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The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis

The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis
The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis
Asthma is an inflammatory disorder of the airways dominated by a Th2-type pattern. Because of this, most research has focused on investigating the role of allergic pathways with the hope of discovering novel therapeutic targets. Unfortunately, this strategy (which has been extended to animal models) has failed to identify any therapeutic modalities other than anti-IgE and leukotriene modifiers directed to targets known about for many years. It seems that the problem lies in placing allergy at the center of disease pathogenesis, when in practice other environmental factors may be equally if not more important in the induction and then progression of asthma. An alternative view is that asthma is primarily a defect of epithelial barrier function that, as in atopic dermatitis, allows greater access of environmental allergens, microorganisms, and toxicants to the airway tissue. Evidence is provided to show that both the physical and functional barrier of the airway epithelium is defective in asthma with disrupted tight junctions, reduced antioxidant activity, and impaired innate immunity. This explains the remarkable susceptibility of asthmatic airways to respiratory viruses and the impact of air pollutants on asthma exacerbations. It also provides a mechanism for programming of dendritic cells to drive a Th2 response in the origins of asthma. Viewing asthma primarily as an epithelial disease with adoption of a chronic wound scenario also provides a route to airway wall remodeling and the varying asthma phenotypes over the life course.
asthma, epithelium, allergens, rhinovirus, exacerbation
1546-3222
655-659
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Arshad, Hasan S.
917e246d-2e60-472f-8d30-94b01ef28958
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Arshad, Hasan S.
917e246d-2e60-472f-8d30-94b01ef28958
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Holgate, Stephen T., Roberts, Graham, Arshad, Hasan S., Howarth, Peter H. and Davies, Donna E. (2009) The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis. Proceedings of the American Thoracic Society, 6 (8), 655-659. (doi:10.1513/pats.200907-072DP). (PMID:20008870)

Record type: Article

Abstract

Asthma is an inflammatory disorder of the airways dominated by a Th2-type pattern. Because of this, most research has focused on investigating the role of allergic pathways with the hope of discovering novel therapeutic targets. Unfortunately, this strategy (which has been extended to animal models) has failed to identify any therapeutic modalities other than anti-IgE and leukotriene modifiers directed to targets known about for many years. It seems that the problem lies in placing allergy at the center of disease pathogenesis, when in practice other environmental factors may be equally if not more important in the induction and then progression of asthma. An alternative view is that asthma is primarily a defect of epithelial barrier function that, as in atopic dermatitis, allows greater access of environmental allergens, microorganisms, and toxicants to the airway tissue. Evidence is provided to show that both the physical and functional barrier of the airway epithelium is defective in asthma with disrupted tight junctions, reduced antioxidant activity, and impaired innate immunity. This explains the remarkable susceptibility of asthmatic airways to respiratory viruses and the impact of air pollutants on asthma exacerbations. It also provides a mechanism for programming of dendritic cells to drive a Th2 response in the origins of asthma. Viewing asthma primarily as an epithelial disease with adoption of a chronic wound scenario also provides a route to airway wall remodeling and the varying asthma phenotypes over the life course.

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More information

Published date: December 2009
Keywords: asthma, epithelium, allergens, rhinovirus, exacerbation
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 145863
URI: https://eprints.soton.ac.uk/id/eprint/145863
ISSN: 1546-3222
PURE UUID: 2e3a31f6-6ec5-4f9d-bc41-858045c2169f
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 19 Apr 2010 15:38
Last modified: 03 Dec 2019 02:07

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