Chest
Volume 127, Issue 3, March 2005, Pages 839-844
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Clinical Investigations: Asthma
Methacholine Challenge: Comparison of Two Methods

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Background

Guidelines for the 2-min tidal-breathing and the five-breath dosimeter methods for methacholine challenge have recently been published by the American Thoracic Society (ATS). Although subjects are exposed to twice as much aerosol at any given concentration during the tidal-breathing method compared to the dosimeter method, they were thought to give equivalent results

Objective

To compare the 2-min tidal-breathing and the five-breath dosimeter methacholine challenges

Setting

Tertiary care university-based bronchoprovocation laboratory

Patients

Forty subjects with currently symptomatic asthma

Interventions

The two methacholine tests were done in random order on separate days at the same time of day at 1-to 7-day intervals

Results

The dosimeter provocation concentration of methacholine causing a 20% fall in FEV1 (PC20) was almost twice that of the tidal-breathing PC20: 2.4 mg/mL vs 1.3 mg/mL (paired t test, p < 0.00005). The difference was greater in those with mild airway hyperresponsiveness (AHR) [PC20 > 1.0 mg/mL; 3.2-fold] compared to those with moderate AHR (PC20 < 1.0 mg/mL; 1.6-fold) [p = 0.04]. Three subjects with mild asthma and mild AHR (tidal-breathing PC20, 1.9 to 4.3 mg/mL) had a nonmeasurable PC20 (> 32 mg/mL) with the dosimeter

Conclusions

The tidal-breathing method, which exposes the subject to twice as much aerosol at each concentration, produced approximately twice the response. The total lung capacity maneuvers with breathhold during the dosimeter method may inhibit the response in some patients with asthma

Section snippets

Subjects

Subjects with asthma6 were recruited from the respiratory clinic at the Royal University Hospital and from advertisements. Inclusion criteria included an FEV1 ≥ 65% predicted and a tidal-breathing provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) < 16 mg/mL. The study was approved by the University of Saskatchewan Ethics Committee, and signed informed consent was obtained.

Study Design

Subjects (n = 40) attended the laboratory on 2 days at the same time of day within 1 week. Inhaled

Results

Forty subjects meeting the inclusion criteria of an FEV1 ≥ 65% and a tidal-breathing PC20 < 16 mg/mL completed the investigation without adverse events. A forty-first subject failed to return for the second methacholine challenge and was not included in the analysis. Demographics of the 40 subjects who completed both challenges are given in Table 1

Individual data points for the two methacholine challenges are compared in Figure 1. Three subjects with tidal-breathing PC20 values ranging from 1.9

Discussion

We have compared the two standardized methacholine challenges with the only differences in protocol being the method of aerosol generation and the method of inhalation. In the entire group, the geometric mean dosimeter PC20 was almost twice that of the tidal-breathing PC20. The discrepancy was greater (2.1-fold) in those with tidal-breathing PC20 > 1.0 mg/mL and less (1.6-fold) in those with tidal-breathing PC20 < 1 mg/mL. Adding to this discrepancy were an additional three subjects with

Acknowledgments

The authors thank Jacquie Bramley for assisting in the preparation of this article.

References (20)

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Dr. Cockcroft is the Ferguson Professor of Respiratory Medicine

Supported by a grant from Methapharm Inc

Supported by the Lung Association of Saskatchewan

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