title: Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats Using Multivariate Statistical Analysis 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 considerably by preprocessing the spectra with probabilistic quotient normalization and glog transformation. Classification of the 106 preprocessed spectra by principal component analysis and partial least squares with discriminant analysis (PLS-DA) appears to be impaired by variances unrelated to eosinophilic asthma. By filtering out confounding variances, orthogonal signal correction (OSC) PLS-DA greatly improved the separation of the healthy and early asthmatic states, attaining 94% specificity and 94% sensitivity in predictions. OSC enhancement of multi-level PLS-DA boosted the specificity of the prediction to 100%. OSC-PLS-DA of the normalized spectra suggest the most promising biomarkers of allergic asthma in cats to include increased acetone, metabolite(s) with overlapped NMR peaks near 5.8 ppm, and a hydroxyphenyl-containing metabolite, as well as decreased phthalate. Acetone is elevated in the EBC of 74% of the cats with early asthma. The noninvasive detection of early experimental asthma, biomarkers in EBC, and metabolic perturbation invite further investigation of the diagnostic potential in humans.
authors.affiliation: Department of Biochemistry, 117 Schweitzer Hall, University of Missouri, Columbia, MO, 65211, United States of America.
authors.forename: Yan G
authors.initials: YG
authors.lastname: Fulcher
authors.affiliation: Department of Biochemistry, 117 Schweitzer Hall, University of Missouri, Columbia, MO, 65211, United States of America.
authors.forename: Martial
authors.initials: M
authors.lastname: Fotso
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, United States of America.
authors.forename: Chee-Hoon
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, United States of America.
authors.forename: Hans
authors.initials: H
authors.lastname: Rindt
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, United States of America.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Reinero
authors.affiliation: Department of Biochemistry, 117 Schweitzer Hall, University of Missouri, Columbia, MO, 65211, United States of America.
authors.forename: Steven R
authors.identifier: http://orcid.org/0000-0003-2838-4598
authors.initials: SR
authors.lastname: Van Doren
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000175:diagnosis* / Q000209:etiology / Q000662:veterinary; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D001826:Body Fluids / Q000737:chemistry; D001944:Breath Tests; D002415:Cats; D004802:Eosinophilia / Q000378:metabolism / Q000473:pathology; D045853:Exhalation; D005163:Factor Analysis, Statistical; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy; D015999:Multivariate Analysis; D037342:Pertussis Toxin / Q000276:immunology; D025341:Principal Component Analysis
chemical_list: D000485:Allergens; D015415:Biomarkers; D037342:Pertussis Toxin