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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)-?, interferon (IFN)-?, 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 ).

SUBMITTER: Bradford E

PROVIDER: S-EPMC5655820 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The value of blood cytokines and chemokines in assessing COPD.

Bradford Eric E Jacobson Sean S Varasteh Jason J Comellas Alejandro P AP Woodruff Prescott P O'Neal Wanda W DeMeo Dawn L DL Li Xingnan X Kim Victor V Cho Michael M Castaldi Peter J PJ Hersh Craig C Silverman Edwin K EK Crapo James D JD Kechris Katerina K Bowler Russell P RP

Respiratory research 20171024 1

<h4>Background</h4>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.<h4>Methods</h4>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: interleu ...[more]

PMID: 29065892

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Project description:Antenatal and preschool factors are key in determining the progression to pre-school wheeze and eosinophilic school age asthma. The conventional view of eosinophilic asthma is that airway inflammation is the fundamental underlying abnormality, and airway inflammation and hyper-responsiveness are secondary; in fact, these three are parallel processes. Very early structural changes, independent of inflammation and infection, are associated with early airway hyper-responsiveness and later adverse respiratory outcomes. There is a bidirectional relationship between structural airway wall changes and airway inflammation, with airway contraction per se leading to the release of growth factors, and inflammatory pathways promoting airway remodeling. Early viral infection (and increasingly being appreciated, bacterial infection) is important in wheeze outcomes. There is evidence of abnormal immune function including cytokine release before the onset of viral infections. However, viral infections may also have prolonged effects on the host immune system, and the evidence for beneficial and adverse effects of viral infection is conflicting. In older children and adults, asthmatic epithelial cells show impaired interferon responses to viral infection, but only in the presence of uncontrolled type 2 inflammation, implying these are secondary phenomena. There are also compelling data relating the innate immune system to later asthma and atopy, and animal studies suggest that the effects of a high endotoxin, microbiologically diverse environment may be modulated via the epithelial alarmin IL-33. Whereas, previously only viral infection was thought to be important, early bacterial colonization of the upper airway is coming to the fore, associated with a mixed pattern of TH1/TH2/TH17 cytokine secretion, and adverse long term outcomes. Bacterial colonization is probably a marker of a subtle immune deficiency, rather than directly causal. The airway and gut microbiome critically impacts the development of Type 2 inflammatory responses. However, Type 2 inflammatory cytokines, which are critical both to progression from pre-school wheeze to eosinophilic asthma, and sustaining the eosinophilic asthmatic state, are not implicated in the very early development of the disease. Taken together, the evidence is that the earliest cytokine and chemokine signals will come from the study of bronchial epithelial cell function and their interactions with viruses and the microbiome.

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The value of blood cytokines and chemokines in assessing COPD.

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The value of blood cytokines and chemokines in assessing COPD.

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