Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma.

Abstract

Inhaled anticholinergic drugs are effective in the treatment of chronic obstructive pulmonary diseases (COPD), of acute asthma, and of some patients with nocturnal asthma. Tiotropium bromide (tiotropium) is a novel anticholinergic agent with a long duration of action and kinetic selectivity for M1- and M3-subtypes of muscarinic receptors. We investigated the duration of protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in 12 male atopic asthmatic volunteers in a double-blind, placebo-controlled study. On four separate occasions 8 to 24 d apart, methacholine PC20 was measured serially for up to 48 h after placebo and after three doses of tiotropium (10, 40, and 80 microg). Each dose of tiotropium produced mild bronchodilatation as measured by an increase in FEV1 of between 5.5 and 11.1% from baseline, that was sustained for 24 h. There was significant dose-dependent protection against methacholine challenge at 2 h of 5.0 +/- 1.1, 7.1 +/- 0.5, and 7.9 +/- 0.7 (mean +/- SEM) doubling doses after 10, 40, and 80 microg respectively, and this persisted for 48 h. There were no adverse effects reported at any dose. The prolonged bronchodilator response and protection against methacholine challenge suggest that tiotropium may be useful in the treatment of COPD and nocturnal asthma and that once-daily dosing may be sufficient.

Tiotropium bromide is effective for severe asthma with noneosinophilic phenotype

“…Tiotropium bromide, a recently developed anticholinergic, is a long-acting bronchodilator with a well-established effectiveness for treating chronic obstructive pulmonary disease [2]. Although some subgroups of asthmatics seem to respond better to anticholinergics, the pathophysiological features of these responders have yet to be established [3,4]. Previous studies that aimed to identify asthma subgroups which respond better to anticholinergics have suggested the following clinical features: patients with nocturnal symptoms, chronic asthma showing concurrent fixed airway obstruction, intrinsic asthma with longer duration of disease and nonatopic asthma [1,5].…”

Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease

“…In vitro studies of isolated guinea pig and human airway have shown that the drug has a very long duration of action and a unique kinetic selectivity for muscarinic (M) 3 and M 1 over M 2 -subtypes of the M receptor [1][2][3]. In early clinical, single-dose studies in chronic obstructive pulmonary disease (COPD) and asthma it was found that tiotropium produced a bronchodilator effect that was sustained for at least 24 h [4][5][6]. Recently published long-term studies demonstrated that 18 mg of tiotropium is a safe and effective bronchodilator, suitable for maintenance therapy in COPD with once-daily dosing [7][8][9].…”

Bronchoprotective Effect of Glycopyrronium Bromide in Patients With Chronic Obstructive Pulmonary Disease

“…Так, между уровнем реактивности бронхов на фоне терапии, т. е. динамикой ПД 20 и изменением симптомов заболевания, определялась существенная корреляционная зависи-мость: r s составил от -0,51 до -0,43 (р ≤ 0,01 во всех случа-ях). Уменьшению выраженности симптомов заболевания и улучшению толерантности к физическим нагрузкам соот-ветствует динамика показателей вопросника САТ: через 3 месяца терапии медиана суммы баллов уменьшилась с 14,8 (11,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)5) до 10,5 (6,5-16,0) балла (р = 0,046).…”

“…С учетом выраженного негативного влияния БГР на течение ХОБЛ воздействие на гиперреактивность дыхательных путей или бронхо-протективный эффект бронходилататоров представляет-ся важной конечной точкой оценки эффективности тера-пии ХОБЛ. В литературе представлены немногочислен-ные данные, подтверждающие бронхопротективный эффект различных антихолинергических препаратов у больных бронхиальной астмой [16,17]. Кроме того, авто-рами было проведено исследование, демонстрирующее бронхопротективный эффект тиотропия бромида и вари-абельность терапевтического ответа у больных средне-тяжелой ХОБЛ в зависимости от уровня реактивности бронхов [9].…”