Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Jeong H. Yun, Andrew Lamb, Robert Chase, Dave Singh, Margaret M. Parker, Aabida Saferali, Jorgen Vestbo, Ruth Tal-Singer, Peter J. Castaldi, Edwin K. Silverman, Craig P. Hersh*, COPDGene Investigator, ECLIPSE Investigators, Emiel Wouters

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

101 Citations (Web of Science)

Abstract

Background: Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk.

Objective: We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD.

Methods: Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time.

Results: COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/mL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/mL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/mL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies.

Conclusions: Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/mL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Original languageEnglish
Pages (from-to)2037-2047
Number of pages21
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number6
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Chronic obstructive pulmonary disease
  • asthma
  • eosinophil
  • exacerbation
  • COPENHAGEN GENERAL-POPULATION
  • RANDOMIZED CONTROLLED-TRIAL
  • SHORT-TERM RESPONSE
  • SPUTUM-EOSINOPHILIA
  • INHALED CORTICOSTEROIDS
  • AIRWAY INFLAMMATION
  • CLINICAL CHARACTERISTICS
  • OVERLAP SYNDROME
  • COPD
  • ASTHMA

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