Original Study
Predicting Outcomes from 6-Minute Walk Distance in Chronic Obstructive Pulmonary Disease

This study has been presented at the American Thoracic Society 2011 Congress, Denver, CO, May 13-18, 2011.
https://doi.org/10.1016/j.jamda.2011.06.009Get rights and content

Abstract

Background

Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test (6MWT). To improve the utility of the 6MWT for patient and health care system management, the interpretation of the functional status measure in relation to death and hospitalization should be elucidated.

Methods

Three-year, prospective, multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD.

Results

We measured 6MWD at baseline and annually in 2110 patients with clinically stable Global Initiative for Obstructive Lung Disease (GOLD) stage II–IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality. During the study, 200 patients died and 650 were hospitalized. Using receiver operating characteristics, the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization (area under the curve 0.67 and 0.60 respectively); however, the discriminatory thresholds, especially for mortality, were influenced by age. The mean (SE) 6MWD declined by 1.6 (1.2) m per year in GOLD II, 9.8 (1.3) m per year in GOLD III, and 8.5 (2.4) m per year in GOLD IV.

Conclusion

The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD.

Section snippets

Material and Methods

ECLIPSE was a 3-year, multicenter, longitudinal, prospective study to identify novel end points in COPD.16 Participants were aged 40 to 75 years with a smoking history of 10 or more pack-years, a baseline post-bronchodilator forced expiratory volume (FEV1) of less than 80% of the predicted value, baseline post-bronchodilator FEV1/forced vital capacity of 0.7 or less, and a diagnosis of COPD.17 We measured baseline post-bronchodilator spirometry and calculated FEV1 as percent predicted.18 This

Patient Characteristics

A total of 2110 COPD patients (65% men) completed the baseline 6MWT and were included in the current report (Figure 1). Patients generally had moderate to very severe COPD, a normal body mass index, and an impaired health status (Table 1). Moreover, 53% scored grade 2 or higher on the mMRC dyspnea scale, and 56% reported the presence of cardiovascular disease(s).

All-Cause Mortality

A total of 200 deaths occurred during the 3-year follow-up period, with an average time from enrollment to death of 86.2 (41.3) weeks.

Discussion

Our data (in a large, multicenter, multinational cohort) confirm the power of 6MWD to identify subsets of the COPD population at higher risk of exacerbation-related admission or death. The distances with best sensitivity and specificity were 357 m and 334 m respectively, suggesting that the previously identified value of 350 m may be a valid, easy-to-remember threshold. Novel aspects of the present data are the demonstration of the interaction with age and the first large-scale evaluation of

Acknowledgments

A full list of principal investigators and centers participating in ECLIPSE, and the members of the ECLIPSE steering and scientific committees is provided in Appendix 1. Editorial support in the form of copyediting and graphic services was provided by Geoff Weller at Gardiner-Caldwell Communications. This support was funded by GlaxoSmithKline.

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      Citation Excerpt :

      Knowledge of the MCID is essential to evaluate outcome measures, such as the 6 MW T distance. The ECLIPSE cohort study, a large, multicenter, prospective observational cohort of patients with a wide range of airflow obstruction, showed that patients with a 6 MW T distance less than 334 m and 357 m have an increased risk of death and hospitalization, respectively [10,25]. Polkey et al. defined an MCID based on mortality and used the ECLIPSE cohort of patients with COPD to demonstrate that a decrease in 6 MW T distance over one year of 30 m or more is significantly associated with the risk of death over the subsequent 12 months (95% CI, 1.29–2.90, p = 0.001) [10].

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    M.A.S. and M.I.P. are joint first authors.

    MAS: No conflicts to declare.

    MIP: Salary is part funded by the NIHR Respiratory Biomedical Research Unit at the Royal Brompton & Harefield NHS Trust and Imperial College London UK. He discloses receiving payment for advisory boards or lecturing from GlaxoSmithKline, Astra Zeneca, Chiesi, Novartis, PortAero and Broncus all of whom would have potential interest in using 6MWT as a study outcome and that his institution holds or has recently held on his behalf as Principal Investigator grants for COPD studies or for consultancy from GlaxoSmithKline, Astra Zeneca, PortAero, Novartis and the EU-IMI Proactive initiative.

    BC: Received grants to the pulmonary division he works in to complete research studies from GlaxoSmithKline, Boehringer-Ingelheim, Forrest Medical, AstraZeneca and Aeris. BC has served on advisory boards for GlaxosmithKline, Boehringer-Ingelheim, Almirall, AstraZeneca, Aeris and Deep Breeze, and has received speaker fees from GlaxosmithKline, Boehringer-Ingelheim, AstraZeneca, Almirall and Esteve.

    LDE: Employee and shareholder of GlaxoSmithKline.

    MLW: Employee and shareholder of GlaxoSmithKline.

    VPP: No conflicts to declare.

    JV: Received fees for advising and/or presenting from GlaxoSmithKline, Astra Zeneca, Pfizer, Boehringer-Ingelheim, Nycomed, Hofmann - la Roche, Talecris, Kamada and Sounds Biotech; has received research support from GlaxoSmithKline.

    PMAC: Received consulting fees from AstraZeneca, GlaxoSmithKline, Nycomed and Pfizer, speaking fees from GlaxoSmithKline and Nycomed, and grant support from Boehringer-Ingelheim and GlaxoSmithKline.

    RT-S: Employee and shareholder of GlaxoSmithKline.

    AA: Received reimbursements, fees, or funding from GlaxoSmithKline, Almirall, AstraZeneca, Boheringer-Ingelheim, Roche, Nycomed, Novartis and Procter & Gamble.

    HOC: Holds a GSK Clinical Scientist Award from GSK Canada but was a Canadian Institutes of Health Research/British Columbia Lung Association New Investigator during the time of this study. HOC has received an honorarium for serving on the steering committee for the ECLIPSE project for GlaxoSmithKline. In addition, HOC was the co-investigator on two multi-center studies sponsored by GlaxoSmithKline and has received travel expenses to attend meetings related to the project. HOC has three contract service agreements with GlaxoSmithKline to quantify the CT scans in subjects with COPD and a service agreement with Spiration Inc. to measure changes in lung volume in subjects with severe emphysema. HOC is the co-investigator (D Sin PI) on a Canadian Institutes of Health - Industry (Wyeth) partnership grant, and has received a fee for speaking at a conference and related travel expenses from AstraZeneca (Australia).

    DAL: Received grant funding, honoraria and travel expenses from GlaxoSmithKline and serves on the Respiratory CEDD Board of GlaxoSmithKline.

    WM: Reimbursed for travel by GlaxoSmithKline, Zambon, Astra Zeneca, Boehringer-Ingelheim, Pfizer and Micromet for attending conferences; has received honoraria from GlaxoSmithKline and AstraZeneca for participating as a speaker in scientific meetings; serves on advisory boards for GlaxoSmithKline, Pfizer, Almirall, Amgen, Bayer and Micromet; serves as a consultant for Pfizer and SMB Pharmaceuticals. SR: consulted or participated in advisory boards for Able Associates, Adelphia Research, Almirall/Prescott, APT Pharma/Britnall, Aradigm, AstraZeneca, Boehringer-Ingelheim, Chiesi, CommonHealth, Consult Complete, COP Forum, DataMonitor, Decision Resources, Defined Health, Dey, Dunn Group, Eaton Associates, Equinox, Gerson, GlaxoSmithKline, Infomed, KOL Connection, M. Pankove, MedaCorp, MDRx Financial, Mpex, Novartis, Nycomed, Oriel Therapeutics, Otsuka, Pennside Partners, Pfizer (Varenicline), PharmaVentures, Pharmaxis, Price Waterhouse, Propagate, Pulmatrix, Reckner Associates, Recruiting Resources, Roche, Schlesinger Medical, Scimed, Sudler and Hennessey, TargeGen, Theravance, UBC, Uptake Medical, VantagePoint Management.

    SR has given lectures for: American Thoracic Society, Astra Zeneca, Boehringer-Ingelheim, California Allergy Society, Creative Educational Concept, France Foundation, Information TV, Network for Continuing Ed, Novartis, Pfizer, SOMA. SR has received industry-sponsored grants from: Astra Zeneca, Biomarck, Centocor, Mpex, Nabi, Novartis, Otsuka.

    EKS: Received grant support and consulting fees from GlaxoSmithKline for studies of COPD genetics and honoraria and consulting fees from Astra Zeneca.

    CC: Employee and shareholder of GlaxoSmithKline.

    JCY: Employee and shareholder of GlaxoSmithKline.

    EFMW: Serves on an advisory board for Nycomed. EFMW has received lecture fees from GlaxoSmithKline, AstraZeneca and Novartis, and has received research grants from GlaxoSmithKline and AstraZeneca.

    This article has an online depository, which is accessible from this issue’s table of contents.

    The ECLIPSE study is funded by GlaxoSmithKline. GlaxoSmithKline had a role in study design, data collection and analyses, decision to publish, and preparation of the manuscript.

    The trial's unique registration number: ClinicalTrials.gov with identifier NCT00292552.

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