Blockage of a “nonspecific” provocational challenge as a model for predicting clinical efficacy

Abstract

After using various techniques in a clinical study comparing the efficacy of theophylline with that of a 13-agonist, Joad et al.1 reported that serial histamine challenge offered the greatest correlation with clinical improvement (Fig. 1) and thus was the best method for evaluating duration of action. This provoked debate on the usefulness of a histamine challenge for assessing both older and newer medications or for comparing generic drugs to prototype prescription drugs. Previously, Ahrens et al.2 noted the disparity between the duration of bronchodilation and suppression of airway responsiveness with metaproterenol compared with isoetharine. Both the bronchodilator and airway responsiveness effects were lost with isoetharine by 21/4 hours. However, the airway responsiveness had diminished by half despite maximal bronchodilator effect at 4 hours with metaproterenol. The researchers suggested that methacholine challenges might provide a more relevant means to estimate duration of effect and dosing intervals than the more traditional methods.