Quadrupling dose step-up for methacholine inhalation has been recommended as a time saving measure over the usual doubling method but has not been assessed. We undertook a study to compare doubling and quadrupling concentration step-up using the tidal volume methacholine challenge.
Fifteen asthmatic subjects were recruited to do two methacholine challenges; one with doubling and one with quadrupling concentrations of methacholine; the order of challenges was randomized. Two subjects’ demonstrated a plateau at <20% FEV1 fall and were not analyzed.
The quadrupling methacholine challenge produced: (1) a trend (p = 0.10) towards a higher PC20 (the concentration at which a 20% fall in FEV1 occurred); (2) an increase in the percent fall of FEV1 (30% vs 22%: p = 0.018) at completion; and (3) an increase in dyspnea on the Borg Scale (3.7 vs 2.6: p = 0.037). Two subjects had a greater than 1 doubling concentration (higher with quadrupling) difference between the PC20's of the two regimes; one of these had a positive test with the doubling but a negative test with the quadrupling regime. Three subjects with quadrupling and no subjects with doubling regimes had severe dyspnea (Borg ≥ 5). The quadrupling dosing regime reduced the test by <1 concentration (<2 minutes) on average.
The trend to higher PC20's in the quadrupling regime was expected because of the greater cumulative amount of methacholine inhaled with the doubling method. The larger FEV1 fall and the greater subject discomfort lead us to conclude that the small time saving does not favor the use of quadrupling methacholine concentrations. There are safer documented measures that can be used to shorten the duration of the methacholine challenge including the appropriate choice of a starting concentration and the omission of occasional concentrations when there has been <5% drop in FEV1 from the previous concentration.
The routine use of a quadrupling dose regime for methacholine challenge is not recommended over the standard doubling regime.
Gregory Peters, No Financial Disclosure Information; No Product/Research Disclosure Information