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Development of a Methacholine Challenge Method to Minimize Methacholine Waste^*

^* From the Division of Respiratory Medicine, Department of Medicine, University of Saskatchewan, Royal University Hospital, Saskatoon, Canada.

Correspondence to: Donald W. Cockcroft, MD, FCCP, Division of Respiratory Medicine, University of Saskatchewan, Ellis Hall, Room 551, Fifth Floor, Saskatoon, SK S7N 0W8, Canada; e-mail: cockcroft{at}sask.usask.ca

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 FEV₁ (PC₂₀) was calculated based on a 2-min equivalent-dose inhalation.

Results: There was no significant difference in the geometric mean PC₂₀ (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.

Key Words: airway responsiveness • asthma • methacholine • provocative concentration causing a 20% fall in FEV₁

This article has been cited by other articles:

				A. Jantikar, S. Sewlikar, B. Brashier, M. Maganji, T. Bal, S. Salvi, D. W. Cockcroft, and B. E. Davis At Least Three FEV1 Blows Are Required at Each Time Point During the Assessment of Bronchial Hyperresponsiveness Chest, July 1, 2005; 128(1): 469 - 470. [Full Text] [PDF]