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Perceptual and Physiologic Responses During Treadmill and Cycle Exercise in Patients With COPD
Original Research COPO
Perceptual and Physiologic Responses During Treadmill and Cycle Exercise in Patients With COPD* James A. Murray, DO; Laurie A. Waterman, BS; Joseph Ward, RCPT; John C. Baird, PhD; and Donald A. Mahler, MD
Background: Although the cycle ergometer is the traditional mode for exercise testing in patients with respiratory disease, this preference over the treadmill does not consider perceptual responses. Our hypotheses were as follows: (I) the regression slope between breathlessness and oxygen consumption (V02 ) is greater on the treadmill than on the cycle ergometer; and (2) the regression slope between leg discomfort and V02 is greater on the cycle ergometer than on the treadmill. Methods: Twenty patients (10 menilO women) with COPD (mean ± SD postbronchodilator FEV1 , 50 ± 15% of predicted) used a continuous method to report changes in breathlessness and in leg discomfort during cycle and treadmill exercise. Results: Patients reported an earlier onset of breathlessness and leg discomfort during cycling. Peak ratings of breathlessness were higher on the treadmill, whereas peak ratings of leg discomfort were higher on the cycle ergometer. The regression slopes for breathlessness as a function ofV02 and of minute ventilation (VE) were higher on the treadmill. The regression slopes between leg discomfort and V02 were similar for treadmill and cycle exercise. Peak V02 was significantly higher with treadmill exercise (mean a = 8%; P = 0.(02). Conclusions: Patients with COPD exhibit different perceptual and physiologic responses during treadmill walking and cycling. Although ratings of breathlessness are initially higher with cycling at equivalent levels ofV02 , the changes in breathlessness as a function ofphysiologic stimuli (V02 and VE) are greater during treadmill exercise. Leg discomfort is the predominant symptom throughout cycling. (CHEST 2009; 135:384-390) Key words: continuous ratings of hreathlessness; continuous ratings of leg discomfort; COPD; cycle ergometry; treadmill exercise
Abbreviations: \1c0 2 = carbon dioxide production; VE = minute ventilation; \102 = oxygen consumption
Cycle ergometry and walking tests are employed to evaluate an individual's responses as part of cardiopulmonary exercise testing. With cycle ergometry, the work performed can be quantified, and the 'From Pulmonary Medicine and Critical Care (Dr. Murray), Unity Health System, Rochester, NY; Pulmonary Function and Cardiopulmonary Exercise Laboratories (Ms. Waterman and Mr. Ward), Dartmouth-Hitchcock Medical Center, Lebanon, NH; Section of Pulmonary and Critical Care Medicine (Dr. Mahler), Dartmouth Medical School, Lebanon, NH; and Psychological Applications, LLC (Dr. Baird), South Pomfret, VT. Dr. Baird is Scientific Director of Psychological Applications, LLC, which owns the copyright of the continuous measurement progran.l. The other authors have no conflicts of interest to disclose. Manuscript received May 23, 2008; revision accepted August I, 2008.
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relationship between oxygen consumption (\102) and work rate can be used to identify abnormalities.l-' Other advantages of the cycle ergometer are safety and less weight bearing compared with the treadmill.s For these reasons, the cycle ergometer has been recommended for exercise testing of patients with respiratory disease. I - :j However, the expressed Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjoumal, org/mtsc/reprints.shtml). Correspondence to: Donald A. Mahler, MD, FCCP, Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 037.560001; e-mail: Donald.a./[email protected] DOl: IO.1378/chest.08-1258 Original Research
preference for the cycle ergometer over the treadmill does not consider perceptual responses during exercise. Exercise tests are "symptom-limited" because individuals stop due to intolerable or unpleasant experiences.v! In general, patients with COPD report that breathlessness limits walking but describe more intense leg effort/fatigue with cycling.5- 7 In these comparative studies,5-7 patients rated symptom intensity only at the end of the exercise test. Although such ratings indicate which symptom causes a person to stop exercise, peak values do not discriminate between healthy individuals and patients with cardiorespiratory disease and are not responsive to therapy.8-10 The recommended procedure is for the individual to rate the intensity of symptoms throughout exercise.s Both discrete (patient is queried at specific periods) and continuous (patient provides a rating whenever he/she experiences a change) methods are available." With either method, the functional relationship between perceptual and physiologic continua can be assessed. The major purpose of the present study was to compare perceptual and physiologic responses obtained during cycle ergometry and treadmill exercise. Patients used the continuous method to report whenever there was a change in breathlessness or a change in leg discomfort throughout exercise. Our hypotheses were as follows: (1) the regression slope between breathlessness and V0 2 is greater on the treadmill than on the cycle ergometer; and (2) the regression slope between leg discomfort and V0 2 is greater on the cycle ergometer than on the treadmill. Preliminary results of this investigation have been presented in abstract form.!' MATERIALS AND METHODS
sorMedics; Yorba Linda, CAl [randomized order], and practiced using the continuous method for rating breathlessness and leg discomfort. For treadmill exercise, a modified Balke protocol was used. The highest speed that the subject could maintain for 10 min at visit 1 was used for subsequent testing, and the incline was increased by 0.5% each minute. For cycle ergometry, a ramp protocol (8 to 12 W/min) was used. The subject was instructed not to take any inhaled bronchodilator medications for 12 h prior to visits 2 and 3. At these visits, the subject performed spirometry before and 20 min after inhaling two puffs of albuterol (180 f.Lg) via metered-dose inhaler, and then completed an incremental exercise test randomized by mode of exercise (cycle ergometer or treadmill). Expired gas was analyzed for minute ventilation (VE), \10 2, and carbon dioxide production (\1c0 2) for every breath using a metabolic measurement system (MedGraphics Cardiorespiratory Diagnostic Systems; MedGraphics; St. Paul, MN). The system was calibrated before each test. Oxygen saturation was recorded using pulse oximeter (Nellcor; Hayward, CAl. At each visit, the patient read written instructions and provided separate ratings of breathlessness and leg discomfort throughout exercise!": This is a scale for rating breathlessness and leg discomfort. The number 0 represents no breathlessness and no leg discomfort. The number 10 represents the strongest or greatest breathlessness or leg discomfort that you have ever experienced. You should adjust the length of the blue bar to represent your perceived level of breathlessness by pressing the left button on the mouse. You should adjust the length of the red bar to represent your perceived level of leg discomfort by pressing the right button on the mouse. Use the written descriptions to the right of the numbers to help guide your selection. You should increase the length of each bar whenever you experience a change in breathlessness or leg discomfort. An illustration of the computer display is shown in Figure 1. The methodology has been described previously.'? At the end of each test, the subject was asked, 'Why did you stop exercise: breathlessness, leg discomfort, or both?" Statistical Analysis
The primary outcomes were the relationships between ratings of breathlessness and of leg discomfort as a function of \10 2,]7-20
Subjects
Inclusion criteria were as follows: age :2: 50 years; diagnosis of COPDI2; :2: 10 pack-year history of cigarette smoking; ability to exercise on the cycle ergometer and treadmill; and clinically stable COPD. Institutional review board approved the study, and written informed consent was obtained from each participant. Experimental protocol
Each patient was tested at three visits, separated from each other by 2 to 4 days. At visit 1, the following assessments were made: medical history, vital signs, current medications, physical examination, resting ECG, and self-administered computerized version of the baseline dyspnea indexes.!? Spirometry and diffusing capacity (Collins model CPL; Collins; Louisville, CO) were performed. Predicted values were taken from Crapo et a!J4 and from Gaensler and Smith.l'' respectively. The patient then walked on the treadmill (Full Vision; Newton, KS), pedaled on an electronically braked cycle ergometer (Ergo-Metrics 800S; Senwww.chestjournal.org
FIGURE 1. Display of dual ratings of breathlessness and leg discomfort during exercise. The subject provides ratings throughout exercise by clicking the left (for a change in breathlessness) or right (for a change in leg discomfort) buttons of the computer mouse. Only the final ratings are shown in the illustration. CHEST/135/2/ FEBRUARY, 2009
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Table I-Descriptive Characteristics of Patients * Characteristics
Data
Female/male gender, No. Age, yr Height, em Weight, kg FVC,L % predicted FEV, Baseline, L % predicted Post-BD, L % predicted Post-BD FEV/FVC, % Diffusing capacity, mUmin/mm Hg % predicted Baseline dyspnea index 1
10/10 62 ± 7 167.6 ± 7.9 7.5.4 ± 14.0 3.05 ± 0.74 83 ± 13 l.l8 45 1.32 50 41 13.8 58 5.9
± 0.35
± 13
± ± ± ± ± ±
0.42 15 13 3.7 18 1.4
*Data are presented as mean ± SO unless otherwise indicated. Post-BO = postbronchodilator. t Self-administered and computerized version. 1.1
Table 2-Postbronchodilator FEV] and Physiologic Results of Cardiopulmonary Exercise Testing* Variables
Treadmill
Cycle Ergometer
Post-BD FEV" L % predicted Peak values Heart rate, beats/min \102, mUkg/min VI', Umin Respiratory rate, breaths/min Ycoz, Umin Sa0 2 , % Change from rest
1.34 ± 0.48 .50 ± 1.5
1.32 ± 0..37 .50 ± 14
130 ± 17
129 ± 19
16.3 ± 5.1 38.7 ± 12.2 .31.8 ± 7.8 l.l0±0.4! 90.4 ± 4.8 - .5.4 ± 4.6
15.1 ± 4.41 42.1 ± 13.9t 36.1 ± 7.9t 1.16 ± 0.33 93.8 ± 2.8t - 2.7 ± 2.71
*Sa0 2 = arterial oxygen saturation. tp < 0.05 comparing results on treadmill vs cycle ergometer.
VC0 2 compared with cycle ergometry. Peak values Both linear regression and power function models were fit to the data. 2 1.22 For each subject, Pearson correlation coefficients were calculated to determine the best-fitting linear and power relationships. Secondary outcomes were the onset of breathlessness and of leg discomfort as previously deflned. 17 .20 In addition, ratings of breathlessness and of leg discomfort were compared between treadmill walking and cycling at a standardized \102' Comparisons of study conditions were performed using paired t tests. Data are reported as mean ± SO. The Cochran Q test was used to test for differences in the reported symptoms that limited exercise under different conditions; p S O.OS (two-tailed test) was considered statistically significant.
RESULTS
Descriptive characteristics of the 20 patients are given in Table 1. There were no significant differences for postbronchodilator values for lung function at the two visits. Respiratory medications included the following: albuterol metered-dose inhaler (n = 20); inhaled long-acting l3-agonist (n = 13); inhaled short- or long-acting anticholinergic medications (n = 15); inhaled corticosteroids (n = 10); and oral theophylline (n
= 4).
Physiologic and perceptual results from incremental cardiopulmonary exercise tests are presented in Tables 2 and 3, respectively. Because there were no differences in the magnitude of the correlations between linear and power function models (all values were 2: 0.91 for individual patients), the results from the linear model are presented. Physiologic Responses
With treadmill exercise, patients exercised longer, had a higher peak V02 (mean Ll = 8%; Fig 2), but exhibited similar values for peak heart rate and peak 386
for VE and respiratory rate were higher with cycling than with walking. Resting values for oxygen saturation were similar, but patients had Significantly greater desaturation with treadmill exercise (mean Ll = - .5.4%) compared with cycle ergometry (mean Ll = - 2.7%) [p < 0.001]. Perceptual Responses
Individual and mean values for the slopes of the regressions between breathlessness and V02 (Fig 3) Table 3-Perceptual Responses of Cardiopulmonary Exercise Testing* Variables Symptom ratings Breathlessness No. of ratings Peak value Leg discomfort No. of ratings Peak value Beason for stopping Breathlessness Leg discomfort Both the same Onset of symptoms vo; mUkg/min Breathlessness Leg discomfort Calculated slopes Y0 2 , breathlessness YE, breathlessness Y0 2 • leg discomfort
Treadmill
Cycle Ergometer
17.4 ± 6.1 8..5 ± 2.2
11.1 ± 4..51 6.7 ± 3.1 t
IIA ± 6.2 5..5 ± 3.2
11.7 ± 3.7 6.8 ± 2.61
19
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11.9 ± 4.0 12.4 ± 4.2
9.4 ± 3.61 9.0 ± 3.11
1.90 ± 0.91 0.76 ± 0.46 1.37 ± 0.90
1.17 ± 0.68t 0.43 ± 0.33t 1.11 ± 0.63
*Data are presented as mean ± SD. Onset of symptoms = Y0 2 value corresponding to a rating of "just noticeable" or 2: 0.5 on the 0-10 scale. The slope refers to linear regression between selected variables. [Treadmill vs cycle ergometer, p < 0.0.5. Original Research
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and between breathlessness and VE were significantly higher on the treadmill than on the cycle ergometer (p < 0.001 for each comparison). Individual and mean values for the slopes of the regression between leg discomfort and V02 were similar between treadmill and cycle exercise (Fig 4) [p = 0.11]' The onset of breathlessness (Fig 3) and leg discomfort (Fig 4) occurred at a lower V02 with cycling compared with treadmill walking (p < 0.05 for each comparison). Peak ratings of breathlessness were significantly higher on the treadmill (a = 1.8 ::t 1.6 U; P < 0.001). Peak ratings of leg discomfort were significantly higher on the cycle ergometer (a = 1.3 ::t 1.1 U; P = 0.03). The main reason for stopping exercise was breathlessness on the treadmill and leg discomfort on the cycle ergometer (p < 0.05). At the onset of breathlessness on the treadmill, a V02 of 12 mUkglmin was associated with perceptual ratings of 0.4 ::t 1.3; at the same V02 level, breathlessness ratings on the cycle were 3.0::t 2.6 (p < 0.001). For this same V02 , ratings of leg discomfort on the treadmill were 0.6 ::t 0.4 compared with 3.6 ::t 2.1 on the cycle ergometer (p < 0.001). DISCUSSION
Our study demonstrates that patients with COPD exhibit different perceptual and physiologic responses during treadmill walking and cycling. The unique findings are as follows: (1) regression slopes between breathlessness as a function of V02 and of VE are significantly higher on the treadmill than on the cycle ergometer; (2) the onset of breathlessness www.chestjournal.org
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3. Top, A: Individual values for the regression slope between breathlessness and \102 during cycle and treadmill exercise. The dashed line is the line of identity. Bottom, B: Mean values for the relationship between breathlessness and V02 during cycle and treadmill exercise. The onset of breathlessness occurs at a lower V0 2 during cycling than with treadmill exercise (p < 0.001). Peak ratings for breathlessness are higher on the treadmill than on the cycle ergometer (p < 0.001). FIGURE
and leg discomfort occurs at a lower V02 with cycling compared with treadmill walking; and (3) leg discomfort is the predominant symptom throughout cycle exercise compared with treadmill walking. In 2000, Palange and colleagues" reported that nine patients with COPD had higher ratings of breathlessness at the end of a shuttle walk test and higher ratings of leg effort at the end of cycle ergometry. Man and colleagues" confirmed these results in 84 patients with COPD, although Pepin et al? found no difference in peak ratings of dyspnea between incremental cycling exercise and incremental shuttle walking. Although peak ratings can identify the reason that an individual stops exercise, the peak intensity of a symptom is neither discriminative nor responsive.s v" A more comprehensive approach is recommended to examine the continuum of perceptual responses over a range of stimuli. 2 . 10.23 CHEST /135/2/ FEBRUARY, 2009
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VO, (ml/kg/min) FIGURE 4. Top, A: Individual values for the regression slope between leg discomfort and V0 2 with the continuous method during cycle and treadmill exercise. The dashed line is the line of identity. Bottom, B: Mean values for the relationship between leg discomfort and Y0 2 during cycle and treadmill exercise. The onset ofleg discomfort occurs at a lower Y0 2 during cycling than with treadmill exercise (p < 0.001). Peak ratings for leg discomfort are higher on the cycle ergometer than on the treadmill (p = 0.048).
After familiarization and practice at the initial visit, our patients successfully used the continuous method to report changes in breathlessness and in leg discomfort throughout exercise. Although the testing protocols that we used (modified Balke and ramp of 8 to 12 W/min) are standard exercise tests.l-' it is possible that different increments of work could have altered the results. Regression analyses showed higher slopes for breathlessness as a function of \10 2 and of VE with treadmill walking compared with cycling (Table 3, Fig 3). These findings indicate that once breathlessness is "just noticeable" by the patient, it increases faster with walking than with cycling for comparable changes in metabolic load and in the level of ventilation. The regression slope between breathlessness and \10 2 has been used by various investigators I 8 - 20,24-26 388
to discriminate between different populations and to examine treatment effects. The regression slope for an individual, however, depends to a great extent on the initial tie, the onset of symptoms) and final tie, peak ratings) data points. The continuous rating method used in the present study enables the calculation of the onset of symptoms using different procedures than typically employed in sensory psychophysics. 21.22 A major finding in our study is that patients had an onset of breathlessness at a lower \10 2 with cycling compared with treadmill walking (Fig 3). Although we did not investigate possible mechanisms for this finding, differences in metabolic requirements and efficiency of the exercising muscles are evident with different modes of activity. For example, during cycling the work is primarily performed by the quadriceps muscles. Man and colleagues> showed that low frequency fatigue develops in the quadriceps muscle after cycling, but not after walking. Cycling uses less muscle mass, but produces higher levels of blood lactate compared with walking.6.27 Higher blood lactate could contribute to the earlier onset of breathlessness as observed in our patients. One or more mechanisms may explain the higher regression slopes for breathlessness as a function of \10 2 and OfVE with treadmill walking compared with cycling. Our patients exhibited greater oxygen desaturation with treadmill walking than with cycle exercise, as has been previously reported by investigators:5--7 Palange and colleagues? attributed this difference to ventilation/perfusion mismatching during walking based on differences in body posture, operating lung volumes, and/or pulmonary hemodynamics. With walking, the arm muscles are active and could be a source of neurogenic impulses to the respiratory center." In contrast, with cycling, the hands are in a fixed position resting on the handle bars, and the arms would be a less likely source of neurogenic reflexes. This stabilized position supports the shoulders and enables accessory muscles to contribute to breathing. Any differences in coupling between the muscles of locomotion and respiration iie, entrainment) and the magnitude of dynamic hyperinflation between cycling and walking remain to be determined. The regression slopes between perceptual and physiologic variables in this study represent a continuum of changes throughout exercise. Examination of Figure 3, Bottom, B, shows that breathlessness is higher with cycle exercise compared with treadmill exercise at low-to-moderate intensities of exertion. For example, at a standardized \10 2 of 12 mUkg/min, patients reported higher ratings of breathlessness with cycle exercise than with treadmill walking. These observations highOriginal Research
light the fact that different aspects of the same data may be relevant, depending on the objective of the investigation. Our results did not support the hypothesis that the regression slope between leg discomfort and \10 2 is greater on the cycle ergometer than with treadmill walking. However, Figure 4, Bottom, B demonstrates clearly that leg discomfort is the predominant symptom throughout cycling. The earlier onset of leg discomfort with cycling compared with treadmill walking may be related to higher levels of lactate being produced during cycling.6 ,27 The cycle ergometer has been used as the traditional mode for exercise testing in patients with lung disease. 2 ,4,28 Cycling is considered safer for the patient than a walking test because body weight is supported and enables the workload to be quantified. Several investigations 2.5,26,28 --3 1 have demonstrated improvements in cycling endurance time and/or breathlessness ratings after bronchodilator therapy, Although walking is a familiar activity for most patients with COPO, cycling is an uncommon physical effort. Man and colleagues" showed that cycling caused low-frequency fatigue of the quadriceps muscle and higher ratings of "leg effort" by patients compared with breathlessness. With treadmill walking, our patients with COPO achieved a Significantly higher peak \10 2 compared with cycling (Ll = 8%), and reported that breathlessness was the major symptom limiting exercise. Pepin and colleagues 7 reported an increase in walking endurance time with the shuttle test after a single dose of nebulized ipratropium bromide (500 f.1g), whereas there was no significant change in cycling endurance time. Morgan and Singh 32 have proposed that walking may be a more appropriate exercise task to demonstrate symptomatic benefit with bronchodilator therapy rather than cycling. In conclusion, the present study extends our previous work by demonstrating that patients with COPO are able to use the continuous method to report breathlessness and leg discomfort concurrently throughout exercise tests, The results enhance our knowledge by showing that patients with CO PO exhibit different perceptual and physiologic responses during treadmill walking and cycling. Measurement of the onset of symptoms, calculation of regression slopes, along with recording peak ratings provide comprehensive information about the relationship between perceptual responses and physiologic stimuli throughout exercise. We encourage additional investigations to compare the efficacy of therapies on perceptual and physiologic responses associated with walking and cycling. www.chestlournat.orq
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Original Research
Perceptual and Physiologic Responses During Treadmill and Cycle Exercise in Patients With COPD* James A. Murray, DO; Laurie A. Waterman, BS; Joseph Ward, RCPT; John C. Baird, PhD; and Donald A. Mahler, MD
Background: Although the cycle ergometer is the traditional mode for exercise testing in patients with respiratory disease, this preference over the treadmill does not consider perceptual responses. Our hypotheses were as follows: (I) the regression slope between breathlessness and oxygen consumption (V02 ) is greater on the treadmill than on the cycle ergometer; and (2) the regression slope between leg discomfort and V02 is greater on the cycle ergometer than on the treadmill. Methods: Twenty patients (10 menilO women) with COPD (mean ± SD postbronchodilator FEV1 , 50 ± 15% of predicted) used a continuous method to report changes in breathlessness and in leg discomfort during cycle and treadmill exercise. Results: Patients reported an earlier onset of breathlessness and leg discomfort during cycling. Peak ratings of breathlessness were higher on the treadmill, whereas peak ratings of leg discomfort were higher on the cycle ergometer. The regression slopes for breathlessness as a function ofV02 and of minute ventilation (VE) were higher on the treadmill. The regression slopes between leg discomfort and V02 were similar for treadmill and cycle exercise. Peak V02 was significantly higher with treadmill exercise (mean a = 8%; P = 0.(02). Conclusions: Patients with COPD exhibit different perceptual and physiologic responses during treadmill walking and cycling. Although ratings of breathlessness are initially higher with cycling at equivalent levels ofV02 , the changes in breathlessness as a function ofphysiologic stimuli (V02 and VE) are greater during treadmill exercise. Leg discomfort is the predominant symptom throughout cycling. (CHEST 2009; 135:384-390) Key words: continuous ratings of hreathlessness; continuous ratings of leg discomfort; COPD; cycle ergometry; treadmill exercise
Abbreviations: \1c0 2 = carbon dioxide production; VE = minute ventilation; \102 = oxygen consumption
Cycle ergometry and walking tests are employed to evaluate an individual's responses as part of cardiopulmonary exercise testing. With cycle ergometry, the work performed can be quantified, and the 'From Pulmonary Medicine and Critical Care (Dr. Murray), Unity Health System, Rochester, NY; Pulmonary Function and Cardiopulmonary Exercise Laboratories (Ms. Waterman and Mr. Ward), Dartmouth-Hitchcock Medical Center, Lebanon, NH; Section of Pulmonary and Critical Care Medicine (Dr. Mahler), Dartmouth Medical School, Lebanon, NH; and Psychological Applications, LLC (Dr. Baird), South Pomfret, VT. Dr. Baird is Scientific Director of Psychological Applications, LLC, which owns the copyright of the continuous measurement progran.l. The other authors have no conflicts of interest to disclose. Manuscript received May 23, 2008; revision accepted August I, 2008.
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relationship between oxygen consumption (\102) and work rate can be used to identify abnormalities.l-' Other advantages of the cycle ergometer are safety and less weight bearing compared with the treadmill.s For these reasons, the cycle ergometer has been recommended for exercise testing of patients with respiratory disease. I - :j However, the expressed Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjoumal, org/mtsc/reprints.shtml). Correspondence to: Donald A. Mahler, MD, FCCP, Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 037.560001; e-mail: Donald.a./[email protected] DOl: IO.1378/chest.08-1258 Original Research
preference for the cycle ergometer over the treadmill does not consider perceptual responses during exercise. Exercise tests are "symptom-limited" because individuals stop due to intolerable or unpleasant experiences.v! In general, patients with COPD report that breathlessness limits walking but describe more intense leg effort/fatigue with cycling.5- 7 In these comparative studies,5-7 patients rated symptom intensity only at the end of the exercise test. Although such ratings indicate which symptom causes a person to stop exercise, peak values do not discriminate between healthy individuals and patients with cardiorespiratory disease and are not responsive to therapy.8-10 The recommended procedure is for the individual to rate the intensity of symptoms throughout exercise.s Both discrete (patient is queried at specific periods) and continuous (patient provides a rating whenever he/she experiences a change) methods are available." With either method, the functional relationship between perceptual and physiologic continua can be assessed. The major purpose of the present study was to compare perceptual and physiologic responses obtained during cycle ergometry and treadmill exercise. Patients used the continuous method to report whenever there was a change in breathlessness or a change in leg discomfort throughout exercise. Our hypotheses were as follows: (1) the regression slope between breathlessness and V0 2 is greater on the treadmill than on the cycle ergometer; and (2) the regression slope between leg discomfort and V0 2 is greater on the cycle ergometer than on the treadmill. Preliminary results of this investigation have been presented in abstract form.!' MATERIALS AND METHODS
sorMedics; Yorba Linda, CAl [randomized order], and practiced using the continuous method for rating breathlessness and leg discomfort. For treadmill exercise, a modified Balke protocol was used. The highest speed that the subject could maintain for 10 min at visit 1 was used for subsequent testing, and the incline was increased by 0.5% each minute. For cycle ergometry, a ramp protocol (8 to 12 W/min) was used. The subject was instructed not to take any inhaled bronchodilator medications for 12 h prior to visits 2 and 3. At these visits, the subject performed spirometry before and 20 min after inhaling two puffs of albuterol (180 f.Lg) via metered-dose inhaler, and then completed an incremental exercise test randomized by mode of exercise (cycle ergometer or treadmill). Expired gas was analyzed for minute ventilation (VE), \10 2, and carbon dioxide production (\1c0 2) for every breath using a metabolic measurement system (MedGraphics Cardiorespiratory Diagnostic Systems; MedGraphics; St. Paul, MN). The system was calibrated before each test. Oxygen saturation was recorded using pulse oximeter (Nellcor; Hayward, CAl. At each visit, the patient read written instructions and provided separate ratings of breathlessness and leg discomfort throughout exercise!": This is a scale for rating breathlessness and leg discomfort. The number 0 represents no breathlessness and no leg discomfort. The number 10 represents the strongest or greatest breathlessness or leg discomfort that you have ever experienced. You should adjust the length of the blue bar to represent your perceived level of breathlessness by pressing the left button on the mouse. You should adjust the length of the red bar to represent your perceived level of leg discomfort by pressing the right button on the mouse. Use the written descriptions to the right of the numbers to help guide your selection. You should increase the length of each bar whenever you experience a change in breathlessness or leg discomfort. An illustration of the computer display is shown in Figure 1. The methodology has been described previously.'? At the end of each test, the subject was asked, 'Why did you stop exercise: breathlessness, leg discomfort, or both?" Statistical Analysis
The primary outcomes were the relationships between ratings of breathlessness and of leg discomfort as a function of \10 2,]7-20
Subjects
Inclusion criteria were as follows: age :2: 50 years; diagnosis of COPDI2; :2: 10 pack-year history of cigarette smoking; ability to exercise on the cycle ergometer and treadmill; and clinically stable COPD. Institutional review board approved the study, and written informed consent was obtained from each participant. Experimental protocol
Each patient was tested at three visits, separated from each other by 2 to 4 days. At visit 1, the following assessments were made: medical history, vital signs, current medications, physical examination, resting ECG, and self-administered computerized version of the baseline dyspnea indexes.!? Spirometry and diffusing capacity (Collins model CPL; Collins; Louisville, CO) were performed. Predicted values were taken from Crapo et a!J4 and from Gaensler and Smith.l'' respectively. The patient then walked on the treadmill (Full Vision; Newton, KS), pedaled on an electronically braked cycle ergometer (Ergo-Metrics 800S; Senwww.chestjournal.org
FIGURE 1. Display of dual ratings of breathlessness and leg discomfort during exercise. The subject provides ratings throughout exercise by clicking the left (for a change in breathlessness) or right (for a change in leg discomfort) buttons of the computer mouse. Only the final ratings are shown in the illustration. CHEST/135/2/ FEBRUARY, 2009
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Table I-Descriptive Characteristics of Patients * Characteristics
Data
Female/male gender, No. Age, yr Height, em Weight, kg FVC,L % predicted FEV, Baseline, L % predicted Post-BD, L % predicted Post-BD FEV/FVC, % Diffusing capacity, mUmin/mm Hg % predicted Baseline dyspnea index 1
10/10 62 ± 7 167.6 ± 7.9 7.5.4 ± 14.0 3.05 ± 0.74 83 ± 13 l.l8 45 1.32 50 41 13.8 58 5.9
± 0.35
± 13
± ± ± ± ± ±
0.42 15 13 3.7 18 1.4
*Data are presented as mean ± SO unless otherwise indicated. Post-BO = postbronchodilator. t Self-administered and computerized version. 1.1
Table 2-Postbronchodilator FEV] and Physiologic Results of Cardiopulmonary Exercise Testing* Variables
Treadmill
Cycle Ergometer
Post-BD FEV" L % predicted Peak values Heart rate, beats/min \102, mUkg/min VI', Umin Respiratory rate, breaths/min Ycoz, Umin Sa0 2 , % Change from rest
1.34 ± 0.48 .50 ± 1.5
1.32 ± 0..37 .50 ± 14
130 ± 17
129 ± 19
16.3 ± 5.1 38.7 ± 12.2 .31.8 ± 7.8 l.l0±0.4! 90.4 ± 4.8 - .5.4 ± 4.6
15.1 ± 4.41 42.1 ± 13.9t 36.1 ± 7.9t 1.16 ± 0.33 93.8 ± 2.8t - 2.7 ± 2.71
*Sa0 2 = arterial oxygen saturation. tp < 0.05 comparing results on treadmill vs cycle ergometer.
VC0 2 compared with cycle ergometry. Peak values Both linear regression and power function models were fit to the data. 2 1.22 For each subject, Pearson correlation coefficients were calculated to determine the best-fitting linear and power relationships. Secondary outcomes were the onset of breathlessness and of leg discomfort as previously deflned. 17 .20 In addition, ratings of breathlessness and of leg discomfort were compared between treadmill walking and cycling at a standardized \102' Comparisons of study conditions were performed using paired t tests. Data are reported as mean ± SO. The Cochran Q test was used to test for differences in the reported symptoms that limited exercise under different conditions; p S O.OS (two-tailed test) was considered statistically significant.
RESULTS
Descriptive characteristics of the 20 patients are given in Table 1. There were no significant differences for postbronchodilator values for lung function at the two visits. Respiratory medications included the following: albuterol metered-dose inhaler (n = 20); inhaled long-acting l3-agonist (n = 13); inhaled short- or long-acting anticholinergic medications (n = 15); inhaled corticosteroids (n = 10); and oral theophylline (n
= 4).
Physiologic and perceptual results from incremental cardiopulmonary exercise tests are presented in Tables 2 and 3, respectively. Because there were no differences in the magnitude of the correlations between linear and power function models (all values were 2: 0.91 for individual patients), the results from the linear model are presented. Physiologic Responses
With treadmill exercise, patients exercised longer, had a higher peak V02 (mean Ll = 8%; Fig 2), but exhibited similar values for peak heart rate and peak 386
for VE and respiratory rate were higher with cycling than with walking. Resting values for oxygen saturation were similar, but patients had Significantly greater desaturation with treadmill exercise (mean Ll = - .5.4%) compared with cycle ergometry (mean Ll = - 2.7%) [p < 0.001]. Perceptual Responses
Individual and mean values for the slopes of the regressions between breathlessness and V02 (Fig 3) Table 3-Perceptual Responses of Cardiopulmonary Exercise Testing* Variables Symptom ratings Breathlessness No. of ratings Peak value Leg discomfort No. of ratings Peak value Beason for stopping Breathlessness Leg discomfort Both the same Onset of symptoms vo; mUkg/min Breathlessness Leg discomfort Calculated slopes Y0 2 , breathlessness YE, breathlessness Y0 2 • leg discomfort
Treadmill
Cycle Ergometer
17.4 ± 6.1 8..5 ± 2.2
11.1 ± 4..51 6.7 ± 3.1 t
IIA ± 6.2 5..5 ± 3.2
11.7 ± 3.7 6.8 ± 2.61
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11.9 ± 4.0 12.4 ± 4.2
9.4 ± 3.61 9.0 ± 3.11
1.90 ± 0.91 0.76 ± 0.46 1.37 ± 0.90
1.17 ± 0.68t 0.43 ± 0.33t 1.11 ± 0.63
*Data are presented as mean ± SD. Onset of symptoms = Y0 2 value corresponding to a rating of "just noticeable" or 2: 0.5 on the 0-10 scale. The slope refers to linear regression between selected variables. [Treadmill vs cycle ergometer, p < 0.0.5. Original Research
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and between breathlessness and VE were significantly higher on the treadmill than on the cycle ergometer (p < 0.001 for each comparison). Individual and mean values for the slopes of the regression between leg discomfort and V02 were similar between treadmill and cycle exercise (Fig 4) [p = 0.11]' The onset of breathlessness (Fig 3) and leg discomfort (Fig 4) occurred at a lower V02 with cycling compared with treadmill walking (p < 0.05 for each comparison). Peak ratings of breathlessness were significantly higher on the treadmill (a = 1.8 ::t 1.6 U; P < 0.001). Peak ratings of leg discomfort were significantly higher on the cycle ergometer (a = 1.3 ::t 1.1 U; P = 0.03). The main reason for stopping exercise was breathlessness on the treadmill and leg discomfort on the cycle ergometer (p < 0.05). At the onset of breathlessness on the treadmill, a V02 of 12 mUkglmin was associated with perceptual ratings of 0.4 ::t 1.3; at the same V02 level, breathlessness ratings on the cycle were 3.0::t 2.6 (p < 0.001). For this same V02 , ratings of leg discomfort on the treadmill were 0.6 ::t 0.4 compared with 3.6 ::t 2.1 on the cycle ergometer (p < 0.001). DISCUSSION
Our study demonstrates that patients with COPD exhibit different perceptual and physiologic responses during treadmill walking and cycling. The unique findings are as follows: (1) regression slopes between breathlessness as a function of V02 and of VE are significantly higher on the treadmill than on the cycle ergometer; (2) the onset of breathlessness www.chestjournal.org
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3. Top, A: Individual values for the regression slope between breathlessness and \102 during cycle and treadmill exercise. The dashed line is the line of identity. Bottom, B: Mean values for the relationship between breathlessness and V02 during cycle and treadmill exercise. The onset of breathlessness occurs at a lower V0 2 during cycling than with treadmill exercise (p < 0.001). Peak ratings for breathlessness are higher on the treadmill than on the cycle ergometer (p < 0.001). FIGURE
and leg discomfort occurs at a lower V02 with cycling compared with treadmill walking; and (3) leg discomfort is the predominant symptom throughout cycle exercise compared with treadmill walking. In 2000, Palange and colleagues" reported that nine patients with COPD had higher ratings of breathlessness at the end of a shuttle walk test and higher ratings of leg effort at the end of cycle ergometry. Man and colleagues" confirmed these results in 84 patients with COPD, although Pepin et al? found no difference in peak ratings of dyspnea between incremental cycling exercise and incremental shuttle walking. Although peak ratings can identify the reason that an individual stops exercise, the peak intensity of a symptom is neither discriminative nor responsive.s v" A more comprehensive approach is recommended to examine the continuum of perceptual responses over a range of stimuli. 2 . 10.23 CHEST /135/2/ FEBRUARY, 2009
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VO, (ml/kg/min) FIGURE 4. Top, A: Individual values for the regression slope between leg discomfort and V0 2 with the continuous method during cycle and treadmill exercise. The dashed line is the line of identity. Bottom, B: Mean values for the relationship between leg discomfort and Y0 2 during cycle and treadmill exercise. The onset ofleg discomfort occurs at a lower Y0 2 during cycling than with treadmill exercise (p < 0.001). Peak ratings for leg discomfort are higher on the cycle ergometer than on the treadmill (p = 0.048).
After familiarization and practice at the initial visit, our patients successfully used the continuous method to report changes in breathlessness and in leg discomfort throughout exercise. Although the testing protocols that we used (modified Balke and ramp of 8 to 12 W/min) are standard exercise tests.l-' it is possible that different increments of work could have altered the results. Regression analyses showed higher slopes for breathlessness as a function of \10 2 and of VE with treadmill walking compared with cycling (Table 3, Fig 3). These findings indicate that once breathlessness is "just noticeable" by the patient, it increases faster with walking than with cycling for comparable changes in metabolic load and in the level of ventilation. The regression slope between breathlessness and \10 2 has been used by various investigators I 8 - 20,24-26 388
to discriminate between different populations and to examine treatment effects. The regression slope for an individual, however, depends to a great extent on the initial tie, the onset of symptoms) and final tie, peak ratings) data points. The continuous rating method used in the present study enables the calculation of the onset of symptoms using different procedures than typically employed in sensory psychophysics. 21.22 A major finding in our study is that patients had an onset of breathlessness at a lower \10 2 with cycling compared with treadmill walking (Fig 3). Although we did not investigate possible mechanisms for this finding, differences in metabolic requirements and efficiency of the exercising muscles are evident with different modes of activity. For example, during cycling the work is primarily performed by the quadriceps muscles. Man and colleagues> showed that low frequency fatigue develops in the quadriceps muscle after cycling, but not after walking. Cycling uses less muscle mass, but produces higher levels of blood lactate compared with walking.6.27 Higher blood lactate could contribute to the earlier onset of breathlessness as observed in our patients. One or more mechanisms may explain the higher regression slopes for breathlessness as a function of \10 2 and OfVE with treadmill walking compared with cycling. Our patients exhibited greater oxygen desaturation with treadmill walking than with cycle exercise, as has been previously reported by investigators:5--7 Palange and colleagues? attributed this difference to ventilation/perfusion mismatching during walking based on differences in body posture, operating lung volumes, and/or pulmonary hemodynamics. With walking, the arm muscles are active and could be a source of neurogenic impulses to the respiratory center." In contrast, with cycling, the hands are in a fixed position resting on the handle bars, and the arms would be a less likely source of neurogenic reflexes. This stabilized position supports the shoulders and enables accessory muscles to contribute to breathing. Any differences in coupling between the muscles of locomotion and respiration iie, entrainment) and the magnitude of dynamic hyperinflation between cycling and walking remain to be determined. The regression slopes between perceptual and physiologic variables in this study represent a continuum of changes throughout exercise. Examination of Figure 3, Bottom, B, shows that breathlessness is higher with cycle exercise compared with treadmill exercise at low-to-moderate intensities of exertion. For example, at a standardized \10 2 of 12 mUkg/min, patients reported higher ratings of breathlessness with cycle exercise than with treadmill walking. These observations highOriginal Research
light the fact that different aspects of the same data may be relevant, depending on the objective of the investigation. Our results did not support the hypothesis that the regression slope between leg discomfort and \10 2 is greater on the cycle ergometer than with treadmill walking. However, Figure 4, Bottom, B demonstrates clearly that leg discomfort is the predominant symptom throughout cycling. The earlier onset of leg discomfort with cycling compared with treadmill walking may be related to higher levels of lactate being produced during cycling.6 ,27 The cycle ergometer has been used as the traditional mode for exercise testing in patients with lung disease. 2 ,4,28 Cycling is considered safer for the patient than a walking test because body weight is supported and enables the workload to be quantified. Several investigations 2.5,26,28 --3 1 have demonstrated improvements in cycling endurance time and/or breathlessness ratings after bronchodilator therapy, Although walking is a familiar activity for most patients with COPO, cycling is an uncommon physical effort. Man and colleagues" showed that cycling caused low-frequency fatigue of the quadriceps muscle and higher ratings of "leg effort" by patients compared with breathlessness. With treadmill walking, our patients with COPO achieved a Significantly higher peak \10 2 compared with cycling (Ll = 8%), and reported that breathlessness was the major symptom limiting exercise. Pepin and colleagues 7 reported an increase in walking endurance time with the shuttle test after a single dose of nebulized ipratropium bromide (500 f.1g), whereas there was no significant change in cycling endurance time. Morgan and Singh 32 have proposed that walking may be a more appropriate exercise task to demonstrate symptomatic benefit with bronchodilator therapy rather than cycling. In conclusion, the present study extends our previous work by demonstrating that patients with COPO are able to use the continuous method to report breathlessness and leg discomfort concurrently throughout exercise tests, The results enhance our knowledge by showing that patients with CO PO exhibit different perceptual and physiologic responses during treadmill walking and cycling. Measurement of the onset of symptoms, calculation of regression slopes, along with recording peak ratings provide comprehensive information about the relationship between perceptual responses and physiologic stimuli throughout exercise. We encourage additional investigations to compare the efficacy of therapies on perceptual and physiologic responses associated with walking and cycling. www.chestlournat.orq
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Original Research