Exercise dyspnea in patients with COPD

Dyspnea, a symptom limiting exercise capacity in patients with COPD, is associated with central perception of an overall increase in central respiratory motor output directed preferentially to the rib cage muscles. On the other hand, disparity between respiratory motor output, mechanical and ventilatory response of the system is also thought to play an important role on the increased perception of exercise in these patients. Both inspiratory and expiratory muscles and operational lung volumes are important contributors to exercise dyspnea. However, the potential link between dyspnea, abnormal mechanics of breathing and impaired exercise performance via the circulation rather than a malfunctioning ventilatory pump per se should not be disregarded. Change in arterial blood gas content may affect dyspnea via direct or indirect effects. An increase in carbon dioxide arterial tension seems to be the most important stimulus overriding all other inputs from dyspnea in hypercapnic COPD patients. Hypoxia may act indirectly by increasing ventilation and indirectly independent of changes in ventilation. A greater treatment effect is often achieved after the addition of pulmonary rehabilitation with pharmacological treatment.     

Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease

Expiratory flow limitation is the pathophysiologic hallmark of chronic obstructive pulmonary disease (COPD), but dyspnea (breathlessness) is its most prominent and distressing symptom. Acute dynamic lung hyperinflation, which refers to the temporary increase in operating lung volumes above their resting value, is a key mechanistic consequence of expiratory flow limitation, and has serious mechanical and sensory repercussions. It is associated with excessive loading and functional weakness of inspiratory muscles, and with restriction of normal VT expansion during exercise. There is a strong correlation between the intensity of dyspnea at a standardized point during exercise, the end-expiratory lung volume, and the increased ratio of inspiratory effort to volume displacement (i.e., esophageal pressure relative to maximum: Vt as a % of predicted VC). This increased effort-displacement ratio in COPD crudely reflects the neuromechanical dissociation of the respiratory system that arises as a result of hyperinflation. The corollary of this is that any intervention that reduces end-expiratory lung volume will improve effort-displacement ratios and alleviate dyspnea. In flow-limited patients, bronchodilators act by improving dynamic airway function, thus enhancing lung emptying and reducing lung hyperinflation. Long-acting bronchodilators have recently been shown to reduce hyperinflation during both rest and exercise in moderate to severe COPD. This lung deflation allows greater Vt expansion for a given inspiratory effort during exercise with consequent improvement in dyspnea and exercise endurance.     

Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at rest and during exercise in COPD

STUDY OBJECTIVES: To investigate the effect of volitional pursed-lips breathing (PLB) on breathing pattern, respiratory mechanics, operational lung volumes, and dyspnea in patients with COPD. SUBJECTS: Eight COPD patients (6 male and 2 female) with a mean (+/-SD) age of 58 +/- 11 years and a mean FEV1 of 1.34 +/- 0.44 L (50 +/- 21% predicted). METHODS: Wearing a tight-fitting transparent facemask, patients breathed for 8 min each, with and without PLB at rest and during constant-work-rate bicycle exercise (60% of maximum). RESULTS: PLB promoted a slower and deeper breathing pattern both at rest and during exercise. Whereas patients had no dyspnea with or without PLB at rest, during exercise dyspnea was variably affected by PLB across patients. Changes in the individual dyspnea scores with PLB during exercise were significantly correlated with changes in the end-expiratory lung volume (EELV) values estimated from inspiratory capacity maneuvers (as a percentage of total lung capacity; r2 = 0.82, p = 0.002) and with changes in the mean inspiratory ratio of pleural pressure to the maximal static inspiratory pressure-generating capacity (PcapI) [r2 = 0.84; p = 0.001], measured using an esophageal balloon, where PcapI was determined over the range of inspiratory lung volumes and adjusted for flow. CONCLUSION: PLB can have a variable effect on dyspnea when performed volitionally during exercise by patients with COPD. The effect of PLB on dyspnea is related to the combined change that it promotes in the tidal volume and EELV and their impact on the available capacity of the respiratory muscles to meet the demands placed on them in terms of pressure generation.     

Breathing retraining and exercise conditioning in patients with chronic obstructive pulmonary disease (COPD): a physiological approach

In this review we shall consider the commonest techniques to reduce dyspnea that are being applied to patients with chronic obstructive pulmonary disease (COPD) subjected to a pulmonary rehabilitation program (PRP). Pursed lip breathing (PLB) and diaphragmatic breathing (DB) are breathing retraining strategies employed by COPD patients in order to relieve and control dyspnea. However, the effectiveness of PLB in reducing dyspnoea is controversial. Moreover, DB may be associated with asynchronous and paradoxical breathing movements, reflecting a decrease in the efficiency ofthe diaphragm. Exercise training (EXT) is a mandatory component of PRP.EXT has been shown to improve exercise performances and peripheral muscle strength. Recent studies have focused on the effect of EXT on breathlessness. However, concerns persist as to whether the decreased sensation of dyspnea for a given exercise stimulus is principally due to psychological benefits of rehabilitation or to improved physiological ability to perform exercise. The effect of EXT on breathlessness may be reinforced by inhaling oxygen. However, two studies have recently shown that breathing supplemental oxygen during training has either a marginal effect or no advantage over training. In a comprehensive PRP, strength training (ST) and arm endurance training (AET) could have a role in decreasing peripheral muscle weakness and metabolic and ventilatory requirements for AET. The role of unloading the respiratory muscles during EXT has to be     

Variability of breathlessness measurement in patients with chronic obstructive pulmonary disease

The purpose of our study was to evaluate the reproducibility of a Borg rating of dyspnea in patients with COPD. We examined nine patients with COPD who performed a SST on four separate days within a ten-day period. The patients walked on a treadmill for 6 min. At the end of each minute, patients matched a Borg rating to the intensity of their breathlessness. We measured the HR, VE, VO2, VT and f at the end of each minute. While the mean VO2, VE, HR, VT and f stabilized after one or two attempts, the Borg ratings decreased with successive tests. We conclude that the Borg scale for measuring breathlessness shows progressive decreases with repetition whereas VO2, VE, HR, VT and f stabilize after one or two practice attempts. This suggests that desensitization to dyspnea may play a role in the improvement of patients after exercise.     

Exercise training improves exertional dyspnea in patients with COPD: evidence of the role of mechanical factors

BACKGROUND: To our knowledge, no data have been reported on the effects of exercise training (EXT) on central respiratory motor output or neuromuscular coupling (NMC) of the ventilatory pump, and their potential association with exertional dyspnea. Accurate assessment of these important clinical outcomes is integral to effective management of breathlessness of patients with COPD. MATERIAL AND METHODS: Twenty consecutive patients with stable moderate-to-severe COPD were tested at 6-week intervals at baseline, after a nonintervention control period (pre-EXT), and after EXT. Patients entered an outpatient pulmonary rehabilitation program involving regular exercise on a bicycle. Incremental symptom-limited exercise testing (1-min increments of 10 W) was performed on an electronically braked cycle ergometer. Oxygen uptake (O(2)), carbon dioxide output (CO(2)), minute ventilation (E), time, and volume components of the respiratory cycle and, in six patients, esophageal pressure swings (Pessw), both as actual values and as percentage of maximal (most negative in sign) esophageal pressure during sniff maneuver (Pessn), were measured continuously over the runs. Exertional dyspnea and leg effort were evaluated by administering a Borg scale. RESULTS: Measurements at baseline and pre-EXT were similar. Significant increase in exercise capacity was found in response to EXT: (1) peak work rate (WR), O(2), CO(2), E, tidal volume (VT), and heart rate increased, while peak exertional dyspnea and leg effort did not significantly change; (2) exertional dyspnea/O(2) and exertional dyspnea/CO(2) decreased while E/O(2) and E/CO(2) remained unchanged. The slope of both exertional dyspnea and leg effort relative to E fell significantly after EXT; (3) at standardized WR, E, and CO(2), exertional dyspnea and leg effort decreased while inspiratory capacity (IC) increased. Decrease in E was accomplished primarily by decrease in respiratory rate (RR) and increase in both inspiratory time (TI) and expiratory time; VT slightly increased, while inspiratory drive (VT/TI) and duty cycle (TI/total time of the respiratory cycle) remained unchanged. The decrease in Pessw and the increase in VT were associated with lower exertional dyspnea after EXT; (4) at standardized E, VT, RR, and IC, Pessw and Pessw(%Pessn)/VT remained unchanged while exertional dyspnea and leg effort decreased with EXT. CONCLUSION: In conclusion, increases in NMC, aerobic capacity, and tolerance to dyspnogenic stimuli and possibly breathing retraining are likely to contribute to the relief of both exertional dyspnea and leg effort after EXT.     

Hyperinflation and its management in COPD

Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation. The pathological hallmarks of COPD are inflammation of the peripheral airways and destruction of lung parenchyma or emphysema. The functional consequences of these abnormalities are expiratory airflow limitation and dynamic hyperinflation, which then increase the elastic load of the respiratory system and decrease the performance of the respiratory muscles. These pathophysiologic features contribute significantly to the development of dyspnea, exercise intolerance and ventilatory failure. Several treatments may palliate flow limitation, including interventions that modify the respiratory pattern (deeper, slower) such as pursed lip breathing, exercise training, oxygen, and some drugs. Other therapies are aimed at its amelioration, such as bronchodilators, lung volume reduction surgery or breathing mixtures of helium and oxygen. Finally some interventions, such as inspiratory pressure support, alleviate the threshold load associated to flow limitation. The degree of flow limitation can be assessed by certain spirometry indexes, such as vital capacity and inspiratory capacity, or by other more complexes indexes such as residual volume/total lung capacity or functional residual capacity/total lung capacity. Two of the best methods to measure flow limitation are to superimpose a flow–volume loop of a tidal breath within a maximum flow–volume curve, or to use negative expiratory pressure technique. Likely this method is more accurate and can be used during spontaneous breathing. A definitive definition of dynamic hyperinflation is lacking in the literature, but serial measurements of inspiratory capacity during exercise will document the trend of end-expiratory lung volume and allow establishing relationships with other measurements such as dyspnea, respiratory pattern, exercise tolerance, and gas exchange.     

Relación entre disfunción de los músculos espiratorios e hiperinflación dinámica en la EPOC avanzada

Background and objectives

Dynamic hyperinflation (DH) and expiratory flow limitation (EFL) are physiologically linked and seem to be involved in the genesis of dyspnea and the quality of life (QL) impairment in chronic obstructive pulmonary disease (COPD). Advanced COPD patients often show expiratory muscles dysfunction that could be involved in DH development. Aim: Study the relationships between expiratory muscle dysfunction and DH, and their association with dyspnea and QL, in advanced COPD.

Patients and methods

In 25 patients we measured lung function, exercise capacity (incremental ergometry and walking test), EFL and end-expiratory lung volume (EELV) at rest and during exercise, respiratory muscles strength and endurance, dyspnea and QL (Saint George Respiratory Questionnaire, SGRQ).

Results

The patients (mean FEV₁=31% predicted) showed a moderate decrease of respiratory muscles strength and endurance. Nineteen patients exhibited EFL at rest and 24 at 70% of maximal workload (W_max). The EELV increased from rest to 70% W_max (9% of predicted FVC). At 70% W_max EELV correlated inversely with the EFL amount (rho=−0.42), the inspiratory and expiratory muscles endurance (rho=−0.43 and −0.42 respectively) and y VO_2max (rho=−0.52). The EELV increase from resting to 70% W_max correlated with dyspnea (rho=0.53) and the amount of EFL at 70%W_max with the activity score of SGRQ. The FEV_1, expiratory muscles endurance and LFE amount were independent predictors of EELV at 70% W_max.

Conclusions

In advanced COPD a poorer expiratory muscles endurance is related with higher DH during exercise (and lower EFL), which is correlated with higher dyspnea and worse QL.     

Is there any treatment other than drugs to alleviate dyspnea in COPD patients?

Patients with chronic obstructive pulmonary disease (COPD) are often limited in their activities by breathlessness. In these patients, exercise training may result in significant improvements in dyspnea, exercise tolerance, and health related quality of life (HRQoL). Further possibilities are to reduce ventilatory demand by decreasing the central respiratory drive or to lessen the perceived breathing effort by increasing respiratory muscle strength through specific respiratory muscle training. Upper limb training may also improve exercise capacity and symptoms in these patients through the modulation of dynamic hyperinflation. Ventilatory assistance during exercise reduces dyspnea and work of breathing and enhances exercise tolerance, although further studies should be required to define their applicability in the routine pulmonary rehabilitation programs. Lung volume resection surgery and lung transplantation in selected patients may control symptoms and improve HRQoL.     

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.     

Relationship of respiratory drives to dyspnea and exercise performance in chronic obstructive pulmonary disease

Frequently, patients with COPD with similar spirometric impairment have marked differences in dyspnea and exercise limitation. As the classic "blue bloater" with attenuated respiratory drive is described as being less dyspneic than his "pink puffer" counterpart, we wondered whether the variability in dyspnea and exercise tolerance in a group of patients with COPD with relatively similar degrees of air-flow obstruction might be partly explained by the variability in resting respiratory drives (unstimulated P0.1 and hypoxic and hypercapnic P0.1 responses). Therefore, we measured unstimulated mouth occlusion pressure (P0.1), hypoxic response (-delta P0.1/delta SaO2), hypercapnic response (delta P0.1/delta PCO2), 6-min walk distance, VO2max, steady-state exercise VE/VO2, exercise SaO2, and dyspnea using an oxygen cost diagram in 15 subjects with severe COPD (mean FEV1% 35.2 +/- 1.9 SEM). No correlations between spirometric impairment and either dyspnea or exercise performance were seen. Unstimulated P0.1 correlated inversely with spirometric impairment but did not correlate with dyspnea, VO2max or 6-min walk distance. Both hypoxic and hypercapnic responses were significantly correlated with greater exercise ventilation (VE/VO2), less exercise O2 desaturation, and a greater VO2max, but not with dyspnea or 6-min walk distance. The results of this study do not support the concept that depressed respiratory drives are associated with less dyspnea or greater exercise capability in COPD.     

Corticospinal pathway and exercise hyperpnea: lessons from a patient with Arnold Chiari malformation

The study of a patient with an Arnold Chiari malformation gave us the opportunity to test the hypothesis that the motor cortex contributes significantly to respiratory control during muscular exercise through the corticospinal pathway. The patient was a 25 years old woman who exhibited a severe impairment of the 'automatic' ventilatory control due to a type I Arnold Chiari malformation. Since she never complained of being breathlessness even on exertion, the breath-by-breath ventilatory (VE) and pulmonary gas exchange responses to a three minute bout of constant work rate exercise at 60 W, 90 W and 120 W were studied before then 16 and 23 months after posterior fossa decompression. The VE response to the three different levels of exercise was dramatically blunted so that the expected vertical relationship between PET(CO(2)) and VE during moderate exercise was replaced by an almost horizontal relationship with a slope ranging from 0.15 to 0.17 l/min/Torr. The reduced VE response was associated with a total lack of respiratory sensation during and following the exercise bouts. This abnormal ventilatory response to exercise persisted despite posterior fossa decompression. There was however no evidence of an alteration of the corticospinal pathway. Indeed, not only was there no sign of motor deficit but the patient was able both to mobilize 96% of her expected vital capacity and to voluntarily increase her ventilation to the level expected in a normal subject during exercise. This observation suggests that during exercise, motor control of respiratory muscles via a direct corticospinal pathway does not play a major role in adjusting phrenic motoneuron activity to the magnitude of the motor inputs to the exercising skeletal muscles.     

Breathlessness and mouth occlusion pressure in patients with chronic obstruction of the airways.

In order to evaluate the hypothesis that the sensation of dyspnea is due to an "inappropriate relationship between length and tension" in the respiratory musculature, studies were performed in 24 patients with chronic obstruction of the airways. They were divided into two groups solely on the basis of subjective and objective presence or absence of breathlessness and dyspnea at rest. Spirometric tests and body plethysmography were performed in each patient. The ventilatory pattern at rest was recorded and repeated measurements of mouth occlusion pressure were made. It is concluded that breathlessness in patients with airways obstruction is not associated with major differences in arterial blood gases or in VO2, VE, f or the pattern of individual breaths; there is a greater degree of airway obstruction and increased inspiratory neuromuscular drive. The minute ventilation achieved for a given inspiratory neuromuscular output, which may be considered analogous to the length-tension relationship of the respiratory musculature, is significantly decreased. These results are in accordance with the theory of mechanical inappropriateness as a cause of dyspnea.     

Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic COPD patients.

Dynamic hyperinflation contributes to exertional breathlessness and reduced exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. This study examined whether oxygen supplementation results in a dose-dependent decrease in hyperinflation associated with functional and symptomatic improvement. Ten severe COPD patients without clinically significant oxygen (O2) desaturation during exercise, and seven healthy subjects, performed five exercise tests at 75% of maximally tolerated work rate. Inspired oxygen fraction (FI,O2) was varied (0.21, 0.3, 0.5, 0.75 and 1.0) among tests in a randomized order. Ventilation (V'E) was measured, and end-inspiratory (EILV) and end-expiratory (EELV) lung volume changes were assessed from inspiratory capacity manoeuvres. In the patients, compared to room air, endurance time increased with FI,O2=0.3 (mean+/-SEM 92+/-20%) and increased further with FI,O2=0.5 (157+/-30%). At isotime, compared to room air, there were significant reductions in dyspnoea score, EELV, EILV, V'E and respiratory frequency (fR) with FI,O2=0.3. Improved endurance time negatively correlated with change in EELV (r=0.48, p=0.002) and EILV (r=0.43, p=0.005). The dyspnoea rating decrease correlated with fR decrease. In healthy subjects, smaller V'E and fR decreases were observed at FI,O2=0.5, accompanied by more modestly increased endurance. Oxygen supplementation during exercise induced dose-dependent improvement in endurance and symptom perception in nonhypoxaemic chronic obstructive pulmonary disease patients, which may be partly related to decreased hyperinflation and slower breathing pattern. This effect is maximized at an inspired oxygen fraction of 0.5.     

Exercise training for heart failure patients improves respiratory muscle endurance,exercise tolerance,breathlessness, and quality of life

PURPOSE: Increased respiratory muscle endurance and peak oxygen consumption (VO(2peak)) induced by respiratory muscle training support the relationship between respiratory muscle function and exercise capacity in patients with heart failure. This raises the question whether exercise-training results in increased respiratory muscle function contributing to an increased exercise tolerance, a decreased perception of breathlessness, and an improved quality of life. METHODS: Prospective cohort analysis was completed on 24 patients with New York Heart Association (NYHA) Class III heart failure [18 men, 6 women; aged = 64 (SD 7.9) years; percent ejection fraction (%EF) = 24.0 (SD 7.8)]. Maximal sustainable ventilatory capacity (MSVC), submaximal and peak exercise responses, perception of breathlessness, and quality of life were measured before (baseline) and after (end of study) 12 weeks of exercise training. RESULTS: As a result of exercise training, VO(2peak) (P=.01) and MSVC (P<.001) increased, with MSVC contributing to a larger proportion of the variability for VO(2peak) at study completion (r=0.57 vs 0.42). Although stroke volume did not increase beyond exercise at 25 W and did not change with exercise training, ventilation decreased during exercise (P<.05), perception of breathing difficulty (P<.05) was reduced, and quality of life was enhanced (P=.008). CONCLUSIONS: Despite no increase in cardiac output and stroke volume, respiratory muscle endurance improved with exercise training, contributing to increased exercise capacity, decreased breathlessness, and decreased perception of breathlessness. Practical implications can include less frequent rest periods and fatigue, greater confidence, maintenance of independence, and enhanced quality of life.     

Inspiratory muscle relaxation rate slows during exhaustive treadmill walking in patients with chronic heart failure

Exercise intolerance is a feature of chronic heart failure (CHF). We hypothesized that excessive loading of the respiratory muscle pump might contribute to exertional breathlessness. One marker of excessive muscle-loading is slowing of maximum relaxation rate (MRR) and, therefore, to test our hypothesis, we investigated the effect of exhaustive treadmill walking on inspiratory muscle MRR in patients with CHF. We studied eight stable patients with mild-moderate CHF walking on a treadmill until termination because of severe dyspnea. Inspiratory muscle MRR was determined from esophageal pressure (Pes) change during submaximal sniffs (Sn) before and immediately after exercise to a mean (SD) minute ventilation of 77 () L/min. For comparison, nine healthy subjects performed a similar protocol; exercise was terminated either by severe dyspnea or when minute ventilation reached 100 L/min. There were no significant differences in terms of heart rate, respiratory rate, tidal volume, or inspiratory duty cycle at cessation of exercise. The mean slowing of Sn Pes MRR in the first minute after termination of exercise in the CHF group was 22.4% and in the normal control group it was 2.8% (p < 0.01). Our data show that slowing of inspiratory muscle relaxation rate occurs in patients with CHF walking to severe breathlessness. We conclude that severe loading of the inspiratory muscles is a feature of exertional dyspnea in CHF.     

Comparison of specific expiratory, inspiratory, and combined muscle training programs in COPD

BACKGROUND: Respiratory muscle weakness may contribute to dyspnea and exercise limitation in patients with significant COPD. In an attempt to reduce the severity of breathlessness and to improve exercise tolerance, inspiratory muscle training has been applied in many COPD patients. On the other hand, there is a paucity of data related to expiratory muscle performance and training in COPD. METHODS: Thirty-two patients with significant COPD (ie, mean FEV(1), 37% of predicted) were recruited for the study. The patients were randomized into four groups: eight patients were assigned to receive specific expiratory muscle training (SEMT); eight patients received specific inspiratory muscle training (SIMT); eight patients received SEMT and SIMT (ie, the SEMT + SIMT group); and eight patients who were assigned to a control group received training with very low load. All patients trained daily, six times a week, with each session consisting of one half hour of training, for 3 months. Spirometry, respiratory muscle strength and endurance, 6-min walk test distance, the perception of dyspnea, and the Mahler baseline dyspnea index (BDI) were measured before and following training. RESULTS: Training caused a statistically significant specific increase in the expiratory muscle strength and endurance (in the SEMT and SEMT + SIMT groups) and in the inspiratory muscle strength and endurance (in the SIMT and SEMT + SIMT groups). There was significant increase in the distance walked in 6 min in the SEMT, SIMT, and SEMT + SIMT groups. However, the increase in the SIMT and SEMT + SIMT groups was significantly greater than that in the SEMT group. There was a statistically significant increase in the BDI, and a decrease in the mean Borg score during breathing against resistance in the SIMT and SEMT + SIMT groups, with no changes in the SEMT and control groups. CONCLUSIONS: The inspiratory and expiratory muscles can be specifically trained with improvement of both muscle strength and endurance. The improvement in the inspiratory muscle performance is associated with an increase in the 6-min walk test distance and the sensation of dyspnea. There is no additional benefit gained by combining SIMT with SEMT, compared to using SIMT alone.     

Exercise responses during incremental and high intensity and low intensity steady state exercise in patients with obstructive lung disease and normal control subjects

A study was undertaken to compare the cardiac and ventilatory responses to different types of exercise between 12 patients with COPD and ten normal age-matched control subjects. Both groups attained comparable heart rates and the percentage of their maximum predicted heart rate. Patients had a higher heart rate and VE with a lower O2P at every level of work load. Patients had a mean VT which approximated their FEV1 and increased their VE predominantly by increasing their respiratory frequency. During the low intensity test, despite the differences in work load, the patients had comparable heart rates and VE. No resting spirometric value accurately predicted work load, VE, or maximal VO2. We conclude that patients have a reduced work tolerance that is not adequately explained by their reduced lung function. Thus, cardiac factors, deconditioning, and the dyspneic sensation may be determinants of exercise limitation in some patients.