Early protective effects of tiotropium bromide in patients with airways hyperresponsiveness

Eur Rev Med Pharmacol Sci. 2004 Nov-Dec;8(6):259-64.


Tiotropium is an anticholinergic drug for Chronic Obstructive Pulmonary Disease (COPD) patients, with a peak bronchodilator effect observed after 1.5 to 2 hours and a long duration of action. The aim of our study was to quantify the early protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in asthmatic patients with airway hyperresponsiveness. Ten subjects (7M, 3F), with history of asthma and a baseline FEV(1) (Forced Expiratory Volume 1 sec) > 80% of predicted, were enrolled in the study. Each subject performed three methacholine challenge tests, with a time of 72 hours between each challenge: Test A (methacholine challenge test), and successively, at random, Test B (methacholine 30 minutes after inhaled Tiotropium) and Test C (methacholine 30 minutes after inhaled Placebo). PD20 (Provocative Dose causing a 20% decrease in basal FEV(1) value) was reached to assess airways responsiveness. All the subjects showed in Test A and Test C a mild-moderate airway hyperresponsiveness. In Test B no PD20 was reached at the inhaled maximum dose of methacholine (1600 microg), FEV(1) before tiotropium was 88.6% +/- 4.4, beginning test FEV(1) 92.6% +/- 4.3, end test FEV(1) 85.7% +/- 4.6. Inhaled tiotropium bromide 18 microg has shown a protective effect against methacholine-induced bronchoconstriction in asthmatic patients, with mild-moderate airways hyperresponsiveness, already 30 minutes after its administration.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Asthma / drug therapy
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Hyperreactivity / prevention & control
  • Bronchial Provocation Tests
  • Bronchoconstriction / drug effects
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Cholinergic Antagonists / administration & dosage
  • Cholinergic Antagonists / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Methacholine Chloride
  • Scopolamine Derivatives / administration & dosage
  • Scopolamine Derivatives / therapeutic use*
  • Tiotropium Bromide


  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Scopolamine Derivatives
  • Methacholine Chloride
  • Tiotropium Bromide