THE UTILITY OF METHACHOLINE AIRWAY RESPONSIVENESS MEASUREMENTS IN EVALUATING ANTIASTHMA DRUGS

Background: Measurements of airway responsiveness are frequently used to evaluate anti-asthma drugs. Objective: This study investigated the utility of methacholine airway responsiveness measurements in evaluati ng anti-asthma medications, both in terms of a bronchoprotective effec t and the ability to attenuate allergen-induced methacholine airway hy perresponsiveness. Methods: Methacholine airway responsiveness was mea sured as PC20 on two occasions (separated by 35 +/- 17 days, mean +/- SD) in 40 subjects with mild, stable asthma. Additional subjects had P C20 measurements made before and af ter administration of either inhal ed salbutamol (200 mu g) (n = 20) or allergen inhalation challenge (n = 31). Results: The reproducibility of the methacholine PC20 with this method was high (intraclass correlation coefficient = 0.94), The aver age shift in PC20 after salbutamol was 4.11 doubling concentrations (S D = 1.08). On the basis of these results, a sample size of 12 subjects would be required to demonstrate a 1 doubling concentration differenc e in the bronchoprotective effect of two drugs with a 90% power. The a verage shift in PC20 after allergen was 1.29 doubling concentrations. On the basis of these results sind an estimated SD of 0.96, a sample s ize of 24 subjects would be required to demonstrate that a drug is eff ective in attenuating 50% of allergen-induced airway hyperresponsivene ss with a 90% power: Conclusion: These results confirm the high reprod ucibility of methacholine PC20 measurements in subjects with mild, sta ble asthma and demonstrate its utility in evaluating the effects of an ti-asthma drugs.