Maximal Airway Response in Adolescents With Long-term Asthma Remission and Persisting Airway Hypersensitivity: FEV1
High-dose methacholine inhalation tests were carried out using a modification of the method described by Chai et al. Briefly, methacholine (Sigma Diagnostics; St. Louis, MO) solutions were prepared at different concentrations (0.075, 0.15, 0.3, 0.625, 1.25, 2.5, 5, 10, 25, 50, 100, 150, and 200 mg/mL) in buffered saline solution (pH 7.4). A Rosenthal-French dosimeter (Laboratory for Applied Immunology; Baltimore, MD), triggered by a solenoid valve set to remain open for 0.6 s, was used to generate the aerosol from a DeVilbiss 646 nebulizer (DeVilbiss Health Care; Somerset, PA), with pressurized air at 20 pounds per square inch. Each subject inhaled five inspiratory capacity breaths of buffered saline solution and increasing concentrations of methacholine at 5-min intervals. This gave an output of 0.009 ± 0.0014 mL (mean ± SD) per inhalation. FEV1 was measured 60 to 90 s after inhalation at each concentration level. The procedure was terminated when the FEV1 level fell to < 50% of the postsaline solution value, or when a maximal response plateau had been established. This was considered to occur if three or more data points at the highest concentrations fell within a 5% response range. An additional 5 or 10 inhalations of the 200 mg/mL solution were taken if the last three data points of a < 50% FEVj fall did not satisfy the above-mentioned criteria. For safety reasons, subjects were given the opportunity to stop the challenge test if they felt too much discomfort. Response, expressed as the percentage fall in FEV1 from the postsaline solution value, was plotted against the log of the concentrations of inhaled metha-choline. The dose-response curves were characterized by their position and maximal response, the former expressed as PC20, which was calculated by log-linear interpolation between two adjacent data points, and the latter defined as the level of maximal response plateau by averaging the consecutive points on the plateau, or as the last data point of the dose-response curve if a plateau could not be obtained.
Parents gave written informed consent for their children to participate in the study. The study protocol was approved by the Hospital Ethics Committee.