High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children - 27/09/17
, Anne M. Fitzpatrick, PhD b, Carl Angelo Medriano, MEng a, Dean P. Jones, PhD cAbstract |
Background |
Corticosteroid (CS) treatment has been established as the first anti-inflammatory treatment for adults and children with asthma. However, a subset of patients fails to respond to combined systemic and inhaled CS treatment.
Objective |
This study was aimed at further understanding CS resistance among children with severe asthma.
Methods |
High-resolution metabolomics was performed on urine samples from CS-respondent (n = 15) and CS-nonrespondent (n = 15) children to determine possible urine biomarkers related to CS resistance. The metabolic phenotypes of CS responders and CS nonresponders were analyzed using bioinformatics including Manhattan plot with false- discovery rate, hierarchical cluster analysis, Kyoto Encyclopedia Genes and Genomes, and Mummichog pathway analysis.
Results |
The 2-way hierarchical cluster analysis study determined 30 metabolites showing significantly different levels between CS responders and CS nonresponders. The important metabolites annotated were 3,6-dihydronicotinic acid (126.05 m/z, RT: 106, [M+H]+), 3-methoxy-4-hydroxyphenyl(ethylene)glycol (185.05 m/z, RT: 155, [M+H]+), 3,4-dihydroxy-phenylalanine (198.07 m/z, RT: 446, [M+H]+), γ-glutamylcysteine (236.06 m/z, RT: 528, [M+S(34)+H]+), Cys-Gly, (253.06 m/z, RT: 528, [M-NH3+H]+), and reduced Flavin mononucleotide (517.0794 m/z, RT: 533, [M+NaCl]+). Tyrosine metabolism, degradation of aromatic compounds, and glutathione metabolism are suggested to be significant pathways relating to CS resistance.
Conclusions |
High-resolution metabolomics is a promising approach in asthma research. Five candidate markers were identified to be related to CS-resistant children with severe asthma. These compounds, upon validation, may contribute further in the understanding of CS resistance among children with severe asthma through the use of urine.
Le texte complet de cet article est disponible en PDF.Key words : Metabolomics, LC-MS, pediatric asthma, corticosteroid resistance
Abbreviations used : CS, CS-NR, CS-R, FDR, GSH, HCA, HRM, KEGG
Plan
| This research was supported in part by Emory University (grant no. R01 NR012021), the National Research Fund of Korea (grant no. NRF-2014R4A4A5286787), and Korea University (Korea Health Industry Development Institute grant no. HI14C2686). |
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| Disclosure of potential conflict of interest: A. M. Fitzpatrick receives grant support from the National Institute of Nursing Research. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 5
P. 1518 - mai 2017 Retour au numéro
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