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具有“肺气肿表型加重者”特征的慢性阻塞性肺疾病严重程度与潜在生物标志物相关。

Severity of chronic obstructive pulmonary disease with 'exacerbator with emphysema phenotype' is associated with potential biomarkers.

机构信息

Department of Respiratory and Critical Care Medicine, Yan'an University Affiliated Hospital, Yan'an, China

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Postgrad Med J. 2020 Jan;96(1131):28-32. doi: 10.1136/postgradmedj-2019-136599. Epub 2019 Aug 2.

Abstract

OBJECTIVE

The present study was designed to investigate the biomarkers levels of fractalkine (FKN), neutrophil elastase (NE) and matrix metalloproteinase-12 (MMP-12) in chronic obstructive pulmonary disease (COPD) with 'exacerbator with emphysema phenotype' and to evaluate the associations between the biomarkers levels and the severity of disease by spirometric measurements.

METHODS

A total of 84 COPD patients and 49 healthy controls were enrolled in our study. ELISA were utilised to detect the FKN, MMP-12 and NE in serum from all subjects.

RESULTS

FKN (p<0.001), NE (p=0.039) and MMP-12 (p<0.001) in serum of COPD patients showed higher levels than that of healthy control subjects. Serum FKN (p<0.001), MMP-12 (p<0.001) and NE (p=0.043) levels were significantly higher in severe and very severe COPD patients than that in mild and moderate COPD patients. Circulating FKN, MMP-12 and NE expression levels were significantly elevated (p<0.001) in COPD smokers compared with COPD non-smokers. The smoke pack years were negatively correlated with FEV%pred (r=-0.5036), FEV/FVC ratio (r=-0.2847) (FEV, forced expiratory volume; FVC, forced vital capacity). Similarly, we observed a strong positive correlation between the smoke pack years and serum levels of FKN (r=0.4971), MMP-12 (r=0.4315) and NE (r=0.2754). FEV%pred was strongly negatively correlated with cytokine levels of FKN (r=-0.4367), MMP-12 (r=-0.3295) and NE (r=-0.2684). Likewise, FEV/FVC ratio was negatively correlated with mediators of inflammation levels of FKN (r=-0.3867), MMP-12 (r=-0.2941) and NE (r=-0.2153).

CONCLUSION

Serum FKN, MMP-12 and NE concentrations in COPD patients are directly associated with the severity of COPD with 'exacerbator with emphysema phenotype'. This finding suggests that FKN, MMP-12 and NE might play an important role in the pathophysiology of COPD.

摘要

目的

本研究旨在探讨慢性阻塞性肺疾病(COPD)伴“肺气肿表型加重者”中趋化因子(FKN)、中性粒细胞弹性蛋白酶(NE)和基质金属蛋白酶-12(MMP-12)的生物标志物水平,并通过肺功能测量评估其与疾病严重程度的相关性。

方法

本研究共纳入 84 例 COPD 患者和 49 名健康对照者。采用 ELISA 法检测所有受试者血清中的 FKN、MMP-12 和 NE。

结果

与健康对照组相比,COPD 患者血清中的 FKN(p<0.001)、NE(p=0.039)和 MMP-12(p<0.001)水平更高。与轻度和中度 COPD 患者相比,重度和极重度 COPD 患者血清中的 FKN(p<0.001)、MMP-12(p<0.001)和 NE(p=0.043)水平显著升高。与 COPD 非吸烟者相比,COPD 吸烟者的循环 FKN、MMP-12 和 NE 表达水平显著升高(p<0.001)。吸烟包年数与 FEV%pred(r=-0.5036)、FEV/FVC 比值(r=-0.2847)(FEV,用力呼气量;FVC,用力肺活量)呈负相关。同样,我们观察到吸烟包年数与血清 FKN(r=0.4971)、MMP-12(r=0.4315)和 NE(r=0.2754)水平呈强正相关。FEV%pred 与 FKN(r=-0.4367)、MMP-12(r=-0.3295)和 NE(r=-0.2684)的细胞因子水平呈强负相关。同样,FEV/FVC 比值与炎症介质 FKN(r=-0.3867)、MMP-12(r=-0.2941)和 NE(r=-0.2153)水平呈负相关。

结论

COPD 患者血清中 FKN、MMP-12 和 NE 浓度与 COPD 伴“肺气肿表型加重者”的严重程度直接相关。这一发现表明,FKN、MMP-12 和 NE 可能在 COPD 的病理生理学中发挥重要作用。

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