Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies. Recent research has focused on identifying the biological processes essential to the development and progression of fibrosis, and on the mediators driving these processes. Lysophosphatidic acid (LPA), a biologically active lysophospholipid, is one such mediator. LPA has been found to be elevated in bronchoalveolar lavage (BAL) fluid of IPF patients, and through interaction with its cell surface receptors, it has been shown to drive multiple biological processes implicated in the development of IPF. Accordingly, the first clinical trial of an LPA receptor antagonist in IPF has recently been initiated. In addition to being a therapeutic target, LPA also has potential to be a biomarker for IPF. There is increasing interest in exhaled breath condensate (EBC) analysis as a non-invasive method for biomarker detection in lung diseases, but to what extent LPA is present in EBC is not known.MethodsIn this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess for the presence of LPA in the EBC and plasma from 11 IPF subjects and 11 controls.ResultsA total of 9 different LPA species were detectable in EBC. Of these, docosatetraenoyl (22:4) LPA was significantly elevated in the EBC of IPF subjects when compared to controls (9.18 pM vs. 0.34 pM; p = 0.001). A total of 13 different LPA species were detectable in the plasma, but in contrast to the EBC, there were no statistically significant differences in plasma LPA species between IPF subjects and controls.ConclusionsThese results demonstrate that multiple LPA species are detectable in EBC, and that 22:4 LPA levels are elevated in the EBC of IPF patients. Further research is needed to determine the significance of this elevation of 22:4 LPA in IPF EBC, as well as its potential to serve as a biomarker for disease severity and/or progression.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies
exhaled breath condensate (EBC) was obtained on all subjects, and plasma was obtained on all 11 IPF patients and 10 of the controls
lysophosphatidic acid (LPA) has emerged as an important pro-fibrotic mediator in multiple organ systems, the lungs, and the first clinical trial of an LPA receptor antagonist has recently been initiated in IPF patients (ClinicalTrials.gov identifier: NCT01766817)
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies. Recent research has focused on identifying the biological processes essential to the development and progression of fibrosis, and on the mediators driving these processes. Research efforts have focused on identifying molecular pathways central to the progression from normal to fibrotic lung, as a better understanding of such pathways may provide potential targets for pharmacologic therapy and biomarkers to aid in diagnosis or prognosis [7]. One such area of interest involves the role of lysophosphatidic acid (LPA) in the development and progression of pulmonary fibrosis
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