Evidence map›Paper›PMID 25042748›Full record

Trial reportThe Journal of allergy and clinical immunology2014

Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma.

Chaoyu Irvin, Iram Zafar, James Good, Donald Rollins, Christina Christianson, Magdalena M Gorska, Richard J Martin, Rafeul Alam

Abstract readClinical TrialMulticenter Study
In one paragraph

Trial report in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 1 pooled it
13.9field-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.

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

186 citing papers in PubMed, 1 synthesis or guideline pooled it, 308 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Targeting CXCR1/2 suppresses TThe journal of allergy and clinical immunology. Global · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. ICOSMolecular medicine (Cambridge, Mass.) · 2026
    Article
  10. Review
  11. Article
  12. Review
  13. Sex Differences in Asthma Pathogenesis.Immunological reviews · 2026
    Review
  14. Article
  15. CAR-T therapy: Advances in respiratory diseases.Chinese medical journal pulmonary and critical care medicine · 2025
    Review
  16. Review
  17. Article
  18. MUC1 in the upper-lower airway inflammatory continuum: an endotype-centered perspective.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Chaoyu IrvinDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo.
Iram ZafarDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo.
James GoodDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo; School of Medicine, University of Colorado at Denver, Denver, Colo.
Donald RollinsDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo; School of Medicine, University of Colorado at Denver, Denver, Colo.
Christina ChristiansonDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo.
Magdalena M GorskaDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo; School of Medicine, University of Colorado at Denver, Denver, Colo.
Richard J MartinDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo; School of Medicine, University of Colorado at Denver, Denver, Colo.
Rafeul AlamDepartment of Medicine, Division of Allergy & Immunology, and Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo; School of Medicine, University of Colorado at Denver, Denver, Colo. Electronic address: alamr@njhealth.org.
University of Colorado Denver · USNational Jewish Health · US

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Project 3: Environmental Determinants of Host DefenseP01ES018181 · NIEHS · NATIONAL JEWISH HEALTH · PI SCHWARTZ, DAVID ALBERT · 2009 to 2013
$5.7M
Colorado Clinical and Translational Sciences InstituteKL2TR001080 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$2.6M
Role of MEK1 in T cell function in asthmaR01AI091614 · NIAID · NATIONAL JEWISH HEALTH · PI ALAM, RAFEUL · 2011 to 2015
$2.0M
Airway Th2Th17 Cells in Refractory AsthmaR01HL126895 · NHLBI · NATIONAL JEWISH HEALTH · PI ALAM, RAFEUL · 2016 to 2019
$1.8M
Sprouty-2 Regulation of Signaling in AsthmaR01AI102943 · NIAID · NATIONAL JEWISH HEALTH · PI ALAM, RAFEUL · 2014 to 2017
$1.6M
Colorado Clinical and Translational Science Institute (KL2)KL2TR000156 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2012 to 2013
$521k
NCATS NIH HHS KL2 TR000156NCATS NIH HHS KL2 TR001080NCATS NIH HHS UL1 TR001082NHLBI NIH HHS R01 HL126895NIAID NIH HHS R01 AI091614NIAID NIH HHS R01 AI102943NIEHS NIH HHS P01 ES-018181
6 · The paper itself

Abstract

backgroundTH2 cells can further differentiate into dual-positive TH2/TH17 cells. The presence of dual-positive TH2/TH17 cells in the airways and their effect on asthma severity are unknown.

objectiveWe sought to study dual-positive TH2/TH17 cells in bronchoalveolar lavage (BAL) fluid from asthmatic patients, examine their response to glucocorticoids, and define their relevance for disease severity.

methodsBronchoscopy and lavage were performed in 52 asthmatic patients and 25 disease control subjects. TH2 and TH2/TH17 cells were analyzed by using multicolor flow cytometry and confocal immunofluorescence microscopy. Cytokines were assayed by means of ELISA.

resultsDual-positive TH2/TH17 cells were present at a higher frequency in BAL fluid from asthmatic patients compared with numbers seen in disease control subjects. High-level IL-4 production was typically accompanied by high-level IL-17 production and coexpression of GATA3 and retinoic acid receptor-related orphan receptor γt. Increased presence of TH2/TH17 cells was associated with increased IL-17 production in lavage fluid. TH2/TH17 cell counts and IL-17 production correlated with PC20 for methacholine, eosinophil counts, and FEV1. TH2/TH17 cells, unlike TH2 cells, were resistant to dexamethasone-induced cell death. They expressed higher levels of mitogen-activated protein-extracellular signal-regulated kinase kinase 1, a molecule that induces glucocorticoid resistance. On the basis of the dominance of BAL fluid TH2 or TH2/TH17 cells, we identified 3 subgroups of asthma: TH2(predominant), TH2/TH17(predominant), and TH2/TH17(low). The TH2/TH17(predominant) subgroup manifested the most severe form of asthma, whereas the TH2/TH17(low) subgroup had the mildest asthma.

conclusionAsthma is associated with a higher frequency of dual-positive TH2/TH17 cells in BAL fluid. The TH2/TH17(predominant) subgroup of asthmatic patients manifested glucocorticoid resistance in vitro. They also had the greatest airway obstruction and hyperreactivity compared with the TH2(predominant) and TH2/TH17(low) subgroups.

Indexed as

Bronchoalveolar LavageAsthmaBronchoscopyDexamethasoneFemaleFlow CytometryGATA3 Transcription FactorGlucocorticoidsHumansInterleukin-17Interleukin-4MaleMiddle AgedSeverity of Illness IndexTh17 CellsTh2 CellsDexamethasoneGATA3 protein, humanGATA3 Transcription FactorGlucocorticoidsIL4 protein, humanInterleukin-17Interleukin-4asthmabronchoalveolar lavageDual-positive T(H)2/T(H)17 cellsglucocorticoid resistanceMEK

Identifiers

PMID25042748
PMCPMC4254017
OpenAlexW2048395646

What OpenQuestion holds

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Registered trials

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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.