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

2018; Elsevier BV; Volume: 141; Issue: 6 Linguagem: Inglês

10.1016/j.jaci.2018.04.010

1097-6825

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

Respiratory Support and Mechanisms

BackgroundEosinophilic 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.ObjectiveWe sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD.MethodsBlood 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.ResultsCOPD 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.ConclusionsPatients 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. 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. We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. 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. 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. 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.