Study objectives: Recent American Thoracic Society guidelines recommend two different methods of methacholine challenge testing: the 2-min tidal breathing method with twofold increases in concentration, and the five-breath dosimeter method with fourfold increases. Since the tidal breathing method delivers more methacholine to the mouthpiece, we hypothesized that the provocative concentration of methacholine required to decrease FEV(1) by 20% (PC(20)) would be lower than with the dosimeter method.
Design: Twelve subjects 18 to 45 years old with stable asthma were selected on the basis of a screening PC(20) (by tidal breathing) of < 1 mg/mL, 1 to 4 mg/mL, or 4 to 16 mg/mL (4 subjects in each concentration range). On subsequent visits within a 7-day period, methacholine challenge testing with tidal breathing or dosimeter were performed on separate days, in a randomized crossover manner.
Results: The geometric mean PC(20) was 1.8 mg/mL (95% confidence interval [CI], 0.7 to 4.3) after tidal breathing and 1.6 mg/mL (95% CI, 0.7 to 3.7) after dosimeter (p = 0.2). There was no significant difference between the screening PC(20) and the PC(20) obtained by either method on randomized study days. The maximum decrease in FEV(1) from diluent baseline after the last concentration was 27.8% (range, 20 to 50%) during tidal breathing and 27.9% (range, 16 to 47%) during the dosimeter method (p = 0.35).
Conclusions: Both methods give similar results. Fourfold increases in methacholine concentration with the dosimeter method are as safe as twofold increases with the tidal breathing method.