The value of blood cytokines and chemokines in assessing COPD.

MS#: 
MS107
TitleThe value of blood cytokines and chemokines in assessing COPD.
Publication TypePublication
Year2017
AuthorsBradford E, Jacobson S, Varasteh J, Comellas AP, Woodruff P, O'Neal W, DeMeo DL, Li X, Kim V, Cho M, Castaldi PJ, Hersh C, Silverman EK, Crapo JD, Kechris K, Bowler RP
JournalRespir Res
Volume18
Issue1
Pagination180
Date Published2017 10 24
ISSN1465-993X
KeywordsAged, Aged, 80 and over, biomarkers, Chemokines, Cohort Studies, Cytokines, Female, Humans, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, smoking
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 (FEV%) and FEV/forced vital capacity (FEV/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 ).

DOI10.1186/s12931-017-0662-2
Alternate JournalRespir. Res.
PubMed ID29065892
PubMed Central IDPMC5655820
Grant ListR01 HL089897 / HL / NHLBI NIH HHS / United States
HHSN268200900019C / HL / NHLBI NIH HHS / United States
U01 HL089897 / HL / NHLBI NIH HHS / United States
R01 HL089856 / HL / NHLBI NIH HHS / United States
U01 HL089856 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
R01 HL129937 / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
R01 HL126596 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Denver (National Jewish Health)
ECI: 
Manuscript Status: 
Published and Public