Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort
Bartolomé R. Celli, Nicholas Locantore, Julie Yates, Per Bakke, Peter M.A. Calverley, Courtney Crim, Harvey O. Coxson, David A. Lomas, William MacNee, Bruce E. Miller, Hana Müllerová, Stephen I. Rennard, Edwin K. Silverman, Emiel F.�M. Wouters, Ruth Tal‐Singer, Àlvar Agustí, Jørgen Vestbo
Abstract
Rationale There are no validated measures of disease activity in COPD. Since “active” disease is expected to have worse outcomes ( e.g. mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality. Methods We investigated 1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; 2) whether these variables inter-relate; and 3) if any clinical, imaging and/or biological marker measured cross-sectionally at baseline relates to any activity component. Results Results showed that 1) after 1 year, hospitalisation for COPD, exacerbation frequency, worsening of body mass index, airflow obstruction, dyspnoea and exercise (BODE) index or health status (St George's Respiratory Questionnaire (SGRQ)) and persistence of systemic inflammation were significantly associated with 8-year mortality; 2) at 3 years, the same markers, plus forced expiratory volume in 1 s (FEV 1 ) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; 3) changes in FEV 1 , inflammatory cytokines and CT emphysema were not inter-related, while the multidimensional indices (BODE and SGRQ) showed modest correlations; and 4) changes in these markers could not be predicted by any baseline cross-sectional measure. Conclusions In COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores and FEV 1 decline are independent markers of disease activity associated with 8-year all-cause mortality. These disease activity markers are generally independent and not predictable from baseline measurements.