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A new look at the pathogenesis of asthma

A new look at the pathogenesis of asthma
A new look at the pathogenesis of asthma
Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.

allergen, asthma, inflammation, remodelling, t-cell, virus infection
0143-5221
439-450
Holgate, Stephen T.
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Arshad, Hasan S.
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Roberts, Graham C.
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Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Thurner, Philipp J.
ab711ddd-784e-48de-aaad-f56aec40f84f
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Arshad, Hasan S.
917e246d-2e60-472f-8d30-94b01ef28958
Roberts, Graham C.
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Thurner, Philipp J.
ab711ddd-784e-48de-aaad-f56aec40f84f
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Holgate, Stephen T., Arshad, Hasan S., Roberts, Graham C., Howarth, Peter H., Thurner, Philipp J. and Davies, Donna E. (2009) A new look at the pathogenesis of asthma. Clinical Science, 118 (7), 439-450. (doi:10.1042/CS20090474). (PMID:20025610)

Record type: Article

Abstract

Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.

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More information

Published date: 23 December 2009
Keywords: allergen, asthma, inflammation, remodelling, t-cell, virus infection

Identifiers

Local EPrints ID: 79686
URI: http://eprints.soton.ac.uk/id/eprint/79686
ISSN: 0143-5221
PURE UUID: 8fb38eb4-ff12-494d-98e4-d6ab693fee7b
ORCID for Philipp J. Thurner: ORCID iD orcid.org/0000-0001-7588-9041
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 18 Mar 2010
Last modified: 17 Dec 2019 02:04

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