{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST000406","ANALYSIS_ID":"AN000646","VERSION":"1","CREATED_ON":"May 31, 2016, 4:27 pm"},

"PROJECT":{"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"},

"STUDY":{"STUDY_TITLE":"Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats using Multivariate Statistics of NMR Spectra of Exhaled Breath Condensate","STUDY_TYPE":"Statistical Analysis of NMR spectra of EBC samples","STUDY_SUMMARY":"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.","INSTITUTE":"University of Missouri-Columbia","DEPARTMENT":"Department of Biochemistry, Department of Veterinary Medicine and Surgery","LABORATORY":"Van Doren Lab & Reinero 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","NUM_GROUPS":"2","TOTAL_SUBJECTS":"53"},

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"COLLECTION":{"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_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)"},

"SAMPLEPREP":{"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."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"-","INSTRUMENT_NAME":"-","COLUMN_NAME":"-"},

"ANALYSIS":{"ANALYSIS_TYPE":"NMR","LABORATORY_NAME":"Van Doren Lab","SOFTWARE_VERSION":"Topspin 3.1"},

"NM":{"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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}