DCM, 51 with CAD (29 LBBB), and 60 without CAD (30 LBBB) were studied with echocardiography and cardiopulmonary exercise testing. The t-IVT (in s/min) was measured by Doppler echocardiography, and maximal oxygen consumption (peak Vo(2)) and percentage of the normal predicted peak Vo(2) (%predicted peak Vo(2)) were obtained from exercise testing. RESULTS: Left bundle branch block reduced peak Vo(2) (by 10.5 ml.kg(-1)min(-1)) and %predicted peak Vo(2) (by 33%, both p < 0.001) compared with patients without LBBB. Coronary artery disease reduced peak Vo(2) (by 5.5 ml.kg(-1)min(-1), p < 0.001) and %predicted peak Vo(2) (by 14%, p < 0.01) compared with those without CAD (p < 0.01). The t-IVT, CAD, LBBB, and QRS duration were univariate predictors of exercise tolerance, but only t-IVT and CAD were independent predictors. The t-IVT at rest correlated with peak Vo(2) (r = -0.68) and %predicted peak Vo(2) (r = -0.74, both p < 0.001). The combination of t-IVT and CAD explained 57% (r = 0.75, p < 0.001) of the total variance in exercise capacity. CONCLUSIONS: Resting t-IVT and less prominently, CAD, are major determinants of exercise tolerance in DCM. Left bundle branch block significantly determines resting t-IVT and thus peak Vo(2). Prediction of maximum exercise capacity in DCM is therefore possible from time-domain analysis of LV function at rest.     

Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic obstructive pulmonary disease

We studied interrelationships between exercise endurance, ventilatory demand, operational lung volumes, and dyspnea during acute hyperoxia in ventilatory-limited patients with advanced chronic obstructive pulmonary disease (COPD). Eleven patients with COPD (FEV(1.0) = 31 +/- 3% predicted, mean +/- SEM) and chronic respiratory failure (Pa(O(2)) 52 +/- 2 mm Hg, Pa(CO(2 ))48 +/- 2 mm Hg) breathed room air (RA) or 60% O(2) during two cycle exercise tests at 50% of their maximal exercise capacity, in randomized order. Endurance time (T(lim)), dyspnea intensity (Borg Scale), ventilation (V E), breathing pattern, dynamic inspiratory capacity (IC(dyn)), and gas exchange were compared. Pa(O(2)) at end-exercise was 46 +/- 3 and 245 +/- 10 mm Hg during RA and O(2), respectively. During O(2), T(lim) increased 4.7 +/- 1.4 min (p < 0.001); slopes of Borg, V E, V CO(2), and lactate over time fell (p < 0.05); slopes of Borg-V E, V E-V CO(2), V E-lactate were unchanged. At a standardized time near end-exercise, O(2) reduced dyspnea 2.0 +/- 0.5 Borg units, V CO(2) 0.06 +/- 0.03 L/min, V E 2.8 +/- 1.0 L/min, and breathing frequency 4.4 +/- 1.1 breaths/min (p < 0.05 each). IC(dyn) and inspiratory reserve volume (IRV) increased throughout exercise with O(2) (p < 0.05). Increased IC(dyn) was explained by the combination of increased resting IRV and decreased exercise breathing frequency (r(2) = 0.83, p < 0.0005). In conclusion, improved exercise endurance during hyperoxia was explained, in part, by a combination of reduced ventilatory demand, improved operational lung volumes, and dyspnea alleviation.     

Utility of cardiopulmonary exercise in the assessment of clinical determinants of functional capacity in hypertrophic cardiomyopathy

The utility of metabolic gas exchange measurements in evaluating the severity and determinants of exercise limitation was studied during upright symptom-limited cardiopulmonary exercise in 135 consecutive patients with hypertrophic cardiomyopathy (HC) and 50 healthy age- and gender-matched volunteers. Peak oxygen consumption (VO(2)) was less than predicted (age, gender, and size) in 99% patients. Peak VO(2) was significantly associated with New York Heart Association functional class; however, there was considerable overlap of peak VO(2) between classes I and III (70 +/- 15%, 56 +/- 15%, 35 +/- 11%, respectively). Patients with abnormal blood pressure responses and patients with chronotropic incompetence during exercise had lower percent-predicted peak VO(2) than patients with normal blood pressure and heart rate responses during exercise (p = 0.0001 and p <0.001, respectively). Percent-predicted peak VO(2) was similar in patients with and without resting left ventricular outflow obstruction. Of those patients with resting gradients, however, there was a strong inverse correlation between the magnitude of the gradient and peak VO(2) (r = 0.5; p <0.001). In conclusion, peak VO(2) is significantly related to New York Heart Association functional class in this group of patients with HC, but peak VO(2) is a superior measure of cardiovascular performance in individual patients. Our peak VO(2) data indicate that mechanical obstruction has an adverse pathophysiologic effect on functional capacity and provide the rationale to support treatments aimed at gradient reduction. Low peak VO(2) characteristics including those with normal or near-normal left ventricular wall thickness suggests that measurement of peak VO(2) may aid in the differential diagnosis between HC and athlete's heart.     

Simplified detection of dynamic hyperinflation

STUDY OBJECTIVE: To detect dynamic hyperinflation by comparing reduction in inspiratory capacity (IC) during both paced hyperventilation and cycle ergometry in patients with moderate-to-severe COPD, studied before and after acute bronchodilation. METHODS: IC and FEV(1) were measured before and after metronome-paced hyperventilation at twice the resting respiratory rate for 20 s in 16 patients with COPD before and after 54 microg aerosolized ipratropium bromide (IB). We also studied the same 16 patients before and after administration of 54 microg aerosolized IB during symptom-limited incremental cycle ergometry when the final respiratory rate was also twice the resting rate. RESULTS: Resting IC was 2.23 +/- 0.53 L (mean +/- SD), and the mean decrease in IC from baseline was 0.36 +/- 0.25 L after exercise (p < 0.001), and not significantly different (p = 0.64) from mean decrease in IC of 0.40 +/- 0.29 L following hyperventilation. Results following hyperventilation and exercise were similar after bronchodilator. The mean difference for decrease of IC between hyperventilation and exercise was 0.138 L (95% confidence interval, - 0.347 to 0.622; r = 0.66, p = 0.006). The decrease in FEV(1) was 0.01 +/- 0.13 L after exercise and 0.06 +/- 0.18 L after hyperventilation. Separately, baseline and peak end-expiratory and end-inspiratory lung volumes were similar with hyperventilation vs exercise both before and after bronchodilator. CONCLUSION: Both metronome-paced hyperventilation and incremental cycle ergometry, when resting respiratory rate was doubled, provoked similar significant decrease in IC, even after administration of 54 microg aerosolized IB. The noninvasive simplicity of hyperventilation for 20 s provides a clinically useful screening surrogate to monitor changes in IC following exercise.     

Factors associated with improvement in breathing capacity during exercise in patients with chronic obstructive pulmonary disease

OBJECTIVES: The aim of this study was to explore the relationship between resting pulmonary function indices and the ratio of minute ventilation at peak exercise to the maximal voluntary ventilation (VEmax/MVV) and to determine whether an improvement in breathing capacity during exercise (i.e. VEmax/MVV > 1) is associated with greater exercise capacity in patients with COPD. METHODOLOGY: The results of pulmonary function tests and incremental, symptom-limited cardiopulmonary exercise testing in 84 patients with predominantly moderate to severe COPD were reviewed. Multiple linear regression analysis was applied to determine the relationship of VEmax/MVV with selected independent variables at rest. Multiple logistic regression was used to determine significant predictors of VEmax/MVV 1. RESULTS: FEV1/FVC and inspiratory capacity (IC) were the only variables among resting pulmonary function indices that were significant independent determinants of VEmax/MVV and the stepwise analysis generated the following equation: VEmax/MVV = (-1.05E-02 x FEV1/FVC) + (0.15 x IC) + 1.28; r= 0.701, P < 0.001. Using multiple logistic regression with VEmax/MVV 1 as a dependent categorical variable, FEV1/FVC was the only significant predictor among resting pulmonary indices of a VEmax/MVV ratio of > 1 (Odds ratio 0.93, 95%CI 0.89, 0.97). There was a significant association between VEmax/MVV and peak oxygen uptake (VO2max) after adjusting for FEV1 (r = 0.66, P < 0.001). If the categorical variable of VEmax/MVV ( 1) was used instead of a continuous variable, a significant association with VO2max remained after adjusting for FEV1 (r = 0.60, P < 0.001). CONCLUSIONS: Among resting pulmonary function indices, the FEV1/FVC ratio is the best determinant of an improvement in breathing capacity during exercise in COPD patients. After adjusting for FEV1, an improvement in breathing capacity during exercise is associated with significantly higher exercise capacity.     

Diffusing capacity for carbon monoxide is linked to ventilatory demand in patients with chronic obstructive pulmonary disease

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (V(D)/V(T)) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P(CO2) allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43-80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological V(D)/V(T) ratios (r = -0.55, p = 0.0015 and r = -0.40, p = 0.032; respectively). The peak physiological V(D)/V(T) ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted VO(2)) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological V(D)/V(T) at peak exercise, respectively. The non-invasive measurement of transcutaneous P(CO2) both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO(2) measurement.     

The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD.

This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema.

Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV₁% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV₁% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.