Evidence map›Paper›PMID 26836936›Full record

ArticleChest2016

NADPH Oxidase-4 Overexpression Is Associated With Epithelial Ciliary Dysfunction in Neutrophilic Asthma.

Wing-Yan Heidi Wan, Fay Hollins, Louise Haste, Lucy Woodman, Robert A Hirst, Sarah Bolton, Edith Gomez, Amanda Sutcliffe, Dhananjay Desai, Latifa Chachi and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Chest, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 54 citations in OpenAlex.

  1. The Mechanism of NLRP3 Inflammasome Activation and Its Roles in Chronic Rhinosinusitis.World journal of otorhinolaryngology - head and neck surgery · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Ciliary Function, Antigen Stasis and Asthma.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Association of the Toll-like receptor 4 and NOX4 gene and protein levels in asthmatic patients with metabolic syndrome: A case-control study.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2023
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  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

17 authors at 3 institutions in 2 countries.

Wing-Yan Heidi WanInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Fay HollinsInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Louise HasteDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester.
Lucy WoodmanInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Robert A HirstCentre for PCD Diagnosis and Research, Department of Infection, Immunity and Inflammation, RK Clinical Sciences Building, University of Leicester, Leicester.
Sarah BoltonInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Edith GomezInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Amanda SutcliffeInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Dhananjay DesaiInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Latifa ChachiInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Vijay MistryInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Cédric SzyndralewiezGenkyotex, Geneva, Switzerland.
Andrew WardlawInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Ruth SaundersInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester.
Christopher O'CallaghanDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester.
Peter W AndrewDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester.
Christopher E BrightlingInstitute for Lung Health, Department of Infection, Immunity & Inflammation, Glenfield Hospital, University of Leicester, Leicester. Electronic address: ceb17@le.ac.uk.
University of Leicester · GBGlenfield Hospital · GBGenkyotex (Switzerland) · CH

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundBronchial epithelial ciliary dysfunction is an important feature of asthma. We sought to determine the role in asthma of neutrophilic inflammation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in ciliary dysfunction.

methodsBronchial epithelial ciliary function was assessed by using video microscopy in fresh ex vivo epithelial strips from patients with asthma stratified according to their sputum cell differentials and in culture specimens from healthy control subjects and patients with asthma. Bronchial epithelial oxidative damage was determined by 8-oxo-dG expression. Nicotinamide adenine dinucleotide phosphate oxidase (NOX)/dual oxidase (DUOX) expression was assessed in bronchial epithelial cells by using microarrays, with NOX4 and DUOX1/2 expression assessed in bronchial biopsy specimens. Ciliary dysfunction following NADPH oxidase inhibition, using GKT137831, was evaluated in fresh epithelial strips from patients with asthma and a murine model of ovalbumin sensitization and challenge.

resultsCiliary beat frequency was impaired in patients with asthma with sputum neutrophilia (n = 11) vs those without (n = 10) (5.8 [0.6] Hz vs 8.8 [0.5] Hz; P = .003) and was correlated with sputum neutrophil count (r = -0.70; P < .001). Primary bronchial epithelial cells expressed DUOX1/2 and NOX4. Levels of 8-oxo-dG and NOX4 were elevated in patients with neutrophilic vs nonneutrophilic asthma, DUOX1 was elevated in both, and DUOX2 was elevated in nonneutrophilic asthma in vivo. In primary epithelial cultures, ciliary dysfunction did not persist, although NOX4 expression and reactive oxygen species generation was increased from patients with neutrophilic asthma. GKT137831 both improved ciliary function in ex vivo epithelial strips (n = 13), relative to the intensity of neutrophilic inflammation, and abolished ciliary dysfunction in the murine asthma model with no reduction in inflammation.

conclusionsCiliary dysfunction is increased in neutrophilic asthma associated with increased NOX4 expression and is attenuated by NADPH oxidase inhibition.

Indexed as

AsthmaRespiratory MucosaAdultAnimalsCiliaDual OxidasesFemaleHumansInflammationMaleMiceMiddle AgedNADPH Oxidase 4NADPH OxidasesNeutrophilsOxidative StressDual OxidasesDUOX1 protein, humanDUOX2 protein, humanNADPH Oxidase 4NADPH OxidasesNOX4 protein, humanasthmaepithelial cellsNOX4oxidative stress

Identifiers

PMID26836936
PMCPMC4893823
OpenAlexW2272254857

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.