Summary of study ST000954

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 PR000655. The data can be accessed directly via it's Project DOI: 10.21228/M80X1K 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 IDST000954
Study TitleExplore Metabolites and Pathways Associated Increased Airway Hyperresponsiveness in Asthma
Study TypeOpen-label, prospective cohort study
Study SummaryAsthma is a heterogeneous disease largely defined by chronic airway inflammation with similar symptomatology in patients that includes wheezing, shortness of breath, chest tightness and cough. However, underlying these common symptoms are varying endotypes with distinct pathophysiological processes. Metabolomic studies in patients with asthma are emerging and suggest that metabolomics can characterize distinct asthma phenotypes. In a completed study, we identified a population of patients with asthma who have increased airway hyperresponsiveness (airway hyperresponsiveness is a marker for asthma disease severity) who are characterized by race (African American) and genotype (ADRB2 Arg16/Arg) compared with patients who have less airway hyperresponsiveness (African Americans and whites with differing ADRB2 genotypes). This group may represent a distinct endotype of asthma with unique metabolomic and lipidomic characteristics. The aims of this project are to (1) use metabolomic and lipidomic analysis to identify metabolites present in plasma in this population of patients with asthma who have increased airway hyperresponsiveness (African Americans who carry the ADRB2 Arg16/Arg genotype) and patients with asthma who have less airway hyperresponsiveness (African Americans and whites with differing ADRB2 genotypes); and (2) identify pathways that will improve the understanding of increased airway hyperresponsiveness in this population. We hypothesize that there will be unique metabolic pathways in the population with increased airway hyperresponsiveness that will be distinct from pathways in patients with lower airway hyperresponsiveness. In this project will use data and samples that were previously collected as part of the NIH funded project “Pharmacogenetics of β2-Agonists in Asthma” (Blake, PI K23 HL081245). Blood was collected in 55 African Americans and whites after receiving 2-weeks treatment with inhaled fluticasone. Samples were stored on ice until processed and plasma frozen at -80°C. If our findings indicate distinct metabolic pathways are present using global metabolomic and lipodomic analysis, we will seek to replicate our findings using samples and data from phenotypically well characterized participants who participated in trials conducted through the American Lung Association Airways Clinical Research Centers network, of which Nemours has been a highly productive site since 1999. Future controlled trials would be conducted to evaluate treatments based upon molecular pathways identified through metabolomic and lipidomic analysis.
Institute
University of Florida
DepartmentSECIM
Last NameBeecher
First NameChris
AddressPO Box 100219 Gainesville FL 32610-0219 , Southeast Center for Integrated Metabolomics
Emailchris@iroatech.com
Phone(352) 294-4385
Submit Date2018-04-13
Num Groups4
Total Subjects55
Study CommentsNubmer of groups : 4 (race x diplotype); SECIM pilot and feasibility, NIH U24 DK097209
Raw Data AvailableYes
Raw Data File Type(s).raw, .RST
Analysis Type DetailLC-MS
Release Date2021-01-19
Release Version1
Chris Beecher Chris Beecher
https://dx.doi.org/10.21228/M80X1K
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000655
Project DOI:doi: 10.21228/M80X1K
Project Title:Explore Metabolites and Pathways Associated Increased Airway Hyperresponsiveness in Asthma
Project Type:Open-label, prospective corhort study
Project Summary:Asthma is a heterogeneous disease largely defined by chronic airway inflammation with similar symptomatology in patients that includes wheezing, shortness of breath, chest tightness and cough. However, underlying these common symptoms are varying endotypes with distinct pathophysiological processes. Metabolomic studies in patients with asthma are emerging and suggest that metabolomics can characterize distinct asthma phenotypes. In a completed study, we identified a population of patients with asthma who have increased airway hyperresponsiveness (airway hyperresponsiveness is a marker for asthma disease severity) who are characterized by race (African American) and genotype (ADRB2 Arg16/Arg) compared with patients who have less airway hyperresponsiveness (African Americans and whites with differing ADRB2 genotypes). This group may represent a distinct endotype of asthma with unique metabolomic and lipidomic characteristics. The aims of this project are to (1) use metabolomic and lipidomic analysis to identify metabolites present in plasma in this population of patients with asthma who have increased airway hyperresponsiveness (African Americans who carry the ADRB2 Arg16/Arg genotype) and patients with asthma who have less airway hyperresponsiveness (African Americans and whites with differing ADRB2 genotypes); and (2) identify pathways that will improve the understanding of increased airway hyperresponsiveness in this population. We hypothesize that there will be unique metabolic pathways in the population with increased airway hyperresponsiveness that will be distinct from pathways in patients with lower airway hyperresponsiveness. In this project will use data and samples that were previously collected as part of the NIH funded project “Pharmacogenetics of β2-Agonists in Asthma” (Blake, PI K23 HL081245). Blood was collected in 55 African Americans and whites after receiving 2-weeks treatment with inhaled fluticasone. Samples were stored on ice until processed and plasma frozen at -80°C. If our findings indicate distinct metabolic pathways are present using global metabolomic and lipodomic analysis, we will seek to replicate our findings using samples and data from phenotypically well characterized participants who participated in trials conducted through the American Lung Association Airways Clinical Research Centers network, of which Nemours has been a highly productive site since 1999. Future controlled trials would be conducted to evaluate treatments based upon molecular pathways identified through metabolomic and lipidomic analysis.
Institute:Nemours Children's Specialty Care
Department:Center for Pharmacogenomics and Translational Research
Laboratory:Pulmonology laboratory
Last Name:Blake
First Name:Kathryn
Address:807 Childrens's Way Jacksonville, Florida 32207
Email:Kathryn.Blake@nemours.org
Phone:(904) 697-3806
Funding Source:SECIM pilot and feasibility, NIH U24 DK097209

Subject:

Subject ID:SU000993
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:11-67 yo
Weight Or Weight Range:32-194 kg
Height Or Height Range:141-388 cm
Gender:Male and female
Human Race:47% white, 53% african american
Human Ethnicity:95% not Hispanic
Human Trial Type:Open-label, prospective cohort study
Human Lifestyle Factors:NA
Human Medications:fluticasone (was not the intervention in this project, all participants received this drug for 2 weeks prior to sample collection)
Human Prescription Otc:prescription
Human Smoking Status:9% current, 20% former

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id race diplotype ethnicity ever_smoked daily_dose
SA057148137791931 1 1 1 2
SA057149137654561 1 1 1 2
SA057150137657051 1 2 1 2
SA057151137792091 1 2 1 2
SA057152137792341 1 2 2 2
SA057153137656051 1 2 2 2
SA057154137656151 1 2 2 2
SA057155137657451 1 2 2 2
SA057156137654401 1 2 2 3
SA057158137658151 2 1 2 2
SA057159137652811 2 2 1 2
SA057160137656681 2 2 1 2
SA057161137791841 2 2 1 3
SA057162137654661 2 2 1 4
SA057163137659021 2 2 1 4
SA057164137654141 2 2 2 2
SA057165137656591 2 2 2 2
SA057166137656781 2 2 2 2
SA057167137652651 2 2 2 2
SA057168137655111 2 2 2 2
SA057169137655291 2 2 2 2
SA057170137655201 2 2 2 2
SA057171137652891 2 2 2 3
SA057172137653681 2 2 2 3
SA057173137653161 2 2 2 3
SA057157137659251 2 - 2 3
SA057174137652072 1 2 1 2
SA057175137653952 1 2 1 4
SA057176137792702 1 2 2 2
SA057177137749732 1 2 2 2
SA057178137651622 1 2 2 2
SA057179137651182 1 2 2 2
SA057180137655792 1 2 2 2
SA057181137655472 1 2 2 2
SA057182137653252 1 2 2 3
SA057183137651812 1 2 2 3
SA057184137657142 1 2 2 3
SA057185137657732 2 2 1 2
SA057186137652272 2 2 1 2
SA057187137653772 2 2 1 2
SA057188137656352 2 2 1 3
SA057189137658932 2 2 1 3
SA057190137652742 2 2 2 1
SA057191137651072 2 2 2 2
SA057192137658072 2 2 2 2
SA057193137652472 2 2 2 2
SA057194137655612 2 2 2 2
SA057195137651242 2 2 2 2
SA057196137650792 2 2 2 2
SA057197137656452 2 2 2 2
SA057198137792602 2 2 2 2
SA057199137653542 2 2 2 2
SA057200137792012 2 2 2 4
SA057201137654322 2 2 2 4
SA057202137658632 2 2 2 4
Showing results 1 to 55 of 55

Collection:

Collection ID:CO000987
Collection Summary:Whole blood is collected in an EDTA vacutainer at Visit 2 after two weeks of fluticasone therapy. 1 ml aliquots at 80°C
Sample Type:Blood (whole)
Collection Method:Whole blood is collected in an EDTA vacutainer (Visit 2; after two weeks of fluticasone therapy) and is stored on ice. Within 2 hr of collection, the sample is centrifuged at 2000 rpm in a 4°C refrigerated benchtop centrifuge and the plasma is recovered and stored in aliquots at -80°C.
Collection Location:Nemours Children's Clinic Phlebotomy Laboratory.
Collection Frequency:One time
Storage Conditions:Described in summary
Collection Vials:10 ml potassium EDTA vacutainer
Storage Vials:1.4 ml Micronic unthreaded 2D data matrix tubes with TPE push caps
Collection Tube Temp:4°C
Additives:potassium EDTA

Treatment:

Treatment ID:TR001007
Treatment Summary:All subjects will be treated with at least 110 mg of fluticasone propionate once or twice daily (Flovent® MDI) during the 2-week treatment period.
Treatment Protocol ID:NCT00708227
Treatment Protocol Comments:Note: Fluticasone was not the intervention in this project; all study participants received this drug for 2 weeks prior to blood collection for the sample being used for the metabolomic analysis. However, participants did receive different doses of fluticasone in order to have them remain on the same dose that they were on prior to study entry. This was to ensure that their asthma remained stable at the end of the 2 week treatment with fluticasone.
Treatment Compound:fluticasone
Treatment Route:nebulizer; inhaled
Treatment Dose:110 mcg, 220 mcg, 440 mcg, 880 mcg
Treatment Doseduration:daily

Sample Preparation:

Sampleprep ID:SP001000
Sampleprep Summary:none
Sampleprep Protocol Filename:GMetabolomics_LCMS_Protocol_092117.pdf
Appendix_A_Internal_Standard_Prep_GLCMS.pdf

Combined analysis:

Analysis ID AN001564 AN001565
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column ACE Excel 2 C18-PFP (100 x 2.1mm, 2um) ACE Excel 2 C18-PFP (100 x 2.1mm, 2um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Peak Height Peak height

Chromatography:

Chromatography ID:CH001097
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:ACE Excel 2 C18-PFP (100 x 2.1mm, 2um)
Flow Rate:350 ul/min
Solvent A:0.1% Formic Acid in Water
Solvent B:Acetonitrile
Chromatography Type:Reversed phase

MS:

MS ID:MS001442
Analysis ID:AN001564
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
Ion Mode:POSITIVE
  
MS ID:MS001443
Analysis ID:AN001565
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
Ion Mode:NEGATIVE
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