Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function. The pathophysiological pathways involved in IPF are not well understood. Abnormal lipid metabolism has been described in various other chronic lung diseases including asthma and chronic obstructive pulmonary disease (COPD). However, its potential role in IPF pathogenesis remains unclear.MethodsIn this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to characterize lipid changes in plasma derived from IPF patients with stable and progressive disease. We further applied a data-independent acquisition (DIA) technique called SONAR, to improve the specificity of lipid identification.ResultsStatistical modelling showed variable discrimination between the stable and progressive subjects, revealing differences in the detection of triglycerides (TG) and phosphatidylcholines (PC) between progressors and stable IPF groups, which was further confirmed by mass spectrometry imaging (MSI) in IPF tissue.ConclusionThis is the first study to characterise lipid metabolism between stable and progressive IPF, with results suggesting disparities in the circulating lipidome with disease progression.

Highlights

  • Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function

  • Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by alveolar epithelial cell activation and damage, resulting in proliferation of activated fibroblasts and extracellular matrix deposition leading to irreversible destruction of gas exchange units and lung remodelling [1]

  • The composition and involvement of the lipidome in various diseases is still poorly understood, abnormal lipid metabolism has been reported in few lung diseases including asthma and chronic obstructive pulmonary disease (COPD) [4, 5]

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Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by alveolar epithelial cell activation and damage, resulting in proliferation of activated fibroblasts and extracellular matrix deposition leading to irreversible destruction of gas exchange units and lung remodelling [1]. Previous studies suggested that IPF is related to abnormalities in a number of biological processes including glycolysis, fatty acid oxidation and vascular remodelling [1,2,3]. Lipidomic studies of complex biological matrices (plasma and tissue extracts) are routinely performed using UPLCQTOF-MS, resulting in excellent metabolite detection. We have applied SONAR, a rapidly scanning method in tandem with UPLC-QTOF-MS acquisition to provide additional information and quantification of metabolites in complex samples [8, 9]

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