TY - JOUR
T1 - Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort
AU - LeMaster, W. Blake
AU - Quibrera, P. Miguel
AU - Couper, David
AU - Tashkin, Donald P.
AU - Bleecker, Eugene R.
AU - Doerschuk, Claire M.
AU - Ortega, Victor E.
AU - Cooper, Christopher
AU - Han, Mei Lan K.
AU - Woodruff, Prescott G.
AU - O'Neal, Wanda K.
AU - Anderson, Wayne H.
AU - Alexis, Neil E.
AU - Bowler, Russell P.
AU - Barr, R. Graham
AU - Kaner, Robert J.
AU - Dransfield, Mark T.
AU - Paine, Robert
AU - Kim, Victor
AU - Curtis, Jeffrey L.
AU - Martinez, Fernando J.
AU - Hastie, Annette T.
AU - Barjaktarevic, Igor
N1 - Funding Information:
Author contributions: W. B. LeM. A. T. H. and I. B. act as guarantors for the content of this manuscript. W. B. LeM. D. C. P. M. Q. A. T. H. and I. B. contributed to the conception and design of the study. P. M. Q. and D. C. undertook data analysis. W. B. LeM. D. P. T. C. C. J. L. C. A. T. H. and I. B. drafted the manuscript. All authors contributed to data acquisition and/or interpretation and critically reviewed the manuscript before submission. Other contributions: The authors thank the SPIROMICS participants and participating physicians, investigators, and staff for making this research possible. More information about the study and how to access SPIROMICS data is available at www.spiromics.org. The authors acknowledge the University of North Carolina at Chapel Hill BioSpecimen Processing Facility for sample processing, storage, and sample disbursements (https://bsp.web.unc.edu/). The authors acknowledge the following current and former investigators of the SPIROMICS sites and reading centers: Neil E Alexis, MD; Wayne H. Anderson, PhD; Mehrdad Arjomandi, MD; Igor Barjaktarevic, MD, PhD; R. Graham Barr, MD, DrPH; Patricia Basta, PhD; Lori A. Bateman, MSc; Surya P. Bhatt, MD; Eugene R. Bleecker, MD; Richard C. Boucher, MD; Russell P. Bowler, MD, PhD; Stephanie A. Christenson, MD; Alejandro P. Comellas, MD; Christopher B. Cooper, MD, PhD; David J. Couper, PhD; Gerard J. Criner, MD; Ronald G. Crystal, MD; Jeffrey L. Curtis, MD; Claire M. Doerschuk, MD; Mark T. Dransfield, MD; Brad Drummond, MD; Christine M. Freeman, PhD; Craig Galban, PhD; MeiLan K. Han, MD, MS; Nadia N. Hansel, MD, MPH; Annette T. Hastie, PhD; Eric A. Hoffman, PhD; Yvonne Huang, MD; Robert J. Kaner, MD; Richard E. Kanner, MD; Eric C. Kleerup, MD; Jerry A. Krishnan, MD, PhD; Lisa M. LaVange, PhD; Stephen C. Lazarus, MD; Fernando J. Martinez, MD, MS; Deborah A. Meyers, PhD; Wendy C. Moore, MD; John D. Newell Jr, MD; Robert Paine III, MD; Laura Paulin, MD, MHS; Stephen P. Peters, MD, PhD; Cheryl Pirozzi, MD; Nirupama Putcha, MD, MHS; Elizabeth C. Oelsner, MD, MPH; Wanda K. O'Neal, PhD; Victor E. Ortega, MD, PhD; Sanjeev Raman, MBBS, MD; Stephen I. Rennard, MD; Donald P. Tashkin, MD; J. Michael Wells, MD; Robert A. Wise, MD; and Prescott G. Woodruff, MD, MPH. The project officers from the Lung Division of the National Heart, Lung, and Blood Institute were Lisa Postow, PhD, and Lisa Viviano, BSN.
Publisher Copyright:
© 2023
PY - 2023/3
Y1 - 2023/3
N2 - Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/μL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD. Research Question: Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes? Study Design and Methods: We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS. Results: We identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, –50 vs –39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of –68 mL/y vs –23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029). Interpretation: In non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov
AB - Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/μL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD. Research Question: Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes? Study Design and Methods: We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS. Results: We identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, –50 vs –39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of –68 mL/y vs –23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029). Interpretation: In non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov
KW - COPD
KW - GOLD group D
KW - eosinophil
KW - inhaled corticosteroid
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U2 - 10.1016/j.chest.2022.10.029
DO - 10.1016/j.chest.2022.10.029
M3 - Article
C2 - 36343688
AN - SCOPUS:85148626973
SN - 0012-3692
VL - 163
SP - 515
EP - 528
JO - Diseases of the chest
JF - Diseases of the chest
IS - 3
ER -