Evidence map›Paper›PMID 33469180›Full record

Trial reportPediatric research2021

Blood metabolomics in infants enrolled in a dose escalation pilot trial of budesonide in surfactant.

Philip L Ballard, Dara Torgerson, Rajan Wadhawan, Mark L Hudak, Joern-Hendrik Weitkamp, Julia Harris, Jeanette Asselin, Cheryl Chapin, Roberta A Ballard, Cindy T McEvoy

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pediatric research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 26% of its field
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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Preterm lung and brain responses to mechanical ventilation and corticosteroids.Journal of perinatology : official journal of the California Perinatal Association · 2023
    Review
  6. Article
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

10 authors at 5 institutions in 1 country.

Philip L BallardPediatrics, University of California San Francisco, San Francisco, CA, USA. Phil.ballard@ucsf.edu.
Dara TorgersonPediatrics, University of California San Francisco, San Francisco, CA, USA.
Rajan WadhawanPediatrics, AdventHealth for Children, Orlando, FL, USA.
Mark L HudakPediatrics, University of Florida College of Medicine - Jacksonville, Jacksonville, FL, USA.
Joern-Hendrik WeitkampPediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
Julia HarrisPediatrics, Oregon Health & Science University, Portland, OR, USA.
Jeanette AsselinOakland Children's Hospital, Oakland, CA, USA.
Cheryl ChapinPediatrics, University of California San Francisco, San Francisco, CA, USA.
Roberta A BallardPediatrics, University of California San Francisco, San Francisco, CA, USA.
Cindy T McEvoyPediatrics, Oregon Health & Science University, Portland, OR, USA.
University of California, San Francisco · USOregon Health & Science University · USAdventHealth for Children · USUniversity of Florida · USVanderbilt University Medical Center · US

Funding

Integrative metabolomics of bronchopulmonary dysplasia in extremely low gestational age infantsR01HL153429 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BALLARD, PHILIP L., TORGERSON, DARA · 2021 to 2024
$1.6M
The Urinary Metabolome and Bronchopulmonary Dysplasia in Premature InfantsR21HD097600 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BALLARD, PHILIP L., TORGERSON, DARA · 2019 to 2020
$444k
NHLBI NIH HHS R01 HL153429NICHD NIH HHS R21 HD097600
6 · The paper itself

Abstract

backgroundThe pathogenesis of BPD includes inflammation and oxidative stress in the immature lung. Corticosteroids improve respiratory status and outcome, but the optimal treatment regimen for benefit with low systemic effects is uncertain.

methodsIn a pilot dose escalation trial, we administered ≤5 daily doses of budesonide in surfactant to 24 intubated premature infants (Steroid And Surfactant in ELGANs (SASSIE)). Untargeted metabolomics was performed on dried blood spots using UPLC-MS/MS. Tracheal aspirate IL-8 concentration was determined as a measure of lung inflammation.

resultsMetabolomics data for 829 biochemicals were obtained on 121 blood samples over 96 h from 23 infants receiving 0.025, 0.05, or 0.1 mg budesonide/kg. Ninety metabolites were increased or decreased in a time- and dose-dependent manner at q ≤ 0.1 with overrepresentation in lipid and amino acid super pathways. Different dose response patterns occurred, with negative regulation associated with highest sensitivity to budesonide. Baseline levels of 22 regulated biochemicals correlated with lung inflammation (IL-8), with highest significance for sphingosine and thiamin.

conclusionsNumerous metabolic pathways are regulated in a dose-dependent manner by glucocorticoids, which apparently act via distinct mechanisms that impact dose sensitivity. The findings identify candidate blood biochemicals as biomarkers of lung inflammation and systemic responses to corticosteroids. IMPACT: Treatment of premature infants in respiratory failure with 0.1 mg/kg intra-tracheal budesonide in surfactant alters levels of ~11% of detected blood biochemicals in discrete time- and dose-dependent patterns. A subset of glucocorticoid-regulated biochemicals is associated with lung inflammatory status as assessed by lung fluid cytokine concentration. Lower doses of budesonide in surfactant than currently used may provide adequate anti-inflammatory responses in the lung with fewer systemic effects, improving the benefit:risk ratio.

Indexed as

Infant, PrematureMetabolomicsAnti-Inflammatory AgentsBudesonideChromatography, LiquidDose-Response Relationship, DrugDried Blood Spot TestingHumansInfantLimit of DetectionPilot ProjectsPulmonary SurfactantsTandem Mass SpectrometryAnti-Inflammatory AgentsBudesonidePulmonary Surfactants

Identifiers

PMID33469180
PMCPMC7814527
OpenAlexW3125757636

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.