The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes.
The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes.
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DOI：
10.1186/s12931-014-0127-9
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发表时间：
2014-10-12
影响因子：
5.8
通讯作者：
Bowler RP
中科院分区：
文献类型：
--
作者：
Carolan BJ;Hughes G;Morrow J;Hersh CP;O'Neal WK;Rennard S;Pillai SG;Belloni P;Cockayne DA;Comellas AP;Han M;Zemans RL;Kechris K;Bowler RP
慢性阻塞性肺疾病(COPD)是一种表型异质性疾病。在慢性阻塞性肺疾病中，肺气肿的存在与死亡率和肺癌风险的增加有关。高分辨率计算机断层扫描(HRCT)在肺气肿的量化方面很有用，但与辐射暴露和假阳性发现(即结节)的高发生率有关。使用综合生物标记物小组，我们试图确定是否存在肺气肿的外周血液生物标记物特征。在参加COPD基因研究的588人中，使用定制的分析方法测量了114个血浆生物标记物。肺气肿定量测量包括低肺密度百分比(%LAA)、 ≤ −950HU、≤ − 910HU和肺密度曲线(LP15A)第15百分位的平均肺密度。进行多元回归分析，以确定与肺气肿相关的血浆生物标志物，与年龄、性别、吸烟状况、体重指数和FEV1无关。随后，使用来自388名参加选择性维甲酸激动剂(TESRA)研究的388名治疗肺气肿的受试者的基线血液样本验证了这一发现。回归分析发现COPD基因中与CT评估的肺气肿相关的多个生物标志物，包括晚期糖基化终产物受体(AGE或RAGE，p <； 0.001)、细胞间黏附分子1(ICAM，p <； 0.001)和趋化因子配体20(CCL20，p <； 0.001)。TESRA队列验证显示RAGE、ICAM 1和CCL20与放射性肺气肿显著相关(荟萃分析后p <； 0.001)。其他与肺气肿相关的生物标记物包括CDH1、CDH13和SERPINA7，但在TESRA研究中没有得到验证。受试者操作特性分析表明，在临床协变量中增加生物标记物面板对检测肺气肿是有好处的，特别是在那些没有严重气流受限(AUC 0.85)的患者。我们的发现表明，包括SRAGE、ICAM1和CCL20在内的一组血液生物标志物可以作为肺气肿的有用替代指标，当与临床协变量结合时，与仅使用协变量相比，在临床上可能有助于预测肺气肿的存在，特别是在那些病情较轻的COPD患者中。最终，生物标记物可能会揭示疾病的发病机制，为新的治疗提供靶点。本文的在线版本(doi：10.1186/s12931-0140127-9)包含补充材料，授权用户可以使用。
Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema. 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ −950 HU, ≤ − 910 HU and mean lung attenuation at the 15th percentile on lung attenuation curve (LP15A). Multiple regression analysis was performed to determine plasma biomarkers associated with emphysema independent of covariates age, gender, smoking status, body mass index and FEV1. The findings were subsequently validated using baseline blood samples from a separate cohort of 388 subjects enrolled in the Treatment of Emphysema with a Selective Retinoid Agonist (TESRA) study. Regression analysis identified multiple biomarkers associated with CT-assessed emphysema in COPDGene, including advanced glycosylation end-products receptor (AGER or RAGE, p < 0.001), intercellular adhesion molecule 1 (ICAM, p < 0.001), and chemokine ligand 20 (CCL20, p < 0.001). Validation in the TESRA cohort revealed significant associations with RAGE, ICAM1, and CCL20 with radiologic emphysema (p < 0.001 after meta-analysis). Other biomarkers that were associated with emphysema include CDH1, CDH 13 and SERPINA7, but were not available for validation in the TESRA study. Receiver operating characteristics analysis demonstrated a benefit of adding a biomarker panel to clinical covariates for detecting emphysema, especially in those without severe airflow limitation (AUC 0.85). Our findings, suggest that a panel of blood biomarkers including sRAGE, ICAM1 and CCL20 may serve as a useful surrogate measure of emphysema, and when combined with clinical covariates, may be useful clinically in predicting the presence of emphysema compared to just using covariates alone, especially in those with less severe COPD. Ultimately biomarkers may shed light on disease pathogenesis, providing targets for new treatments. The online version of this article (doi:10.1186/s12931-014-0127-9) contains supplementary material, which is available to authorized users.
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影响因子：
9.6
作者：
Hoesein, Firdaus A. A. Mohamed;Zanen, Pieter;Lammers, Jan-Willem J.
通讯作者：
Lammers, Jan-Willem J.
影响因子：
9.6
作者：
de Torres, Juan P.;Bastarrika, Gorka;Zulueta, Javier J.
通讯作者：
Zulueta, Javier J.
DOI：
10.1164/ajrccm.149.3.7509705
发表时间：
1994-03-01
影响因子：
24.7
作者：
DISTEFANO, A;MAESTRELLI, P;SAETTA, M
通讯作者：
SAETTA, M
影响因子：
--
作者：
Buckley ST;Ehrhardt C
通讯作者：
Ehrhardt C
影响因子：
5.7
作者：
Agusti, Alvar;Sin, Don D.
通讯作者：
Sin, Don D.