In the atopic patient with
asthma,
allergens are an important cause of chronic airway
inflammation and symptoms. Natural exposure to seasonal
allergens, such as grass pollen, may result in exacerbation of
asthma, increased airway responsiveness (i.e., increased susceptibility of the airways to constrict), and an increased frequency of emergency room visits. Removal of patients from exposure to indoor
allergens, such as dust mites, results in a marked reduction in symptoms, less airway responsiveness, and a decrease in
drug requirements. In the pulmonary function laboratory, inhalation of increasing doses of
allergen, in a safe and controlled manner (
allergen bronchoprovocation), produces physiological responses similar to those observed after natural exposure. These include an immediate decrease in the forced expiratory volume in 1 second (FEV1) that is rapid in onset but short in duration (early response), a subsequent gradual decline in FEV1 4-8 hours after
allergen inhalation that is sustained (late response), an increase in airway responsiveness, and infiltration of the airway mucosa by inflammatory cells. Drugs that are effective as maintenance
therapy for chronic
asthma generally attenuate the late response to
allergen bronchoprovocation, and those with antiinflammatory effects (e.g., inhaled
corticosteroids) also attenuate the
allergen-induced increase in airway responsiveness and cellular infiltration of the airways. However, the magnitude of
drug effect in this clinical model does not correlate well with the
drug's relative efficacy in chronic
asthma. In contrast, drugs that have no effect in this clinical model, such as
calcium channel blockers,
ketotifen, and
antihistamines, are ineffective as maintenance
therapy for chronic
asthma. Thus, it appears that
allergen bronchoprovocation is most useful as a screening tool for excluding drugs that are unlikely to be effective for chronic
asthma and for determining whether a
drug has antiinflammatory and/or immunomodulatory actions on the airway mucosa.