Regular Use Tiotropium and Tolerance to Bronchoprotection in Mild Asthma

Daily Dosing of Tiotropium and Tolerance to Bronchoprotection Against Methacholine Challenge

The study will assess if regular use of tiotropium (i.e. daily) results in loss of bronchoprotection against methacholine induced bronchoconstriction in those with mild asthma.

A single dose of an inhaled muscarinic antagonist will protect against methacholine induced bronchoconstriction and increase the dose of methacholine required to cause bronchoconstriction about 4 doubling doses. Beta agonist bronchodilators also shift the dose response curve to the right but the protection against methacholine induced bronchoconstriction is lost (i.e. tolerance develops) with regular use. This study will determine if bronchoprotection is lost following regular use of tiotropium.

This will be a randomized, double-blind placebo controlled study to assess the development of tolerance following regular use of tiotroium in a population of mild asthmatics.

Tiotropium will be administered at the clinically recommended dose (5mcg/day) for a total of 8 days. Methacholine challenges will be performed at baseline (pre-treatment), at one hour post first dose and on day 8, one hour after the final dose. The same will dosing schedule and assessments will occur with an identical placebo inhaler.

Inclusion Criteria:

• diagnosis of asthma
• asthma is currently well controlled using only occasional bronchodilators
• baseline lung function (FEV1) is greater than 65% of the predicted value
• exhibit bronchoconstriction to inhaled methacholine at a dose of 200mcg or less

Exclusion Criteria:

• women who are pregnant or breastfeeding.
• diagnosis of another lung condition or medical condition that would pose a risk to the participant if enrolled in the study
• current smokers of nicotine products (e.g., cigarettes).
• users of cannabis or other inhaled recreational products (e.g., e-cigarettes or other vaping products) on a daily basis
• respiratory infection within 4 weeks of entering the study
• use of any anticholinergic agent within 30 days prior to the beginning of the study (e.g., ipratropium or the study treatment tiotropium).
• known hypersensitivity to tiotropium bromide or components of tiotropium formulation (e.g., benzalkonium chloride), to atropine or its derivatives.