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

COPDGene and ECLIPSE Investigators

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2037-2047.e10
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Eosinophils
Chronic Obstructive Pulmonary Disease
Biomarkers
Cell Count
Molecular Epidemiology
Incidence
Disease Progression
Asthma
Steroids
Inflammation

Keywords

  • asthma
  • Chronic obstructive pulmonary disease
  • eosinophil
  • exacerbation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. / COPDGene and ECLIPSE Investigators.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 6, 01.06.2018, p. 2037-2047.e10.

Research output: Contribution to journalArticle

@article{447011168eec43e5b1db101ecca5d14d,
title = "Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease",
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 = "asthma, Chronic obstructive pulmonary disease, eosinophil, exacerbation",
author = "{COPDGene and ECLIPSE Investigators} and Yun, {Jeong H.} and Andrew Lamb and Robert Chase and Dave Singh and Parker, {Margaret M.} and Aabida Saferali and J{\o}rgen Vestbo and Ruth Tal-Singer and Castaldi, {Peter J.} and Silverman, {Edwin K.} and Hersh, {Craig P.} and Crapo, {James D.} and Silverman, {Edwin K.} and Make, {Barry J.} and Regan, {Elizabeth A.} and Terri Beaty and Ferdouse Begum and Robert Busch and Castaldi, {Peter J.} and Michael Cho and DeMeo, {Dawn L.} and Boueiz, {Adel R.} and Foreman, {Marilyn G.} and Eitan Halper-Stromberg and Hansel, {Nadia N.} and Hardin, {Megan E.} and Hayden, {Lystra P.} and Hersh, {Craig P.} and Jacqueline Hetmanski and Hobbs, {Brian D.} and Hokanson, {John E.} and Nan Laird and Christoph Lange and Lutz, {Sharon M.} and McDonald, {Merry Lynn} and Parker, {Margaret M.} and Dandi Qiao and Stephanie Santorico and Wan, {Emily S.} and Sungho Won and {Al Qaisi}, Mustafa and Coxson, {Harvey O.} and Teresa Gray and Han, {Mei Lan K.} and Hoffman, {Eric A.} and Stephen Humphries and Jacobson, {Francine L.} and Judy, {Philip F.} and Anzueto, {Antonio R} and Adams, {Sandra G}",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.jaci.2018.04.010",
language = "English (US)",
volume = "141",
pages = "2037--2047.e10",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

AU - COPDGene and ECLIPSE Investigators

AU - Yun, Jeong H.

AU - Lamb, Andrew

AU - Chase, Robert

AU - Singh, Dave

AU - Parker, Margaret M.

AU - Saferali, Aabida

AU - Vestbo, Jørgen

AU - Tal-Singer, Ruth

AU - Castaldi, Peter J.

AU - Silverman, Edwin K.

AU - Hersh, Craig P.

AU - Crapo, James D.

AU - Silverman, Edwin K.

AU - Make, Barry J.

AU - Regan, Elizabeth A.

AU - Beaty, Terri

AU - Begum, Ferdouse

AU - Busch, Robert

AU - Castaldi, Peter J.

AU - Cho, Michael

AU - DeMeo, Dawn L.

AU - Boueiz, Adel R.

AU - Foreman, Marilyn G.

AU - Halper-Stromberg, Eitan

AU - Hansel, Nadia N.

AU - Hardin, Megan E.

AU - Hayden, Lystra P.

AU - Hersh, Craig P.

AU - Hetmanski, Jacqueline

AU - Hobbs, Brian D.

AU - Hokanson, John E.

AU - Laird, Nan

AU - Lange, Christoph

AU - Lutz, Sharon M.

AU - McDonald, Merry Lynn

AU - Parker, Margaret M.

AU - Qiao, Dandi

AU - Santorico, Stephanie

AU - Wan, Emily S.

AU - Won, Sungho

AU - Al Qaisi, Mustafa

AU - Coxson, Harvey O.

AU - Gray, Teresa

AU - Han, Mei Lan K.

AU - Hoffman, Eric A.

AU - Humphries, Stephen

AU - Jacobson, Francine L.

AU - Judy, Philip F.

AU - Anzueto, Antonio R

AU - Adams, Sandra G

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - asthma

KW - Chronic obstructive pulmonary disease

KW - eosinophil

KW - exacerbation

UR - http://www.scopus.com/inward/record.url?scp=85047417721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047417721&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2018.04.010

DO - 10.1016/j.jaci.2018.04.010

M3 - Article

C2 - 29709670

AN - SCOPUS:85047417721

VL - 141

SP - 2037-2047.e10

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -