Evidence map›Paper›PMID 39031511›Full record

ArticleImmunity, inflammation and disease2024

Urine metabolomics signature reveals novel determinants of adrenal suppression in children taking inhaled corticosteroids to control asthma symptoms.

Dung T Tran, Yulu Chen, Yi Zheng, Julian Hecker, Daniel B Hawcutt, Munir Pirmohamed, Jessica Lasky-Su, Ann C Wu, Kelan G Tantisira, Michael J McGeachie and 2 more

Abstract read
In one paragraph

Article in Immunity, inflammation and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Dung T TranChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0009-0006-7304-1358
Yulu ChenChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Yi ZhengChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Julian HeckerChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Daniel B HawcuttUniversity of Liverpool, Liverpool, UK.
Munir PirmohamedUniversity of Liverpool, Liverpool, UK.
Jessica Lasky-SuChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ann C WuChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Kelan G TantisiraDivision of Pediatric Respiratory Medicine, University of California San Diego and Rady Children's Hospital, San Diego, California, USA.
Michael J McGeachieChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Scott T WeissChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Amber DahlinChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Funding

Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and EndotypingR01HL161362 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EUGENE ROLAND BLEECKER, GEOFFREY L CHUPP · 2022 to 2026
$8.4M
Pharmacogenomics of Adrenal Suppression with Inhaled Corticosteroids (PhASIC)R01HL152244 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DAHLIN, AMBER · 2020 to 2024
$4.4M
Asthma Exacerbations and MicroRNA prediction: Treatment Response in an Underserved Ethnicity (AEM-TRUE)R01HL139634 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MCGEACHIE, MICHAEL JOHN · 2018 to 2022
$4.3M
Omic Determinants of Longitudinal Lung Function in AsthmaR01HL155742 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LASKY-SU, JESSICA A, MCGEACHIE, MICHAEL JOHN · 2021 to 2025
$3.9M
Genomics and Pharmacogenomics of Symptoms in AsthmaR01HL162570 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TANTISIRA, KELAN G · 2021 to 2024
$2.9M
NHLBI NIH HHS HL139634NHLBI NIH HHS HL152244NHLBI NIH HHS HL155742NHLBI NIH HHS HL161362NHLBI NIH HHS R01 HL139634NHLBI NIH HHS R01 HL152244NHLBI NIH HHS R01 HL155742NHLBI NIH HHS R01 HL161362NHLBI NIH HHS R01 HL162570
6 · The paper itself

Abstract

backgroundAsthma is routinely treated with inhaled corticosteroids (ICS). Asthma patients on ICS are at increased risk of adrenal suppression, a potentially serious effect of long-term glucocorticoid exposure; however, this relationship is poorly understood. Therefore, this study aims to identify metabolite biomarkers related to adrenal suppression in asthma patients taking ICS.

methodsA total of 571 urine metabolites from 200 children with asthma on ICS in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) cohort were profiled. Samples were grouped by peak plasma cortisol measurement as adrenal sufficient (>350 nmol/L) or insufficient (≤350 nmol/L) (outcome). Regression and discriminant-based statistical models combined with network analyses were utilized to assess relationships between metabolites and the outcome. Finally, prioritized metabolites were validated using data from an ancillary study of the Childhood Asthma Management (CAMP) cohort with similar characteristics to PASS.

resultsNinety metabolites were significantly associated with adrenal suppression, of which 57 also could discriminate adrenal status. While 26 metabolites (primarily steroids) were present at lower levels in the adrenal insufficient patients, 14 were significantly elevated in this group; the top metabolite, mannitol/sorbitol, was previously associated with asthma exacerbations. Network analyses identified unique clusters of metabolites related to steroids, fatty acid oxidation, and nucleoside metabolism, respectively. Four metabolites including urocanic acid, acetylcarnitine, uracil, and sorbitol were validated in CAMP cohort for adrenal suppression.

conclusionsUrinary metabolites differ among asthma patients on ICS, by adrenal status. While steroid metabolites were reduced in patients with poor adrenal function, our findings also implicate previously unreported metabolites involved in amino acid, lipid, and nucleoside metabolism.

Indexed as

Adrenal Cortex HormonesAsthmaMetabolomicsAdministration, InhalationAdolescentAdrenal GlandsAdrenal InsufficiencyBiomarkersChildChild, PreschoolCohort StudiesFemaleHumansHydrocortisoneMaleMetabolomeAdrenal Cortex HormonesBiomarkersHydrocortisoneadrenal functionasthmabiomarkerICSmetabolomics

Identifiers

PMID39031511
PMCPMC11259003

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.