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.
Study ID | ST000954 |
Study Title | Explore Metabolites and Pathways Associated Increased Airway Hyperresponsiveness in Asthma |
Study Type | Open-label, prospective cohort study |
Study 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 | University of Florida |
Department | SECIM |
Last Name | Beecher |
First Name | Chris |
Address | PO Box 100219 Gainesville FL 32610-0219 , Southeast Center for Integrated Metabolomics |
chris@iroatech.com | |
Phone | (352) 294-4385 |
Submit Date | 2018-04-13 |
Num Groups | 4 |
Total Subjects | 55 |
Study Comments | Nubmer of groups : 4 (race x diplotype); SECIM pilot and feasibility, NIH U24 DK097209 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2021-01-19 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
Species Group: | Mammals |
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 |
---|---|---|---|---|---|---|
SA057148 | 13779193 | 1 | 1 | 1 | 1 | 2 |
SA057149 | 13765456 | 1 | 1 | 1 | 1 | 2 |
SA057150 | 13765705 | 1 | 1 | 2 | 1 | 2 |
SA057151 | 13779209 | 1 | 1 | 2 | 1 | 2 |
SA057152 | 13779234 | 1 | 1 | 2 | 2 | 2 |
SA057153 | 13765605 | 1 | 1 | 2 | 2 | 2 |
SA057154 | 13765615 | 1 | 1 | 2 | 2 | 2 |
SA057155 | 13765745 | 1 | 1 | 2 | 2 | 2 |
SA057156 | 13765440 | 1 | 1 | 2 | 2 | 3 |
SA057158 | 13765815 | 1 | 2 | 1 | 2 | 2 |
SA057159 | 13765281 | 1 | 2 | 2 | 1 | 2 |
SA057160 | 13765668 | 1 | 2 | 2 | 1 | 2 |
SA057161 | 13779184 | 1 | 2 | 2 | 1 | 3 |
SA057162 | 13765466 | 1 | 2 | 2 | 1 | 4 |
SA057163 | 13765902 | 1 | 2 | 2 | 1 | 4 |
SA057164 | 13765414 | 1 | 2 | 2 | 2 | 2 |
SA057165 | 13765659 | 1 | 2 | 2 | 2 | 2 |
SA057166 | 13765678 | 1 | 2 | 2 | 2 | 2 |
SA057167 | 13765265 | 1 | 2 | 2 | 2 | 2 |
SA057168 | 13765511 | 1 | 2 | 2 | 2 | 2 |
SA057169 | 13765529 | 1 | 2 | 2 | 2 | 2 |
SA057170 | 13765520 | 1 | 2 | 2 | 2 | 2 |
SA057171 | 13765289 | 1 | 2 | 2 | 2 | 3 |
SA057172 | 13765368 | 1 | 2 | 2 | 2 | 3 |
SA057173 | 13765316 | 1 | 2 | 2 | 2 | 3 |
SA057157 | 13765925 | 1 | 2 | - | 2 | 3 |
SA057174 | 13765207 | 2 | 1 | 2 | 1 | 2 |
SA057175 | 13765395 | 2 | 1 | 2 | 1 | 4 |
SA057176 | 13779270 | 2 | 1 | 2 | 2 | 2 |
SA057177 | 13774973 | 2 | 1 | 2 | 2 | 2 |
SA057178 | 13765162 | 2 | 1 | 2 | 2 | 2 |
SA057179 | 13765118 | 2 | 1 | 2 | 2 | 2 |
SA057180 | 13765579 | 2 | 1 | 2 | 2 | 2 |
SA057181 | 13765547 | 2 | 1 | 2 | 2 | 2 |
SA057182 | 13765325 | 2 | 1 | 2 | 2 | 3 |
SA057183 | 13765181 | 2 | 1 | 2 | 2 | 3 |
SA057184 | 13765714 | 2 | 1 | 2 | 2 | 3 |
SA057185 | 13765773 | 2 | 2 | 2 | 1 | 2 |
SA057186 | 13765227 | 2 | 2 | 2 | 1 | 2 |
SA057187 | 13765377 | 2 | 2 | 2 | 1 | 2 |
SA057188 | 13765635 | 2 | 2 | 2 | 1 | 3 |
SA057189 | 13765893 | 2 | 2 | 2 | 1 | 3 |
SA057190 | 13765274 | 2 | 2 | 2 | 2 | 1 |
SA057191 | 13765107 | 2 | 2 | 2 | 2 | 2 |
SA057192 | 13765807 | 2 | 2 | 2 | 2 | 2 |
SA057193 | 13765247 | 2 | 2 | 2 | 2 | 2 |
SA057194 | 13765561 | 2 | 2 | 2 | 2 | 2 |
SA057195 | 13765124 | 2 | 2 | 2 | 2 | 2 |
SA057196 | 13765079 | 2 | 2 | 2 | 2 | 2 |
SA057197 | 13765645 | 2 | 2 | 2 | 2 | 2 |
SA057198 | 13779260 | 2 | 2 | 2 | 2 | 2 |
SA057199 | 13765354 | 2 | 2 | 2 | 2 | 2 |
SA057200 | 13779201 | 2 | 2 | 2 | 2 | 4 |
SA057201 | 13765432 | 2 | 2 | 2 | 2 | 4 |
SA057202 | 13765863 | 2 | 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: | 100% water; 0.1% formic acid |
Solvent B: | 100% 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 |