Methacholine challenge: test-shortening procedures
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Updated: Oct 3, 2026

Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
D W Cockcroft1, D D Marciniuk, T S Hurst
1Division of Respiratory Medicine, Royal University Hospital, Saskatoon, Canada. cockcroft@sask.usask.ca
Study Objectives:
Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method.
Design:
Retrospective chart review.
Setting:
Tertiary-care university clinical pulmonary function laboratory.
Patients:
One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge.
Intervention:
Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures.
Measurements And Results:
There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up.
Conclusions:
The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.
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