Deep inhalation has a bronchodilating and bronchoprotective effect, particularly in subjects who are normal or who have mild asthma. We have anecdotally observed that during bronchoprovocation testing using the five breath dosimeter method, the standard full inhalations compared to sub-maximal inhalations may reduce or prevent the response to methacholine. We therefore compared the standard maximal inhalation five-breath dosimeter method with a sub-maximal inhalation dosimeter challenge to determine the effect on methacholine PC20.
Sixteen subjects with asthma and a tidal breathing PC20 < 8 mg/mL performed two methacholine challenges in random order. The two methods tested were the conventional five-breath dosimeter method and a modified five-breath dosimeter challenge in which methacholine inhalations were done to about 50-60% below total lung capacity (TLC).
The standard methacholine challenge PC20 was almost twice that obtained with the modified sub-maximal inhalation method (geometric mean PC20 5.2 mg/mL versus 2.8 mg/mL for the standard and sub-maximal inhalation method respectively, p = 0.0216). In the five patients with the mildest airway hyper-responsiveness, there was a 2.5- to 14-fold difference in PC20 between methods. The standard (full TLC) PC20s were falsely negative (> 16 mg/mL) in these five subjects with current asthma, four of whom required inhaled corticosteroids.
A sub-maximal inhalation dosimeter methacholine challenge results in a significantly lower PC20 compared to the standard five-breath dosimeter method. This effect is limited to the mildly responsive group and is probably due to the bronchoprotective effect of the deep inhalation.
Our findings demonstrate that false negative methacholine challenges may occur in patients with mild airway hyper-responsive using the five-breath dosimeter method.
D.C. Todd, None.