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.
To compare the 2-min tidal-breathing and the five-breath dosimeter methacholine challenges.
Tertiary care university-based bronchoprovocation laboratory.
Forty subjects with currently symptomatic asthma.
The two methacholine tests were done in random order on separate days at the same time of day at 1- to 7-day intervals.
The dosimeter provocation concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was almost twice that of the tidal-breathing PC(20): 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) [PC(20) > 1.0 mg/mL; 3.2-fold] compared to those with moderate AHR (PC(20) < 1.0 mg/mL; 1.6-fold) [p = 0.04]. Three subjects with mild asthma and mild AHR (tidal-breathing PC(20), 1.9 to 4.3 mg/mL) had a nonmeasurable PC(20) (> 32 mg/mL) with the dosimeter.
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.
Chest 03/2005; 127(3):839-44. DOI:10.1378/chest.127.3.839 · 7.13 Impact Factor
We have observed that dosimeter-run nebulizers have a much smaller output when manually activated than when breath activated; however, this has not been adequately investigated.
To evaluate the effect of different calibration methods on nebulizer output.
Six healthy subjects performed all calibrations. The nebulizers were operated by 2 different dosimeters and were calibrated to produce 9 microL per actuation by breath activation followed by exhalation to the room. The nebulizers were then operated at these identical settings, and the output determined in 3 ways: (1) breath activation followed by exhalation to the room, (2) breath activation with exhalation into the nebulizer, and (3) manual activation (with no subject using the nebulizer). These 3 methods were termed regular, rebreathe, and manual, respectively.
There was a large and statistically significant difference in nebulizer output among the 3 methods. The measured rebreathe outputs (5.6 and 5.7 microL per actuation) were approximately two thirds and the manual outputs (3.2 and 3.9 microL per actuation) were approximately one third of the regular calibration outputs (8.6 and 8.9 microL per actuation); the 2 values are for the 2 dosimeters. The results were highly statistically significant (P < .001).
The method by which a nebulizer-dosimeter system is calibrated results in different nebulizer outputs. This has a high likelihood of influencing the concentration of methacholine causing a 20% decrease in volume in the first second of forced expiration.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2005; 94(1):45-7. DOI:10.1016/S1081-1206(10)61284-7 · 2.75 Impact Factor
Chest 10/2004; 126(4_MeetingAbstracts). DOI:10.1378/chest.126.4_MeetingAbstracts.744S · 7.13 Impact Factor
The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine being discarded.
To develop a method with reduced methacholine waste and to compare it to the standard method.
Twelve subjects with mild, well-controlled asthma volunteered for this investigation. They underwent three methacholine challenges in random order. The first challenge was the conventional 2-min tidal breathing method using 3 mL of doubling concentrations inhaled for 2 min at 5-min intervals. The first modification utilized 1.5 mL of quadrupling concentrations inhaled for 1 min and then 2 min, keeping the time interval constant at 3 min between completion of one inhalation and commencement of the next inhalation. The second modification utilized 1.5 mL of eightfold concentration step-ups inhaled for 30 s, 60 s, and 120 s with a time interval of 3 min between completion of one inhalation and commencement of the next inhalation. For each method, the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was calculated based on a 2-min equivalent-dose inhalation.
There was no significant difference in the geometric mean PC(20) (1.5 mg/mL, 1.6 mg/mL, and 1.6 mg/mL for the three methods, respectively; p = 0.47). The quadrupling concentration method was preferred because it was less subject to error than the other modification.
The amount of methacholine discarded during a methacholine challenge can be reduced by two thirds by decreasing the volume from 3 to 1.5 mL, and by using quadrupling concentrations inhaled either with quadrupling-dose step-ups, or with doubling-dose step-ups by using sequential 1-min and 2-min inhalations.
Chest 11/2003; 124(4):1522-5. DOI:10.1378/chest.124.4.1522 · 7.13 Impact Factor