Lack of tachyphylaxis to methacholine at 24 h

To examine for tachyphylaxis to methacholine at 24 h and to use these data to assess the repeatability of the provocative concentration of a substance causing a 20% fall in FEV1 (PC20) for methacholine and to obtain statistical power calculations.

Retrospective review of four double-blind, placebo-controlled studies with two methacholine PC20 values measured at 24-h intervals.

Tertiary university hospital bronchoprovocation laboratory.

Thirty-two subjects with mild-to-moderate well-controlled asthma.

The placebo arms of the four studies were examined.

Methacholine PC20 (using 2-min tidal breathing method) initial determination and repeat testing at 24 h.

The geometric mean PC20 values were 1.57 mg/mL (95% confidence interval [CI], 1.0 to 2.4 mg/mL) and 1.62 mg/mL (95% CI, 1.0 to 2.6 mg/mL NSD; p = 0.64). The mean absolute difference between the two measurements was < 0.4 doubling concentrations, and 31 of 32 measurements had both values within one doubling concentration. These data provide a statistical power of 92% for 10 subjects to show a one-half concentration deltaPC20 and a mean power of 99 +/- 1% to show a one-concentration deltaPC20.

There is no evidence for methacholine tachyphylaxis at 24 h in subjects with asthma. At 24 h, the average repeatability was well within a one-half concentration change, and individually 31 of 32 measurements (97%) were within one doubling concentration.