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The value of blood cytokines and chemokines in assessing COPD

BACKGROUND: Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former sm...

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Autores principales: Bradford, Eric, Jacobson, Sean, Varasteh, Jason, Comellas, Alejandro P., Woodruff, Prescott, O’Neal, Wanda, DeMeo, Dawn L., Li, Xingnan, Kim, Victor, Cho, Michael, Castaldi, Peter J., Hersh, Craig, Silverman, Edwin K., Crapo, James D., Kechris, Katerina, Bowler, Russell P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655820/
https://www.ncbi.nlm.nih.gov/pubmed/29065892
http://dx.doi.org/10.1186/s12931-017-0662-2
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author Bradford, Eric
Jacobson, Sean
Varasteh, Jason
Comellas, Alejandro P.
Woodruff, Prescott
O’Neal, Wanda
DeMeo, Dawn L.
Li, Xingnan
Kim, Victor
Cho, Michael
Castaldi, Peter J.
Hersh, Craig
Silverman, Edwin K.
Crapo, James D.
Kechris, Katerina
Bowler, Russell P.
author_facet Bradford, Eric
Jacobson, Sean
Varasteh, Jason
Comellas, Alejandro P.
Woodruff, Prescott
O’Neal, Wanda
DeMeo, Dawn L.
Li, Xingnan
Kim, Victor
Cho, Michael
Castaldi, Peter J.
Hersh, Craig
Silverman, Edwin K.
Crapo, James D.
Kechris, Katerina
Bowler, Russell P.
author_sort Bradford, Eric
collection PubMed
description BACKGROUND: Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers. METHODS: We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS. These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17. Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV(1)%) and FEV(1)/forced vital capacity (FEV(1)/FVC), chronic bronchitis, COPD exacerbations, and emphysema. Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs). RESULTS: Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3–5% of the measurement variance on top of clinical variables. IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years. None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations. We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements. CONCLUSION: When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone. TRIAL REGISTRATION: COPDGene (ClinicalTrials.gov Identifier: NCT02445183). Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-56558202017-10-31 The value of blood cytokines and chemokines in assessing COPD Bradford, Eric Jacobson, Sean Varasteh, Jason Comellas, Alejandro P. Woodruff, Prescott O’Neal, Wanda DeMeo, Dawn L. Li, Xingnan Kim, Victor Cho, Michael Castaldi, Peter J. Hersh, Craig Silverman, Edwin K. Crapo, James D. Kechris, Katerina Bowler, Russell P. Respir Res Research BACKGROUND: Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers. METHODS: We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS. These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17. Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV(1)%) and FEV(1)/forced vital capacity (FEV(1)/FVC), chronic bronchitis, COPD exacerbations, and emphysema. Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs). RESULTS: Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3–5% of the measurement variance on top of clinical variables. IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years. None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations. We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements. CONCLUSION: When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone. TRIAL REGISTRATION: COPDGene (ClinicalTrials.gov Identifier: NCT02445183). Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-24 2017 /pmc/articles/PMC5655820/ /pubmed/29065892 http://dx.doi.org/10.1186/s12931-017-0662-2 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bradford, Eric
Jacobson, Sean
Varasteh, Jason
Comellas, Alejandro P.
Woodruff, Prescott
O’Neal, Wanda
DeMeo, Dawn L.
Li, Xingnan
Kim, Victor
Cho, Michael
Castaldi, Peter J.
Hersh, Craig
Silverman, Edwin K.
Crapo, James D.
Kechris, Katerina
Bowler, Russell P.
The value of blood cytokines and chemokines in assessing COPD
title The value of blood cytokines and chemokines in assessing COPD
title_full The value of blood cytokines and chemokines in assessing COPD
title_fullStr The value of blood cytokines and chemokines in assessing COPD
title_full_unstemmed The value of blood cytokines and chemokines in assessing COPD
title_short The value of blood cytokines and chemokines in assessing COPD
title_sort value of blood cytokines and chemokines in assessing copd
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655820/
https://www.ncbi.nlm.nih.gov/pubmed/29065892
http://dx.doi.org/10.1186/s12931-017-0662-2
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