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通过检测血浆生物标志物来识别慢性阻塞性肺疾病(COPD)患者。

Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers.

作者信息

Shaker Saher B, von Wachenfeldt Karin A, Larsson Susanne, Mile Iréne, Persdotter Sofia, Dahlbäck Magnus, Broberg Per, Stoel Berend, Bach Karen S, Hestad Marianne, Fehniger Thomas E, Dirksen Asger

机构信息

Department of Cardiology and Respiratory Medicine, Hvidovre University Hospital, Copenhagen, Denmark.

出版信息

Clin Respir J. 2008 Jan;2(1):17-25. doi: 10.1111/j.1752-699X.2007.00032.x.

Abstract

INTRODUCTION

Inflammation is an important constituent of the pathology of chronic obstructive pulmonary disease (COPD), leading to alveolar destruction and airway remodelling.

OBJECTIVE

The aim of this study was to assess the difference in plasma biomarkers of inflammation between asymptomatic smokers and patients with COPD.

METHODS

We used commercially available enzyme-linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) on two occasions with a 2-week interval in patients with COPD (n = 20), asymptomatic smokers (n = 10) and healthy lifelong non-smokers (n = 10). The participants were characterised clinically, physiologically and by quantitative computed tomography by measuring the relative area of emphysema below -910 Hounsfield units (RA-910).

RESULTS

The results of the biomarker measurements on the two occasions were highly reproducible. Patients with COPD had significantly higher plasma levels of IL-8 (P = 0.004) and significantly lower levels of TIMP-1 (P = 0.02) than smokers and non-smokers. There was no statistically significant difference between the three groups in the level of TNF-alpha, MMP-9, MCP-1 and TIMP-2. The IL-8/TIMP-1 ratio correlated significantly with the degree of airway obstruction measured as forced expiratory volume in 1 second (FEV(1)) % predicted (r = -0.47, P < 0.01); with the diffusion capacity (r = -0.41, P < 0.01); and with the grade of emphysema measured as RA-910 (r = 0.39, P = 0.01).

CONCLUSION

These findings suggest that the measurement of plasma biomarkers, such as IL-8/TIMP-1, may aid to discriminate patients with COPD from smokers at lower risk of developing COPD.

摘要

引言

炎症是慢性阻塞性肺疾病(COPD)病理的重要组成部分,可导致肺泡破坏和气道重塑。

目的

本研究旨在评估无症状吸烟者与COPD患者炎症血浆生物标志物的差异。

方法

我们使用市售酶联免疫吸附测定试剂盒,在间隔2周的两个时间点测量COPD患者(n = 20)、无症状吸烟者(n = 10)和健康终身不吸烟者(n = 10)血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、基质金属蛋白酶-9(MMP-9)、单核细胞趋化蛋白-1(MCP-1)、金属蛋白酶组织抑制剂-1(TIMP-1)和金属蛋白酶组织抑制剂-2(TIMP-2)的水平。通过测量低于-910亨氏单位的肺气肿相对面积(RA-910),对参与者进行临床、生理和定量计算机断层扫描特征分析。

结果

两次生物标志物测量结果具有高度可重复性。COPD患者的IL-8血浆水平显著高于吸烟者和不吸烟者(P = 0.004),而TIMP-1水平显著低于吸烟者和不吸烟者(P = 0.02)。三组之间TNF-α、MMP-9、MCP-1和TIMP-2水平无统计学显著差异。IL-8/TIMP-1比值与以1秒用力呼气量(FEV(1))预测值百分比衡量的气道阻塞程度显著相关(r = -0.47,P < 0.01);与弥散能力相关(r = -0.41,P < 0.01);与以RA-910衡量的肺气肿分级相关(r = 0.39,P = 0.01)。

结论

这些发现表明,测量血浆生物标志物,如IL-8/TIMP-1,可能有助于将COPD患者与患COPD风险较低的吸烟者区分开来。

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