The utility of methacholine airway responsiveness measurements in evaluating anti-asthma drugs

Abstract

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 evaluating anti-asthma medications, both in terms of a bronchoprotective effect and the ability to attenuate allergen-induced methacholine airway hyperresponsiveness. Methods: Methacholine airway responsiveness was measured as PC 20 on two occasions (separated by 35 ± 17 days, mean ± SD) in 40 subjects with mild, stable asthma. Additional subjects had PC 20 measurements made before and after administration of either inhaled salbutamol (200 μg) ( n = 20) or allergen inhalation challenge ( n = 31). Results: The reproducibility of the methacholine PC 20 with this method was high (intraclass correlation coefficient = 0.94). The average shift in PC 20 after salbutamol was 4.11 doubling concentrations (SD = 1.08). On the basis of these results, a sample size of 12 subjects would be required to demonstrate a 1 doubling concentration difference in the bronchoprotective effect of two drugs with a 90% power. The average shift in PC 20 after allergen was 1.29 doubling concentrations. On the basis of these results and an estimated SD of 0.96, a sample size of 24 subjects would be required to demonstrate that a drug is effective in attenuating 50% of allergen-induced airway hyperresponsiveness with a 90% power. Conclusion: These results confirm the high reproducibility of methacholine PC 20 measurements in subjects with mild, stable asthma and demonstrate its utility in evaluating the effects of anti-asthma drugs. (J Allergy Clin Immunol 1998;101:342-8.)