Correlates of 5-year decline in 6-min walk distance in the COPDGene cohort

Background Change in 6-min walk distance (6MWD) over time serves as a measure of change in functional exercise performance. We analysed a large cohort of current or former tobacco smokers over a 5-year period to identify correlates of 6MWD decline. Methods A total of 4734 participants with normal spirometry or spirometric evidence of chronic obstructive pulmonary disease (COPD) who completed a 5-year follow-up in the COPDGene study were included. Baseline and 5-year assessments included 6MWD, spirometry, St. George’s Respiratory Questionnaire (SGRQ), gender, race and CT measures of emphysema, gas trapping and airway wall thickness. 6MWD decline correlates relative to baseline and 5-year changes were examined using univariate and multivariate linear regression. Results At baseline, 2573 had normal spirometry; 487 were classified as GOLD1, 1044 as GOLD2, 514 as GOLD3 and 116 as GOLD4. Average 5-year decline in 6MWD was 35.6±101.7 (SD) metres (p<0.001). COPD participants experienced greater 6MWD decline (44.1±101.9 m, p<0.001) compared with those with normal spirometry (28.5±101.0 m, p<0.001). Only baseline 6MWD and study site accounted for appreciable fractions of 6MWD decline variance (R 2 =12.1% and 9.1%, respectively). 5 year change in variables assessed (including FEV 1 and SGRQ) explained only small fractions of 6MWD decline variance (each R 2 ≤5%). Conclusion 6MWD declined significantly, but with high variability; spirometry, CT, health status, demographic and anthropometric measures accounted for only small portions of this variance. Our findings suggest that a meaningful decline in 6MWD observed over 5 years in COPD patients is in large part related to factors other than decline in pulmonary structure or function.