Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics.

Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics.
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DOI:
10.3390/ijms19030666
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发表时间:
2018-02-27
影响因子:
5.6
通讯作者:
Altraja A
Altraja A
中科院分区:
生物学2区
文献类型:
--
作者:
Kilk K;Aug A;Ottas A;Soomets U;Altraja S;Altraja A

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除了慢性阻塞性肺疾病(COPD)的精细化管理导向的临床分层外,这种高度流行疾病背后的分子病理学仍然不清楚。本研究的目的是在定义的临床和人口统计学变量的背景下,基于外周血和呼出气冷凝液(EBC)的代谢组学特征描述COPD患者的特征。对不同临床特征的COPD患者(n = 25)和对照个体(n = 21)进行基于质谱的血清代谢物(主要是氨基酸和脂质物质)、血清和EBC的非靶向谱的靶向分析。根据合并的临床/人口统计学和代谢组学数据,检索临床/人口统计学和代谢参数之间的关联,并尝试重新进行COPD表型分型。结合临床参数,鞘磷脂是区分COPD患者和对照组的最佳指标。来自非靶向分析的含不饱和脂肪酸的脂质、鸟氨酸代谢和血浆蛋白组成相关信号区分了COPD全球倡议(GOLD)类别。分层聚类未显示临床代谢组学分层优于GOLD共识设定的分层上级。我们的结论是,虽然代谢组学方法是很好的发现生物标志物和阐明疾病的机制,有没有明显的协变量独立的临床代谢表型。
Apart from the refined management-oriented clinical stratification of chronic obstructive pulmonary disease (COPD), the molecular pathologies behind this highly prevalent disease have remained obscure. The aim of this study was the characterization of patients with COPD, based on the metabolomic profiling of peripheral blood and exhaled breath condensate (EBC) within the context of defined clinical and demographic variables. Mass-spectrometry-based targeted analysis of serum metabolites (mainly amino acids and lipid species), untargeted profiles of serum and EBC of patients with COPD of different clinical characteristics (n = 25) and control individuals (n = 21) were performed. From the combined clinical/demographic and metabolomics data, associations between clinical/demographic and metabolic parameters were searched and a de novo phenotyping for COPD was attempted. Adjoining the clinical parameters, sphingomyelins were the best to differentiate COPD patients from controls. Unsaturated fatty acid-containing lipids, ornithine metabolism and plasma protein composition-associated signals from the untargeted analysis differentiated the Global Initiative for COPD (GOLD) categories. Hierarchical clustering did not reveal a clinical-metabolomic stratification superior to the strata set by the GOLD consensus. We conclude that while metabolomics approaches are good for finding biomarkers and clarifying the mechanism of the disease, there are no distinct co-variate independent clinical-metabolic phenotypes.
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