Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma

Background The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC₂₀). The dose-response effect of inhaled corticosteroids (ICS) on PC₂₀ has been inconsistent and within-patient variability of PC ₂₀ is not well established. Objective To determine the effect of high- vs low-dose ICS on PC₂₀ and within-patient variability in those with repeated measurements of PC₂₀. Methods A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC₂₀ of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC₂₀. In addition, the variability of PC₂₀ was assessed in participants who underwent 2 or 3 PC ₂₀ measurements on the same dose of ICS (n = 27) over a 4-week interval. Results Because there was a significant period effect, dose comparison of the change in PC₂₀ was assessed in the first treatment period. There was no significant difference in the change in PC₂₀ for high- vs low-dose ICS (39% vs 30% increase, respectively; P =.87). The within- and between-participant variances for log PC₂₀ were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC₂₀ in those with repeated measurements. Conclusion The effect of ICS on PC₂₀ is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC₂₀ is large. A lack of precise measurements should be taken into account when interpreting any change in PC₂₀.