Exploring breath biomarkers in BLM-induced pulmonary fibrosis mice with associative ionization time-of-flight mass spectrometry

• Published in: Talanta (Oxford) 2022-03, Vol.239, p.123120-123120, Article 123120
• Main Authors: Wu, Xiaoxue, Li, Zhen, Shu, Jinian, Lu, Zhongbing, Gao, Junling, Yang, Bo, Jiang, Kui, Guo, Yedong, Huang, Jingyun
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Bleomycin; Breath; Breath Tests; Exhalation; Humans; Idiopathic Pulmonary Fibrosis - chemically induced; Idiopathic Pulmonary Fibrosis - diagnosis; Mass Spectrometry; Mice; Pulmonary fibrosis
• ISSN: 0039-9140; 1873-3573
• DOI: 10.1016/j.talanta.2021.123120

Pulmonary fibrosis (PF) is a common but fatal disease that threatens human health worldwide. Developing effective diagnostic methods is of great importance for the early detection of PF in patients. In this study, bleomycin (BLM) was used in mice to mimic idiopathic pulmonary fibrosis (IPF). The exhaled breath of BLM-induced PF, PF plus DDAH1 overexpression, and healthy control mice were analyzed in real-time using a newly developed associative ionization time-of-flight mass spectrometry method (AI-TOFMS), which is uniquely sensitive, especially to oxygenated volatile organic compounds (VOCs). Multivariate data analyses and discriminant modeling analyses revealed that four exhaled compounds, i.e., acrolein, ethanol, nitric oxide, and ammonia, had a strong correlation with PF symptoms. An Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA) score plot showed an excellent separation between these three groups. The area under the receiver operating characteristic (ROC) curve for these four compounds distinguished PF mice from healthy controls at 0.989. In addition, the degrees of acute inflammation and fibrosis were assessed with Hematoxylin and Eosin (H&E) staining and Masson's Trichrome staining. Finally, combined with pathological characteristics and mRNA expression levels, the formation of the above-mentioned volatile compounds was explored. The obtained experimental results indicated that these four breath compounds, acrolein, ethanol, nitric oxide, and ammonia, were potential exhaled biomarkers for pulmonary fibrosis. [Display omitted] •Exhaled breathes of the pulmonary fibrosis and healthy control mice were analyzed in real-time.•The ultra-sensitive associative ionization mass spectrometry was used to analyze the mouse breathes.•The study found acrolein, ethanol, nitric oxide, and ammonia to be the potential biomarkers.•Formation of the biomarkers was explored via pathological characteristics and mRNA levels.