USE OF ALLERGEN BRONCHOPROVOCATION TO SCREEN DRUGS FOR ANTIASTHMA ACTIVITY

In the atopic patient with asthma, allergens are an important cause of chronic airway inflammation and symptoms. Natural exposure to seasona l allergens, such as grass pollen, may result in exacerbation of asthm a, increased airway responsiveness (i.e., increased susceptibility of the airways to constrict), and an increased frequency of emergency roo m 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 phy siological responses similar to those observed after natural exposure. These include an immediate decrease in the forced expiratory volume i n 1 second (FEV(1)) that is rapid in onset but short in duration (earl y response), a subsequent gradual decline in FEV(1) 4-8 hours after al lergen inhalation that is sustained (late response), an increase in ai rway responsiveness, and infiltration of the airway mucosa by inflamma tory cells. Drugs that are effective as maintenance therapy for chroni c asthma generally attenuate the late response to allergen bronchoprov ocation, and those with antiinflammatory effects (e.g., inhaled cortic osteroids) also attenuate the allergen-induced increase in airway resp onsiveness and cellular infiltration of the airways. However, the magn itude of drug effect in this clinical model does not correlate well wi th the drug's relative efficacy in chronic asthma. In contrast, drugs that have no effect in this clinical model, such as calcium channel bl ockers, ketotifen, and antihistamines, are ineffective as maintenance therapy for chronic asthma. Thus, it appears that allergen bronchoprov ocation is most useful as a screening tool for excluding drugs that ar e unlikely to be effective for chronic asthma and for determining whet her a drug has antiinflammatory and/or immunomodulatory actions on the airway mucosa.