Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity.
Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity.
复制标题
DOI：
10.1371/journal.pone.0038629
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fine JS
中科院分区：
文献类型：
--
作者：
Cockayne DA;Cheng DT;Waschki B;Sridhar S;Ravindran P;Hilton H;Kourteva G;Bitter H;Pillai SG;Visvanathan S;Müller KC;Holz O;Magnussen H;Watz H;Fine JS
生物标志物的鉴定和验证以支持COPD新疗法的评估仍然是一个重要的研究领域。当前研究的目的是确定与COPD严重程度测量相关的全身性蛋白质生物标志物，以及与代谢综合征等合并症相关的特定蛋白质特征。对140例稳定期COPD患者、15例非COPD吸烟者和30例非吸烟对照的142种蛋白质进行了血清分析。7项指标（sRAGE、EN-RAGE、NGAL、纤维蛋白原、MPO、TGF-α、HB-EGF）在重度/极重度COPD、轻度/中度COPD、吸烟对照组和非吸烟对照组之间存在显著差异。在COPD受试者中，单变量和多变量分析发现分析物与FEV1、FEV1/FVC和DLCO显著相关。最值得注意的是，一组5种分析物（HB-EGF，纤维蛋白原，MCP-4， sRAGE和Sortilin）预测了21%的DLCO值变异性。为了确定共同的功能/途径，分析物通过表达谱的相似性聚集在一个相关网络中。中性粒细胞功能相关的分析物（EN-RAGE， NGAL， MPO）聚集在一起形成与FEV1相关参数的簇，与EGFR途径相关的分析物（HB-EGF, TGF-α）形成与DLCO和FEV1相关参数的另一个簇。与合并代谢综合征的患者（r = - 0.25, p = 0.47和r = - 0.15, p = 0.96）相比，无代谢综合征患者纤维蛋白原与DLCO和MPO与FEV1/FVC的相关性更强（分别为r = - 0.52, p = 0.005和r = - 0.61, p = 0.023），这可能推动了一般队列的整体相关性。总之，我们的研究已经确定了已知的和新的血清蛋白生物标志物，并证明了与COPD疾病严重程度、FEV1、FEV1/FVC和DLCO的特定关联。这些数据强调了系统性炎症途径、中性粒细胞激活和上皮组织损伤/修复过程是与COPD相关的关键途径。
The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters. Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r = −0.52, p = 0.005 and r = −0.61, p = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r = −0.25, p = 0.47 and r = −0.15, p = 0.96, respectively), and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO. These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD.
登录
查看更多内容
影响因子：
5.8
作者：
Dickens JA;Miller BE;Edwards LD;Silverman EK;Lomas DA;Tal-Singer R;Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators
通讯作者：
Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators
DOI：
10.1165/rcmb.2005-0259oc
发表时间：
2006-08-01
影响因子：
6.4
作者：
Baginski, Tomasz K.;Dabbagh, Karim;Swinney, David C.
通讯作者：
Swinney, David C.
影响因子：
--
作者：
Buckley ST;Ehrhardt C
通讯作者：
Ehrhardt C
影响因子：
4.3
作者：
Braido, Fulvio;Riccio, Anna M.;Canonica, Giorgio Walter
通讯作者：
Canonica, Giorgio Walter
影响因子：
10
作者：
Calfee, C. S.;Ware, L. B.;Matthay, M. A.
通讯作者：
Matthay, M. A.