FWT Syst Rev Online Supplement

Measurement properties of field exercise tests in chronic respiratory disease:
a systematic review.
Online Supplement
Singh SJ1,2, Puhan MA3, Andrianopoulos V4, Hernandes NA5, Mitchell KE1, Hill CJ6,7, Lee AL7,8,
Camillo CA9, Troosters T9, Spruit MA4,10, Carlin BW11,12, Wanger J13, Pepin V14,15, Saey D16,17,
Pitta F5, Kaminsky DA18, McCormack MC19, MacIntyre N20, Culver BH21, Scuirba FC22, Revill
SM23, Delafosse V24, Holland AE7,8,25
1 Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS
Trust, Leicester, United Kingdom
2 Faculty of Health and Life Sciences, Coventry University, Coventry; United Kingdom
3 Institute for Social and Preventive Medicine, University of Zurich, Ch-8001 Zurich,
Switzerland
4 Department of Research & Education; CIRO+, centre of expertise for chronic organ failure;
Horn, the Netherlands
5 Laboratory of Research in Respiratory Physiotherapy, Department of Physiotherapy,
UniversidadeEstadual de Londrina, Brazil.
6 Physiotherapy Department, Austin Health, Melbourne, Australia
7 Institute for Breathing and Sleep, Austin Health, Melbourne, Australia
8 Physiotherapy Department, Alfred Health, Melbourne, Australia
9 Faculty of Kinesiology and rehabilitation Sciences, Department of Rehabilitation Sciences,
Katholieke Universiteit Leuven, Leuven, Belgium.
10 Rehabilitation Research Center, BIOMED - Biomedical Research Institute, Faculty of

Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
11 Drexel University School of Medicine, Pittsburgh, Pennsylvania
12 Sleep Medicine and Lung Health Consultants, Pittsburgh, Pennsylvania
13 ATS Proficiency Standards for Pulmonary Function Laboratories Committee; Rochester,
Minnesota, USA
14 Axe maladies chroniques, Centre de recherche de lHpital du Sacr-Coeur de Montral,
Canada
15 Department of Exercise Science, Faculty of Arts and Science, Concordia University;
Montreal, Canada
16 Centre de recherche, Institut Universitaire de cardiologie et de pneumologie de Qubec,
Canada
17 Facult de mdecine; Universit Laval, Qubec, Canada.
18 University of Vermont College of Medicine, Burlington, VT USA
19 Johns Hopkins University, Pulmonary and Critical Care Medicine, Baltimore MD USA
20 Duke University, Durham NC, USA
21 Pulmonary and Critical Care Medicine, University of Washington, USA
22 University of Pittsburgh School of Medicine, Pittsburgh PA USA
23 The Orchard, Lowdham, Notts, United Kingdom
24 Health Sciences Library, Caulfield Hospital, Alfred Health, Caulfield, Victoria, Australia
25 Physiotherapy Department, La Trobe University, Melbourne, Australia
Corresponding Author:
Sally J Singh
Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust,
Leicester, United Kingdom
sally.singh@uhl-tr.nhs.uk
Phone +44 116 2502535
Fax +44 116 2583149
Date of submission: 27th December 2013

Word count: 9906
Key words: Exercise Test, Respiratory Tract Diseases, Reliability and Validity.
Acknowledgements: The realization of this systematic review was not possible without the
financial support of the ERS and ATS.
Table of Contents
Search strategies for 6-minute walk test (6MWT)
Search strategies for incremental shuttle walk test (ISWT)
Search strategies for endurance shuttle walk test (ESWT)
Specific inclusion criteria and outcomes for each systematic review question
Reliability additional data
Reliability of the 6-minute walk distance
Reliability of oxyhaemoglobin measures during the 6-minute walk test
Reliability of heart rate measures during the 6-minute walk test
Reliability of symptom scores during the 6-minute walk test
Validity Additional Data
Table S1. Characteristics of reliability studies for patients with COPD
Table S2. Intraclass correlation coefficients for 6-minute walk distance
Table S3. Proportion of individuals with COPD who had improved 6-minute walk distance on
repeat testing
Table S4 Characteristics of reliability studies for individuals with interstitial lung disease (ILD)
Table S5. Mean improvement in distance on second 6-minute walk test in interstitial lung
disease
Table S6 Characteristics of reliability studies for individuals with cystic fibrosis
Table S7. Mean improvement in distance on second 6-minute walk test in cystic fibrosis
Table S8. Reliability of oxyhaemoglobin measures during the 6MWT
Table S9 Reliability of heart rate measures during the 6-minute walk test
Table S10 Reliability of symptom scores measured during the 6MWT
Table S11 Characteristics of validity studies for patients with COPD
Table S12 Characteristics of validity studies for patients with interstitial lung disease
Table S13. Characteristics of validity studies for patients with systemic sclerosis
Table S14. Characteristics of validity studies for patients with cystic fibrosis
Table S15 Characteristics of validity studies for patients with pulmonary arterial
hypertension
Table S16. Relationship between 6MWD and disease severity in adults with COPD
Table S17. Relationship between 6MWD and disease severity in adults with ILD
Table S18. Relationship between 6MWD and disease severity in adults with SSc
Table S19. Relationship between 6MWD and measures of dyspnoea
Table S20. Relationship between 6MWD and measures of health-related quality of life
Table S21. Independent predictors of 6MWD in COPD
Table S22. Independent predictors of 6MWD in SSC
Table S23. Relationship between 6MWD and prognosis in COPD
Table S24. Relationship between 6MWD and prognosis in ILD
Table S25. Relationship between 6MWD and prognosis in PAH
Table S26. Relationship between 6MWD and prognosis in other lung diseases
Table S27 Associations between fatigue on 6MWD and measures of disease severity and
impact in adults with chronic respiratory disease
Table S28 Predictors of oxyhaemoglobin desaturation on 6-minute walk test in adults with
chronic respiratory disease
Table S29. Standardization of the 6-Minute Walking Test in studies with healthy individuals
Table S30. Full text assessment of papers on MID of 6MWT
Table S31. Description of studies that determined MID of the 6-minute walk test in patients with
chronic lung disease
Table S32. Description of studies designed to assess the responsiveness of shuttle walk tests in
patients with chronic lung disease
References
Search strategies for 6-minute walk test (6MWT)

Medline
1. ((six min$ walk$ or 6 min$ walk$ or 6MW or 6MWD or 6MWT) adj2 (test$ or
distance$ or work$)).ti,ab.
2. Walking/
3. Exercise Test/
4. 2 or 3
5. 1 and 4
6. Limit 5 to (human and yr=2000 2013)
Embase
1. ((six min$ walk$ or 6 min$ walk$ or 6MW or 6MWD or 6MWT) adj2 (test$ or
distance$ or work$)).ti,ab.
2. Walking/
3. Exercise Test/
4. 2 or 3
5. 1 and 4
Strategy was adapted for use in CINAHL, PEDro and the Cochrane Library.
Search strategies for incremental shuttle walk test (ISWT)

Medline
1. ((incremental shuttle walk$ or shuttle walk$ or ISWT$) adj2 (test$ or distance$ or
time$)).ti,ab.
2. (incremental adj3 endurance adj3 shuttle walk$).ti,ab
3. 1 or 2
4. Walking/
5. Exercise Test/
6. 4 or 5
7. 3 and 6
Embase
1. ((incremental shuttle walk$ or shuttle walk$ or ISWT$) adj2 (test$ or distance$ or
time$)).ti,ab.
2. (incremental adj3 endurance adj3 shuttle walk$).ti,ab
3. 1 or 2
4. Walking/
5. Exercise Test/
6. 4 or 5
7. 3 and 6
Search strategies for endurance shuttle walk test (ESWT)

Medline
1. endurance shuttle walk$.ti,ab.
2. (ESWT adj5 (walk$ or time$ or distance$)).ti,ab.
3. (Incremental adj3 endurance adj3 shuttle walk$).ti,ab.
4. 1 or 2 or 3
5. Walking/
6. Exercise Test/
7. 5 or 6
8. 4 and 7
9. Limit 8 to (humans and yr=2000 2013)
Embase
1. endurance shuttle walk$.ti,ab.
2. (ESWT adj5 (walk$ or time$ or distance$)).ti,ab.
3. (Incremental adj3 endurance adj3 shuttle walk$).ti,ab.
4. 1 or 2 or 3
5. Walking/
6. Exercise Test/
7. 5 or 6
8. 4 and 7
9. Limit 8 to (humans and yr=2000 2013)
Specific inclusion criteria and outcomes for each systematic review question
1. Are the 6MWT, ISWT and ESWT reliable and valid tests of exercise capacity in people
with chronic respiratory disease?
1a. What is the reproducibility of the 6MWT/ISWT/ ESWT tests in adults with chronic
respiratory disease?
1b. What kinds of validity have been demonstrated for the 6MWT/ISWT/ ESWT?
Inclusion criteria:
To determine reliability, we included studies that evaluated intra-rater or inter-rater
reliability of the 6MWT, ISWT or ESWT. There was no restriction on the time interval
between repeated tests.
To determine validity, we evaluated the relationship of the 6-minute walk distance (6MWD),
ISWT or ESWT to measures of physical fitness (cardiopulmonary exercise test, CPET), disease
severity, physical activity and patient reported outcomes (PRO) in cross-sectional studies.
Studies were included if their aim was to validate the field tests against the specified
measures; studies were not included where the 6MWD was used as a validation measure for
another outcome (eg used to validate a PRO). Survival was not addressed in this question.
Outcomes of interest: Measures of intra-rater and inter-rater reliability; measures of validity
for 6MWD, ISWT distance or time, ESWT distance or time.
2. Which methodological factors affect performance on field walking tests in adults with
chronic respiratory disease?
2a. Do track layout, use of oxygen and use of walking aids affect test performance?
Outcomes of interest: Differences in 6MWD, ISWT or ESWT outcomes related to
methodology used.
3. What is the relationship of 6MWT, ISWT or ESWT performance to clinical outcomes in

people with chronic respiratory disease?
3a. Does the 6MWT, ISWT or ESWT predict hospitalisation and survival in adults with
Inclusion criteria: Longitudinal studies were included.
Outcomes of interest: proportion of variability in hospitalisation or survival explained by
6MWD, ISWT or ESWT outcomes; odds ratios, hazard ratios or incidence rate ratios for the
association of 6MWD and mortality, respectively.
4. Which test parameters, apart from distance, should be reported from field walking tests
in people with chronic respiratory disease?
4a. Do test parameters derived from heart rate, oxyhaemoglobin saturation, body
weight, and symptoms provide additional information on patient outcomes when
compared to distance alone in adults with chronic respiratory disease?
Outcomes of interest: predictive value of new parameters compared to distance alone.
5. What kind of monitoring is required during the 6MWT, ISWT and ESWT in people with
5a. What is the rate of adverse events during field walking tests?
5b. How do different monitoring protocols affect detection of changes in heart rate
and oxyhaemoglobin saturation during field walking tests?
Outcomes of interest: rate of adverse events in different patient groups; effect of

differences in monitoring on detection of changes in heart rate and oxyhaemoglobin
saturation.
6. Which reference equations can be used for the 6MWT, ISWT and ESWT?
6a. Which variables determine performance on the 6MWT, ISWT and ESWT in
disease-free individuals?
6b. What proportion of variability in distance/time can be explained by reference
equations for the 6MWT/ISWT/ESWT?
Outcomes of interest: variables predicting distance/time and proportion of variability
explained in each population in cross-sectional analysis.
7. Can the 6MWT/ISWT/ ESWT identify clinically meaningful change in people with chronic
respiratory disease?
7a. How responsive is the 6MWT to clinical change in adults with chronic respiratory
disease?
7b. What is the MID for improvement and decline for the 6MWT, ISWT and ESWT in
adults with chronic respiratory disease?
Inclusion criteria: studies were included in this section if (1) their stated aim was to evaluate
test responsiveness OR (2) the study was a systematic review which reported the
responsiveness of the field walking test to an intervention of known effectiveness.
Outcomes of interest: measures of responsiveness, minimal important difference (MID)
estimates and their confidence intervals obtained from longitudinal studies, randomised
trials or observational studies.
Reliability additional data

Forty-four studies were retrieved in full text. Fourteen were excluded after full text review
(review articles n=7, no reliability data n=1, data related to other walk tests n=6).
Thirty studies were included in this section: 19 studies in COPD, six studies in CF, six studies
in ILD (of which two were also included in the COPD section) and one study in pulmonary
arterial hypertension (PAH). Twenty-nine studies examined the reliability of the 6MWD, nine
studies reported reliability of oxyhaemoglobin saturation (SpO2) measures, six studies
reported the reliability of heart rate (HR) and nine studies reported reliability of symptom
scores.
Reliability of the 6-minute walk distance

Chronic obstructive pulmonary disease
Participants: Nineteen studies examined the reliability of the 6MWD in people with COPD.
Sample sizes ranged from n=10 to n=1514, with a pooled total of 3162 participants. The
mean age ranged from 63 to 69 years. Most participants had moderate to severe disease, with
the mean FEV1predicted ranging from 26 to 62%. The characteristics of included studies for
participants with COPD are shown in Table S4.
Track lengths were reported in 12 studies. Where reported, the track lengths ranged from 26
120 meters, with a median track length of 39 meters.
Track layout was reported in 15 studies. Eleven papers (73%) reported using a straight track;
three (20%) used continuous tracks (oval, rectangular and triangular); and one paper (7%)
reported on tests conducted using a variety of track layouts.
Standardized encouragement during the 6MWT was used in eight studies (44%); five
studies (28%) stated that no encouragement was given; one study (6%)[1] compared
encouraged and non-encouraged tests; and five studies (28%) did not report whether
encouragement was provided.
Test-retest intervals varied. Seven studies repeated the 6MWT on the same day; five studies
repeated it the next day; five studies had a retest interval between two and 14 days. For tests
on the same day, the rest interval between tests was 20 minutes (n=1), 30 mins (n=4), 45
minutes (n=1) and not stated (n=1).
Predictors of an increased 6MWD on the second test
Two studies reported predictors of an improved 6MWD on the second test.
In a large sample of patients entering a pulmonary rehabilitation program [2], predictors of a
clinically important increase ( 42 meters) on the second walk were:
6MWD<350m (OR 2.49, 1.80 - 3.46)
absence of comorbidities (OR 0.76, 0.58 to 0.99)
BMI<30 kg.m-2 (OR 0.60, 0.43 to 0.85)
In a sample of patients with severe disease entering a trial of lung volume reduction surgery
[3], the only independent predictor of an increase in 6MWD on the second test was a higher
maximum inspiratory pressure (0.99 (0.34) ft.cmH2O, p<0.005).
Other measures reported
In a secondary analysis of data from the NETT trial, one study reported change in the 6MWD
over time with pulmonary rehabilitation, LVRS or usual care [4]. Calculating the change in
6MWD based on the best of two 6MWDs reduced the variance of the change scores by 14%
to 33% compared to using the first 6MWD alone. The authors suggest that using the best of
two 6MWDs will therefore reduce the required sample size for clinical trials by between 14
and 33%.
One study reported the effects of a repeat test on the proportion of individuals who recorded a
poor walk distance, defined as less than 350 meters [2]. Thirty-five percent of the patients
had a poor walk distance after the first 6MWT; after the second 6MWT this proportion
decreased to 28%.
Interstitial Lung Disease

Participants: Six studies examined the reliability of the 6MWD in people with ILD (Table
S4). Sample sizes ranged from n=21 to n=822, with a pooled total of 1100 participants. The
mean age ranged from 47 to 73 years and mean FVC from 59 81% predicted. Two studies
included participants with IPF [5, 6], two included participants with mixed ILDs [7, 8] and
two included participants with SScILD [9, 10].
Track lengths were reported in three papers and ranged from 20 45 meters.
Track layout was reported in three papers, all of which used straight tracks.
Standardized encouragement during the 6MWT was used in four studies, whilst two did
not report whether encouragement was used.
Test-retest intervals ranged from 30 minutes to four weeks.
Cystic Fibrosis
Participants: Six studies evaluated the reliability of the 6MWD in CF, with a pooled total of
123 participants. The mean age ranged from 11 to 24 years and the mean FEV1 from 61
94%predicted. The characteristics of included studies are shown in Table S6.
Track lengths were reported in five studies and ranged from 8 to 40 meters.
Track layout: a straight track was used in all six studies.
Standardized encouragement was used in four of the six studies.
Test-retest intervals ranged from 15 minutes to 6 months.
Pulmonary arterial hypertension

Participants: One study published in abstract form reported the effects of repeat testing on
the 6MWD in PAH [11].
Mean difference in 6MWD between tests: The mean difference in distance between two
6MWTs performed at an unspecified time interval was 16 meters (95%CI 9-23m).
Proportion improving on repeat 6MWT: 66% of individuals walked further on the second
6MWT [11].
Reliability of oxyhaemoglobin measures during the 6-minute walk test

Five studies evaluated the reliability of different measures related to oxyhaemoglobin
saturation (SpO2) during the 6MWT [2, 12-15] (Table S8). All studies used pulse oximetry to
obtain measures of SpO2.
Intra-class correlation coefficients: One study reported that the ICC for change in SpO2
during the 6MWT was 0.81 [2].
Coefficient of variation: no studies reported the coefficient of variation for SpO2 measures.
Mean difference in SpO2 between tests: Two studies reported that the mean difference in
SpO2 at the beginning or end of a repeat 6MWT was small, ranging from between -2% to
+2% [13, 14].
Limits of Agreement: one study reported that the limits of agreement for change in SpO2
with repeat 6MWT ranged from -7% to 8% [2].
Other measures: One study with 10 participants reported a significant difference in the SpO2
half way through the second 6MWT [12]. There was no significant difference in end-test
SpO2.
Detecting desaturation during the 6MWT
One study evaluated the agreement between repeat 6MWTs for detecting desaturation in a
group of patients undertaking pulmonary rehabilitation. Three 6MWTs were conducted over
a median of 11.5 days.
Desaturation of at least 4%: kappa = 0.52; 55/88 (63%) desaturated on all 3
tests while 76/88 (86%) did so on at least one test
Desaturation SpO288%: kappa = 0.62; 26/88 (30%) desaturated 88% on all
three tests while 51/88 (58%) did so on at least one test
A large study of 1514 participants reported that the sensitivity and specificity to detect
desaturation during the 2nd test based on SpO2 measures from the first test were 80% and
77% respectively; desaturation was defined as either a drop of at least 4% in SpO2 or end
SpO2<88% [2].
Interstitial Lung Disease

Two studies reported the reliability of SpO2 measures during the 6MWT in ILD [8, 10](Table
S8).
Intra-class correlation coefficients: one study in 30 individuals with SSc-ILD reported
differing ICCs depending on the location of the pulse oximeter probe [10]. The ICC for
forehead SpO2 measurements was 0.64, while the ICC for finger probe measurements was 0.6
and the ICC for earlobe SpO2 measures was 0.24. The authors postulated that this might be
related to the difficulty in a good quality oximetry signal in some patients with SSc-ILD.
Coefficient of variation: One study in a group of patients with IPF and NSIP reported that
the coefficient of variation for the magnitude of desaturation during the 6MWT was 0.283
[8].
Mean difference and limits of agreement: The mean difference for SpO2 at the end of the
6MWT using a finger probe was -1% with limits of agreement -17.5 15.5. Using a forehead
probe, the mean difference was 1.5% with limits of agreement -10 to 13% [10].
Detecting desaturation during the 6MWT: One study evaluated the agreement between
measures of desaturation obtained during 6MWTs performed one week apart [8]. The kappa
for desaturation 88% was 0.93.
Cystic Fibrosis
Two studies reported the reliability of SpO2 measures obtained during the 6MWT in CF
(Table S8).
Intra-class correlation coefficients: Two studies reported ICCs for SpO2 of 0.81 and 0.97
[16, 17].
Coefficient of variation: The coefficients of variation ranged from 0.009 for pre-test SpO2 to
1.04 for change in SpO2 [17].
Mean difference and limits of agreement: The mean differences between repeat 6MWTs
for change in SpO2 was 0.6% with limits of agreement of -3.9% to 5.2% [17].
Detecting desaturation during the 6MWT: No studies in CF reported agreement between
6MWTs in detecting desaturation.

No studies reported the reliability of SpO2 measures collected during the 6MWT in PAH.
Reliability of heart rate measures during the 6-minute walk test

Four studies evaluated the reliability of heart rate (HR) measured during the 6MWT [2, 1214]. One study obtained heart rate measures using a polar monitor, one used a pulse oximeter
and two studies did not state how HR variables were measured (Table S9).
Intra-class correlation coefficients: One study reported that the ICC for change in HR
during the 6MWT was 0.62 [2].
Coefficient of variation: One study reported a low coefficient of variation of 0.0387 [12].
Mean difference in HR between tests: Three studies reported that the mean difference in
HR at the beginning or end of a repeat 6MWT ranged from -2% to +8 bpm [13, 14].
Limits of Agreement: no studies reported the limits of agreement for HR measures.
Interstitial lung disease

No studies reported the reliability of HR measures collected during the 6MWT in ILD.
Cystic fibrosis
Two studies evaluated the reliability of HR measures during the 6MWT [16, 17]. One study
obtained HR measures from a pulse oximeter and the other did not state how the HR
measures were obtained (Table S9).
Intra-class correlation coefficients: The data were inconsistent, with one study reporting an
ICC of 0.82 for change in HR [16], whilst another reported ICCS of 0.52 and 0.28 for pre and
post HR respectively [17].
Coefficient of variation: one study reported CVs of 11.1 and 6.8 for pre and post HR
respectively [17].
Mean difference in HR between tests: No studies reported mean difference.
Limits of Agreement: no studies reported the limits of agreement for HR measures.
No studies reported the reliability of HR measures collected during the 6MWT in PAH
Reliability of symptom scores during the 6-minute walk test

Four studies reported reliability of symptom scores in patients with COPD (Table S10).
Intra-class correlation coefficients: One study reported similar ICCs for Borg dyspnoea and
VAS dyspnoea scores at the end of the 6MWT [18]. However another study reported a lower
ICC for change in Borg dyspnoea (0.59) and an identical ICC for change in Borg fatigue
(0.59)[2].
Coefficient of variation: One study reported a CV for VAS dyspnoea at the end of the
6MWT of 0.22 [12].
Mean difference in symptom scores between tests: Borg dyspnoea and fatigue scores
showed little variation with mean differences of 0-0.2 units [13, 14, 18]. VAS dyspnoea
scores had mean differences of 3.6mm [18] and 4mm [12].
Limits of Agreement: no studies reported the limits of agreement for symptom scores.
Interstitial lung disease

Three studies reported reliability of symptom scores in patients with ILD (Table S10).
Intra-class correlation coefficients: One study in patients with SSC-ILD reported an ICC
for Borg dyspnoea at the end of the test of 0.85 [10].
Coefficient of variation: No studies reported CVs for symptom scores in ILD.

Mean difference and limits of agreement: The mean difference in Borg dyspnoea scores at
the end of the 6MWT were reported as 0.8 units (LOA -1.36 to 2.96 units) [9] and -0.15 units
(-1.6 to 1.35 units)[10].
Other measures: One study reported weighted kappas for Borg dyspnoea at rest of 0.67 and
Borg dyspnoea at the end of the 6MWT of 0.79 [8].
Cystic fibrosis
Two studies evaluated the reliability of symptom scores during the 6MWT [16, 17].
Intra-class correlation coefficients: One study reported the ICC for change in Borg
dyspnoea as 0.92 and change in Borg fatigue as 0.66 6MWT [16].
Other measures: The kappa for the Borg dyspnoea score at the end of the 6MWT (0.71) was
higher than for the Borg fatigue scale (0.52) [17].

No studies reported the reliability of symptom scores during the 6MWT in PAH.
Validity Additional Data

78 studies were retrieved in full text. 27 were excluded after full text review (review articles
n=9, no validity data n=5, not the 6-minute walk test n=4, data for participants with chronic
lung disease not reported separately to other participants n=1, no outcomes of interest n=2).
67 studies were included in this section:
33 studies in chronic obstructive pulmonary disease (COPD)
12 studies in interstitial lung disease (ILD), one of which is also included in the
COPD section
7 studies in systemic sclerosis (SSc), one of which is also included in the ILD section
3 studies in cystic fibrosis (CF)
8 studies in pulmonary arterial hypertension (PAH), one of which is also included in

the SSc section and one in the ILD section
8 studies in other disease groups
Validity of 6MWD in other patient groups

The validity of the 6MWD has also been evaluated in patients with sarcoid [19],
bronchiectasis [20, 21], asbestos-related lung disease [22], patients awaiting lung
transplantation [23-25] and one group with a mixture of chronic lung diseases, many of
whom were being assessed for transplantation [26].
The 6MWD in sarcoid: A study of 142 participants with median age of 51 years, 87% of
whom were receiving systemic therapies, found significant relationships between the 6MWD
and FEV1 rS=0.518) and FVC (rS=0.529). There were also moderate relationships between
6MWD and all domains of the SGRQ (rS -0.67 to -0.50). The relationship to MRC dyspnoea
score was weak (rS=-0.06), however a stronger relationship was evident with Borg dyspnoea
at the end of the 6MWT (rS-0.47). Independent predictors of 6MWD were SGRQ activity
domain, FVC and lowest SpO2 on the 6MWT [19].
The 6MWD in bronchiectasis: In a study of 27 adults with bronchiectasis and moderately
impaired lung function, there were moderate correlations between the 6MWD and FEV1%
predicted (r=0.485) and FVC (r=0.513). The relationships between 6MWD and the domains
of HRQoL were stronger, with Pearsons r for the SGRQ total score of -0.82, and all domains
ranging from -0.768 to -0.642. The relationship between 6MWD and the physical component
score of the SF36 (r=0.709) was stronger than the relationship with the mental component
score (r=-0.0509). Independent predictors of 6MWD were SGRQ symptom, SGRQ activity
and generations of bronchial divisions involved [20]. An additional study found no
significant differences in HRQoL for adults with bronchiectasis who had a 6MWD above or
below the lower limit of normal, however the 6MWD was not analysed as a continuous
variable and the precision of this approach is not clear [21].
The 6MWD in patients awaiting transplantation: Two studies in which many of the
patients were undergoing assessment prior to lung transplantation reported moderate
relationships between the 6MWD and VO2peak [23, 26].
Table S1. Characteristics of reliability studies for patients with COPD

Study
Age
FEV1
6MWD Track
65(8) 0.97(0.25)L
Track
Encouraged Retest
length
layout
interval
450
33
straight
2 weeks
Guyatt 1984[1]
43
Guyatt 1985[27]
43
ns
0.97(0.25)L
ns
ns
straight
2 weeks
Leach 1992[28]
30
63(7)
0.74
266
ns
ns
ns
45 mins
299
51
straight
Same
(0.25)L
Cahalin 1995[23]
60
44 (11) 1.01(0.65)L
day
Roomi 1996[29]
15
76
49(5)%
196(98)
29
straight
2-10
days
Stevens 1999[30]
21
65(11)
1.07
374(77)
ns
straight
30 mins
498(117)
26
rectangle
1 week
(0.53)L
Rejeski 2000[31]
30
ns
ns
Irriberri 2002[32]
30
63(8) 1.27(0.31)L 508(57)
60
straight
20 mins
Troosters
20
66(6)
45(14)
539(56)
90
straight
ns
Eiser 2003[18]
23
69(8)
35(13)%
428
120
straight
30 mins
Poulain 2003[12]
10
67(2)
59(5)%
500(85)
31.5
straight
6 days
Sciurba 2003[3]
470
67(6)
26(7)%
370(94) variety
variety
1 day
Rodrigues
35
65(8)
62(24)%
515(82)
ns
ns
ns
1 day
Spencer 2008[14]
44
66(8)
56(19)%
491(82)
32
oval
30 mins
Chatterjee
88
75*
52(19)
362(117)
61
rectangular
ns
ns
2002[33]
2004[13]
2010[15]
26
Jenkins 2010[7]
245
68(9)
Kozu 2010[6]
45
67(5)
Hernandez
41(18)% 427(122)
45(12)
1514 64(10) 45(18)%
45
straight
30 mins
315(110)
30
straight
ns
1 day
391(99)
125
triangular
1 day
355*
ns
ns
ns
1 day
2011[2]
Chandra 2012[4]
396
68*
26*
* median; did not report reliability of 6MWD, SpO2 data only; ns not stated. FEV1 values
are reported as liters (L) or percent predicted (%).
27
Table S2. Intraclass correlation coefficients for 6-minute walk distance

Study
Diagnosis
Retest interval
ICC
Guyatt 1984[1]
COPD
43
2 weeks
0.909
Guyatt 1984[1]
COPD
43
2 weeks
0.921
Leach 1992[28]
COPD
30
45 mins apart
0.99
Cahalin 1995[23]
COPD
60
Same day
0.99
Sciurba 2003[3]
COPD
470
Next day
0.88
Eiser 2003[18]
COPD
23
1 week
0.923
Hernandez 2011[2]
COPD
1514
Next day
0.93
Mandrusiak
CF
16
Next day
0.93
Ziegler 2010[17]
CF
31
30 mins
0.94
Ziegler 2010[17]
CF
31
30 mins
0.93*
Du Bois 2011[5]
IPF
821
mean 24 days
0.82
Du Bois 2011[5]
IPF, not using oxygen 718
mean 24 days
0.83
103
mean 24 days
0.72
25
1 week
0.95
2009[16]
during test
Du Bois 2011[5]
IPF, using oxygen

during test
Wilsher 2012[10]
SSc
28
CF- cystic fibrosis; COPD chronic obstructive pulmonary disease; ICC intra-class
correlation coefficient; IPF idiopathic pulmonary fibrosis; SSc systemic sclerosis. * data
are %predicted 6-minute walk distance.
29
Table S3. Proportion of individuals with COPD who had improved 6-minute walk distance on repeat testing
Study
Timepoint
% walking further
% walking
on second test
significantly
further
Sciurba 2003[3]
470
1 day
70%
Spencer 2008[14]
44
Pre PR, same day
70%
44
Post PR , same
50%
15%
day
40
3 months, same
78%
day
Jenkins 2010[7]
245
Same day
87%
Hernandez 2011[2]
1514
1 day
82%
PR - pulmonary rehabilitation, N - number
30
28%
Table S4 Characteristics of reliability studies for individuals with interstitial lung disease (ILD)
Study
Diagnosis
Age
FVC
6MWD
Track
length
Track layout
Encouraged Retest interval
(m)
Eaton 2005[8]
IPF
29
73(9)
81(19)
426(143)
ns
ns
1 week
Buch 2007[9]
SSc ILD
163
52(12)
ns
398(84)
ns
ns
2 hours to 4
weeks
Jenkins 2010[7]
ILD
21
62(13)
59(18)
487(135)
45
Straight
30 mins
Kozu 2010[6]
IPF
35
67(8)
72(17)
325(113)
30
Straight
ns
1 day
Du Bois 2011[5]
IPF
822
66(8)
73(13)
392(108)
20-40
straight
ns
ns
Wilsher 2012[10]
SSc ILD
30
47(12)
77(20)
503*
ns
ns
1 week
Data are mean (SD) except for *median. NS- not stated; y- yes; 6MWD 6-minute walk distance; FVC forced vital capacity; N- number; nsnot stated; m- metres; y- yes.
31
Table S5. Mean improvement in distance on second 6-minute walk test in interstitial lung disease
Study
Diagnosis
Mean difference
95% confidence interval
Limits of agreement
metres
metres
metres
Buch 2007[9]
SSc-ILD
163
20.75
Kozu 2010[6]
IPF
25
11
7 -15
Jenkins 2010[7]
ILD
21
41
27 - 55
SSc-ILD
Wilsher 2012[10]
Pooled Mean
19.55
IPF Idiopathic pulmonary fibrosis; N Number; SSc-ILD - systemic sclerosis interstitial lung disease.
32
-54 to 69
Table S6 Characteristics of reliability studies for individuals with cystic fibrosis

Study
Age
FEV1
6MWD
Track
%predicted
length m
Track layout
Encouraged Retest interval
Gulmans 1996[34]
23
11(2)
94(17)
742(90)
Straight
1 week
Nixon 1996[35]
15(3)
41(20)
407(143)
40
Straight
6 months
Guillen 1999[36]
29
16(4)
83(25)
477(48)
35
Straight
Ns
15 minutes
Cunha 2006[37]
16
11(2)
63(21)
598 (57)
28
Straight
30 minutes
Mandrusiak 2009[16]
16
13(3)
65(18)
ns
Ns
Straight
1 day
Ziegler 2010[17]
31
24(7)
61(28)
590(72)
30
Straight
60 minutes
Data are mean (SD) except for *median. 6MWD 6-minute walk distance; FEV1 forced expiratory volume in one second; N - number; ns - not
stated; m metres; y- yes;.
.
33
Table S7. Mean improvement in distance on second 6-minute walk test in cystic fibrosis
Study
Mean difference
95% confidence interval
Limits of agreement
metres
metres
metres
--16 - 4
-59 - 48
Gulmans 1996[34]
23
Guillen 1999[36]
29
-6
Cunha 2006[37]
16
16
-101 - 133
Ziegler 2010[17]
31
-75 - 62
Pooled Mean
4.18
n- number
34
Study
Diagnosis
Measure
ICC
95% CI for ICC
Coefficient of
Mean
Limits of
variation
difference
agreement %
%
Rodrigues 2004[13]
Spencer 2008[14]
Hernandes 2011[2]
COPD
COPD
SpO2 pre
SpO2 post
-2
SpO2 pre
SpO2 post
COPD
Change in SpO2
Eaton 2005[8]
IPF
Change in SpO2
Wilsher 2012[10]
SSc-
Change in SpO2
ILD
forehead
Change in SpO2 finger
0.81
-7 to 8
0.283
0.64
1.5
-10 to 13
0.60
-1
-17.5 to 15.5
Change in SpO2 earlobe 0.24

Mandrusiak 2009[16]
CF
Change in SpO2
0.81
0.50 0.87
Ziegler 2010[17]
CF
SpO2 pre
0.94
0.87 - 0.97
0.009
SpO2 post
0.97
350.94 - 0.99
0.017
Change in SpO2 pre -
0.92
0.84 - 0.96
0.04
0.6
-3.9 to 5.2
post
Table S8. Reliability of oxyhaemoglobin measures during the 6MWT
CF cystic fibrosis; CI confidence interval; COPD chronic obstructive pulmonary disease; ICC intra-class correlation coefficient; IPF
Idiopathic pulmonary fibrosis; SSc-ILD Systemic sclerosis -interstitial lung disease; SpO2 oxyhaemoglobin saturation.
36
Table S9 Reliability of heart rate measures during the 6-minute walk test
Study
Diagn
Measure
Method
ICC
95% CI for ICC Coefficient of
osis
variation
Poulain 2003[12]
COPD
HR post
Polar monitor
Rodrigues 2004[13]
COPD
HR pre
ns
0.0387
COPD
HR pre
Mandrusiak
Pulse oximeter
bpm
bpm
-2
COPD
Change in HR
ns
0.62
CF
Change in HR
Pulse oximeter
0.87
0.63-0.95
CF
HR pre
ns
0.52
0.008 - 0.77
11.1
0.28
-0.49 - 0.65
6.8
HR post
agreement
2009[16]
Ziegler 2010[17]
difference
HR post
Hernandes 2011[2]
Limits of
-4
HR post
Spencer 2008[14]
Mean
37
COPD chronic obstructive pulmonary disease; ILD interstitial lung disease; CF cystic fibrosis; HR heart rate; ICC intraclass correlation
coefficient; CI confidence interval; bpm beats per minute; ILD interstitial lung disease; ns not stated
38
Table S10 Reliability of symptom scores measured during the 6MWT

Study
Diagn
Measure
ICC
95% CI for ICC Coefficient of
osis
Mean
Limits of
variation
difference
agreement
0.22
4mm
Poulain 2003[12]
COPD
VAS dyspnoea end
Eiser 2003[18]
COPD
Borg dyspnoea end
0.74
0.2 units
VAS dyspnoea end
0.72
3.6mm
Rodrigues 2004[13]
COPD
Borg dyspnoea end
Borg fatigue end
0
0
Spencer 2008[14]
COPD
Borg dyspnoea end
Hernandes 2011[2]
COPD
Change in Borg
0.59
Changedyspnoea
in Borg fatigue
0.59
Eaton 2005[8]
Buch 2007[9]
ILD
SSc-
kappa
Borg dyspnoea at rest
0.67*
Borg dyspnoea end
0.79*
Borg dyspnoea end
0.8
ILD
39
-1.36 to 2.96
Wilsher 2012[10]
SSc-
Borg dyspnoea end
0.85
-0.15
Change in Borg
0.92
0.56-0.95
Change in 15c dyspnoea 0.66
0.02-0.88
-1.6 to 1.35
ILD
Mandrusiak
CF
2009[16]
Ziegler 2010[17]
dyspnoea
CF
Borg dyspnoea pre
-0.79
Borg dyspnoea post
0.71
Borg fatigue pre
0.34
Borg fatigue post
0.52
* weighted kappa. CF cystic fibrosis; CI confidence interval ; COPD chronic obstructive pulmonary disease; ICC intraclass correlation
coefficient; ILD interstitial lung disease; SSc systemic sclerosis; SpO2 oxyhaemoglobin saturation.
40
Table S11 Characteristics of validity studies for patients with COPD

Study
Age
FEV1
6MWD
Variables measured
%pred
Annegarn 2012[38]
79
64(9)
54(19)
452(106)
FEV1
Borges 2012[39]
20
69(11)
49(14)
373(135)
Physical activity
1217 67 (6)
67(6)
348(95)
FEV1, HRQoL, dyspnoea
Brown 2008[40]
Bruyneel 2012[41]
82
62(10)
56(19)
477(89)
Respiratory function, HRQoL
Carter 2003[42]
124
67(7)
46(13)
403(82)
VO2peak, Wpeak
Chandra 2012[43]
396
68**
26**
355**
Change in Wpeak, FEV1, HRQoL,

dyspnoea
Chen 2012[44]
150
67
60
460
Chuang 2001[45]
27
65(6)
49(10)
456(84)
Diaz 2010[46]
81
67 (8)
64(24)
FEV1>50%:
FEV1
FEV1, VO2peak
VO2peak
512(80)
FEV1<50%:
430(87)
Garcia-Aymerich
341
68(9)
52(16)
442(95)
Physical activity
Garcia-Rio
110
63(8)
47(14)
314(125)
Physical activity
2009[48]
Guyatt
1985a[49]
25
65(8) 0.97(0.25)L*
Hernandes
40
66(8)
46(16)
419(111)
Physical activity
2009[50]
Hill
2008[51]
50
68(8)
37(11)
464(110)
VO2peak, Wmax
2009[47]
41
Cycle ergometer
Hill 2012[52]
26
66(7)
50(16)
466(66)
Physical activity
Hillman 2012[53]
26
71(8)
32(11)
349(146)
FEV1, dyspnoea
Holland 2010[54]
75
70(9)
52(21)
359(104)
Participant rating of change in

walking
Kozu 2010[6]
45
67(5)
45(12)
315(110)
Peak power
Luxton 2008[55]
22
65(9)
52(20)
508(83)
Wpeak
Mak 1993[56]
42
62(9)
40(22)
406 (149)
Oga 2002[57]
36
69(7)
40(17)
492(66)
FEV1, dyspnoea
FEV1, dyspnoea, HRQoL, Wpeak,
VO2peak, endurance
Rambod 2012[58]
1273
64
56
366
FEV1
Redelmeier
112
67(10) 0.98(0.45)L*
371(129)
Participant rating of walking
Rejeski 2009[31]
209
67(6)
57(17)
496(116)
FEV1, dyspnoea,HRQoL, VO2peak
Roomi 1996[29]
17
76
49(5)
195(98)
dyspnoea
Santos 2009[60]
91
65(9)
63(25)
476(99)
FEV1
Satake 2003[61]
12
72(7)
54(22)
490(93)
Wpeak
Sillen 2012[62]
2906
63(9)
44(18)
400(120)
Wpeak
Starobin 2006[63]
50
64(12)
46(20)
435(88)
VO2peak
Troosters 2002[33]
20
66(6)
45(14)
539
VO2peak
Turner 2004[64]
20
64(8)
29(8)
475(88)
VO2peak, Wpeak
Van Gestel
154
63(11)
43(19)
452(106)
FEV1
370
62(6)
49(13)
NS
1997[59]
2012[65]
Waatervik 2012[66]
42
FEV1, dyspnoea, physical activity
Wijkstra 1994[67]
40
62(5)
44(11)
448(105)
Wpeak, HRQoL, RFTs
* data reported as Litres; ** median; ns not stated. 6MWD 6-minute walk distance; FEV1
forced expiratory volume in one second; HRQoL healthrelated quality of life; N
Number; RFTs respiratory function tests; VO2peak peak oxygen uptake; Wpeak peak
workload on incremental cycle ergometer.
43
Table S12 Characteristics of validity studies for patients with interstitial lung disease
Study
Diagnosis
Age
FVC
6MWD
Variables measured
Pulmonary hypertension
%pred
Andersen
ILD
212
61(15)
71(30)
424(116)
Baldi 2012[69]
LAM
40
42(11)
93(15)
547*
Blanco
DILD
13
63(9)
73(22)
451(80)
2012[68]
2010[70]
Chetta
VO2peak
Cardiorespiratory
responses
ILD
40
ILA in
194
smokers
IPF
822
54(14)
87(26)
487(96)
FVC, TLCO
2001[71]
Doyle 2012[72]
du Bois
64(56-72) 88(77-98) 403(308-480)* FVC, dyspnoea, HRQoL

66(8)
73(13)
392(109)
2011[5]
Eaton 2005[8]
FVC, TLCO, dyspnoea,

HRQoL
IPF
29
73(9)
VO2peak, FVC%pred,
TLCO%pred
Garin 2009[73]
IPF
48
63
NS
379
Holland
ILD
48
69(9)
78(16)
403(118)
ILD
15
70(12)
NR
NR
FVC%pred, TLCO%pred
Patient rating of change
2009[74]
Holland
2010[75]
Cardiorespiratory
responses
Kozu 2010[6]
IPF
35
67(8)
72(17)
325(113)
Wpeak
Minai 2012[76]
IPF
124
55(9)
49(15)
348(88)
FVC%pred, TLCO%pred,
mPAP
44
All data are mean (SD) except * median and interquartile range. 6MWD 6-minute walk
distance; DILD diffuse interstitial lung disease; FVC forced vital capacity; HRQoL
health-related quality of life; ILA interstitial lung abnormalities; ILD interstitial lung
disease; IPF idiopathic pulmonary fibrosis; LAM ymphangioleiomyomatosis; mPAP
mean pulmonary artery pressure; n number; NR not reported; TLCO transfer factor of
the lung for carbon monoxide; VO2peak peak oxygen uptake; Wpeak peak workload on
incremental cycle ergometer.
45
Table S13. Characteristics of validity studies for patients with systemic sclerosis
Study
Diagnosis
Age
FVC
6MWD
Variables measured
%pred
Buch 2007[9]
SSc-ILD,
163
52(12)
398(84)
worsening over
FVC%pred,
TLCO%pred, dyspnoea
12 months
Cuomo 2012[5]
SSc
63
56*
ns
Deuschle 2011[77]
SSc
95
56*
99 (56-
420*
HRQoL
491(86665) FVC%pred, TLCO%pred
128)*
Garin 2009[73]
SSc-ILD
80
52(46-
ns
349
FVC%pred, TLCO%pred
60)
Mainguy 2011[78]
SSc-PAH
10
58(10)
Schoindre2009[79]
SSc
87
55(13)
349 (129) Physical activity
97(25)
461(103) FVC%pred,
TLCO%pred, SPAP
Villalba 2007[80]
SSc
110
45.5*
81.5*
FVC, SPAP
All data are mean (SD) except *median and range. 6MWD 6-minute walk distance; ILD
interstitial lung disease; ILA interstitial lung abnormalities; PAH pulmonary arterial
hypertension; FVC forced vital capacity; HRQoL health-related quality of life; ns not
stated; n number; PAH pulmonary arterial hypertension; SSc- systemic sclerosis; TLCO
transfer factor of the lung for carbon monoxide; SPAP systolic pulmonary artery pressure.
46
Table S14. Characteristics of validity studies for patients with cystic fibrosis
All data are mean (SD). 6MWD 6-minute walk distance; FEV1 forced expiratory volume
Study
Age
FEV1
6MWD (m)
Variables measured
%pred
Chetta 2001[57]
25
25(5)
69(23)
626(49)
Respiratory function
Troosters 2009[81]
64
26(8)
65(19)
702(82)
Physical activity
Zeigler 2007[82]
41
23.7(6.5)
55(28)
557(77)
Respiratory function,
dyspnoea
in one second; n number.
47
Table S15 Characteristics of validity studies for patients with pulmonary arterial
hypertension
Study
Diagnosis
Age
mPAP
Blanco
PAH
14
42(15)
49(11)
6MWD (m) Variables measured

542(100) Cardiorespiratory
2010[70]
Cicero
responses
PAH
34
36*
PAH
20
53(3)
EIPAH
17
57(13)
PAH
15
47(15)
PAH
43
37
399*
HRQoL
57(8)
450(22)
VO2peak
18(4)
575(86)
VO2peak, cardiac output
2012[83]
Deboeck
2005[84]
Fowler
2011[85]
Mainguy
401 (89) Physical activity
2011[78]
Miyamoto
332*
2000[86]
Pulmonary
hemodynamics,
VO2peak
Pugh
PAH
20
54(14)
46(13)
CTEPH
50
53(14)
48(14)
Physical activity
2012[87]
Reesink
391(134) Pulmonary
2007[88]
hemodynamics
All data are mean (SD) except for *median. CTEPH chronic thromboembolic pulmonary
hypertension; EIPAH exercise induced pulmonary hypertension; HRQoL health-related
quality of life; mPAP mean pulmonary artery pressure; N number; PAH pulmonary
arterial hypertension; VO2peak peak oxygen uptake.
48
Table S16. Relationship between 6MWD and disease severity in adults with COPD
Study
Diagnosis
Variable
Pearsons r
Spearmans
rho
Mak 1993[56]
COPD
42
FEV1 %pred
0.53
Wijkstra
COPD
40
FEV1 %pred
0.55
COPD
209
FEV1 %pred
0.37
COPD
27
FEV1 %pred
0.31
Oga 2002[89]
COPD
36
FEV1 %pred
Brown
COPD
1217
FEV1 %pred
0.38
COPD
91
FEV1 %pred
0.40
COPD
370
FEV1 %pred
0.34
1994[67]
Rejeski
2000[31]
Chuang
2001[45]
0.41
2008[40]
Santos
2009[60]
Waatervik
2012[66]
49
Chen 2012[44]
COPD
150
FEV1 %pred
0.17 mild COPD

0.05 mod COPD
0.47 severe COPD
0.59 v severe
COPD
Annegarn
COPD
79
FEV1
0.452
COPD
26
FEV1
0.7
COPD
154
FEV1 %pred
0.56
COPD
82
FEV1
0.54
2012[38]
Hillman
2012[53]
Van Gestel
2012[65]
Bruyneel
2012[41]
N number; COPD chronic obstructive pulmonary disease; FEV1 forced expiratory
volume in one second.
50
Table S17. Relationship between 6MWD and disease severity in adults with ILD
Study
Variable
Pearsons r
ILD
40
FVC %pred
0.4
IPF
29
FVC %pred
IPF
46
FVC %pred
ILA
194
FVC %pred
0.38
IPF
822
FVC %pred
0.121
IPF
124
FVC %pred
IPF
29
DLCO %pred
ILD
40
DLCO %pred
0.42
IPF
46
DLCO %pred
0.59
Diagnosi
Spearmans rho
s
Chetta
2001[71]
Eaton
0.06
2005[8]
Garin
0.36
2009[73]
Doyle
2012[72]
Du Bois
2011[5]
Minai
0.1
2012[76]
Eaton
0.61
2005[8]
Chetta
2001[71]
Garin
2009[73]
51
Du Bois
IPF
822
DLCO %pred
IPF
124
DLCO %pred
0.135
2011[5]
Minai
0.3
2012[76]
DLCO carbon monoxide diffusing capacity; FVC forced vital capacity; ILD
interstitital lung disease; IPF idiopathic pulmonary fibrosis; ILA interstitial lung
abnormalities; ILD interstitial lung disease; n number.
52
Table S18. Relationship between 6MWD and disease severity in adults with SSc
Study
Diagnosis
Variable
Pearsons r
Spearmans rho
Buch 2007[9]
SSc-ILD
163
FVC%pred
0.19
Garin
SSc-ILD
80
FVC%pred
0.12
SSc
87
FVC%pred
0.37
SSc
95
FVC%pred
0.309
Buch 2007[9]
SSc-ILD
163
TLCO%pred
0.06
Garin
SSc-ILD
80
TLCO%pred
0.23
SSc
87
TLCO%pred
0.49
SSc
95
TLCO%pred
0.336
sPAP
0.44
2009[73]
Schoindre
2009[79]
Deuschle
2011[77]
2009[73]
Schoindre
2009[79]
Deuschle
2011[77]
Schoindre
SSc
2009[79]
FVC forced vital capacity; N number; SSc ILD systemic sclerosis interstitial lung
disease, sPAP systolic pulmonary arterial pressure; TLCO - transfer factor of the lung for
carbon monoxide
53
Table S19. Relationship between 6MWD and measures of dyspnoea
Study
Diagnosis
Dyspnoea Measure
Pearsons r
Spearmans
rho
Mak
COPD
42
MRC scale
-0.52
COPD
209
0-10 rating scale
-0.38
COPD
36
Oxygen cost diagram
0.66
COPD
1217
UCSD SOBQ
-0.37
COPD
26
Modified MRC scale
-0.7
ILA
194
Modified MRC scale
-0.48
IPF
822
UCSD SOBQ
-0.29
CF
41
Borg post 6MWT
1993[56]
Rejeski
2000[31]
Oga
2002[89]
Brown
2008[40]
Hillman
2012[53]
Doyle
2012[72]
Du Bois
2011[5]
Zeigler
NR (not sig)
2007[82]
COPD chronic obstructive pulmonary disease; ILA interstitial lung abnormalities; IPF
idiopathic pulmonary fibrosis; MRC medical research council; N number; NR not
reported; not sig not statistically significant; UCSD SOBQ University of California San
54
Diego Shortness of Breath Questionnaire..
55
Table S20. Relationship between 6MWD and measures of health-related quality of life
Study
Wijkstra 1994[67]
Diagnosis
COPD
42
HRQoL measure
Pearsons
Spearmans
rho
CRQ fatigue
0.03
CRQ emotional function
0.02
CRQ mastery
0.25
CRQ dyspnoea
0.41
Roomi 1996[29]
COPD
17
Log CRQ dyspnoea
0.65
Rejeski 2000[31]
COPD
209
CRQ fatigue
0.25
CRQ emotional function
0.08
CRQ mastery
0.25
Oga 2002[89]
Brown 2008[40]
Bruyneel
COPD
COPD
COPD
36
SGRQ activity
-0.68
SGRQ total
-0.56
1217 SF-36 PCS
82
0.19
SGRQ symptoms
-0.03
SGRQ activity
-0.35
SGRQ impacts
-0.22
SGRQ total
-0.26
SGRQ activity
-0.45
56
2012[41]
SGRQ symptoms
-0.24
SGRQ total
-0.42
Du Bois 2011[5]
IPF
822
SGRQ total
-0.255
Doyle 2012[72]
ILA
194
SGRQ total
-0.48
Cuomo 2012[90]
SSc
63
SF36 PCS
0.41
Dale 2013[22]
ARPD
25
SGRQ total
-0.57
SGRQ activity
-0.50
Cicero 2012[83]
PAH
31
SF36 physical functioning
0.44
SF36 role physical
-0.02
SF 36 bodily pain
-0.03
SF36 general health
0.24
SF36 vitality
0.32
SF36 social functioning
0.18
SF36 role emotional
-0.014
SF36 mental health
0.19
ARPD asbestos related pleural disease; COPD chronic obstructive pulmonary disease;
CRQ chronic respiratory questionnaire; HRQoL health-related quality of life; ILA
interstitial lung abnormalities; ILD interstitial lung disease; PAH pulmonary arterial
hypertension; SSc- systemic sclerosis; SGRQ St Georges Respiratory Questionnaire; SF36
PCS SF36 physical component score; SF36 short form 36.
57
Table S21. Independent predictors of 6MWD in COPD
Study
Predictors
r- squared
Brown 2008[40]
SGRQ total score
0.31
FEV1%pred
Female gender
Height
Weight
Age
Bruyneel 2012[41]
FEV1
0.35
TLC
IC
TLCO/VA
Mak 1993[56]
TLCO
0.50
Age
Peak expiratory flow
Oga 2002[89]
Oxygen cost diagram
0.36
Roomi 1996[29]
Maximal expiratory mouth pressure
0.70
Calorie intake
BMI
Wijkstra 1994 [67]
PImaxPOES
TLCO
Inspiratory vital capacity
58
0.62
Residual volume
FEV1
Dyspnoea
BMI body mass index; FEV1 forced expiratory volume in one second; IC inspiratory
capacity; PImaxPOES peak oesophageal pressure during inspiration; SGRQ St Georges
Respiratory Questionnaire; TLC total lung capacity; TLCO - transfer factor of the lung for
carbon monoxide/ alveolar volume.
59
Table S22. Independent predictors of 6MWD in SSC
Study
Diagnosis
Predictors
r- squared
Villalba 2007[80]
SSc
Age
ns
Ethnicity
Dyspnoea index
Garin 2009[73]
SSc
Pre 6MWT Borg

Minimum SpO2 during
6MWT Resting SpO2
gender
0.26
All SSc without lower limb Pre 6MWT Borg

pain
Minimum SpO2 during

6MWT Resting SpO2
gender
SSc-ILD
0.36
DLCO%pred
Minimum SpO2 during
6MWT
Pre 6MWT Borg
0.46
SSc-PH
Post 6MWT Borg
0.41
SSc with both PH and ILD
Minimum SpO2 during

6MWT
0.29
SSc with neither PH or ILD Minimum SpO2 during

6MWT
60
0.32
Schoindre 2009[79] SSc
Presence of calcinosis
ns
6MWT 6-minute walk test; DLCO diffusing capacity for carbon monoxide; ILD
interstitial lung disease; PH pulmonary hypertension; SpO2 oxyhaemoglobin saturation in
arterial blood; SSc systemic sclerosis; ns not stated.
61
Table S23. Relationship between 6MWD and prognosis in COPD

6MWD Threshold
Sample FollowStudy
Findings
(n=)
up
Mortalit Hospitalizatio
y
n
The inability to walk 200m in 6MWT is
Szekely
excellent preoperative predictor of
47
6-12 mo
<200
<200
unacceptable post operative outcomes
1997[91]
which are related to death within 6 months
or hospital course >3 weeks
A longer 6MWD were associated with
Bowen
increase survival. For every 30m increase in
(133)
44 mo
<300
2000[92]
6MWD, estimated survival was increased by
approximately 11%
In severe COPD, the 6MWD predicts
mortality better than other traditional
Pinto-Plata
markers. 6MWD was significant predictor of
198
24 mo
<200
2004[93]
survival with a risk ratio of death 0.82 per
50m increase in 6MWD. The rate of decline
6MWD was -26m.yr-1
The 6MWD declines over time, but the
Casanova
decline is really significant in severe COPD
294
60 mo
(FEV1<50%pred). During 3yrs follow-up,
2007[94]
patients who died had a steeper rate of
decline (-25m.yr-1)
The 6MWD is as good predictor of mortality
as the peak VO2 in patients with COPD.
Cote2007
Patients with 6MWD <250m have a 5-year
365
60 mo
<250
[95]
survival rate only 26%. Survival decreases
by 20% for each one hundred meter
difference in 6MWD
The 6MWT was very useful for predicting
Takigawa
the prognosis in COPD patients. Short
144
96 mo
<340
2007[96]
walking distance <340m is an independent
predictor of the risk of death
The 6MWT helps predict mortality primarily
Casanova
in patients with severe COPD
576
60 mo
<361
2008[97]
(FEV1<50%pred)
Cote
2008[98]
1379
55 mo
<350
62
A 6MWD <350m is associated with

increased mortality and should be regarded
as abnormal.
Puhan
2009[99]
Enfield
2010[100]
Torres
2011[101]
Spruit
2012[102]
Ozgur
2012[103]
Tertemiz
2012[104]
574
815
223
2110
73
427
36 mo
PR
length
49 mo
36 mo
<350
<200
<350
<334
<357
A new point system based on the updated

BODE index is assigned to give a higher
number of points to 6MWD than other
variables because it was the strongest
predictor of mortality.
Differences from the pre to post 6MWD
(6MWD) was related with the length of
survival. For 6MWD, the upper tertile was
>113m, middle tertile 52 to 113m, and
lower tertile <52m with median survival
rate of 50.4, 34.4 and 33.7 months
respectively
A 350m 6MWD is a valid threshold to
differentiate survival in women
independently of age
The 6MWD provides prognostic information
that may be useful for identifying high-risk
patients with COPD
47 mo
<440
The cumulative survival rate was

significantly lower in the patients with
IC/TLC > 4 and with 6MWD < 439.56 m,
using these values as thresholds
16 mo
<336
The 6MWD was correlated with mortality
Parenthesis includes the number of COPD patients. This study also included patients with
other lung diseases.
6MWT 6-minute walk test; 6MWD 6-minute walk distance; < - less than; BODE body mass index, obstruction, dyspnoea and exercise capacity index; COPD chronic
obstructive pulmonary disease; FEV1 forced expiratory volume in one second; IC
inspiratory capacity; mo months; n - number; TLC total lung capacity; VO2max peak oxygen uptake
63
Table S24. Relationship between 6MWD and prognosis in ILD

6MWD Threshold
Follo
Study
n
wup
Mortalit Hospitalizatio Diagnosi
y
n
s
Lama
2003[105]
Lederer
2006[106]
Lettieri
2006[107]
Han 2008[108]
Caminati
2009[109]
Swigris
2009[110]
Andersen
2012[111]
105
36 mo
IIP
454
4 mo
<207
IPF
81
12 mo
<300
IPF
215
12 mo
IPF
44
12 mo
<212
IPF
76
16 mo
IPF
212
13 mo
<345
ILD & PH
64
Findings
The knowledge of desaturation
(88%) during 6MWT adds
prognostic information for
patients with usual and
nonspecific interstitial
pneumonia
Patients with 6MWD <207m had
a more than fourfold greater
mortality rate than those who
walked more than 207m. Lower
6MWD was strongly associated
with mortality for walt-listed IPF
patients
Distance saturation product
(DSP) was predictor of mortality.
The most accurate DSP
breakpoint (200m%) was
slightly more predictive of
mortality than the 6MWD
(300m) or SpO2 (88%)
Females with IPF who did not
desaturate below 88% have
better survival compared to
males who did not desaturate
below 88% during the 6MWT
The 6MWD can serve as a
surrogate outcome
measurement and reflect the
risk of progression to death.
Patients with 6MWD <212m
had significantly lower survival
than those walking farther
Abnormal Heart Rate Recovery
after 6MWT predicts mortality
in IPF patients
Mortality was higher in PH
patients, and the presence of PH
reduced 6MWT independently
of lung function and the
presence of IPF. A 6MWD

<345m is an independent risk
factor for PH which is related
with mortality
Impaired chronotropic response
Holland
IPF & other to 6MWT is associated with
62 48 mo
2013[112]
ILD
reduced 6MWD and reduced
survival
6MWD 6-minute walk distance;6MWT 6-minute walk test; < - less than; - less
than or equal to; IIP idiopathic interstitial pneumonia; DSP distance saturation
product; ILD interstitial lung disease; IPF idiopathic pulmonary fibrosis; mo
months; n number; PH pulmonary hypertension; SpO2 oxyhaemoglobin saturation
of arterial blood.
65
Table S25. Relationship between 6MWD and prognosis in PAH

6MWD Threshold
Follo
Study
n
w
up
y
n
s
Miyamoto
2000[113]
Paciocco
2001[114]
Saouti
2009[115]
Lee
2010[116]
Benza
2010[117]
Minai
2012[118]
Lee
2012[119]
43
21 mo
<332
PPH
34
26 mo
300
PPH
84
32 mo
<298
CTEPH
137
6 mo
IPAH
2716
17 mo
<340
PAH
75
13 mo
<332
IPAH
182
25 mo
<300
PAH
66
Findings
The 6MWD is the only variable
independently r elated to
mortality in PPH. Patients
walking <332 m had a
significantly lower survival rate
than those walking farther
A 6MWD 300m increased
mortality risk by 2.4 and SaO2
of 10% increased mortality risk
by 2.9. An 18% reduction in risk
of death occurred with each
50m increase in distance
Patients with 6MWD <298m had
a significantly lower survival
rate than those with a higher
6MWD
The 6MWD % predicted could
help clinicians to interpret the
6MWT but its prognostic value
is not superior to that absolute
6MWD
PAH associated with low 6MWD
predicts mortality. Based on risk
stratification a 6MWD of 340m
and 200m is high and very high
risk factor for mortality in 1st
year, respectively.
A 6MWD <332m demonstrated
increased hazard ratio for
worsening events. The addition
of Heart Rate Recovery to
6MWD increases the capacity of
6MWD to predict clinical
worsening.
A 6MWD <300 was retained as
independent predictor of
mortality
Nickel
2012[120]
Scholzel
109
32
38 mo
<358
IPAH
41 mo
CTEPH
2012[121]
Baseline 6MWD of 358m was

an independent predictor of
mortality in the multivariate
model
The 6MWD was predictor for
survival
6MWD 6-minute walk distance; < - less than; - less than or equal to; - greater than
or equal to; CTEPH chronic thromboembolic pulmonary hypertension; IPAH
idiopathic pulmonary arterial hypertension; mo months; n - number; PAH pulmonary
arterial hypertension; PPH primary pulmonary hypertension
67
Table S26. Relationship between 6MWD and prognosis in other lung diseases
6MWD Threshold
Follo
Study
n
w
Findings
up
y
n
s
Prognostic values of 6MWD
Budweiser
absolute and % predicted were
424
72 mo
<303
CHRF
observed in patients with median
2008[122]
values as cutoff 303m or 6MWD
64.8%pred, respectively
6MWD was a significant predictor
of survival after adjusting for
other important covariates when
transplant was considered as a
Martinu
LTC
time-varying covariate. 6MWD
376
28 mo
<274
2008[123]
mixed
remained an important predictor
of survival among patients with
lung transplant. 6MWD
Improvement of 152m leads to
50% reduce of mortality.
6MWD is useful for stratifying
patients on the LT waiting list by
Tuppin
LTC
identifying those patients with a
163
17 mo
315
2008[124]
mixed
significantly higher risk of
mortality. Each meter increase in
the 6MWD has protective effect
Nathan
42
40 mo
<300
BOS
The best cut off point to discern
survival was the distance of
2009[125]
300m. The 1 year survival for
patients who walked >300m was
100% versus 38.5 for those who
walked <300m. The 6MWT
provided important prognostic
information and might perform
better than spirometry
6MWD 6-minute walk distance; < - less than; - less than or equal to; > - greater than;
BOS -bronchiolitis obliterans syndrome; CHRF chronic hypercapnic respiratory failure;
LT lung transplant; LTC(mixed) lung transplant candidates (mixed: several groups of
lung diseases),;mo = months; n number.
68
69
Table S27 Associations between fatigue on 6MWD and measures of disease severity
and impact in adults with chronic respiratory disease
6MWT 6-minute walk test; 6MWD 6-minute walk distance; COPD chronic
Study
Katsura
Diagnosis
COPD
90
2005[126]
Fatigue
Associations with fatigue on
variable
6MWT
Borg scale at
6MWD
end 6MWT
Dyspnoea during 6MWT

HRQOL SGRQ total, symptoms,
activity, impacts
Change in SGRQ total score after PR
Change in Borg
fatigue after PR
Al-Shair
COPD
122
2009[127]
Borg scale at
Physical, cognitive and psychosocial
end 6MWT
domains of fatigue and total fatigue

in daily life, measured with
Manchester COPD Fatigue scale
Mangueira
COPD
30
2009[128]
Ilgin 2010[129]
COPD
52
Borg scale at
Health related quality of life on
end 6MWT
SGRQ
Modified Borg
FEV1, gait speed
scale at end
6MWT
obstructive pulmonary disease; FEV1 forced expiratory volume in one second; HRQOL
70
health related quality of life; N number; PR pulmonary rehabilitation; SGRQ St

Georges Respiratory Questionnaire.
71
Table S28 Predictors of oxyhaemoglobin desaturation on 6-minute walk test in

adults with chronic respiratory disease
Study
Diagnosis
Desaturation
Predictors of desaturation
variable
Knower
COPD
81
Desaturation 88%
Resting SpO295%
COPD
36
SpO2 at end test
MRC dyspnoea score (r = 0.49,
2001[130]
Gallego
2002[131]
Nomori
p = 0.004)
COPD
83
Decrease in SpO2
FER (p<0.001)
COPD
60
SpO2 at end test
6MWD, DLCO
Nishiyama
COPD,
82
SpO2 at end test
Dyspnoea at end 6MWT (IPF
2007[134]
IPF
2004[132]
Zimmermann
2006[133]
only)
72
Villalba
SSc
110
Desaturation4%
2007[80]
Anti-Scl-70 autoantibody
positive
Dyspnoea index
Fibrosis on chest radiograph
FVC < 80% predicted
PASP 30 mm Hg
Presence of ground-glass or
reticular opacities on HRCT
Ziegler
CF
41
End test SpO2
FEV1 %predicted
COPD
67
Desaturation to less
Desaturation during daily life
2007[82]
GarciaTalaverna
than 90% during first
2008[135]
minute of 6MWT
Santos
COPD
91
Lowest SpO2
FEV1, HR at rest, 6MWD
CF
88
Desaturation4%
resting SpO2 < 96%
2009[60]
Ziegler
2009[136]
Pimenta
2010[137]
FEV < 40% predicted

1
ILD
49
Nadir SpO2
FEV1%, FVC%, DLCO%
Change in SpO2
FEV1%, FVC%, DLCO%
73
Garcia-
Desaturation to less
6MWD
Talaverna
than 90% during first
More likely to have home
2011[138]
minute of 6MWT
oxygen therapy at five years
SpO2 88% after
Quadriceps maximum
6MWT
voluntary contraction strength
Walk distance until
Minimum SpO2, duration of
SpO2<80%
SpO2<88% and mean SpO2
Gutierrez
COPD
COPD
83
75
2011[139]
Park 2011[140]
ILD
19
during waking hours
van Gestel
COPD
154
Walk duration until
Minimum SpO2 during waking
SpO2<80%
hours
Desaturation>4%
FEV1%predicted, DLCO
Desaturation>4% to
FEV1%predicted, daily physical
<90%
activity
2011 [141]
van Gestel
2012[142]
COPD
6MWD 6-minute walk distance; - less than or equal to; - greater than or equal to; >
- greater than; < - less than; CF cystic fibrosis; COPD chronic obstructive pulmonary
disease; DLCO diffusing capacity for carbon monoxide; FER ration of FEV1 to FVC;
FEV1 forced expiratory volume in one second; FVC forced vital capacity; HRQOL
health related quality of life; ILD interstitial lung disease; IPF idiopathic pulmonary
fibrosis; MRC Medical Research Council; N number; PASP pulmonary artery
systolic pressure; PR pulmonary rehabilitation; SGRQ St Georges Respiratory
Questionnaire; SpO2 oxyhaemoglobin saturation in arterial blood; SSc- systemic
sclerosis
74
Table S29. Standardization of the 6-Minute Walking Test in studies with healthy
individuals
Interval
Study
Track
Tests, #
Encouragement
Measurements
between tests
Casanova
6MWD, SpO2%
Two
2011[143]
30min at least
HR
Standardized each
60 s. (e.g. You are 6MWD, HR, BP,
Dourado
27-30m in
Two
2011[144]
24hours
doing well, Keep
breathlessness,
up the good
leg fatigue
length
work)
Standardised each
Hill 2011 [145]
30m
Two
20-30 mins
6MWD
60 seconds
Standardized each
30m
recovery time to
Soares
outdoor
Three
6MWD, SpO2%
doing well, Good
HR, Borg Scale
10 bpm of
2011[146]
corridor
60 s. (e.g. You are
baseline HR
job, keep it up)
Standardized each
30m
Osses
indoor
Two
60 s. (e.g. You are
6MWD, SpO2%
doing well. You are
HR
30min
2010[147]
corridor
halfway done)
75
Standardized each
30m
60 s. (e.g. You are
6MWD, SpO2%
doing well, Keep
HR, BP, Borg
up the good
Scale
Alameri
indoor
One
2009[148]
corridor
work)
40m
6MWD, SpO2%
Ben Saad
Standardized only
indoor,
Two
60min
HR, BP,
nd
2009[149]
at the 2 test
corridor
Dyspnoea
Standardized each
30m
Iwama
60 s. (e.g. You are 6MWD, HR, RR,

indoor
Two
30min at least
2009[150]
doing well, Good
BP, Borg Scale
corridor
job, keep it up)
Standardized each
45m
At least 20min &
60 s. (e.g. You are
Jenkins
6MWD,
indoor,
Two
HR10 bpm of
doing well, Keep
baseline HR
up the good
2009[151]
HR, Borg Scale

corridor
work)
Standardized each
30m
Masmoudi
indoor
Two
60 s. (e.g. You are
6MWD,
doing well. You are
HR, Borg Scale
30min at least
2008[152]
corridor
halfway done)
76
Standardized each
45m
At least 20min &
Camarri
indoor,
Three
2006[153]
corridor
60 s. (e.g. You are
6MWD, SpO2%
doing well. Do
HR, Borg Scale
HR10 bpm of
baseline HR
your best)
30m
6MWD, SpO2%
Chetta
Standardized each
indoor
Two
60min
2006[154]
HR,
30 s.
corridor
breathlessness
Standardized each
45m
Poh 2006[155]
indoor,
Three
60 s. (e.g. You are
6MWD,
doing well, Good
HR, Borg Scale
At least 20min
corridor
job, keep it up)
Standardized each
20m
30 s. (e.g. You are
Gibbons
6MWD, HR, RR,

indoor
Four
30min
doing well, Keep
2001[156]
BP
corridor
up the good
work)
Standardized each
30.48m
Enright
6MWD,
doing well, Keep
HR, BP, Borg
up the good
Scale
(100feet)i
One
2003[157]
60 s. (e.g. You are

-
ndoor
corridor
work)
77
Standardized each
50m
Troosters
indoor,
Two
30 s. (e.g. You are
6MWD, SpO2%
doing well. Do
HR
150min
1999[158]
corridor
your best)
Standardized each
30.48m
Enright &
30 s. (e.g. You are

(100feet)
Sherrill
6MWD, SpO2%
One
doing well, Keep
indoor
HR
1998[159]
up the good
corridor
work)
6MWD- six-minute walking distance, bpm beats per minute; HR- Heart Rate, BP- blood
pressure, RR- respiratory rate; SpO2 - oxyhaemoglobin saturation of arterial blood.
78
Table S30. Full text assessment of papers on MID of 6MWT

Study
Inclusion for MID
Exclusion, reason
Avouac 2010[160]
Review, no primary data
Bradley 2011[161]
MID not assessed
de Torres 2002[162]
MID not assessed
du Bois 2011[5]
MID 6MWT ILD
Eaton 2006[163]
MID not assessed
Evans 2011[164]
No field tests of interest
Gilbert 2009[165]
MID 6MWT PAH
Holland 2009[74]
MID 6MWT ILD
Holland 2010[54]
MID 6MWT COPD
King 2000[166]
No pulmonary disease
Laviolette 2008[167]
MID not assessed
Mathai 2012[168]
MID 6MWT PAH
Pepin 2007[169]
MID not assessed
Polkey 2013[170]
MID 6MWT COPD
Puhan 2008[171]
MID 6MWT COPD
Puhan 2011[172]
MID 6MWT COPD
Redelmeier 1997[59]
MID 6MWT COPD
Revill 2010[173]
MID not assessed
Solway 2001[174]
Review, no primary data.
79
Swigris 2010[175]
MID 6MWT ILD
Wise 2005[176]
MID 6MWT COPD
Ziegler 2010[177]
MID not assessed
6MWT- 6-minute walk test; ILD - interstitial lung disease; MID minimal important
difference; PAH - pulmonary arterial hypertension
80
Table S31. Description of studies that determined MID of the 6-minute walk test in patients with chronic lung disease
Study
Patient
Single or
author
population multicenter
Intervention
Mean age
Male/female Disease severity Mean field test
in years
in %
result at baseline
study
Redelmeier
COPD
1997[59]
(n=112)
Wise
COPD
2005[176]
(n=470)
Puhan
COPD
2008[171]
(460)
Gilbert
PAH
2009[165]
(n=207)
Single
Rehabilitation 67.0
Multicenter None
67.2
47/53
FEV1 975 ml
371 m
61/39
FEV1 26.3 %
343 m
pred.
Multicenter Rehabilitation 68.9
71/29
FEV1 39.2 %
361 m
pred.
Multicenter Sildenafil
n.r.
49/51
WHO II: 36%
344 m
WHO III: 62%

WHO IV: 2%
Holland
DPLD
2009[74]
(n=48,
n.r.
81
FVC 78% pred.
403 m
50% with
IPF)
Swigris
IPF
2010[175]
(n=123)
Holland
COPD
2010[54]
(n=75)
du Bois
IPF
2011[5]
(n=822)
Puhan
COPD
2011[172]
(n=1001)
Multicenter Bosentan
65.1
73/27
FVC 67.8%
373 m
pred.
59/41
52.3 % pred.
359 m
Multicenter Interferon
71/29
FVC 72.5%
392 m
66.0
gamma-1b
Multicenter LVRS or
pred.
66.4
61/39
26.9 % pred.
372 m
54.0
22/78
WHOII: 1%;
343 m
medical
treatment
Mathai
2012[168]
PAH (405)
Multicenter Tadalafil or
placebo
WHO II: 32%;

WHO III: 65%;
WHO IV: 2%
82
Polkey
2013[170]
COPD
(n=1847)
Multicenter
None
63.3
65/35
FEV1 49.1 % pred.
378 m
COPD- chronic obstructive pulmonary disease; DPLD - diffuse parenchymal lung disease; FVC forced vital capacity; FEV1 forced expiratory
volume in one second; IPF - idiopathic pulmonary fibrosis; LVRS lung volume reduction surgery;n.r not reported; PAH - pulmonary arterial
hypertension; WHO World Health Organization.
83
Table S32. Description of studies designed to assess the responsiveness of shuttle walk tests in
patients with chronic lung disease
Study
Dyer
2002[178]
Study design
Controlled, single
treatment arm
Pepin
Randomized, Double2005[179] blind, Placebo-controlled,
Crossover
Pepin
Randomised, Double2007[169] blind, Placebo-controlled,
Crossover trial
Brouillard
Crossover
Sandland
Crossover
Revill
Counterbalanced
2010[173]
Eaton
Prospective, Single
2006[163]
treatment arm
Intervention
Bronchodilation:
Combined nebulised
salbutamol 5mg/IB 0.5
mg
Bronchodilation:
Nebulised IB 0.5 mg
Field test studied

ISWT
Bronchodilation:
Nebulised IB 0.5 mg
ESWT
6MWT
ESWT
Bronchodilation:
ESWT
Nebulised salmeterol
0.05 mg
Ambulatory oxygen:
ISWT
Cylinder oxygen at
ESWT
2L/min
Ambulatory oxygen:
ESWT
Oxygen at 2L/min
6MWT
Pulmonary
ESWT
rehabilitation:
6MWT
8 weeks, 2
sessions/week
Leung
Prospective,
Pulmonary
ISWT
2010[182] Randomized, Two parallel
rehabilitation:
ESWT
treatment arms
8 weeks, 3
sessions/week, 45
min/session
Ground walking
training: 75% peak
walking speed
Stationary cycling
training: 60% of peak
work rate
6MWT - six-minute walking test; IB - ipratropium bromide; ESWT - endurance shuttle walk;
ISWT - incremental shuttle walk test.
84
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Measurement properties of field exercise tests in chronic respiratory disease:

10 Rehabilitation Research Center, BIOMED - Biomedical Research Institute, Faculty of

Date of submission: 27th December 2013

Search strategies for 6-minute walk test (6MWT)

Search strategies for incremental shuttle walk test (ISWT)

Search strategies for endurance shuttle walk test (ESWT)

Reliability additional data

Reliability of the 6-minute walk distance

Reliability of oxyhaemoglobin measures during the 6-minute walk test

Reliability of heart rate measures during the 6-minute walk test

Reliability of symptom scores during the 6-minute walk test

Validity Additional Data

Table S1. Characteristics of reliability studies for patients with COPD

Table S2. Intraclass correlation coefficients for 6-minute walk distance

Table S6 Characteristics of reliability studies for individuals with cystic fibrosis

Table S8. Reliability of oxyhaemoglobin measures during the 6MWT

Table S10 Reliability of symptom scores measured during the 6MWT

Table S11 Characteristics of validity studies for patients with COPD

Table S19. Relationship between 6MWD and measures of dyspnoea

Table S21. Independent predictors of 6MWD in COPD

Table S22. Independent predictors of 6MWD in SSC

Table S23. Relationship between 6MWD and prognosis in COPD

Table S24. Relationship between 6MWD and prognosis in ILD

Table S25. Relationship between 6MWD and prognosis in PAH

Table S30. Full text assessment of papers on MID of 6MWT

Search strategies for 6-minute walk test (6MWT)

Search strategies for incremental shuttle walk test (ISWT)

Search strategies for endurance shuttle walk test (ESWT)

3. What is the relationship of 6MWT, ISWT or ESWT performance to clinical outcomes in

Outcomes of interest: rate of adverse events in different patient groups; effect of

Reliability additional data

Reliability of the 6-minute walk distance

Interstitial Lung Disease

Pulmonary arterial hypertension

Reliability of oxyhaemoglobin measures during the 6-minute walk test

Interstitial Lung Disease

Pulmonary arterial hypertension

Reliability of heart rate measures during the 6-minute walk test

Chronic obstructive pulmonary disease

Interstitial lung disease

Reliability of symptom scores during the 6-minute walk test

Interstitial lung disease

Coefficient of variation: No studies reported CVs for symptom scores in ILD.

Pulmonary arterial hypertension

Validity Additional Data

33 studies in chronic obstructive pulmonary disease (COPD)

3 studies in cystic fibrosis (CF)

8 studies in pulmonary arterial hypertension (PAH), one of which is also included in

8 studies in other disease groups

Validity of 6MWD in other patient groups

Table S1. Characteristics of reliability studies for patients with COPD

63(8) 1.27(0.31)L 508(57)

1514 64(10) 45(18)%

Table S2. Intraclass correlation coefficients for 6-minute walk distance

IPF, not using oxygen 718

IPF, using oxygen

Pre PR, same day

PR - pulmonary rehabilitation, N - number

Encouraged Retest interval

95% confidence interval

Table S6 Characteristics of reliability studies for individuals with cystic fibrosis

Encouraged Retest interval

95% confidence interval

95% CI for ICC