Role of airway reactivity in pathogenesis of asthma.

Airway reactivity is taken to mean the bronchoconstrictor response of airways to non-specific (i.e. non-allergic) stimuli, most commonly to aerosols of histamine, methacholine or prostaglandin F2 alpha, to exercise, cold air or hyperventilation. Reactivity is greatly increased in subjects with asthma when compared with normal. Normal subjects may transiently acquire hyperreactivity following viral infections or exposure to ozone, although usually not in the asthmatic range. In asthma, an initiating stimulus may also be required for the development of hyperreactivity, but genetic susceptibility may be important. Once acquired, the hyperreactivity which is characteristic of asthma varies with time, and with environmental factors. The mechanisms underlying hyperreactivity are incompletely understood. One important feature appears to be the role of continuing mediator release and inflammation in the airways. Reactivity may be increased by levels of mediators which are themselves insufficient to affect lung function, as we have shown in a recent study using histamine challenge following pre-treatment with small doses of prostaglandin F2 alpha. It is possible to imagine how a succession of sub-threshold allergic, or even physical stimuli might maintain bronchial hyperreactivity in this way. Recent studies have described the importance of bronchial hyperreactivity in the pathogenesis of asthma in allergic individuals. The level of bronchial hyperreactivity can determine the asthmatic response to an inhaled allergen, since a high degree of allergy coupled with a low reactivity to released mediators such as histamine would only produce a small response, whereas even a small amount of mediator might produce a large response in a very reactive individual.