HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holgate, S. T. Articles by Davies, D. E. Search for Related Content PubMed PubMed Citation Articles by Holgate, S. T. Articles by Davies, D. E.

The Role of the Airway Epithelium and its Interaction with Environmental Factors in Asthma Pathogenesis

¹ Infection, Inflammation and Immunity Division, School of Medicine, Southampton University, Southampton General Hospital, Southampton, United Kingdom

Correspondence and requests for reprints should be addressed to Stephen T. Holgate, M.D., F.R.C.P., F.Med.Sci., Infection, Inflammation and Immunity Division, School of Medicine, Southampton University, Southampton General Hospital, Southampton SO166YD, UK. E-mail: sth{at}soton.ac.uk

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.

Key Words: asthma • epithelium • allergens • rhinovirus • exacerbation

This article has been cited by other articles:

				L. G. Gregory, S. A. Mathie, S. A. Walker, S. Pegorier, C. P. Jones, and C. M. Lloyd Overexpression of Smad2 Drives House Dust Mite-mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25 Am. J. Respir. Crit. Care Med., July 15, 2010; 182(2): 143 - 154. [Abstract] [Full Text] [PDF]

				L. M. Crosby and C. M. Waters Epithelial repair mechanisms in the lung Am J Physiol Lung Cell Mol Physiol, June 1, 2010; 298(6): L715 - L731. [Abstract] [Full Text] [PDF]

				R. Martinez-Giron and H. C. van Woerden Disruption of Airway Epithelium in Asthma Pathogenesis: Are Protozoa Responsible? Proceedings of the ATS, May 1, 2010; 7(2): 161 - 161. [Full Text] [PDF]