PT - JOURNAL ARTICLE AU - Yidan D Zhao AU - Li Yin AU - Stephen Archer AU - Catherine Lu AU - George Zhao AU - Yan Yao AU - Licun Wu AU - Michael Hsin AU - Thomas K Waddell AU - Shaf Keshavjee AU - John Granton AU - Marc de Perrot TI - Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study AID - 10.1136/bmjresp-2017-000183 DP - 2017 Jun 01 TA - BMJ Open Respiratory Research PG - e000183 VI - 4 IP - 1 4099 - http://bmjopenrespres.bmj.com/content/4/1/e000183.short 4100 - http://bmjopenrespres.bmj.com/content/4/1/e000183.full SO - BMJ Open Resp Res2017 Jun 01; 4 AB - Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown cause characterised by progressive fibrotic formation in lung tissue. We hypothesise that disrupted metabolic pathways in IPF contribute to disease pathogenesis.Methods Metabolomics of human IPF was performed using mass spectroscopy (IPF lung=8; donor lung=8). Gene expression of key metabolic enzymes was measured using microarrays. Of the 108 metabolites whose levels were found altered, 48 were significantly increased, whereas 60 were significantly decreased in IPF samples compared with normal controls.Results Specific metabolic pathways mediating the IPF remodelling were found with a downregulated sphingolipid metabolic pathway but an upregulated arginine pathway in IPF. In addition, disrupted glycolysis, mitochondrial beta-oxidation and tricarboxylic acid cycle, altered bile acid, haem and glutamate/aspartate metabolism were found in IPF samples compared with control.Conclusions Our results show alterations in metabolic pathways for energy consumption during lung structural remodelling, which may contribute to IPF pathogenesis. We believe that this is the first report of simultaneously and systemically measuring changes of metabolites involving nine metabolic pathways in human severe IPF lungs. The measurement of the metabolites may serve in the future diagnosis and prognosis of IPF.