Abstract
The 6-minute walk test (6MWT) is recommended to be performed twice to accurately assess exercise performance in stable chronic obstructive pulmonary disease (COPD) due to the presence of a learning effect. It is unknown whether a learning effect exists when the 6MWT is performed during hospitalisation for acute exacerbation of COPD (AECOPD). This study investigated whether repeat 6MWTs are necessary when conducted in inpatients with AECOPD. Pooled analysis was undertaken of data from two studies (Australia and Brazil) involving 46 participants (25 males, mean age 67.2 years, FEV1 43% predicted) admitted with AECOPD. Two 6MWTs, separated by ≥20 minutes, were performed on the day of discharge. Six-minute walk distance (6MWD; primary outcome), perceived dyspnoea (Borg scale), heart rate and oxyhaemoglobin saturation were recorded. 6MWD data from tests one (T1) and two (T2) were analysed via visual inspection of Bland-Altman plots. Factors associated with test improvement or decline were explored. Mean 6MWD difference between T1 and T2 was 6.2 m, however limits of agreement were wide (−92.2 m to 104.5 m). 32 (70%) participants improved (by any distance) from T1 to T2 by a mean (± standard deviation) of 32 m ± 28 m. Of these, 14 (30%) improved by a distance > 30 m. Fourteen (30%) participants recorded poorer 6MWD at T2 by a mean of 52 m ± 36 m. No factors were able to identify participants who improved or declined upon repeat testing. When performed in patients admitted to hospital with AECOPD, the 6MWT needs to be conducted twice in order to better estimate 6MWD.
Introduction
The 6-minute walk test (6MWT) is one of the most widely used, valid and reliable measures of exercise tolerance for individuals with COPD. Its main outcome, the six-minute walk distance (6MWD), is used to individualize exercise programs to an intensity that is both effective and safe to achieve. In addition to its usefulness for exercise prescription, evaluation of 6MWT performance can be important in this patient group due to its ability to predict exacerbations and mortality (Citation1). Although a strong body of evidence supports its use during stable disease, little attention has been given to its measurement properties during an acute exacerbation of COPD (AECOPD).
AECOPDs are characterised by worsening symptoms, increased ventilatory limitation and rapid deconditioning. Despite this, evaluation of exercise tolerance during the inpatient hospitalisation may be necessary. For example, it offers clinicians the opportunity to assess patients' rehabilitation needs, to prescribe exercise programs for completion after discharge (particularly for those unable to attend post-exacerbation pulmonary rehabilitation), and to evaluate the potential for re-hospitalisation (Citation2). It is reasonable, however, to assume physiological responses to physical exertion may differ during an AECOPD compared to stable disease.
A key recommendation for conducting the 6MWT during stable COPD is the need to perform it twice (Citation3) due to well-documented learning effects and difficulty predicting repeat test performance (Citation4–6). The presence of learning effects during AECOPDs has not been explored. This is important to identify as complex, standardized exercise testing protocols can be difficult to implement and may not be well tolerated by some individuals during an inpatient admission for AECOPD. Marked exercise intolerance during an AECOPD may also be associated with less 6MWD variability than in stable COPD, thus enhancing clinicians' ability to predict test improvement or decline on repeat testing. Such knowledge would offer clear potential to reduce unnecessary patient exertion and disruption to inpatient care.
The primary aim of this study was to investigate whether repeat 6MWT performance is necessary at the time of discharge from a hospitalised AECOPD. The secondary aim was to explore factors associated with 6MWD improvement and decline on repeat testing.
Methods
Participants
Patients admitted to hospital with an AECOPD were recruited as part of two randomised controlled trials of physiotherapy interventions in AECOPD in Australia and Brazil (Citation7, Citation8). All eligibility criteria were similar between the two sites however patients must have been productive of sputum in the Australian study (Citation7), and data were not collected from patients discharged within five days of admission in the Brazilian study (Citation8). All participants provided written, informed consent to participate in the study. Ethics approval was obtained from all participating institutions and the two studies were registered on clinicaltrials.gov (identifiers: NCT01101282; NCT01786928).
Protocol
Participants performed two 6MWTs (T1 and T2, respectively) in accordance with ATS standards (Citation9) on the day of hospital discharge. Briefly, testing was performed in a quiet indoor 30-m corridor with a minimum of 20 minutes between tests to enable sufficient rest. Participants were instructed to walk as quickly as they could in order to cover as much ground as possible during six minutes. Standardised encouragement was provided each minute. Tests were performed with oxygen only for those who usually required it at home. Perception of dyspnoea was recorded via a modified Borg scale (0–10) prior to and immediately after each test. Oxyhaemoglobin saturation (SpO2%) and heart rate were monitored continuously during testing via portable pulse oximetry.
Outcomes and analysis
The primary study outcome of interest was the 6MWD. Secondary outcomes, measured for each test, were end-test heart rate, end-test SpO2%, nadir SpO2%, end-test Borg dyspnoea score and the requirement to rest. The presence of a learning effect (‘improvers’) was evaluated via two methods: method A, as any improvement on repeated testing (T2 – T1 > 0 m); and method B, as improvement greater than or equal to the minimal important difference of 30 m (Citation3) (T2 – T1 ≥ 30 m). ‘Decliners’ were defined as those who recorded no improvement on repeated testing (T2 – T1 ≤ 0 m).
Agreement between the distance walked after T1 and T2 (principal analysis) was analyzed via the Bland–Altman method (Citation10). The difference (T2 – T1) between 6MWDs (T2 – T1; Y-axis) was plotted against the mean value obtained from the tests (T1 + T2 / 2; X-axis) and inspected visually for systematic differences across the range of values. Mean difference (agreement) and limits of agreement (± 1.96 standard deviations) were calculated and Pitman's test used to evaluate the difference in variance (or correlation) between the X- and Y-variables.
Secondary analyses consisted of exploratory comparisons between 6MWD ‘improvers’ and those who did not improve to identify factors associated with a learning effect; and between 6MWD ‘decliners’ and those who did not decline to identify factors associated with worsened performance. This included comparison of baseline variables related to the individual and hospital admission (e.g., age, body mass index, disease severity, comorbidities, length of stay, use of non-invasive ventilation, quality of life, BODE index), as well as variables obtained from the initial 6MWT (e.g., 6MWD, nadir SpO2%, heart rate, perceived exertion and dyspnoea, and supplemental oxygen use).
For these analyses, unpaired t-test (scale data) and Chi square (categorical data) test were used for normally distributed data, and Mann–Whitney U-test (scale data) used for non-normally distributed data. Shapiro–Wilk tests were used to determine data normality. Absolute reliability of test-retest measures of 6MWT performance was evaluated via calculation of intraclass correlation coefficients (ICC2,1) for 6MWD, end-test heart rate, nadir SpO2 and perceived dyspnoea. ICCs between 0–0.4 were considered weak, 0.4–0.7 moderate, and > 0.7 strong. Statistical significance was set as p < 0.05 for all analyses.
Results
Forty-six participants (25 males, mean age 67.2 years, FEV1 43% predicted during stable disease state) completed the study protocol and provided suitable data for analysis. In the Australian study, 51 additional participants did not perform a repeat 6MWT, while another 22 did not perform a 6MWT at all. This was most commonly due to logistical reasons (e.g., competing time demands) or patient preference. All walk tests were performed without any adverse events. Baseline demographic characteristics of participants are summarized in .
Table 1. Participant characteristics, according to total cohort, region and 6MWD change status
The mean difference in 6MWD between T1 and T2 for the entire sample was 6.2 m, however the limits of agreement were wide (from −92.2 to 104.5 m). Visual inspection of the plot () revealed a consistent and broad spread of data across a large range of mean 6MWD values (X-axis) without systematic bias.
Figure 1. Bland-Altman plot of agreement between repeated performance of the 6-minute walk test. Black circles represent data from Australia; open circles represent data from Brazil. T1 = test one; T2 = test two.
The 6MWD improved (by any distance) from T1 to T2 in 32 (70%) participants with a mean (± standard deviation) increase of 32 m ± 28 m on repeat testing. Of these participants, 14 (30%) improved by an amount in excess of the minimal important difference (mean increase 56 m ± 25 m). Fourteen (30%) participants recorded worse performance at T2, with a mean decrease of 52 m ± 36 m. Individual variability in 6MWD responses from T1 to T2, according to ‘decliner’ or ‘improver’ status, is presented in .
Figure 2. Six-minute walk distance performance on tests 1 and 2. “Decliner” denotes test worsening on repeat testing; “Improver” (method A) denotes improvement by any distance on repeat testing.
There were no significant differences in the proportion of participants who improved or worsened on repeat testing, or the magnitude of 6MWD change on repeat testing between the Australian and Brazilian cohorts. The ICCs were high for most parameters, with the exception of end heart rate values, where ICCs were only moderate ().
Table 2. Intraclass correlation coefficients (ICC2,1) and 95% confidence intervals for 6-minute walk test outcomes
Exploratory comparisons between ‘improvers’ (either method) and those who did not improve revealed no significant differences across any test outcome or baseline characteristic. Improvement by any amount (method A) on repeated testing (n = 32) tended to occur more in participants who achieved a low initial 6MWD value (cutoff threshold < 350 m) compared to those with an initial walk distance ≥350 m (24/31 [77%] vs 8/15 [53%], respectively), however the difference in these proportions was not statistically significant (χ2 = 2.77, p = 0.10). Eleven of the 14 (79%) participants who improved >30 m (method B) on repeated testing recorded an initial 6MWD of < 350 m. Improvement > 30 m occurred exclusively in those who walked less than 400 m on initial testing compared to those who walked ≥400 m (14/38 [37%] vs 0/8 [0%]). This difference in proportions was statistically significant (χ2 = 4.24, p = 0.04).
When “decliners” were compared to those who did not decline, to explore factors related to worsening test performance, no significant differences were found for any test outcome or baseline characteristic. A summary of results for these groups is presented in .
Table 3. Six-minute walk test performance.
Discussion
Despite the widespread popularity of the 6MWT in COPD research and clinical practice, this is the first study to assess its repeatability in the acute COPD population. Data from this international study confirm maximal walk distance is unable to be accurately identified from a single 6MWT in the majority (70%) of patients admitted to hospital due to AECOPD. The magnitude of improvement from first to second test appears variable, with no clear relationships between test improvement or decline and factors that may be predictive of repeat test performance.
Learning effects occurred in participants with both low and high initial 6MWD (ranging from 55 m to 490 m). Most “improvers,” however, achieved a 6MWD that was lower than 350 m on initial testing. The precise reason for this is difficult to ascertain. It may simply demonstrate a true ‘learning effect’ where practice and familiarization with the initial test protocol, personnel, environment and physical demand results in better performance on repeated testing. It may also reflect the realistic limits of exercise tolerance in individuals who are experiencing an acute flare-up of respiratory symptoms. This would not be unexpected given the characteristics of patients who typically present to hospital with AECOPD, for example those with more severe airways disease, significant symptoms or frequent exacerbations.
Despite significant clinical differences between the acute and stable COPD states, the incidence of a learning effect of any magnitude (method A) in individuals with AECOPD was very similar to that observed in stable COPD (Citation3). The difficulty in predicting individuals who improved or declined on repeated testing was also similar to that encountered in stable COPD (Citation11). Our data also demonstrated the presence of a learning effect was unrelated to initial ‘high’ or ‘low’ 6MWD, defined according to the commonly used cut-off value of 350 m (Citation12).
Increasing this threshold to ± 400 m, however, did distinguish those who improved by a clinically important amount compared to those who did not. This has potential implications for clinicians. As repeated testing may not always be possible in the clinical environment, it is useful to know there is a low likelihood that an initial 6MWD will improve by a significant amount in individuals who achieve a high (> 400 m) initial 6MWD. Prescription of aerobic exercise training programs from a single 6MWT in these individuals may therefore pose a relatively low risk of inaccuracy or ineffectiveness compared to those with poorer initial test performance.
The 6MWT is not routinely conducted for individuals experiencing AECOPDs in the acute inpatient setting. Reasons may include logistical challenges, ward or environment layout, patient co-operation and acceptability. The present study findings, including issues related to poor uptake of repeat 6MWTs (only 19% of participants in the Australian study underwent repeat testing), relate specifically to the day of hospital discharge. It is not clear whether learning effects would be more or less likely to occur if testing had occurred earlier during the hospitalisation period. As our Brazilian data excluded patients admitted to the intensive care unit, it is also possible that results may be less applicable to this specific patient sub-group.
Despite these issues, the inpatient setting remains a useful environment to assess exercise tolerance and prescribe individually tailored exercise programs for appropriate individuals. This may best be directed at those with significantly impaired physical function and/or limited access to pulmonary rehabilitation after discharge. Unless simpler tests of physical function (e.g., sit-to-stand or gait speed tests) emerge as valid alternatives to tests of exercise tolerance in the AECOPD population, efforts to conduct repeat 6MWTs should be made in collaboration with patients and the medical, nursing and allied healthcare team to ensure feasibility and maintenance of robust test standards.
Considering these issues, the failure of two tests to yield agreement of 6MWD within 30 minutes of each other during the period of hospitalisation for AECOPD may reasonably result in one of three possible scenarios: a) recommendation to perform a third test (if possible); b) delay of exercise testing until the period after discharge from hospital, perhaps for individuals with less urgent rehabilitation needs; or c) consideration of 6MWT results as poorly repeatable, implying caution for their interpretation and use in making clinical decisions such as exercise prescription or prognostication.
A potential limitation of our study to be noted relates to the modest number of patients that contributed repeat test data compared to the size of the original studies (Citation7, Citation8). This may have introduced an element of selection bias in the present analysis. While acknowledging this point, it is important this issue is considered representative of the feasibility and acceptability of conducting repeated exercise testing during an AECOPD, and not as a limitation of the validity of the study findings, which remain robust relative to total sample size.
Conclusion
Our data suggest approximately three quarters of patients with AECOPD who achieve a 6MWD < 350 m on initial testing will improve on repeated testing. The magnitude of expected improvement is difficult to ascertain. If the 6MWT is to be conducted during a hospitalised AECOPD, repeat testing is essential in order to accurately determine the best attainable distance.
Declaration of Interest Statement
CM has received conference support from Boehringer Ingelheim, is a member of advisory boards for Astra Zeneca, Glaxo Smith Kline and Novartis, and has received speaker fees from Glaxo Smith Kline, all outside the submitted work. All other authors report no conflicts of interest.
The authors alone are responsible for the content and writing of the paper.
References
- Spruit MA, Polkey MI, Celli B, Edwards LD, Watkins ML, Pinto-Plata V et al. Predicting outcomes from 6-minute walk distance in chronic obstructive pulmonary disease. J Am Med Dir Assoc 2012; 13(3):291–297.
- Emtner MI, Arnardottir HR, Hallin R, Lindberg E, Janson C. Walking distance is a predictor of exacerbations in patients with chronic obstructive pulmonary disease. Respir Med 2007; 101(5): 1037–1040.
- Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J 2014; 44(6):1428–1446.
- Hernandes NA, Wouters EF, Meijer K, Annegarn J, Pitta F, Spruit MA.. Reproducibility of 6-minute walking test in patients with COPD. Eur Respir J 2011; 38(2):261–267.
- Troosters T, Vilaro J, Rabinovich R, Casas A, Barberà JA, Rodriguez-Roisin R. Physiological responses to the 6-min walk test in patients with chronic obstructive pulmonary disease. Eur Respir J 2002; 20(3):564–569.
- Spencer LM, Alison JA, McKeough ZJ. Six-minute walk test as an outcome measure: are two six-minute walk tests necessary immediately after pulmonary rehabilitation and at three-month follow-up? Am J Phys Med Rehabil 2008; 87(3):224–228.
- Osadnik CR, McDonald CF, Miller BR, Hill CJ, Tarrant B, Steward Ret al. The effect of positive expiratory pressure (PEP) therapy on symptoms, quality of life and incidence of re-exacerbation in patients with acute exacerbations of chronic obstructive pulmonary disease: a multicentre, randomised controlled trial. Thorax 2014; 69(2):137–143.
- Borges RC, Carvalho CR. Impact of resistance training in chronic obstructive pulmonary disease patients during periods of acute exacerbation. Arch Phys Med Rehabil 2014; 95(9):1638–1645.
- ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111–117.
- Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1(8476):307–310.
- Singh SJ, Puhan MA, Andrianopoulos V, Hernandes NA, Mitchell KE, Hill CJ, et al. An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease. Eur Respir J 2014; 44(6):1447–1478.
- Casanova C, Cote C, Marin JM, Pinto-Plata V, de Torres JP, Aguirre-Jaíme A, et al. Distance and oxygen desaturation during the 6-min walk test as predictors of long-term mortality in patients with COPD. Chest 2008; 134(4):746–752.
- Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106(2):196–204.