Summary of Study ST000406

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000318. The data can be accessed directly via it's Project DOI: 10.21228/M8C59F This work is supported by NIH grant, U2C- DK119886.

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Study IDST000406
Study TitleNoninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats using Multivariate Statistics of NMR Spectra of Exhaled Breath Condensate
Study TypeStatistical Analysis of NMR spectra of EBC samples
Study SummaryAsthma 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.
Institute
University of Missouri-Columbia
DepartmentDepartment of Biochemistry, Department of Veterinary Medicine and Surgery
LaboratoryVan Doren Lab & Reinero Lab
Last NameVan Doren
First NameSteven
Address117 Schweitzer Hall, Biochemistry Department, University of Missouri-Columbia, Columbia, MO 65211
EmailVanDorenS@missouri.edu
Phone5738846405
Submit Date2016-04-13
Num Groups2
Total Subjects53
Analysis Type DetailNMR
Release Date2016-06-18
Release Version1
Steven Van Doren Steven Van Doren
https://dx.doi.org/10.21228/M8C59F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000318
Project DOI:doi: 10.21228/M8C59F
Project Title:Biomarker Identification of EBC samples
Project Type:Data processing and multivariate statistical analysis of NMR spectra
Project Summary:Multivariate Statistics of NMR Spectra of Exhaled Breath Condensate of Early Allergic Asthma in Cats
Institute:University of Missouri-Columbia
Department:Biochemistry Department, Department of Veterinary Medicine and Surgery
Laboratory:Van Doren Lab
Last Name:Van Doren
First Name:Steven
Address:117 Schweitzer Hall, Biochemistry Department, University of Missouri-Columbia, Columbia, MO 65211
Email:VanDorenS@missouri.edu
Phone:5738846405
Funding Source:Morris Animal Foundation grants D10FE-803A and D14FE-507 and University of Missouri Research Council grant URC-13-040

Subject:

Subject ID:SU000427
Subject Type:Animal
Subject Species:Felis catus
Taxonomy ID:9685
Species Group:Mammals

Factors:

Subject type: Animal; Subject species: Felis catus (Factor headings shown in green)

mb_sample_id local_sample_id Type
SA019467Lancer-AAsthamtic
SA019468Kitkat-AAsthamtic
SA019469Marti-AAsthamtic
SA019470Maxima-AAsthamtic
SA019471Mcfly-AAsthamtic
SA019472Fox-AAsthamtic
SA019473Expo-AAsthamtic
SA019474Dino-AAsthamtic
SA019475Diablo-AAsthamtic
SA019476Eagle-AAsthamtic
SA019477Echo-AAsthamtic
SA019478Metro-AAsthamtic
SA019479Focus-AAsthamtic
SA019480Morgen-AAsthamtic
SA019481Sully-AAsthamtic
SA019482Snickers-AAsthamtic
SA019483Tacoma-AAsthamtic
SA019484Titan-AAsthamtic
SA019485Tux-AAsthamtic
SA019486Skittles-AAsthamtic
SA019487Sedona-AAsthamtic
SA019488Paris-AAsthamtic
SA019489Randall-AAsthamtic
SA019490Rio-AAsthamtic
SA019491Sable-AAsthamtic
SA019492Dexter-AAsthamtic
SA019493Deb-AAsthamtic
SA019494Clyde-AAsthamtic
SA019495Fry-AAsthamtic
SA019496Cleopatra-AAsthamtic
SA019497Bonnie-AAsthamtic
SA019498Anthony-AAsthamtic
SA019499Hansolo-AAsthamtic
SA019500Jill-AAsthamtic
SA019501Romeo-AAsthamtic
SA019502Mickey-AAsthamtic
SA019503Katniss-AAsthamtic
SA019504Juliet-AAsthamtic
SA019505Accent-AAsthamtic
SA019506Aerio-AAsthamtic
SA019507Camry-AAsthamtic
SA019508Butterfinger-AAsthamtic
SA019509Capri-AAsthamtic
SA019510Civic-AAsthamtic
SA019511Cudberry-AAsthamtic
SA019512Boxer-AAsthamtic
SA019513Boo-AAsthamtic
SA019514Altima-AAsthamtic
SA019515Amigo-AAsthamtic
SA019516Aspen-AAsthamtic
SA019517Biff-AAsthamtic
SA019518Twix-AAsthamtic
SA019519Vixen-AAsthamtic
SA019520Marti-HHealthy
SA019521Lancer-HHealthy
SA019522Maxima-HHealthy
SA019523Mcfly-HHealthy
SA019524Metro-HHealthy
SA019525Kitcat-HHealthy
SA019526Fox-HHealthy
SA019527Eagle-HHealthy
SA019528Dino-HHealthy
SA019529Echo-HHealthy
SA019530Expo-HHealthy
SA019531Focux-HHealthy
SA019532Morgan-HHealthy
SA019533Paris-HHealthy
SA019534Tacoma-HHealthy
SA019535Sully-HHealthy
SA019536Titan-HHealthy
SA019537Tux-HHealthy
SA019538Twix-HHealthy
SA019539Snickers-HHealthy
SA019540Skittles-HHealthy
SA019541Randall-HHealthy
SA019542Rio-HHealthy
SA019543Sable-HHealthy
SA019544Sedona-HHealthy
SA019545Diablo-HHealthy
SA019546Dexter-HHealthy
SA019547Cleopatra-HHealthy
SA019548Clyde-HHealthy
SA019549Bonnie-HHealthy
SA019550Anthony-HHealthy
SA019551Accent-HHealthy
SA019552Fry-HHealthy
SA019553Hansolo-HHealthy
SA019554Mickey-HHealthy
SA019555Romeo-HHealthy
SA019556Katniss-HHealthy
SA019557Juliet-HHealthy
SA019558Jill-HHealthy
SA019559Aerio-HHealthy
SA019560Altima-HHealthy
SA019561Capri-HHealthy
SA019562Camry-HHealthy
SA019563Civic-HHealthy
SA019564Cudberry-HHealthy
SA019565Deb-HHealthy
SA019566Butterfinger-HHealthy
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Collection:

Collection ID:CO000421
Collection Summary:1D 1H NMR spectra were collected using W5-WATERGATE water suppression supplemented by presaturation of the water resonance at minimal power.
Collection Protocol Filename:protocol.pdf
Sample Type:EBC (Exhaled breath condensate) and BALF (bronchoalveolar lavage fluid)

Treatment:

Treatment ID:TR000441
Treatment Summary:The care of the 53 cats in the study followed the NIH Guide for the Care and Use of Laboratory Animals. The University of Missouri Animal Care and Use Committee approved the study design (ACUC protocols #6912 and 7891). In order to induce allergic asthma, on day 0, cats <1 year of age were administered 12 µg of Bermuda grass allergen (BGA) in 10 mg of alum and 100 ng Bordetella pertussis toxin (both subcutaneously). On day 14, intranasal BGA (75 µg of BGA in 200 µL of phosphate-buffered saline) was given; and on day 21, 12 µg of BGA in 10 mg alum was injected subcutaneously. On day 28, the formation of wheals on an intradermal test confirmed sensitization to BGA. For the next 2 weeks, intensive aerosol challenges were administered to all cats with BGA (500 µg of BGA in 4 mL of phosphate-buffered saline) over 10 min in awake and unrestrained cats in a sealed plastic chamber. A nebulizer (Acorn nebulizer, model 646, Devilbis Health Care, Somerset, PA) delivered an aerosol of the BGA solution at an air flow rate of 9.3 l /min. An air compressor (Easy Air 15, Precision Medical, Inc., Northampton, PA) supplied the compressed air flow at a pressure of 2.93 kg/cm2. At week 6, samples were collected 24 h after challenge with BGA aerosol (see below).
Treatment Compound:Bermuda grass allergen (BGA)

Sample Preparation:

Sampleprep ID:SP000434
Sampleprep Summary:In all cats, Exhaled breath condensate (EBC)and Bronchoalveolar lavage fluid (BALF) and were collected before (day 0) and after (week 6) sensitization to BGA. The EBC was collected non-invasively just prior to BALF collection by placing cats in a 25 L plexiglass chamber for 20-30 min according to a previously published design with modifications [29]. BALF was collected in a blind fashion under anesthesia using an 8 French red rubber catheter passed through an endotracheal tube according to a previously described protocol [30]. The percentage of eosinophils in each BALF modified Wright’s stained cytospin was determined by counting 200 nucleated cells, with an asthmatic phenotype defined as >17% eosinophils.The EBC and the supernatant of centrifuged BALF remaining were promptly stored at -80 °C until further analysis. NMR spectra of the EBC were measured for use in training and evaluating statistical approaches and biomarkers.

Analysis:

Analysis ID:AN000646
Laboratory Name:Van Doren Lab
Analysis Type:NMR
Software Version:Topspin 3.1
Num Factors:2

NMR:

NMR ID:NM000068
Analysis ID:AN000646
Instrument Name:Bruker Avance III
Instrument Type:FT-NMR
NMR Experiment Type:1D 1H
Spectrometer Frequency:800 MHz
Binned Increment:0.02
Binned Data Excluded Range:4.5-5.38
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