%0 Journal Article %A Thomas Conlon %A Martin Irmler %A Johannes Beckers %A Jerzy Adamski %A Oliver Eickelberg %A Ali Önder Yildirim %T Metabolomic profiling of the lung in a murine model of emphysema %D 2014 %J European Respiratory Journal %P P3831 %V 44 %N Suppl 58 %X COPD is characterized by chronic bronchitis, small airway remodeling and emphysema. Metabolomics offers a powerful new tool for understanding changes in disease pathology. Indeed, increases in ceramide levels have been shown to cause pulmonary cell apoptosis and emphysema in mice. Here we aimed to use targeted metabolomics to fully characterize profiles in serum, lung and BAL of the porcine pancreatic elastase (PPE) induced model of emphysema and relate to changes in the transcriptome.A single oropharyngeal application of PPE (80U/kg) to C57BL/6 mice resulted in a progressive severe emphysema on d28, 56 & 161 as demonstrated by declining lung function and increased airspace enlargement (d28 64.2±16.2 v 28.0±4.7; d56 71.4±17.2 v 25.6±8.7; d161 74.0±18.5 v 47.2μm (mean±s.d.) for PPE v PBS). Targeted metabolite analysis was subsequently performed on serum, lung and BAL using the AbsoluteIDQ Kit (Biocrates Life Sciences). In parallel microarray analysis of lung tissue was undertaken.Interestingly, we found a significant time dependent reduction of phosphatidylcholines (67.5%) in BAL, acylcarnitines (38.2%) in lung, sphingomyelins (45.4% & 14.9%) and lysophosphatidylcholines (25.5% & 10.7%) in both BAL and lung respectively of PPE exposed mice. To substantiate, microarray data demonstrated changes in the expression pattern of genes important for the metabolism of sphingolipids (eg Asah1), that confirmed the metabolism of sphinogolipids towards ceramide. However, no significant change to the metabolic profile of serum was observed. Thus, changes in the metabolome local to the lung may contribute to disease pathology, lead to the discovery of new biomarkers of emphysema development and raise new therapeutic targets. %U