Separation Science and Metabolomics Laboratory, Murdoch University, Murdoch, WA, Australia.
School of Biomedical Sciences, University of Western Australia, Nedlands, WA, Australia.
Proteomics Clin Appl. 2021 May;15(2-3):e2000039. doi: 10.1002/prca.202000039. Epub 2021 Mar 18.
Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation and progressive airflow limitation, whereas idiopathic pulmonary fibrosis (IPF) is characterised by a restrictive pattern due to fibrosis and impaired gas exchange. We undertook metabolomic analysis of blood samples in IPF, COPD and healthy controls (HC) to determine differences in circulating molecules and identify novel pathogenic pathways. An untargeted metabolomics using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) was performed to profile plasma of patients with COPD (n = 21), and IPF (n = 24) in comparison to plasma from healthy controls (HC; n = 20). The most significant features were identified using multiple database matching. One-way ANOVA and variable importance in projection (VIP) scores were also used to highlight metabolites that influence the specific disease groups. Non-polar metabolites such as fatty acids (FA) and membrane lipids were well resolved and a total of 4805 features were identified. The most prominent metabolite composition differences in lipid mediators identified at ∼2-3 fold higher in both diseases compared to HC were palmitoleic acid, oleic acid and linoleic acid; and dihydrotestosterone was lower in both diseases. We demonstrated that COPD and IPF were characterised by systemic changes in lipid constituents such as essential FA sampled from circulating plasma.
慢性阻塞性肺疾病（COPD）的特征是气道炎症和进行性气流受限，而特发性肺纤维化（IPF）则表现为纤维化和气体交换受损导致的限制模式。我们对 IPF、COPD 和健康对照组（HC）的血液样本进行了代谢组学分析，以确定循环分子的差异并确定新的致病途径。采用超高效液相色谱-四极杆飞行时间质谱联用仪（UHPLC-QTOF-MS）进行非靶向代谢组学分析，以分析 COPD（n=21）和 IPF（n=24）患者的血浆与健康对照组（HC；n=20）的血浆之间的差异。使用多个数据库匹配来鉴定最显著的特征。还使用单向方差分析和投影变量重要性（VIP）得分来突出影响特定疾病组的代谢物。非极性代谢物（如脂肪酸（FA）和膜脂质）得到了很好的解析，共鉴定出 4805 种特征。在两种疾病中脂质介质的代谢物组成差异最为明显，与 HC 相比，其丰度约高出 2-3 倍，分别是棕榈油酸、油酸和亚油酸；两种疾病中的二氢睾酮水平都较低。我们表明，COPD 和 IPF 以循环血浆中采样的必需 FA 等脂质成分的系统性变化为特征。
