Evidence map›Paper›PMID 20451039›Full record

ArticleThe Journal of allergy and clinical immunology2010

Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma.

Ryan H Dougherty, Sukhvinder S Sidhu, Kavita Raman, Margaret Solon, Owen D Solberg, George H Caughey, Prescott G Woodruff, John V Fahy

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05078021 (Phenotyping Disease Severity in Asthma), which is not on this map. Cited by 146 papers.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed
9.7field-weighted citation impact, top 1% 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.

NCT05078021 unknown statusnot on this mapstarted 2022, after this paper: background citation

Phenotyping Disease Severity in Asthma: Molecular Investigations of Corticosteroid

TypeobservationalSponsorUniversity of CalgaryRan2022 to 2024Enrolled60ConditionsAsthmaArmsBronchoscopy
3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 285 citations in OpenAlex.

  1. Trial
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  3. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2014
    Trial
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  10. Platelets engage mast cells in a bilateral IL-33-driven feed-forward loop.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Targeting carboxypeptidase A/B activity with the phosphinic inhibitor C28 reduces the asthmatic response in a mouse model of house dust mite-induced asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  12. Clinical and Biological Features of a Thickened Basement Membrane Zone in Asthma.American journal of respiratory and critical care medicine · 2025
    Article
  13. Review
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  20. Article

86 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 1 country.

Ryan H DoughertyDivision of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
Sukhvinder S Sidhu
Kavita Raman
Margaret Solon
Owen D Solberg
George H Caughey
Prescott G Woodruff
John V Fahy
University of California, San Francisco · USSan Francisco VA Medical Center · USUniversity of San Francisco · US

Funding

Tools for Analysis of Airway InflammationP01HL024136 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CAUGHEY, GEORGE H · 1985 to 2014
$23.3M
Protein carbohydrate interactions in the pathophysiology of asthma exacerbationsR01HL080414 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI John V Fahy · 2005 to 2026
$9.2M
Molecular Phenotyping of AsthmaR01HL095372 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WOODRUFF, PRESCOTT G · 2008 to 2011
$3.1M
Role of the Intra-Epithelial Mast Cell in Acute and Chronic AsthmaF32HL093999 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DOUGHERTY, RYAN · 2008 to 2008
$50k
NHLBI NIH HHS F32 HL093999NHLBI NIH HHS F32HL093999-01NHLBI NIH HHS P01 HL024136NHLBI NIH HHS R01 HL08041NHLBI NIH HHS R01 HL080414NHLBI NIH HHS R01 HL095372PHS HHS A1077439-02
6 · The paper itself

Abstract

backgroundPreviously, we found that mast cell tryptases and carboxypeptidase A3 (CPA3) are differentially expressed in the airway epithelium in asthmatic subjects. We also found that asthmatic subjects can be divided into 2 subgroups ("T(H)2 high" and "T(H)2 low" asthma) based on epithelial cell gene signatures for the activity of T(H)2 cytokines.

objectivesWe sought to characterize intraepithelial mast cells (IEMCs) in asthma.

methodsWe performed gene expression profiling in epithelial brushings and stereology-based quantification of mast cell numbers in endobronchial biopsy specimens from healthy control and asthmatic subjects before and after treatment with inhaled corticosteroids (ICSs). We also performed gene expression and protein quantification studies in cultured airway epithelial cells and mast cells.

resultsBy means of unsupervised clustering, mast cell gene expression in the airway epithelium related closely to the expression of IL-13 signature genes. The levels of expression of mast cell genes correlate positively with lung function improvements with ICSs. IEMC density was 2-fold higher than normal in subjects with T(H)2-high asthma compared with that seen in subjects with T(H)2-low asthma or healthy control subjects (P = .015 for both comparisons), and these cells were characterized by expression of tryptases and CPA3 but not chymase. IL-13 induced expression of stem cell factor in cultured airway epithelial cells, and mast cells exposed to conditioned media from IL-13-activated epithelial cells showed downregulation of chymase but no change in tryptase or CPA3 expression.

conclusionIEMC numbers are increased in subjects with T(H)2-high asthma, have an unusual protease phenotype (tryptase and CPA3 high and chymase low), and predict responsiveness to ICSs. IL-13-stimulated production of stem cell factor by epithelial cells potentially explains mast cell accumulation in T(H)2-high asthmatic epithelium.

Indexed as

AsthmaAdultCarboxypeptidases ACells, CulturedChymasesCytokinesEpithelial CellsFemaleGene Expression ProfilingGene Expression RegulationHumansInterleukin-13MaleMast CellsMiddle AgedPeptide HydrolasesCarboxypeptidases AChymasesCPA3 protein, humanCytokinesInterleukin-13Peptide HydrolasesStem Cell FactorTryptases

Identifiers

PMID20451039
PMCPMC2918406
OpenAlexW2023364946

What OpenQuestion holds

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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.