Should We View Chronic Obstructive Pulmonary Disease Differently after ECLIPSE? A Clinical Perspective from the Study Team

Rationale and objectives: Chronic obstructive pulmonary disease (COPD) seems a heterogeneous disease with a variable course. Methods: In the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study of 2164 clinically stable COPD patients, 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 COPD patients with poor correlations between FEV1, symptoms and 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 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 gender. Conclusions: By following a large well characterized cohort of COPD patients 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