title: Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) seems to be a heterogeneous disease with a variable course.
  
  
  OBJECTIVE
  We wished to characterize the heterogeneity and variability of COPD longitudinally.
  
  
  METHODS
  In the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study of 2,164 patients with clinically stable COPD, 337 smokers with normal lung function, and 245 never-smokers, we measured a large number of clinical parameters, lung function, exercise tolerance, biomarkers, and amount of emphysema by computed tomography. All three groups were followed for 3 years.
  
  
  RESULTS
  We found a striking heterogeneity among patients with COPD, with poor correlations between FEV1, symptoms, quality of life, functional outcomes, and biomarkers. Presence of systemic inflammation was found in only a limited proportion of patients, and did not relate to baseline characteristics or disease progression, but added prognostic value for predicting mortality. Exacerbations tracked over time and added to the concept of the "frequent exacerbator phenotype." Disease course was very variable, with close to a third of patients not progressing at all. Risk factors for 3-year change in both FEV1 and lung density were assessed. For FEV1 decline, continued smoking and presence of emphysema were the strongest predictors of progression; club cell protein was found to be a potential biomarker for disease activity. For progression of emphysema, the strongest predictors were continued smoking and female sex.
  
  
  CONCLUSIONS
  By following a large, well characterized cohort of patients with COPD over 3 years, we have a clearer picture of a heterogeneous disease with clinically important subtypes ("phenotypes") and a variable and not inherently progressive course. Clinical trial registered with www.clinicaltrials.gov (NCT00292552).
authors.affiliation: 1 Department of Respiratory Medicine, Odense University Hospital, and Clinical Institute, University of Southern Denmark, Odense, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Alvar
authors.initials: A
authors.lastname: Agusti
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.forename: Harvey
authors.initials: H
authors.lastname: Coxson
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Edwards
authors.forename: Nicholas
authors.initials: N
authors.lastname: Locantore
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Julie C
authors.initials: JC
authors.lastname: Yates
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
mesh_terms: D015415:Biomarkers; D018450:Disease Progression; D004646:Emphysema / Q000000981:diagnostic imaging / Q000473:pathology; D023381:Endpoint Determination; D017079:Exercise Tolerance; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000473:pathology*; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers