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Epithelial stress and structural remodelling in childhood asthma

Epithelial stress and structural remodelling in childhood asthma
Epithelial stress and structural remodelling in childhood asthma
Background: In adult asthma the bronchial epithelium shows high expression of the epidermal growth factor receptor (EGFR) and the cyclin dependent kinase inhibitor, p21waf, linked to ongoing stress and injury. 
Methods: To determine if these are early markers of disease, sections of bronchial specimens obtained post mortem or by bronchoscopy from non-asthmatic (n = 7), moderate (n = 7), or severe (n = 9) asthmatic children aged 5–15 years were examined immunohistochemically. All severe and one moderately asthmatic children were receiving inhaled corticosteroids. 
Results: The lamina reticularis of the asthmatic biopsy sections was found to be thicker (p = 0.01) than normal with increased deposition of collagen III (p = 0.007); submucosal eosinophil numbers did not differ between groups. As in adults, there was an asthma-related increase in epithelial EGFR (p<0.002) but there was no evidence of proliferation, with Ki67 being reduced (p = 0.001) and p21waf increased (p<0.004). The thickness of the lamina reticularis was significantly correlated with epithelial EGFR (rho = 0.77, p<0.001). 
Conclusions: These data provide evidence that, in asthmatic children, the epithelium is stressed or injured without significant eosinophilic inflammation. This change in the epithelial phenotype is associated with collagen deposition in the lamina reticularis, suggesting that the epithelial mesenchymal trophic unit is active early in, and may contribute to, the pathogenesis of asthma.
airway remodelling, asthma, epidermal growth factor receptor, epithelium, children
0040-6376
389-394
Fedorov, I.A.
2c84851b-bee2-48cc-808a-60bd685d2dd7
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Davies, D.E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Fedorov, I.A.
2c84851b-bee2-48cc-808a-60bd685d2dd7
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Davies, D.E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc

Fedorov, I.A., Wilson, S.J., Davies, D.E. and Holgate, S.T. (2005) Epithelial stress and structural remodelling in childhood asthma. Thorax, 60 (5), 389-394. (doi:10.1136/thx.2004.030262).

Record type: Article

Abstract

Background: In adult asthma the bronchial epithelium shows high expression of the epidermal growth factor receptor (EGFR) and the cyclin dependent kinase inhibitor, p21waf, linked to ongoing stress and injury. 
Methods: To determine if these are early markers of disease, sections of bronchial specimens obtained post mortem or by bronchoscopy from non-asthmatic (n = 7), moderate (n = 7), or severe (n = 9) asthmatic children aged 5–15 years were examined immunohistochemically. All severe and one moderately asthmatic children were receiving inhaled corticosteroids. 
Results: The lamina reticularis of the asthmatic biopsy sections was found to be thicker (p = 0.01) than normal with increased deposition of collagen III (p = 0.007); submucosal eosinophil numbers did not differ between groups. As in adults, there was an asthma-related increase in epithelial EGFR (p<0.002) but there was no evidence of proliferation, with Ki67 being reduced (p = 0.001) and p21waf increased (p<0.004). The thickness of the lamina reticularis was significantly correlated with epithelial EGFR (rho = 0.77, p<0.001). 
Conclusions: These data provide evidence that, in asthmatic children, the epithelium is stressed or injured without significant eosinophilic inflammation. This change in the epithelial phenotype is associated with collagen deposition in the lamina reticularis, suggesting that the epithelial mesenchymal trophic unit is active early in, and may contribute to, the pathogenesis of asthma.

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More information

Published date: 2005
Keywords: airway remodelling, asthma, epidermal growth factor receptor, epithelium, children

Identifiers

Local EPrints ID: 40614
URI: http://eprints.soton.ac.uk/id/eprint/40614
ISSN: 0040-6376
PURE UUID: 1913caf5-f090-419a-813f-6f4258571c6e
ORCID for S.J. Wilson: ORCID iD orcid.org/0000-0003-1305-8271
ORCID for D.E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 06 Jul 2006
Last modified: 16 Mar 2024 02:34

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Contributors

Author: I.A. Fedorov
Author: S.J. Wilson ORCID iD
Author: D.E. Davies ORCID iD
Author: S.T. Holgate

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