Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, 1400 Jackson St., K715, Denver, CO, 80206, USA.
University of Iowa, Internal Medicine, 200 Hawkins Dr C331-GH, Iowa City, IA, 52242, USA.
Respir Res. 2017 Oct 24;18(1):180. doi: 10.1186/s12931-017-0662-2.
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.
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).
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.
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.
COPDGene (ClinicalTrials.gov Identifier: NCT02445183 ). Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) ( ClinicalTrials.gov Identifier: NCT 01969344 ).
血液生物标志物越来越多地用于分层高危慢性阻塞性肺疾病（COPD）患者；然而，很少有研究调查了多种生物标志物，并在多个易感的当前和以前的吸烟者的大型特征良好的队列中进行了复制。
我们使用两个 MSD 多重面板在 COPDGene 中的 2123 名受试者和 SPIROMICS 中的 1117 名受试者中测量了 9 种细胞因子和趋化因子。这些生物标志物包括白细胞介素（IL）-2、IL-6、IL-8、IL-10、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、嗜酸性粒细胞趋化因子/CCL-11、嗜酸性粒细胞趋化因子 3/CCL-26 和胸腺激活调节趋化因子（TARC）/CCL-17。调整临床协变量的回归模型用于确定哪些生物标志物与以下 COPD 表型相关：气流阻塞（1 秒用力呼气量 (FEV%) 和 FEV/用力肺活量 (FEV/FVC)）、慢性支气管炎、COPD 加重和肺气肿。通过单核苷酸多态性 (SNP) 的全基因组关联评估生物标志物-基因型关联。
嗜酸性粒细胞趋化因子和 IL-6 与气流阻塞密切相关，在临床变量之外占测量方差的 3-5%。IL-6 与 5 年内进行性气流阻塞有关，IL-6 和 IL-8 均与 5 年内进行性肺气肿有关。没有一种生物标志物与慢性支气管炎或 COPD 加重一致相关。我们确定了一个与 CCL17 血浆测量相关的新 SNP（rs9302690 SNP）。
在评估与吸烟相关的肺部疾病时，炎症标志物如 IL-2、IL-6、IL-8 和嗜酸性粒细胞趋化因子可能在单独的临床变量之外提供额外的适度预测价值。
COPDGene（ClinicalTrials.gov 标识符：NCT02445183）。慢性阻塞性肺疾病的亚群和中间结局测量研究（SPIROMICS）（ClinicalTrials.gov 标识符：NCT01969344）。
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