Wang Yating, Chang Chun, Tian Sifan, Wang Juan, Gai Xiaoyan, Zhou Qiqiang, Chen Yahong, Gao Xu, Sun Yongchang, Liang Ying
Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.
Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China.
Front Mol Biosci. 2023 Jul 12;10:1204985. doi: 10.3389/fmolb.2023.1204985. eCollection 2023.
In this study, we aimed to investigate the differences in serum lipid metabolite profiles and their relationship with clinical characteristics between patients with eosinophilic and non-eosinophilic AECOPD. A total of 71 AECOPD patients were enrolled. Eosinophilic AECOPD was defined as blood EOS% ≥ 2% ( = 23), while non-eosinophilic AECOPD, as blood EOS< 2% ( = 48). Clinical data were collected, and serum lipid metabolism profiles were detected by liquid chromatography-mass spectrometry (LC-MS). The XCMS software package was used to pre-process the raw data, and then, lipid metabolite identification was achieved through a spectral match using LipidBlast library. Differences in lipid profiles and clinical features between eosinophilic and non-eosinophilic groups were analyzed by generalized linear regression. The least absolute shrinkage and selection operator (LASSO) was applied to screen the most characteristic lipid markers for the eosinophilic phenotype. Eosinophilic AECOPD patients had less hypercapnic respiratory failures, less ICU admissions, a shorter length of stay in the hospital, and a lower fibrinogen level. In the lipid metabolism profiles, 32 significantly different lipid metabolites were screened through a -test adjusted by using FDR (FDR-adjusted < 0.05 and VIP> 1). Nine differential lipid metabolites were found to be associated with the three clinical features, namely, hypercapnia respiratory failure, ICU admission, and fibrinogen in further integration analysis. The species of triacylglycerol (TAG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and diacylglyceryl trimethylhomoserine (DGTS) were high in these eosinophilic AECOPD. The LASSO was applied, and three lipid metabolites were retained, namely, LPC (16:0), TAG (17:0/17:2/17:2), and LPC (20:2). The logistic regression model was fitted using these three markers, and the area under the ROC curve of the model was 0.834 (95% CI: 0.740-0.929). Patients with eosinophilic AECOPD had a unique lipid metabolism status. Species of TAGs and LPCs were significantly increased in this phenotype and were associated with better clinical outcomes.
在本研究中,我们旨在调查嗜酸性粒细胞性与非嗜酸性粒细胞性慢性阻塞性肺疾病急性加重(AECOPD)患者血清脂质代谢物谱的差异及其与临床特征的关系。共纳入71例AECOPD患者。嗜酸性粒细胞性AECOPD定义为血液嗜酸性粒细胞百分比(EOS%)≥2%(n = 23),而非嗜酸性粒细胞性AECOPD定义为血液EOS<2%(n = 48)。收集临床资料,并采用液相色谱-质谱联用(LC-MS)检测血清脂质代谢谱。使用XCMS软件包对原始数据进行预处理,然后通过与LipidBlast库进行光谱匹配实现脂质代谢物鉴定。采用广义线性回归分析嗜酸性粒细胞性和非嗜酸性粒细胞性组之间脂质谱和临床特征的差异。应用最小绝对收缩和选择算子(LASSO)筛选嗜酸性粒细胞表型最具特征性的脂质标志物。嗜酸性粒细胞性AECOPD患者发生高碳酸血症性呼吸衰竭的情况较少,入住重症监护病房(ICU)的次数较少,住院时间较短,纤维蛋白原水平较低。在脂质代谢谱中,通过使用错误发现率(FDR)调整的t检验筛选出32种显著不同的脂质代谢物(FDR调整后P<0.05且变量重要性投影(VIP)>1)。在进一步的整合分析中,发现9种差异脂质代谢物与三种临床特征相关,即高碳酸血症性呼吸衰竭、入住ICU和纤维蛋白原。这些嗜酸性粒细胞性AECOPD患者中三酰甘油(TAG)、磷脂酰胆碱(PC)、溶血磷脂酰胆碱(LPC)和二酰甘油基三甲基高丝氨酸(DGTS)的种类较高。应用LASSO,保留了三种脂质代谢物,即LPC(16:0)、TAG(17:0/17:2/17:2)和LPC(20:2)。使用这三种标志物拟合逻辑回归模型,该模型的受试者工作特征曲线下面积为0.834(95%可信区间:0.740-0.929)。嗜酸性粒细胞性AECOPD患者具有独特的脂质代谢状态。在这种表型中,TAG和LPC的种类显著增加,并与更好的临床结局相关。