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Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort

Alvar Agusti, Lisa D. Edwards, Bartolomé Celli, William MacNee, Peter M. A. Calverley, Hana Müllerova, David A. Lomas, Emiel Wouters, Per Bakke, Steve Rennard, Courtney Crim, Bruce E. Miller, Harvey O. Coxson, Julie C. Yates, Ruth Tal-Singer, Jørgen Vestbo on behalf of the ECLIPSE investigators
European Respiratory Journal 2013 42: 636-646; DOI: 10.1183/09031936.00195212
Alvar Agusti
1Thorax Institute, Hospital Clinic, IDIBAPS, Universitat de Barcelona and CIBER Enfermedades Respiratorias, FISIB, Mallorca, Spain
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  • For correspondence: alvar.agusti@clinic.ub.es
Lisa D. Edwards
2GlaxoSmithKline, Research Triangle Park, NC
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Bartolomé Celli
3Dept of Respiratory Medicine; Brigham and Women's Hospital, Boston, MA
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William MacNee
4University of Edinburgh & Royal Infirmary, Edinburgh
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Peter M. A. Calverley
5Dept of Respiratory Medicine, University Hospital Aintree, Liverpool
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Hana Müllerova
6Epidemiology, GlaxoSmithKline R&D, Middlesex
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David A. Lomas
7Dept of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge
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Emiel Wouters
8Dept of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
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Per Bakke
9Institute of Medicine, University of Bergen, Bergen
10Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway
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Steve Rennard
11University of Nebraska Medical Center, Omaha, NE
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Courtney Crim
2GlaxoSmithKline, Research Triangle Park, NC
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Bruce E. Miller
12GlaxoSmithKline, King of Prussia, PA, USA
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Harvey O. Coxson
13Dept of Radiology, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada
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Julie C. Yates
2GlaxoSmithKline, Research Triangle Park, NC
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Ruth Tal-Singer
12GlaxoSmithKline, King of Prussia, PA, USA
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Jørgen Vestbo
14Dept of Respiratory Medicine, Odense University Hospital/University of Southern Denmark, Denmark
15Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
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    Figure 1–

    Frequency distribution of the chronic obstructive pulmonary patients studied here according to the 2007 (a) or 2011 (b) Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. Two subjects were classified as having GOLD stage I but were not included in a) or b). c) Shows the cumulative distribution of the four patient groups for the 2011 GOLD classification within each 2007 GOLD stage.

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    Figure 2–

    Temporal variation of the four 2011 Global Initiative for Chronic Obstructive Lung Disease groups at recruitment and during the 3-year follow-up. Boxes with percentages indicate the proportion of baseline patients available for examination at the 3-year follow-up. #: death/drop-out/lost for follow-up/missing data.

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    Figure 3–

    Kaplan–Meier curves for exacerbations (a, d and g), hospitalisations during follow-up (b, e and h) and all-cause mortality (c, f and i) for the 2007 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations for all patients (a–c), 2011 GOLD recommendations for all patients (d–f) and 2011 GOLD recommendations for patients with forced expiratory volume in 1 s (FEV1) ≥50% of the reference (GOLD stage II) (g–i).

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    Figure 4–

    Percentage of patients with at least one self-reported comorbidity (a) or persistent, systemic inflammation (b), as described by Agusti et al. [14], in the four groups of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) patient classification. a) p<0.05 for all comparisons except for group A versus group B. b) p<0.05 for all comparisons except for group B versus group D. It is of note that both were highest in B patients.

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  • Table 1– Outcomes of the four groups of patients as per the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations [2].
    Distribution2011 GOLD groupsp-value
    ABCD
    Patients495 (24)293 (14)483 (23)830 (40)
    GOLD 2011 assessment variables
     mMRC dyspnoea score0.6±0.52.3±0.60.8±0.42.6±0.7<0.001
     FEV1 % predicted64.2±8.161.6±8.242.2±11.537.2±11.2<0.001
     Exacerbations previous 12 months0.2±0.40.3±0.51.0±1.41.3±1.4<0.001
    Demographics
     Age years63.2±7.264.1±7.362.9±7.263.6±6.90.078
     Female191(39)106(36)149(31)280(34)0.07
     Body mass index kg·m−226.7±4.828.5±6.125.2±4.926.5±6.1<0.001
     Fat-free mass index kg·m−217.3±2.518.0±3.516.7±2.517.1±2.9<0.001
     Smoking, pack-years48.0±29.447.5±25.845.2±23.251.1±27.7<0.001
     Current smoker188 (38)101 (34)207 (43)267 (32)0.001
    Symptoms
     Chronic bronchitis131 (26)104 (35)182 (38)318 (38)<0.001
     SGRQ-C total score31.9±17.355.3±15.544.6±16.862.2±15.6<0.001
     CESD total score8.3±8.013.8±9.49.5±8.213.5±9.7<0.001
    Self-reported comorbidities
     With any comorbidity383 (77)248 (85)350 (72)690 (83)<0.001
     Number of comorbidities2.0±1.72.8±2.21.7±1.72.3±1.9<0.001
    Physiology
     FEV1 % reversibility11.4±13.211.8±12.910.3±13.510.2±14.50.035
     SaO2 %95.7±2.195.1±2.594.4±3.293.7±3.2<0.001
     6-min walking distance m440±106360±101408±106307±114<0.001
     BODE index0.8±0.82.7±1.22.6 (1.25.1±1.6<0.001
    Imaging
     % LAA -950 HU11.8±9.712.5±9.918.9±11.522.5±12.8<0.001
    Outcomes during 3-year follow-up
     ECOPD per year0.6±0.80.9±1.01.3±1.41.7±1.7<0.001
     ≥1 hospitalisation56 (11)71 (25)143 (30)378 (46)<0.001
     Mortality rate22 (4)28 (10)41 (8)114 (14)<0.001
     Mortality rate per 100 patient-years1.6±7.43.7±11.53.2±10.55.5±13.7<0.001
     Rate of annual FEV1 decline mL per year-33.4 (46.2)-38.0 (47.0)-30.2 (45.5)-31.9 (34.6)0.157
    • Data are presented as n (%) or mean±sd, unless otherwise stated. mMRC: dyspnoea score according to the modified Medical Research Council questionnaire; FEV1; forced expiratory volume in 1 s; SGRQ-C: St George’s Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD) patients; CESD: Center for Epidemiological Studies Depression Scale; SaO2; arterial oxygen saturation; BODE: body mass index, airflow obstruction, dyspnoea, exercise capacity index; % LAA: percentage of low attenuation areas (i.e. emphysema) in the computed tomography; ECOPD: exacerbation of COPD.

  • Table 2– Cox proportional hazards regression analyses for all-cause mortality and hospitalisations during follow-up
    Independent variableEstimatep-value
    Mortality
     Forced expiratory volume in 1 s % predicted0.982 (0.969–0.996)0.011
     Age years1.052 (1.021–1.085)<0.001
     Body mass index kg·m−20.931 (0.882–0.983)0.01
     Fat-free mass index kg·m−21.146 (1.036–1.267)0.008
     Number of comorbidities1.100 (1.001–1.210)0.048
     6-min walking distance m0.997 (0.996–0.999)0.002
    Hospitalisations
     Modified Medical Research Council dyspnoea score1.246 (1.119–1.387)<0.001
     Forced expiratory volume in 1 s % predicted0.974 (0.966–0.982)<0.001
     Exacerbations in previous 12 months1.195 (1.123–1.270)<0.001
     Age years1.021 (1.005–1.038)0.01
     Body mass index kg·m−20.979 (0.960–0.999)0.04
     Hypertension0.669 (0.526–0.851)0.001
     Angina0.565 (0.371–0.858)0.007
     Osteoarthritis0.695 (0.489–0.987)0.042
     Diabetes0.604 (0.392–0.932)0.023
     Depression requiring treatment0.657 (0.473–0.912)0.012
     Number of comorbidities1.209 (1.113–1.314)<0.001
     Arterial oxygen saturation %0.929 (0.902–0.956)<0.001
    • Data are presented as hazard ratio (95% confidence interval), unless otherwise stated.

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Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort
Alvar Agusti, Lisa D. Edwards, Bartolomé Celli, William MacNee, Peter M. A. Calverley, Hana Müllerova, David A. Lomas, Emiel Wouters, Per Bakke, Steve Rennard, Courtney Crim, Bruce E. Miller, Harvey O. Coxson, Julie C. Yates, Ruth Tal-Singer, Jørgen Vestbo
European Respiratory Journal Sep 2013, 42 (3) 636-646; DOI: 10.1183/09031936.00195212

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Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort
Alvar Agusti, Lisa D. Edwards, Bartolomé Celli, William MacNee, Peter M. A. Calverley, Hana Müllerova, David A. Lomas, Emiel Wouters, Per Bakke, Steve Rennard, Courtney Crim, Bruce E. Miller, Harvey O. Coxson, Julie C. Yates, Ruth Tal-Singer, Jørgen Vestbo
European Respiratory Journal Sep 2013, 42 (3) 636-646; DOI: 10.1183/09031936.00195212
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