The value of blood cytokines and chemokines in assessing COPD

Eric Bradford; Sean Jacobson; Jason Varasteh; Alejandro P. Comellas; Prescott Woodruff; Wanda O'Neal; Dawn L. DeMeo; Xingnan Li; Victor Kim; Michael Cho; Peter J. Castaldi; Craig Hersh; Edwin K. Silverman; James D. Crapo; Katerina Kechris; Russell P. Bowler

doi:10.1186/s12931-017-0662-2

The value of blood cytokines and chemokines in assessing COPD

Eric Bradford
, Sean Jacobson
, Jason Varasteh
, Alejandro P. Comellas
, Prescott Woodruff
, Wanda O'Neal
, Dawn L. DeMeo
, Xingnan Li
, Victor Kim
, Michael Cho
, Peter J. Castaldi
, Craig Hersh
, Edwin K. Silverman
, James D. Crapo
, Katerina Kechris
, Russell P. Bowler

Medicine

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

96 Scopus citations

Abstract

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 (FEV1%) and FEV1/forced vital capacity (FEV1/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 ).

Original language	English (US)
Pages (from-to)	180
Number of pages	1
Journal	Respiratory Research
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12931-017-0662-2
State	Published - Oct 24 2017

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1186/s12931-017-0662-2

Cite this

@article{9165262b819e46de9c42f0ca3b391323,

title = "The value of blood cytokines and chemokines in assessing COPD",

abstract = "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 (FEV1\%) and FEV1/forced vital capacity (FEV1/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 ).",

author = "Eric Bradford and Sean Jacobson and Jason Varasteh and Comellas, \{Alejandro P.\} and Prescott Woodruff and Wanda O'Neal and DeMeo, \{Dawn L.\} and Xingnan Li and Victor Kim and Michael Cho and Castaldi, \{Peter J.\} and Craig Hersh and Silverman, \{Edwin K.\} and Crapo, \{James D.\} and Katerina Kechris and Bowler, \{Russell P.\}",

note = "Funding Information: This research was supported by Award Number R01 HL129937 from the National Heart, Lung, and Blood Institute. COPDGene was supported by Award Number R01 HL089897 and Award Number R01 HL089856 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. The COPDGene{\textregistered} 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. SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN2682009 00013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C HHSN268200900019C, HHSN2 68200900020C), which were supplemented by contributions made through the Foundation for the NIH from AstraZeneca; Bellerophon Pharmaceuticals; Boehringer-Ingelheim Pharmaceuticals, Inc.; Chiesi Farmaceutici SpA; Forest Research Institute, Inc.; GSK; Grifols Therapeutics, Inc.; Ikaria, Inc.; Nycomed GmbH; Takeda Pharmaceutical Company; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals, Inc.; and Sanofi.",

year = "2017",

month = oct,

day = "24",

doi = "10.1186/s12931-017-0662-2",

language = "English (US)",

volume = "18",

pages = "180",

journal = "Respiratory Research",

issn = "1465-9921",

publisher = "BioMed Central",

number = "1",

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TY - JOUR

T1 - The value of blood cytokines and chemokines in assessing COPD

AU - Bradford, Eric

AU - Jacobson, Sean

AU - Varasteh, Jason

AU - Comellas, Alejandro P.

AU - Woodruff, Prescott

AU - O'Neal, Wanda

AU - DeMeo, Dawn L.

AU - Li, Xingnan

AU - Kim, Victor

AU - Cho, Michael

AU - Castaldi, Peter J.

AU - Hersh, Craig

AU - Silverman, Edwin K.

AU - Crapo, James D.

AU - Kechris, Katerina

AU - Bowler, Russell P.

N1 - Funding Information: This research was supported by Award Number R01 HL129937 from the National Heart, Lung, and Blood Institute. COPDGene was supported by Award Number R01 HL089897 and Award Number R01 HL089856 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. 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. SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN2682009 00013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C HHSN268200900019C, HHSN2 68200900020C), which were supplemented by contributions made through the Foundation for the NIH from AstraZeneca; Bellerophon Pharmaceuticals; Boehringer-Ingelheim Pharmaceuticals, Inc.; Chiesi Farmaceutici SpA; Forest Research Institute, Inc.; GSK; Grifols Therapeutics, Inc.; Ikaria, Inc.; Nycomed GmbH; Takeda Pharmaceutical Company; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals, Inc.; and Sanofi.

PY - 2017/10/24

Y1 - 2017/10/24

N2 - 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 (FEV1%) and FEV1/forced vital capacity (FEV1/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 ).

AB - 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 (FEV1%) and FEV1/forced vital capacity (FEV1/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 ).

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U2 - 10.1186/s12931-017-0662-2

DO - 10.1186/s12931-017-0662-2

M3 - Article

C2 - 29065892

AN - SCOPUS:85046002407

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VL - 18

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JO - Respiratory Research

JF - Respiratory Research

IS - 1

ER -

The value of blood cytokines and chemokines in assessing COPD

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