Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort

W. Blake LeMaster; P. Miguel Quibrera; David Couper; Donald P. Tashkin; Eugene R. Bleecker; Claire M. Doerschuk; Victor E. Ortega; Christopher Cooper; Mei Lan K. Han; Prescott G. Woodruff; Wanda K. O'Neal; Wayne H. Anderson; Neil E. Alexis; Russell P. Bowler; R. Graham Barr; Robert J. Kaner; Mark T. Dransfield; Robert Paine; Victor Kim; Jeffrey L. Curtis; Fernando J. Martinez; Annette T. Hastie; Igor Barjaktarevic

doi:10.1016/j.chest.2022.10.029

Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort

W. Blake LeMaster, P. Miguel Quibrera, David Couper, Donald P. Tashkin, Eugene R. Bleecker, Claire M. Doerschuk, Victor E. Ortega, Christopher Cooper, Mei Lan K. Han, Prescott G. Woodruff, Wanda K. O'Neal, Wayne H. Anderson, Neil E. Alexis, Russell P. Bowler, R. Graham Barr, Robert J. Kaner, Mark T. Dransfield, Robert Paine, Victor Kim, Jeffrey L. CurtisFernando J. Martinez, Annette T. Hastie, Igor Barjaktarevic

Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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

Original language	English (US)
Pages (from-to)	515-528
Number of pages	14
Journal	CHEST
Volume	163
Issue number	3
DOIs	https://doi.org/10.1016/j.chest.2022.10.029
State	Published - Mar 2023

Keywords

COPD
GOLD group D
eosinophil
inhaled corticosteroid

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine
Cardiology and Cardiovascular Medicine

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10.1016/j.chest.2022.10.029

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LeMaster, W. B., Quibrera, P. M., Couper, D., Tashkin, D. P., Bleecker, E. R., Doerschuk, C. M., Ortega, V. E., Cooper, C., Han, M. L. K., Woodruff, P. G., O'Neal, W. K., Anderson, W. H., Alexis, N. E., Bowler, R. P., Barr, R. G., Kaner, R. J., Dransfield, M. T., Paine, R., Kim, V., ... Barjaktarevic, I. (2023). Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort. CHEST, 163(3), 515-528. https://doi.org/10.1016/j.chest.2022.10.029

LeMaster, WB, Quibrera, PM, Couper, D, Tashkin, DP, Bleecker, ER, Doerschuk, CM, Ortega, VE, Cooper, C, Han, MLK, Woodruff, PG, O'Neal, WK, Anderson, WH, Alexis, NE, Bowler, RP, Barr, RG, Kaner, RJ, Dransfield, MT, Paine, R, Kim, V, Curtis, JL, Martinez, FJ, Hastie, AT & Barjaktarevic, I 2023, 'Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort', CHEST, vol. 163, no. 3, pp. 515-528. https://doi.org/10.1016/j.chest.2022.10.029

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title = "Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort",

abstract = "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",

keywords = "COPD, GOLD group D, eosinophil, inhaled corticosteroid",

author = "LeMaster, {W. Blake} and Quibrera, {P. Miguel} and David Couper and Tashkin, {Donald P.} and Bleecker, {Eugene R.} and Doerschuk, {Claire M.} and Ortega, {Victor E.} and Christopher Cooper and Han, {Mei Lan K.} and Woodruff, {Prescott G.} and O'Neal, {Wanda K.} and Anderson, {Wayne H.} and Alexis, {Neil E.} and Bowler, {Russell P.} and Barr, {R. Graham} and Kaner, {Robert J.} and Dransfield, {Mark T.} and Robert Paine and Victor Kim and Curtis, {Jeffrey L.} and Martinez, {Fernando J.} and Hastie, {Annette T.} and Igor Barjaktarevic",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = mar,

doi = "10.1016/j.chest.2022.10.029",

language = "English (US)",

volume = "163",

pages = "515--528",

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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

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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Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort

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