Asthma diagnosis and treatment
Dosimeter methacholine challenge: Comparison of maximal versus submaximal inhalations

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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 PC20 <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 PC20 was almost twice that obtained with the modified submaximal inhalation method (geometric mean PC20, 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 PC20 between methods. The standard (full TLC) PC20s 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 PC20 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.

Section snippets

Subjects

Sixteen subjects with asthma, FEV1 ≥65% predicted, and a methacholine PC20 <8 mg/mL (range, 0.28-5.5) by the tidal breathing method11 were studied. The study was approved by the University of Saskatchewan Ethics Committee, and informed signed consent was obtained.

Methacholine challenge methods

Standard 5-breath dosimeter methacholine challenge The standard dosimeter methacholine challenge was performed as outlined by the ATS5 by using a DeVilbiss 646 Nebulizer (Sunrise Medical HHG, Somerset, Pa) and the Micro-Dosimeter (S&M

Results

Sixteen subjects completed the study with no adverse events (Table I). On average, subjects' submaximal inhalation volume was 43.3% (range, 24% to 55%) of their inspiratory capacity above functional residual capacity.

Results are shown in Fig 1. The geometric mean PC20 for the submaximal and full TLC maneuvers were 2.8 mg/mL (95% CI, 1.6-4.9) and 5.2 mg/mL (95% CI, 1.9-13.9), respectively (P = .0216). This represents almost a 2-fold difference between the 2 methods. The 5 subjects with the mildest

Discussion

This study demonstrates that the TLC maneuvers (and breath hold at TLC) during methacholine inhalations inhibit the bronchoconstriction in some subjects with mild AHR. This was observed in 5 of 16 (31%) subjects; these five had the mildest AHR (ie, highest PC20), yet all had current asthma, and 4 of the 5 required inhaled corticosteroids for control. Thus we observed a significant number of false-negative methacholine inhalation tests in subjects with mild AHR, the range in which diagnostic

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