Untargeted metabolomics of human plasma reveal lipid markers unique to chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

• Published in: Proteomics (Weinheim) Vol. 15; no. 2-3; pp. e2000039 - n/a
• Main Authors: Nambiar, Shabarinath, Tan, Dino Bee Aik, Clynick, Britt, Bong, Sze How, Rawlinson, Catherine, Gummer, Joel, Corte, Tamera J., Glaspole, Ian, Moodley, Yuben P., Trengove, Robert
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.05.2021
• Subjects: Aged; Air flow; Biomarkers - blood; Blood plasma; Case-Control Studies; Chromatography, High Pressure Liquid; Chronic obstructive pulmonary disease; COPD; Dihydrotestosterone; Disease; Fatty acids; Female; Fibrosis; Gas exchange; Humans; Idiopathic Pulmonary Fibrosis - blood; Idiopathic Pulmonary Fibrosis - metabolism; Inflammation; IPF; Linoleic acid; Lipid metabolism; Lipids; Lipids - blood; Liquid chromatography; Lung diseases; Male; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Obstructive lung disease; Oleic acid; Palmitoleic acid; Plasma; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary fibrosis; Quadrupoles; Respiratory tract diseases; Variance analysis; plasma; metabolomics; IPF; COPD
• ISSN: 1862-8346; 1615-9853; 1862-8354; 1862-8354; 1615-9861
• DOI: 10.1002/prca.202000039

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.