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How should we measure function in patients with chronic heart and lung disease?
J
Chron Dis Vol. 38, No. 6, pp. 517-524,
0021-9681185 %3.00+0.00 Copyright :c> 1985 PergamonPressLtd
1985
Printed in Great Britain. All rights reserved
HOW SHOULD IN PATIENTS AND
WE MEASURE FUNCTION WITH CHRONIC HEART LUNG DISEASE?
GORDON H. GUYATT,‘.~ PENELOPE J. THOMPSON, LESLIE B. BERMAN,’ MICHAEL J. SULLIVAN,’ MARIE TOWNSEND, NORMAN L. JONES~ and STEWART 0. PUGSLEY Departments
of ‘Clinical
Epidemiology Hamilton,
& Biostatistics Ontario, Canada
and ‘Medicine L8N 325
McMaster
University,
(Receioed in revised form 5 October 1984)
Abstract-To elucidatethe characteristicsof measuresof function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman’s rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579). and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand. correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease.
INTRODUCTION MEASURES of function are routinely used in patients with chronic heart failure and chronic airflow limitation to assess prognosis and to quantitate the effects of treatment. These measures include physiological tests (such as spirometry [l-4], cardiac index and pulmonary capillary wedge pressure [S-7], and cycle or treadmill exercise tests [g-11]), performance in day-to-day activities (walking tests [12-141) and patients’ own assessment of their capabilities and symptoms (questionnaires [15, 161). Clinicians and investigators must decide which of these measures to use in dealing with particular problems. An idea1 measure would be highly reproducible, reflect physiological function, but also relate closely to patients’ ability to cope with the physical demands of daily living. To determine the reproducibility of and correlation between commonly used measures of function, we administered four functional status questionnaires, a 6-min walk test, and a conventional cycle ergometer exercise test, to 25 patients with chronic airflow limitation and to 18 with chronic heart failure, and repeated the tests up to six times over a lo-12 week period.
METHODS
Patients
We recruited two groups of subjects who experienced fatigue or dyspnea while performing activities of daily living. The first, a respiratory group, attended a regional referral centre for patients with respiratory problems (shortness of breath, cough, 517
518
GORDON H. GUYATT et 01.
hemoptysis, etc.) and had a best recorded forced expired volume in 1 set (FEVI) less than 0.7 of that predicted. The second group, patients with heart failure who were referred by local cardiologists, had impaired left ventricular function demonstrated by angiography, radionuclide scanning, or echocardiography. Patients were excluded if they had been in hospital in the last two months, or had their medication changed in the previous month. Once in the study, they were judged stable if they felt well enough to come to the clinic and undertake the walk tests and questionnaires. Exclusion criteria for both groups included: (1) Limitation of exercise performance as a result of factors other than fatigue exertional dyspnea, such as lower extremity arthritis, angina or leg claudication. (2) Inability to accurately complete the questionnaires because of language difficulty psychiatric disease. Study
or or
design
Patients were evaluated six times at 2 week intervals. The following tests, chosen on the basis of attention to instrument development and extensive prior use in patients with chronic heart and lung disease, were administered to the subjects. I. The Rand instrument. A simple four question instrument was developed by investigators at the Rand Corporation (modified from the British Medical Reasearch Council Dyspnea Questionnaire) to measure the effects of CHF and chronic airflow limitation on an ambulatory non-institutionalized population [I 5, 171. The instrument has been shown to meet Guttam scaling criteria, with a coefficient of reproducibility of 0.97 and a coefficient of scalability of 0.85. 2. The Baseline Dyspnea Index. This instrument was developed by Mahler and colleagues to measure functional status in patients with CAL [13]. An interviewer is asked to rate the patient according to the magnitude of the task that evokes dyspnea, the associated magnitude of the effort and the functional impairment. The index has been shown to have excellent interobserver agreement, correlates strongly with the 12-min walk test and less strongly with pulmonary function measures [13]. 3. The Oxygen Cost Diagram. This is a 10 cm line along which activities are written at intervals which correspond to the metabolic equivalents required to carry them out. Patients are asked to make a mark on the line indicating their exercise capacity. The scale was devised as a measure of functional status for patients with CAL [12], and has been used as an outcome measure in a clinical trial of theophylline in CAL [I]. Although, prior to the present study, no information regarding its reliability was available, results had correlated well with walk test scores in a previous investigation [12]. 4. The Spec$c Actiaity Scale (SAS). This index has been developed as an alternative to the New York Heart Association (NYHA) Functional Classification. Patients are asked about their ability to undertake activities of known metabolic cost and are placed in one of four functional classes on the basis of their responses. The SAS has been shown to have better interobserver reliability than the NYHA classification (kappa, or chance-corrected agreement of 0.62 and 0.41 respectively), and relates more closely to the results of conventional exercise testing than the older instrument (kappa 0.54 and 0.33, respectively) [16]. 5. The 6-min walk test. The 6-min walk test was administered by asking patients to cover as much ground as they could in a 6-min period [14]. Walk tests have been shown to be highly reproducible when repeated at fortnightly intervals (coefficient of variation approx. 10% [IS]). The walk test has been shown to bear weak to moderate correlations with tests of pulmonary function and conventional tests of exercise capacity [19], and correlations of over 0.5 with recently developed functional status questionnaires [ 12, 131. In the present study, the walk test was conducted in an enclosed corridor free of distractions with standardized encouragement provided by the test supervisor. All questionnaires, as well as the 6min walk, were administered by one of us (PJT) on all occasions. Of these five tests, the walk test was administered at each visit, and the functional status questionnaires were administered on at least four visits to each subject.
Function
in Patients
with Chronic
Heart
and Lung
Disease
519
6. A progressive multistage exercise test. This test, using a cycle ergometer [1 1] was conducted once with each patient. The test was conducted within the 12 week interval in which the other tests were administered, but not on the same day. Patients began at 100 kpm and the workload was increased by 100 kpm each minute until exhaustion. Exercise time to exhaustion was the variable of interest. Cycle ergometer and treadmill exercise tests have long been accepted as the gold standard for measuring maximum exercise capacity [I 11. Statistical
methods
Because the Specific Activity Scale and the Rand instrument provided ordinal data, the relation between the variables was measured by Spearman correlation coefficients. For the questionnaire data each subject’s score was taken as the mean of all administrations. In the case of the walking test, a learning effect was seen over the first three administrations. Therefore, the mean performance on the third to sixth repetitions was used for the correlations. The data from the single administration of the cycle exercise test was used in the correlations. For examining the precision of the tests, the within-person standard deviation (WPSD) was calculated as the mean of the individual subject standard deviations. This was related to the overall mean score as a coefficient of variation. That is, the WPSD was calculated and its magnitude expressed as a per cent of the overall mean score. RESULTS
Patient characteristics
Forty-three subjects completed the study, 34 males and 9 females aged 64.7 f 8.3 (mean i SD) years. In the 25 respiratory patients, the FEVl was 0.97 i 0.25 1and the vital capacity 2.4 + 0.87 I. Of the 18 cardiac patients, five were in New York Heart Association [20] class II, 12 in class III and one in class IV. Of the patients with heart failure, all but two had a cardiothoracic ratio of greater than 0.5 on posteroanterior chest radiograph, all were taking both digoxin and one or more diuretics and 12 were taking vasodilators (prazosin, hydralazine, captopril or nitrates). Although the patients were classified into groups according to the major cause of their disability, the frequent coexistence of chronic cardiac and respiratory disease is reflected in the fact that 8 of the participants met inclusion criteria for both groups. Further, results of walk and exercise tests, and of the functional status questionnaires, were comparable in the cardiac and respiratory patients and differences that did exist were not statistically significant for any test. Test results
The distributions of the values of the five tests that were repeatedly administered is depicted in Figs 1 to 5. The duration of the cycle ergometer test was 237 f 115 set, corresponding to a mean workload of just less than 400 kpm. Correlations between the four functional status questionnaires are shown in Table 1. Correlations were comparable for the respiratory and cardiac patients, and therefore the results were pooled for all subsequent data analysis. The Rand instrument, the Oxygen Cost Diagram, the Baseline Dyspnea Index, and the Specific Activity Scale correlated well (between 0.423 and 0.729) with one another (Table 1). The walking test showed good correlations with both the functional status questionnaires (0.473-0.589) and with the cycle ergometer results (0.579) (Fig. 6). However, we found very low correlations between the cycle ergometer and the questionnaires (0.1 14-0.295) which in all cases failed to reach conventional levels of statistical significance (Fig. 7). To ensure that the differences between the cycle ergometer and the walk test were not due to our using the mean score of the last four walk tests, we repeated the correlations using the results of each of the six repetitions. The correlations were almost identical for each repetition and for the mean. The reproducibility of the methods used is presented in Table 2. The meaning of the within-person standard deviation (WPSD) is that if subjects were to repeat the test 100
520
H.
Gonoozr
Score Ea 1
GUYATT
cr ~1
score
SCOW
SCOR
Eq 2
Eq. 3
Eq. 4
m
Vlslt
FIG I. Results
number
of serial administration
Score Eq. o-3
of the Rand
instrument
score Eq
Score Ec, 4-7
8-12
m 0.7 0.6 F
In
t I D
05
2
04
b .-5 t
0.3
8 o
0.2
& 0.1
0.0 2 Vtstt
FIG. 2. Results
of serial administration
3
4
number
of the Baseline
Dyspnea
Index
Standard deviation +
Meon 0 2018 16 14 -
v, a64-
+
+
12 P fj IO-
+
1+ 1+ f
+
2-
1
2 Visit
FIG.
3. Results
of serial administration
3
4
number
of the Oxygen
Cost Diagram
Function
in Patients
with Chronic
Heart
and Lung
SCOW Eq.2
SCOE
Eq 1
521
Disease Score Eq.4
SCOW Eq.3 =
Visit (Note: no subjects FIG. 4. Results
responded
number with
of serial administration
(1 score
-
500
-
visit
I
Scale.
Standard deviation
Mean
600
of 4 at any
of the Specific Activity
7 z
400-
“3 8 6 ‘, 0
300-
200
-
1001
I
I
1
I
I
2
3
4
Visit
FIG.
5. Results
I.
Oxygen
Rand instrument Rand instrument
CoRRtLArloN Baseline dyspnea index
of the 6-min walk test.
MATRIX
Specific activity scale
6.Min walk
Cycle ergometer
X
Oxygen cost diagram Baseline dyspnea index Specific activity scale h-Mill walk Cycle ergometer ‘Spearman l-p-value.
cost diagram
I
6
number
of serial administration TABLk
I 5
correlation
0.651 (0.001)
X
0.729 (0.001)
0.589 (0.001)
X
0.455 (0.002)
0.423 (0.005)
0.556 (0.001)
X
0.589 (0.001)
0.495 (0.001)
0.590 (0.001)
0.473 (0.001)
X
0.230 (0.144)
0.022 (0.891
0.295 (0.069)
0.1 I4 (0.474)
0.579* (o.ool)t
coefficients.
X
522
G~RDW
H. GUVATT et al
Six
Minute
FIG.
6. Six-minute
walk correlations.
FIG.
7. Cycle ergometer
correlations.
times, their score would fall within one WPSD of their mean score on 65 of those times, and within two WPSD of their mean score 95 times. The WPSD is related to the mean subject score in the second column of Table 2. The results show that the 6-min walk is substantially more reproducible than the functional status questionnaires. WPSD and the coefficient of variation for FEVl and Vital Capacity are included in Table 2 for comparison. The 6-min walk remains more reproducible than the other measures even if the first two walk scores are included (WPSD 29.8, coefficient of variation 0.07). Alternative ways of measuring stability of test score include an intraclass correlation coefficient, which relates the variance between subjects to the total variance and kappa, which is a special case of the intraclass correlation coefficient for nonparametic data. The intraclass correlation coefficient for the walk test was 0.909 for visits 3 to 6 and 0.921 for all six visits; 0.64 for the Oxygen Cost Diagram; and 0.28 for the Baseline Dyspnea Index. Kappa for the Specific Activity Scale was 0.66 and for the Rand instrument 0.38. All intraclass correlations and kappas were significant at a level of p = 0.001 or less. DISCUSSION
The goal of this study was to elucidate the usefulness of available measures of functional status and exercise capacity in patients with CAL and CHF. The results in 25 patients with
Test h-Min walk Oxygen cost diagram Specific activity scale Baseline dyspnea Rand instrument FEVI Vital capacity
Within-person standard deviatmn 22.52 1.966 0.559
1.058 0.797 0.078 0.29
Coefficient of variation 0.05
0.22 0.29 0.23 0.33 0.08 0.12
Function
in Patients
with Chronic
Heart
and Lung
Disease
523
CAL and 18 patients with CHF showed that the four functional status questionnaires bore substantial relation to one another (Spearman correlations of 0.423-0.729) and to the 6 min walk (correlations 0.495-0.590), but the correlations between the questionnaires and the cycle ergometer were very weak (0.002-0.230) (Table 1, Figs 6 and 7). At the same time, the correlation between the two exercise tests, the 6-min walk and the cycle ergometer, was substantial (0.579). Use of measures of health status to detect change over time depends on their reproducibility in stable subjects. Within the limits of the day-to-day fluctuation that is inevitable in moderate to severely limited patients with CAL and CHF, the patients in this investigation were stable throughout the period of study. The walking test results proved extremely reproducible (Table 2), a result consistent with previous work [18]. None of the functional status measures were as reproducible (Table 2). The content of the four questionnaires, and their substantial correlation with one another, suggest that they all provide an indication of patients’ ability to undertake the physically stressful activities of daily living. The cycle ergometer results did not relate closely to any of the questionnaires suggesting that laboratory exercise capacity may not be a good measure of the activities patients with chronic cardiorespiratory disease can undertake in their day to day lives. On the other hand, the 6 min walk not only correlated as well with the functional status questionnaires as they did with one another, but also showed a good correlation with the cycle ergometer, These data suggest that the walk test provides a measure of both the activities patients actually undertake, and how they feel (that is, functional status as measured by the questionnaires), and of exercise capacity as determined in the laboratory. The walk test appears to be measuring what one might call functional exercise capacity, the patient’s ability to undertake the physically demanding activities of daily living. The walk test has an advantage over the functional status questionnaires used in this study, in that it is more objective, and more reproducible (Table 2). Given that walk tests are responsive to change with treatment [21-241, they appear to be suitable as one measure of outcome in clinical trials in chronic cardiorespiratory disease. The results of this study suggest that measurement of endpoints that are relevant to patients in their day-to-day lives is both necessary and feasible when we try to determine the usefulness of therapies in patients with CAL and CHF. The 6 min walk appears to be one such endpoint which can be reproducibly measured, and which relates well to both questionnaire measures of functional status and conventional exercise tests. Acknowledgements-We would like to thank Drs .I. L. C. Morse, F. E. Hargreave, M. T. Newhouse and E. L. Fallen for their help in recruiting patients for this study. This work was supported, in part, by the St. Joseph’s Hospital Foundation, Hamilton, Ontario; the Medical Research Council of Canada; and the Ontario Ministry of Health.
REFERENCES I 2 3. 4. 5 6. 7. 8. 9.
Eaton ML, MacDonald FN, Church TR et al: Effects of theophylline on breathlessness and exercise tolerance in patients with chronic airflow obstruction. Chest 82: 538-542, 1982 Mahler DA, Matthay RA, Berger HJ et al: Sustained-release theophylline reduces dyspnea in non-reversible obstructive airway disease. Am Rev Resp Dis 127: 87. 1983 Anderson G, Peei ET, Pardoe T, et al: &stained-release theophylline in chronic bronchitis. Br J Dis Chest 76: 261-265, 1982 Alexander MR, Dull WL, Kasik JE: Treatment of chronic obstructive pulmonary disease with orally administered theophylline. JAMA 244: 2286-2290, 1980 Franciosa JA, Ziesche S, Wilen M: Functional capacity of patients with chronic left ventricular failure. Am J Med 67: 460466, 1979 Rubin SA, Chatterjee K, Parmley WW: Metabolic assessment of exercise in chronic heart failure patients treated with short term vasodilators. Circulation 61: 955-959, 1980 Massie BM, Kramer B, Haugham F: Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance. Circulation 64: 1218-l 226, 198 1 Franciosa JA, Park M., Levine TB: Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 47: 33-39. 1981 Benge W, Litchfield RL, Marcus ML: Exercise capacity in patients with severe left ventricular dysfunction. Circulation 61: 955-959, 1980
524 10.
11. 12. 13. 14. 15.
16. 17. 18. 19. 20. 21. 22. 23. 24.
GORVON H. GUYATT et al. Francis GS, Goldsmith SR, Cohn JN: Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J 104: 725-731, 1982 Jones ML, Campbell EJM: Clinical Exercise Testing. Philadelphia: WB Saunders, 1982 McGavin CR, Artvinli M, Naoe H: Dyspnea, disability and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J 2: 241-243, 1978 Mahler DA, Weinberg DH, Wells CK et al: The measurement of dyspnea. Chest 85: 751-758, 1984 Guyatt GH, Pugsley SO, Sullivan MJ et al: Walking test performance: the effect of encouragement. Thorax In press Rosenthal N, Lohr KN, Rubenstein RS, Goldberg GA, Brook RH: Conceptualization and measurement of physiological health for adults. V Congestive Heart Failure. Santa Monica, Calif: Rand Corporation, Sept. 1981 Goldman L, Hashimoto D, Cook EF: Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new Specific Activity Scale. Circulation 64: 1227-l 234, 198 1 Foxman B, Lohr KN, Brook RH et al: Conceptualization and measurement of physiological health in . adults. Santa Monica, Calif: Rand Corporation, September 1982 Mungall IPF, Hainsworth R: Assessment of respiratory function in patients with chronic obstructive airway disease. Thorax 34: 254-258, 1979. McGavin CR, Gupta SP, McHardy GJR: Twelve-minute walking test for assessing disability in chronic bronchitis. Br Med J 1: 822-823, 1976 The criteria committee of the New York Heart Association Incorporated: Diseases of the Heart and Blood Vessels; Nomenclature and Criteria for Diagnosis, 6th edn Boston: Little Brown, 1964 Leitch AG, Morgan A, Ellis DA et al: Effect of oral salbutamol and slow release-between aminophylline on exercise tolerance in chronic bronchitis. Thorax 36: 787-789, 1981 Woodcock A, Gross ER, Geddes DM: Oxygen relieves breathlessness in “pink puffers”. Lancet 1: 907-909, 1981 Sinclair DJM, Ingram CG: Controlled trial of supervised exercise training in chronic bronchitis. Br Med J 1: 519-521, 1980 McGavin CR, Gupta SP, Lloyd EL: Physical rehabilitation for the chronic bronchitic: results of a controlled trial of exercises in the home. Thorax 32: 307-31 I, 1977
Chron Dis Vol. 38, No. 6, pp. 517-524,
0021-9681185 %3.00+0.00 Copyright :c> 1985 PergamonPressLtd
1985
Printed in Great Britain. All rights reserved
HOW SHOULD IN PATIENTS AND
WE MEASURE FUNCTION WITH CHRONIC HEART LUNG DISEASE?
GORDON H. GUYATT,‘.~ PENELOPE J. THOMPSON, LESLIE B. BERMAN,’ MICHAEL J. SULLIVAN,’ MARIE TOWNSEND, NORMAN L. JONES~ and STEWART 0. PUGSLEY Departments
of ‘Clinical
Epidemiology Hamilton,
& Biostatistics Ontario, Canada
and ‘Medicine L8N 325
McMaster
University,
(Receioed in revised form 5 October 1984)
Abstract-To elucidatethe characteristicsof measuresof function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman’s rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579). and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand. correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease.
INTRODUCTION MEASURES of function are routinely used in patients with chronic heart failure and chronic airflow limitation to assess prognosis and to quantitate the effects of treatment. These measures include physiological tests (such as spirometry [l-4], cardiac index and pulmonary capillary wedge pressure [S-7], and cycle or treadmill exercise tests [g-11]), performance in day-to-day activities (walking tests [12-141) and patients’ own assessment of their capabilities and symptoms (questionnaires [15, 161). Clinicians and investigators must decide which of these measures to use in dealing with particular problems. An idea1 measure would be highly reproducible, reflect physiological function, but also relate closely to patients’ ability to cope with the physical demands of daily living. To determine the reproducibility of and correlation between commonly used measures of function, we administered four functional status questionnaires, a 6-min walk test, and a conventional cycle ergometer exercise test, to 25 patients with chronic airflow limitation and to 18 with chronic heart failure, and repeated the tests up to six times over a lo-12 week period.
METHODS
Patients
We recruited two groups of subjects who experienced fatigue or dyspnea while performing activities of daily living. The first, a respiratory group, attended a regional referral centre for patients with respiratory problems (shortness of breath, cough, 517
518
GORDON H. GUYATT et 01.
hemoptysis, etc.) and had a best recorded forced expired volume in 1 set (FEVI) less than 0.7 of that predicted. The second group, patients with heart failure who were referred by local cardiologists, had impaired left ventricular function demonstrated by angiography, radionuclide scanning, or echocardiography. Patients were excluded if they had been in hospital in the last two months, or had their medication changed in the previous month. Once in the study, they were judged stable if they felt well enough to come to the clinic and undertake the walk tests and questionnaires. Exclusion criteria for both groups included: (1) Limitation of exercise performance as a result of factors other than fatigue exertional dyspnea, such as lower extremity arthritis, angina or leg claudication. (2) Inability to accurately complete the questionnaires because of language difficulty psychiatric disease. Study
or or
design
Patients were evaluated six times at 2 week intervals. The following tests, chosen on the basis of attention to instrument development and extensive prior use in patients with chronic heart and lung disease, were administered to the subjects. I. The Rand instrument. A simple four question instrument was developed by investigators at the Rand Corporation (modified from the British Medical Reasearch Council Dyspnea Questionnaire) to measure the effects of CHF and chronic airflow limitation on an ambulatory non-institutionalized population [I 5, 171. The instrument has been shown to meet Guttam scaling criteria, with a coefficient of reproducibility of 0.97 and a coefficient of scalability of 0.85. 2. The Baseline Dyspnea Index. This instrument was developed by Mahler and colleagues to measure functional status in patients with CAL [13]. An interviewer is asked to rate the patient according to the magnitude of the task that evokes dyspnea, the associated magnitude of the effort and the functional impairment. The index has been shown to have excellent interobserver agreement, correlates strongly with the 12-min walk test and less strongly with pulmonary function measures [13]. 3. The Oxygen Cost Diagram. This is a 10 cm line along which activities are written at intervals which correspond to the metabolic equivalents required to carry them out. Patients are asked to make a mark on the line indicating their exercise capacity. The scale was devised as a measure of functional status for patients with CAL [12], and has been used as an outcome measure in a clinical trial of theophylline in CAL [I]. Although, prior to the present study, no information regarding its reliability was available, results had correlated well with walk test scores in a previous investigation [12]. 4. The Spec$c Actiaity Scale (SAS). This index has been developed as an alternative to the New York Heart Association (NYHA) Functional Classification. Patients are asked about their ability to undertake activities of known metabolic cost and are placed in one of four functional classes on the basis of their responses. The SAS has been shown to have better interobserver reliability than the NYHA classification (kappa, or chance-corrected agreement of 0.62 and 0.41 respectively), and relates more closely to the results of conventional exercise testing than the older instrument (kappa 0.54 and 0.33, respectively) [16]. 5. The 6-min walk test. The 6-min walk test was administered by asking patients to cover as much ground as they could in a 6-min period [14]. Walk tests have been shown to be highly reproducible when repeated at fortnightly intervals (coefficient of variation approx. 10% [IS]). The walk test has been shown to bear weak to moderate correlations with tests of pulmonary function and conventional tests of exercise capacity [19], and correlations of over 0.5 with recently developed functional status questionnaires [ 12, 131. In the present study, the walk test was conducted in an enclosed corridor free of distractions with standardized encouragement provided by the test supervisor. All questionnaires, as well as the 6min walk, were administered by one of us (PJT) on all occasions. Of these five tests, the walk test was administered at each visit, and the functional status questionnaires were administered on at least four visits to each subject.
Function
in Patients
with Chronic
Heart
and Lung
Disease
519
6. A progressive multistage exercise test. This test, using a cycle ergometer [1 1] was conducted once with each patient. The test was conducted within the 12 week interval in which the other tests were administered, but not on the same day. Patients began at 100 kpm and the workload was increased by 100 kpm each minute until exhaustion. Exercise time to exhaustion was the variable of interest. Cycle ergometer and treadmill exercise tests have long been accepted as the gold standard for measuring maximum exercise capacity [I 11. Statistical
methods
Because the Specific Activity Scale and the Rand instrument provided ordinal data, the relation between the variables was measured by Spearman correlation coefficients. For the questionnaire data each subject’s score was taken as the mean of all administrations. In the case of the walking test, a learning effect was seen over the first three administrations. Therefore, the mean performance on the third to sixth repetitions was used for the correlations. The data from the single administration of the cycle exercise test was used in the correlations. For examining the precision of the tests, the within-person standard deviation (WPSD) was calculated as the mean of the individual subject standard deviations. This was related to the overall mean score as a coefficient of variation. That is, the WPSD was calculated and its magnitude expressed as a per cent of the overall mean score. RESULTS
Patient characteristics
Forty-three subjects completed the study, 34 males and 9 females aged 64.7 f 8.3 (mean i SD) years. In the 25 respiratory patients, the FEVl was 0.97 i 0.25 1and the vital capacity 2.4 + 0.87 I. Of the 18 cardiac patients, five were in New York Heart Association [20] class II, 12 in class III and one in class IV. Of the patients with heart failure, all but two had a cardiothoracic ratio of greater than 0.5 on posteroanterior chest radiograph, all were taking both digoxin and one or more diuretics and 12 were taking vasodilators (prazosin, hydralazine, captopril or nitrates). Although the patients were classified into groups according to the major cause of their disability, the frequent coexistence of chronic cardiac and respiratory disease is reflected in the fact that 8 of the participants met inclusion criteria for both groups. Further, results of walk and exercise tests, and of the functional status questionnaires, were comparable in the cardiac and respiratory patients and differences that did exist were not statistically significant for any test. Test results
The distributions of the values of the five tests that were repeatedly administered is depicted in Figs 1 to 5. The duration of the cycle ergometer test was 237 f 115 set, corresponding to a mean workload of just less than 400 kpm. Correlations between the four functional status questionnaires are shown in Table 1. Correlations were comparable for the respiratory and cardiac patients, and therefore the results were pooled for all subsequent data analysis. The Rand instrument, the Oxygen Cost Diagram, the Baseline Dyspnea Index, and the Specific Activity Scale correlated well (between 0.423 and 0.729) with one another (Table 1). The walking test showed good correlations with both the functional status questionnaires (0.473-0.589) and with the cycle ergometer results (0.579) (Fig. 6). However, we found very low correlations between the cycle ergometer and the questionnaires (0.1 14-0.295) which in all cases failed to reach conventional levels of statistical significance (Fig. 7). To ensure that the differences between the cycle ergometer and the walk test were not due to our using the mean score of the last four walk tests, we repeated the correlations using the results of each of the six repetitions. The correlations were almost identical for each repetition and for the mean. The reproducibility of the methods used is presented in Table 2. The meaning of the within-person standard deviation (WPSD) is that if subjects were to repeat the test 100
520
H.
Gonoozr
Score Ea 1
GUYATT
cr ~1
score
SCOW
SCOR
Eq 2
Eq. 3
Eq. 4
m
Vlslt
FIG I. Results
number
of serial administration
Score Eq. o-3
of the Rand
instrument
score Eq
Score Ec, 4-7
8-12
m 0.7 0.6 F
In
t I D
05
2
04
b .-5 t
0.3
8 o
0.2
& 0.1
0.0 2 Vtstt
FIG. 2. Results
of serial administration
3
4
number
of the Baseline
Dyspnea
Index
Standard deviation +
Meon 0 2018 16 14 -
v, a64-
+
+
12 P fj IO-
+
1+ 1+ f
+
2-
1
2 Visit
FIG.
3. Results
of serial administration
3
4
number
of the Oxygen
Cost Diagram
Function
in Patients
with Chronic
Heart
and Lung
SCOW Eq.2
SCOE
Eq 1
521
Disease Score Eq.4
SCOW Eq.3 =
Visit (Note: no subjects FIG. 4. Results
responded
number with
of serial administration
(1 score
-
500
-
visit
I
Scale.
Standard deviation
Mean
600
of 4 at any
of the Specific Activity
7 z
400-
“3 8 6 ‘, 0
300-
200
-
1001
I
I
1
I
I
2
3
4
Visit
FIG.
5. Results
I.
Oxygen
Rand instrument Rand instrument
CoRRtLArloN Baseline dyspnea index
of the 6-min walk test.
MATRIX
Specific activity scale
6.Min walk
Cycle ergometer
X
Oxygen cost diagram Baseline dyspnea index Specific activity scale h-Mill walk Cycle ergometer ‘Spearman l-p-value.
cost diagram
I
6
number
of serial administration TABLk
I 5
correlation
0.651 (0.001)
X
0.729 (0.001)
0.589 (0.001)
X
0.455 (0.002)
0.423 (0.005)
0.556 (0.001)
X
0.589 (0.001)
0.495 (0.001)
0.590 (0.001)
0.473 (0.001)
X
0.230 (0.144)
0.022 (0.891
0.295 (0.069)
0.1 I4 (0.474)
0.579* (o.ool)t
coefficients.
X
522
G~RDW
H. GUVATT et al
Six
Minute
FIG.
6. Six-minute
walk correlations.
FIG.
7. Cycle ergometer
correlations.
times, their score would fall within one WPSD of their mean score on 65 of those times, and within two WPSD of their mean score 95 times. The WPSD is related to the mean subject score in the second column of Table 2. The results show that the 6-min walk is substantially more reproducible than the functional status questionnaires. WPSD and the coefficient of variation for FEVl and Vital Capacity are included in Table 2 for comparison. The 6-min walk remains more reproducible than the other measures even if the first two walk scores are included (WPSD 29.8, coefficient of variation 0.07). Alternative ways of measuring stability of test score include an intraclass correlation coefficient, which relates the variance between subjects to the total variance and kappa, which is a special case of the intraclass correlation coefficient for nonparametic data. The intraclass correlation coefficient for the walk test was 0.909 for visits 3 to 6 and 0.921 for all six visits; 0.64 for the Oxygen Cost Diagram; and 0.28 for the Baseline Dyspnea Index. Kappa for the Specific Activity Scale was 0.66 and for the Rand instrument 0.38. All intraclass correlations and kappas were significant at a level of p = 0.001 or less. DISCUSSION
The goal of this study was to elucidate the usefulness of available measures of functional status and exercise capacity in patients with CAL and CHF. The results in 25 patients with
Test h-Min walk Oxygen cost diagram Specific activity scale Baseline dyspnea Rand instrument FEVI Vital capacity
Within-person standard deviatmn 22.52 1.966 0.559
1.058 0.797 0.078 0.29
Coefficient of variation 0.05
0.22 0.29 0.23 0.33 0.08 0.12
Function
in Patients
with Chronic
Heart
and Lung
Disease
523
CAL and 18 patients with CHF showed that the four functional status questionnaires bore substantial relation to one another (Spearman correlations of 0.423-0.729) and to the 6 min walk (correlations 0.495-0.590), but the correlations between the questionnaires and the cycle ergometer were very weak (0.002-0.230) (Table 1, Figs 6 and 7). At the same time, the correlation between the two exercise tests, the 6-min walk and the cycle ergometer, was substantial (0.579). Use of measures of health status to detect change over time depends on their reproducibility in stable subjects. Within the limits of the day-to-day fluctuation that is inevitable in moderate to severely limited patients with CAL and CHF, the patients in this investigation were stable throughout the period of study. The walking test results proved extremely reproducible (Table 2), a result consistent with previous work [18]. None of the functional status measures were as reproducible (Table 2). The content of the four questionnaires, and their substantial correlation with one another, suggest that they all provide an indication of patients’ ability to undertake the physically stressful activities of daily living. The cycle ergometer results did not relate closely to any of the questionnaires suggesting that laboratory exercise capacity may not be a good measure of the activities patients with chronic cardiorespiratory disease can undertake in their day to day lives. On the other hand, the 6 min walk not only correlated as well with the functional status questionnaires as they did with one another, but also showed a good correlation with the cycle ergometer, These data suggest that the walk test provides a measure of both the activities patients actually undertake, and how they feel (that is, functional status as measured by the questionnaires), and of exercise capacity as determined in the laboratory. The walk test appears to be measuring what one might call functional exercise capacity, the patient’s ability to undertake the physically demanding activities of daily living. The walk test has an advantage over the functional status questionnaires used in this study, in that it is more objective, and more reproducible (Table 2). Given that walk tests are responsive to change with treatment [21-241, they appear to be suitable as one measure of outcome in clinical trials in chronic cardiorespiratory disease. The results of this study suggest that measurement of endpoints that are relevant to patients in their day-to-day lives is both necessary and feasible when we try to determine the usefulness of therapies in patients with CAL and CHF. The 6 min walk appears to be one such endpoint which can be reproducibly measured, and which relates well to both questionnaire measures of functional status and conventional exercise tests. Acknowledgements-We would like to thank Drs .I. L. C. Morse, F. E. Hargreave, M. T. Newhouse and E. L. Fallen for their help in recruiting patients for this study. This work was supported, in part, by the St. Joseph’s Hospital Foundation, Hamilton, Ontario; the Medical Research Council of Canada; and the Ontario Ministry of Health.
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Eaton ML, MacDonald FN, Church TR et al: Effects of theophylline on breathlessness and exercise tolerance in patients with chronic airflow obstruction. Chest 82: 538-542, 1982 Mahler DA, Matthay RA, Berger HJ et al: Sustained-release theophylline reduces dyspnea in non-reversible obstructive airway disease. Am Rev Resp Dis 127: 87. 1983 Anderson G, Peei ET, Pardoe T, et al: &stained-release theophylline in chronic bronchitis. Br J Dis Chest 76: 261-265, 1982 Alexander MR, Dull WL, Kasik JE: Treatment of chronic obstructive pulmonary disease with orally administered theophylline. JAMA 244: 2286-2290, 1980 Franciosa JA, Ziesche S, Wilen M: Functional capacity of patients with chronic left ventricular failure. Am J Med 67: 460466, 1979 Rubin SA, Chatterjee K, Parmley WW: Metabolic assessment of exercise in chronic heart failure patients treated with short term vasodilators. Circulation 61: 955-959, 1980 Massie BM, Kramer B, Haugham F: Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance. Circulation 64: 1218-l 226, 198 1 Franciosa JA, Park M., Levine TB: Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 47: 33-39. 1981 Benge W, Litchfield RL, Marcus ML: Exercise capacity in patients with severe left ventricular dysfunction. Circulation 61: 955-959, 1980
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