Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun;141(6):2037-2047.e10.
doi: 10.1016/j.jaci.2018.04.010. Epub 2018 Apr 28.

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

Jeong H Yun  1 , Andrew Lamb  2 , Robert Chase  2 , Dave Singh  3 , Margaret M Parker  4 , Aabida Saferali  4 , Jørgen Vestbo  5 , Ruth Tal-Singer  6 , Peter J Castaldi  4 , Edwin K Silverman  1 , Craig P Hersh  7 ; COPDGene and ECLIPSE Investigators
Collaborators, Affiliations

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

Jeong H Yun et al. J Allergy Clin Immunol. 2018 Jun.

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/μL 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/μL 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/μL 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/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Keywords: Chronic obstructive pulmonary disease; asthma; eosinophil; exacerbation.

PubMed Disclaimer

Conflict of interest statement

Disclosure of potential conflict of interest

D. Singh has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, GlaxoSmithKline, Gelnmark, Menarini, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Therevance, Verona and has served as consultant for Apellis, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genetech, GlaxoSmithKline, Glenmark, Menarini, Merck, Mundipharam, Novartis, Peptinnovate, Pfizer, Pulmatrix, Skyepharma, Teva, Tehrevance and Verona. J. Vestbo has served as consultant for GlaxoSmithKline, Chiesi Pharmaceuticals, Boehringer Ingelheim, Novartis and AstraZeneca. R. Tal-Singer is a employee and shareholder of GlaxoSmithKline. P. Castaldi has received personal fees and grant support from GlaxoSmithKline. E. Silverman has received grants and travel expenses from COPD Foundation and GlaxoSmithKline. C. Hersh has served as a consultant for AstraZeneca, Concert Pharmaceuticals, Mylan, and 23andMe, and has received grants from Boehringer-Ingelheim and Novartis. The other authors report no disclosures.

Figures

Figure 1
Figure 1
Risk of COPD exacerbations with increasing blood eosinophil levels in COPDGene. (A) Mean 1 year exacerbation frequency reported at phase 2 visit per blood eosinophil count range in moderate to severe COPD subjects. Error bars indicate standard errors. Difference between group means determined by one-way ANOVA and Tukey honestly significant difference test. (B) Mean 1 year exacerbation frequency reported at phase 2 visit per blood eosinophil percent range in moderate to severe COPD subjects. Error bars indicate standard errors. Difference between group means determined by one-way ANOVA and Tukey honestly significant difference test. (C) Adjusted incidence rate ratios for COPD exacerbations with different eosinophil cutoff values. Risk estimates are derived from negative binomial regression models adjusted for age, sex, race, gastroesophageal reflux, Saint George’s Respiratory Questionnaire score, post bronchodilator forced expiratory volume at 1 second percent predicted, and white blood cell count. IRR: incidence rate ratio. CI: confidence interval.
Figure 2
Figure 2
Risk of prospective COPD exacerbations with increasing blood eosinophil levels in ECLIPSE. (A) Mean exacerbation rate during overall study period per blood eosinophil count range in moderate to severe COPD subjects. Error bars indicate standard errors. Difference between group means determined by one-way ANOVA and Tukey honestly significant difference test. (B) Mean exacerbation rate during overall study period per blood eosinophil percent range in moderate to severe COPD subjects. Error bars indicate standard errors. Difference between group means determined by one-way ANOVA and Tukey honestly significant difference test. (C) Adjusted incidence rate ratios for COPD exacerbations with different eosinophil cutoffs. Risk estimates are derived from negative binomial regression models adjusted for age, sex, race, previous exacerbations, gastroesophageal reflux, Saint George’s Respiratory Questionnaire score, post bronchodilator forced expiratory volume at 1 second percent predicted, and white blood cell count. IRR: incidence rate ratio. CI: confidence interval.
Figure 3
Figure 3
Venn Diagrams of the number of subjects with asthma-COPD overlap (defined by asthma diagnosis before the age of 40) and COPD subjects with blood eosinophil counts ≥ 300 cells/μL in COPDGene and ECLIPSE.
See this image and copyright information in PMC

Comment in

  • Reply.
    Yun JH, Hersh CP. Yun JH, et al. J Allergy Clin Immunol. 2018 Dec;142(6):2013-2014. doi: 10.1016/j.jaci.2018.07.043. Epub 2018 Oct 10. J Allergy Clin Immunol. 2018. PMID: 30316523 No abstract available.
  • The specificity and definition of blood eosinophil.
    Xing YF, Zhou YH, Liu T, Feng DY, Ren JH, Wang C, Tan SL, Jiang WH. Xing YF, et al. J Allergy Clin Immunol. 2018 Dec;142(6):2013. doi: 10.1016/j.jaci.2018.07.042. Epub 2018 Oct 10. J Allergy Clin Immunol. 2018. PMID: 30316524 No abstract available.

References

    1. O’Donnell R, Breen D, Wilson S, Djukanovic R. Inflammatory cells in the airways in COPD. Thorax. 2006;61:448–54. - PMC - PubMed
    1. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. NatRevImmunol. 2008;8:183–92. - PubMed
    1. Aleman F, Lim HF, Nair P, Fang H, Mbbs L, Uk M, et al. Eosinophilic Endotype of Asthma. Immunol Allergy Clin North Am. 2016;36:559–68. - PubMed
    1. Saha S, Brightling CE. Eosinophilic airway inflammation in COPD. Int J Chron Obstruct Pulmon Dis. 2006;1:39–47. - PMC - PubMed
    1. Siva R, Green RH, Brightling CE, Shelley M, Hargadon B, McKenna S, et al. Eosinophilic airway inflammation and exacerbations of COPD: A randomised controlled trial. Eur Respir J. 2007;29:906–13. - PubMed

Publication types