Evidence map›Paper›PMID 33455043›Full record

ArticleRespirology (Carlton, Vic.)2021

ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma.

Peter A B Wark, Prabuddha S Pathinayake, Gerard Kaiko, Kristy Nichol, Ayesha Ali, Ling Chen, Erika N Sutanto, Luke W Garratt, Sukhwinder S Sohal, Wenying Lu and 11 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respirology (Carlton, Vic.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
9.0field-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

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Exploring Asthma as a Protective Factor in COVID-19 Outcomes.International journal of molecular sciences · 2025
    Review
  5. Article
  6. Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024
    Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. The Complex Association between COPD and COVID-19.Journal of clinical medicine · 2023
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 5 institutions in 1 country.

Peter A B WarkPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.ORCID 0000-0001-5676-6126
Prabuddha S PathinayakePriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
Gerard KaikoPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
Kristy NicholPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
Ayesha AliPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
Ling ChenPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
Erika N SutantoTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Luke W GarrattTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Sukhwinder S SohalRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
Wenying LuRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
Mathew S EapenRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.ORCID 0000-0003-0570-7059
Christopher OldmeadowClinical Research Design and Statistics, Hunter Medical Research Institute, Newcastle, NSW, Australia.
Nathan BartlettPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
Andrew ReidPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
Punnam VeeratiPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
Alan C-Y HsuPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
Kevin LooiTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Thomas IosifidisTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.ORCID 0000-0001-8462-5865
Stephen M StickTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Philip M HansbroCentre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Anthony KicicTelethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Hunter Medical Research Institute · AUThe Kids Research Institute Australia · AUUniversity of Tasmania · AUJohn Hunter Hospital · AUUniversity of Technology Sydney · AU

Funding

Clifford Craig Foundation Launceston General HospitalHunter Medical Research InstituteNational Health and Medical Research Council 1079187National Health and Medical Research Council 1175134Rebecca L. Cooper Medical Research FoundationSPHERE
6 · The paper itself

Abstract

BACKGROUND AND

objectiveCOVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD.

methodsWe obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC.

resultsIncreased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients.

conclusionIncreased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.

Indexed as

Gene Expression RegulationSARS-CoV-2AsthmaAustraliaComorbidityCOVID-19Epithelial CellsFemaleHumansMaleMiddle AgedPeptidyl-Dipeptidase APeptidyl-Dipeptidase Abronchial asthmachronic obstructive pulmonary diseasecoronavirus diseaseCOVID-19pandemicSARS-CoV-2viral infections

Identifiers

PMID33455043
PMCPMC8014151
OpenAlexW3123124999

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.