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Journal of Allergy and Clinical Immunology

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Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease - 06/06/18

Doi : 10.1016/j.jaci.2018.04.010 
Jeong H. Yun, MD, MPH a, b, c, Andrew Lamb, MS a, Robert Chase, MS a, Dave Singh, MD d, Margaret M. Parker, PhD a, c, Aabida Saferali, PhD a, c, Jørgen Vestbo, DMSc d, e, Ruth Tal-Singer, PhD f, Peter J. Castaldi, MD a, c, Edwin K. Silverman, MD, PhD a, b, c, Craig P. Hersh, MD, MPH a, b, c, ⁎
for the

COPDGene and ECLIPSE Investigators

James D. Crapo, MD, Edwin K. Silverman, MD, PhD, Barry J. Make, MD, Elizabeth A. Regan, MD, PhD, Terri Beaty, PhD, Ferdouse Begum, PhD, Robert Busch, MD, Peter J. Castaldi, MD, MSc, Michael Cho, MD, Dawn L. DeMeo, MD, MPH, Adel R. Boueiz, MD, Marilyn G. Foreman, MD, MS, Eitan Halper-Stromberg, Nadia N. Hansel, MD, MPH, Megan E. Hardin, MD, Lystra P. Hayden, MD, MMSc, Craig P. Hersh, MD, MPH, Jacqueline Hetmanski, MS, MPH, Brian D. Hobbs, MD, John E. Hokanson, MPH, PhD, Nan Laird, PhD, Christoph Lange, PhD, Sharon M. Lutz, PhD, Merry-Lynn McDonald, PhD, Margaret M. Parker, PhD, Dandi Qiao, PhD, Elizabeth A. Regan, MD, PhD, Stephanie Santorico, PhD, Edwin K. Silverman, MD, PhD, Emily S. Wan, MD, Sungho Won, Mustafa Al Qaisi, MD, Harvey O. Coxson, PhD, Teresa Gray, MeiLan K. Han, MD, MS, Eric A. Hoffman, PhD, Stephen Humphries, PhD, Francine L. Jacobson, MD, MPH, Philip F. Judy, PhD, Ella A. Kazerooni, MD, Alex Kluiber, David A. Lynch, MB, John D. Newell, MD, Elizabeth A. Regan, MD, PhD, James C. Ross, PhD, Raul San Jose Estepar, PhD, Joyce Schroeder, MD, Jered Sieren, Douglas Stinson, Berend C. Stoel, PhD, Juerg Tschirren, PhD, Edwin Van Beek, MD, PhD, Bram van Ginneken, PhD, Eva van Rikxoort, PhD, George Washko, MD, Carla G. Wilson, MS, Robert Jensen, PhD, Douglas Everett, PhD, Jim Crooks, PhD, Camille Moore, PhD, Matt Strand, PhD, Carla G. Wilson, MS, John E. Hokanson, MPH, PhD, John Hughes, PhD, Gregory Kinney, MPH, PhD, Sharon M. Lutz, PhD, Katherine Pratte, MSPH, Kendra A. Young, PhD, Jeffrey L. Curtis, MD, Carlos H. Martinez, MD, MPH, Perry G. Pernicano, MD, Nicola Hanania, MD, MS, Philip Alapat, MD, Mustafa Atik, MD, Venkata Bandi, MD, Aladin Boriek, PhD, Kalpatha Guntupalli, MD, Elizabeth Guy, MD, Arun Nachiappan, MD, Amit Parulekar, MD, Dawn L. DeMeo, MD, MPH, Craig Hersh, MD, MPH, Francine L. Jacobson, MD, MPH, George Washko, MD, R. Graham Barr, MD, DrPH, John Austin, MD, Belinda D'Souza, MD, Gregory D.N. Pearson, MD, Anna Rozenshtein, MD, MPH, FACR, Byron Thomashow, MD, Neil MacIntyre, MD, H. Page McAdams, MD, Lacey Washington, MD, Charlene McEvoy, MD, MPH, Joseph Tashjian, MD, Robert Wise, MD, Robert Brown, MD, Nadia N. Hansel, MD, MPH, Karen Horton, MD, Allison Lambert, MD, MHS, Nirupama Putcha, MD, MHS, Richard Casaburi, MD, PhD, Alessandra Adami, PhD, Matthew Budoff, MD, Hans Fischer, MD, Janos Porszasz, MD, PhD, Harry Rossiter, PhD, William Stringer, MD, Amir Sharafkhaneh, MD, PhD, Charlie Lan, DO, Christine Wendt, MD, Brian Bell, MD, Marilyn G. Foreman, MD, MS, Eugene Berkowitz, MD, PhD, Gloria Westney, MD, MS, Russell Bowler, MD, PhD, David A. Lynch, MB, Richard Rosiello, MD, David Pace, MD, Gerard Criner, MD, David Ciccolella, MD, Francis Cordova, MD, Chandra Dass, MD, Gilbert D'Alonzo, DO, Parag Desai, MD, Michael Jacobs, PharmD, Steven Kelsen, MD, PhD, Victor Kim, MD, A. James Mamary, MD, Nathaniel Marchetti, DO, Aditi Satti, MD, Kartik Shenoy, MD, Robert M. Steiner, MD, Alex Swift, MD, Irene Swift, MD, Maria Elena Vega-Sanchez, MD, Mark Dransfield, MD, William Bailey, MD, Surya Bhatt, MD, Anand Iyer, MD, Hrudaya Nath, MD, J. Michael Wells, MD, Joe Ramsdell, MD, Paul Friedman, MD, Xavier Soler, MD, PhD, Andrew Yen, MD, Alejandro P. Comellas, MD, John Newell, MD, Brad Thompson, MD, MeiLan K. Han, MD, MS, Ella Kazerooni, MD, Carlos H. Martinez, MD, MPH, Joanne Billings, MD, Abbie Begnaud, MD, Tadashi Allen, MD, Frank Sciurba, MD, Jessica Bon, MD, Divay Chandra, MD, MSc, Carl Fuhrman, MD, Joel Weissfeld, MD, MPH, Antonio Anzueto, MD, Sandra Adams, MD, Diego Maselli-Caceres, MD, Mario E. Ruiz, MD, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, P. de Mallorca, Y. Feschenko, V. Gavrisyuk, L. Yashina Kiev, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, D. Lomas, W. MacNee, E. Silverman, R. Tal Singer, J. Vestbo, J. Yates
A. Agusti, P. Calverley, B. Celli, C. Crim, B. Miller, W. MacNee, S. Rennard, R. Tal-Singer, E. Wouters, J. Yates

a Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass 
b Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass 
c Harvard Medical School, Boston, Mass 
d University of Manchester, Manchester, United Kingdom 
e NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom 
f GlaxoSmithKline R&D, King of Prussia, Pa 

∗Corresponding author: Craig P. Hersh, MD, MPH, Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA 02115.Channing Division of Network MedicineBrigham and Women's Hospital181 Longwood AveBostonMA02115

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.

Le texte complet de cet article est disponible en PDF.

Key words : Chronic obstructive pulmonary disease, asthma, eosinophil, exacerbation

Abbreviations used : ACO, CBC, COPD, COPDGene, CT, ECLIPSE, FVC, GERD, GOLD, ICS, IRR, ROC, SGRQ, WBC


Plan


 Supported by National Institute of Health grants R01HL125583, R01HL130512, R01HL124233, R01HL126596, U01HL089897, U01HL089856, T32HL007427, P01HL105339, and P01HL132825. J.V. was supported by the National Institute of Health Research Manchester Biomedical Research Centre. The COPDGene project is also supported by the COPD foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion. ECLIPSE was funded by GlaxoSmithKline.
 Disclosure of potential conflict of interest: D. Singh has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, GlaxoSmithKline, Glenmark, Menarini, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Therevance, and Verona and has served as a consultant for Apellis, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, GlaxoSmithKline, Glenmark, Menarini, Merck, Mundipharam, Novartis, Peptinnovate, Pfizer, Pulmatrix, Skyepharma, Teva, Therevance, and Verona. J. Vestbo has served a as consultant for GlaxoSmithKline, Chiesi Pharmaceuticals, Boehringer Ingelheim, Novartis, and AstraZeneca. R. Tal-Singer is an employee and shareholder of GlaxoSmithKline. P. J. Castaldi has received personal fees and grant support from GlaxoSmithKline. E. K. Silverman has received grants and travel expenses from the COPD Foundation and GlaxoSmithKline. C. P. Hersh has served as a consultant for AstraZeneca, Concert Pharmaceuticals, Mylan, and 23andMe and has received grants from Boehringer Ingelheim and Novartis. The rest of the authors declare that they have no relevant conflicts of interest.


© 2018  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 141 - N° 6

P. 2037 - juin 2018 Retour au numéro
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