Development of a methacholine challenge method to minimize methacholine waste.

BACKGROUND The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine being discarded. OBJECTIVE To develop a method with reduced methacholine waste and to compare it to the standard method. METHODS Twelve subjects with mild, well-controlled asthma volunteered for this investigation. They underwent three methacholine challenges in random order. The first challenge was the conventional 2-min tidal breathing method using 3 mL of doubling concentrations inhaled for 2 min at 5-min intervals. The first modification utilized 1.5 mL of quadrupling concentrations inhaled for 1 min and then 2 min, keeping the time interval constant at 3 min between completion of one inhalation and commencement of the next inhalation. The second modification utilized 1.5 mL of eightfold concentration step-ups inhaled for 30 s, 60 s, and 120 s with a time interval of 3 min between completion of one inhalation and commencement of the next inhalation. For each method, the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was calculated based on a 2-min equivalent-dose inhalation. RESULTS There was no significant difference in the geometric mean PC(20) (1.5 mg/mL, 1.6 mg/mL, and 1.6 mg/mL for the three methods, respectively; p = 0.47). The quadrupling concentration method was preferred because it was less subject to error than the other modification. CONCLUSION The amount of methacholine discarded during a methacholine challenge can be reduced by two thirds by decreasing the volume from 3 to 1.5 mL, and by using quadrupling concentrations inhaled either with quadrupling-dose step-ups, or with doubling-dose step-ups by using sequential 1-min and 2-min inhalations.