Summary of Study ST002251

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 PR001439. The data can be accessed directly via it's Project DOI: 10.21228/M8QD9Z This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002251
Study TitleUntargeted metabolomics on plasma from children with asthma, comparing exacerbation-prone to non-exacerbation-prone
Study TypeUntargeted MS
Study SummaryBackground: Some children with asthma remain poorly controlled and have recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and limited understanding of potential underlying mechanisms. Objective: We sought to quantify small molecules in the plasma of children with exacerbation- prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation- prone asthma. Methods: Plasma metabolites were extracted from four pediatric asthma cohorts (n=215 total, n=41 with exacerbation-prone asthma) and detected using a ZIC-HILIC column coupled to a Q Exactive HF mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects on high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. Metaboanalyst was used to identify pathways of interest. Concentrations were calculated by reference standardization to NIST SRM 1950. Results: We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted. Conclusions: Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.
Institute
Emory University
DepartmentPediatrics
LaboratoryJoshua Chandler, PhD
Last NameChandler
First NameJoshua
Address2015 Upper Gate Drive NE, Atlanta, GA 30322
Emailjoshua.chandler@emory.edu
Phone404-727-3536
Submit Date2022-07-25
Num Groups2
Total Subjects215
Num Males135
Num Females80
PublicationsJACI-D-22-00220
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-01-02
Release Version1
Joshua Chandler Joshua Chandler
https://dx.doi.org/10.21228/M8QD9Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Subject:

Subject ID:SU002337
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:6-17 years
Weight Or Weight Range:Non-exacerbation-prone IQR: 30-68 kg; Exacerbation-prone IQR: 42-63 kg
Height Or Height Range:Non-exacerbation-prone IQR: 131-165 cm; Exacerbation-prone IQR: 140-163 cm
Gender:Male and female
Human Race:18 white, 189 Black, 7 more than one race, 1 Asian
Human Ethnicity:2 Hispanic, 113 Not Hispanic
Human Medications:92 on high-dose inhaled corticosteroids; 94 on long-acting beta adrenergic receptor agonists; 111 on Montelukast
Human Smoking Status:24 exposed to tobacco smoke
Human Inclusion Criteria:1) current or historical evidence of >=12% reversibility in forced expiratory volume in one second (FEV1) relative to baseline after bronchodilator administration; 2) airway hyperresponsiveness to methacholine, with a provocative concentration of methacholine causing a 20% drop in FEV1
Human Exclusion Criteria:1) premature birth before 35 weeks of gestation; 2) other chronic airway disorders that could mimic asthma.
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