Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma

Holgate, Stephen T., Lackie, Peter, Wilson, Susan, Roche, William and Davies, Donna (2000) Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma. American Journal of Respiratory and Critical Care Medicine, 162 (3), S113-S117. (doi:10.1164/ajrccm.162.supplement_2.ras-12).

Abstract

Asthma is a chronic inflammatory disorder of the airways manifesting as intermittent airflow limitation, which over time may become progressive (1). Both in the allergic and nonallergic forms of the disease there is evidence of an altered local T cell response in favor of Th2 cytokine release resulting in B cell isotype switching to IgE; mast cell, eosinophil, and basophil recruitment; and activation and release of a wide range of inflammatory mediators (2). However, it has become clear that, by itself, inflammation is not able to explain many of the features characteristic of chronic asthma and that restructuring of the airway wall is also required (3). This “remodeling” response presumably accounts for the incomplete therapeutic efficacy of corticosteroids, with persistence of bronchial hyperresponsiveness (BHR), and the progressive decline in pulmonary function over time that occurs in those asthmatic individuals with more chronic and severe disease (1). Although atopy, the propensity to generate allergen-specific IgE, is one of the strongest risk factors for asthma, especially in children and young adults, only 10% of atopics develop chronic asthma and, as adults, asthma occurs in the absence of atopy, most notably in those with more severe and chronic disease. It seems plausible that, rather than IgE-mediated inflammation being the initiator of disordered airway function, the epithelium itself is abnormal and it is this that predisposes the individual with asthma toward local allergen sensitization, and the injurious effects of respiratory viruses and air pollutants (including tobacco smoke). A disordered epithelium could also provide a basis for airway remodeling in asthma.

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Contributors

Author: Peter Lackie

Author: Susan Wilson

Author: Donna Davies

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