The Bronchial Response, but not the Pulmonary Response to Inhaled Methacholine Is Dependent on the Aerosol Deposition Pattern: Material and Methods
Five female and three male subjects (mean age, 34 ±8 years) with proved bronchial hyperresponsiveness to inhaled methacholine participated in the study. The patients had a clinical diagnosis of bronchial asthma, and their baseline value of forced expiratory volume in 1 s (FEVi) was at least 80 percent of predicted normal value, and the upper limit of the interstudy day variability in the baseline value of specific airway conductance (sGaw) was set to 15 percent, to allow inclusion to the study. The patients were not receiving any regular treatment with inhaled or oral glucocorticosteroids, and inhaled B-agonists were allowed on an “as required” basis, except for the last 24 h prior to the experiments. Subjects with respiratory tract infections within the last 3 weeks preceding the experiments were excluded from the study, and all subjects denied regular tobacco smoking. Approval of the study was obtained from the Ethics Committee at the University of Uppsala. canadian neighbor pharmacy online
Titration of Methacholine: To titrate the individual dose of methacholine required to induce a significant airway response, increasing doses of methacholine dissolved in saline solution to a final volume of 3 ml were nebulized by means of a jet nebulizer (Pari Inhalierboy, Germany; mass median aerodynamic diameter [MMAD] «9 Mm)- Each aerosol was inhaled for 3 min during tidal breathing, and the airway responses were immediately recorded with a constant volume body plethysmograph (see below). A decrease of at least 50 percent from the baseline sGaw value (PC50Gaw) was to be attained, and if an insufficient decrease in sGaw was obtained after the initial dose, successively doubled doses of methacholine were inhaled 3 min after the previous one. The aerosols were given in a nonrandomized way, and a single dose of methacholine was deposited on the central airway mucosa within 3 weeks after the titration of methacholine. The radio-labeled aerosol, composed of methacholine, Technetium” diethylenetriamine-pentaacetic acid (“mTc-DTPA), and saline solution, was formed by the same nebulizer used in the titration study.