The value of blood cytokines and chemokines in assessing COPD

Respir Res. 2017 Oct 24;18(1):180. doi: 10.1186/s12931-017-0662-2.

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 ).

Trial registration: ClinicalTrials.gov NCT02445183 NCT01969344.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Chemokines / blood*
  • Cohort Studies
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Smoking / blood
  • Smoking / epidemiology

Substances

  • Biomarkers
  • Chemokines
  • Cytokines

Associated data

  • ClinicalTrials.gov/NCT02445183
  • ClinicalTrials.gov/NCT01969344