Methacholine Challenge: Comparison of Airway Responsiveness Produced by a Vibrating Mesh Nebulizer Versus a Jet Nebulizer.

BACKGROUND: The latest methacholine challenge testing (MCT) guidelines published by the European Respiratory Society recommend the characterization of nebulizers before their use in clinics and research. Such investigations are necessary for accurately determining the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) delivered by a given device. The standard English Wright (Wright) jet nebulizer recommended in the 1999 guidelines by the American Thoracic Society has become difficult to obtain and possesses some characteristics that complicate the calculation of dose delivery from this device (e.g. evaporation). Our objective was to determine if the Aerogen® Solo (Solo) vibrating mesh nebulizer provides similar methacholine challenge test results compared to the currently used Wright jet nebulizer. METHODS: Sixty mild-to-moderate asthmatics were studied across three research sites in a randomized crossover study. Both methacholine challenges were completed at least 24 hours apart within a 2-week period. Testing with the Wright device was performed as per the 2-minute tidal breathing protocol. The Solo study arm followed the same procedure except for a shorter inhalation time of 1 minute. The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) and the methacholine PD20 were calculated following each methacholine challenge. RESULTS: The geometric mean methacholine PC20 values for the Solo and the Wright differed statistically (0.65 mg/mL vs. 2.58 mg/mL, respectively, p < 0.00001) and clinically. Between-nebulizer geometric mean methacholine PD20 results are comparable by clinical standards [81.7 µg (Solo) vs. 64.7 µg (Wright)], although the slight difference in dose was statistically significant (p = 0.018). CONCLUSIONS: The comparability of PD20 values between the Solo and the Wright validates the importance of reporting airway responsiveness to methacholine in terms of dose and not concentration, as stressed in the latest testing guidelines. This finding along with several benefits associated with the Solo make it a promising nebulizer for performing MCT.

Comparison of the provocative concentration of methacholine causing a 20% fall in FEV1 between the AeroEclipse II breath-actuated nebulizer and the wright nebulizer in adult subjects with asthma.

RATIONALE: The American Thoracic Society guidelines for methacholine testing for the diagnosis of asthma recommends the 2-minute tidal breathing protocol with the Wright nebulizer, which produces more aerosol than required, generates a small particle size, and requires cleaning between tests. OBJECTIVES: To evaluate methacholine testing using a disposable, breath-actuated AeroEclipse II, which produces aerosol during inspiration and was developed for single-patient use. METHODS: Forty-six adult subjects with asthma (19 men), aged 27.3 (SD, 9.5) years, with FEV1 98.5 (SD, 18.1) % predicted participated in a randomized, crossover, observational study. Subjects were first screened using the Wright nebulizer, then assigned to 2 minutes of tidal breathing from the Wright or 20 seconds of tidal breathing from the AeroEclipse nebulizer on 2 separate days, in random order. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) values were calculated by linear interpolation of log dose-versus-response curves, log-transformed, and compared using paired Student t test and Pearson correlation. MEASUREMENTS AND MAIN RESULTS: The 38 subjects demonstrating reproducible PC20 measurements of within 1.5 doubling concentrations were included in the comparison. The geometric mean methacholine PC20 measured with the AeroEclipse nebulizer was approximately 1 doubling concentration lower than the geometric mean methacholine PC20 of the Wright nebulizer (P < 0.05). The Pearson correlation coefficient between the two nebulizers was 0.86 (P < 0.05). CONCLUSIONS: The PC20 measurements using the two nebulizers were highly correlated; however, the PC20 determined with the AeroEclipse nebulizer was significantly lower than those determined using the Wright nebulizer. Clinical trial registered with www.clinicaltrials.gov (NCT 01919424).