title: Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics.
abstract: Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) = sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 microg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg x mL(-1). MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters. In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log, EC50 were not significantly different between the groups. We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response.
authors.affiliation: Dept of Pulmonary Diseases, University Hospital Rotterdam-Dijkzigt, Erasmus University, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: Overbeek
authors.forename: P R
authors.initials: PR
authors.lastname: Rijnbeek
authors.forename: C
authors.initials: C
authors.lastname: Vons
authors.forename: P G
authors.initials: PG
authors.lastname: Mulder
authors.forename: H C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: J M
authors.initials: JM
authors.lastname: Bogaard
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D016210:Methacholine Chloride; D000068298:Fluticasone