Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team

Am J Respir Crit Care Med. 2014 May 1;189(9):1022-30. doi: 10.1164/rccm.201311-2006PP.


Rationale: Chronic obstructive pulmonary disease (COPD) seems to be a heterogeneous disease with a variable course.

Objectives: 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.

Measurements and main 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 (NCT00292552).

Publication types

  • Clinical Trial

MeSH terms

  • Biomarkers
  • Disease Progression
  • Emphysema / diagnostic imaging
  • Emphysema / pathology
  • Endpoint Determination
  • Exercise Tolerance
  • Female
  • Forced Expiratory Volume
  • Humans
  • Longitudinal Studies
  • Lung / diagnostic imaging
  • Lung / pathology*
  • Male
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / diagnostic imaging
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Respiratory Function Tests
  • Risk Factors
  • Severity of Illness Index
  • Smoking / adverse effects
  • Tomography, X-Ray Computed


  • Biomarkers

Associated data