Summary of Study ST002948

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 PR001833. The data can be accessed directly via it's Project DOI: 10.21228/M8SB0G 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 IDST002948
Study TitleMulti-omics Approach Reveals a Specific Profile in Severe Asthmatic Patients Treated with Mepolizumab or Omalizumab
Study SummaryThe prevalence and severity of asthma continue to increase, and patients with uncontrolled severe asthma may require additional biological treatment. Given the pathophysiological heterogeneity underlying severe asthma, there is a lack of reliable biomarkers to monitor treatment response. In this context, this study aimed to identify potential biomarkers for monitoring the response to either Mepolizumab or Omalizumab in severe asthmatic patients using metabolomics and proteomics. Severe asthmatic patients who were prescribed either Mepolizumab (n=36) or Omalizumab (n=20) were followed during treatment, and serum samples were collected before treatment (T0), and both at 6 (T1) and 18 months (T2) after starting biological treatment. Treatment monitoring was performed by the analysis of a set of inflammatory metabolites and proteins using targeted metabolomic and proteomic approaches, along with the study of clinical variables such as the number of blood eosinophils, hospitalizations, and severe exacerbations. Mepolizumab and Omalizumab induced changes in the metabolomic and proteomic profiles of severe asthmatic patients. For both treatments, the greatest differences in metabolites were seen at T1 and maintained up to T2, whereas protein changes were seen throughout the treatment. Notable changes associated with anti-inflammatory effects included a decrease in several fatty acids, sphingosine-1-phosphate (S1P), L-arginine, and IL-10RA. Interestingly, S1P was the main feature that correlated significantly with eosinophilia in both treatments. These results unveil underlying molecular mechanisms that occur during Mepolizumab and Omalizumab treatments and provide potential biomarkers for monitoring treatment response in severe asthmatic patients.
Institute
CEMBIO
Last NameContreras
First NameNuria
AddressUrb. Montepríncipe s/n, Ctra. Boadilla del Monte km 5.3, Madrid 28668, Spain
Emailnuria.contrerasgomez1@ceu.es
Phone+3491372470014750
Submit Date2023-10-27
Num Groups2
Total Subjects54
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-01-20
Release Version1
Nuria Contreras Nuria Contreras
https://dx.doi.org/10.21228/M8SB0G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001833
Project DOI:doi: 10.21228/M8SB0G
Project Title:Targeted metabolomics in severe asthmatic patients treated with biologics.
Project Type:Targeted MS analysis
Project Summary:Severe asthmatic patients prescribed either Mepolizumab or Omalizumab were followed during treatment, and serum samples were collected before treatment (T0), and both at 6 (T1) and 18 months (T2) after starting biological treatment. Treatment monitoring was performed by the analysis of a set of inflammatory metabolites using targeted metabolomics.
Institute:CEMBIO
Last Name:Contreras
First Name:Nuria
Address:Urb. Montepríncipe s/n, Ctra. Boadilla del Monte km 5.3, Madrid 28668, Spain
Email:nuria.contrerasgomez1@ceu.es
Phone:+3491372470014750

Subject:

Subject ID:SU003061
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:≥ 18 years
Gender:Male and female
Human Medications:Mepolizumab or Omalizumab
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Time Treatment
SA320904Me-T0-19T0 Mepolizumab
SA320905Me-T0-18T0 Mepolizumab
SA320906Me-T0-17T0 Mepolizumab
SA320907Me-T0-20T0 Mepolizumab
SA320908Me-T0-21T0 Mepolizumab
SA320909Me-T0-23T0 Mepolizumab
SA320910Me-T0-22T0 Mepolizumab
SA320911Me-T0-16T0 Mepolizumab
SA320912Me-T0-10T0 Mepolizumab
SA320913Me-T0-05T0 Mepolizumab
SA320914Me-T0-04T0 Mepolizumab
SA320915Me-T0-03T0 Mepolizumab
SA320916Me-T0-06T0 Mepolizumab
SA320917Me-T0-07T0 Mepolizumab
SA320918Me-T0-25T0 Mepolizumab
SA320919Me-T0-08T0 Mepolizumab
SA320920Me-T0-11T0 Mepolizumab
SA320921Me-T0-27T0 Mepolizumab
SA320922Me-T0-40T0 Mepolizumab
SA320923Me-T0-39T0 Mepolizumab
SA320924Me-T0-38T0 Mepolizumab
SA320925Me-T0-41T0 Mepolizumab
SA320926Me-T0-42T0 Mepolizumab
SA320927Me-T0-45T0 Mepolizumab
SA320928Me-T0-43T0 Mepolizumab
SA320929Me-T0-37T0 Mepolizumab
SA320930Me-T0-35T0 Mepolizumab
SA320931Me-T0-30T0 Mepolizumab
SA320932Me-T0-29T0 Mepolizumab
SA320933Me-T0-01T0 Mepolizumab
SA320934Me-T0-31T0 Mepolizumab
SA320935Me-T0-32T0 Mepolizumab
SA320936Me-T0-34T0 Mepolizumab
SA320937Me-T0-33T0 Mepolizumab
SA320938Me-T0-26T0 Mepolizumab
SA320939Me-T0-12T0 Mepolizumab
SA320940O-T0-04T0 Omalizumab
SA320941O-T0-08T0 Omalizumab
SA320942O-T0-23T0 Omalizumab
SA320943O-T0-03T0 Omalizumab
SA320944O-T0-12T0 Omalizumab
SA320945O-T0-14T0 Omalizumab
SA320946O-T0-13T0 Omalizumab
SA320947O-T0-05T0 Omalizumab
SA320948O-T0-06T0 Omalizumab
SA320949O-T0-01T0 Omalizumab
SA320950O-T0-22T0 Omalizumab
SA320951O-T0-16T0 Omalizumab
SA320952O-T0-18T0 Omalizumab
SA320953O-T0-09T0 Omalizumab
SA320954O-T0-17T0 Omalizumab
SA320955O-T0-20T0 Omalizumab
SA320956O-T0-02T0 Omalizumab
SA320957O-T0-10T0 Omalizumab
SA320958Me-T1-20T1 Mepolizumab
SA320959Me-T1-11T1 Mepolizumab
SA320960Me-T1-29T1 Mepolizumab
SA320961Me-T1-10T1 Mepolizumab
SA320962Me-T1-21T1 Mepolizumab
SA320963Me-T1-31T1 Mepolizumab
SA320964Me-T1-30T1 Mepolizumab
SA320965Me-T1-19T1 Mepolizumab
SA320966Me-T1-18T1 Mepolizumab
SA320967Me-T1-26T1 Mepolizumab
SA320968Me-T1-25T1 Mepolizumab
SA320969Me-T1-17T1 Mepolizumab
SA320970Me-T1-16T1 Mepolizumab
SA320971Me-T1-22T1 Mepolizumab
SA320972Me-T1-12T1 Mepolizumab
SA320973Me-T1-27T1 Mepolizumab
SA320974Me-T1-23T1 Mepolizumab
SA320975Me-T1-08T1 Mepolizumab
SA320976Me-T1-06T1 Mepolizumab
SA320977Me-T1-39T1 Mepolizumab
SA320978Me-T1-01T1 Mepolizumab
SA320979Me-T1-38T1 Mepolizumab
SA320980Me-T1-03T1 Mepolizumab
SA320981Me-T1-40T1 Mepolizumab
SA320982Me-T1-41T1 Mepolizumab
SA320983Me-T1-45T1 Mepolizumab
SA320984Me-T1-43T1 Mepolizumab
SA320985Me-T1-42T1 Mepolizumab
SA320986Me-T1-35T1 Mepolizumab
SA320987Me-T1-37T1 Mepolizumab
SA320988Me-T1-34T1 Mepolizumab
SA320989Me-T1-33T1 Mepolizumab
SA320990Me-T1-04T1 Mepolizumab
SA320991Me-T1-32T1 Mepolizumab
SA320992Me-T1-07T1 Mepolizumab
SA320993Me-T1-05T1 Mepolizumab
SA320994O-T1-01T1 Omalizumab
SA320995O-T1-16T1 Omalizumab
SA320996O-T1-02T1 Omalizumab
SA320997O-T1-06T1 Omalizumab
SA320998O-T1-05T1 Omalizumab
SA320999O-T1-04T1 Omalizumab
SA321000O-T1-03T1 Omalizumab
SA321001O-T1-08T1 Omalizumab
SA321002O-T1-09T1 Omalizumab
SA321003O-T1-22T1 Omalizumab
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Collection:

Collection ID:CO003054
Collection Summary:Whole blood from the three hospital-scheduled visits was incubated with a clotting agent in Vacutainer SST II tubes. Samples were placed at room temperature for 30 min and then centrifuged at 2000 x g for 10 min for serum recovery. Serum samples were stored at -80ºC until further metabolomic analyses.
Sample Type:Blood (serum)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003070
Treatment Summary:Patients were prescribed add-on biological treatments following the GINA guidelines. Mepolizumab was used in patients with >300 eosinophils/µL (without corticosteroids treatment) or >100 eosinophils/µL (with corticosteroids). Meanwhile, Omalizumab was chosen in uncontrolled severe allergic asthmatics with serum IgE levels between 30 and 1500 IU/mL and body weight within the dosing range.

Sample Preparation:

Sampleprep ID:SP003067
Sampleprep Summary:For sample preparation, 50 µL of serum was mixed with 150 µL of cold (−20 °C) methanol: ethanol mix (MeOH:EtOH) (1:1). Then, serum samples were vortex-mixed for 1 min, placed on ice for 15 min and centrifuged at 16000× g for 20 min at 4 °C. Subsequently, 70 µL of the supernatant was transferred into an LC vial and mixed with 50 µL of ISTD mix, (with a final concentration of 0.2 µg/mL for HILIC and 0.3 µg/mL for re-versed-phase method) and 440 µL of the initial conditions of the mobile phases for the HILIC method. For blank preparation, 50 µL of water was used and the same steps as described above were followed.
Extract Storage:-20℃

Combined analysis:

Analysis ID AN004834 AN004835
Analysis type MS MS
Chromatography type HILIC Reversed phase
Chromatography system Agilent 1260 Infinity II Agilent 1260 Infinity II
Column Phenomenex Kinetex HILIC (150 x 2.1mm, 2.6um, 100Å) Merck Supelco Ascentis Express C8 (150 x 2.1mm, 2.7um, 90Å)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Agilent 6470 QQQ Agilent 6470 QQQ
Ion Mode POSITIVE UNSPECIFIED
Units Areas Areas

Chromatography:

Chromatography ID:CH003653
Chromatography Summary:Used to detect small polar metabolites (adenosine, betaine, L-carnitine d3, cortisol, creatine, creatinine, hexanoylcarnitine, hippuric acid hypoxanthine, L-isoleucine d7, L-arginine, L-carnitine, L-leucine/isoleucine, L-phenylalanine, L-phenylalanine d5, L-proline, propionylcarnitine, urea, and valine d8). To achieve metabolite separation, a gradient elution on a Kinetex HILIC (150 mm × 2.1 mm × 100 Å) column maintained at 25 °C was used. The mobile phases consisted of (A) water, and (B) ACN, both with 7.5 mM ammonium acetate and 0.1% acetic acid, obtaining a final pH of 4.0 in the aqueous phase. The flow rate was 0.5 mL/min. The gradient started with 5% of A for 2 min, then increased up to 50% until 12 min, and back to initial conditions until 22 min.
Instrument Name:Agilent 1260 Infinity II
Column Name:Phenomenex Kinetex HILIC (150 x 2.1mm, 2.6um, 100Å)
Column Temperature:25ºC
Flow Gradient:The gradient started with 5% of A for 2 min, then increased up to 50% until 12 min, and back to initial conditions until 22 min.
Flow Rate:0.5mL/min
Solvent A:100% water; 0.1% acetic acid; 7.5mm ammonium acetate
Solvent B:100% acetonitrile; 0.1% acetic acid; 7.5mm ammonium acetate
Chromatography Type:HILIC
  
Chromatography ID:CH003654
Chromatography Summary:To detect metabolites with medium polarity (arachidonic acid, bilirubin, lactic acid, lauric acid, LPC 14:0, LPC 16:0, LPC 17:0, LPC 17:1, LPC 18:0, LPC 18:1, LPC 18:1 d7, LPC 19:0, LPC 20:0, LPE 18:0, LPI 20:4, oleic acid, palmitic acid d31, palmitoleic acid, sphingosine, sphingosine d7, and S1P). For metabolite separation, a gradient elution on a Supelco Ascentis Express reversed-phase (150 mm × 2.1 mm × 2.7 μm) column maintained at 60 °C was used. The mobile phases consisted of (A) water, and (B) ACN, both with 0.1% acetic acid, obtaining a final pH of 3.3 in the aqueous phase. The flow rate was 0.6 mL/min. The gradient started with 20% of B for 2 min, then increased up to 100% until 10 min and maintained for 5 min, then returned to initial conditions until 20 min.
Instrument Name:Agilent 1260 Infinity II
Column Name:Merck Supelco Ascentis Express C8 (150 x 2.1mm, 2.7um, 90Å)
Column Temperature:60ºC
Flow Gradient:The gradient started with 20% of B for 2 min, then increased up to 100% until 10 min and maintained for 5 min, then returned to initial conditions until 20 min.
Flow Rate:0.6mL/min
Solvent A:100% water; 0.1% acetic acid
Solvent B:100% acetonitrile; 0.1% acetic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS004580
Analysis ID:AN004834
Instrument Name:Agilent 6470 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The MS conditions were as follows: 5500 V of capillary voltage in positive ESI mode, a nebulizer gas flow rate of 11.0 L/min, a source temperature of 250 °C; and a source pressure of 60 psi. Chromatogram visualization and peak areas were obtained using MassHunter Workstation B.05.00 and MassHunter QQQ Quantitative Analysis B.08.00, respectively.
Ion Mode:POSITIVE
  
MS ID:MS004581
Analysis ID:AN004835
Instrument Name:Agilent 6470 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The MS was done with polarity switching with the following conditions: 3500 V of capillary voltage in positive ESI mode and 3000V in negative ESI mode, a nebulizer gas flow rate of 10.0 L/min, a source temperature of 250 °C; and a source pressure of 45 psi. Chromatogram visualization and peak areas were obtained using MassHunter Workstation B.05.00 and MassHunter QQQ Quantitative Analysis B.08.00, respectively.
Ion Mode:UNSPECIFIED
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