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Peter M A Calverley - One of the best experts on this subject based on the ideXlab platform.
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Tiotropium Respimat^® Versus HandiHaler^®: Comparison of Bronchodilator Efficacy of Various Doses in Clinical Trials
Advances in Therapy, 2016Co-Authors: Peter M A Calverley, Michael Könen-bergmann, Frank Richard, Susan Bell, Jens M. HohlfeldAbstract:Introduction The long-acting muscarinic antagonist Tiotropium Bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler^® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat^® Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of Tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of Tiotropium delivered by Respimat is the closest match to Tiotropium HandiHaler. Methods Evaluation of six clinical trials (duration from 3 weeks to 2–3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes. Results In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg). Conclusion These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD. Funding Boehringer Ingelheim.
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Tiotropium respimat versus handihaler comparison of bronchodilator efficacy of various doses in clinical trials
Advances in Therapy, 2016Co-Authors: Peter M A Calverley, Frank Richard, Susan Bell, Michael Konenbergmann, Jens M. HohlfeldAbstract:Introduction The long-acting muscarinic antagonist Tiotropium Bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of Tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of Tiotropium delivered by Respimat is the closest match to Tiotropium HandiHaler.
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the Tiotropium safety and performance in respimat trial tiospir a large scale randomized controlled parallel group trial design and rationale
Respiratory Research, 2013Co-Authors: Robert A Wise, Daniel Dusser, Gordon Pledger, Michael Koenenbergmann, Elizabeth Joseph, Daniel Cotton, Antonio Anzueto, Peter M A Calverley, Ronald Dahl, Bernd DisseAbstract:Background Tiotropium Bromide is an effective therapy for COPD patients. Comparing across programs Tiotropium Respimat® Soft Mist™ inhaler was at least as efficacious as Tiotropium HandiHaler®, however, concerns have been raised about Tiotropium’s safety when given via Respimat®.
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the prevention of chronic obstructive pulmonary disease exacerbations by salmeterol fluticasone propionate or Tiotropium Bromide
American Journal of Respiratory and Critical Care Medicine, 2008Co-Authors: Jadwiga A Wedzicha, Peter M A Calverley, Gerry Hagan, Terence A R Seemungal, Zainab Ansari, Robert A StockleyAbstract:Rationale: Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD).Objectives: We compared the relative efficacy of the long-acting inhaled bronchodilator/antiinflammatory combination (salmeterol/fluticasone propionate) 50/500 μg twice daily and the long-acting bronchodilator (Tiotropium) 18 μg once daily in preventing exacerbations and related outcomes in severe and very severe COPD.Methods: A total of 1,323 patients (mean age, 64 yr, post-bronchodilator FEV1, 39% predicted) were randomized in this 2-year, double-blind, double-dummy parallel study.Measurements and Main Results: Primary endpoint was health care utilization exacerbation rate. Other endpoints included health status measured by St. George's Respiratory Questionnaire (SGRQ), mortality, adverse events, and study withdrawal. Probability of withdrawing from the study was 29% greater with Tiotropium than salmeterol/fluticasone propionate (P = 0.005). The modeled annual exacerbation rate was 1.28 in...
Jens M. Hohlfeld - One of the best experts on this subject based on the ideXlab platform.
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Tiotropium Respimat^® Versus HandiHaler^®: Comparison of Bronchodilator Efficacy of Various Doses in Clinical Trials
Advances in Therapy, 2016Co-Authors: Peter M A Calverley, Michael Könen-bergmann, Frank Richard, Susan Bell, Jens M. HohlfeldAbstract:Introduction The long-acting muscarinic antagonist Tiotropium Bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler^® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat^® Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of Tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of Tiotropium delivered by Respimat is the closest match to Tiotropium HandiHaler. Methods Evaluation of six clinical trials (duration from 3 weeks to 2–3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes. Results In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg). Conclusion These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD. Funding Boehringer Ingelheim.
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Tiotropium respimat versus handihaler comparison of bronchodilator efficacy of various doses in clinical trials
Advances in Therapy, 2016Co-Authors: Peter M A Calverley, Frank Richard, Susan Bell, Michael Konenbergmann, Jens M. HohlfeldAbstract:Introduction The long-acting muscarinic antagonist Tiotropium Bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of Tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of Tiotropium delivered by Respimat is the closest match to Tiotropium HandiHaler.
Paola Rogliani - One of the best experts on this subject based on the ideXlab platform.
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pharmacological characterization of the interaction between Tiotropium Bromide and olodaterol on human bronchi and small airways
Pulmonary Pharmacology & Therapeutics, 2019Co-Authors: Luigino Calzetta, Paola Rogliani, Clive P Page, Barbara RinaldiAbstract:: Combining a long-acting β2-agonist (LABA) with a long-acting muscarinic antagonist (LAMA) is the cornerstone to treat patients with chronic obstructive pulmonary disease (COPD). In this study we have characterized the interaction between the LAMA Tiotropium Bromide, and the LABA olodaterol, on the contractile tone of human medium bronchi and small airways. The response to a combination of Tiotropium Bromide and olodaterol was assessed at sub-maximal contractile tone induced by carbachol. The duration of action was studied in tissue contracted by transmural stimulation. Relaxation of bronchial tone was expressed as % of maximal response to papaverine. Drug interactions were analyzed by the Bliss Independence method and Unified Theory. Tiotropium Bromide/olodaterol combination induced a significant synergistic relaxant response (P < 0.05 vs. expected additive effect) in medium bronchi and small airways pre-contracted by carbachol, by enhancing relaxation +22.13 ± 4.42% and +26.31 ± 12.39%, respectively. The combination of Tiotropium Bromide and olodaterol also reduced the airway smooth muscle contractility elicited by transmural stimulation by 73.60 ± 3.10%. The extent of synergy was strong to very strong, and was supported by the release of neuronal acetylcholine, cyclic adenosine monophosphate levels, and activation of iberiotoxin-sensitive KCa++ channels. Conversely, the interaction between Tiotropium Bromide and olodaterl was independent of the activity at M2 muscarinic receptors. These results indicate that Tiotropium Bromide/olodaterol combination leads to a potent and durable synergistic relaxation of human medium bronchi and small airways. Further pharmacological studies are needed to confirm these results in clinical settings.
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interaction between Tiotropium Bromide and olodaterol in small human airways
European Respiratory Journal, 2017Co-Authors: Luigino Calzetta, Paola Rogliani, Francesco FaccioloAbstract:Background: Combining a long-acting β2-agonist (LABA) with a long-acting muscarinic antagonist (LAMA) may improve chronic obstructive pulmonary disease therapy. Aim: We investigated the pharmacological interaction of Tiotropium Bromide (LAMA) and olodaterol (LABA) in small human bronchi. Methods: Precision cut lung slices (PCLSs) were incubated in Krebs-Henseleit solution (37°C) aerated with O2/CO2 (95:5%). The concentration response to Tiotropium Bromide and olodaterol, administered alone and in combination at isoeffective concentrations, was assessed at sub-maximal contraction (70% maximum, EC70) induced by carbachol (CCh). PCLS relaxation was expressed as % of maximal response (lumen area enhancement) induced by papaverine (Emax) and potency as the negative logarithm of IC50 or EC50 (pEC50). Drug mixture effects were analyzed by Bliss Independence theory. Values (n=4) are mean±SEM. Results: Tiotropium Bromide and olodaterol induced potent concentration-dependent relaxation of PCLSs (overall pEC50 8.2±0.4). Both drugs abolished the CCh-induced bronchiolar contraction (overall Emax: 105.5±10.1%). Tiotropium Bromide plus olodaterol induced a significant synergistic relaxant response on PCLSs by enhancing relaxation +32.7±5.4%, compared with the expected response (P Low concentrations (EC30) of Tiotropium Bromide with olodaterol induced significant (p Conclusions: Tiotropium Bromide and olodaterol had a synergistic interaction on the lumen area enhancement of human bronchioles. Funding: This study was supported by Boehringer Ingelheim International GmbH, Germany.
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olodaterol Tiotropium Bromide for the treatment of chronic obstructive pulmonary disease
Expert Review of Clinical Pharmacology, 2015Co-Authors: Paola RoglianiAbstract:A solid scientific rationale and an increasing body of clinical evidence for combining a β2-agonist with an antimuscarinic agent in COPD fully support the opinion that patients not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Tiotropium is an established choice for the management of patients with stable COPD, and olodaterol is a new effective and safe once-daily long-acting β2-agonist. The parallel bronchodilating modes of action of olodaterol and Tiotropium make them an attractive combination in COPD. The large ongoing TOviTO Phase III trial program is documenting the efficacy and safety of olodaterol/Tiotropium fixed dose combination delivered via the Respimat Soft Mist Inhaler as maintenance therapy in patients with moderate to very severe COPD. However, we must still know whether this fixed-dose combination will affect exacerbations and hospitalizations, and ultimately death, and also the precise estimates of its relative cardiovascular...
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Olodaterol + Tiotropium Bromide for the treatment of chronic obstructive pulmonary disease
Expert review of clinical pharmacology, 2015Co-Authors: Paola Rogliani, Josuel OraAbstract:A solid scientific rationale and an increasing body of clinical evidence for combining a β2-agonist with an antimuscarinic agent in COPD fully support the opinion that patients not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Tiotropium is an established choice for the management of patients with stable COPD, and olodaterol is a new effective and safe once-daily long-acting β2-agonist. The parallel bronchodilating modes of action of olodaterol and Tiotropium make them an attractive combination in COPD. The large ongoing TOviTO Phase III trial program is documenting the efficacy and safety of olodaterol/Tiotropium fixed dose combination delivered via the Respimat Soft Mist Inhaler as maintenance therapy in patients with moderate to very severe COPD. However, we must still know whether this fixed-dose combination will affect exacerbations and hospitalizations, and ultimately death, and also the precise estimates of its relative cardiovascular safety.
G. Senna - One of the best experts on this subject based on the ideXlab platform.
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Frequency of Tiotropium Bromide Use and Clinical Features of Patients with Severe Asthma in a Real-Life Setting : Data from the Severe Asthma Network in Italy (SANI) Registry
'Dove Medical Press Ltd.', 2020Co-Authors: F. Puggioni, L. Brussino, G.w. Canonica, F. Blasi, P. Paggiaro, M. Caminati, M. Latorre, E. Heffler, G. SennaAbstract:Purpose: Patients with uncontrolled asthma despite high doses of inhaled corticosteroid therapy plus another controller are defined as severe asthmatics. Tiotropium Bromide respi-mat (TBR) is the only long-acting muscarinic antagonists (LAMA) approved for severe asthma. The aim of this study was to explore the frequency of severe asthmatics treated with TBR and characterize their clinical features in a real-life, registry-based setting. Materials and Methods: Baseline data from the Severe Asthma Network in Italy (SANI) registry have been analyzed to determine the use of TBR and other LAMA, and to compare clinical, functional and inflammatory features associated with the use of LAMA. Results: Among a total of 698 enrolled patients, 35.9% were treated with LAMA (23.3% TBR, 4.5% Tiotropium Bromide handihaler, 4.5% aclidinium, 3.4% glycopyrronium Bromide 0.3% umeclidinium Bromide). Age of asthma onset was higher in patients taking LAMA, whom, compared to others were more frequently former smokers. They also had a higher annual exacerbation rate, experienced worst asthma control, worst disease-related quality of life and poorer lung function. Bronchiectasis was more frequently found in LAMA users (25.9% vs 13.1%). Conclusion: TBR is still underused in severe asthma in a real-life setting, while a relevant proportion of patients are treated with other LAMA that are not approved for severe asthma treatment. Patients taking LAMA have features characteristic of even more severe asthma
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long acting anti muscarinic agents lama frequency of use and clinical features of patients with severe asthma in real life setting data from the severe asthma network in italy sani registry
European Respiratory Journal, 2019Co-Authors: F. Puggioni, G.w. Canonica, F. Blasi, P. Paggiaro, M. Caminati, M. Latorre, E. Heffler, G. SennaAbstract:Background: Patients with uncontrolled asthma despite high doses of inhaled corticosteroid plus another controller are defined as severe asthmatics. Tiotropium Bromide Respimat is the only long acting muscarinic agonists (LAMA) approved for severe asthma. Aims: to explore the frequency of severe asthmatics treated with LAMAs and characterize their clinical features in a real-life, registry-based setting. Methods: baseline data from the Severe Asthma Network in Italy (SANI) registry have been analysed to study the use of LAMA and possible clinical features associated to it in severe asthmatics. Results: among a total of 698 enrolled patients, 35.9% were treated with LAMAs (23.3% Tiotropium Bromide Respimat, 4.5% Tiotropium Bromide Handihaler, 4.5% Aclidinium, 3.4% glycopyrronium Bromide 0,3% umeclidinium Bromide). Patients taking LAMAs had higher age of asthma onset (35.3 vs 32.4, p=0.045) and were more frequently former smokers (26.6% vs 17.5%, p=0.001). They had higher annual exacerbation rate (3.9 vs 2.4, p=0.004), worst asthma control (ACT: 17.2 vs 18.4, p=0.012; ACQ: 2.88 vs 2.47, p=0.008), worst disease-related quality of life (AQLQ: 4.24 vs 4.69, p=0.001) and poorer lung function (FEV1%: 70.26% vs 75.48%, p=0.007). Bronchiectasis were more frequently found in LAMA users (25.9% vs 13.1%, p=0.001). Patients taking LAMAs were also more frequently treated also with biologicals (64.4% vs 54.5%, p=0.011). Conclusions: Tiotropium Bromide is still underused in severe asthma in a real-life setting. Patients taking LAMAs have features of the most severe asthmatics
Herman Meurs - One of the best experts on this subject based on the ideXlab platform.
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Meurs H. Protective effects of Tiotropium Bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med 2005;171:1096–1102
2013Co-Authors: Reinoud Gosens, Johan Zaagsma, I. Sophie, T. Bos, Herman MeursAbstract:Rationale: Recent findings have demonstrated that muscarinic M 3 receptor stimulation enhances airway smooth muscle proliferation to peptide growth factors in vitro. Because both peptide growth factor expression and acetylcholine release are known to be augmented in allergic airway inflammation, it is possible that anticholinergics protect against allergen-induced airway smooth muscle remodeling in vivo. Objective: We investigated the effects of treatment with the longacting muscarinic receptor antagonist Tiotropium on airway smooth muscle changes in a guinea pig model of ongoing allergic asthma. Results: Twelve weekly repeated allergen challenges induced an increase in airway smooth muscle mass in the noncartilaginous airways. This increase was not accompanied by alterations in cell size, indicating that the allergen-induced changes were entirely from increased airway smooth muscle cell number. Morphometric analysis showed no allergen-induced changes in airway smooth muscle area in the cartilaginous airways. However, repeated ovalbumin challenge enhanced maximal contraction of open tracheal ring preparations ex vivo. This was associated with an increase in smooth muscle–specific myosin expression in the lung. Treatment with inhaled Tiotropium considerably inhibited the increase in airway smooth muscle mass, myosin expression, and contractility. Conclusions: These results indicate a prominent role for acetylcholine in allergen-induced airway smooth muscle remodeling in vivo, a process that has been thus far considered to be primarily caused by growth factors and other mediators of inflammation. Therefore, muscarinic receptor antagonists, like the long-acting anticholinergic Tiotropium Bromide, could be beneficial in preventing chronic airway hyperresponsiveness and decline in lung function in allergic asthma
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inhibition of allergen induced airway remodelling by Tiotropium and budesonide a comparison
European Respiratory Journal, 2007Co-Authors: Reinoud Gosens, Herman Meurs, Andrew J Halayko, Anetta Zuidhof, Dedmer Schaafsma, Johan ZaagsmaAbstract:Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using Tiotropium Bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of Tiotropium to the glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with Tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that Tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia. This study demonstrates that Tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of Tiotropium Bromide might exceed those of bronchodilation.
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protective effects of Tiotropium Bromide in the progression of airway smooth muscle remodeling
American Journal of Respiratory and Critical Care Medicine, 2005Co-Authors: Reinoud Gosens, Johan Zaagsma, Herman MeursAbstract:Rationale: Recent findings have demonstrated that muscarinic M3 receptor stimulation enhances airway smooth muscle proliferation to peptide growth factors in vitro. Because both peptide growth factor expression and acetylcholine release are known to be augmented in allergic airway inflammation, it is possible that anticholinergics protect against allergen-induced airway smooth muscle remodeling in vivo. Objective: We investigated the effects of treatment with the long-acting muscarinic receptor antagonist Tiotropium on airway smooth muscle changes in a guinea pig model of ongoing allergic asthma. Results: Twelve weekly repeated allergen challenges induced an increase in airway smooth muscle mass in the noncartilaginous airways. This increase was not accompanied by alterations in cell size, indicating that the allergen-induced changes were entirely from increased airway smooth muscle cell number. Morphometric analysis showed no allergen-induced changes in airway smooth muscle area in the cartilaginous airw...