Metabolomic profiling of asthma: Diagnostic utility of urine nuclear magnetic resonance spectroscopy - 10/08/11
Reprint requests: Darryl J. Adamko, MD, FRCPC, Department of Pediatrics, Faculty of Medicine and Dentistry, 550A HMRC, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2.Abstract |
Background |
The ability to diagnose and monitor asthma on the basis of noninvasive measurements of airway cellular dysfunction is difficult in the typical clinical setting.
Objective |
Metabolomics is the study of molecules created by cellular metabolic pathways. We hypothesized that the metabolic activity of children with asthma would differ from healthy children without asthma. Furthermore, children having an asthma exacerbation would be different compared with children with stable asthma in outpatient clinics. Finally, we hypothesized that 1H-nuclear magnetic resonance (NMR) would measure such differences using urine samples, one of the least invasive forms of biofluid sampling.
Methods |
Children (135 total, ages 4-16 years) were enrolled, having met the criteria of healthy controls (C), stable asthma in the outpatient clinic (AO), or unstable asthma in the emergency department (AED). Partial least squares discriminant analysis was performed on the NMR data to create models of separation (70 metabolites were measured/urine sample). Some NMR data were withheld from modeling to be run blindly to determine possible diagnostic accuracy.
Results |
On the basis of the model of AO versus C, 31 of 33 AO samples were correctly diagnosed with asthma (94% accuracy). Only 1 of 20 C samples was incorrectly labeled as asthma (5% misclassification). On the basis of the AO versus AED model, 31 of the 33 AO samples were correctly diagnosed as outpatient asthma (94% accurate).
Conclusion |
This is the first report suggesting that 1H-NMR analysis of human urine samples has the potential to be a useful clinical tool for physicians treating asthma.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, inflammation, biomarkers, urine, NMR, metabolomics
Abbreviations used : ED, EPX, NMR, PLS-DA, Q2, R2, VIP
Plan
| Supported by the Sick Kids Foundation, AllerGen, the Magnetic Resonance Diagnostic Centre (MRDC), and the Canadian Institutes for Health Research (CIHR). The MRDC has received funding from CIHR, Genome Prairie, Genome Canada, an establishment grant from AHFMR, the Canadian National High Field NMR Centre, the Natural Science and Engineering Research Council of Canada, the University of Alberta Hospital Foundation, the Alberta Science and Research Authority, and Western Economic Development. D.J.A. was an AHFMR Clinical Investigator and R.M. an AHFMR Medical Scientist. B.H.R.’s research is supported by the 21st Century Research Chairs Program from the Government of Canada (Ottawa, Ontario). |
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| Disclosure of potential conflict of interest: R. Moqbel has a consultancy with GlaxoSmithKline. B. H. Rowe has received speaking fees and research support from GlaxoSmithKline; has received research support from MedImmune and the Canadian Institutes of Health Research; and is on the Canadian Thoracic Society Asthma Guidelines Committee. D. J. Adamko has received research support from Afexa and Merck. The rest of the authors have declared that they have no conflict of interest. |
Vol 127 - N° 3
P. 757 - mars 2011 Retour au numéro
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