Duration of bronchoprotection of the long-acting muscarinic antagonists tiotropium & glycopyrronium against methacholine-induced bronchoconstriction in mild asthmatics

Respir Med. 2016 Sep;118:96-101. doi: 10.1016/j.rmed.2016.07.017. Epub 2016 Jul 30.


The duration of bronchoprotection against methacholine-induced bronchoconstriction by long-acting muscarinic antagonists (LAMA's) in asthmatics and whether these drugs differ in their pharmacodynamic properties remain to be determined. The most recent published guidelines for methacholine challenge testing (MCT) suggest that LAMA's should be abstained from for 48 h prior to testing, perhaps one week in the case of tiotropium. The objectives were to determine and compare the duration of protection of a single dose of two different LAMA's, tiotropium and glycopyrronium, against methacholine-induced bronchoconstriction. Thirteen mild-to-moderate asthmatics [with a forced expiratory volume in 1 s (FEV1) > 65% of predicted and a baseline methacholine provocation concentration causing a 20% reduction in FEV1 (PC20) ≤ 8 mg/mL] completed this double-blind, double-dummy, crossover study. Methacholine challenges were performed before treatment (5 μg tiotropium or 50 μg glycopyrronium) and at 1, 24, 48, 72, 96 and 168 h post-treatment. The minimum duration between treatment administration was 11 days. Both drugs provided significant bronchoprotection, each producing greater than a 16-fold increase in mean PC20 by 1 h. Tiotropium still provided statistically significant protection at 7 days (p = 0.0282) while glycopyrronium provided bronchoprotection until day 7 (p = 0.0590). Tiotropium provided statistically superior bronchoprotection at 24 and 72 h compared to glycopyrronium. To minimize the occurrence of false negatives, MCT guidelines should be updated to recommend a minimum one-week abstinence period from all LAMA's. MCT was also able to statistically differentiate between tiotropium and glycopyrronium with respect to the degree and duration of bronchoprotection provided by each.

Clinical trial registration number: NCT02622243.

Keywords: Bronchoprotection; Glycopyrronium; Long acting muscarinic antagonists; Methacholine challenge testing; Tiotropium.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy*
  • Asthma / prevention & control
  • Bronchial Provocation Tests / methods*
  • Bronchoconstriction / drug effects*
  • Cholinergic Antagonists / therapeutic use
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Glycopyrrolate / administration & dosage
  • Glycopyrrolate / pharmacology*
  • Guidelines as Topic
  • Humans
  • Male
  • Methacholine Chloride / adverse effects*
  • Muscarinic Antagonists / therapeutic use
  • Tiotropium Bromide / administration & dosage
  • Tiotropium Bromide / pharmacology*


  • Cholinergic Antagonists
  • Muscarinic Antagonists
  • Methacholine Chloride
  • Glycopyrrolate
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT02622243