Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort

Abstract

RationaleThere are no validated measures of disease activity in chronic obstructive pulmonary disease (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.MethodsWe 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.ResultsResults 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 (FEV1) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; (3) Changes in FEV1, 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.ConclusionsIn COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores, and FEV1 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.

Towards precision in defining COPD exacerbations

“…A high white cell count has been associated repeatedly with some exacerbations and exacerbation propensity, but is a nonspecific finding, indicative of many types of infection and likely to rise if patients have already commenced systemic steroids. High blood neutrophil counts were also associated with a frequent exacerbation phenotype and mortality in ECLIPSE [ 35 , 73 ]. Similarly, elevation of blood eosinophils ≥3% or ≥300 cells·mm −3 appears to identify a subpopulation of patients at higher risk of exacerbations and a greater probability of a positive benefit from short-course corticosteroids, but this feature varies and may be evident when clinically stable and during an exacerbation.…”

Behaviour change: The key to implementing evidence on COPD prevention, diagnosis and management

“…4 For example, in the ECLIPSE study, markers of mortality at 8 years of follow-up included frequent exacerbations and hospitalizations, airflow obstruction and markers of systemic inflammation (IL-6, neutrophils and surfactant protein D). 5 To be relevant for clinical use, biomarkers Translation from bench to bedside, especially for molecular biomarkers for COPD, first requires clinicians to understand the biomarker discovery process, which is increasingly more complex with '-omics' technologies. 6 Then, clinicians would need to adopt the use of biomarkers in day-to-day clinical practice, once they are convinced that evidence shows testing would improve patient outcomes.…”

“…Many putative biomarkers have been investigated in COPD 4 . For example, in the ECLIPSE study, markers of mortality at 8 years of follow‐up included frequent exacerbations and hospitalizations, airflow obstruction and markers of systemic inflammation (IL‐6, neutrophils and surfactant protein D) 5 . To be relevant for clinical use, biomarkers should add significant value to routine clinical decision‐making, to facilitate precision health.…”

Fibrinogen, a Promising Marker to Evaluate Severity and Prognosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective Observational Study.

“…COPD is associated with chronic in ammation both locally and systemically, which increases further during acute exacerbations (2). It has been known that the levels of some in ammatory biomarkers are associated with acute exacerbation (3), disease progression and severity of air ow obstruction (4)(5)(6)(7). The identi cation of these biomarkers not only provided a method to predict prognosis but also shed light upon a better understanding of the pathogenesis of COPD.…”