Has the time come to rethink the pathogenesis of asthma?
OBJECTIVE
To explore new ground in asthma pathogenesis. Asthma is an inflammatory disorder of the airways that has strong association with allergy as characterized by a Th2-type T cell response. However, ranges of approaches that have targeted this immunological component have so far been disappointing. Most asthma therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms.


RESULTS
In this review, a case is made that asthma has its primary origin in the airways that involves defective behaviour of the epithelium in relation to environmental exposures. These include defects in barrier function and an impaired innate immunity to provide the substrate upon which allergic sensitization can occur. Once the airways are sensitized repeated allergen exposure leads to disease persistence. Such mechanisms could explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by viruses, air pollution, certain drugs, and biologically active allergens.


CONCLUSIONS
Activation of the epithelial-mesenchymal trophic unit could be responsible for the emergence of different asthma phenotypes and direct a more targeted approach to treatment. There is also the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than focusing on the suppression of inflammation once established.
Holgate
Stephen T
ST
University of Southampton, Hampshire, UK. sth@soton.ac.uk
D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D015824:Blood-Air Barrier; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D007113:Immunity, Innate; D015994:Incidence; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors
D000485:Allergens