Dosimeter methacholine challenge: comparison of maximal versus submaximal inhalations

J Allergy Clin Immunol. 2004 Sep;114(3):517-9. doi: 10.1016/j.jaci.2004.06.016.


Background: Deep inhalation has bronchodilating and bronchoprotective effects, particularly in subjects who are normal or have mild airway hyperresponsiveness (AHR). We have anecdotally observed that the 5 breath to total lung capacity (TLC) dosimeter method reduced the response to methacholine in some subjects with mild AHR.

Objective: To compare prospectively submaximal inhalations with TLC inhalations during the dosimeter methacholine challenge.

Methods: Sixteen subjects with asthma and a methacholine PC 20 <8 mg/mL performed 2 methacholine challenges in random order; the standard dosimeter method was compared with a modified dosimeter challenge in which methacholine inhalations were performed to approximately 50% to 60% below TLC.

Results: The standard methacholine challenge PC 20 was almost twice that obtained with the modified submaximal inhalation method (geometric mean PC 20, 5.2 mg/mL vs 2.8 mg/mL, respectively; P = 0.0216). In the 5 subjects with the mildest AHR, there was a 2.5-fold to 14-fold difference in PC 20 between methods. The standard (full TLC) PC 20 s were falsely negative (>16 mg/mL) in these 5 subjects with current asthma, 4 of whom required inhaled corticosteroids.

Conclusion: A submaximal inhalation dosimeter methacholine challenge results in a significantly lower PC 20 compared with the standard 5-breath dosimeter method. This effect is limited to the mildly responsive group, probably because of the bronchoprotective effect of the deep inhalation during the standard method, and results in false-negative tests in some subjects.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Asthma / diagnosis*
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents / administration & dosage*
  • False Negative Reactions
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Methacholine Chloride / administration & dosage*
  • Middle Aged
  • Nebulizers and Vaporizers*
  • Spirometry


  • Bronchoconstrictor Agents
  • Methacholine Chloride