What is the schedule for dosing in a methacholine challenge test?

Updated: May 14, 2020
  • Author: Kevin McCarthy, RPFT; Chief Editor: Nader Kamangar, MD, FACP, FCCP, FCCM  more...
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The following list shows the most common schedule of methacholine dosing in use in the United States today. Some labs begin with the lowest strength methacholine solution immediately after baseline. Others experts advocate the use of a diluent stage between baseline and methacholine. This allows identification of a small percentage of individuals who exhibit significant bronchoconstriction in response to the diluent itself, suggestion, or repeated spirometry efforts. Abbreviated protocols that start with higher concentrations of methacholine should be used cautiously, if at all.

Methacholine challenge schedule: After establishing baseline spirometry measurements, the patient inhales five breaths of saline or diluent aerosol and then five breaths of each of the following strengths of aerosolized methacholine in solution: 0.0625 mg/mL, 0.25 mg/mL, 1 mg/mL, 4 mg/mL, and 16 mg/mL.

An alternative longer (10-stage) dosing schedule that may yield a more precise assessment of airway hyperreactivity calls for the patient to inhale five breaths of methacholine aerosol in the following strengths: 0.031 mg/mL, 0.0625 mg/mL, 0.125 mg/mL, 0.25 mg/mL, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, 4 mg/mL, 8 mg/mL, and 16 mg/mL.

The following dosing schedule is approved by the US Food and Drug Administration and also may be used, although the ATS guidelines for methacholine challenge testing recommend one of the two schedules outlined above because the dosing steps are more even: 0.025 mg/mL, 0.25 mg/mL, 2.5 mg/mL, 10 mg/mL, and 25 mg/mL. [15]

Methacholine aerosol is delivered in a standardized fashion by using a dosimeter, a device that applies a 0.6-second burst of compressed air to the nebulizer at the start of the inhalation from FRC to TLC. Subjects should hold their breath for 5 seconds. Spirometry is performed 30-90 seconds after the end of the last breath of each stage of the challenge. Symptoms volunteered by the subject are recorded. The challenge is discontinued when a fall in FEV1 of greater than 20% is observed upon repeat efforts or a final cumulative dose of 188.64 cumulative dose units is received. Administration of a bronchodilator should immediately follow the final postmethacholine assessment.

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