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https://www.readbyqxmd.com/read/29664681/effect-of-bronchodilation-and-exercise-training-with-behavior-modification-on-exercise-tolerance-and-downstream-effects-on-symptoms-and-physical-activity-in-copd
#1
Thierry Troosters, François Maltais, Nancy Leidy, Kim L Lavoie, Maria Sedeno, Wim Janssens, Judith Garcia-Aymerich, Damijan Erzen, Dorothy De Sousa, Lawrence Korducki, Alan Hamilton, Jean Bourbeau
RATIONALE: Bronchodilation and exercise training (ExT) improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD); however, behavior modification is required to impact on daily physical activity (PA). OBJECTIVES: To assess whether tiotropium/olodaterol, ±ExT, would improve exercise endurance time (EET) and PA compared with placebo in patients participating in a self-management behavior-modification (SMBM) program. METHODS: A 12-week, randomized, partially double-blind, placebo-controlled, parallel-group trial in patients with COPD (PHYSACTO®; NCT02085161)...
April 17, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29605624/tiotropium-and-olodaterol-in-the-prevention-of-chronic-obstructive-pulmonary-disease-exacerbations-dynagito-a-double-blind-randomised-parallel-group-active-controlled-trial
#2
Peter M A Calverley, Antonio R Anzueto, Kerstine Carter, Lars Grönke, Christoph Hallmann, Christine Jenkins, Jadwiga Wedzicha, Klaus F Rabe
BACKGROUND: Combinations of long-acting bronchodilators are recommended to reduce the rate of chronic obstructive pulmonary disease (COPD) exacerbations. It is unclear whether combining olodaterol, a long-acting beta-agonist, with tiotropium, a long-acting anti-muscarinic, reduces the rate of exacerbations compared with tiotropium alone. METHODS: This 52-week, double-blind, randomised, parallel-group, active-controlled trial randomly assigned (1:1) patients with COPD with a history of exacerbations using a randomised block design to receive tiotropium-olodaterol 5 μg-5 μg or tiotropium 5 μg once daily...
March 28, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29582435/combining-long-acting-bronchodilators-with-different-mechanisms-of-action-a-pharmacological-approach-to-optimize-bronchodilation-of-equine-airways
#3
L Calzetta, P Rogliani, E Pistocchini, M Mattei, G Cito, P Alfonsi, C Page, M G Matera
The ultra long-acting β2 -adrenoceptor agonist olodaterol plus the ultra long-acting muscarinic antagonist tiotropium bromide are known to relax equine airways. In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration-Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combination (1:1)...
March 26, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29439648/effect-of-12-weeks-of-once-daily-tiotropium-olodaterol-on-exercise-endurance-during-constant-work-rate-cycling-and-endurance-shuttle-walking-in-chronic-obstructive-pulmonary-disease
#4
François Maltais, Denis O'Donnell, Juan Bautista Gáldiz Iturri, Anne-Marie Kirsten, Dave Singh, Alan Hamilton, Kay Tetzlaff, Yihua Zhao, Richard Casaburi
BACKGROUND: The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment. METHODS: The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29355547/%C3%AE-blockers-in-copd-a-cohort-study-from-the-tonado-research-program
#5
François Maltais, Roland Buhl, Andrea Koch, Valeria C Amatto, Jim Reid, Lars Grönke, Ulrich Bothner, Florian Voß, Lorcan McGarvey, Gary T Ferguson
BACKGROUND: Cardiovascular disease is a frequent comorbidity in patients with COPD. Many physicians, particularly pulmonologists, are reluctant to use β-adrenoceptor blocking agents (β-blockers) in patients with COPD, despite their proven effectiveness in preventing cardiovascular events. METHODS: The large (5,162 patients) phase III TONADO 1 and 2 studies assessed lung function and patient-reported outcomes in patients with moderate to very severe COPD receiving long-acting bronchodilator treatment across 1 year...
January 31, 2018: Chest
https://www.readbyqxmd.com/read/29332320/the-role-of-tiotropium-olodaterol-dual-bronchodilator-therapy-in-the-management-of-chronic-obstructive-pulmonary-disease
#6
REVIEW
David M G Halpin
Bronchodilator therapy is central to the management of chronic obstructive pulmonary disease and are recommended as the preferred treatment by the Global Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA) and long acting β₂ agonists (LABA) are both more effective than regular short-acting drugs but many patients remain symptomatic despite monotherapy with these drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit while minimizing dose-dependent side effects of long-acting bronchodilator therapy...
January 2018: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29200840/lung-function-and-long-term-safety-of-tiotropium-olodaterol-in-east-asian-patients-with-chronic-obstructive-pulmonary-disease
#7
Chunxue Bai, Masakazu Ichinose, Sang Haak Lee, Kwan Ho Lee, Olaf Jöns, Ulrich Bothner, Yihua Zhao, Roland Buhl
Background and purpose: While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29183838/abediterol-las100977-an-inhaled-long-acting-%C3%AE-2-adrenoceptor-agonist-has-a-fast-association-rate-and-long-residence-time-at-receptor
#8
Israel Ramos, Mònica Aparici, Maria Letosa, Carlos Puig, Amadeu Gavaldà, Josep Maria Huerta, Sonia Espinosa, Dolors Vilella, Montserrat Miralpeix
This study describes the association rate and residence time of abediterol, a novel long-acting β2 -adrenoceptor agonist (LABA) in Phase II development for treatment of asthma and COPD, in comparison with indacaterol, olodaterol, vilanterol and salmeterol, for both human β1 - and β2 -adrenoceptors. Abediterol association and dissociation rates were monitored directly by using its tritiated form. Moreover, association was determined indirectly using experimental Ki and koff obtained from assays performed with unlabelled compound...
January 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29178871/efficacy-and-safety-of-tiotropium-and-olodaterol-in-copd-a-systematic-review-and-meta-analysis
#9
Marc Miravitlles, Gerard Urrutia, Alexander G Mathioudakis, Julio Ancochea
BACKGROUND: Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD. The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD. This article analyses the evidence of efficacy and safety of the TIO/OLO combination. METHODS: A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator...
November 25, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29175450/crosstalk-between-machrm3-and-%C3%AE-2ar-via-acetylcholine-pi3-pkc-pbep1-raf-1-mek1-2-erk1-2-pathway-activation-in-human-bronchial-epithelial-cells-after-long-term-cigarette-smoke-exposure
#10
Giusy Daniela Albano, Anna Bonanno, Monica Moscato, Giulia Anzalone, Caterina Di Sano, Loredana Riccobono, Sally E Wenzel, Mirella Profita
BACKGROUND: Cigarette smoke extract (CSE) affects the expression of non-neuronal components of cholinergic system in bronchial epithelial cells and, as PEBP1/Raf-mediated MAPK1/2 and ERK1/2 pathway, promotes inflammation and oxidative stress. AIMS: We studied whether Acetylcholine (ACh) is involved in the mechanism of crosstalk between mAChRM3 and β2Adrenergic receptors (β2AR) promoting, via PI3/PKC/PBEP1/Raf/MEK1/2/ERK1/2 activation, β2AR desensitization, inflammation and, oxidative stress in a bronchial epithelial cell line (16HBE) after long-term exposure to cigarette smoke extract (LECSE)...
January 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29104624/smart-watch-based-coaching-with-tiotropium-and-olodaterol-ameliorates-physical-activity-in-patients-with-chronic-obstructive-pulmonary-disease
#11
Osamu Hataji, Yoichi Nishii, Kentaro Ito, Tadashi Sakaguchi, Haruko Saiki, Yuta Suzuki, Corina D'Alessandro-Gabazza, Hajime Fujimoto, Tetsu Kobayashi, Esteban C Gabazza, Osamu Taguchi
Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29094315/comparative-efficacy-of-once-daily-umeclidinium-vilanterol-and-tiotropium-olodaterol-therapy-in-symptomatic-chronic-obstructive-pulmonary-disease-a-randomized-study
#12
Gregory J Feldman, Ana R Sousa, David A Lipson, Lee Tombs, Neil Barnes, John H Riley, Sadhana Patel, Ian Naya, Chris Compton, Bernardino Alcázar Navarrete
INTRODUCTION: We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2 -agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD. METHODS: This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1 ) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy...
November 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29061968/comprehensive-assessment-of-the-safety-of-olodaterol-5-%C3%A2%C2%B5g-in-the-respimat-%C3%A2-device-for-maintenance-treatment-of-copd-comparison-with-the-long-acting-%C3%AE-2-agonist-formoterol
#13
Andrea Koch, Henrik Watz, M Reza Maleki-Yazdi, Ulrich Bothner, Kay Tetzlaff, Florian Voß, Lorcan McGarvey
This analysis provides a comprehensive clinical assessment of the long-term safety of the licensed dose of olodaterol (5 µg once daily [QD] via Respimat® inhaler) in patients with chronic obstructive pulmonary disease by exploring the occurrence of acknowledged side effects of long-acting β2 -agonists as well as those included in the olodaterol and formoterol labels. We analysed pooled data from two replicate, double-blind studies of olodaterol (5 µg QD via Respimat® ) compared to formoterol (12 µg twice daily [BID]) or placebo over 48 weeks (1222...
October 23, 2017: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/28891349/next-generation-beta-adrenoreceptor-agonists-for-the-treatment-of-asthma
#14
REVIEW
Ernesto Crisafulli, Annalisa Frizzelli, Alberto Fantin, Alessandra Manco, Angelo Mangia, Giovanna Pisi, Valentina Fainardi, Veronica Alfieri, Marina Aiello, Giuseppina Bertorelli, Alfredo Chetta
A fixed-dose inhalation of a long-acting β-agonist (LABA) and inhaled corticosteroids (ICS) is commonly recommended for moderate to severe asthmatic patients not adequately controlled by an ICS only. In order to improve the patients' adherence and the control of disease there is a noteworthy interest for the next generation inhaled β adrenoreceptor agonists maintaining an over 24 hours bronchodilatation and used once-daily (ultra-LABAs). This review focuses on the currently available evidences on the clinical role of any single ultra-LABAs in the treatment of asthmatic patients...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#15
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenoceptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -adrenoceptor agonists has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -adrenoceptor agonist olodaterol in primary human lung fibroblasts (HLF) and in murine models of pulmonary fibrosis...
November 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28745522/pharmacological-characterization-of-the-interaction-between-tiotropium-and-olodaterol-administered-at-5-5-concentration-ratio-in-equine-bronchi
#16
Luigino Calzetta, Paola Rogliani, Maurizio Mattei, Pietro Alfonsi, Giuseppe Cito, Elena Pistocchini, Mario Cazzola, Maria Gabriella Matera
Equine airways represent a suitable ex vivo model to study the functional impact of pharmacological treatments on human chronic obstructive pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to characterize the pharmacological interaction between the long-acting muscarinic antagonist (LAMA) tiotropium and the long-acting β2-agonist (LABA) olodaterol in equine airways. The effect of tiotropium and olodaterol, administered alone and in combination at the ratio of concentrations reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combination (FDC) (5:5), was investigated on the cholinergic contractile tone induced by the parasympathetic activation of equine isolated airways...
July 26, 2017: COPD
https://www.readbyqxmd.com/read/28729041/pharmacological-preclinical-characterization-of-las190792-a-novel-inhaled-bifunctional-muscarinic-receptor-antagonist-%C3%AE-2-adrenoceptor-agonist-maba-molecule
#17
Mònica Aparici, Carla Carcasona, Israel Ramos, José Luís Montero, José Luís Ortiz, Julio Cortijo, Carlos Puig, Dolors Vilella, Chris Doe, Amadeu Gavaldà, Montserrat Miralpeix
LAS190792 is a novel muscarinic antagonist and β2-adrenoceptor agonist in development for chronic respiratory diseases. This study investigated the pharmacological profile of LAS190792 in comparison to batefenterol, tiotropium, indacaterol and olodaterol. LAS190792 is potent at the human M3 receptor (pIC50: 8.8 in binding assays). It is selective for the β2-adrenoceptor over the β1-and β3-adrenoceptor, and shows a functional potency in a similar range to batefenterol and LABA compounds (pEC50 in spontaneous tone isolated trachea: 9...
October 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28687462/the-effect-of-tiotropium-in-combination-with-olodaterol-on-house-dust-mite-induced-allergic-airway-disease
#18
Gerrit John-Schuster, Stan de Kleijn, Yolanda van Wijck, Veerle Kremer, Hermelijn H Smits, Michael P Pieper, Pieter S Hiemstra, Christian Taube
One of the major goals of asthma therapy is to maintain asthma control and prevent acute exacerbations. Long-acting bronchodilators are regularly used for the treatment of asthma patients and in clinical studies the anti-cholinergic tiotropium has recently been shown to reduce exacerbations in patients with asthma. So far it is unclear how tiotropium exerts this effect. For this purpose, we designed an allergen-driven rechallenge model of allergic airway inflammation in mice, to assess the effectiveness of tiotropium and the long-acting β-2 adrenoceptor agonist olodaterol on allergen-induced exacerbations of airway disease...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28537001/study-design-of-vesuto-%C3%A2-efficacy-of-tiotropium-olodaterol-on-lung-hyperinflation-exercise-capacity-and-physical-activity-in-japanese-patients-with-chronic-obstructive-pulmonary-disease
#19
COMPARATIVE STUDY
Masakazu Ichinose, Yoshiaki Minakata, Takashi Motegi, Jun Ueki, Tetsuo Seki, Tatsuhiko Anzai, Ayako Takizawa, Lars Grönke, Kazuto Hirata
INTRODUCTION: The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD. METHODS: A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD...
July 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28424359/effects-of-combined-tiotropium-olodaterol-on-inspiratory-capacity-and-exercise-endurance-in-copd
#20
Denis E O'Donnell, Richard Casaburi, Peter Frith, Anne Kirsten, Dorothy De Sousa, Alan Hamilton, Wenqiong Xue, François Maltais
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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