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通过代谢组学研究,通过 LOX 代谢的类二十烷代谢物可区分哮喘-COPD 重叠与 COPD。

Eicosanoids metabolized through LOX distinguish asthma-COPD overlap from COPD by metabolomics study.

机构信息

Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.

Department of Laboratory Medicine, Shenzhen People's Hospital, Shenzhen, People's Republic of China.

出版信息

Int J Chron Obstruct Pulmon Dis. 2019 Aug 6;14:1769-1778. doi: 10.2147/COPD.S207023. eCollection 2019.

DOI:10.2147/COPD.S207023
PMID:31496676
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6689553/
Abstract

BACKGROUND AND OBJECTIVE

The prevalence of asthma is greater than 20% in patients previously diagnosed with COPD. Patients with asthma-COPD overlap (ACO) are at risk of rapid progression of disease and severe exacerbations. However, in some patients with ACO, a clear distinction from COPD is very difficult by using physiological testing techniques. This study aimed to apply a novel metabolomic approach to identify the metabolites in sera in order to distinguish ACO from COPD.

METHODS

In the study, blood samples were collected from patients with COPD, ACO, and healthy controls. Cholamine derivatization-ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to investigate serum metabolites of eicosanoids.

RESULTS

A clear intergroup separation existed between the patients with ACO and those with COPD, while ACO tends to have higher serum metabolic levels of eicosanoids. A robust Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) model was found for discriminating between ACO and COPD (R2Y =0.81, Q2=0.79). In addition, there is a significant correlation between some metabolites and clinical indicators, such as hydroxyeicosatetraenoic acids (HETEs), hydroperoxyeicosatetraenoic acids (HPETEs) and FEV1/FVC. The higher values of area under the receiver operating characteristic curves (ROC) of HETEs, which were metabolized from HPETEs through lipoxygenase (LOX), indicated that they should be the potential biomarkers to distinguish ACO from COPD.

CONCLUSION

Eicosanoids can clearly discriminate different biochemical metabolic profiles between ACO and COPD. The results possibly provide a new perspective to identify potential biomarkers of ACO and may be helpful for personalized treatment.

摘要

背景和目的

既往诊断为 COPD 的患者中哮喘的患病率大于 20%。哮喘-COPD 重叠(ACO)患者疾病进展迅速且易发生严重加重。然而,在一些 ACO 患者中,使用生理测试技术很难将其与 COPD 明确区分。本研究旨在应用一种新的代谢组学方法来鉴定血清中的代谢物,以区分 ACO 与 COPD。

方法

本研究采集了 COPD、ACO 和健康对照组患者的血液样本。采用胆碱衍生物-超高效液相色谱-四级杆飞行时间质谱联用(UHPLC-Q-TOF/MS)技术研究了类二十烷酸的血清代谢物。

结果

ACO 患者与 COPD 患者之间存在明显的组间分离,而 ACO 患者的类二十烷酸血清代谢水平较高。发现了一种用于区分 ACO 和 COPD 的稳健正交偏最小二乘判别分析(OPLS-DA)模型(R2Y=0.81,Q2=0.79)。此外,一些代谢物与临床指标(如羟二十碳四烯酸(HETEs)、过氧二十碳四烯酸(HPETEs)和 FEV1/FVC)之间存在显著相关性。通过脂氧合酶(LOX)代谢生成 HPETEs 的 HETEs 的曲线下面积(ROC)的更高值表明其可能是区分 ACO 与 COPD 的潜在生物标志物。

结论

类二十烷酸可以明确区分 ACO 和 COPD 之间不同的生化代谢特征。结果可能为识别 ACO 的潜在生物标志物提供新视角,并可能有助于个性化治疗。

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