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

[email protected]

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

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

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, 12-

14]. 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].

26

Table S1. Characteristics of reliability studies for patients with COPD

Study N Age FEV1 6MWD

m

Track

length

Track

layout

Encouraged Retest

interval

Guyatt 1984[1] 43 65(8) 0.97(0.25)L 450 33 straight y 2 weeks

Guyatt 1985[27] 43 ns 0.97(0.25)L ns ns straight y 2 weeks

Leach 1992[28] 30 63(7) 0.74

(0.25)L

266 ns ns ns 45 mins

Cahalin 1995[23] 60 44 (11) 1.01(0.65)L 299 51 straight n Same

day

Roomi 1996[29] 15 76 49(5)% 196(98) 29 straight n 2-10

days

Stevens 1999[30] 21 65(11) 1.07

(0.53)L

374(77) ns straight y 30 mins

Rejeski 2000[31] 30 ns ns 498(117) 26 rectangle n 1 week

Irriberri 2002[32] 30 63(8) 1.27(0.31)L 508(57) 60 straight n 20 mins

Troosters

2002[33]

20 66(6) 45(14) 539(56) 90 straight y ns

Eiser 2003[18] 23 69(8) 35(13)% 428 120 straight y 30 mins

Poulain 2003[12] 10 67(2) 59(5)% 500(85) 31.5 straight n 6 days

Sciurba 2003[3] 470 67(6) 26(7)% 370(94) variety variety y 1 day

Rodrigues

2004[13]

35 65(8) 62(24)% 515(82) ns ns ns 1 day

Spencer 2008[14] 44 66(8) 56(19)% 491(82) 32 oval y 30 mins

Chatterjee

2010[15]

88 75* 52(19) 362(117) 61 rectangular ns ns

27

Jenkins 2010[7] 245 68(9) 41(18)% 427(122) 45 straight y 30 mins

Kozu 2010[6] 45 67(5) 45(12) 315(110) 30 straight ns 1 day

Hernandez

2011[2]

1514 64(10) 45(18)% 391(99) 125 triangular y 1 day

Chandra 2012[4] 396 68* 26* 355* ns ns ns 1 day

* median; did not report reliability of 6MWD, SpO2 data only; ns not stated. FEV1 values

are reported as liters (L) or percent predicted (%).

28

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

Study Diagnosis N 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

2009[16]

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

during test

718 mean 24 days 0.83

Du Bois 2011[5] IPF, using oxygen

during test

103 mean 24 days 0.72

Wilsher 2012[10] SSc 25 1 week 0.95

29

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.

30

Table S3. Proportion of individuals with COPD who had improved 6-minute walk distance on repeat testing

PR - pulmonary rehabilitation, N - number

Study N Timepoint % walking further

on second test

% walking

significantly

further

Sciurba 2003[3] 470 1 day 70% 15%

Spencer 2008[14] 44 Pre PR, same day 70%

44 Post PR , same

day

50%

40 3 months, same

day

78%

Jenkins 2010[7] 245 Same day 87%

Hernandez 2011[2] 1514 1 day 82% 28%

31

Table S4 Characteristics of reliability studies for individuals with interstitial lung disease (ILD)

Study Diagnosis N Age FVC 6MWD

m

Track

length

(m)

Track layout Encouraged Retest interval

Eaton 2005[8] IPF 29 73(9) 81(19) 426(143) ns ns y 1 week

Buch 2007[9] SSc ILD 163 52(12) ns 398(84) ns ns y 2 hours to 4

weeks

Jenkins 2010[7] ILD 21 62(13) 59(18) 487(135) 45 Straight y 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 y 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; ns-

not stated; m- metres; y- yes.

32

Table S5. Mean improvement in distance on second 6-minute walk test in interstitial lung disease

Study Diagnosis n Mean difference

metres

95% confidence interval

metres

Limits of agreement

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

Wilsher 2012[10] SSc-ILD 3 8 -54 to 69

Pooled Mean 19.55

IPF Idiopathic pulmonary fibrosis; N Number; SSc-ILD - systemic sclerosis interstitial lung disease.

33

Table S6 Characteristics of reliability studies for individuals with cystic fibrosis

Study N Age FEV1

%predicted

6MWD

m

Track

length m

Track layout Encouraged Retest interval

Gulmans 1996[34] 23 11(2) 94(17) 742(90) 8 Straight Y 1 week

Nixon 1996[35] 8 15(3) 41(20) 407(143) 40 Straight N 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 Y 30 minutes

Mandrusiak 2009[16] 16 13(3) 65(18) ns Ns Straight Y 1 day

Ziegler 2010[17] 31 24(7) 61(28) 590(72) 30 Straight Y 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;.

.

34

Table S7. Mean improvement in distance on second 6-minute walk test in cystic fibrosis

Study n Mean difference

metres

95% confidence interval

metres

Limits of agreement

metres

Gulmans 1996[34] 23 5

Guillen 1999[36] 29 -6 --16 - 4 -59 - 48

Cunha 2006[37] 16 16 -101 - 133

Ziegler 2010[17] 31 7 -75 - 62

Pooled Mean 4.18

n- number

35

Study Diagnosis Measure ICC 95% CI for ICC Coefficient of

variation

Mean

difference

%

Limits of

agreement %

Rodrigues 2004[13] COPD SpO2 pre 0

SpO2 post -2

Spencer 2008[14] COPD SpO2 pre 2

SpO2 post 1

Hernandes 2011[2] COPD Change in SpO2 0.81 -7 to 8

Eaton 2005[8] IPF Change in SpO2 0.283

Wilsher 2012[10] SSc-

ILD

Change in SpO2

forehead

0.64 1.5 -10 to 13

Change in SpO2 finger 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 0.94 - 0.99 0.017

36

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.

Change in SpO2 pre -

post

0.92 0.84 - 0.96 0.04 0.6 -3.9 to 5.2

37

Table S9 Reliability of heart rate measures during the 6-minute walk test

Study Diagn

osis

Measure Method ICC 95% CI for ICC Coefficient of

variation

Mean

difference

bpm

Limits of

agreement

bpm

Poulain 2003[12] COPD HR post Polar monitor 0.0387 1

Rodrigues 2004[13] COPD HR pre ns -4

HR post 8

Spencer 2008[14] COPD HR pre Pulse oximeter 2

HR post -2

Hernandes 2011[2] COPD Change in HR ns 0.62

Mandrusiak

2009[16]

CF Change in HR Pulse oximeter 0.87 0.63-0.95

Ziegler 2010[17] CF HR pre ns 0.52 0.008 - 0.77 11.1

HR post 0.28 -0.49 - 0.65 6.8

38

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

39

Table S10 Reliability of symptom scores measured during the 6MWT

Study Diagn

osis

Measure ICC 95% CI for ICC Coefficient of

variation

Mean

difference

Limits of

agreement

kappa

Poulain 2003[12] COPD VAS dyspnoea end 0.22 4mm

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 0

Borg fatigue end 0

Spencer 2008[14] COPD Borg dyspnoea end 0

Hernandes 2011[2] COPD Change in Borg

dyspnoea

0.59

Change in Borg fatigue 0.59

Eaton 2005[8] ILD Borg dyspnoea at rest 0.67*

Borg dyspnoea end 0.79*

Buch 2007[9] SSc-

ILD

Borg dyspnoea end 0.8 -1.36 to 2.96

40

* 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.

Wilsher 2012[10] SSc-

ILD

Borg dyspnoea end 0.85 -0.15 -1.6 to 1.35

Mandrusiak

2009[16]

CF Change in Borg

dyspnoea

0.92 0.56-0.95

Change in 15c dyspnoea 0.66 0.02-0.88

Ziegler 2010[17] CF Borg dyspnoea pre -0.79

Borg dyspnoea post 0.71

Borg fatigue pre 0.34

Borg fatigue post 0.52

41

Table S11 Characteristics of validity studies for patients with COPD

Study N Age FEV1

%pred

6MWD Variables measured

Annegarn 2012[38] 79 64(9) 54(19) 452(106) FEV1

Borges 2012[39] 20 69(11) 49(14) 373(135) Physical activity

Brown 2008[40] 1217 67 (6) 67(6) 348(95) FEV1, HRQoL, dyspnoea

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 FEV1

Chuang 2001[45] 27 65(6) 49(10) 456(84) FEV1, VO2peak

Diaz 2010[46] 81 67 (8) 64(24) FEV1>50%:

512(80)

FEV1

42

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) FEV1, dyspnoea

Oga 2002[57] 36 69(7) 40(17) 492(66) FEV1, dyspnoea, HRQoL, Wpeak,

VO2peak, endurance

Rambod 2012[58] 1273 64 56 366 FEV1

Redelmeier

1997[59]

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

2012[65]

154 63(11) 43(19) 452(106) FEV1

Waatervik 2012[66] 370 62(6) 49(13) NS FEV1, dyspnoea, physical activity

43

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.

44

Table S12 Characteristics of validity studies for patients with interstitial lung disease

Study Diagnosis n Age FVC

%pred


Andersen

2012[68]

ILD 212 61(15) 71(30) 424(116) Pulmonary hypertension

Baldi 2012[69] LAM 40 42(11) 93(15) 547* VO2peak

Blanco

2010[70]

DILD 13 63(9) 73(22) 451(80) Cardiorespiratory

responses

Chetta

2001[71]

ILD 40 54(14) 87(26) 487(96) FVC, TLCO

Doyle 2012[72] ILA in

smokers

194 64(56-72) 88(77-98) 403(308-480)* FVC, dyspnoea, HRQoL

du Bois

2011[5]

IPF 822 66(8) 73(13) 392(109) FVC, TLCO, dyspnoea,

HRQoL

Eaton 2005[8] IPF 29 73(9) VO2peak, FVC%pred,

TLCO%pred

Garin 2009[73] IPF 48 63 NS 379 FVC%pred, TLCO%pred

Holland

2009[74]

ILD 48 69(9) 78(16) 403(118) Patient rating of change

Holland

2010[75]

ILD 15 70(12) NR NR 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

45

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.

46

Table S13. Characteristics of validity studies for patients with systemic sclerosis

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.

Study Diagnosis n Age FVC

%pred


Buch 2007[9] SSc-ILD,

worsening over

12 months

163 52(12) 398(84) FVC%pred,

TLCO%pred, dyspnoea

Cuomo 2012[5] SSc 63 56* ns 420* HRQoL

Deuschle 2011[77] SSc 95 56* 99 (56-

128)*

491(86665) FVC%pred, TLCO%pred

Garin 2009[73] SSc-ILD 80 52(46-

60)

ns 349 FVC%pred, TLCO%pred

Mainguy 2011[78] SSc-PAH 10 58(10) 349 (129) Physical activity

Schoindre2009[79] SSc 87 55(13) 97(25) 461(103) FVC%pred,

TLCO%pred, SPAP

Villalba 2007[80] SSc 110 45.5* 81.5* FVC, SPAP

47

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

in one second; n number.

Study n Age FEV1

%pred

6MWD (m) Variables measured

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

48

Table S15 Characteristics of validity studies for patients with pulmonary arterial

hypertension

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.

Study Diagnosis n Age mPAP 6MWD (m) Variables measured

Blanco

2010[70]

PAH 14 42(15) 49(11) 542(100) Cardiorespiratory

responses

Cicero

2012[83]

PAH 34 36* 399* HRQoL

Deboeck

2005[84]

PAH 20 53(3) 57(8) 450(22) VO2peak

Fowler

2011[85]

EIPAH 17 57(13) 18(4) 575(86) VO2peak, cardiac output

Mainguy

2011[78]

PAH 15 47(15) 401 (89) Physical activity

Miyamoto

2000[86]

PAH 43 37 332* Pulmonary

hemodynamics,

VO2peak

Pugh

2012[87]

PAH 20 54(14) 46(13) Physical activity

Reesink

2007[88]

CTEPH 50 53(14) 48(14) 391(134) Pulmonary

hemodynamics

49

Table S16. Relationship between 6MWD and disease severity in adults with COPD

Study Diagnosis n Variable Pearsons r Spearmans

rho

Mak 1993[56] COPD 42 FEV1 %pred 0.53

Wijkstra

1994[67]

COPD 40 FEV1 %pred 0.55

Rejeski

2000[31]


Chuang

2001[45]


Oga 2002[89] COPD 36 FEV1 %pred 0.41

Brown

2008[40]


Santos

2009[60]


Waatervik

2012[66]


50

N number; COPD chronic obstructive pulmonary disease; FEV1 forced expiratory volume in one second.

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

2012[38]

COPD 79 FEV1 0.452

Hillman

2012[53]

COPD 26 FEV1 0.7

Van Gestel

2012[65]


Bruyneel

2012[41]

COPD 82 FEV1 0.54

51

Table S17. Relationship between 6MWD and disease severity in adults with ILD

Study Diagnosi

s

n Variable Pearsons r Spearmans rho

Chetta

2001[71]

ILD 40 FVC %pred 0.4

Eaton

2005[8]

IPF 29 FVC %pred 0.06

Garin

2009[73]


Doyle

2012[72]

ILA 194 FVC %pred 0.38

Du Bois

2011[5]


Minai

2012[76]


Eaton

2005[8]

IPF 29 DLCO %pred 0.61

Chetta

2001[71]

ILD 40 DLCO %pred 0.42

Garin

2009[73]


52

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.

Du Bois

2011[5]


Minai

2012[76]


53

Table S18. Relationship between 6MWD and disease severity in adults with SSc

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

Study Diagnosis n Variable Pearsons r Spearmans rho

Buch 2007[9] SSc-ILD 163 FVC%pred 0.19

Garin

2009[73]

SSc-ILD 80 FVC%pred 0.12

Schoindre

2009[79]

SSc 87 FVC%pred 0.37

Deuschle

2011[77]

SSc 95 FVC%pred 0.309

Buch 2007[9] SSc-ILD 163 TLCO%pred 0.06

Garin

2009[73]

SSc-ILD 80 TLCO%pred 0.23

Schoindre

2009[79]

SSc 87 TLCO%pred 0.49

Deuschle

2011[77]

SSc 95 TLCO%pred 0.336

Schoindre

2009[79]

SSc sPAP 0.44

54

Table S19. Relationship between 6MWD and measures of dyspnoea

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

Study Diagnosis n Dyspnoea Measure Pearsons r Spearmans

rho

Mak

1993[56]

COPD 42 MRC scale -0.52

Rejeski

2000[31]

COPD 209 0-10 rating scale -0.38

Oga

2002[89]

COPD 36 Oxygen cost diagram 0.66

Brown

2008[40]

COPD 1217 UCSD SOBQ -0.37

Hillman

2012[53]

COPD 26 Modified MRC scale -0.7

Doyle

2012[72]

ILA 194 Modified MRC scale -0.48

Du Bois

2011[5]

IPF 822 UCSD SOBQ -0.29

Zeigler

2007[82]

CF 41 Borg post 6MWT NR (not sig)

55

Diego Shortness of Breath Questionnaire..

56

Table S20. Relationship between 6MWD and measures of health-related quality of life

Study Diagnosis n HRQoL measure Pearsons

r

Spearmans

rho

Wijkstra 1994[67] COPD 42 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] COPD 36 SGRQ activity -0.68

SGRQ total -0.56

Brown 2008[40] COPD 1217 SF-36 PCS 0.19

SGRQ symptoms -0.03

SGRQ activity -0.35

SGRQ impacts -0.22

SGRQ total -0.26

Bruyneel COPD 82 SGRQ activity -0.45

57

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.

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

SGRQ activity

-0.57

-0.50

Cicero 2012[83] PAH 31 SF36 physical functioning

SF36 role physical

SF 36 bodily pain

SF36 general health

SF36 vitality

SF36 social functioning

SF36 role emotional

SF36 mental health

0.44

-0.02

-0.03

0.24

0.32

0.18

-0.014

0.19

58

Table S21. Independent predictors of 6MWD in COPD

Study Predictors r- squared

Brown 2008[40] SGRQ total score

FEV1%pred

Female gender

Height

Weight

Age

0.31

Bruyneel 2012[41] FEV1

TLC

IC

TLCO/VA

0.35

Mak 1993[56] TLCO

Age

Peak expiratory flow

0.50

Oga 2002[89] Oxygen cost diagram 0.36

Roomi 1996[29] Maximal expiratory mouth pressure

Calorie intake

BMI

0.70

Wijkstra 1994 [67] PImaxPOES

TLCO

Inspiratory vital capacity

0.62

59

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.

Residual volume

FEV1

Dyspnoea

60

Table S22. Independent predictors of 6MWD in SSC

Study Diagnosis Predictors r- squared

Villalba 2007[80] SSc Age

Ethnicity

Dyspnoea index

ns

Garin 2009[73] SSc Pre 6MWT Borg

Minimum SpO2 during

6MWT Resting SpO2

gender 0.26

All SSc without lower limb

pain

Pre 6MWT Borg

Minimum SpO2 during

6MWT Resting SpO2

gender 0.36

SSc-ILD 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 0.32

61

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.

Schoindre 2009[79] SSc Presence of calcinosis ns

62

Table S23. Relationship between 6MWD and prognosis in COPD

Study Sample

(n=) Follow-

up

6MWD Threshold

Findings

Mortality

Hospitalization

Szekely

1997[91] 47 6-12 mo

63

Puhan

2009[99] 574 36 mo

64

Table S24. Relationship between 6MWD and prognosis in ILD

Study n Followup

6MWD Threshold

Diagnosis

Findings

Mortality

Hospitalization

Lama

2003[105] 105 36 mo - - IIP

The knowledge of desaturation (88%) during 6MWT adds prognostic information for patients with usual and nonspecific interstitial pneumonia

Lederer

2006[106] 454 4 mo

65

presence of IPF. A 6MWD

66

Table S25. Relationship between 6MWD and prognosis in PAH

Study n Follo

w up

6MWD Threshold

Diagnosis

Findings

Mortality

Hospitalization

Miyamoto

2000[113] 43 21 mo

67

Nickel

2012[120] 109 38 mo

68

Table S26. Relationship between 6MWD and prognosis in other lung diseases

Study n Follo

w up

6MWD Threshold

Diagnosis

Findings

Mortality

Hospitalization

Budweiser

2008[122] 424 72 mo

70

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

obstructive pulmonary disease; FEV1 forced expiratory volume in one second; HRQOL

Study Diagnosis n Fatigue

variable

Associations with fatigue on

6MWT

Katsura

2005[126]

COPD 90 Borg scale at

end 6MWT

Change in Borg

fatigue after PR

6MWD

Dyspnoea during 6MWT

HRQOL SGRQ total, symptoms,

activity, impacts

Change in SGRQ total score after PR

Al-Shair

2009[127]


end 6MWT

Physical, cognitive and psychosocial

domains of fatigue and total fatigue

in daily life, measured with

Manchester COPD Fatigue scale

Mangueira

2009[128]


end 6MWT

Health related quality of life on

SGRQ

Ilgin 2010[129] COPD 52 Modified Borg

scale at end

6MWT

FEV1, gait speed

71

health related quality of life; N number; PR pulmonary rehabilitation; SGRQ St Georges Respiratory Questionnaire.

72

Table S28 Predictors of oxyhaemoglobin desaturation on 6-minute walk test in

adults with chronic respiratory disease

Study Diagnosis n Desaturation

variable

Predictors of desaturation

Knower

2001[130]

COPD 81 Desaturation 88% Resting SpO295%

Gallego

2002[131]

COPD 36 SpO2 at end test MRC dyspnoea score (r = 0.49,

p = 0.004)

Nomori

2004[132]

COPD 83 Decrease in SpO2 FER (p

73

Villalba

2007[80]

SSc 110 Desaturation4% 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

2007[82]

CF 41 End test SpO2 FEV1 %predicted

Garcia-

Talaverna

2008[135]

COPD 67 Desaturation to less

than 90% during first

minute of 6MWT

Desaturation during daily life

Santos

2009[60]

COPD 91 Lowest SpO2 FEV1, HR at rest, 6MWD

Ziegler

2009[136]

CF 88 Desaturation4% resting SpO2 < 96%

FEV1 < 40% predicted

Pimenta

2010[137]

ILD 49 Nadir SpO2

Change in SpO2

FEV1%, FVC%, DLCO%

FEV1%, FVC%, DLCO%

74

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

Garcia-

Talaverna

2011[138]

COPD 83 Desaturation to less

than 90% during first

minute of 6MWT

6MWD

More likely to have home

oxygen therapy at five years

Gutierrez

2011[139]

COPD 75 SpO2 88% after

6MWT

Quadriceps maximum

voluntary contraction strength

Park 2011[140] ILD 19 Walk distance until

SpO2

75

Table S29. Standardization of the 6-Minute Walking Test in studies with healthy

individuals

Study Track Tests, # Interval

between tests Encouragement Measurements

Casanova

2011[143]

- Two 30min at least -

6MWD, SpO2%

HR

Dourado

2011[144]

27-30m in

length Two 24hours

Standardized each

60 s. (e.g. You are

doing well, Keep

up the good

work)

6MWD, HR, BP,

breathlessness,

leg fatigue

Hill 2011 [145] 30m Two 20-30 mins Standardised each

60 seconds 6MWD

Soares

2011[146]

30m

outdoor

corridor

Three

recovery time to

10 bpm of

baseline HR

Standardized each

60 s. (e.g. You are

doing well, Good

job, keep it up)

6MWD, SpO2%

HR, Borg Scale

Osses

2010[147]

30m

indoor

corridor

Two 30min

Standardized each

60 s. (e.g. You are

doing well. You are

halfway done)

6MWD, SpO2%

HR

76

Alameri

2009[148]

30m

indoor

corridor

One -

Standardized each

60 s. (e.g. You are

doing well, Keep

up the good

work)

6MWD, SpO2%

HR, BP, Borg

Scale

Ben Saad

2009[149]

40m

indoor,

corridor

Two 60min Standardized only

at the 2nd test

6MWD, SpO2%

HR, BP,

Dyspnoea

Iwama

2009[150]

30m

indoor

corridor

Two 30min at least

Standardized each

60 s. (e.g. You are

doing well, Good

job, keep it up)

6MWD, HR, RR,

BP, Borg Scale

Jenkins

2009[151]

45m

indoor,

corridor

Two

At least 20min &

HR10 bpm of

baseline HR

Standardized each

60 s. (e.g. You are

doing well, Keep

up the good

work)

6MWD,

HR, Borg Scale

Masmoudi

2008[152]

30m

indoor

corridor

Two 30min at least

Standardized each

60 s. (e.g. You are

doing well. You are

halfway done)

6MWD,

HR, Borg Scale

77

Camarri

2006[153]

45m

indoor,

corridor

Three

At least 20min &

HR10 bpm of

baseline HR

Standardized each

60 s. (e.g. You are

doing well. Do

your best)

6MWD, SpO2%

HR, Borg Scale

Chetta

2006[154]

30m

indoor

corridor

Two 60min Standardized each

30 s.

6MWD, SpO2%

HR,

breathlessness

Poh 2006[155]

45m

indoor,

corridor

Three At least 20min

Standardized each

60 s. (e.g. You are

doing well, Good

job, keep it up)

6MWD,

HR, Borg Scale

Gibbons

2001[156]

20m

indoor

corridor

Four 30min

Standardized each

30 s. (e.g. You are

doing well, Keep

up the good

work)

6MWD, HR, RR,

BP

Enright

2003[157]

30.48m

(100feet)i

ndoor

corridor

One -

Standardized each

60 s. (e.g. You are

doing well, Keep

up the good

work)

6MWD,

HR, BP, Borg

Scale

78

6MWD- six-minute walking distance, bpm beats per minute; HR- Heart Rate, BP- blood

pressure, RR- respiratory rate; SpO2 - oxyhaemoglobin saturation of arterial blood.

Troosters

1999[158]

50m

indoor,

corridor

Two 150min

Standardized each

30 s. (e.g. You are

doing well. Do

your best)

6MWD, SpO2%

HR

Enright &

Sherrill

1998[159]

30.48m

(100feet)

indoor

corridor

One -

Standardized each

30 s. (e.g. You are

doing well, Keep

up the good

work)

6MWD, SpO2%

HR

79

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.

80

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

81

Table S31. Description of studies that determined MID of the 6-minute walk test in patients with chronic lung disease

Study

author

Patient

population

Single or

multicenter

study

Intervention Mean age

in years

Male/female

in %

Disease severity Mean field test

result at baseline

Redelmeier

1997[59]

COPD

(n=112)

Single Rehabilitation 67.0 47/53 FEV1 975 ml 371 m

Wise

2005[176]

COPD

(n=470)

Multicenter None 67.2 61/39 FEV1 26.3 %

pred.

343 m

Puhan

2008[171]

COPD

(460)

Multicenter Rehabilitation 68.9 71/29 FEV1 39.2 %

pred.

361 m

Gilbert

2009[165]

PAH

(n=207)

Multicenter Sildenafil n.r. 49/51 WHO II: 36%

WHO III: 62%

WHO IV: 2%

344 m

Holland

2009[74]

DPLD

(n=48,

Multicenter Rehabilitation 69.0 n.r. FVC 78% pred. 403 m

82

50% with

IPF)

Swigris

2010[175]

IPF

(n=123)

Multicenter Bosentan 65.1 73/27 FVC 67.8%

pred.

373 m

Holland

2010[54]

COPD

(n=75)

Multicenter Rehabilitation 70.3 59/41 52.3 % pred. 359 m

du Bois

2011[5]

IPF

(n=822)

Multicenter Interferon

gamma-1b

66.0 71/29 FVC 72.5%

pred.

392 m

Puhan

2011[172]

COPD

(n=1001)

Multicenter LVRS or

medical

treatment

66.4 61/39 26.9 % pred. 372 m

Mathai

2012[168]

PAH (405) Multicenter Tadalafil or

placebo

54.0 22/78 WHOII: 1%;

WHO II: 32%;

WHO III: 65%;

WHO IV: 2%

343 m

83

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.

84

Table S32. Description of studies designed to assess the responsiveness of shuttle walk tests in patients with chronic lung disease

Study Study design Intervention Field test studied

Dyer 2002[178]

Controlled, single treatment arm

Bronchodilation: Combined nebulised

salbutamol 5mg/IB 0.5 mg

ISWT

Pepin 2005[179]

Randomized, Double-blind, Placebo-controlled,

Crossover

Bronchodilation: Nebulised IB 0.5 mg

ESWT

Pepin 2007[169]

Randomised, Double-blind, Placebo-controlled,

Crossover trial

Bronchodilation: Nebulised IB 0.5 mg

ESWT 6MWT

Brouillard 2008[180]


Crossover

Bronchodilation: Nebulised salmeterol

0.05 mg

ESWT

Sandland 2008[181]


Crossover

Ambulatory oxygen: Cylinder oxygen at

2L/min

ISWT ESWT

Revill 2010[173]

Counterbalanced Ambulatory oxygen: Oxygen at 2L/min

ESWT 6MWT

Eaton 2006[163]

Prospective, Single treatment arm

Pulmonary rehabilitation:

8 weeks, 2 sessions/week

ESWT 6MWT

Leung 2010[182]

Prospective, Randomized, Two parallel

treatment arms

Pulmonary rehabilitation:

8 weeks, 3 sessions/week, 45

min/session

Ground walking training: 75% peak walking speed

Stationary cycling training: 60% of peak work rate

ISWT ESWT

6MWT - six-minute walking test; IB - ipratropium bromide; ESWT - endurance shuttle walk; ISWT - incremental shuttle walk test.

85

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