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J Allergy Clin Immunol. 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.

Collaborators (231)

Crapo JD, Silverman EK, Make BJ, Regan EA, Beaty T, Begum F, Busch R, Castaldi PJ, Cho M, DeMeo DL, Boueiz AR, Foreman MG, Halper-Stromberg E, Hansel NN, Hardin ME, Hayden LP, Hersh CP, Hetmanski J, Hobbs BD, Hokanson JE, Laird N, Lange C, Lutz SM, McDonald ML, Parker MM, Qiao D, Regan EA, Santorico S, Silverman EK, Wan ES, Won S, Al Qaisi M, Coxson HO, Gray T, Han MK, Hoffman EA, Humphries S, Jacobson FL, Judy PF, Kazerooni EA, Kluiber A, Lynch DA, Newell JD Jr, Regan EA, Ross JC, San Jose Estepar R, Schroeder J, Sieren J, Stinson D, Stoel BC, Tschirren J, Van Beek E, van Ginneken B, van Rikxoort E, Washko G, Wilson CG, Jensen R, Everett D, Crooks J, Moore C, Strand M, Wilson CG, Hokanson JE, Hughes J, Kinney G, Lutz SM, Pratte K, Young KA, Curtis JL, Martinez CH, Pernicano PG, Hanania N, Alapat P, Atik M, Bandi V, Boriek A, Guntupalli K, Guy E, Nachiappan A, Parulekar A, DeMeo DL, Hersh C, Jacobson FL, Washko G, Barr RG, Austin J, D'Souza B, Pearson GDN, Rozenshtein A, Thomashow B, MacIntyre N Jr, McAdams HP, Washington L, McEvoy C, Tashjian J, Wise R, Brown R, Hansel NN, Horton K, Lambert A, Putcha N, Casaburi R, Adami A, Budoff M, Fischer H, Porszasz J, Rossiter H, Stringer W, Sharafkhaneh A, Lan C, Wendt C, Bell B, Foreman MG, Berkowitz E, Westney G, Bowler R, Lynch DA, Rosiello R, Pace D, Criner G, Ciccolella D, Cordova F, Dass C, D'Alonzo G, Desai P, Jacobs M, Kelsen S, Kim V, Mamary AJ, Marchetti N, Satti A, Shenoy K, Steiner RM, Swift A, Swift I, Vega-Sanchez ME, Dransfield M, Bailey W, Bhatt S, Iyer A, Nath H, Wells JM, Ramsdell J, Friedman P, Soler X, Yen A, Comellas AP, Newell J Jr, Thompson B, Han MK, Kazerooni E, Martinez CH, Billings J, Begnaud A, Allen T, Sciurba F, Bon J, Chandra D, Fuhrman C, Weissfeld J, Anzueto A, Adams S, Maselli-Caceres D, Ruiz ME, Ivanov Y, Kostov K, Bourbeau J, Fitzgerald M, Hernandez P, Killian K, Levy R, Maltais F, O'Donnell D, Krepelka J, Vestbo J, Wouters E, Quinn D, Bakke P, Kosnik M, Agusti A, Sauleda J, de Mallorca P, Feschenko Y, Gavrisyuk V, Kiev LY, Monogarova N, Calverley P, Lomas D, MacNee W, Singh D, Wedzicha J, Anzueto A, Braman S, Casaburi R, Celli B, Giessel G, Gotfried M, Greenwald G, Hanania N, Mahler D, Make B, Rennard S, Rochester C, Scanlon P, Schuller D, Sciurba F, Sharafkhaneh A, Siler T, Silverman E, Wanner A, Wise R, ZuWallack R, Coxson H, Crim C, Edwards L, Lomas D, MacNee W, Silverman E, Singer RT, Vestbo J, Yates J, Agusti A, Calverley P, Celli B, Crim C, Miller B, MacNee W, Rennard S, Tal-Singer R, Wouters E, Yates J.

Author information

1
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
2
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass.
3
University of Manchester, Manchester, United Kingdom.
4
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
5
University of Manchester, Manchester, United Kingdom; NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
6
GlaxoSmithKline R&D, King of Prussia, Pa.
7
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: craig.hersh@channing.harvard.edu.

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

PMID:
29709670
PMCID:
PMC5994197
[Available on 2019-06-01]
DOI:
10.1016/j.jaci.2018.04.010

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