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Airway remodeling in asthma: new insights

Airway remodeling in asthma: new insights
Airway remodeling in asthma: new insights
Asthma is increasing in prevalence worldwide as a result of factors associated with a Western lifestyle. The prevalence and chronic nature of the disease represent significant economic burdens. Despite advances in understanding the inflammatory and immunologic components of asthma, there is relatively little understanding of the cellular and molecular mechanisms underlying the structural changes seen in the asthmatic lung (airway remodeling). These changes include hypertrophy of bronchial smooth muscle, transformation of fibroblasts to myofibroblasts, and deposition of subepithelial collagen. Airway remodeling is linked to bronchial hyperresponsiveness to diverse triggers and a steeper trajectory of long-term decrease in lung function in asthmatic patients. Until recently, these remodeling changes have been considered to be secondary phenomena, developing late in the disease process as a consequence of persistent inflammation. We discuss an alternative view of asthma pathogenesis by emphasizing the importance of the airway microenvironment (the epithelial mesenchymal trophic unit) in the origins of the disease. Our proposals are supported by the recent identification of ADAM33 as an asthma susceptibility gene, the expression of which is abundant in airway fibroblasts and smooth muscle but absent from T lymphocytes or inflammatory cells that infiltrate the airway wall in patients with asthma.
asthma, remodeling, ADAM33, airway epithelium, airway mesenchyme
0091-6749
215-225
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Wicks, James
6b178ed1-5c0c-448c-97f1-5c505d1e530a
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Puddicombe, Sarah M.
124e2c4e-ab9a-46f3-855c-b54ed0b61cc4
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Wicks, James
6b178ed1-5c0c-448c-97f1-5c505d1e530a
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Puddicombe, Sarah M.
124e2c4e-ab9a-46f3-855c-b54ed0b61cc4
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc

Davies, Donna E., Wicks, James, Powell, Robert M., Puddicombe, Sarah M. and Holgate, Stephen T. (2003) Airway remodeling in asthma: new insights. Journal of Allergy and Clinical Immunology, 111 (2), 215-225. (doi:10.1067/mai.2003.128).

Record type: Article

Abstract

Asthma is increasing in prevalence worldwide as a result of factors associated with a Western lifestyle. The prevalence and chronic nature of the disease represent significant economic burdens. Despite advances in understanding the inflammatory and immunologic components of asthma, there is relatively little understanding of the cellular and molecular mechanisms underlying the structural changes seen in the asthmatic lung (airway remodeling). These changes include hypertrophy of bronchial smooth muscle, transformation of fibroblasts to myofibroblasts, and deposition of subepithelial collagen. Airway remodeling is linked to bronchial hyperresponsiveness to diverse triggers and a steeper trajectory of long-term decrease in lung function in asthmatic patients. Until recently, these remodeling changes have been considered to be secondary phenomena, developing late in the disease process as a consequence of persistent inflammation. We discuss an alternative view of asthma pathogenesis by emphasizing the importance of the airway microenvironment (the epithelial mesenchymal trophic unit) in the origins of the disease. Our proposals are supported by the recent identification of ADAM33 as an asthma susceptibility gene, the expression of which is abundant in airway fibroblasts and smooth muscle but absent from T lymphocytes or inflammatory cells that infiltrate the airway wall in patients with asthma.

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More information

Published date: 2003
Keywords: asthma, remodeling, ADAM33, airway epithelium, airway mesenchyme

Identifiers

Local EPrints ID: 27015
URI: https://eprints.soton.ac.uk/id/eprint/27015
ISSN: 0091-6749
PURE UUID: 15eaf1b6-cf12-439d-9bce-7968c598984d

Catalogue record

Date deposited: 26 Apr 2006
Last modified: 17 Jul 2017 16:05

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