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6-Minute walk test in patients with COPD: clinical applications in pulmonary rehabilitation
Physiotherapy 93 (2007) 175–182
Expert article
6-Minute walk test in patients with COPD: clinical applications in pulmonary rehabilitation Sue C. Jenkins a,b,c,∗ a
School of Physiotherapy, Curtin University of Technology, GPO Box U1987, Perth, Western Australia 6845, Australia b Physiotherapy Department, Sir Charles Gairdner Hospital, Australia c Lung Institute of Western Australia, Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Australia
Abstract Pulmonary rehabilitation is an evidence-based intervention for the management of patients with chronic obstructive pulmonary disease (COPD). In clinical practice, the 6-minute walk test (6MWT) is commonly used to assess changes in functional exercise capacity in COPD patients following pulmonary rehabilitation with the primary outcome reported being the distance walked during the test (i.e. 6MWD). The 6MWD has demonstrated validity, reliability after one familiarisation test and the capacity to detect changes following pulmonary rehabilitation. In addition to assessing the outcomes of pulmonary rehabilitation, 6MWD may be used to quantify the magnitude of a patient’s disability, prescribe a walking programme, identify patients likely to benefit from a rollator and to identify the presence of exercise-induced hypoxaemia. This review describes the applications of the 6MWD in patients with COPD undergoing pulmonary rehabilitation. © 2007 Published by Elsevier Ltd on behalf of Chartered Society of Physiotherapy. Keywords: Pulmonary disease; Chronic obstructive; Exercise test; Walking; Rehabilitation
Introduction Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide [1]. Individuals with COPD develop progressive disability and impairment in quality of life. The disease is associated with high health care costs, of which hospitalisations for exacerbations are a major contributor [2]. There is a scarcity of good prevalence studies that include spirometric measures; however, based on the available literature the prevalence of physiologically defined COPD in adults aged 40 years or above is between 9 and 10% [1]. The prevalence of COPD is projected to increase in many parts of the world as a result of the ageing population and an increase in cigarette smoking [1].
∗
Tel.: +61 8 9266 3639; fax: +61 8 9266 3699. E-mail address: [email protected].
Assessment of functional exercise capacity in pulmonary rehabilitation Pulmonary rehabilitation is strongly endorsed as an evidence-based intervention for the management of patients with COPD [3,4]. The benefits of exercise training, the mandatory component of pulmonary rehabilitation, have been convincingly demonstrated [3,5,6]. In clinical practice, the 6-minute walk test (6MWT) and the incremental shuttle walking test are commonly used to assess changes in functional exercise capacity following pulmonary rehabilitation with the primary outcome reported being the distance walked during the test. Both tests have demonstrated validity, reliability after one familiarisation test, and have the capacity to detect changes following pulmonary rehabilitation [6–11]. The clinical preference for these field walking tests compared to laboratory-based tests using a cycle ergometer or treadmill is due to their increased availability and low cost, and because ground-based walking is more representative of activities of daily living [8].
0031-9406/$ – see front matter © 2007 Published by Elsevier Ltd on behalf of Chartered Society of Physiotherapy. doi:10.1016/j.physio.2007.02.001
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This article reviews the clinical applications of the 6MWT in pulmonary rehabilitation and is based on the literature and the author’s clinical and research experience. The review commences with a discussion of the validity and reliability of the 6MWD and predicted values for 6MWD. This is followed by the applications of 6MWD in pulmonary rehabilitation and includes the use of 6MWD as an outcome measure, for prescribing a walking programme and for selecting patients likely to benefit from a rollator. Also included is a discussion of the 6MWT to identify exercise-induced hypoxaemia. The final section gives an overview of the information provided by the 6MWD in patients recovering from an acute exacerbation of COPD.
Is the 6MWD a valid measure of exercise capacity in COPD? The validity of the 6MWD is demonstrated by the moderate to good relationship (r ≥ 0.5) between 6MWD and ˙ 2peak ) measured during a peak oxygen consumption (VO laboratory-based incremental exercise test to peak work capacity in patients with COPD [12–15]. The relationship tends to be strongest (r > 0.7) in patients with more severe functional limitation because a self-paced walking test in these individuals more closely represents maximal exercise performance [12,16]. Examination of the relationship between 6-minute walk work (6MWW, determined as the ˙ 2peak reveals product of body weight and 6MWD) and VO a stronger relationship (r = 0.81) than between 6MWD and ˙ 2peak because 6MWW represents the work done (i.e. force VO [body weight] × distance travelled) when performing the test [14].
Does 6MWD provide information about physical activity during daily life? Dyspnoea during activities of daily living is frequently reported by patients with COPD and can result in inactivity and the associated problems of deconditioning and muscle weakness. To the author’s knowledge only one study has objectively measured daily physical activity in COPD patients (n = 50) and compared the findings to data obtained in age- and gender-matched healthy controls (n = 25) [17,18]. Compared to the healthy controls, COPD patients spent significantly less time standing and walking during daily activities (P < 0.001, for both). In the COPD cohort, walking time and walking intensity were significantly correlated with 6MWD (r = 0.76 and r = 0.62, respectively, P < 0.001). In contrast, the correlations between these variables and maximal exercise capacity (r ≤ 0.33), lung function (r ≤ 0.38), respiratory (r ≤ 0.38) and peripheral muscle strength (r ≤ 0.45) were more modest. Pitta et al. [17] concluded that a reduced 6MWD (<400 m) is the best surrogate marker of inactivity during daily life in patients with COPD.
Is 6MWD associated with survival? In patients with severe airflow obstruction, longitudinal data demonstrate that the decline in 6MWD occurs independent of the change in the forced expiratory volume in one second (FEV1 ) [19]. Further, 6MWD is a stronger predictor of survival than FEV1 [19]. This is possibly because 6MWD is influenced by skeletal muscle dysfunction as well as pulmonary impairment and so reflects both the primary pulmonary and secondary systemic manifestations of COPD. The 6MWD is one of four variables, together with FEV1 , body mass index (BMI) and the Modified Medical Research Council (MMRC) dyspnoea scale, that comprise a multidimensional grading system known as the BODE Index [20]. The BODE Index has been shown to be a valid measure for predicting mortality from any cause and from respiratory causes in COPD patients [20]. This study [20] was carried out in 625 patients recruited from clinics in the USA, Europe and South America. However, limitations of the study include the predominance of male patients and the presence of geographical differences in 6MWD that are apparent independent of the severity of limitation in FEV1 [20,21]. In patients undergoing pulmonary rehabilitation, the change in BODE Index has been linked to survival and an improvement in the BODE Index has been shown to be associated with a reduction in hospitalisations for COPD exacerbations [22]. This is most likely due to the improvements that occur in 6MWD and dyspnoea following pulmonary rehabilitation in the absence of any changes in FEV1 or BMI. Is 6MWD a useful measure for selecting patients for lung volume reduction surgery or lung transplantation? Few studies have attempted to determine threshold values of 6MWD for successful outcome following lung volume reduction surgery (LVRS) or for listing patients for lung transplantation. In patients undergoing LVRS, Szekely et al. [23] reported that a 6MWD <200 m (achieved before or after pulmonary rehabilitation) was associated with a high level of mortality 6 months postoperatively (specificity 84%). In a retrospective review of 145 patients (58 with COPD) who underwent lung transplantation or died while awaiting surgery, the sensitivity, specificity and positive and negative predictive values for 6MWDs of 300 m and 400 m as a predictor of mortality were calculated [24]. The authors concluded that the 6MWT was a useful tool in the assessment of when to list patients for lung transplantation and that a 6MWD of less than 400 m appeared to be a reasonable marker corresponding to when a patient should be listed [24]. Is 6MWD a reliable measure? The 6MWT requires strict standardisation of the test protocol if reliable data are to be obtained. The factors
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that influence 6MWD (e.g. track length and course layout, instructions and encouragement, number of tests) and require standardisation have been reviewed in detail elsewhere [25,26]. A familiarisation effect for the test has been demonstrated with the majority of patients na¨ıve to the test increasing their 6MWD after one familiarisation test and little or no further increase occurring when a subsequent test is performed on the same day [27,28]. Dyspnoea is the most commonly cited symptom that limits performance on a walking test in COPD patients [29] and a repeat 6MWT is usually well tolerated after a 20–30 minute rest period by which time patients have recovered from the dyspnoea elicited during their familiarisation test. Analysis of 6MWD data obtained from 121 COPD patients referred to our programme showed that nearly all patients (106 patients, 87%) walked further following a familiarisation test. The mean increase for the group was 36 ± 32 m (mean ± SD, P < 0.001), which is of a similar magnitude to that reported by others in COPD patients [27,30] but significantly greater than the increase (18 ± 30 m, P < 0.001) we observed in 70 healthy subjects tested using an identical 6MWT protocol [31]. This is most likely explained by habituation to dyspnoea in individuals with COPD, which is not a factor in healthy individuals. However, in clinical practice and studies of pulmonary rehabilitation a familiarisation 6MWT is not always performed and there is sometimes poor standardisation of the test protocol with little attempt to ensure an individual achieves their maximal performance on the test [32–37].
Is a familiarisation test always necessary? Where performance on the test is limited by symptoms from co-morbid conditions, for example musculoskeletal or claudication pain, it is reasonable to omit a second test at pre-training assessment. In patients with co-morbid cardiac disease, consideration should be given to terminating the test when heart rate reaches 85% of age-predicted maximal heart rate. Finally, in patients who demonstrate profound oxygen desaturation (SpO2 <80%) during the initial 6MWT, the test should not be repeated unless assessment for ambulatory oxygen is undertaken. There are limited data to indicate whether a familiarisation 6MWT is necessary at follow-up assessments [38]. Our data in 32 COPD patients showed only a small increase in 6MWD (9 ± 19 m, P > 0.05) following a familiarisation test at the end of an 8-week training programme [38]; however, when the 6MWT is repeated at long-term follow-up a familiarisation test may be necessary [39].
Does a standardised protocol exist for the 6MWT? In 2002, the American Thoracic Society (ATS) published guidelines for the 6MWT with the aim of providing a stan-
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dardised approach to test performance [26]. These guidelines however raise some important concerns. Notably, the guidelines state that the use of pulse oximetry is optional and a familiarisation test is not needed in most clinical settings. Failure to monitor oxygen saturation (SpO2 ) raises safety concerns as a proportion of patients with moderate to severe COPD demonstrate significant desaturation during the 6MWT [15,40]. The absence of a familiarisation test at pre-training assessment is likely to lead to an overestimate of the effects of training on 6MWD. For details of a standardised 6MWT protocol the reader is referred to the Pulmonary Rehabilitation Toolkit developed by the Australian Physiotherapy Association and The Australian Lung Foundation [41]. The protocol described in the Toolkit is based on the ATS guidelines [26] with modifications to include monitoring of SpO2 , standard instructions if a patient rests during the test and a familiarisation test.
Can a patient’s 6MWD be referenced to a ‘normal’ 6MWD? In recent years there has been interest in expressing an individual’s 6MWD as a percentage of their predicted 6MWD in an attempt to quantify the magnitude of a patient’s disability. Several reference equations are available for this purpose [31,42–45]. The amount of variance in 6MWD explained by these equations ranges from 19 to 66% with most reporting that age, height, weight and gender are significant contributors to 6MWD. The weighting of gender as a contributor, independent of height, varies among the equations with some equations predicting a similar 6MWD for males and females of the same height [31,45]. Only the extremes of body weight appear to influence 6MWD [45] and equations that include weight as an inverse contributor to 6MWD [42,43] will overestimate the 6MWD for a patient who is underweight. The published equations predict 6MWDs that vary by up to 175 m for the same individual. Possible explanations for this discrepancy include differences in the subject sample used to generate the equation (i.e. random vs convenience sample) and in the 6MWT protocol. For example, the equation generated by Enright et al. [42] predicts significantly lower 6MWDs than other equations generated in Caucasian samples [31,43,44]. Explanations for this discrepancy may include the performance of a single 6MWT only in the study by Enright et al. [42] in contrast to other studies that used between two and four repetitions of the test [31,43,44]. Further, the very modest increase in heart rate in Enright’s sample [42], compared to other studies [31,43], suggests that the subject’s effort was submaximal despite being instructed to cover as much ground as possible in 6 minutes and receiving standardised encouragement. Six-minute walk distance appears to vary in individuals from different geographical regions [20,21] with race and ethnicity contributing to 6MWD [45–47]. This suggests there is a need for facilities providing pulmonary rehabilitation to
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develop their own regression equation to predict 6MWD if a valid estimate of the impact of COPD on 6MWD is to be obtained.
6MWD as an outcome of pulmonary rehabilitation: what is the minimum clinically important difference (MCID)? The 6MWD has been shown to be responsive to change following pulmonary rehabilitation [7]. The 6MWT is unique among walking-based tests of exercise capacity in that it is self-paced and allows patients to rest in the event that dyspnoea becomes intolerable. Therefore, patients with severe disability can increase their 6MWD by walking faster or reducing the number or duration of rest periods. In contrast, patients with a high pre-training 6MWD, for example a 6MWD of 600 m implies an average walking speed of 6 kilometres per hour on the test, may be limited in their ability to demonstrate improvements in 6MWD because mechanical factors such as stride length may limit performance and give rise to a ceiling effect for the test [48]. When reporting change in 6MWD, the ATS guidelines for the 6MWT recommend that the absolute change and not the percentage change is reported [26]. The magnitude of improvement in 6MWD that represents the threshold for a clinically significant change has not been extensively researched. It is widely quoted in the literature that 54 m (95% confidence intervals [CI] 37, 71 m) represents the threshold value for a clinically significant change regardless of pre-training 6MWD [26,49]. Using these data, the Cochrane Review of pulmonary rehabilitation for COPD [6] concluded that the clinical significance of the improvement in 6MWD (weighted mean difference 48 m [95% CI 32, 65 m]), obtained from a meta-analysis of 16 trials, was uncertain because the lower 95% CI (32 m) was outside the lower 95% CI (37 m) around the estimate of the MCID [50]. This MCID of 54 m is based on one cross-sectional study of 112 COPD patients attending a residential pulmonary rehabilitation programme [50]. The patients were asked to rate their ability to walk compared to their peers on five consecutive days. The patients’ subjective ratings were then compared with the measured 6MWDs achieved (range 119–705 m). The authors found that 6MWD needed to differ by about +40 m and −70 m for patients to stop rating themselves as about the same, and to begin rating themselves as a little bit better or a little bit worse respectively compared to other patients. These values were averaged to provide a threshold value of 54 m (95% CI 37, 71 m) [50]. This averaging technique could yield an overestimate for the threshold value if patients are more perceptive to a change in their own performance when compared to differences between themselves and others. A further consideration is that a mean threshold value for a group of patients may not provide a good representation of the perception of an individual [51]
or reflect a meaningful change across a range of pre-training 6MWDs.
What percentage of patients achieve the MCID for the 6MWD following pulmonary rehabilitation? When a standardised 6MWT protocol that includes a familiarisation test at pre-training assessment is utilised, the average improvement in 6MWD following pulmonary rehabilitation is below the 54 m threshold [7,52–54] with studies showing that only approximately one third of patients improve their 6MWD by 54 m [55] although the mean change reported exceeds the lower 95% CI of 37 m [7,52–55]. In contrast, studies that have failed to standardise the 6MWT protocol or provide a familiarisation test have reported much larger increases in 6MWD (e.g. as much as 90 m) following exercise training [34–37]. Some of the improvement in these studies is likely to be due to a familiarisation effect for the 6MWT. The mean increase in 6MWD following our pulmonary rehabilitation programme, which includes supervised, high intensity lower limb exercise training prescribed in accordance with published guidelines [3,4], is approximately 40 m (95% CI 31, 47 m), which exceeds the lower 95% CI for the MCID reported in the literature [50]. This magnitude of improvement in 6MWD is comparable to that reported in other studies of exercise training in COPD patients in which a standardised 6MWT protocol and familiarisation test at pretraining assessment were employed [52–54]. Further research is necessary to determine the threshold value for a clinically significant change when the 6MWD is used as an outcome of pulmonary rehabilitation. Such research should utilise a within-subject study design, consider the influence of pretraining 6MWD and consider what an individual perceives to be a meaningful difference in their 6MWD rather than accepting a group consensus.
How can a walking programme be prescribed using 6MWD? Clinical recommendations for exercise training in COPD patients include a component of high intensity, greater than 60% peak exercise capacity, lower limb endurance training with the aim of eliciting some physiological training effects [3,56]. To achieve this, ground-based or treadmill walking and cycling are the commonest exercise modalities used. In practice, many patients can tolerate training at intensities well in excess of 60% peak exercise capacity especially during ground-based walking and training at a higher percentage of peak capacity is likely to confer greater physiological benefits [56,57]. In moderate to severe COPD, the 6MWT represents a maximal or near maximal symptom-limited test [15,58,59] and data from the 6MWT can be used to prescribe the intensity of a walking programme.
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During the past 7 years, we have used the patient’s pretraining 6MWD to prescribe the intensity of a walking programme. Consistent with the findings of others [56,59] we observe that patients are able to sustain, for periods of at least 20 minutes, a training intensity that represents a high percentage (≥80%) of their peak performance measured using the 6MWT. In our programme, patients perform two 6MWTs at pre-training assessment using a highly standardised protocol [38,39] with the aim of achieving a maximal 6MWD and optimising training intensity. We prescribe the initial training intensity (i.e. speed) equivalent to 80% of the average speed achieved during the pre-training 6MWT [39,41]. This prescription applies irrespective of whether the patient requires a rest during the 6MWT. The prescribed walking programme is easily transferred into the community setting although modifications are required when the walking course incorporates inclines, uneven terrain or environmental conditions (e.g. high humidity, strong winds) that elicit greater dyspnoea than occurs when walking in the enclosed corridor. We use the same method to prescribe the intensity for treadmill walking; however, due to the unfamiliar nature of treadmill walking, the initial prescription is usually at a speed 0.5–1 kilometres per hour slower than would be prescribed for ground-based walking. Further methodological details pertaining to the prescription of a walking programme using 6MWD can be found in the Pulmonary Rehabilitation Toolkit [41]. Cycling is a common form of exercise training used in pulmonary rehabilitation and several studies have shown physiological responses following exercise training at a high percentage of the patient’s peak exercise capacity achieved on a symptom-limited incremental cycle ergometry test [57,60]. In clinical practice, many patients do not undergo a cycle ergometry test; however, it is possible to estimate a patient’s peak workload (Wpeak ) from 6MWD or 6MWW because a strong relationship exists between these variables and Wpeak [14,15,61]. At present, there is a paucity of literature describing workload prescription for cycle training based on the performance on a timed walking test [62] and further research is required to enable clinicians to use this method for prescribing training workload.
How can the 6MWD be used to select individuals likely to benefit from a rollator? Patients with COPD frequently report less dyspnoea when pushing a shopping trolley because the trolley enables the patient to adopt a forward lean position and to fix their shoulder girdle, a position that many patients with COPD spontaneously adopt in an attempt to gain relief from dyspnoea. This position is associated with improved inspiratory muscle function, due to the more favourable position of the diaphragm, and facilitates recruitment of the pectoral muscles to assist rib cage elevation during inspiration [63,64].
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The use of a rollator allows a patient to adopt this forward lean position with arm support. The 6MWD has been used to quantify the benefits of a rollator and to identify which patients benefit [65–68]. Studies have shown that using a rollator increases 6MWD as a result of a faster walking pace or a reduction in rest time, decreases dyspnoea at iso-distance and may be associated with a reduction in the magnitude of exercise-induced hypoxaemia [65–68]. Benefit is seen in individuals with a low 6MWD (unaided 6MWD <375 m) and those who require rests during the test [66,68]. The improvements obtained with a rollator are consistent over time [68]. From an exercise training perspective, it may be possible to achieve a higher walking intensity or longer duration of walking when a patient uses a rollator. The mechanisms responsible for the benefits are an increase in ventilatory capacity (minute ventilation, maxi˙ 2 /m) mal voluntary ventilation) and walking efficiency (VO that together explained 67% of the variance of the change in 6MWD [67]. Limitations of this study [67] however were the relatively small sample size (n = 14) and the inclusion of some patients with a high 6MWD for whom clinically a rollator would not be considered.
Can the 6MWT be used to identify exercise-induced hypoxaemia? Monitoring of SpO2 is commonly performed in patients with COPD undergoing supervised exercise training and the data used to assist with determining safe guidelines for exercise prescription. Several studies have shown that the 6MWT, in common with the incremental shuttle and other walking tests, is more sensitive than a symptom-limited incremental cycle ergometry test for detecting exercise-induced hypoxaemia in patients with COPD [15,40,69–71]. The underlying mechanisms for this finding have not been elucidated and are likely to be multifactorial. Differences in body position and the lack of arm support when walking, as compared to cycling, are thought to be contributory factors [70]. The presence of marked desaturation during the 6MWT is an indication to prescribe an intermittent walking training protocol and identifies the requirement for more frequent SpO2 monitoring during exercises that involve the use of large muscle groups, for example walking, step-ups/stair climbing and cycling.
Is 6MWD useful in acute exacerbations of COPD? A low 6MWD (≤367 m) has been associated with an increased risk of admission for an acute exacerbation of COPD [72] thus 6MWD may have a role in assisting in prioritising patients for exercise training. The 6MWT is appropriate for assessing patients recovering from an acute exacerbation of COPD as such individuals
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generally have poor exercise tolerance and require frequent rests when walking. Once the patient’s condition is stable, the test can be used to diagnose the presence of oxygen desaturation [73] and thus to determine whether assessment for ambulatory oxygen is indicated [74]. Comparison with a previous 6MWD, measured when the patient’s condition was stable, enables quantification of the impact of an exacerbation on a patient’s functional exercise capacity. The 6MWD can be used to prescribe a walking programme to be undertaken while the patient is in hospital and following discharge. In a cohort of 29 COPD patients recovering from an acute exacerbation of COPD, Kirsten et al. [75] performed a randomised controlled trial (RCT) comparing usual inpatient care with supervised exercise training. Subjects in the exercise training group performed a daily 6MWT (on a treadmill) and each day were instructed to perform five walking sessions per day with the goal of walking at least 75% of the 6MWD on the respective day without time limit. This prescription proved to be feasible and after 10 days of training resulted in an increase in 6MWD from 237 ± 28 to 420 ± 42 m in the exercise group compared to only 230 ± 23 to 255 ± 27 m in the usual care group (P < 0.001 compared to the increase in 6MWD in usual care group). The 6MWD has been used as an outcome measure of pulmonary rehabilitation in patients following an acute exacerbation of COPD. A systematic review of four RCTs comparing supervised exercise training versus usual care following an acute exacerbation of COPD showed a significant benefit of pulmonary rehabilitation on 6MWD [76]. During hospitalisation for an acute exacerbation of COPD patients are extremely inactive and, in the absence of pulmonary rehabilitation, activity levels remain low at 1 month following discharge from hospital [77]. Further, patients with the lowest physical activity levels are more likely to be readmitted [77]. A prospective study of 340 patients (92% males) followed for 1 year following a hospital admission for acute exacerbation of COPD showed that a high level of usual physical activity (equivalent to walking at least 60 minutes a day) was associated with a 46% reduction in the risk of readmission to hospital with COPD [78]. Improving physical activity is therefore likely to have a role in preventing hospital admissions for acute exacerbation of COPD. In patients with stable COPD, a low 6MWD (<400 m) is the best surrogate marker for physical inactivity during daily life [18] and thus 6MWD may assist in prioritising patients for pulmonary rehabilitation.
Conclusion This review has highlighted the clinical applications of 6MWD in patients with COPD undergoing pulmonary rehabilitation. Future research and clinical experience are likely to further refine these applications and identify new applications of the 6MWD in patients with COPD undergoing pulmonary rehabilitation.
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Expert article
6-Minute walk test in patients with COPD: clinical applications in pulmonary rehabilitation Sue C. Jenkins a,b,c,∗ a
School of Physiotherapy, Curtin University of Technology, GPO Box U1987, Perth, Western Australia 6845, Australia b Physiotherapy Department, Sir Charles Gairdner Hospital, Australia c Lung Institute of Western Australia, Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Australia
Abstract Pulmonary rehabilitation is an evidence-based intervention for the management of patients with chronic obstructive pulmonary disease (COPD). In clinical practice, the 6-minute walk test (6MWT) is commonly used to assess changes in functional exercise capacity in COPD patients following pulmonary rehabilitation with the primary outcome reported being the distance walked during the test (i.e. 6MWD). The 6MWD has demonstrated validity, reliability after one familiarisation test and the capacity to detect changes following pulmonary rehabilitation. In addition to assessing the outcomes of pulmonary rehabilitation, 6MWD may be used to quantify the magnitude of a patient’s disability, prescribe a walking programme, identify patients likely to benefit from a rollator and to identify the presence of exercise-induced hypoxaemia. This review describes the applications of the 6MWD in patients with COPD undergoing pulmonary rehabilitation. © 2007 Published by Elsevier Ltd on behalf of Chartered Society of Physiotherapy. Keywords: Pulmonary disease; Chronic obstructive; Exercise test; Walking; Rehabilitation
Introduction Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide [1]. Individuals with COPD develop progressive disability and impairment in quality of life. The disease is associated with high health care costs, of which hospitalisations for exacerbations are a major contributor [2]. There is a scarcity of good prevalence studies that include spirometric measures; however, based on the available literature the prevalence of physiologically defined COPD in adults aged 40 years or above is between 9 and 10% [1]. The prevalence of COPD is projected to increase in many parts of the world as a result of the ageing population and an increase in cigarette smoking [1].
∗
Tel.: +61 8 9266 3639; fax: +61 8 9266 3699. E-mail address: [email protected].
Assessment of functional exercise capacity in pulmonary rehabilitation Pulmonary rehabilitation is strongly endorsed as an evidence-based intervention for the management of patients with COPD [3,4]. The benefits of exercise training, the mandatory component of pulmonary rehabilitation, have been convincingly demonstrated [3,5,6]. In clinical practice, the 6-minute walk test (6MWT) and the incremental shuttle walking test are commonly used to assess changes in functional exercise capacity following pulmonary rehabilitation with the primary outcome reported being the distance walked during the test. Both tests have demonstrated validity, reliability after one familiarisation test, and have the capacity to detect changes following pulmonary rehabilitation [6–11]. The clinical preference for these field walking tests compared to laboratory-based tests using a cycle ergometer or treadmill is due to their increased availability and low cost, and because ground-based walking is more representative of activities of daily living [8].
0031-9406/$ – see front matter © 2007 Published by Elsevier Ltd on behalf of Chartered Society of Physiotherapy. doi:10.1016/j.physio.2007.02.001
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This article reviews the clinical applications of the 6MWT in pulmonary rehabilitation and is based on the literature and the author’s clinical and research experience. The review commences with a discussion of the validity and reliability of the 6MWD and predicted values for 6MWD. This is followed by the applications of 6MWD in pulmonary rehabilitation and includes the use of 6MWD as an outcome measure, for prescribing a walking programme and for selecting patients likely to benefit from a rollator. Also included is a discussion of the 6MWT to identify exercise-induced hypoxaemia. The final section gives an overview of the information provided by the 6MWD in patients recovering from an acute exacerbation of COPD.
Is the 6MWD a valid measure of exercise capacity in COPD? The validity of the 6MWD is demonstrated by the moderate to good relationship (r ≥ 0.5) between 6MWD and ˙ 2peak ) measured during a peak oxygen consumption (VO laboratory-based incremental exercise test to peak work capacity in patients with COPD [12–15]. The relationship tends to be strongest (r > 0.7) in patients with more severe functional limitation because a self-paced walking test in these individuals more closely represents maximal exercise performance [12,16]. Examination of the relationship between 6-minute walk work (6MWW, determined as the ˙ 2peak reveals product of body weight and 6MWD) and VO a stronger relationship (r = 0.81) than between 6MWD and ˙ 2peak because 6MWW represents the work done (i.e. force VO [body weight] × distance travelled) when performing the test [14].
Does 6MWD provide information about physical activity during daily life? Dyspnoea during activities of daily living is frequently reported by patients with COPD and can result in inactivity and the associated problems of deconditioning and muscle weakness. To the author’s knowledge only one study has objectively measured daily physical activity in COPD patients (n = 50) and compared the findings to data obtained in age- and gender-matched healthy controls (n = 25) [17,18]. Compared to the healthy controls, COPD patients spent significantly less time standing and walking during daily activities (P < 0.001, for both). In the COPD cohort, walking time and walking intensity were significantly correlated with 6MWD (r = 0.76 and r = 0.62, respectively, P < 0.001). In contrast, the correlations between these variables and maximal exercise capacity (r ≤ 0.33), lung function (r ≤ 0.38), respiratory (r ≤ 0.38) and peripheral muscle strength (r ≤ 0.45) were more modest. Pitta et al. [17] concluded that a reduced 6MWD (<400 m) is the best surrogate marker of inactivity during daily life in patients with COPD.
Is 6MWD associated with survival? In patients with severe airflow obstruction, longitudinal data demonstrate that the decline in 6MWD occurs independent of the change in the forced expiratory volume in one second (FEV1 ) [19]. Further, 6MWD is a stronger predictor of survival than FEV1 [19]. This is possibly because 6MWD is influenced by skeletal muscle dysfunction as well as pulmonary impairment and so reflects both the primary pulmonary and secondary systemic manifestations of COPD. The 6MWD is one of four variables, together with FEV1 , body mass index (BMI) and the Modified Medical Research Council (MMRC) dyspnoea scale, that comprise a multidimensional grading system known as the BODE Index [20]. The BODE Index has been shown to be a valid measure for predicting mortality from any cause and from respiratory causes in COPD patients [20]. This study [20] was carried out in 625 patients recruited from clinics in the USA, Europe and South America. However, limitations of the study include the predominance of male patients and the presence of geographical differences in 6MWD that are apparent independent of the severity of limitation in FEV1 [20,21]. In patients undergoing pulmonary rehabilitation, the change in BODE Index has been linked to survival and an improvement in the BODE Index has been shown to be associated with a reduction in hospitalisations for COPD exacerbations [22]. This is most likely due to the improvements that occur in 6MWD and dyspnoea following pulmonary rehabilitation in the absence of any changes in FEV1 or BMI. Is 6MWD a useful measure for selecting patients for lung volume reduction surgery or lung transplantation? Few studies have attempted to determine threshold values of 6MWD for successful outcome following lung volume reduction surgery (LVRS) or for listing patients for lung transplantation. In patients undergoing LVRS, Szekely et al. [23] reported that a 6MWD <200 m (achieved before or after pulmonary rehabilitation) was associated with a high level of mortality 6 months postoperatively (specificity 84%). In a retrospective review of 145 patients (58 with COPD) who underwent lung transplantation or died while awaiting surgery, the sensitivity, specificity and positive and negative predictive values for 6MWDs of 300 m and 400 m as a predictor of mortality were calculated [24]. The authors concluded that the 6MWT was a useful tool in the assessment of when to list patients for lung transplantation and that a 6MWD of less than 400 m appeared to be a reasonable marker corresponding to when a patient should be listed [24]. Is 6MWD a reliable measure? The 6MWT requires strict standardisation of the test protocol if reliable data are to be obtained. The factors
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that influence 6MWD (e.g. track length and course layout, instructions and encouragement, number of tests) and require standardisation have been reviewed in detail elsewhere [25,26]. A familiarisation effect for the test has been demonstrated with the majority of patients na¨ıve to the test increasing their 6MWD after one familiarisation test and little or no further increase occurring when a subsequent test is performed on the same day [27,28]. Dyspnoea is the most commonly cited symptom that limits performance on a walking test in COPD patients [29] and a repeat 6MWT is usually well tolerated after a 20–30 minute rest period by which time patients have recovered from the dyspnoea elicited during their familiarisation test. Analysis of 6MWD data obtained from 121 COPD patients referred to our programme showed that nearly all patients (106 patients, 87%) walked further following a familiarisation test. The mean increase for the group was 36 ± 32 m (mean ± SD, P < 0.001), which is of a similar magnitude to that reported by others in COPD patients [27,30] but significantly greater than the increase (18 ± 30 m, P < 0.001) we observed in 70 healthy subjects tested using an identical 6MWT protocol [31]. This is most likely explained by habituation to dyspnoea in individuals with COPD, which is not a factor in healthy individuals. However, in clinical practice and studies of pulmonary rehabilitation a familiarisation 6MWT is not always performed and there is sometimes poor standardisation of the test protocol with little attempt to ensure an individual achieves their maximal performance on the test [32–37].
Is a familiarisation test always necessary? Where performance on the test is limited by symptoms from co-morbid conditions, for example musculoskeletal or claudication pain, it is reasonable to omit a second test at pre-training assessment. In patients with co-morbid cardiac disease, consideration should be given to terminating the test when heart rate reaches 85% of age-predicted maximal heart rate. Finally, in patients who demonstrate profound oxygen desaturation (SpO2 <80%) during the initial 6MWT, the test should not be repeated unless assessment for ambulatory oxygen is undertaken. There are limited data to indicate whether a familiarisation 6MWT is necessary at follow-up assessments [38]. Our data in 32 COPD patients showed only a small increase in 6MWD (9 ± 19 m, P > 0.05) following a familiarisation test at the end of an 8-week training programme [38]; however, when the 6MWT is repeated at long-term follow-up a familiarisation test may be necessary [39].
Does a standardised protocol exist for the 6MWT? In 2002, the American Thoracic Society (ATS) published guidelines for the 6MWT with the aim of providing a stan-
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dardised approach to test performance [26]. These guidelines however raise some important concerns. Notably, the guidelines state that the use of pulse oximetry is optional and a familiarisation test is not needed in most clinical settings. Failure to monitor oxygen saturation (SpO2 ) raises safety concerns as a proportion of patients with moderate to severe COPD demonstrate significant desaturation during the 6MWT [15,40]. The absence of a familiarisation test at pre-training assessment is likely to lead to an overestimate of the effects of training on 6MWD. For details of a standardised 6MWT protocol the reader is referred to the Pulmonary Rehabilitation Toolkit developed by the Australian Physiotherapy Association and The Australian Lung Foundation [41]. The protocol described in the Toolkit is based on the ATS guidelines [26] with modifications to include monitoring of SpO2 , standard instructions if a patient rests during the test and a familiarisation test.
Can a patient’s 6MWD be referenced to a ‘normal’ 6MWD? In recent years there has been interest in expressing an individual’s 6MWD as a percentage of their predicted 6MWD in an attempt to quantify the magnitude of a patient’s disability. Several reference equations are available for this purpose [31,42–45]. The amount of variance in 6MWD explained by these equations ranges from 19 to 66% with most reporting that age, height, weight and gender are significant contributors to 6MWD. The weighting of gender as a contributor, independent of height, varies among the equations with some equations predicting a similar 6MWD for males and females of the same height [31,45]. Only the extremes of body weight appear to influence 6MWD [45] and equations that include weight as an inverse contributor to 6MWD [42,43] will overestimate the 6MWD for a patient who is underweight. The published equations predict 6MWDs that vary by up to 175 m for the same individual. Possible explanations for this discrepancy include differences in the subject sample used to generate the equation (i.e. random vs convenience sample) and in the 6MWT protocol. For example, the equation generated by Enright et al. [42] predicts significantly lower 6MWDs than other equations generated in Caucasian samples [31,43,44]. Explanations for this discrepancy may include the performance of a single 6MWT only in the study by Enright et al. [42] in contrast to other studies that used between two and four repetitions of the test [31,43,44]. Further, the very modest increase in heart rate in Enright’s sample [42], compared to other studies [31,43], suggests that the subject’s effort was submaximal despite being instructed to cover as much ground as possible in 6 minutes and receiving standardised encouragement. Six-minute walk distance appears to vary in individuals from different geographical regions [20,21] with race and ethnicity contributing to 6MWD [45–47]. This suggests there is a need for facilities providing pulmonary rehabilitation to
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develop their own regression equation to predict 6MWD if a valid estimate of the impact of COPD on 6MWD is to be obtained.
6MWD as an outcome of pulmonary rehabilitation: what is the minimum clinically important difference (MCID)? The 6MWD has been shown to be responsive to change following pulmonary rehabilitation [7]. The 6MWT is unique among walking-based tests of exercise capacity in that it is self-paced and allows patients to rest in the event that dyspnoea becomes intolerable. Therefore, patients with severe disability can increase their 6MWD by walking faster or reducing the number or duration of rest periods. In contrast, patients with a high pre-training 6MWD, for example a 6MWD of 600 m implies an average walking speed of 6 kilometres per hour on the test, may be limited in their ability to demonstrate improvements in 6MWD because mechanical factors such as stride length may limit performance and give rise to a ceiling effect for the test [48]. When reporting change in 6MWD, the ATS guidelines for the 6MWT recommend that the absolute change and not the percentage change is reported [26]. The magnitude of improvement in 6MWD that represents the threshold for a clinically significant change has not been extensively researched. It is widely quoted in the literature that 54 m (95% confidence intervals [CI] 37, 71 m) represents the threshold value for a clinically significant change regardless of pre-training 6MWD [26,49]. Using these data, the Cochrane Review of pulmonary rehabilitation for COPD [6] concluded that the clinical significance of the improvement in 6MWD (weighted mean difference 48 m [95% CI 32, 65 m]), obtained from a meta-analysis of 16 trials, was uncertain because the lower 95% CI (32 m) was outside the lower 95% CI (37 m) around the estimate of the MCID [50]. This MCID of 54 m is based on one cross-sectional study of 112 COPD patients attending a residential pulmonary rehabilitation programme [50]. The patients were asked to rate their ability to walk compared to their peers on five consecutive days. The patients’ subjective ratings were then compared with the measured 6MWDs achieved (range 119–705 m). The authors found that 6MWD needed to differ by about +40 m and −70 m for patients to stop rating themselves as about the same, and to begin rating themselves as a little bit better or a little bit worse respectively compared to other patients. These values were averaged to provide a threshold value of 54 m (95% CI 37, 71 m) [50]. This averaging technique could yield an overestimate for the threshold value if patients are more perceptive to a change in their own performance when compared to differences between themselves and others. A further consideration is that a mean threshold value for a group of patients may not provide a good representation of the perception of an individual [51]
or reflect a meaningful change across a range of pre-training 6MWDs.
What percentage of patients achieve the MCID for the 6MWD following pulmonary rehabilitation? When a standardised 6MWT protocol that includes a familiarisation test at pre-training assessment is utilised, the average improvement in 6MWD following pulmonary rehabilitation is below the 54 m threshold [7,52–54] with studies showing that only approximately one third of patients improve their 6MWD by 54 m [55] although the mean change reported exceeds the lower 95% CI of 37 m [7,52–55]. In contrast, studies that have failed to standardise the 6MWT protocol or provide a familiarisation test have reported much larger increases in 6MWD (e.g. as much as 90 m) following exercise training [34–37]. Some of the improvement in these studies is likely to be due to a familiarisation effect for the 6MWT. The mean increase in 6MWD following our pulmonary rehabilitation programme, which includes supervised, high intensity lower limb exercise training prescribed in accordance with published guidelines [3,4], is approximately 40 m (95% CI 31, 47 m), which exceeds the lower 95% CI for the MCID reported in the literature [50]. This magnitude of improvement in 6MWD is comparable to that reported in other studies of exercise training in COPD patients in which a standardised 6MWT protocol and familiarisation test at pretraining assessment were employed [52–54]. Further research is necessary to determine the threshold value for a clinically significant change when the 6MWD is used as an outcome of pulmonary rehabilitation. Such research should utilise a within-subject study design, consider the influence of pretraining 6MWD and consider what an individual perceives to be a meaningful difference in their 6MWD rather than accepting a group consensus.
How can a walking programme be prescribed using 6MWD? Clinical recommendations for exercise training in COPD patients include a component of high intensity, greater than 60% peak exercise capacity, lower limb endurance training with the aim of eliciting some physiological training effects [3,56]. To achieve this, ground-based or treadmill walking and cycling are the commonest exercise modalities used. In practice, many patients can tolerate training at intensities well in excess of 60% peak exercise capacity especially during ground-based walking and training at a higher percentage of peak capacity is likely to confer greater physiological benefits [56,57]. In moderate to severe COPD, the 6MWT represents a maximal or near maximal symptom-limited test [15,58,59] and data from the 6MWT can be used to prescribe the intensity of a walking programme.
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During the past 7 years, we have used the patient’s pretraining 6MWD to prescribe the intensity of a walking programme. Consistent with the findings of others [56,59] we observe that patients are able to sustain, for periods of at least 20 minutes, a training intensity that represents a high percentage (≥80%) of their peak performance measured using the 6MWT. In our programme, patients perform two 6MWTs at pre-training assessment using a highly standardised protocol [38,39] with the aim of achieving a maximal 6MWD and optimising training intensity. We prescribe the initial training intensity (i.e. speed) equivalent to 80% of the average speed achieved during the pre-training 6MWT [39,41]. This prescription applies irrespective of whether the patient requires a rest during the 6MWT. The prescribed walking programme is easily transferred into the community setting although modifications are required when the walking course incorporates inclines, uneven terrain or environmental conditions (e.g. high humidity, strong winds) that elicit greater dyspnoea than occurs when walking in the enclosed corridor. We use the same method to prescribe the intensity for treadmill walking; however, due to the unfamiliar nature of treadmill walking, the initial prescription is usually at a speed 0.5–1 kilometres per hour slower than would be prescribed for ground-based walking. Further methodological details pertaining to the prescription of a walking programme using 6MWD can be found in the Pulmonary Rehabilitation Toolkit [41]. Cycling is a common form of exercise training used in pulmonary rehabilitation and several studies have shown physiological responses following exercise training at a high percentage of the patient’s peak exercise capacity achieved on a symptom-limited incremental cycle ergometry test [57,60]. In clinical practice, many patients do not undergo a cycle ergometry test; however, it is possible to estimate a patient’s peak workload (Wpeak ) from 6MWD or 6MWW because a strong relationship exists between these variables and Wpeak [14,15,61]. At present, there is a paucity of literature describing workload prescription for cycle training based on the performance on a timed walking test [62] and further research is required to enable clinicians to use this method for prescribing training workload.
How can the 6MWD be used to select individuals likely to benefit from a rollator? Patients with COPD frequently report less dyspnoea when pushing a shopping trolley because the trolley enables the patient to adopt a forward lean position and to fix their shoulder girdle, a position that many patients with COPD spontaneously adopt in an attempt to gain relief from dyspnoea. This position is associated with improved inspiratory muscle function, due to the more favourable position of the diaphragm, and facilitates recruitment of the pectoral muscles to assist rib cage elevation during inspiration [63,64].
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The use of a rollator allows a patient to adopt this forward lean position with arm support. The 6MWD has been used to quantify the benefits of a rollator and to identify which patients benefit [65–68]. Studies have shown that using a rollator increases 6MWD as a result of a faster walking pace or a reduction in rest time, decreases dyspnoea at iso-distance and may be associated with a reduction in the magnitude of exercise-induced hypoxaemia [65–68]. Benefit is seen in individuals with a low 6MWD (unaided 6MWD <375 m) and those who require rests during the test [66,68]. The improvements obtained with a rollator are consistent over time [68]. From an exercise training perspective, it may be possible to achieve a higher walking intensity or longer duration of walking when a patient uses a rollator. The mechanisms responsible for the benefits are an increase in ventilatory capacity (minute ventilation, maxi˙ 2 /m) mal voluntary ventilation) and walking efficiency (VO that together explained 67% of the variance of the change in 6MWD [67]. Limitations of this study [67] however were the relatively small sample size (n = 14) and the inclusion of some patients with a high 6MWD for whom clinically a rollator would not be considered.
Can the 6MWT be used to identify exercise-induced hypoxaemia? Monitoring of SpO2 is commonly performed in patients with COPD undergoing supervised exercise training and the data used to assist with determining safe guidelines for exercise prescription. Several studies have shown that the 6MWT, in common with the incremental shuttle and other walking tests, is more sensitive than a symptom-limited incremental cycle ergometry test for detecting exercise-induced hypoxaemia in patients with COPD [15,40,69–71]. The underlying mechanisms for this finding have not been elucidated and are likely to be multifactorial. Differences in body position and the lack of arm support when walking, as compared to cycling, are thought to be contributory factors [70]. The presence of marked desaturation during the 6MWT is an indication to prescribe an intermittent walking training protocol and identifies the requirement for more frequent SpO2 monitoring during exercises that involve the use of large muscle groups, for example walking, step-ups/stair climbing and cycling.
Is 6MWD useful in acute exacerbations of COPD? A low 6MWD (≤367 m) has been associated with an increased risk of admission for an acute exacerbation of COPD [72] thus 6MWD may have a role in assisting in prioritising patients for exercise training. The 6MWT is appropriate for assessing patients recovering from an acute exacerbation of COPD as such individuals
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generally have poor exercise tolerance and require frequent rests when walking. Once the patient’s condition is stable, the test can be used to diagnose the presence of oxygen desaturation [73] and thus to determine whether assessment for ambulatory oxygen is indicated [74]. Comparison with a previous 6MWD, measured when the patient’s condition was stable, enables quantification of the impact of an exacerbation on a patient’s functional exercise capacity. The 6MWD can be used to prescribe a walking programme to be undertaken while the patient is in hospital and following discharge. In a cohort of 29 COPD patients recovering from an acute exacerbation of COPD, Kirsten et al. [75] performed a randomised controlled trial (RCT) comparing usual inpatient care with supervised exercise training. Subjects in the exercise training group performed a daily 6MWT (on a treadmill) and each day were instructed to perform five walking sessions per day with the goal of walking at least 75% of the 6MWD on the respective day without time limit. This prescription proved to be feasible and after 10 days of training resulted in an increase in 6MWD from 237 ± 28 to 420 ± 42 m in the exercise group compared to only 230 ± 23 to 255 ± 27 m in the usual care group (P < 0.001 compared to the increase in 6MWD in usual care group). The 6MWD has been used as an outcome measure of pulmonary rehabilitation in patients following an acute exacerbation of COPD. A systematic review of four RCTs comparing supervised exercise training versus usual care following an acute exacerbation of COPD showed a significant benefit of pulmonary rehabilitation on 6MWD [76]. During hospitalisation for an acute exacerbation of COPD patients are extremely inactive and, in the absence of pulmonary rehabilitation, activity levels remain low at 1 month following discharge from hospital [77]. Further, patients with the lowest physical activity levels are more likely to be readmitted [77]. A prospective study of 340 patients (92% males) followed for 1 year following a hospital admission for acute exacerbation of COPD showed that a high level of usual physical activity (equivalent to walking at least 60 minutes a day) was associated with a 46% reduction in the risk of readmission to hospital with COPD [78]. Improving physical activity is therefore likely to have a role in preventing hospital admissions for acute exacerbation of COPD. In patients with stable COPD, a low 6MWD (<400 m) is the best surrogate marker for physical inactivity during daily life [18] and thus 6MWD may assist in prioritising patients for pulmonary rehabilitation.
Conclusion This review has highlighted the clinical applications of 6MWD in patients with COPD undergoing pulmonary rehabilitation. Future research and clinical experience are likely to further refine these applications and identify new applications of the 6MWD in patients with COPD undergoing pulmonary rehabilitation.
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