Evidence map›Paper›PMID 39497092›Full record

ArticleBMC pulmonary medicine2024

Circulating microRNAs associated with bronchodilator response in childhood asthma.

Rinku Sharma, Anshul Tiwari, Alvin T Kho, Alberta L Wang, Upasna Srivastava, Shraddha Piparia, Brinda Desai, Richard Wong, Juan C Celedón, Stephen P Peters and 6 more

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC pulmonary medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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.

NCT00021840 completednot on this map

Genetic Epidemiology of Asthma in Costa Rica

TypeobservationalSponsorBrigham and Women's HospitalRan2001 to 2011Enrolled4,245ConditionsAsthma, Lung Diseases
NCT00156819 phase4completednot on this map

The Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial

TypeinterventionalSponsorJHSPH Center for Clinical TrialsRan2003 to 2006Enrolled500ConditionsAsthmaArmsfluticasone, montelukast, Fluticasone plus salmeterol
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Rinku SharmaChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. rersh@channing.harvard.edu.
Anshul TiwariChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Alvin T KhoChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Alberta L WangChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Upasna SrivastavaDivision of Pediatric Respiratory Medicine, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA.
Shraddha PipariaDivision of Pediatric Respiratory Medicine, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA.
Brinda DesaiDivision of Pediatric Respiratory Medicine, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA.
Richard WongDivision of Pediatric Respiratory Medicine, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA.
Juan C CeledónDivision of Pediatric Pulmonary Medicine, University of Pittsburgh, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Stephen P PetersDepartment of Medicine, Wake Forest University, Winston-Salem, NC, USA.
Lewis J SmithDepartment of Medicine, Northwestern University, Chicago, IL, USA.
Charles G IrvinPulmonary and Critical Care Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Mario CastroUniversity of Kansas School of Medicine, Kansas City, KS, USA.
Scott T WeissChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Kelan G Tantisira *Division of Pediatric Respiratory Medicine, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA.
Michael J McGeachie *Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 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
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
MICRORNAS IN CIRCULATION: ONTOLOGIES OF ASTHMA SEVERITY AND TREATMENT (MICROCOAST)R01HL127332 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G · 2015 to 2018
$3.4M
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 R01 HL127332NHLBI NIH HHS R01 HL139634NHLBI NIH HHS R01 HL139634, R01 HL162570, R01 HL161362, and R01 HL127332NHLBI NIH HHS R01 HL161362NHLBI NIH HHS R01 HL162570
6 · The paper itself

Abstract

backgroundBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.

objectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.

methodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.

resultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.

conclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.

trial registrationLOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].

Indexed as

AsthmaBronchodilator AgentsCirculating MicroRNAAdolescentChildDown-RegulationFemaleHumansMaleMicroRNAsBronchodilator AgentsCirculating MicroRNAMicroRNAsAsthmaBronchodilator responsemicroRNA

Identifiers

PMID39497092
PMCPMC11536898

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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.