Evidence map›Paper›PMID 35239513›Full record

ArticleThe Journal of clinical investigation2022

Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.

Aran Singanayagam, Joseph Footitt, Matthias Marczynski, Giorgia Radicioni, Michael T Cross, Lydia J Finney, Maria-Belen Trujillo-Torralbo, Maria Calderazzo, Jie Zhu, Julia Aniscenko and 12 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 2 pooled it
10.4field-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

49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Mucolytics for acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis.European respiratory review : an official journal of the European Respiratory Society · 2023
    Pooled it
  3. Mucins and Respiratory Virus Infection.Annual review of virology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. The triple-hit hypothesis: exploring pulmonary e-cigarette, PMEuropean respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Airway mucus in infection.Frontiers in physiology · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

22 authors at 5 institutions in 5 countries.

Aran SinganayagamNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Joseph FootittNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Matthias MarczynskiSchool of Engineering and Design, Department of Materials Engineering and.
Giorgia RadicioniMarsico Lung Institute/Cystic Fibrosis and Pulmonary Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Michael T CrossDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Lydia J FinneyNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Maria-Belen Trujillo-TorralboNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Maria CalderazzoNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Jie ZhuNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Julia AniscenkoNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Thomas B ClarkeCentre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
Philip L MolyneauxNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Nathan W BartlettNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Miriam F MoffattNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
William O CooksonNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Jadwiga WedzichaNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Christopher M EvansDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Richard C BoucherMarsico Lung Institute/Cystic Fibrosis and Pulmonary Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Mehmet KesimerMarsico Lung Institute/Cystic Fibrosis and Pulmonary Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Oliver LielegSchool of Engineering and Design, Department of Materials Engineering and.
Patrick MalliaNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Sebastian L JohnstonNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Imperial College London · GBUniversity of North Carolina at Chapel Hill · USCenter for Integrated Protein Science Munich · DEUniversity of Colorado Anschutz Medical Campus · USHunter Medical Research Institute · AU

Funding

Role of Mucin in Lung Homeostasis and PathophysiologyR01HL080396 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Christopher M Evans · 2009 to 2026
$8.6M
Mechanisms of lung macrophage programming by MUC5B during health and diseaseR01HL130938 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI EVANS, CHRISTOPHER M · 2016 to 2025
$5.2M
Medical Research Council G0600879Medical Research Council MR/V000098/1NHLBI NIH HHS R01 HL080396NHLBI NIH HHS R01 HL130938Wellcome Trust 107660/Z/15
6 · The paper itself

Abstract

The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway mucin 5AC (MUC5AC) and MUC5B concentrations during spontaneous and experimentally induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with viral load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation, as Muc5ac-deficient (Muc5ac-/-) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.

Indexed as

Mucin 5ACPulmonary Disease, Chronic ObstructiveAdenosine TriphosphateAnimalsDisease Models, AnimalHumansInflammationMiceMucin-5BMucusRespiratory MucosaAdenosine TriphosphateMuc5ac protein, mouseMucin 5ACMucin-5BCOPDInnate immunityPulmonology

Identifiers

PMID35239513
PMCPMC9012283
OpenAlexW4214833760

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.