Optimizing the 6-min walk test as a measure of exercise capacity in COPD

Abstract

Background: It is uncertain whether the effort and expense of performing a second walk for the 6-min walk test improves test performance. Hence, we attempted to quantify the improvement in 6-min walk distance if an additional walk were to be performed.

Methods: We studied patients consecutively enrolled into the National Emphysema Treatment Trial who prior to randomization and after 6 to 10 weeks of pulmonary rehabilitation performed two 6-min walks on consecutive days (N = 396). Patients also performed two 6-min walks at 6-month follow-up after randomization to lung volume reduction surgery (n = 74) or optimal medical therapy (n = 64). We compared change in the first walk distance to change in the second, average-of-two, and best-of-two walk distances.

Results: Compared with the change in the first walk distance, change in the average-of-two and best-of-two walk distances had better validity and precision. Specifically, 6 months after randomization to lung volume reduction surgery, changes in the average-of-two (r = 0.66 vs r = 0.58, P = .01) and best-of-two walk distances (r = 0.67 vs r = 0.58, P = .04) better correlated with the change in maximal exercise capacity (ie, better validity). Additionally, the variance of change was 14% to 25% less for the average-of-two walk distances and 14% to 33% less for the best-of-two walk distances than the variance of change in the single walk distance, indicating better precision.

Conclusions: Adding a second walk to the 6-min walk test significantly improves its performance in measuring response to a therapeutic intervention, improves the validity of COPD clinical trials, and would result in a 14% to 33% reduction in sample size requirements. Hence, it should be strongly considered by clinicians and researchers as an outcome measure for therapeutic interventions in patients with COPD.

Figure 1.

Layout of the National Emphysema Treatment Trial showing timing of measurements, sample sizes for the current analysis, and differences that were calculated using data from different time points. Beyond the 6-mo follow-up visit, there were too few patients with two walks per 6-min walk test for a meaningful analysis. LVRS = lung volume reduction surgery; OMT = optimal medical therapy; REHAB = rehabilitation.

Figure 2.

A, B, Scatterplots for change in walk distance vs change in exercise capacity measured on cardiopulmonary exercise testing in patients undergoing lung volume reduction surgery (n = 74). Each plot has a fitted regression line with 95% confidence bands. The scatter was closer to the line, the 95% confidence bands were narrower, and the correlation (r) was stronger for best-of-two walk distances compared with change in the first walk distance. The increase in the correlation was significant for the best-of-two-walk distances vs that for the first walk distance (r = 0.58 vs r = 0.67, respectively, P = .04).

Figure 3.

Power curves for a parallel-arm clinical trial designed to identify an improvement in walk distance of 131.2 ft (40 m) with a two-tailed α of .05. The solid curve uses an SD of 180.2 ft that was observed using the first walk distance during rehabilitation in the National Emphysema Treatment Trial. The dashed and dotted curves represent the left shift in the power curve due to a 14% and 33% reduction in variance, respectively, with a resulting reduction in sample size if patients in the trial performed two instead of one walk for the 6-min walk test and either change in average-of-two or in best-of-two walk distance was used as the final test result.