title: The 6-Minute-Walk Distance Test as a Chronic Obstructive Pulmonary Disease Stratification Tool. Insights from the COPD Biomarker Qualification Consortium.
abstract: The 6-minute-walk distance (6MWD) test predicts mortality in chronic obstructive pulmonary disease (COPD). Whether variability in study type (observational vs. interventional) or region performed limits use of the test as a stratification tool or outcome measure for therapeutic trials is unclear.
  
  
  
  To analyze the original data from several large observational studies and from randomized clinical trials with bronchodilators to support the qualification of the 6MWD test as a drug development tool in COPD.
  
  
  
  Original data from 14,497 patients with COPD from six observational (n = 9,641) and five interventional (n = 4,856) studies larger than 100 patients and longer than 6 months in duration were included. The geographical, anthropometrics, FEV1, dyspnea, comorbidities, and health status scores were measured. Associations between 6MWD and mortality, hospitalizations, and exacerbations adjusted by study type, age, and sex were evaluated. Thresholds for outcome prediction were calculated using receiver operating curves. The change in 6MWD after inhaled bronchodilator treatment and surgical lung volume reduction were analyzed to evaluate the responsiveness of the test as an outcome measure.
  
  
  
  The 6MWD was significantly lower in nonsurvivors, those hospitalized, or who exacerbated compared with those without events at 6, 12, and greater than 12 months. At these time points, the 6MWD receiver operating characteristic curve-area under the curve to predict mortality was 0.71, 0.70, and 0.68 and for hospitalizations was 0.61, 0.60, and 0.59, respectively. After treatment, the 6MWD was not different between placebo and bronchodilators but increased after surgical lung volume reduction compared with medical therapy. Variation across study types (observational or therapeutic) or regions did not confound the ability of 6MWD to predict outcome.
  
  
  
  The 6MWD test can be used to stratify patients with COPD for clinical trials and interventions aimed at modifying exacerbations, hospitalizations, or death.
authors.affiliation: 1 Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.affiliation: 2 Boehringer Ingelheim, Ingelheim, Germany.|3 Department of Sports Medicine, University of Tuebingen, Tuebingen, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Tetzlaff
authors.affiliation: 4 Temple University Medical Center, Philadelphia, Pennsylvania.
authors.forename: Gerard
authors.initials: G
authors.lastname: Criner
authors.affiliation: 5 National Institute for Health Research Respiratory Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College, London, United Kingdom.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: 6 University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Frank
authors.initials: F
authors.lastname: Sciurba
authors.affiliation: 7 Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.affiliation: 8 GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: 9 Evidera, Bethesda, Maryland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Kawata
authors.affiliation: 10 COPD Foundation, Washington, District of Columbia; and.
authors.forename: Debora
authors.initials: D
authors.lastname: Merrill
authors.affiliation: 11 Division of Pulmonary, Allergy, Sleep and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
mesh_terms: D000368:Aged; D015415:Biomarkers; D003245:Consensus Statements as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000503:physiopathology*; D015203:Reproducibility of Results; D000070857:Walk Test / Q000379:methods* / Q000706:statistics & numerical data*
chemical_list: D015415:Biomarkers
keywords: 6-minute-walk distance; chronic obstructive pulmonary disease; outcomes