Evidence map›Paper›PMID 39592603›Full record

ArticleNature communications2024

Dual therapy with corticosteroid ablates the beneficial effect of DP2 antagonism in chronic experimental asthma.

Md Ashik Ullah, Sonja Rittchen, Jia Li, Bodie F Curren, Patricia Namubiru, Tufael Ahmed, Daniel R Howard, Muhammed Mahfuzur Rahman, Md Al Amin Sikder, Ridwan B Rashid and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Md Ashik UllahRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Sonja RittchenRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Jia LiRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Bodie F CurrenRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.ORCID 0000-0002-1165-6406
Patricia NamubiruRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Tufael AhmedRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Daniel R HowardRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Muhammed Mahfuzur RahmanRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Md Al Amin SikderRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Ridwan B RashidRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Natasha CollinsonRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Mary LorRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Mark L SmytheInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia.
Simon PhippsRespiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia. simon.phipps@qimrberghofer.edu.au.ORCID 0000-0002-7388-3612

Funding

Department of Health | National Health and Medical Research Council (NHMRC) FWF, W1241European Molecular Biology Organization (EMBO) 8109
6 · The paper itself

Abstract

Prostaglandin D2 (PGD2) signals via the DP1 and DP2 receptors. In Phase II trials, DP2 antagonism decreased airway inflammation and airway smooth muscle (ASM) area in moderate-to-severe asthma patients. However, in Phase III, DP2 antagonism failed to lower the rate of exacerbations, and DP2 as a target was shelved. Here, using a preclinical model of chronic experimental asthma, we demonstrate that rhinovirus-induced exacerbations increase PGD2 release, mucus production, transforming growth factor (TGF)-β1 and type-2 inflammation. DP2 antagonism or DP1 agonism ablates these phenotypes, increases epithelial EGF expression and decreases ASM area via increased IFN-γ. In contrast, dual DP1-DP2 antagonism or dual corticosteroid/DP2 antagonism, which attenuates endogenous PGD2, prevented ASM resolution. We demonstrate that DP2 antagonism resolves ASM remodelling via PGD2/DP1-mediated upregulation of IFN-γ expression, and that dual DP2 antagonism/corticosteroid therapy, as often occurred in the human trials, impairs the efficacy of DP2 antagonism by suppressing endogenous PGD2 and IFN-γ production.

Indexed as

Adrenal Cortex HormonesAsthmaInterferon-gammaProstaglandin D2Receptors, ImmunologicReceptors, ProstaglandinAirway RemodelingAnimalsDisease Models, AnimalDrug Therapy, CombinationFemaleHumansInflammationMaleMiceMuscle, SmoothAdrenal Cortex HormonesInterferon-gammaProstaglandin D2prostaglandin D2 receptorprostanoid D receptor 1, mouseReceptors, ImmunologicReceptors, ProstaglandinTransforming Growth Factor beta1

Identifiers

PMID39592603
PMCPMC11599388

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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.