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Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats using Multivariate Statistics of NMR Spectra of Exhaled Breath Condensate

ABSTRACT: Asthma is prevalent in children and cats, and needs means of noninvasive diagnosis. We sought to distinguish noninvasively the differences in 53 cats before and soon after induction of allergic asthma, using NMR spectra of exhaled breath condensate (EBC). Statistical pattern recognition was improved by preprocessing the spectra with glog transformation. Classification of the 106 preprocessed spectra by principal component analysis, partial least squares with discriminant analysis (PLS-DA), and multi-level PLS-DA appears to be impaired by variances unrelated to eosinophilic asthma. By subtracting out confounding variances, orthogonal signal correction (OSC) PLS-DA greatly improved the separation of the healthy and early asthmatic states, attaining 94% specificity and 71% sensitivity in predictions. OSC-PLS-DA results highlight the elevation of acetone in two-thirds of the cats with early asthma. Asthma also decreased at least a dozen compounds, especially carboxylic acids such as short chain fatty acids and amino acids. These trends suggest that a majority of the cats with allergic asthma underwent alteration of metabolic fluxes through pyruvate and acetyl-CoA to promote ketosis. The noninvasive detection of early experimental asthma, its biomarkers in EBC, and metabolic rerouting invite further investigation of the diagnostic potential in humans.

ORGANISM(S): Cat Felis Catus

TISSUE(S): Lung

DISEASE(S): Asthma

SUBMITTER: Steven Van Doren

PROVIDER: ST000406 | MetabolomicsWorkbench | Wed Apr 13 00:00:00 BST 2016

REPOSITORIES: MetabolomicsWorkbench

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Project description:Background: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored. Aim: To analyze dysfunctions of epithelium in dust mite allergic respiratory disease (rhinitis ¬± asthma) in children. Methods: Expression profilings of nasal epithelial cells collected by brushing were performed on Affymetrix Hugene 1.0 ST arrays. All allergic patients were sensitized to dust mite. 19 patients had an isolated allergic rhinitis (AR). 14 patients had AR associated with asthma. Patients were compared to 12 controls, their severity and control being assessed according to NAEPP and ARIA criteria. Infections by respiratory viruses were excluded by real-time PCR measurements. Results: 61 probes were able to distinguish allergic rhinitis children from healthy controls. A majority of these probes was under the control of Th2 cytokines, as evidenced by parallel experiments performed on primary cultures of nasal epithelial cells. In uncontrolled asthmatic patients, we observed not only an enhanced expression of these Th2-responsive transcripts, but also a down-regulation of interferon-responsive genes. Conclusion: Our study identifies a Th2 driven epithelial phenotype common to all dust mite allergic children. Besides, it suggests that epithelium is involved in the severity of the disease. Expression profiles observed in uncontrolled asthmatic patients suggest that severity of asthma is linked at the same time to atopy and to impaired viral response. Nasal epithelium gene expression profiling of dust mite allergic children with isolated rhinitis, rhinitis associated with asthma and controls. 38 samples classified in 4 categories : 14 isolated rhinitis (R), 6 rhinitis with uncontrolled asthma (UA), 7 rhinitis with controlled asthma (CA) and 11 healthy subjects (C )

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Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats using Multivariate Statistics of NMR Spectra of Exhaled Breath Condensate

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