Six-Minute Walk Distance in Chronic Obstructive
Pulmonary Disease
Reproducibility and Effect of Walking Course Layout and Length
Frank Sciurba, Gerard J. Criner, Shing M. Lee, Zab Mohsenifar, David Shade, William Slivka, and Robert A. Wise
for the National Emphysema Treatment Trial Research Group
Johns Hopkins University, Baltimore, Maryland; Cedars Sinai-University of California, Los Angeles, California; Temple University School of
Medicine, Philadelphia; and University of Pittsburgh, Pittsburgh, Pennsylvania
The 6-minute walk test is used in clinical practice and clinical trials
of lung diseases; however, it is not clear whether replicate tests
need to be performed to assess performance. Furthermore, little is
known about the impact of walking course layout on test perfor-
mance. We conducted 6-minute walks on 761 patients with severe
emphysema (mean ⫾ SD FEV1% predicted ⫽ 26.3 ⫾ 7.2) who were
participants in the National Emphysema Treatment Trial. Four hun-
dred seventy participants had repeated walks on a separate day.
The second test was improved by an average of 7.0 ⫾ 15.2% (66.1 ⫾
146 feet, p ⬍ 0.0001, by paired t test), with an intraclass correlation
coefficient of 0.88 between days. The course layout had an effect
on the distance walked. Participants tested on continuous (circular
or oval) courses had a 92.2-foot longer walking distance than those
tested on straight (out and back) courses. Course length had no
significant effect on walking distance. The training effect found in
these patients with severe emphysema is less than in previous re-
ports of patients with chronic obstructive pulmonary disease. Fur-
thermore, the layout of the track may influence the 6-minute walk
performance.
Keywords: emphysema; exercise tests; reproducibility of results; diag-
nostic techniques; clinical trials
The 6-minute walk test is used as an outcome measure in
clinical trials of lung disease. Although the test has been
somewhat standardized, there are differences in the testing
technique in different clinical centers and laboratories (1).
In particular, there is not agreement on the length of the test
course, the shape of the test course (straight versus continu-
ous circle or oval), whether a practice walk should be done
before the final test, and whether the better of two walks or
the second of two walks should be the reported value. These
questions are of particular importance in longitudinal
multicenter clinical trials in which test results may vary be-
tween centers and over time.
The National Emphysema Treatment Trial (NETT) is a
(Received in original form March 3, 2002; accepted in final form February 18, 2003)
Supported by contracts with the National Heart, Lung, and Blood Institute
(N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105,
N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR761010,
N01HR761011, N01HR761012, N01HR761013, N01HR761014, N01HR761015,
N01HR761016, N01HR76118, and N01HR761019), the Center for Medicare and
Medicaid Services (formerly the Health Care Financing Administration), and the
Agency for Healthcare Research and Quality.
Correspondence and requests for reprints should be addressed to Robert A. Wise,
M.D., Pulmonary and Critical Care Medicine, Johns Hopkins University School of
Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: rwise@
jhmi.edu
This article has an online supplement, which is accessible from this issue’s table
of contents online at www.atsjournals.org
Am J Respir Crit Care Med Vol 167. pp 1522–1527, 2003
Originally Published in Press as DOI: 10.1164/rccm.200203-166OC on February 20, 2003
Internet address: www.atsjournals.org
multicenter trial of lung volume reduction surgery compared
with medical treatment for advanced emphysema. The study
investigators conduct 6-minute walk tests in participants at
entry into the study and periodically thereafter. In this report,
we analyze results of 6-minute walks for the first 761 random-
ized participants. Of these, 470 participants undertook two
6-minute walks on successive days. This afforded us the op-
portunity to examine the reproducibility of repeated 6-min-
ute walks in this patient population. Because the length of
the walking course differed among the 17 clinical centers, we
were also able to examine what effects this would have on
6-minute walking distance. Furthermore, because some walk-
ing courses were continuous (circular or oval) and others
were straight, requiring turns, we were able to evaluate the
effect of walking course layout on performance.
METHODS
Additional details on the methods of this research are available in the
online supplement.
NETT
The NETT is a multicenter clinical trial comparing lung volume reduc-
tion surgery with medical treatment in patients with emphysema. The
details of the trial design have been published (2, 3).
Major enrollment criteria include bilateral emphysema judged suit-
able for lung volume reduction surgery documented by computed chest
tomography, FEV1 less than or equal to 45% predicted (4), total lung
capacity of at least 100% predicted (5), residual volume of at least
150% predicted (5), and PaCO2 less than 60 mm Hg (or less than 55
mm Hg in Denver). Enrollees had to be validated nonsmokers for 4
months and had to be free of important comorbid conditions.
Data Collection Schedule
Participants had a baseline evaluation before enrollment, including a
medical history and examination, lung function testing, blood testing,
chest computed tomography, dobutamine cardiac stress testing, and
echocardiography. If necessary, additional studies such as cardiac con-
sultation and cardiac catherization were performed to exclude people
with coronary artery disease or moderate to severe pulmonary hyper-
tension. The data that are presented here are taken from the baseline
evaluation in participants ultimately enrolled in the trial, representing
those with severe emphysema who are free of important comorbid
conditions. We analyzed data from 761 randomized participants who
had 6-minute walk tests at the 17 clinical centers. In 470 of the initial
enrollees, the 6-minute walk test was repeated on the day after the first
test to account for the effect of repeated testing.
Six-minute Walk Test Procedure
On a day before the first 6-minute walk, participants underwent cardio-
pulmonary exercise testing with a cycle ergometer to exclude important
cardiac rhythm disturbances or ischemic electrocardiographic changes.
Before the first 6-minute walk, participants also undertook a 1- to 2-mile-
per-hour treadmill test to determine whether they needed oxygen dur-
ing the 6-minute walk test.
Each clinical site used the same walking course for all participants,
Sciurba, Criner, Lee, et al.: Six-minute Walk in Emphysema 1523

TABLE 1. PARTICIPANT CHARACTERISTICS (MEAN ⫾ SD)

Participants with Participants with
Characteristics* at Least One Test Two Tests

n 761 470
Age, yr 67.2 ⫾ 5.9 67.2 ⫾ 5.8
Female, % 39 39
Height, cm 168.9 ⫾ 9.61 168.5 ⫾ 9.5
Weight, kg 70.3 ⫾ 13.8 70.1 ⫾ 13.7
BMI, kg/m2 24.6 ⫾ 3.85 24.6 ⫾ 3.78
FEV1, L BTPS 0.76 ⫾ 0.24 0.75 ⫾ 0.24
FEV1 % predicted 26.3 ⫾ 7.2 26.3 ⫾ 7.4
FVC, L BTPS 2.45 ⫾ 0.77 2.45 ⫾ 0.77
FVC % predicted 65.7 ⫾ 15.3 66.0 ⫾ 15.4
FEV1/FVC % 31.6 ⫾ 6.6 31.4 ⫾ 6.4
MVV, L/min 30.4 ⫾ 10.2 30.4 ⫾ 10.4
TLC, L BTPS 7.75 ⫾ 1.52 7.78 ⫾ 1.49
TLC % predicted 129.2 ⫾ 13.9 130.4 ⫾ 13.4
RV % predicted 227.6 ⫾ 48.0 230.0 ⫾ 45.9
RV/TLC % 65.7 ⫾ 8.0 66.0 ⫾ 7.7
DCO % predicted 27.5 ⫾ 9.6 27.8 ⫾ 9.7
Required oxygen at rest, % 9.9 10.6
Required oxygen during test, % 76.8 78.1 Figure 1. Scatter plot of first-day and second-day 6-minute walk dis-
SGRQ, total score 56.1 ⫾ 12.8 56.2 ⫾ 13.3
tance. The bold line shows the line of identity. The dashed line is the
6MW distance % predicted† 70.1 ⫾ 19.2 67.4 ⫾ 18.1
Dyspnea score† 5.1 ⫾ 2.0 5.0 ⫾ 2.0
regression of the second test to the first. The intraclass correlation
Muscle fatigue score† 3.5 ⫾ 2.3 3.4 ⫾ 2.2 between the two tests is 0.88, with the majority of points above the
line of identity.
Definition of abbreviations: 6MW ⫽ 6-minute walk; DCO ⫽ diffusing capacity for
carbon monoxide; L BTPS ⫽ liters, body temperature and pressure saturated with
water vapor; RV ⫽ residual volume; SGRQ ⫽ St. George’s Respiratory Question-
naire; TLC ⫽ total lung capacity.
* Dyspnea Score and Muscle Fatigue Score are based on the Borg CR-10 scale. cient of 0.88 (p ⬍ 0.0001), but with a definite learning effect on
†
Values are taken from the initial test. the second test (Figures 1 and 2). On average, the second 6-
minute walk distance was greater by 66.1 ⫾ 146 feet (p ⬍ 0.0001,
by paired t test) (Figure 3). The mean improvement was 7.0 ⫾
15.2% on the second test, with 70% of people improving on the
although the length and shape of the walking course differed among second day. The mean absolute change between the two test
centers. Participants took a short-acting bronchodilator within 2 hours days was 118 ⫾ 108 feet. On the second test day, 14.9% of the
before testing. patients increased the walking distance more than the estimated
Clinic staff gave identical scripted instructions to participants and clinically significant threshold of 180 feet, and 4.7% of the pa-
explained the Borg category ratio scale (CR-10) (6, 7). A staff member tients decreased more than this amount (11).
walked behind the participant and carried the oxygen delivery system People with greater distances on the first test had a tendency
if required. At each minute during the walk, the staff member told the to improve more on the second test, suggesting that there was
participant how much time had elapsed and the remaining time and gave
not simply regression to the mean. The Bland-Altman plot con-
scripted encouragement. At the end of the 6 minutes, the participant was
firms that the second-day test was consistently and significantly
told to stop, and the distance walked was recorded. Predicted values
were calculated using the normative values of Enright and Sherrill (8). longer (Figure 2). The effect of using different strategies for test

Statistical Analysis
Results are presented as means and SDs. Changes in 6-minute walk
distances were compared using a paired t test. Trends in differences
between the first and second walk distances were evaluated using Bland-
Altman analysis (9). Changes in the Borg scores were compared with
zero using the Wilcoxon signed rank test. The effect of course layout
and length was estimated using multiple linear regression adjusting for
age, sex, height, and FEV1 percentage predicted.

RESULTS
The characteristics of the study population are presented in
Table 1. The first 470 participants with replicated 6-minute walks
were similar to those who performed only one walk in terms of
age, sex, and lung function. As expected, the study population
had evidence of severe obstructive lung disease with diminished
single-breath carbon monoxide diffusing capacity, hyperinfla-
tion, and air trapping. Disease impact on quality of life, measured
by the St. George’s Respiratory Questionnaire, was considerable
with a score of 56 ⫾ 12.8 on a scale of 100, with 100 representing Figure 2. Scatter plot of the difference between the two walks plotted
the worst quality of life (10). against the mean value (Bland-Altman plot). The dashed line is the re-
In general, we found that the 6-minute walk test was repro- gression of change in walking distance against mean value, indicating that
ducible on subsequent days, with an intraclass correlation coeffi- those with higher values tended to improve more on the second day.
1524 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 167 2003

Figure 3. The distribution of differences between the second-day walk

distance and the first-day walk distance. The mean ⫾ SD improvement
was 66.1 ⫾ 146 feet, which is significantly larger than zero (p ⫽ 0.0001).

selection is shown in Table 2. The better of the two tests was,

on average, 92.1 feet longer than the first test (Table 2).
Linear regression models adjusting for baseline measures and
including demographic, anthropometric, physiologic, previous
rehabilitation, and quality-of-life measures showed that partici-
pants with higher maximum inspiratory pressure had more im-
provement on the second walk (0.99 ⫾ 0.34 feet/cm H2O, p ⬍
0.005). There were no other clinical features that predicted which
participants increased walking distance.
Borg scores for breathlessness and leg fatigue were also repro-
ducible on subsequent tests on average (Figure 4). The Borg
score for breathlessness increased 0.33 ⫾ 1.74 U (median change
0, interquartile range 0 to 1) on the second test (p ⬍ 0.0001,
Wilcoxon signed rank test). There was no significant change in
the Borg score for leg fatigue on the second test with a mean
change of 0.002 ⫾ 1.70 U (median change ⫽ 0, interquartile
range ⫺1 to 1) (Figure 5). Regression models did not reveal
any clinical, demographic, or physiologic features that predicted
changes in the dyspnea or leg fatigue scores.
Among the 14 clinics with straight walking courses, the mean
length of the course ranged from 50 to 164 feet (mean 99.9 ⫾
34.1 feet). Three clinics had continuous layout courses (either
oval or square) that ranged in length from 185 to 397 feet in
circumference (mean 298 ⫾ 75.4 feet). The 6-minute walk dis-
tance was greater in those individuals who completed the test
on a continuous track (1,156 ⫾ 302 feet for straight courses and Figure 4. Scatter plots are shown for Borg scores for breathlessness (A )
1,266 ⫾ 360 feet for continuous courses, p ⫽ 0.003, t test). The and for muscle fatigue (B ) at the end of the 6-minute walk (6MW)
effect of course layout persisted when adjusted for FEV1 percent- comparing the first and second test days. Data points are offset to allow
age predicted, age, sex, and height (adjusted difference 92.2 feet, better display of the individual data points. The bold diagonal line is the
p ⬍ 0.001). Among the 14 clinics with straight course layout, line of identity.
there was no statistically significant effect of track length on
6-minute walk distance in bivariate as well as multivariate anal-
yses.
DISCUSSION
The 6-minute walk test is widely used for the evaluation of
TABLE 2. SIX-MINUTE WALK RESULTS FOR PARTICIPANTS functional status in patients with lung disease in both clinical
WITH TWO SESSIONS (N ⫽ 470)* practice as well as clinical trials (12–16). The test is widely used
because it involves a familiar daily activity and involves the use
First Test Second Test Best Test
of minimal technical resources (17).
Distance walked, feet 1,124.0 ⫾ 298.6 1,190.1 ⫾ 312.8 1,216.1 ⫾ 307.5 Because verbal encouragement can improve test perfor-
Distance, % predicted 67.4 ⫾ 18.1 71.4 ⫾ 19.1 72.9 ⫾ 18.6 mance, most protocols use standardized verbal prompts that are
Borg score dyspnea 5.01 ⫾ 2.02 5.34 ⫾ 2.05 5.26 ⫾ 2.04
similar to those that we have used (18). Less well documented,
Borg score leg fatigue 3.45 ⫾ 2.20 3.45 ⫾ 2.28 3.51 ⫾ 2.30
however, is the short-term variability of the test in patients with
* Results are expressed as mean ⫾ SD. advanced chronic obstructive pulmonary disease (COPD). Be-
Sciurba, Criner, Lee, et al.: Six-minute Walk in Emphysema
Figure 5. The distribution of differences between the second-day walk
Borg scores for breathlessness (A ) and for leg fatigue (B ). The distribu-
tions are skewed in opposite directions. The mean change in the Borg
dyspnea score is 0.33 ⫾ 1.74 U, which is significantly greater than zero
(p ⬍ 0.0001). The mean change for the leg fatigue score on the second
test is 0.002 ⫾ 1.70 U, which is not statistically different from zero.
cause the test requires some degree of strategy and pacing, some
laboratories require a practice walk before the test walk, whereas
others do not. There is also little known about the effects of the
walking course on test results. This analysis was performed on
enrollees in the NETT to address these questions.
On the second day of testing, we found a statistically signifi-
cant improvement of approximately 66 feet. This was likely due
to familiarity with the walking course, better pacing, or motiva-
tional factors. It is also possible that the patients were less fa-
tigued on the second test day because the test had not been
preceded by an oxygen titration test requiring treadmill walking
at 1 to 2 miles per hour. Similar short-term improvement in
6-minute walking distance and treadmill exercise testing has
been reported in cardiac patients, which has been attributed to
a learning effect (19, 20). Gibbons and colleagues performed
four 6-minute walks on the same day in 79 healthy adults. They
found that the longest distance occurred on the first walk 14%
of the time and that the longest of the four walks averaged
6.6% longer than the initial test, similar to the magnitude of
improvement in our COPD patients (21).
1525
There have been several studies of repeated walking tests in
COPD patients. Leach and colleagues found in 30 patients with
hypoxemia from COPD and restrictive lung diseases that the
learning effect of subsequent 6-minute walks was 14.9% (22).
This is a greater learning effect than we found in our more
impaired patients who were given supplemental oxygen to pre-
vent hypoxemia. McGavin and colleagues found that a second
12-minute walking test was associated with a 7% improvement,
closer to what we found in this study (23). Swinburn and col-
leagues found a 16% improvement on four successive 12-minute
walks in 17 COPD patients over the course of 1 week (24). Knox
and colleagues performed 12 5-minute walks over 3 consecutive
days in 36 COPD patients. He found that there was a 33% im-
provement in walking distance, with half of the improvement
occurring in the first three walks on Day 1. If the 12 walks were
repeated over a 4-week interval, however, the total learning
effect was only approximately one-fourth as large (25). Stevens
and colleagues performed three 6-minute walk tests in 21 COPD
patients on separate days and found a mean increase of 10%
on the second test and an additional 3% on the third test (26).
We are not certain why we found a smaller learning effect
than other series, but it may relate to the severity of disease, the
scripted encouragements, the instructions to perform a maximal
test, the prior treadmill and cycle exercise testing, or the familiar-
ity of the patients with the testing staff and environment. A
possible explanation of our findings is that some of the NETT
patients had previous experience with pulmonary rehabilitation
and therefore were not truly “naive” to the test procedures. We
could not, however, find any difference in learning effect based
on prior pulmonary rehabilitation exposure.
The obvious implication of our results and the results of
others is that clinical trials that rely on 6-minute walks before
and after an intervention should include appropriate control
groups, or repeated tests, to account for this learning effect. If
a single 6-minute walk test is used, there should be a contempora-
neous control group and the tests should be spaced several weeks
apart to minimize the learning effect. The selection of reference
equations also depends on the testing method. Normative values
for 6-minute walk tests have been derived from single test ses-
sions (8). Reference equations from healthy volunteers who per-
formed multiple tests on a single day predict significantly longer
distances if the best of multiple tests is chosen as the study
value (21, 27). There can be statistically and potentially clinically
important differences depending on whether the first, second,
best, or mean value is reported. Because of the small difference
and the burden of a second day of exhaustive exercise testing
in patients with advanced obstructive lung disease and the little
additional information that such testing provides, we have elimi-
nated the second 6-minute walk from the NETT protocol. The
recent American Thoracic Society guidelines for 6-minute walk
tests do not require a practice walk. They do recommend, how-
ever, that if a practice walk is done, the repeat test should be
done on the same day at least 1 hour later and that the larger
of the two values should be reported (28).
The data presented here may be useful in interpreting changes
in walking distance after an intervention in individual patients.
If the study is repeated within a short period such that a learning
effect may be involved, an individual patient would need to
improve by more than 352 feet (66 feet ⫹ 1.96 ⫻ 146 feet) to
be 95% confident that there had been improvement. If the short-
term learning effect is discounted, for example in tests done 4
weeks apart, then an improvement of 286 feet (1.96 ⫻ 146) is
necessary to be 95% confident that the change was not random
variation. This threshold is similar to the upper 95% confidence
interval of clinically important changes in 6-minute walk distance
of 280 feet reported by Redelmeier and colleagues (11).
1526 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 167 2003
The impairment of 6-minute walk distance (70.1% predicted)
on average was not as severe as one might predict from the
severity of impairment of FEV1 (26.3% predicted) or quality of
life (St. George’s Respiratory Questionnaire, 56.2 out of 100).
It is possible that this reflects the selected population enrolling
in NETT or may reflect the benefit of oxygen supplementation,
which was used by 78% of the patients. For clinical purposes,
it is important to consider other factors than walking distance.
Van Stel and colleagues found that half of 53 COPD patients
experienced declines in 6-minute walk distance after rehabilita-
tion, whereas 83% reported improved exercise capacity that
could be attributed to cardiovascular conditioning, less oxygen
desaturation, and less dyspnea with everyday activities (29).
Thus, the 6-minute walking distance is only one dimension of
functional assessment of COPD treatments.
The Borg score for dyspnea at the end of the 6-minute walk
was slightly higher on the second walk, perhaps corresponding
to greater effort expenditure to achieve the longer distance. This
is different from the findings of Belman and colleagues who
found lower dyspnea scores on four successive treadmill tests in
nine patients with COPD despite comparable maximal exercise
achievement (30). The Borg score for leg fatigue was not greater
on the second test day. The range of Borg scores was quite large.
There was a weak negative correlation between distance walked
and the dyspnea score (r ⫽ ⫺0.22) but none for the leg fatigue
score. The average degree of dyspnea on study Day 1 was 5.01 ⫾
2.01, corresponding to a descriptor of “severe.” This is slightly
lower than the value of 5.2 reported by Hamilton and colleagues
during symptom-limited ergometer exercise testing in untrained
patients with pulmonary disease (31). We found a lower mean
Borg score for leg fatigue than dyspnea in our study population
3.45 ⫾ 2.2. This is in contrast to two previous studies that have
found similar or higher scores for leg fatigue at maximal exercise
in pulmonary disease patients performing symptom-limited cycle
ergometer exercise (31, 32). The difference between these find-
ings may be related to the greater severity of disease in our
patient population or the different type of exercise challenge.
Because the NETT study involved centers that used the same
6-minute walk protocol but differed in terms of walking course
length and layout, it afforded us the opportunity to examine
whether these factors affected the distance walked. We found
that the three centers that used continuous walking courses,
either oval or square, produced longer 6-minute walk distances
than those with straight courses. The difference attributable to
the walking course layout was 110 feet, an approximate 10%
advantage for the continuous courses. Because the same subjects
were not tested on different courses, we cannot be certain that
there are not subtle differences in patient or other clinical center
characteristics that account for this effect. However, we could
not eliminate this difference by adjustment for age, sex, height,
and FEV1 percentage predicted in the patient populations at the
different clinical centers. Therefore, we believe it is a reasonable
inference that the shape of the 6-minute walk course has an
impact on the distance walked and supports the need for stan-
dardization of this variable on subsequent tests. We speculate
that the advantage of continuous walking courses is due to the
effort and time required for the test subject to turn around on
a straight course. Timed treadmill distance testing, where an
individual is free to alter the speed of the treadmill, might be
considered comparable to a continuous walking course, but ex-
perimental evidence indicates that the treadmill tests result in
shorter distances than straight courses, possibly because of diffi-
culty in pacing accurately with a treadmill (26).
We also hypothesized that longer courses could offer an
advantage over shorter courses for the same reason. However,
the 6-minute walk distance was not longer in clinics with longer
walking courses, which does not support this hypothesis. It is
possible that the range of course lengths was insufficient to test
this adequately or that our hypothesized mechanism for the
effect of track layout in incorrect. Whichever explanation is
correct, we note that literature reference values derived from a
20-m course are similar to those derived from a 50-m course
(21, 27). Thus, it seems less important to standardize the length
of the course as long as it exceeds the minimum of 50 feet, which
was the shortest distance among the 14 centers with straight
courses. The American Thoracic Society guidelines suggest that
the minimum course length be at least 100 feet and suggests a
straight rather than a continuous course (28).
In summary, we have found that the 6-minute walking test
in patients with advanced emphysema is a measure that can be
implemented in a large multicenter trial. There is a statistically
significant improvement, averaging 7% when the test is repeated
on a second day. The shape of the walking course (continuous
versus straight) appears to be a determinant of distance walked
but not the length of a straight course.
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