Abstract

Introduction: Metabolomics is the identification and quantification of small molecular weight metabolites in a biofluid. Specific profiles of volatile compounds and metabolites in EBC are potentially useful surrogate markers of distinct phenotypes in asthma. Aim: To detect possible differences in the metabolic profile between mild-to-moderate and severe asthmatic patients based on Gas Chromatography-Mass Spectrometry (GC-MS) metabolomics of EBC. Methods: 37 asthmatic patients at stable state for at least 6 months were studied (15 with severe asthma, non-smokers). EBC was collected with Ecoscreen device (Jaeger, Germany) and EBC metabolomics were analyzed with GC-MS. PCA and further PLS/OPLS analysis were performed to separate the two groups of asthmatic patients. T-test and VIP total were performed to detect the peaks that were statistically different in the groups. Results: PCA and PLS-DA UV Scaling could not separate mild-to-moderate from severe asthmatics whereas OPLS-DA UV Scaling demonstrated distinct separation between the two groups. In VIP total diagram 20 unidentified peaks differed significantly between the groups according to 2-tail t-test assuming unequal variances. Further analysis was performed to identify the metabolites and 2 metabolites have been identified so far using available libraries. Further identification will be performed using public available libraries and software systems. Conclusion: EBC is a difficult-to-handle biofluid for metabolomic analysis. GC-MS based metabolomics analysis of biofluids is a novel, promising method to distinguish different asthma phenotypes and could add information used in personalized therapy.

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