title: COPD: Do Imaging Measurements of Emphysema and Airway Disease Explain Symptoms and Exercise Capacity?
abstract: OBJECTIVE
  To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease.
  
  
  METHODS
  Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements.
  
  
  RESULTS
  Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (β = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (β = 0.60, P = .0008), and residual volume/total lung capacity (β = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (β = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: β = 0.60, P = .005; RA950: β = -0.52, P = .02; FEV1: β = -0.45, P = .0002) and in grade III or IV disease (ADC: β = 0.95, P = .01; RA950: β = -0.62, P = .07; airway count: β = -0.49, P = .01).
  
  
  CONCLUSIONS
  In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms.
authors.affiliation: From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7.
authors.forename: Miranda
authors.initials: M
authors.lastname: Kirby
authors.affiliation: From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7.
authors.forename: Damien
authors.initials: D
authors.lastname: Pike
authors.affiliation: From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7.
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.affiliation: From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7.
authors.forename: David G
authors.initials: DG
authors.lastname: McCormack
authors.affiliation: From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7.
authors.forename: Grace
authors.initials: G
authors.lastname: Parraga
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003627:Data Interpretation, Statistical; D004646:Emphysema / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000473:pathology / Q000503:physiopathology*; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed; D014853:Walkers