Tiotropium in patients with moderate COPD naive to maintenance therapy: a randomised placebo-controlled trial

Abstract

Background:The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated. However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).Aims:To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.Methods:A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy–naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.Results:A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)). Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0–3h) at week 24 (primary endpoint): 0.19 vs. −0.03 l (least-squares mean difference 0.23 l, P<0.001). FVC AUC0–3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001). Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS). Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24. The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.Conclusions:Tiotropium improved lung function and patient-reported outcomes in maintenance therapy–naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early.

Downregulation of the cough reflex by aclidinium and tiotropium in awake and anesthetized rabbits

“…Apart from the study by Birrell et al [17] on guinea pigs, there are a few other investigations on the antitussive effects of tiotropium both in animal species [44] and patients [12,13,16,18,19]. Recently, at variance with previous and present results, a lack of tiotropium antitussive effects on ozone-induced hypertussive responses in rabbits has been reported [7].…”

“…The diameter of the droplets ranged from 0.5 to 8 mm and the nebulizer output was always set at 1 mL/min. The opening of the tracheal cannula, through which the rabbits were spontaneously breathing, was exposed to a steady stream of the nebulized MCh solution for 30 s. In preliminary trials (two rabbits), MCh was delivered at increasing concentrations (8,16 and 32 mg/mL) as previously reported [30] to select the dose able to induce a submaximal increase of R L . The selected dose was 16 mg/mL.…”

Evaluation of physical activity in patients with chronic obstructive pulmonary disease: recommendations of European Respiratory Society

“…В нерандо мизированном открытом исследовании (n = 23) ис пользовался длительно действующий β агонист [150], тогда как в другое исследование был включен рет роспективный анализ подгрупп [151]. В 2 рандоми зированных плацебо контролируемых многоцент ровых исследованиях не установлено изменений ФА на фоне терапии длительно действующим бронходи лататором [149,152]. Остается неизвестным, можно ли при бронхолитической терапии, при которой, как известно, повышается переносимость физических нагрузок, улучшить ФА больных ХОБЛ или пред отвратить ее снижение с течением времени.…”

CTS position statement: Pharmacotherapy in patients with COPD—An update

“…We suggest the use of a treatment with an inhaled longacting bronchodilator(s), i.e. LAMA, LABA, or LAMA plus LABA dual therapy, to improve physical activity levels in stable COPD patients 30,43,[77][78][79][80] (Grade 2A). 4.…”