tiotropium-bromide and Asthma

The journey of using anticholinergics in the treatment of asthma started with anticholinergic-containing plants such as Datura stramonium and Atropa belladonna, followed by ipratropium bromide and continued with tiotropium, glycopyrronium, and umeclidinium. Although antimuscarinics were used in the maintenance treatment of asthma over a century ago, after a long time (since 2014), it has been recommended to be used as an add-on long-acting antimuscarinic agent (LAMA) therapy in the maintenance treatment of asthma. The airway tone controlled by the vagus nerve is increased in asthma. Allergens, toxins, or viruses cause airway inflammation and inflammation-related epithelial damage, increased sensory nerve stimulation, ganglionic and postganglionic acetylcholine (ACh) release by inflammatory mediators, intensification of ACh signaling at M1 and M3 muscarinic ACh receptors (mAChRs), and dysfunction of M2 mAChR. Optimal anticholinergic drug for asthma should effectively block M3 and M1 receptors, but have minimal effect on M2 receptors. Tiotropium, umeclidinium, and glycopyrronium are anticholinergic agents with this feature. Tiotropium has been used in a separate inhaler as an add-on treatment to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), and glycopyrronium and umeclidinium have been used in a single inhaler as a combination of ICS/LABA/LAMA in asthma in recent years. Guidelines recommend this regimen as an optimization step for patients with severe asthma before initiating any biologic or systemic corticosteroid therapy. In this review, the history of antimuscarinic agents, their effectiveness and safety in line with randomized controlled trials, and real-life studies in asthma treatment will be discussed according to the current data.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Glycopyrrolate; Humans; Inflammation; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Long-acting muscarinic antagonists (LAMAs) have been used in the treatment of obstructive pulmonary diseases for years. Long-acting muscarinic antagonists were previously mainly used as bronchodilators in chronic obstructive pulmonary disease, but the use of LAMAs in the treatment of asthma has gained great interest. There is now ample evidence of the efficacy and safety of LAMAs as add-on therapy to inhaled corticosteroid (ICS) plus long-acting β. PubMed review using the following words: long-acting muscarinic antagonists, asthma, muscarinic receptors, tiotropium, glycopyrronium, umeclidinium.. This review focused on the key trials that led to the inclusion of LAMAs in asthma guidelines. In addition, we highlighted a number of studies with other study designs and populations.. We identified 6 major studies that led to inclusion in asthma guidelines and 3 studies with other study designs and populations.. Long-acting muscarinic antagonists add-on therapy to ICS-LABA improves lung function, reduces exacerbations, and modestly improves asthma control in patients with moderate to severe asthma who are uncontrolled despite the use of ICS-LABA. Long-acting muscarinic antagonists are effective in all asthma phenotypes and endotypes.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Tiotropium bromide is a long-acting muscarinic antagonist (LAMA) and is the only LAMA licensed for management for patients' ≥6 years old with severe asthma who have experienced one or more severe asthma exacerbations in the preceding year. Recent clinical trials have demonstrated that once-daily tiotropium is safe and efficacious in 6-17 year-olds with symptomatic asthma despite treatment with inhaled corticosteroids (ICSs), with or without additional controllers. In this paper, we review the evidence of the safety and efficacy of tiotropium add-on maintenance treatment in children and adolescents with symptomatic moderate and severe asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Child; Humans; Muscarinic Antagonists; Tiotropium Bromide

The role of long-acting muscarinic antagonists (LAMAs) is well established in uncontrolled asthma, but not in milder stages.. This review examines the main randomized controlled trials (RCTs) that have investigated LAMAs administered as monotherapy or in combination to asthmatic patients, according to the different phenotypes. It offers an overview of the role of LAMAs or their fixed dose combinations (FDCs) in the treatment across all the different stages of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

OCS play an important role in the management of asthma. However, steroid-related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies across countries and recent registry data indicate that at least 25-60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add-on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS-sparing interventions, such as improving guideline adherence and add-on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS-weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker-based strategies.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Biological Products; Disease Progression; Guideline Adherence; Humans; Macrolides; Practice Guidelines as Topic; Tiotropium Bromide

Asthma is a major cause of morbidity in children, despite the availability of various treatments. In adults, tiotropium-a long-acting muscarinic antagonist-as add-on therapy to an inhaled corticosteroid with or without a long-acting β. To review published evidence on the efficacy and safety of tiotropium as add-on a long-acting muscarinic antagonist therapy in children and adolescents with asthma that is uncontrolled despite use of an inhaled corticosteroid with or without additional controller medication(s).. We searched PubMed from inception until June 12, 2018, for randomized controlled trials of children and adolescents aged 1 to 17 years treated with tiotropium and reporting a primary outcome of any pulmonary function test and a secondary outcome of adverse events.. Overall, 7 randomized controlled trials of 1902 preschool children (aged 1-5 years; n = 102), school-age children (aged 6-11 years; n = 905), and adolescents (aged 12-17 years; n = 895) with moderate to severe asthma were included in the analysis. Once-daily tiotropium (5, 2.5, or 1.25 μg) improved lung function parameters, including peak and trough forced expiratory volume in 1 second, vs placebo. Commonly reported adverse events across treatment groups included asthma worsening or exacerbations, decreased peak expiratory flow rate, nasopharyngitis, viral respiratory tract infection, and respiratory tract infection.. Once-daily tiotropium as add-on therapy is efficacious and safe in adolescents and children with moderate to severe asthma. These results support the expanded indication by regulatory authorities for add-on tiotropium in patients 6 years or older.

Topics: Adolescent; Age Factors; Asthma; Bronchodilator Agents; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Infant; Male; Publication Bias; Tiotropium Bromide; Treatment Outcome

Diagnosing and treating asthma in paediatric patients remains challenging, with many children and adolescents remaining uncontrolled despite treatment. Selecting the most appropriate pharmacological treatment to add onto inhaled corticosteroids (ICS) in children and adolescents with asthma who remain symptomatic despite ICS can be difficult. This literature review compares the efficacy and safety of long-acting β

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Delayed-Action Preparations; Disease Progression; Humans; Leukotriene Antagonists; Lung; Randomized Controlled Trials as Topic; Tiotropium Bromide

Cough in asthma predicts disease severity, prognosis, and is a common and troublesome symptom. Cough is the archetypal airway neuronal reflex, yet little is understood about the underlying neuronal mechanisms. It is generally assumed that symptoms arise because of airway hyper-responsiveness and/or airway inflammation, but despite using inhaled corticosteroids and bronchodilators targeting these pathologies, a large proportion of patients have persistent coughing. This review focuses on the prevalence and impact of cough in asthma and explores data from pre-clinical and clinical studies which have explored neuronal mechanisms of cough and asthma. We present evidence to suggest patients with asthma have evidence of neuronal dysfunction, which is further heightened and exaggerated by both bronchoconstriction and airway eosinophilia. Identifying patients with excessive coughing with asthma may represent a neuro-phenotype and hence developing treatment for this symptom is important for reducing the burden of disease on patients' lives and currently represents a major unmet clinical need.

Topics: Animals; Asthma; Axons; Bronchoconstriction; Bronchodilator Agents; Cough; Humans; Neurons, Efferent; Parasympathetic Nervous System; Tiotropium Bromide

The increased acetylcholine signaling in asthma pathophysiology offers the rationale for the use of LAMAs in the treatment of asthmatic patients. Tiotropium is still the only LAMA approved for use in asthma but there is a real interest in developing novel LAMAs for the treatment of asthma, or at least to extend this indication to other LAMAs already on the market.. We examined and discussed trials and research that have studied or are evaluating the role of LAMAs already on the market in asthma and possible novel muscarinic acetylcholine receptor antagonists.. Glycopyrronium and umeclidinium will soon be included in the GINA strategy with the same current indications of tiotropium. It is likely that the choice of the LAMA will be influenced not so much by its pharmacological profile as by the type of triple therapy chosen. It is extremely difficult to identify a new LAMA that is more effective than tiotropium, but is it plausible that new technologies that will allow delivering the drug in a more targeted way and with a lower risk of adverse effects may represent the real progress in the use of LAMAs in asthma in the coming years.

Topics: Acetylcholine; Animals; Anti-Asthmatic Agents; Asthma; Drug Delivery Systems; Drug Development; Humans; Muscarinic Antagonists; Tiotropium Bromide

There is increasing evidence that tiotropium, a long-acting muscarinic agent (LAMA), is useful in the presence of severe-uncontrolled asthma despite the optimization of therapy with inhaled corticosteroids (ICSs) and long-acting β. We have conducted an extensive search on muscarinic antagonists in asthma therapy throughout several sources and discuss what has emerged in the last 3 years (January 2017-March 2020).. New evidence indicates that the effectiveness of adding a LAMA, at least tiotropium, is independent of the degree of the type 2 inflammation and age of patient. Therefore, tiotropium can be administered without the need for patient phenotyping. Umeclidinium and glycopyrronium also appear effective in asthma. Initial treatment with LAMA+ICS for those with mild asthma may be an equally effective therapeutic option as LABA+ICS but this hypothesis should be confirmed by statistically powered trials.

Topics: Adrenal Cortex Hormones; Asthma; Drug Therapy, Combination; Glycopyrrolate; Humans; Muscarinic Antagonists; Quinuclidines; Tiotropium Bromide

Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and long-acting muscarinic antagonists. A combination of aclidinium bromide and formoterol fumarate was approved in the United States. The combination was superior to its components alone, as well as tiotropium and a salmeterol-fluticasone combination. Increased risk of an asthma exacerbation was reported in children exposed to electronic nicotine delivery systems. A smart inhaler capable of recording inspiratory flow was approved in the United States. The use of as-needed budesonide-formoterol was reported to be superior to scheduled budesonide and as-needed terbutaline for the treatment of adults with mild-to-moderate asthma. A survey among teens with asthma and their caregivers revealed a disagreement in the number of inhaled controller medications the teen was taking. Treatment with inhaled hypertonic saline resulted in a decreased lung clearance index in infants and preschool children with cystic fibrosis. Surgical masks were well tolerated and significantly decreased the burden of aerosolized bacteria generated by coughing in adults with cystic fibrosis. Inhaled liposomal amikacin in addition to guideline-based therapy was reported to be superior to guideline-based therapy alone in achieving negative sputum cultures in adult subjects with

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Electronic Nicotine Delivery Systems; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; Tropanes

Topics: Adolescent; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Female; Humans; Male; Tiotropium Bromide

The use of tiotropium is approved for the treatment of asthma. There are several studies completed or currently ongoing with the long-acting muscarinic antagonists (LAMAs) umeclidinium and glycopyrronium as an add-on asthma treatment. Adding a second bronchodilator with a different mechanism of action for the treatment of uncontrolled asthma may be a suitable therapeutic approach, although several issues still under discussion.. The reality of LAMA plus long-acting beta-agonists (LABA) treatment for adult asthma. A systematic search was conducted on March 2020, and included 6 electronic databases: EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science and Google Scholar.. A growing body of evidence generated from several randomized clinical trials is supporting the use of LAMA in adulthood asthma always in association with inhaled corticosteroid (ICS). Currently, only tiotropium has been approved and included in the guidelines. Other LAMAs are under evaluation in clinical trials. Several clinical trials are supporting the use of a triple therapy (ICS/LABA/LAMA) in uncontrolled asthmatic patients under ICS/LABA.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Age of Onset; Asthma; Bronchodilator Agents; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Quinuclidines; Tiotropium Bromide

This review explores the effect of tiotropium Respimat® add-on therapy on asthma exacerbations and worsenings, adverse events (AEs) related to exacerbations and symptoms and any effects on seasonality across the 10 UniTinA-asthma® clinical trials comprising over 6000 patients. When added on to inhaled corticosteroids ± additional therapies, tiotropium significantly reduced the risk of exacerbations and worsenings in adults with symptomatic severe asthma and provided a non-significant improvement in worsenings in adults with symptomatic moderate and mild asthma, which was significant for patients with moderate asthma receiving tiotropium 2.5 µg once daily vs. placebo. Trials in paediatric patients were not powered to assess exacerbations or worsenings, but when AEs related to asthma exacerbations and symptoms were grouped into a composite endpoint and pooled, tiotropium improved outcomes vs. placebo (rate ratio 0.76; 95% confidence interval 0.63, 0.93). The reduction in exacerbations with tiotropium is apparent across all patients during the observed seasonal peaks of these events.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Middle Aged; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome; Young Adult

The Global Initiative for Asthma recommends a stepwise approach to adjust asthma treatment to the needs of individual patients; inhaled corticosteroids (ICS) remain the core pharmacological treatment. However, many patients remain poorly controlled, and evidence-based algorithms to decide on the best order and rationale for add-on therapies are lacking. We explore the challenges of asthma management in primary care and review outcomes from randomised controlled trials and meta-analyses comparing the long-acting muscarinic antagonist (LAMA) tiotropium with long-acting β

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Child; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Muscarinic Antagonists; Primary Health Care; Tiotropium Bromide

The aim of this manuscript is to outline an approach to severe asthma, which is among the most challenging problems faced by paediatric pulmonologists. A logical, protocolised approach is essential. The first step is to rule out alternative diagnoses. The next step is a multidisciplinary assessment. Severe, therapy resistant asthma (STRA) is rare, and most of those referred will improve if basic management is corrected, especially adherence to treatment. However some are unable or unwilling to make necessary changes (refractory asthma plus or refractory difficult asthma). Some, especially asthma in the obese, and those thought to have STRA, progress to bronchoscopic airway phenotyping and a parenteral steroid trial to determine an individualised treatment plan. Those with persistent eosinophilc airway inflammation should be considered for omalizumab, and mepolizumab. Pauci-inflammatory asthma remains a therapeutic challenge, with a paucity of evidence; increasing steroid therapy seems neither logical nor efficacious, but options include tiotropium and azithromycin. However the most important message to the paediatrician looking after a child with apprently severe asthma is that the answer is not uncritically escalating treatment, but finding the answer to the question, what is it about this child, and his/her environment, which means there is no response to what should be easily treated airway pathology? The answer usually requires input from a skilled and experienced multi-disciplinary team, without which management is unlikely to be succesful. CONCLUSION: When managing a child with severe asthma, a detailed multi-disciplinary is essential to get the basic management right, before prescribing biologicals.

Topics: Algorithms; Allergens; Anti-Asthmatic Agents; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Asthma; Asthma, Exercise-Induced; Azithromycin; Bronchodilator Agents; Bronchoscopy; Child; Comorbidity; Environmental Exposure; Eosinophilia; Glucocorticoids; Humans; Medication Adherence; Obesity; Omalizumab; Patient Care Team; Severity of Illness Index; Smoking; Tiotropium Bromide; Tobacco Smoke Pollution

Asthma guidelines provide clinicians with evidence-based management strategies for this chronic condition. The preferred therapy for patient with persistent asthma is inhaled corticosteroids. However, ∼40% of the patients with persistent asthma continue to present with symptoms while treated according to the guidelines. Multiple factors are being explored to explain the variability in response to inhaled corticosteroids including asthma phenotype and genetic predisposition among others. The nonatopic asthma phenotype has been described in the literature. These patients tend to have milder symptoms of asthma and typically outgrow their asthma by adolescence. They present with chronic asthma symptoms in the absence of a positive allergy test, either skin prick test or specific immunoglobulin E blood test. Although patients with nonatopic asthma share many characteristics with patients with atopic asthma, there are several studies that suggest a different inflammatory pathway may be involved in their pathophysiology. Therefore, it is possible that children with nonatopic asthma could respond differently to inhaled corticosteroids compared with those with atopic asthma. Currently there is a variable definition of this phenotype. Furthermore, there is a paucity of therapeutic trial directed toward the patients with nonatopic asthma specifically. Future research should be guided toward identifying the inflammatory pathways in nonatopic asthma and potential phenotype-guided therapies.

Topics: Allergy and Immunology; Anti-Asthmatic Agents; Asthma; Bronchi; Child; Chronic Disease; Diagnosis, Differential; Gastroesophageal Reflux; Humans; Mometasone Furoate; Practice Guidelines as Topic; Proton Pump Inhibitors; Respiratory Mucosa; Respiratory Sounds; Tiotropium Bromide; Treatment Outcome

The goal of the current meta-analysis and systematic review was to explore the efficacy of tiotropium in treating patients with moderate-to-severe asthma on the basis of qualified randomized controlled trials (RCTs).. The following online electronic databases, such as Cochrane, PubMed, and Embase database were screened to identify qualified studies updated to January 2019 through the use of index words. Several literatures that were relevant to the present analysis were also included. To further analyze the main outcomes, we utilized the odds rations (OR), and mean difference (MD) along with its 95% confidence interval (95% CI).. A total of 14 RCTs with 4998 patients in the tiotropium group and 5074 patients in the control group were included in the present study. On the basis of the pooled results, tiotropium was significantly associated with improved morning PEF (SMD: 3.29, 95%CI: 2.03-4.55), evening PEF (SMD: 3.36, 95%CI: 2.24-4.48), peak FEV (SMD: 2.67, 95%CI: 1.47-3.88), and trough FEV (SMD: 1.90, 95%CI: 0.87-2.92) vs the control group. Nevertheless, no significant difference was observed in peak FVC (SMD: 0.77, 95%CI: -0.21-1.76), trough FVC (SMD: 0.67, 95%CI: -0.18-1.53), AE (RR: 0.98, 95%CI: 0.94-1.02) and serious AE (RR: 1.08, 95%CI: 0.77-1.52) between the 2 groups.. In this review, we summarized the significant effect of tiotropium for the treatment of moderate-to-severe asthma, mainly in increasing morning PEF, evening PEF, peak FEV and trough FEV based on high-quality RCTs. Nevertheless, no significant difference in peak FVC, trough FVC, AE and serious AE was found between the 2 groups. A close comparison of the 2 groups revealed that more high-quality larger-sample RCTs are needed to gather more strong evidence on the therapeutic efficacy and safety of tiotropium for clinical practice.

Topics: Adult; Asthma; Bronchodilator Agents; Child; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Severity of Illness Index; Tiotropium Bromide; Vital Capacity

Tiotropium, a long-acting muscarinic antagonist, is approved for maintenance treatment of asthma in patients at least 6 years of age in the USA. We systematically reviewed published evidence on the efficacy and safety of 2.5 µg tiotropium Respimat. We searched PubMed from inception until October 3, 2018, for phase 2 and 3 randomized controlled trials (RCTs) evaluating the effects of 2.5 µg tiotropium Respimat. Overall, 11 RCTs (three phase 2 and eight phase 3 studies) including 3244 patients (2.5 µg tiotropium Respimat. On the basis of the results of phase 2 and 3 studies, 2.5 µg tiotropium Respimat. Development of the manuscript was funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI).

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Child; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Tiotropium Bromide

For the last three decades, the guidelines for asthma management have supported a stepwise therapeutic approach, based on the administration of controller medications (especially inhaled corticosteroids) complemented by on-demand use of rescue medication. Classically, the rescue medication recommended comprised short-acting β agonists (SABA). Some years ago, the use of Symbicort Maintenance and Reliever Therapy (SMART) demonstrated the benefits of a combination of budesonide-formoterol, an inhaled corticosteroid, and a long-acting β agonist (ICS-LABA) as rescue medication in moderate and severe asthma. The results were enthusiastically received, and this therapeutic option was adopted in the guidelines for moderate to severe asthma patients. Recently, four trials (two randomised placebo control trials under the auspices of the SYGMA project and two real-life studies, Novel START, and the PRACTICAL trial) have explored the potential benefits of substituting SABA with budesonide-formoterol as rescue medication in mild asthma patients. The SYGMA 1 and 2 studies showed that the combination with formoterol-budesonide as rescue medication provides better asthma control than short-acting β-agonists alone in GINA step 2 patients, although the superiority was slight. Compared to budesonide maintenance therapy, the fixed combination of ICS-LABA on demand provides poorer asthma control. Regarding exacerbations, the fixed dose ICS-LABA combination on demand showed the same benefits for the prevention of exacerbations as chronic ICS treatment in mild asthma patients. The Novel START study, which assessed a population with milder symptoms, concluded that the fixed dose ICS-LABA combination used as needed was superior to SABA (albuterol) as needed for the prevention of asthma exacerbations. These results in fact show that, in undertreated GINA step 2 with only SABA as needed, ICS-LABA is more effective than SABA. The authors of PRACTICAL concluded that the study provided modest evidence that the ICS-LABA combination used as-needed for symptom relief reduces the rate of severe exacerbations compared with maintenance low-dose budesonide plus terbutaline as needed, although the study was not limited to mild asthma since according to the treatment consumed, it was evident that they had recruited some moderate asthma patients. Despite this poor evidence, and ignoring the clinical histological benefits of chronic inhaled corticosteroids (especially when administered promptly)

Topics: Administration, Inhalation; Adrenergic beta-Antagonists; Asthma; Humans; Mometasone Furoate; Tiotropium Bromide

Topics: Asthma; Budesonide, Formoterol Fumarate Drug Combination; Eosinophils; Humans; Mometasone Furoate; Sputum; Tiotropium Bromide

Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Child; Clinical Trials as Topic; Eosinophilia; Forced Expiratory Volume; Humans; Sputum; Surveys and Questionnaires; Tiotropium Bromide

To assess the efficacy and safety profile of tiotropium when added to low- to medium-dose inhaled corticosteroid (ICS) regimen versus low- to medium-dose ICS alone for adults with mild to moderate uncontrolled persistent asthma.. The online databases Pubmed, Embase and the Cochrane Library were searched for relevant data published up to November 14, 2017; we also conducted a supplementary search using clinicaltrials.gov.. Only randomized control trials were included in this review.. Four studies met our inclusion criteria for this review. In our review, two crossover studies were rated as "high risk" in the domain of "other bias" because a washout was not performed between each intervention. Lung function was significantly improved in the patient group receiving low- to medium-dose ICS with tiotropium. Results were consistent between each of three subgroups (tiotropium dry powder inhaler 18 μg or Respimat Soft Mist inhaler 5 µg, Respimat Soft Mist inhaler 2.5 μg, and Respimat Soft Mist inhaler 1.25 μg). Although no significant difference in Asthma Control Questionnaire (ACQ) score was found between the two treatment groups, substantial heterogeneity was observed. The incidence of serious adverse events between the two treatment groups was not statistically significant.. Tiotropium as a once daily add-on to low- to medium-dose ICS may be efficacious and well-tolerated treatment in adults with moderate uncontrolled asthma. However, as only a few studies were identified, more studies of better design and long-term trial duration are required in the future.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Quality of Life; Randomized Controlled Trials as Topic; Respiratory Function Tests; Tiotropium Bromide

To provide a fast overview about the introduction and development of anticholinergic drugs in Western medicine to their current indications particularly in asthma.. Although short-acting muscarinic antagonists have been positioned in the last 15 years for the treatment of adults and children with moderate-to-severe acute asthma in the emergency setting (reducing the risk of hospital admissions and improving lung function), a growing body of evidence has recently emerged that positions the long-acting muscarinic anticholinergic tiotropium bromide as add-on therapy to at least inhaled corticosteroids (ICS) maintenance therapy in adults, adolescents, and children with symptomatic asthma. Thus, the addition of tiotropium bromide to ICS alone or ICS and another controller was associated with significant improvements in spirometric measures and asthma control, and a significantly decrease in the rate of asthma exacerbations.. Short-acting muscarinic antagonists and tiotropium bromide have a well established role in the treatment of different phases of asthma. Further data are needed to provide more evidence on other selective long-acting muscarinic antagonists in addition to tiotropium as potential treatment options.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Animals; Asthma; Child; Cholinergic Antagonists; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Muscarinic Antagonists; Tiotropium Bromide

Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years.. An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the development of tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed.. A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms.. Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults and two in adolescents aged 12-17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescents with mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo.. Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profile similar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.

Topics: Adolescent; Asthma; Child; Humans; Tiotropium Bromide; Treatment Outcome; Young Adult

Asthma is one of the most common chronic diseases in children, with a high proportion of patients demonstrating poor control despite the availability of disease management guidelines. Global Initiative for Asthma guidelines include tiotropium as an add-on therapy option at Steps 4 and 5 in patients aged ≥ 12 years with a history of exacerbations, and tiotropium delivered via the Respimat

Topics: Administration, Inhalation; Adolescent; Asthma; Child; Child, Preschool; Cholinergic Antagonists; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Tiotropium Bromide; Treatment Outcome

Asthma is a chronic disease of airway inflammation with a large global burden. Despite established, guideline-based stepwise therapy, a significant proportion of patients remain symptomatic and poorly controlled. As such, there is a need for additional safe, effective, convenient, and cost-effective therapies that can be broadly applied across a range of asthma phenotypes. Tiotropium is a long-acting muscarinic antagonist (LAMA) that leads to bronchodilation by blocking endogenous acetylcholine receptors in the airways. Tiotropium has long been approved for the treatment of chronic obstructive pulmonary disease, and it has recently been recognized for its safety and efficacy in improving lung function and controlling asthma. Evidence from several Phase III trials in the adult and paediatric population has shown that tiotropium is well tolerated and significantly improves a range of endpoints as an add-on treatment to ICS therapy, regardless of baseline characteristics and clinical phenotypes. Consequently, regulatory authorities worldwide have recently licensed tiotropium as the only LAMA approved for the treatment of asthma. This review provides an overview of safety and efficacy data and discusses the use of tiotropium in patients across the range of asthma severities, ages, and phenotypes.

Topics: Asthma; Bronchodilator Agents; Humans; Patient Selection; Tiotropium Bromide

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Maintenance Chemotherapy; Severity of Illness Index; Tiotropium Bromide

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Tiotropium Bromide

Chronic obstructive pulmonary disease (COPD) and asthma are leading causes of morbidity and mortality. This narrative review provides an appraisal of the pharmacological and clinical characteristics of tiotropium in COPD and asthma, and examines how these compare with other long-acting bronchodilators. The evidence base is placed into context by relating it to factors affecting clinicians' choice of therapy.. Desirable attributes of a long-acting muscarinic antagonist (LAMA) maintenance therapy include effective pharmacological bronchodilation, improved lung function, exacerbation efficacy, and positive effects on symptom control, exercise capacity and quality of life across a broad patient population. Tolerability and convenience of use are also important for patient well-being and treatment adherence. Tiotropium shows higher affinity for muscarinic receptors than ipratropium, and prolonged binding to the M. With over 10 years' prescribing history and 50 million patient-years of use, tiotropium has the benefit of a more extensive clinical evidence base than other long-acting bronchodilators, with demonstrated efficacy and safety in COPD and symptomatic asthma.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Disease Progression; Exercise Tolerance; Forced Expiratory Volume; Humans; Ipratropium; Muscarinic Antagonists; Nebulizers and Vaporizers; Patient Outcome Assessment; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Tiotropium Bromide

Recently published data support the benefits and safety of the once-daily (OD) long-acting anticholinergic tiotropium bromide bronchodilator for the treatment of uncontrolled moderate-to-severe asthma in adults and adolescents. However, its role for the treatment of school-age asthmatics has not yet been clearly defined. The aim of this systematic review was to assess the efficacy and safety of tiotropium Respimat. Randomized, placebo-controlled trials were included. Primary outcomes were peak forced expiratory volume in 1 s measured within 3 h post-dosing) [FEV. Three studies (more than 900 patients) were selected. Tiotropium was associated with significant improvements in FEV. OD tiotropium Respimat

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Humans; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

Evidence is emerging on the use of long-acting muscarinic antagonists (LAMAs) in the management of asthma. Tiotropium bromide (Spiriva

Topics: Adolescent; Asthma; Bronchodilator Agents; Child; Clinical Trials, Phase III as Topic; Humans; Muscarinic Antagonists; Phenotype; Tiotropium Bromide

Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Drug Discovery; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leukotriene Antagonists; Long-Term Care; Macrolides; Muscarinic Antagonists; Phosphodiesterase 4 Inhibitors; Protein Kinase Inhibitors; Quinuclidines; Small Molecule Libraries; Tiotropium Bromide

Asthma is a prevalent disease affecting millions of individuals. Despite receiving guideline therapy with inhaled corticosteroids (ICS) with or without a long-acting β

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Child; Cholinergic Antagonists; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Tiotropium Bromide

Higher parasympathetic tone has been reported in asthmatics. In general, cholinergic contractile tone is increased by airway inflammation associated with asthma. Nevertheless, the role of muscarinic antagonists for the treatment of asthma has not yet been clearly defined. Areas covered: The use of SAMAs and LAMAs in asthma has been examined and discussed according with the published evidence. Particular attention has been given to the large Phase III clinical trial program designed to evaluate the efficacy and safety of tiotropium respimat added to standard treatment in adults, adolescents and children with persistent asthma across the spectrum of asthma severity. Expert commentary: The current evidence is that in patients with poorly controlled severe asthma despite the use of ICS and LABA, the addition of tiotropium significantly increases the time to the first severe exacerbation and provides a modest but sustained bronchodilation. Identical results should be produced using other LAMAs. In any case, the documentation that, at least in animal or in vitro models, LAMAs show significant anti-inflammatory and anti-proliferative capacities and are able to inhibit airway remodeling induced by allergens makes a strong presumption that the use of LAMAs in asthma may go beyond the simple bronchodilator effect.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Airway Remodeling; Asthma; Bronchodilator Agents; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Tiotropium Bromide

Maintenance treatment with long-acting beta2-agonists and inhaled corticosteroids (LABA/ICS) can relieve asthma symptoms and reduce the frequency of exacerbations, but there are limited treatment options for people who do not gain control on combination LABA/ICS. Long-acting muscarinic antagonists (LAMA) are a class of inhaled drug which have been effective for people with chronic obstructive pulmonary disease and are now becoming available for people with asthma to take alongside their LABA/ICS inhaler.. To assess the effects of adding a long-acting muscarinic antagonist (LAMA) to combination long-acting beta2-agonists (LABA) and inhaled corticosteroids (ICS) in adults whose asthma is not well controlled by LABA/ICS.. We identified trials from the Cochrane Airways Review Group Specialised Register (CAGR) up to January 2016. We also searched ClinicalTrials.gov, the WHO trials portal, and reference lists of other reviews, and we contacted trial authors for additional information.. We included parallel randomised controlled trials (RCTs) of at least 12 weeks' duration. Studies met the inclusion criteria if they compared LAMA as an add-on to LABA/ICS versus LABA/ICS alone for adults with asthma. We included studies reported as full text, those published as abstract only, and unpublished data. Primary outcomes were exacerbations requiring oral corticosteroids (OCS), validated measures of asthma control, and serious adverse events (including mortality).. Two review authors screened searches and independently extracted details on risk of bias and numerical data. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MD) using a random-effects model. We rated all outcomes using GRADE.. We found four double-blind, double-dummy trials comparing LAMA to placebo, including 1197 people with asthma taking combination LABA/ICS. One of the trials was designed to study glycopyrronium bromide but was withdrawn prior to enrolment, and the other three all studied tiotropium bromide (mostly 5 µg once daily via Respimat) over 48 to 52 weeks. People in the trials had a mean forced expiratory volume in one second (FEV1) of 55% of their predicted value, indicating severe asthma.People randomised to take tiotropium add-on had fewer exacerbations requiring oral corticosteroids than those continuing to take LABA/ICS alone, but the confidence intervals did not rule out no difference (OR 0.76, 95% CI 0.57 to 1.02; moderate quality evidence). Over 48 weeks, 328 out of 1000 people taking their usual LABA/ICS would have to take oral corticosteroids for an exacerbation compared with 271 if they took tiotropium as well (95% CI 218 to 333 per 1000). Analyses comparing the number of exacerbations per patient in each group (rate ratio) and the time until first exacerbation (hazard ratio) were in keeping with the main result. Quality of life, as measured by the Asthma Quality of Life Questionnaire (AQLQ) was no better for those taking tiotropium add-on than for those taking LABA/ICS alone when considered in light of the 0.5 minimal clinically important difference on the scale (MD 0.09, 95% CI - 0.03 to 0.20), and evidence for whether tiotropium increased or decreased serious adverse events in this population was inconsistent (OR 0.60, 95% CI 0.24 to 1.47; I(2) = 76%).Within the secondary outcomes, exacerbations requiring hospital admission were too rare to tell whether tiotropium was beneficial over LABA/ICS alone. There was high quality evidence showing benefits to lung function (trough FEV1 and forced vital capacity (FVC)) and potentially small benefits to asthma control. People taking tiotropium add-on were less likely to experience non-serious adverse events.. Tiotropium add-on may have additional benefits over LABA/ICS alone in reducing the need for rescue oral steroids in people with severe asthma. The effect was imprecise, and there was no evidence for other LAMA preparations. Possible benefits on quality of life were negligible, and evidence for the effect on serious adverse events was inconsistent. There are likely to be small added benefits for tiotropium Respimat 5 µg daily on lung function and asthma control over LABA/ICS alone and fewer non-serious adverse events. The benefit of tiotropium add-on on the frequency of hospital admission is still unknown, despite year-long trials.Ongoing and future trials should clearly describe participants' background medications to help clinicians judge how the findings relate to stepwise care. If studies test LAMAs other than tiotropium Respimat for asthma, they should be at least six months long and use accepted and validated outcomes to allow comparisons of the safety and effectiveness between different preparations.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Disease Progression; Drug Therapy, Combination; Humans; Middle Aged; Muscarinic Antagonists; Quality of Life; Randomized Controlled Trials as Topic; Tiotropium Bromide

Asthma is a chronic inflammatory disorder of the airways that is a major global burden on both individuals and healthcare systems. Despite guideline-directed treatment, a significant proportion of patients with asthma do not achieve control. This review focuses on the potential use of long-acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add-on to inhaled corticosteroid maintenance therapy, with or without a long-acting β2-agonist, in patients across asthma severities. Recent studies using the Respimat Soft Mist inhaler have identified 5 µg once daily as the preferred dosing regimen, which has shown promising results in adults, adolescents and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future clinical trials will be beneficial in determining where long-acting anticholinergic agents fit in future treatment guidelines across a variety of patient populations and disease severities.

Topics: Administration, Inhalation; Asthma; Bronchoconstriction; Bronchodilator Agents; Drug Therapy, Combination; Humans; Lung; Muscarinic Antagonists; Nebulizers and Vaporizers; Time Factors; Tiotropium Bromide; Treatment Outcome

In the treatment of chronic obstructive pulmonary disease (COPD), bronchodilators such as long acting muscarinic antagonist (LAMA) and long acting β agonist(LABA) play key roles for improving respiratory function and symptoms, and reducing risk of exacerbation. However, inhaled corticosteroid (ICS), a key medicine for bronchial asthma, is limitedly used in COPD treatment. Japanese Respiratory Society recommends to use ICS for severe COPD patients who have been frequently exacerbated, because previous clinical studies indicated that ICS reduces exacerbation in moderate to severe COPD patients. Asthma sometimes overlaps with COPD, and symptoms of those patients are not well controlled by the bronchodilation therapy alone. Therefore, ICS/LABA or ICS/LAMA should be prescribed to those overlapped patients. Concentration of exhaled nitrogen oxide and percentage of peripheral eosinophil may be good biomarkers for discriminating the COPD patients who have good response to ICS treatment.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Biomarkers; Breath Tests; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Delayed-Action Preparations; Disease Progression; Drug Combinations; Drug Therapy, Combination; Eosinophils; Fluticasone; Glucocorticoids; Humans; Leukocyte Count; Muscarinic Antagonists; Nitrogen Oxides; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Severity of Illness Index; Tiotropium Bromide

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has recently been approved for use in the treatment of asthma in a number of countries, including the EU and the USA, and was incorporated into the 2015 update of the Global Initiative for Asthma treatment guidelines. Here we review safety data from published clinical trials to help inform the use of tiotropium in the treatment of patients with asthma.. Safety data from recently published clinical trials, which compared tiotropium with placebo or an active control, were reviewed. Trials included children, adolescents, and adults across severities of symptomatic asthma, and assessed tiotropium delivered via the Respimat and HandiHaler devices.. Based on the reviewed scientific evidence, tiotropium is a safe and well-tolerated long-acting anticholinergic bronchodilator for use in the treatment of asthma. In the trials assessed, the safety of tiotropium was found to be comparable with that of placebo and alternative therapeutic options, including a doubling in the dose of inhaled corticosteroids and the long-acting β2-agonist salmeterol.

Topics: Administration, Inhalation; Adolescent; Adult; Animals; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cholinergic Antagonists; Delayed-Action Preparations; Humans; Practice Guidelines as Topic; Tiotropium Bromide

Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma. These studies led to FDA approval for tiotropium use in asthma. In this review, we discuss how the neurotransmitter acetylcholine itself contributes to inflammation, bronchoconstriction, and remodeling in asthma. We further describe the current clinical studies evaluating LAMAs in adult and adolescent patients with asthma, providing a comprehensive review of the current known physiological benefits of LAMAs in respiratory disease.

Topics: Acetylcholine; Anti-Asthmatic Agents; Asthma; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Parasympathetic Nervous System; Receptor Cross-Talk; Receptors, Muscarinic; Tiotropium Bromide

Topics: Asthma; Bronchodilator Agents; Humans; Lung; Models, Neurological; Muscarinic Antagonists; Muscle, Smooth; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; Vagus Nerve

Asthma is a chronic inflammatory airway disease, and its treatment is frequently challenging despite detailed national and international guidelines. While basic anti-inflammatory therapy usually consists of inhaled corticosteroids in doses adapted to the asthma severity, add-on treatment with bronchodilators is essential in more severe asthma. Only recently, the long-acting anticholinergic tiotropium was introduced into the GINA guidelines. This review reports on the studies that have been performed with tiotropium in adult asthmatic patients. Following early proof-of-concept studies, several studies with tiotropium as an add-on therapy to inhaled corticosteroids (ICS), with or without a long-acting beta agonist (LABA), demonstrated convincing clinical benefit for patients. Important lung function parameters and quality of life scores significantly improved shortly after onset of the add-on therapy with tiotropium, and some studies even demonstrated non-inferiority against salmeterol. All studies reported an excellent safety profile of tiotropium. The still growing body of tiotropium studies, both in adults and children, will help to identify the position of tiotropium in future asthma guidelines and might also indicate which patients benefit most from an add-on therapy with tiotropium.

Topics: Adrenal Cortex Hormones; Adult; Animals; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Humans; Quality of Life; Tiotropium Bromide

The role of tiotropium for the treatment of asthma has not yet been clearly defined. The aim of this systematic review was to assess the efficacy and safety of tiotropium in patients with asthma.. Randomized placebo-controlled trials were included. Primary outcomes were peak and trough FEV1 and morning and evening peak expiratory flow (PEF).. Thirteen studies (4,966 patients) were included. Three different therapeutic protocols were identified. Tiotropium as an add-on to inhaled corticosteroids (ICSs) showed statistically and clinically significant increases in PEF (22-24 L/min) and FEV1 (140-150 mL). Additionally, tiotropium decreased the rate of exacerbations (number needed to treat for benefit [NNTB], 36) and improved asthma control. The use of tiotropium in patients poorly controlled despite the use of medium to high doses of ICS was not inferior to salmeterol. Finally, the use of tiotropium as an add-on to ICS/salmeterol combination increased pulmonary function to a clinically significant magnitude, reduced asthma exacerbations (relative risk, 0.70; 95% CI, 0.53-0.94; P < .02; I2 = 0%; NNTB, 17), and improved asthma control compared with ICS/salmeterol. Tiotropium was well tolerated, and no potential safety signals were observed.. Tiotropium resulted noninferiorly to salmeterol and superiorly to placebo in patients with moderate to severe asthma who were not adequately controlled by ICS or ICS/salmeterol. Major benefits were concentrated in the increase in lung function and in the case of patients with severe asthma, in the reduction of exacerbations.

Topics: Adrenal Cortex Hormones; Albuterol; Asthma; Cholinergic Antagonists; Disease Progression; Drug Therapy, Combination; Humans; Intention to Treat Analysis; Quality of Life; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Tiotropium bromide (Spiriva®) solution for inhalation via the Respimat® Soft Mist™ inhaler is a long-acting anticholinergic agent approved in the EU for the add-on maintenance treatment of asthma in adults currently receiving maintenance therapy with an inhaled corticosteroid (ICS) (≥800 µg budesonide per day or equivalent) and a long-acting β2-adrenergic agonist (LABA) and who have experienced at least one severe exacerbation in the previous year. Tiotropium Respimat® added to maintenance ICS/LABA treatment significantly improved lung function after 6 months' treatment and extended the time to the first asthma exacerbation in two well-designed, replicate, phase III trials in patients with poorly controlled asthma despite treatment with an ICS (≥800 µg budesonide/day or equivalent) and a LABA. Tiotropium Respimat® was also associated with a reduced incidence of severe asthma exacerbations and an increase in the median time to asthma worsening. The drug was well tolerated in asthma patients throughout 48 weeks' treatment, with a generally similar incidence of serious adverse events in tiotropium Respimat® and placebo treatment groups. Thus, in patients with poorly controlled asthma despite receiving high-dose ICS and a LABA, tiotropium Respimat® provides a valuable treatment option.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Tiotropium Bromide

Asthma management guidelines emphasize the importance of effective treatment to achieve and maintain control of asthma. However, despite widely available and effective treatments, achieving control of asthma is still an unmet need for many patients. Adding a second bronchodilator with a different mechanism of action for the treatment of uncontrolled asthma can be a suitable therapeutic approach. This review focuses on the role of long-acting muscarinic antagonists, particularly tiotropium, in the treatment of asthma. A number of studies have evaluated the efficacy and safety of tiotropium in asthma patients whose disease is poorly controlled with inhaled corticosteroids (ICSs) with or without long-acting β2-agonists (LABAs). The effect on several clinical and lung function variables of adding tiotropium to an ICS is greater than doubling the dose of the latter and is not inferior to the addition of a LABA (salmeterol). Studies assessing the role of tiotropium as add-on therapy to ICS combined with a LABA have shown modest but clinically significant and dose-dependent improvements in forced expiratory volume in 1 second, as well as a decrease in the risk of exacerbations. In addition, time to the next episode is longer, particularly in patients who experience severe exacerbations. In conclusion, tiotropium proved noninferior to salmeterol and superior to placebo in patients with moderate-severe asthma who were not adequately controlled using ICSs or ICSs combined with a LABA. The major benefits are the increase in lung function and, in the case of severe asthma, the reduction in the frequency of exacerbations. In patients with asthma, tiotropium is usually well tolerated, and no potential safety signals have been observed.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Humans; Lung; Muscarinic Antagonists; Salmeterol Xinafoate; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

Poorly controlled asthma and preventable exacerbations place a significant strain on healthcare, often requiring additional medications, hospital stays or treatment in the emergency department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment for adults with asthma whose symptoms are not well controlled on inhaled corticosteroids (ICS), but have important safety concerns in asthma. Long-acting muscarinic antagonists (LAMA) have confirmed efficacy in chronic obstructive pulmonary disease and are now being considered as an alternative add-on therapy for people with uncontrolled asthma.. To assess the efficacy and safety of adding a LAMA to ICS compared with adding a LABA for adults whose asthma is not well controlled on ICS alone.. We searched the Cochrane Airways Group's Specialised Register (CAGR) from inception to April 2015, and imposed no restriction on language of publication. We searched additional resources to pick up unpublished studies, including ClinicalTrials.gov, World Health Organization trials portal, reference lists of primary studies and existing reviews, and manufacturers' trial registries. The most recent search was conducted in April 2015.. We searched for parallel and cross-over RCTs in which adults whose asthma was not well controlled with ICS alone were randomised to receive LAMA add-on or LABA add-on for at least 12 weeks.. Two review authors independently screened the electronic and additional searches and extracted data from study reports. We used Covidence for duplicate screening, extraction of study characteristics and numerical data, and risk of bias ratings.The pre-specified primary outcomes were exacerbations requiring oral corticosteroids (OCS), quality of life and serious adverse events.. We included eight studies meeting the inclusion criteria, but four double-blind, double-dummy studies of around 2000 people dominated the analyses. These four trials were between 14 and 24 weeks long, all comparing tiotropium (usually Respimat) with salmeterol on top of medium doses of ICS.Studies reporting exacerbations requiring OCS showed no difference between the two add-ons, but our confidence in the effect was low due to inconsistency between studies and because the confidence intervals (CI) included significant benefit of either treatment (odds ratio (OR) 1.05, 95% CI 0.50 to 2.18; 1753 participants; 3 studies); three more people per 1000 might have an exacerbation on LAMA, but the CIs ranged from 29 fewer to 61 more. Imprecision was also an issue for serious adverse events and exacerbations requiring hospital admission, rated low (serious adverse events) and very low quality (exacerbations requiring hospital admission), because there were so few events in the analyses.People taking LAMA scored slightly worse on two scales measuring quality of life (Asthma Quality of Life Questionnaire; AQLQ) and asthma control (Asthma Control Questionnaire; ACQ); the evidence was rated high quality but the effects were small and unlikely to be clinically significant (AQLQ: mean difference (MD) -0.12, 95% CI -0.18 to -0.05; 1745 participants; 1745; 4 studies; ACQ: MD 0.06, 95% CI 0.00 to 0.13; 1483 participants; 3 studies).There was some evidence to support small benefits of LAMA over LABA on lung function, including on our pre-specified preferred measure trough forced expiratory volume in one second (FEV1) (MD 0.05 L, 95% CI 0.01 to 0.09; 1745 participants, 4 studies). However, the effects on other measures varied, and it is not clear whether the magnitude of the differences were clinically significant.More people had adverse events on LAMA but the difference with LABA was not statistically significant.. Direct evidence of LAMA versus LABA as add-on therapy is currently limited to studies of less than six months comparing tiotropium (Respimat) to salmeterol, and we do not know how they compare in terms of exacerbations and serious adverse events. There was moderate quality evidence that LAMAs show small benefits over LABA on some measures of lung function, and high quality evidence that LABAs are slightly better for quality of life, but the differences were all small. Given the much larger evidence base for LABA versus placebo for people whose asthma is not well controlled on ICS, the current evidence is not strong enough to say that LAMA can be substituted for LABA as add-on therapy.The results of this review, alongside pending results from related reviews assessing the use of LAMA in other clinical scenarios, will help to define the role of these drugs in asthma and it is important that they be updated as results from ongoing and planned trials emerge.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Tiotropium Bromide

Long-acting muscarinic antagonists (LAMA), a class of drugs with proven effectiveness in chronic obstructive pulmonary disease (COPD), are being considered as an add-on option for adults with asthma whose condition is uncontrolled on inhaled corticosteroids (ICS). It is important to assess the safety and efficacy of LAMA add-on as an alternative to the prolonged use of higher doses of ICS, which are known to cause undesirable side effects in some people.. To compare the effects of adding a LAMA to any dose of ICS versus increasing the dose of ICS, for uncontrolled asthma in adults.. We searched the Cochrane Airways Group Specialised Register (CAGR) from its inception in 1995 to April 2015, imposing no restriction on language of publication. We also handsearched trial registries, reference lists of primary studies and existing reviews, as well as manufacturers' websites.. We looked for parallel or cross-over randomised controlled trials lasting at least 12 weeks, in which adults whose asthma was not well controlled on ICS alone were randomised to treatment with LAMA add-on to ICS or with an increased dose of ICS. Trials were excluded if patients were taking long-acting beta2-agonists during the study period.. Two review authors independently screened the searches and extracted data from studies meeting all the inclusion criteria. We used Covidence to manage duplicate screening, data extraction and risk of bias judgements, and to form a consensus where discrepancies arose. We used standard methods expected by The Cochrane Collaboration.The pre-specified primary outcomes were exacerbations requiring a course of oral corticosteroids (OCS), effects on quality of life and serious adverse events.. One cross-over randomised controlled trial met the inclusion criteria. The trial was performed in 210 patients with moderate to severe asthma and compared the use of the LAMA tiotropium bromide with double dose beclomethasone (an ICS) using a cross-over design and 14-week treatment periods.Compared with people taking a double dose of ICS, fewer people taking a LAMA add-on had an exacerbation requiring treatment with OCS (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.22 to 1.43) or an exacerbation resulting in emergency department admission (OR 0.49, 95% CI 0.09 to 2.77), but the confidence intervals for both outcomes did not exclude the possibility that double dose ICS was more effective. Serious adverse events and exacerbations requiring hospitalisation occurred in similarly low numbers of people taking each treatment, but confidence intervals were too wide to suggest that the two treatment options were equivalent.Asthma-related quality of life was similar in both treatment groups (mean difference (MD) in change from baseline 0.10, 95% CI - 0.07 to 0.27). Those taking LAMA add-on scored slightly better on a scale measuring asthma control than those increasing their ICS dose (MD in change from baseline - 0.18, 95% CI - 0.34 to - 0.02), although the difference was clinically small. Evidence was deemed low quality for both quality of life and asthma control.There was moderate-quality evidence that participants' trough forced expiratory volume in one second (FEV1) was 100 mL better when taking LAMA add-on than with increased ICS dose (MD in change from baseline 0.10, 95% CI 0.03 to 0.17).. Only one randomised trial was found, comparing tiotropium add-on to increased dose beclomethasone. Differences between the treatments were too small or imprecise to understand whether adding a LAMA to ICS is safer or more effective than increasing the dose of ICS, and there is a possibility of carry-over effects due to the study's cross-over design. LAMA add-on may lead to more improvement in lung function (FEV1) than an increased dose of ICS.The results of this review, alongside pending results from related reviews assessing the use of LAMA against other treatments, will help to define the role of these drugs in asthma management, and this review should be updated as results from future trials emerge. Studies assessing the role of LAMA add-on should be longer and include a double-ICS treatment arm so that the results can be interpreted in the context of the guideline-recommended treatment options that are available to physicians.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Tiotropium Bromide

The role of tiotropium for the treatment of adolescents with asthma has not yet been clearly defined.. To assess the efficacy and safety of inhaled tiotropium in adolescents with moderate to severe symptomatic asthma.. Randomized, placebo-controlled trials were included in this systematic review. Primary outcomes were peak and trough forced expiratory volume in 1 second (FEV1).. Three studies (approximately 1,000 patients) were included. Tiotropium was associated with significant improvements in FEV1 peak (mean change from baseline) by 120 mL (P < .001) and trough by 100 mL (P < .001) compared with placebo. Tiotropium significantly reduced the percentage of patients who experienced an Asthma Control Questionnaire 7 worsening episode defined as a change from trial baseline of 0.5 points or more compared with placebo (2.1% vs 4.8%, number needed to treat = 38) and also was associated with a significantly decreased in the number of patients with at least one exacerbation compared with placebo (17.6 vs 23.8%, number needed to treat = 16). Finally, no significant differences were found in rescue medication use, withdrawals, withdrawals due to adverse events (AEs), AEs (27.3% vs 27.1%), and serious AEs (6.5% vs 7.1%). Tiotropium in doses of 2.5 μg once daily or 5.0 μg once daily resulted in equivalent effects.. Tiotropium was well tolerated and efficacious as an addition to maintenance treatment with an inhaled corticosteroid or an inhaled corticosteroid plus a long-acting β-agonist in adolescents with moderate to severe asthma. Available data do not suggest an advantage of the 5-μg once-daily dose (used in adults) compared with the 2.5-μg once-daily dose of tiotropium.

Topics: Adolescent; Asthma; Bronchodilator Agents; Drug Administration Schedule; Female; Humans; Male; Respiratory Function Tests; Surveys and Questionnaires; Tiotropium Bromide; Treatment Outcome

Asthma is a chronic inflammatory disorder of the airways with increasing worldwide prevalence. Despite treatment according to guidelines, a considerable proportion of patients with asthma remain symptomatic. Different potential therapeutic options for the treatment of these patients are currently in development and undergoing clinical trials, and it is important to regularly review their status.. A search of ClinicalTrials.gov was performed and supported by a PubMed literature search and restricted to the previous 10 years to ensure currency of data. The results were manually filtered to identify relevant articles.. Emerging therapies that are currently in phase 2 and 3 development include anti-interleukin agents (benralizumab, reslizumab, dupilumab, brodalumab, lebrikizumab, and mepolizumab), a chemoattractant receptor-homologous molecule expressed on a T-helper type 2 lymphocyte antagonist (OC000459), a phosphodiesterase-4 inhibitor (roflumilast), and long-acting muscarinic antagonists (glycopyrronium bromide, umeclidinium bromide, and tiotropium bromide).. The clinical trial program of the long-acting muscarinic antagonist tiotropium is currently the most advanced, with data available from different phase 2 and 3 studies. Results demonstrate that it is an efficacious add-on to at least inhaled corticosteroid maintenance therapy across severities of symptomatic asthma.. The results of ongoing and future studies will help to determine whether these emerging therapeutic options will help address the unmet need for improvement in asthma management.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Indoleacetic Acids; Interleukins; Muscarinic Antagonists; Phosphodiesterase 4 Inhibitors; Quinolines; Tiotropium Bromide

Anticholinergic bronchodilators such as tiotropium, a potent long-acting drug, are central to the symptomatic treatment of chronic obstructive pulmonary disease. Its role in asthma treatment has been recently investigated. This review critically evaluates documented evidence of clinical trials and assesses the therapeutic implications of anticholinergic drugs in asthma management. So far, the results of 10 Phases II and III randomized controlled trials evaluating the effect of adding tiotropium to the treatment of mild-to-moderate or severe asthma have been published. These trials had a duration of 4 to 52 weeks and involved 3368 subjects with mild-to-moderate asthma and 1019 subjects with severe asthma [corrected]. Also, 1 systematic review and 6 meta-analyses have appraised the results of published and unpublished trials investigating the role of tiotropium in asthma. The results of the trials in mild to moderate asthma showed that adding tiotropium to inhaled corticosteroids (ICSs) was not inferior to adding long-acting β2-agonists (LABAs). In addition, the safety and efficacy of tiotropium were similar to those of salmeterol. The results of studies on severe asthma showed that adding tiotropium to a treatment with high doses of an ICS plus LABA results in further improvement in lung function, increases the time to the first severe exacerbation of asthma and to worsening of asthma, and improves asthma control. Except for dry mouth, the safety profile of tiotropium was similar to placebo both in moderate and in severe asthma. Adding tiotropium to an ICS or ICS plus LABA improves lung function, symptoms, and asthma control, and in severe asthma, it increases the time to exacerbations, with good safety profile. The effect seems independent of baseline characteristics such as age, level of bronchial obstruction, smoking status, allergic status, and bronchial reversibility.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Drug Administration Schedule; Glucocorticoids; Humans; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Tiotropium Bromide; Treatment Outcome

This meta-analysis was performed to evaluate the efficacy and safety of the addition of tiotropium to standard treatment regimens for inadequately controlled asthma.. A systematic search was made of PubMed, EMBASE, MEDLINE, and CENTRAL databases, and ClinicalTrials.gov, and a hand search of leading respiratory journals. Randomized, double-blind clinical trials on the treatment of inadequately controlled asthma for ≥ 4 weeks with the addition of tiotropium, compared with placebo, were reviewed. Studies were pooled to odds ratio (OR) and weighted mean differences (WMDs), with 95% CI.. Six trials met the inclusion criteria. The addition of tiotropium, compared with placebo, significantly improved all spirometric indices, including morning and evening peak expiratory flow (WMD 20.59 L/min, 95% CI 15.36-25.81 L/min, P < .001; and WMD 24.95 L/min, 95% CI 19.22-30.69 L/min, P < .001, respectively), trough and peak FEV1 (WMD 0.13 L, 95% CI 0.09-0.18 L, P < .001; and WMD 0.10 L, 95% CI 0.06-0.14 L, P < .001, respectively), the area under the curve of the first 3 h of FEV1 (WMD 0.13 L, 95% CI 0.08-0.18 L, P < .001), trough and peak FVC (WMD 0.1 L, 95% CI 0.05-0.15 L, P < .001; and WMD 0.08 L, 95% CI 0.04-0.13 L, P < .001, respectively), the area under the curve of the first 3 h of FVC (WMD 0.11 L, 95% CI 0.06-0.15 L, P < .001). The mean change in the 7-point Asthma Control Questionnaire score (WMD -0.12, 95% CI -0.21 to -0.03, P = .01) was markedly lower in tiotropium group, but not clinically important. There were no significant differences in Asthma Quality of Life Questionnaire score (WMD 0.09, 95% CI -0.01 to 0.20, P = .09), night awakenings (WMD 0.00, 95% CI -0.05 to 0.05, P = .99) or rescue medication use (WMD -0.18, 95% CI -0.36 to 0.00, P = .06). No significant increase was noticed in adverse events in the tiotropium group (OR 0.80, 95% CI 0.62-1.03, P = .08).. The addition of tiotropium to standard treatment regimens has significantly improved lung function without increasing adverse events in patients with inadequately controlled asthma. Long-term trials are required to assess the effects of the addition of tiotropium on asthma exacerbations and mortality.

Topics: Asthma; Bronchodilator Agents; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Severity of Illness Index; Spirometry; Tiotropium Bromide; Vital Capacity

Asthma is a chronic disease with a significant disease burden, and many patients fail to achieve disease control despite recommended medical therapy. Recent evidence suggests that there may be benefits to the use of the long-acting anticholinergic agent tiotropium in patients with asthma.. We performed a systematic review of the literature to determine the role of tiotropium in management of adult patients with asthma.. In six studies, 1773 patients were randomized and 1057 received tiotropium as an intervention. The mean prebronchodilator forced expiratory volume in 1 second was 60.1%. All six studies reported a small but statistically significant improvement in spirometry when using tiotropium as compared with the control. Improvement was reported in patients with both moderate and severe asthma, patients uncontrolled on previous regimens, patients treated with low- to high-dose inhaled corticosteroids regimens, and patients treated with and without long-acting β-agonist therapy. Five studies evaluated clinical outcomes with tiotropium with variable success rates. Although a large randomized trial demonstrated a reduction in the frequency of severe asthma exacerbation with tiotropium, there is insufficient evidence to support the argument that tiotropium therapy leads to improvements in asthma symptom measures, asthma control days, asthma-related quality-of-life-scores, or rescue inhaler use.. There is strong evidence supporting improvement in spirometry and asthma exacerbations with tiotropium in patients with moderate and severe asthma; therefore, tiotropium may be an effective intervention in patients with asthma.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Evidence-Based Medicine; Forced Expiratory Volume; Glucocorticoids; Humans; Quality of Life; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

A novel effective treatment is necessary for severe asthma.. To review clinical trials examining the role of tiotropium in patients with poorly controlled asthma despite inhaled corticosteroid use with or without long-acting β₂-agonists.. A computerised search of electronic databases (Medline, EMBASE and Cochrane Central Register) was performed. Randomised controlled trials of at least a 4-week treatment duration with findings published in English were included.. Five studies involving 1635 patients were analysed. Compared with a placebo or a double dose of inhaled corticosteroids, the addition of tiotropium increased mean trough and peak forced expiratory volume in 1 second by 97 ml (95%CI 71-122) and 103 ml (95%CI 42-163), respectively. The mean differences in morning peak expiratory flow were 19.2 l/min (95%CI 11.8-26.6). Tiotropium also reduced the risk of severe acute exacerbation (OR 0.73, 95%CI 0.56-0.96) and improved Asthma Quality-of-Life Questionnaire score significantly by 0.10 (95%CI 0.04-0.16). There were no differences in serious adverse events.. The addition of tiotropium may be beneficial for patients with poorly controlled asthma, although exacerbation or safety issues should be clarified in long-term trials before its wide use in asthma.

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Chi-Square Distribution; Cholinergic Antagonists; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Lung; Odds Ratio; Quality of Life; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

In uncontrolled asthma, the suboptimally inhibited airways inflammation is the main pathogenic event. Addition of other medications to the regular regimen might be able to improve disease control by enhancing bronchodilation and/or by reducing the bronchial inflammation. Tiotropium is currently under evaluation as a potential such therapy.. The long-term efficacy and safety of tiotropium was recently evaluated in two studies in patients with poorly controlled asthma under inhaled corticosteroids + long-acting β2 agonists. Tiotropium was able to improve lung function and the effect was sustained, reduced the exacerbations risk (and in particular severe exacerbations risk), but had a marginal effect on symptoms and on quality of life.. In asthma, inhaled tiotropium is able to increase the bronchodilation, and might also be able to exert an anti-inflammatory effect.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide

To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma.. A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics.. Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not.. Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting β-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the β2-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified.. Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.

Topics: Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glucocorticoids; Humans; Neutrophils; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Respiratory Function Tests; Saliva; Scopolamine Derivatives; Tiotropium Bromide

The use of anticholinergic medications is well established as maintenance therapy for chronic obstructive pulmonary disease (COPD). There is a growing interest in the use of anticholinergic medications in the treatment of moderate to severe asthma. The purpose of this review is to summarize the scientific evidence for the use of anticholinergic therapy in the management of asthma.. Early case reports and small studies evaluated the use of the anticholinergic agent, tiotropium bromide, as maintenance therapy in asthma. Included in this review are several recent clinical trials which provide additional evidence for the use of tiotropium as add-on therapy for asthma. The use of tiotropium was demonstrated to be superior to doubling the dose of an inhaled corticosteroid (ICS) and more effective than placebo based on change in morning peak expiratory flow (PEF). Two large multinational trials provide evidence for the use of tiotropium in a subset of asthmatic patients who have not achieved control using combination therapy with an ICS and a long-acting β2 agonist (LABA).. The use of the long-acting anticholinergic agent, tiotropium, as maintenance of therapy in asthma, has been shown to be effective in some patients with moderate to severe asthma who are uncontrolled on combination therapy with ICS and LABA. Further studies are needed to better define which phenotypic subset of patients would benefit from the use of tiotropium.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Cholinergic Antagonists; Drug Therapy, Combination; Humans; Multicenter Studies as Topic; Peak Expiratory Flow Rate; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Asthma is an inflammatory disease of the lower airways. The typical symptoms of asthma are cough, wheezing and shortness of breath. Asthma is diagnosed based on measures of pulmonary function showing variable or reversible airways obstruction. The basic pharmacological treatment consists of alleviating the asthmatic inflammation with regular inhaled glucocorticoids and relieving sudden obstructions with as-needed inhaled beta2-agonists. The treatment is adjusted based on asthma control. If good control of asthma is not achieved with low to medium doses of inhaled glucocorticoids, additional control medication (inhaled long acting beta2-agonists, antileukotrienes, in adults also theophylline or tiotrohium) should be introduced.

Topics: Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Glucocorticoids; Humans; Leukotriene Antagonists; Practice Guidelines as Topic; Respiratory Function Tests; Scopolamine Derivatives; Theophylline; Tiotropium Bromide

Olodaterol (Striverdi(®) Respimat(®)) is a novel, long-acting, β2-adrenergic receptor agonist developed by Boehringer Ingelheim for the treatment of chronic obstructive pulmonary disease (COPD). The drug is delivered via the Respimat(®) Soft Mist™ inhaler. Olodaterol received its first global approval for the once-daily maintenance treatment of COPD in Canada and Russia, and submissions for regulatory approval have also been made in the USA, the EU and elsewhere. Phase II trials have been conducted in patients with asthma. The company is also developing a fixed-dose combination of olodaterol with tiotropium bromide, a long-acting anti-muscarinic agent, for the treatment of COPD. This article summarizes the milestones in the development of olodaterol leading to this first approval for COPD.

Topics: Administration, Inhalation; Asthma; Benzoxazines; Bronchodilator Agents; Clinical Trials, Phase II as Topic; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed, its stated mission was to perform multiple controlled clinical trials for treating patients with asthma by dispassionately examining new and existing therapies, and to rapidly communicate its findings to the medical community. The ACRN conducted 15 major clinical trials. In addition, clinical data, manual of operations, protocols and template informed consents from all ACRN trials are available via NHLBI BioLINCC (https://biolincc.nhlbi.nih.gov/studies/). This network contributed major insights into the use of inhaled corticosteroids, short-acting and long-acting ß-adrenergic agonists, leukotriene receptor antagonists, and novel agents (tiotropium, colchicine and macrolide antibiotics). They also pioneered studies of the variability in drug response, predictors of treatment response and pharmacogenetics. This review highlights the major research observations from the ACRN that have impacted the current management of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Biomarkers; Biomedical Research; Bronchodilator Agents; Humans; Macrolides; Scopolamine Derivatives; Tiotropium Bromide

Topics: Asthma; Cholinergic Antagonists; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

For many years, chronic obstructive pulmonary disease (COPD) was considered a disease of fixed airflow obstruction for which there was no good treatment. Out of desperation and frustration, health care providers extrapolated from asthma to COPD, and standard asthma therapy was adopted without evidence for efficacy. In recent years, we have gained a better understanding of the pathophysiologic differences between asthma and COPD, and prospective controlled trials have provided a rationale for therapy. Smoking cessation is critically important, both as primary prevention and as an effective way to slow the decrease in lung function in patients with established disease. beta(2)-Adrenergic and anticholinergic agonists improve lung function and relieve symptoms in most patients. Tiotropium improves exercise tolerance and quality of life and reduces exacerbations and hospitalizations. The increase in lung function seen with tiotropium is sustained with continued use over at least 3 to 4 years. Inhaled corticosteroids decrease exacerbations and improve quality of life, and their effect seems greatest in patients with lower lung function and in exacerbation-prone patients. There is no evidence that inhaled corticosteroids alone affect mortality, despite the reduction in exacerbations and increased risk of pneumonia. In some patient populations, inhaled fluticasone, salmeterol, or the combination might slow the rate of loss of lung function. Rather than reflexively using effective asthma therapy in the patient with COPD, current and future therapy for COPD is increasingly evidence based and targeted to specific inflammatory pathways that are important in patients with COPD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Albuterol; Androstadienes; Antioxidants; Asthma; Bacterial Vaccines; Bronchodilator Agents; Clinical Trials as Topic; Fluticasone; Humans; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Viral Vaccines

The prevalence of chronic airways diseases such as chronic obstructive pulmonary disease and asthma is increasing. They lead to symptoms such as a cough and shortness of breath, partially through bronchoconstriction. Inhaled anticholinergics are one of a number of treatments designed to treat bronchoconstriction in airways disease. Both short-acting and long-acting agents are now available and this review highlights their efficacy and adverse event profile in chronic airways diseases.

Topics: Asthma; Cholinergic Antagonists; Chronic Disease; Cost-Benefit Analysis; Humans; Ipratropium; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide

Anticholinergic agents have important uses as bronchodilators for the treatment of obstructive airway diseases, both asthma and, more particularly, chronic obstructive pulmonary disease (COPD). Those in approved clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide, each of which is very poorly absorbed when given by inhalation. Ipratropium and oxitropium have relatively short durations of action (4-8 h). They have been widely used for many years, either alone or in combination with short-acting beta-adrenergic agents such as albuterol and fenoterol, for both maintenance treatment of stable disease and for acute exacerbations of airway obstruction. Tiotropium, which was introduced in the early 2000s, has a duration of action of at least 1-2 days making it suitable for once-daily maintenance treatment of COPD. All of the above agents have a wide therapeutic margin and are safe and well tolerated by patients.

Topics: Asthma; Bronchodilator Agents; Cholinergic Antagonists; Clinical Trials as Topic; Humans; Ipratropium; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Long-acting beta(2) agonists are an effective and convenient treatment for chronic obstructive pulmonary disease (COPD), but do not significantly improve lung function. The long-acting anticholinergic tiotropium, which can be taken once daily, decreases exertional dyspnoea and increases endurance by reducing hyperinflation. The role in COPD of the combination of a long-acting beta(2) agonist and a glucocorticoid in a single inhaler remains unclear. The minimum duration of an effective pulmonary rehabilitation program that includes exercise training is 6 weeks. Long-term treatment with inhaled glucocorticoids may reduce the rate of decline in lung function, but the effect is small. Aminophylline should no longer be routinely used in acute exacerbations of COPD. Non-invasive positive pressure ventilation (NPPV) reduces mortality and hospital stay in patients with acute hypercapnic ventilatory failure; it is also an effective weaning strategy for patients who require intubation. Further studies are required to clarify the role of NPPV in the long-term management of stable COPD.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-Agonists; Asthma; Australia; Bronchodilator Agents; Diagnosis, Differential; Drug Combinations; Evidence-Based Medicine; Expectorants; Glucocorticoids; Humans; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Factors; Scopolamine Derivatives; Social Support; Tiotropium Bromide; Vaccination

Anticholinergics are widely used for the treatment of COPD, and to a lesser extent for asthma. Primarily used as bronchodilators, they reverse the action of vagally derived acetylcholine on airway smooth muscle contraction. Recent novel studies suggest that the effects of anticholinergics likely extend far beyond inducing bronchodilation, as the novel anticholinergic drug tiotropium bromide can effectively inhibit accelerated decline of lung function in COPD patients. Vagal tone is increased in airway inflammation associated with asthma and COPD; this results from exaggerated acetylcholine release and enhanced expression of downstream signaling components in airway smooth muscle. Vagally derived acetylcholine also regulates mucus production in the airways. A number of recent research papers also indicate that acetylcholine, acting through muscarinic receptors, may in part regulate pathological changes associated with airway remodeling. Muscarinic receptor signalling regulates airway smooth muscle thickening and differentiation, both in vitro and in vivo. Furthermore, acetylcholine and its synthesizing enzyme, choline acetyl transferase (ChAT), are ubiquitously expressed throughout the airways. Most notably epithelial cells and inflammatory cells generate acetylcholine, and express functional muscarinic receptors. Interestingly, recent work indicates the expression and function of muscarinic receptors on neutrophils is increased in COPD. Considering the potential broad role for endogenous acetylcholine in airway biology, this review summarizes established and novel aspects of muscarinic receptor signaling in relation to the pathophysiology and treatment of asthma and COPD.

Topics: Acetylcholine; Animals; Asthma; Bronchodilator Agents; Cell Differentiation; Cell Proliferation; Fibroblasts; Humans; Lung; Lymphocytes; Mucus; Muscarinic Antagonists; Muscle, Smooth; Neutrophils; Pulmonary Disease, Chronic Obstructive; Receptors, Muscarinic; Scopolamine Derivatives; Signal Transduction; Tiotropium Bromide

Topics: Asthma; Bronchoconstriction; Bronchodilator Agents; Cholinergic Antagonists; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Tiotropium bromide (Spiriva, BA679BR, Boehringer Ingelheim) is a novel inhaled, long-acting anticholinergic bronchodilator that is employed as a once-daily maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). Like ipratropium bromide, tiotropium bromide is a quaternary ammonium derivative that binds to muscarinic receptors. However, although tiotropium binds with high affinity to muscarinic receptors of M1-, M2- and M3-subtypes, it dissociates very slowly from M1- and M3-receptors but more rapidly from M2-receptors, thereby giving it a unique kinetic selectivity. To date, the short-acting anticholinergic agents ipratropium and oxitropium bromide have been extensively employed as bronchodilator therapy for patients with COPD. Indeed, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy emphasises the role of bronchodilators in symptomatic management of all stages of COPD. It is encouraging that tiotropium given once daily from a dry powder inhaler at 18 g has been shown to cause greater improvement in lung function and reduction in symptoms than ipratropium bromide given four times daily. Furthermore, clinical studies over a 1-year period have demonstrated that tiotropium has impressive and maintained effects on lung function, symptoms and health-related quality of life, and may also reduce exacerbations. In a recent large scale comparative study over 6 months, tiotropium has been shown to cause superior bronchodilation and symptomatic improvement when compared to twice daily salmeterol in COPD. The only significant reported adverse event is dry mouth, which is found in approximately 10%-15% of subjects, but this is reversible and rarely causes discontinuation of therapy. Based on these promising features, it is likely that tiotropium used alone or in combination with other bronchodilators will emerge as first-line maintenance treatment for patients with airway obstruction due to COPD.

Topics: Administration, Inhalation; Albuterol; Area Under Curve; Asthma; Biological Availability; Bronchodilator Agents; Clinical Trials as Topic; Half-Life; Humans; Pulmonary Disease, Chronic Obstructive; Receptors, Muscarinic; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Inhalation is the preferred route for the application of drugs in the management of airway diseases. Therefore it was aimed at developing drugs suitable for inhalation. An important step was the introduction of the short- and long-acting beta 2-agonists and of a new generation of anticholinergics with longer duration of action. Most important was the development of inhaled glucocorticoids allowing good asthma control without relevant side effects even in a long run. Furthermore, the devices for drug application have been improved, and CFCs were substituted by HFAs.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Aerosols; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Clinical Trials as Topic; Drug Combinations; Fluticasone; Glucocorticoids; Humans; Ipratropium; Patient Compliance; Placebos; Powders; Salmeterol Xinafoate; Scopolamine Derivatives; Time Factors; Tiotropium Bromide

Prior to a drug achieving its effects (ie, pharmacodynamics), there are numerous events within the body that determine its ultimate fate. The effects of the "body on the drug" has been referred to as pharmacokinetics-how the favorable lung-to-systemic effects predicted from this exercise translate into practice. Inhaled drugs have enjoyed the major feature of having "local" effects on the target organ of the lung. Broadly, lower doses can be used and adverse effects are often less than with oral or parenteral administration. Nevertheless, key features of respiratory drugs and their administration can impact their fate and ultimate utility. This review has provided some relevant examples of basic pharmacokinetics principles as related to inhaled products, with emphasis on those factors that help to partition lung-to-systemic effects.

Topics: Administration, Inhalation; Aerosols; Albuterol; Asthma; Bronchodilator Agents; Cholinergic Agents; Forced Expiratory Volume; Glucocorticoids; Humans; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Inhaled antimuscarinics, often called anticholinergics in clinical medicine, are established as first line bronchodilators in COPD. Tiotropium has been developed as a new generation antimuscarinic following ipratropium. Tiotropium is a specific, highly potent antimuscarinic, demonstrating very slow dissociation from muscarinic receptors. Dissociation from M2-receptors is faster than from M3 or M1, which in functional in vitro studies, appeared as kinetic receptor subtype selectivity of M3 and M1 over M2. The high potency and slow receptor dissociation found its clinical correlate in significant and long lasting bronchodilatation and bronchoprotection in patients with COPD and asthma. In asthma, protection against methacholine challenge exceeded the study period of 48 hours. In COPD, bronchodilatation of about 80% of the plateau was demonstrated after the first dose. Following chronic once daily inhalation for 28 days, the improvement in pulmonary function was sustained and there was a further increase in peak effects, but more importantly a rising baseline, achieving steady state within 2 weeks. Tiotropium achieves very stable long lasting effects with comparatively low variation of bronchodilatation between peak and trough (the level before the next administration). Stable 24 hour effectiveness profiles the compound as the first once daily bronchodilator. Clinical correlates of kinetic receptor subtype selective blockade remain to be shown. Plasma levels of tiotropium at trough are in the low pg/ml range and are unlikely to explain the sustained effectiveness in the airways. Slow dissociation from muscarinic receptors is likely to be responsible for the long duration of action.

Topics: Animals; Asthma; Binding Sites; Bronchodilator Agents; Cell Membrane; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Lung Diseases, Obstructive; Muscarinic Agonists; Muscarinic Antagonists; Receptors, Muscarinic; Scopolamine Derivatives; Tiotropium Bromide

We previously reported in an uncontrolled study that tiotropium alleviated chronic cough in asthma refractory to inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) by modulating capsaicin cough reflex sensitivity (C-CRS).. We sought to determine the antitussive effects of tiotropium for refractory cough in asthma in a randomized, parallel, open-label trial.. A total of 58 patients with asthma having chronic cough refractory to ICS/LABA were randomized in a 2:1 ratio to add tiotropium 5 μg (39 patients) or theophylline 400 mg (19 patients) for 4 weeks. Patients underwent workups, including capsaicin cough challenge test and subjective measures such as cough severity visual analog scales (VAS). We adopted C5, the lowest capsaicin concentration to induce at least 5 coughs, as an index of C-CRS. We also performed a posthoc analysis to identify factors predicting tiotropium responders, who found an improvement of at least 15 mm in cough severity VAS.. A total of 52 patients (tiotropium, 38; theophylline, 14) completed the study. Both tiotropium and theophylline significantly improved cough severity VAS and cough-specific quality of life. Tiotropium, but not theophylline, significantly increased C5, whereas pulmonary function did not change in either group. In addition, changes in cough severity VAS correlated with changes in C5 values in the tiotropium group. A posthoc analysis revealed that heightened C-CRS (C5 ≤1.22 µM) before the addition of tiotropium was an independent predictor for tiotropium responders.. Tiotropium may alleviate chronic cough in asthma refractory to ICS/LABA by modulating C-CRS. Heightened C-CRS may predict responsiveness to tiotropium for refractory cough in asthma.. Clinical Trials Registry ID: UMIN000021064 (https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000024253).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Capsaicin; Cough; Drug Therapy, Combination; Humans; Quality of Life; Reflex; Theophylline; Tiotropium Bromide

Loss of bronchoprotection against direct and indirect acting stimuli following regular use of inhaled beta. We performed a randomized, double-blind, placebo-controlled cross-over study comparing tiotropium Respimat® 5 μg to placebo in adult asthmatics. Each treatment arm began with baseline methacholine challenge followed immediately by treatment administration. One hour later a post treatment methacholine challenge was performed. Participants dosed daily (two puffs) at home for the next six days and returned to the lab on Day 8 for a final dose of treatment 1 h prior to methacholine challenge.. The average doubling dose increase in methacholine PD. LAMA are indicated for use as add-on monotherapy or in triple therapy combination for poorly controlled asthma. It may be reassuring to know therefore, that regular use does not result in loss of bronchoprotection like that which occurs with beta

Topics: Administration, Inhalation; Adult; Asthma; Bronchoconstriction; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Humans; Methacholine Chloride; Muscarinic Antagonists; Receptors, Muscarinic; Tiotropium Bromide

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4-5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2-5, a post hoc analysis of five double-blind trials (12-48-weeks; patients aged 18-75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Humans; Lung; Male; Middle Aged; Tiotropium Bromide; Treatment Outcome

Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control.. We investigated the effects on small airways of adding long-acting beta-agonist (LABA) alone or with long-acting muscarinic antagonist (LAMA) to ICS in asthmatic smokers.. Sixteen current smokers were enrolled: mean age 44 year, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack year . Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800 µg/day. Open label olodaterol 5 µg od (OLO) or olodaterol 5 µg/tiotropium 5 µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 weeks in a randomized cross over design, including run-in and washout periods on HFA-BDP. IOS and spirometry were measured after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP).. After chronic dosing, IOS outcomes at trough except for R20 were all significantly improved with OLO/TIO compared to OLO. For the primary end-point of total airway resistance (as R5), the mean difference (95%CI) at trough was 0.06 (0.015-0.10) kPa/l/s, peripheral airways resistance (as R5-R20) 0.03 (0.003-0.06) kPa/l/s, peripheral lung reactance area (as AX) 0.38 (0.08-0.68) kPa/l and resonant frequency (as RF) 2.28 (0.45-4.12) Hz. FEF25-75 at trough was also better with OLO/TIO vs TIO: 0.93 (0.86 - 0.95) l/s while FEV1 was not different.. ICS/LABA/LAMA was superior to ICS/LABA on trough small airway outcomes in asthma patients who smoke.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Benzoxazines; Cross-Over Studies; Drug Combinations; Female; Humans; Lung; Male; Muscarinic Antagonists; Nebulizers and Vaporizers; Recovery of Function; Scotland; Smokers; Smoking; Time Factors; Tiotropium Bromide; Treatment Outcome

Exacerbations account for much of the morbidity in asthma. In a large intervention study, we sought to test the hypothesis that a Black adult exacerbation-prone phenotype - a group of Black people with asthma who are at high risk of repeat exacerbation within one year - exists in asthma independent of clinical control.. We analyzed exacerbation risk factors in 536 self-identified Black Americans with asthma eligible for, or on, Step 3 National Asthma Education and Prevention Program (NAEPP) therapy who participated in a randomized 6-18 month trial of tiotropium versus long acting beta agonist as add-on therapy to inhaled corticosteroids. Exacerbations were defined as events treated by oral or systemic corticosteroids. Clinical control was assessed by a validated asthma control questionnaire (ACQ5).. Exacerbations became more likely with loss of clinical control. The mean baseline ACQs for exacerbators and non-exacerbators were 2.41 and 1.91, respectively (p < 0.001). The strongest independent factor associated with exacerbations across all ACQ levels was an exacerbation in the preceding year (adjusted OR 3.26; p < 0.001). The severity of prior exacerbations did not correlate with the likelihood of a future exacerbation. Lower baseline FEV1/FVC was also associated with increased risk of exacerbations.. Even though exacerbations increase with loss of clinical control, an exacerbation susceptibility phenotype exists in Black adults with asthma, independent of clinical control. This phenotype requires precision therapeutic targeting.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Black or African American; Disease Progression; Female; Humans; Male; Middle Aged; Risk Factors; Tiotropium Bromide

To compare the efficacy of inhaled glucocorticoid with or without tiotropium bromide in the treatment of patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS).. An experimental study.. Department of Respiratory Medicine, Wuwei People's Hospital, Gansu Province, China, from October 2016 to October 2017.. A total of 86 ACOS patients were randomly divided into the control group and the observation group, with 43 cases in each group. Control group was given inhaled glucocorticoid. Observation group was treated with tiotropium bromide on the basis of the control group. The asthma control test (ACT) score, chronic obstructive pulmonary disease assessment test (CAT) score, serum high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels were compared.. Before treatment, there was no significant difference in ACT score, CAT score, serum hs-CRP and IL-6 levels between the two groups (p=0.808, 0.612, 0.872 and 0.921, respectively). After treatment, ACT score in observation group was higher than that in control group (p <0.001). CAT score, serum hs-CRP, and IL-6 levels in observation group were lower than those in control group (all p <0.001). The incidence of adverse reactions was lower in observation group than that in control group (p=0.033).. Compared with inhaled glucocorticoid, inhaled glucocorticoid combined with tiotropium bromide treatment can more effectively reduce the serum levels of hs-CRP and IL-6 and is beneficial to control the development of ACOS.

Topics: Administration, Inhalation; Adult; Age Factors; Aged; Asthma; China; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Assessment; Sex Factors; Tiotropium Bromide; Treatment Outcome; Undifferentiated Connective Tissue Diseases

There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cholinergic Antagonists; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Infant; Male; Nebulizers and Vaporizers; Seasons; Tiotropium Bromide; Treatment Outcome

In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown.. In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level.. A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P = 0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P = 0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%).. The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level. (Funded by the National Heart, Lung, and Blood Institute; SIENA ClinicalTrials.gov number, NCT02066298.).

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Glucocorticoids; Humans; Leukocyte Count; Male; Medication Adherence; Middle Aged; Mometasone Furoate; Sputum; Tiotropium Bromide; Young Adult

Black patients with asthma have a higher disease burden and greater morbidity compared with other racial/ethnic groups. Tiotropium Respimat. Data were pooled from 12 randomized, placebo-controlled, parallel-group, Phase II or III trials from the global Boehringer Ingelheim program with once-daily tiotropium Respimat. Of the 5165 patients treated with tiotropium or placebo, 3.2% were black or African American. For both doses of tiotropium, the proportion of patients reporting adverse events (AEs) was approximately 10% lower compared with placebo and was generally comparable with the proportion of patients reporting AEs in all groups of the overall population. The number of investigator-assessed drug-related AEs, AEs leading to trial drug discontinuation or serious AEs reported by patients was low and comparable between treatment groups and with the overall population.. Tiotropium Respimat. NCT01634113, NCT01634139, NCT01634152, NCT01257230, NCT01277523, NCT01316380, NCT00350207, NCT01172808, NCT01172821, NCT01340209, NCT00772538, NCT00776984.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Black or African American; Child; Child, Preschool; Cholinergic Antagonists; Drug Therapy, Combination; Humans; Infant; Middle Aged; Placebos; Safety; Tiotropium Bromide; Treatment Outcome; Young Adult

Few studies have assessed the safety and efficacy of potential asthma medications in children younger than 5 years. We descriptively assessed the safety and efficacy of tiotropium, a long-acting anticholinergic drug, in children aged 1-5 years with persistent asthmatic symptoms.. This exploratory 12-week, randomised, double-blind, placebo-controlled, parallel-group, phase 2/3, regulatory multicentre trial was done at 32 hospitals, clinics, and clinical research units in 11 countries in Asia, Europe, and North America. Children aged 1-5 years with at least a 6-month history of persistent asthmatic symptoms and a need for inhaled corticosteroids were eligible. Patients were randomly allocated using an interactive voice or web-based response system to receive once-daily tiotropium 2·5 μg, tiotropium 5 μg, or placebo as an add-on to inhaled corticosteroids with or without additional controller medication. Patients and investigators were masked to study group assignment. Tiotropium was given via the Respimat inhaler once daily as two puffs of 1·25 μg in the 2·5 μg group, two puffs of 2·5 μg in the 5 μg group, or two puffs of placebo. The primary outcomes were safety, which was assessed by comparing adverse events between the tiotropium and placebo groups, and efficacy, which was measured as the change in weekly mean combined daytime asthma symptom score from baseline to week 12. Statistical analyses of treatment effects were exploratory; although endpoints were defined, they were used for descriptive analyses only. The safety and primary analyses were done in all patients who received at least one dose of their assigned treatment. This study is registered with ClinicalTrials.gov (NCT01634113), and is completed.. Between July 26, 2012, and Dec 4, 2014, 102 children were randomly assigned to the three treatment groups (36 to receive tiotropium 2·5 μg, 32 to receive tiotropium 5 μg, and 34 to receive placebo). 101 children completed the study and were included in the analyses. The changes in adjusted weekly mean combined daytime asthma symptom scores between baseline and week 12 were not significantly different between any of the groups. The adjusted mean difference between the tiotropium 2·5 μg group and placebo group was -0·080 (95% CI -0·312 to 0·152) and the difference between tiotropium 5 μg and placebo group was -0·048 (-0·292 to 0·195). Adverse events were less frequent with tiotropium treatment than with placebo (20 [56%] of 36 children with tiotropium 2·5 μg, 18 [58%] of 31 with tiotropium 5 μg, and 25 [74%] of 34 with placebo), although no formal statistical comparison between groups was performed. A greater proportion of children reported asthma exacerbations as adverse events in the placebo group (ten [29%] of 34) than in the tiotropium groups (five [14%] of 36 in the 2·5 μg group and two [6%] of 31 in the 5 μg group). Serious adverse events were reported in three patients (all of whom received placebo); no adverse events led to discontinuation of treatment or death.. To our knowledge, our small study is the first to assess the safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms. Tolerability of tiotropium was similar to that of placebo, which is consistent with previous findings in older populations. Although mean daytime asthma symptom scores were not significantly different between groups, tiotropium showed the potential to reduce asthma exacerbation risk compared with placebo. The findings of the study are limited by the small sample size and descriptive statistical analyses. Additional well powered trials are needed to further assess the safety and efficacy of tiotropium in young children.. Boehringer Ingelheim.

Topics: Asia; Asthma; Bronchodilator Agents; Child, Preschool; Double-Blind Method; Europe; Female; Humans; Infant; Male; North America; Tiotropium Bromide; Treatment Outcome

BACKGROUND The aim of this study was to evaluate the therapeutic effects of tiotropium bromide on asthma. MATERIAL AND METHODS A total of 160 patients with moderate persistent asthma were randomly divided into 4 groups (n=40): the 3 control groups were given fluticasone propionate aerosol (group A), salmeterol-fluticasone propionate inhalant (group B), and tiotropium bromide inhalation powder combined with salmeterol-fluticasone propionate inhalant (group C), respectively, and the experimental group received tiotropium bromide inhalation powder combined with fluticasone propionate aerosol (group D) and salbutamol was used to relieve symptoms when necessary. RESULTS After 8 weeks of treatment, the pulmonary function of group D, which was significantly better than those of group A (P<0.05), was similar to those of groups B and C (P>0.05). Group D had significantly better asthma control test scores and nighttime symptom scores than in group A (P<0.05), without significant differences from those of group B or group C (P>0.05). The number of times salbutamol was used to alleviate symptoms was significantly different (P<0.05) between group D and group A (P<0.05), as well as between group C and group D (P<0.05). Groups D and B had similar results (P>0.05). IL-13 levels in induced sputum had significant differences (P<0.05). The levels in group D, which were higher than those of groups A and B (P<0.05), were similar to those of group C (P>0.05). CONCLUSIONS Tiotropium bromide combined with fluticasone propionate improved the respiratory function and quality of life, and is a new therapy for moderate, persistent asthma.

Topics: Adult; Albuterol; Asthma; Cholinergic Antagonists; Female; Humans; Inflammation; Interleukin-13; Male; Respiratory Function Tests; Sputum; Tiotropium Bromide; Treatment Outcome

Topics: Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Humans; Male; Tiotropium Bromide; Treatment Outcome

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Double-Blind Method; Humans; Leukotriene Antagonists; Nedocromil; Pulmonary Eosinophilia; Tiotropium Bromide; Treatment Outcome; Xanthine

We present results from the first phase III trial of once-daily tiotropium add-on to inhaled corticosteroids (ICS) plus one or more controller therapies in adolescents with severe symptomatic asthma.In this double-blind, parallel-group trial (NCT01277523), 392 patients aged 12-17 years were randomised to receive once-daily tiotropium 5 µg or 2.5 µg, or placebo, as an add-on to ICS plus other controller therapies over 12 weeks. The primary and key secondary end-points were change from baseline (response) in peak forced expiratory volume in 1 s (FEV

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Child; Cholinergic Antagonists; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; International Cooperation; Male; Proportional Hazards Models; Tiotropium Bromide; Treatment Outcome

Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.. We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.. In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy.. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV. Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Chemotherapy, Adjuvant; Child; Cholinergic Antagonists; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Placebo Effect; Respiratory Function Tests; Tiotropium Bromide; Treatment Outcome

To evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma.. Reports of randomized controlled trials (RCTs) describing tiotropium for treatment of severe persistent asthma published from January 1946 to February 2015 were searched in Cochrane Library, ClinicalTrials.gov, PubMed, Ovid Medline, CNKI, and CSJD. The data of the included RCTs were extracted and the data quality was evaluated. Meta-analyses were performed with Revman 5.3 software.. Five RCTs including 1433 patients were analyzed. Meta-analysis of the data showed that compared with the placebo group, tiotropium treatment significantly improved the patients' peak forced expiratory volume in one second (FEV1) [weighted mean difference (WMD): 0.13 L, 95% confidence interval (CI): 0.10-0.16 L, P<0.00001], trough FEV1 (WMD: 0.09 L, 95%CI: 0.06-0.12 L, P<0.00001), peak forced vital capacity (FVC) (WMD: 0.10 L, 95%CI: 0.06-0.14 L, P<0.00001), trough FVC (WMD: 0.12 L, 95%CI: 0.08-0.17 L, P<0.00001), morning peak expiratory flow (PEF) (WMD: 9.21 L/min, 95%CI: 4.2-14.23 L/min, P=0.0003), evening PEF (WMD: 22.06 L/min, 95%CI 13.05-31.08 L/min, P<0.00001). The scores of asthma control questionnaire (ACQ) (WMD: 0.01, 95% CI: -0.07-0.09, P=0.86) or asthma quality of life questionnaire (AQLQ)(WMD: 0.06, 95% CI:-0.18-0.06, P=0.33) were not affected by tiotropium. No significant difference with adverse events between tiotropium group and placebo group were reported in these included studies (P>0.05).. Tiotropium for severe persistent asthma treatment can improve FEV1, FVC, and PEF but may not improve the quality of life of the patients. Tiotropium is well tolerated and can be an add-on therapy for severe persistent asthma.

Topics: Asthma; Bronchodilator Agents; Humans; Quality of Life; Tiotropium Bromide

Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid (ICS) maintenance therapy.. We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma.. In this 48-week, double-blind, placebo-controlled, parallel-group study, 398 patients aged 12 to 17 years were randomized to receive 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg) of once-daily tiotropium or placebo (2 puffs) administered through the Respimat device every evening, each as add-on treatment to ICS background therapy, with or without a leukotriene receptor antagonist; long-acting β2-agonist therapy was not permitted during the study.. Improvement in peak FEV1 within 3 hours after dosing at 24 weeks (primary end point) was statistically significant with both tiotropium doses compared with placebo: 5 μg of tiotropium, 174 mL (95% CI, 76-272 mL); 2.5 μg of tiotropium, 134 mL (95% CI, 34-234 mL). Significant improvements in trough FEV1 at week 24 (a secondary end point) were observed with the 5-μg dose only. Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed.. Once-daily tiotropium significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma. Larger responses were observed with the 5-μg tiotropium dose.

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Area Under Curve; Asthma; Child; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Risk Factors; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

Many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic asthma.. To determine whether the efficacy of tiotropium add-on therapy is dependent on patients' baseline characteristics.. Two randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat(®) 5 μg add-on to ICS plus a LABA were performed in parallel in patients with severe symptomatic asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, time to first severe exacerbation, time to first episode of asthma worsening, and seven-question Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by baseline characteristics.. 912 patients were randomized: 456 received tiotropium and 456 received placebo. Tiotropium improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, compared with placebo, independent of baseline characteristics including gender, age, body mass index, disease duration, age at asthma onset, and FEV1 % predicted at screening and reversibility.. Once-daily tiotropium 5 μg compared with placebo improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, independent of a broad range of baseline characteristics, as add-on to ICS plus LABAs in patients with severe symptomatic asthma.. ClinicalTrials.gov; numbers NCT00772538 and NCT00776984 URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Airway Obstruction; Asthma; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Hypersensitivity; Male; Middle Aged; Severity of Illness Index; Smoking; Tiotropium Bromide

Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma.. To evaluate safety and tolerability of tiotropium delivered via the Respimat(®) device, compared with placebo, each as add-on to at least ICS therapy, in a pooled sample of adults with symptomatic asthma at different treatment steps.. Data were pooled from seven Phase II and III, randomised, double-blind, parallel-group trials of 12-52 weeks' treatment duration, which investigated once-daily tiotropium Respimat(®) (5 μg, 2.5 μg) versus placebo as add-on to different background maintenance therapy including at least ICS. Adverse events (AEs) including serious AEs were assessed throughout treatment + 30 days after the last dose of trial medication.. Of 3474 patients analysed, 2157 received tiotropium. The percentage of patients with AEs was comparable between treatment groups: tiotropium 5 μg, 60.8%; placebo 5 μg pool, 62.5%; tiotropium 2.5 μg, 57.1%; placebo 2.5 μg pool, 55.1%. Consistent with the disease profile, the most frequent AEs overall were asthma, decreased peak expiratory flow rate (both less frequent with tiotropium) and nasopharyngitis. Overall incidence of dry mouth, commonly associated with use of anticholinergics, was low: tiotropium 5 μg, 1.0%; placebo 5 μg pool, 0.5%; tiotropium 2.5 μg, 0.4%; placebo 2.5 μg pool, 0.5%. The percentage of cardiac disorder AEs was comparable between tiotropium and placebo: tiotropium 5 μg, 1.4%; placebo 5 μg pool, 1.4%; tiotropium 2.5 μg, 1.4%; placebo 2.5 μg pool, 1.1%. The proportions of patients with serious AEs were balanced across groups: tiotropium 5 μg, 4.0%; placebo 5 μg pool, 4.9%; tiotropium 2.5 μg, 2.0%; placebo 2.5 μg pool, 3.3%.. Tiotropium Respimat(®) demonstrated safety and tolerability comparable with those of placebo, as add-on to at least ICS therapy, at different treatment steps in adults with symptomatic asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Tiotropium Bromide; Treatment Outcome

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.. NCT02622243.

Topics: Adult; Aged; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Cholinergic Antagonists; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Glycopyrrolate; Guidelines as Topic; Humans; Male; Methacholine Chloride; Muscarinic Antagonists; Tiotropium Bromide

Tiotropium, a once-daily, long-acting anticholinergic bronchodilator, has shown efficacy and safety as an add-on to maintenance therapy in patients with symptomatic asthma.. The aim of the present study was to assess the effect of tiotropium on airway geometry and airway inflammation in patients with asthma who were symptomatic despite treatment with inhaled corticosteroid (ICS) plus a long-acting beta 2agonist (LABA).. In total, 53 patients with symptomatic asthma who received ICS plus LABA and who had a prebronchodilator forced expiratory volume in 1 second of 6090% of the predicted value were randomized to the addition of tiotropium 5 g once daily (n = 25) or no add-on (n = 28) to maintenance therapy for 48 weeks. Quantitative computed tomography, fractional exhaled nitric oxide, and pulmonary function were measured.. Compared with maintenance therapy, the addition of tiotropium significantly decreased airway wall area (WA) corrected for body surface area (BSA) (WA/BSA) (p 0.05) and wall thickness (T) (T/BSA, p 0.05), and improved airflow obstruction. No significant difference in the change of fractional exhaled nitric oxide was observed between the two treatment groups. Changes in WA/BSA and T/BSA were significantly correlated with the change in predicted forced expiratory volume in 1 second (r = 0.87, p 0.001, and r = 0.82, p 0.001, respectively).. The addition of once-daily tiotropium to maintenance therapy improved airflow limitation and reduced airway T. A triple combination of tiotropium and ICS plus LABA may have additive protective effects of bronchodilation and remodeling.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Biomarkers; Bronchioles; Bronchodilator Agents; Female; Glucocorticoids; Humans; Immunoglobulin E; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Spirometry; Tiotropium Bromide; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

Data comparing various second-line treatments for asthma with subjective and objective assessment are lacking. This study aimed to compare the efficacy and safety of montelukast, doxofylline, and tiotropium with a low-dose budesonide in patients with mild to moderate persistent asthma.. Patients, all of whom were concurrently using inhaled budesonide (400 µg), were treated for 6 months with formoterol (12 µg), montelukast (10 mg), doxofylline (400 mg), or tiotropium (18 µg). Outcomes included forced expiratory volume in 1 second (FEV1), Saint George Respiratory Questionnaire (SGRQ) scores, asthma symptom scores (daytime and nighttime), and assessment of tolerability and rescue medication use.. A total of 297 patients completed the study. In all 4 groups, significant improvements were observed in all the outcome measures, with formoterol treatment having greater and earlier improvements than the other 3 second-line controller medications with budesonide. Among the second-line treatments, monteradlukast improved the FEV1 from day 45 (P < 0.01), SGRQ scores from day 30 (P < 0.0001), daytime scores from day 30 (P < 0.05), nighttime scores from day 30 (P < 0.0001), and rescue medication use from day 15 (P < .0001) at a faster rate than doxofylline or tiotropium with budesonide. No patients discontinued the treatment because of adverse reactions.. Among the tested second-line treatment regimens, the budesonide/montelukast combination was found to be superior to either the budesonide/doxofylline or budesonide/tiotropium combination in all the outcome measures without adversely affecting the tolerability of the patients. Further clinical studies with blinding techniques are likely to be useful.

Topics: Acetates; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Quinolines; Respiratory Function Tests; Sulfides; Theophylline; Tiotropium Bromide

Once-daily tiotropium Respimat(®) 5 μg is an efficacious add-on therapy to inhaled corticosteroids (ICS) with or without long-acting β2-agonists in patients with symptomatic asthma. The objective of this study was to investigate whether the dosing regimen of tiotropium (once- versus twice-daily), delivered via the Respimat(®) SoftMist™ inhaler, affected 24-h bronchodilator efficacy and safety versus placebo Respimat(®) in patients with asthma who were symptomatic despite medium-dose ICS therapy.. A randomised, double-blind, placebo-controlled, crossover study with 4-week treatment periods of tiotropium 5 μg (once-daily, evening) and 2.5 μg (twice-daily, morning and evening). The primary efficacy end point was forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 24 h (AUC)(0-24h) at the end of each treatment period. Secondary end points included peak forced expiratory volume in 1 s measured within 24 h of the last evening inhalation (peak FEV1(0-24h)), trough FEV1 measured prior to evening dosing, morning and evening peak expiratory flow (PEFam and PEFpm) and pharmacokinetic assessments.. 94 patients were randomised (mean age 44.3 years; mean asthma duration 21.3 years) and 89 (94.7%) completed the study. Significant and comparable bronchodilation was achieved over a 24-h period with both tiotropium dosing regimens. FEV1 AUC(0-24h) response (mean ± standard error) was significantly greater with both tiotropium dosing regimens (once-daily 5 μg: 158 ± 24 mL; twice-daily 2.5 μg; 149 ± 24 mL; both p < 0.01) when compared with placebo. Improvements in peak FEV1(0-24h), trough FEV1 and pre-dose PEFam/pm with both dosing regimens versus placebo were statistically significant (all p < 0.01), with no statistically significant differences between the tiotropium treatment regimens. Total systemic exposure and tolerability were comparable between treatment regimens.. Lung function improvements with tiotropium Respimat(®) add-on to medium-dose ICS were sustained and similar for once-daily 5 μg and twice-daily 2.5 μg, supporting tiotropium Respimat(®) 5 μg as a once-daily bronchodilator that provides efficacy over the whole 24-h dosing interval in patients with symptomatic asthma. ClinicalTrials.gov identifier: NCT01152450.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Austria; Bronchodilator Agents; Cross-Over Studies; Czech Republic; Dose-Response Relationship, Drug; Double-Blind Method; Estonia; Female; Forced Expiratory Volume; Germany; Humans; Latvia; Male; Middle Aged; Risk Factors; Tiotropium Bromide; Treatment Outcome

In patients with severe asthma, tiotropium improves lung function and exacerbation risk when added to high-dose inhaled corticosteroids plus long-acting β2 agonists. We aimed to assess the safety and efficacy of tiotropium in patients with moderate asthma who were symptomatic despite treatment with medium-dose inhaled corticosteroids.. We did two 24-week, replicate, randomised, double-blind, placebo-controlled, parallel-group, active-comparator trials at 233 sites in 14 countries. Eligible patients were aged 18-75 years with symptomatic asthma and a pre-bronchodilator forced expiratory volume in 1 s (FEV1) of 60-90% predicted despite use of medium-dose inhaled corticosteroids, and had never smoked or were ex-smokers for 1 year or more with 10 pack-years or less. Patients were randomly assigned (1:1:1:1), with computer-generated pseudorandom numbers, to receive once-daily tiotropium 5 μg or 2·5 μg, twice-daily salmeterol 50 μg, or placebo, while maintaining inhaled corticosteroids. Patients and study investigators were masked to treatment allocation. Prespecified co-primary endpoints, assessed at week 24 in the full analysis set, were peak FEV1 response, measured within the first 3 h after evening dosing; trough FEV1 response; and responder rate assessed according to the seven-question Asthma Control Questionnaire (ACQ-7). These studies are registered with ClinicalTrials.gov, numbers NCT01172808 and NCT01172821.. Between Aug 24, 2010, and Nov 13, 2012, we randomly assigned 2103 patients to the tiotropium 5 μg group (n=519), the tiotropium 2·5 μg group (n=520), the salmeterol group (n=541), or the placebo group (n=523); 1972 (94%) patients completed the study. Peak and trough FEV1 responses were significantly greater with tiotropium and salmeterol than with placebo and were similar in both studies. With pooled data, difference versus placebo in peak FEV1 was 185 mL (95% CI 146-223) in the tiotropium 5 μg group, 223 mL (185-262) in the tiotropium 2·5 μg group, and 196 mL (158-234) in the salmeterol group (all p<0·0001); difference in trough FEV1 was 146 mL (95% CI 105-188), 180 mL (138-221), and 114 mL (73-155; all p<0·0001), respectively. There were more ACQ-7 responders in the tiotropium 5 μg (OR 1·32, 95% CI 1·02-1·71; p=0·035) and 2·5 μg (1·33, 1·03-1·72; p=0·031) groups, and the salmeterol group (1·46, 1·13-1·89; p=0·0039), than in the placebo group. 48 (2%) of 2100 patients had serious adverse events (tiotropium 5 μg n=11, tiotropium 2·5 μg n=12, salmeterol n=11, placebo n=14).. Once-daily tiotropium add-on to medium-dose inhaled corticosteroids reduces airflow obstruction and improves asthma control in patients with moderate symptomatic asthma. Patterns of response with both tiotropium doses were similar to those of salmeterol, and all active compounds had good safety and tolerability. Tiotropium is a safe and effective bronchodilator, and an alternative to salmeterol in this patient population.. Boehringer Ingelheim.

Topics: Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome

A considerable number of children with asthma remain symptomatic despite treatment with inhaled corticosteroids, resulting in significant morbidity, reduced quality of life, increased healthcare costs and lost school days. The aim of our study was to assess the efficacy, safety and tolerability of once-daily tiotropium Respimat® 5 μg, 2.5 μg and 1.25 μg add-on to medium-dose inhaled corticosteroids, with or without a leukotriene modifier, in children aged 6-11 years with symptomatic asthma.. In this Phase II, double-blind, placebo-controlled, incomplete-crossover, dose-ranging study, patients were randomised to receive three of the four treatments evaluated: once-daily tiotropium Respimat® 5 μg, 2.5 μg or 1.25 μg or placebo Respimat®, in the evening during the 12-week (three × 4-week) treatment period.. In total, 76, 74, 75 and 76 patients aged 6-11 years received tiotropium Respimat® 5 μg, 2.5 μg, 1.25 μg and placebo Respimat®, respectively. For the primary end point (peak forced expiratory volume in 1 second measured within 3 hours post-dosing), the adjusted mean responses with tiotropium Respimat® 5 μg (272 mL), 2.5 μg (290 mL) and 1.25 μg (261 mL) were significantly greater than with placebo Respimat® (185 mL; p = 0.0002, p < 0.0001 and p = 0.0011, respectively). The safety and tolerability of all doses of tiotropium Respimat® were comparable with those of placebo Respimat®, with no serious adverse events and no events leading to discontinuation.. Tiotropium Respimat® add-on to medium-dose inhaled corticosteroids, with or without a leukotriene modifier, was efficacious in paediatric patients with symptomatic asthma and had comparable safety and tolerability with placebo Respimat®.. ClinicalTrials.gov identifier NCT01383499.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Age Factors; Asthma; Bronchodilator Agents; Child; Cholinergic Antagonists; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Lung; Male; Nebulizers and Vaporizers; Time Factors; Tiotropium Bromide; Treatment Outcome

This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β2-agonist (LABA).. 285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209).. to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV1) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.. At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.. The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.. ClinicalTrials.gov NCT01340209.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Treatment Outcome; Young Adult

The efficacy and safety of long-acting β-agonists (LABAs) have been questioned. Black populations may be disproportionately affected by LABA risks.. To compare the effectiveness and safety of tiotropium vs LABAs, when used with inhaled corticosteroids (ICS) in black adults with asthma and to determine whether allelic variation at the Arg16Gly locus of the β2-adrenergic receptor (ADRB2) geneis associated with treatment response.. A multisite (n = 20), open-label, parallel-group, pragmatic randomized clinical trial conducted from March 2011 through July 2013, enrolling black adults with moderate to severe asthma in the United States.. Patients eligible for, or receiving, step 3 or step 4 combination therapy per National Heart, Lung, and Blood Institute guidelines, received ICS plus either once-daily tiotropium (n = 532) or twice-daily LABAs (n = 538,) and were followed up for up to 18 months. Patients underwent genotyping, attended study visits at baseline, 1, 6, 12, and 18 months, and completed monthly questionnaires.. The primary outcome was time to asthma exacerbation, defined as a worsening asthma event requiring oral or parenteral corticosteroids. Secondary outcomes included patient-reported outcomes (Asthma Quality of Life Questionnaire, Asthma Control Questionnaire [ACQ], Asthma Symptom Utility Index, and Asthma Symptom-Free Days questionnaire), spirometry (FEV1), rescue medication use, asthma deteriorations, and adverse events.. There was no difference between LABA + ICS vs tiotropium + ICS in time to first exacerbation (mean No. of exacerbations/person-year, 0.42 vs 0.37 (rate ratio, 0.90 [95% CI, 0.73 to 1.11], log-rank P = .31). There was no difference in change in FEV1 at 12 months (0.003 L for LABA + ICS vs -0.018 L for tiotropium + ICS; between-group difference, 0.020 [95% CI, -0.021 to 0.061], P = .33) and at 18 months (-0.053 L vs -0.078 L; between-group difference, 0.025 [95% CI, -0.045 to 0.095], P = .49). There were no differences in ACQ score at 18 months (change in score from baseline, -0.68 for LABA + ICS vs -0.72 for tiotropium + ICS; between-group difference, 0.04 [95% CI, -0.18 to 0.27], P = .70). There were no differences in other patient-reported outcomes. Arg16Gly ADRB2 alleles were not associated with differences in the effects of tiotropium + ICS vs LABA + ICS (hazard ratio for time to first exacerbation, 0.84 [95% CI, 0.47 to 1.51] for Arg/Arg vs 0.85 [95% CI, 0.63 to 1.15] for Arg/Gly or Gly/Gly, P = .97).. Among black adults with asthma treated with ICS, adding a LABA did not improve time to asthma exacerbation compared with adding tiotropium. These findings were not affected by polymorphisms at the Arg16Gly locus of ADRB2. These findings do not support the superiority of LABA + ICS compared with tiotropium + ICS for black patients with asthma.. ClinicalTrials.gov identifier: NCT01290874.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Black or African American; Cholinergic Antagonists; Disease Progression; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Flow Rates; Formoterol Fumarate; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Despite their benefits in the treatment of cardiovascular disease, β-blockers are seldom used to treat asthmatics. We assessed the safety and tolerability of acute dosing with esmolol and propranolol in patients with asthma.. Post-hoc analysis of a double blind, randomised, placebo controlled trial of β-blocker use in asthma.. Mild-to-moderate asthmatics on inhaled corticosteroids.. Each participant underwent a 6-8 week dose titration of oral propranolol. A subgroup received an intravenous bolus dose of esmolol (0.5 mg/kg). Measurements were recorded pre- and post-esmolol and first dose exposure to 10 mg, 20 mg, and 80 mg of propranolol. Tiotropium was given concurrently with propranolol. Bronchoconstriction was reflected as a fall in forced expiratory volume in 1 s (FEV1) or increase in total airway resistance at 5 Hz (R5).. 12 patients completed the trial. There were no adverse effects on FEV1% or R5% following intravenous esmolol. There were significant reductions at 2 min post-esmolol in heart rate (-4.7 beats/min (bpm), 95% CI -7.9 to -1.3 bpm; p=0.002) and systolic blood pressure (-5.9 mm Hg, 95% CI -11.4 to -0.4 mm Hg; p=0.03). No bronchoconstriction was seen during up titration following the first dose of 10 mg, 20 mg or 80 mg of propranolol in the presence of tiotropium. No difference in the asthma control questionnaire at 80 mg propranolol was seen versus placebo in the presence of tiotropium.. Intravenous esmolol was administered without any adverse effects on pulmonary function in selected, stable, mild-to-moderate asthmatics controlled on inhaled corticosteroids. Tiotropium prevented propranolol induced bronchoconstriction after acute dosing during up-titration to 80 mg with no adverse impact on asthma control.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-Antagonists; Adult; Aged; Airway Resistance; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Injections, Intravenous; Male; Middle Aged; Propanolamines; Propranolol; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Young Adult

There is no comparative study among asthma patients receiving first-line versus various second-line treatment regimens for mild to moderate persistent asthma.. We assessed the pulmonary function in asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide in a pilot group.. Patients were recruited as per the study criteria and randomly allocated to 4 groups to receive budesonide (400 µg) with formoterol (12 µg), doxofylline (400 mg), montelukast (10 mg), or tiotropium (18 µg) for a period of 3 months. Outcomes included forced expiratory volume in 1 second (FEV1) and rescue medication use.. A total of 167 patients were recruited; among them, 123 patients completed the study. At baseline, no significant difference (P > 0.05) was observed in any of the outcome measures. Significant within-group improvement in FEV1 was observed in all the groups. At day 90, between-group difference revealed that improvement in FEV1 was significantly (P < 0.05) high for budesonide plus formoterol followed by budesonide plus doxofylline, budesonide plus montelukast, and, lastly, budesonide plus tiotropium. Similarly, within-group comparison revealed a significant (P < 0.05) reduction in rescue medication use in all the groups. The intensity in decrease was more in budesonide plus formoterol group followed by budesonide plus doxofylline, budesonide plus montelukast, and budesonide plus tiotropium groups.. On the basis of our findings, among the second-line treatment regimens, budesonide plus doxofylline and budesonide plus montelukast was found to be better than budesonide plus tiotropium in patients with mild to moderate persistent asthma. Further studies with a larger sample size are likely to be useful.

Topics: Acetates; Adult; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Quinolines; Respiratory Function Tests; Sulfides; Theophylline; Tiotropium Bromide

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat® SoftMist™ inhaler (tiotropium Respimat®) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting β2-agonists. To further explore the dose-response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat® as add-on to ICS in symptomatic patients with moderate persistent asthma.. In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotropium Respimat® 5 μg, 2.5 μg or 1.25 μg or placebo Respimat®, once daily in the evening. Each treatment was administered for 4 weeks, without washout between treatment periods. Eligibility criteria included ≥60% and ≤90% of predicted normal forced expiratory volume in 1 second (FEV1) and seven-question Asthma Control Questionnaire mean score of ≥1.5. Patients were required to continue maintenance treatment with stable medium-dose ICS for at least 4 weeks prior to and during the treatment period. Long-acting β2-agonists were not permitted during the treatment phase. The primary efficacy end point was peak FEV1 measured within 3 hours after dosing (peak FEV1(0-3h)) at the end of each 4-week period, analysed as a response (change from study baseline).. In total, 149 patients were randomised and 141 completed the study. Statistically significant improvements in peak FEV1(0-3h) response were observed with each tiotropium Respimat® dose versus placebo (all P < 0.0001). The largest difference from placebo was with tiotropium Respimat® 5 μg (188 mL). Trough FEV1 and FEV1 area under the curve (AUC)(0-3h) responses were greater with each tiotropium Respimat® dose than with placebo (all P < 0.0001), and both were greatest with 5 μg. Peak forced vital capacity (FVC)(0-3h), trough FVC and FVC AUC(0-3h) responses, versus placebo, were greatest with tiotropium Respimat® 5 μg (P < 0.0001, P = 0.0012 and P < 0.0001, respectively). Incidence of adverse events was comparable between placebo and all tiotropium Respimat® groups.. Once-daily tiotropium Respimat® add-on to medium-dose ICS improves lung function in symptomatic patients with moderate asthma. Overall, improvements were largest with tiotropium Respimat® 5 μg.. ClinicalTrials.gov identifier NCT01233284.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Scopolamine Derivatives; Tiotropium Bromide

Tiotropium, a once-daily long-acting anticholinergic agent, has been shown to be an efficacious and safe add-on treatment for adults with symptomatic asthma, despite treatment with inhaled corticosteroids (ICS). A large proportion of asthmatic adolescents have symptomatic disease despite a wide range of therapeutic options. We investigated the efficacy and safety of three doses of tiotropium, administered in the evening (via Respimat(®) SoftMist™ inhaler), versus placebo in asthmatic adolescents symptomatic despite ICS treatment.. This randomised, double-blind, placebo-controlled, incomplete crossover study evaluated once-daily tiotropium 5 μg, 2.5 μg and 1.25 μg versus placebo in three 4-week treatment periods. Primary efficacy end point was change in peak forced expiratory volume in 1 s within 3 h post-dose from baseline (peak FEV1(0-3h)).. From 139 enrolled patients, 105 were randomised to receive one of four treatment sequences. Peak FEV1(0-3h) response for tiotropium 5 μg was significantly greater versus placebo (p = 0.0043). Trough FEV1 responses were significantly greater for tiotropium 5 μg (p < 0.00001) and 1.25 μg (p = 0.0134) versus placebo, but not for 2.5 μg (p = 0.0975), while FEV1 area under the curve(0-3h) responses were significant for all doses (p = 0.00001-0.0398). Overall incidence of adverse events was balanced across treatment groups, with no dose-dependent observations. The majority of adverse events were mild to moderate in intensity.. This first study of tiotropium in adolescents with symptomatic asthma demonstrates that tiotropium is well tolerated and efficacious as add-on to maintenance treatment with ICS. ClinicalTrials.gov identifier; NCT01122680.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Child; Cholinergic Antagonists; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Peak Expiratory Flow Rate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Tiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.. We sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.. Data from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs).. Although approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not.. Although these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cross-Over Studies; Female; Humans; Male; Middle Aged; Prognosis; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

The effects of tiotropium, an inhaled long-acting anti-cholinergic agent, on lung function were investigated in obstructed severe asthmatics with and without emphysematous changes despite maximal recommended treatments with high-dose of inhaled glucocorticoids and inhaled long-acting β(2)-agonists. We conducted a double-blind, placebo-controlled study of an inhaled single-dose of tiotropium in 18 asthmatics with emphysema and 18 without emphysema in a crossover manner. The primary efficacy outcome was the relative change in forced expiratory volume in 1 s (FEV(1)) from baseline to 60 min, and the secondary outcome was a relative change in FEV(1) from baseline to 12 h. Subsequently, the patients were treated with tiotropium inhaled once daily for 12 weeks in an open label manner, and lung function and symptoms were evaluated. At baseline, patients with or without emphysema had a mean FEV(1) of 55.9% before tiotropium and 56.8% before placebo, or 77.4% before tiotropium and 77.6% before placebo of the predicted value and were taking a mean dose of inhaled glucocorticoids of 1444 or 1422 μg/day. Among patients with emphysema, the increase from baseline FEV(1) was 12.6 percentage points higher at 60 min after tiotropium than after placebo. Among patients without emphysema, the increase from baseline FEV(1) was 5.4 percentage points higher at 60 min after tiotropium than after placebo. Tiotropium resulted in improved lung function and symptoms in asthmatics with and without emphysema. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma and of overlapping asthma and COPD.

Topics: Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Emphysema; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Scopolamine Derivatives; Tiotropium Bromide; Vital Capacity

Some patients with asthma have frequent exacerbations and persistent airflow obstruction despite treatment with inhaled glucocorticoids and long-acting beta-agonists (LABAs).. In two replicate, randomized, controlled trials involving 912 patients with asthma who were receiving inhaled glucocorticoids and LABAs, we compared the effect on lung function and exacerbations of adding tiotropium (a total dose of 5 μg) or placebo, both delivered by a soft-mist inhaler once daily for 48 weeks. All the patients were symptomatic, had a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of 80% or less of the predicted value, and had a history of at least one severe exacerbation in the previous year.. The patients had a mean baseline FEV(1) of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV(1) from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P=0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV(1) also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P=0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerbation (hazard ratio, 0.79; P=0.03). No deaths occurred; adverse events were similar in the two groups.. In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984.).

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Scopolamine Derivatives; Tiotropium Bromide

Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent, might be an effective bronchodilator in such patients.. We sought to compare the efficacy and safety of 2 doses of tiotropium (5 and 10 μg daily) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma (Asthma Control Questionnaire score, ≥ 1.5; postbronchodilator FEV₁, ≤ 80% of predicted value) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a long-acting β₂-agonist.. This was a randomized, double-blind, crossover study with three 8-week treatment periods. The primary end point was peak FEV₁ at the end of each treatment period.. Of 107 randomized patients (54% female patients; mean, 55 years of age; postbronchodilator FEV₁, 65% of predicted value), 100 completed all periods. Peak FEV₁ was significantly higher with 5 μg (difference, 139 mL; 95% CI, 96-181 mL) and 10 μg (difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P < .0001). There was no significant difference between the active doses. Trough FEV₁ at the end of the dosing interval was higher with tiotropium (5 μg: 86 mL [95% CI, 41-132 mL]; 10 μg: 113 mL [95% CI, 67-159 mL]; both P < .0004). Daily home peak expiratory flow measurements were higher with both tiotropium doses. There were no significant differences in asthma-related health status or symptoms. Adverse events were balanced across groups except for dry mouth, which was more common on 10 μg of tiotropium.. The addition of once-daily tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting β₂-agonist, significantly improves lung function over 24 hours in patients with inadequately controlled, severe, persistent asthma.

Topics: Adult; Aged; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Scopolamine Derivatives; Severity of Illness Index; Surveys and Questionnaires; Tiotropium Bromide; Treatment Outcome

The efficacy and safety of inhaled long-acting β(2)-adrenergic agonists in asthmatic patients with the B16-Arg/Arg genotype has been questioned, and the use of antimuscarinics has been proposed as an alternative in patients whose symptoms are not controlled by inhaled corticosteroids (ICSs).. We compared the efficacy and safety of the long-acting anticholinergic tiotropium with salmeterol and placebo added to an ICS in B16-Arg/Arg patients with asthma that was not controlled by ICSs alone.. In a double-blind, double-dummy, placebo-controlled trial, after a 4-week run-in period with 50 μg of twice-daily salmeterol administered through a metered-dose inhaler, 388 asthmatic patients were randomized 1:1:1 to 16 weeks of treatment with 5 μg of Respimat tiotropium administered daily in the evening, 50 μg of salmeterol administered twice daily through a metered-dose inhaler, or placebo. Patients aged 18 to 67 years demonstrated reversibility to bronchodilators, and their symptoms were uncontrolled by regular ICSs (400-1000 μg of budesonide/equivalent). ICS regimens were maintained throughout the trial. The mean weekly morning peak expiratory flow (PEF) before randomization was 358 ± 115.7 L/min (range, 80.3-733.0 L/min).. Changes in weekly PEF from the last week of the run-in period to the last week of treatment (primary end point: change in PEF) were -3.9 ± 4.87 L/min (n = 128) for tiotropium and -3.2 ± 4.64 L/min (n = 134) for salmeterol, and these were superior to placebo (-24.6 ± 4.84 L/min, n = 125, P < .05). Tiotropium was noninferior to salmeterol (estimated difference, -0.78 L/min [95% CI, -13.096 to 11.53]; P = .002; α = .025, 1-sided; noninferiority, 20 L/min). Tiotropium and salmeterol were numerically superior to placebo in some patient-reported secondary outcomes. Adverse events were comparable across treatments.. Tiotropium was more effective than placebo and as effective as salmeterol in maintaining improved lung function in B16-Arg/Arg patients with moderate persistent asthma. Safety profiles were comparable.

Topics: Administration, Inhalation; Albuterol; Arginine; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Genotype; Humans; Male; Peak Expiratory Flow Rate; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed.. In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison).. The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthma-control days, with a difference of 0.079 (P=0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P=0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P=0.003).. When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Cholinergic Antagonists; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

The protective effect of inhaled anticholinergic drugs in the methacholine-induced bronchospasm is well-known. The objective of this study was to assess if any possible differences may be found among Ipratropium (IB), Oxitropium (OXI) and Tiotropium (TIO) pre-treatments to obtain the protective effect. Forty-four patients with intermittent bronchial asthma and PD(20)FEV(1) < 200 microg were selected (24 M, 20 F; mean age 32 +/- 8.8). On the baseline, they had mean FEV(1)%: 98.8 +/- 8.54 of theoretical and mean PD(15)FEV(1) 111.8 +/- 61.04 microg. After 72 hours, all patients underwent a second methacholine challenge and were given Ipratropium (40 microg by MDI in 14 pts) or Oxitropium (200 microg by MDI in 14 pts) or Tiotropium (18 microg by Handihaler in 16 pts) sixty minutes before the test. Sixty minutes after the bronchodilator inhalation, the FEV(1)% increase was higher (p < 0.05) in OXI (6.7 +/- 4.83%) and TIO groups (6.11 +/- 2.54%) than in the IB group (3.8 +/- 1.96%). In the IB group PD(15)FEV(1) and PD(20)FEV(1) were obtained in all patients, while in the OXI group they were obtained in 12 and 5 pts respectively and in the TIO group in 14 and 5 pts respectively. Normal hyperreactivity was obtained in 2 patients, in both OXI and TIO groups. In OXI and TIO, the PD(15) obtained after drug pre-medication, was similar (respectively 1628 +/- 955.7 and 1595.5 +/- 990 microg), but higher (p < 0.0001) in comparison to the PD(15) measured in the IB group (532.2 +/- 434.8 microg). Also, the dose-response slope (decline percentage of FEV(1)/cumulative methacholine dose) after PD(15) was similar in both OXI and TIO groups but different in the IB group. A significant relationship (p < 0.01) was found between PD(15)FEV(1) (obtained in 40 pts) and the increase in FEV(1)% obtained 60 minutes after bronchodilator inhalations (r = 0.53). In conclusion, with a standard dose, both Oxitropium and Tiotropium seem to have the same protective effect in bronchial asthma but higher than Ipratropium. It's probable that the best dose of Ipratropium should be a higher one than the usual dose taken.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Ipratropium; Male; Methacholine Chloride; Premedication; Probability; Reference Values; Respiratory Function Tests; Scopolamine Derivatives; Sensitivity and Specificity; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) and asthma have different diagnostic criteria and treatment paradigms. Both are common and can occur in the same patient. We sought to determine the spirometric effects of tiotropium in COPD patients with concomitant asthma.. A 12-week randomized, double-blind, placebo-controlled, parallel group trial with tiotropium 18 mcg daily was performed. Patients continued usual respiratory medications except for inhaled anticholinergics.. Physician diagnosis of COPD and asthma, age >or= 40 years, smoking >10 pack years, post-bronchodilator forced expiratory volume in 1s (FEV(1))<80% predicted, FEV(1)/forced vital capacity (FVC)<70%, >or= 12%, and >or= 200 ml increase in FEV(1) following inhaled bronchodilator, treatment with inhaled steroids >or= 1 year. Spirometry was measured serially for 6h on days 1, 29 and 85.. Four hundred and seventy-two patients were randomized. Baseline characteristics were balanced. Mean age=59.6 years, 61.4% were men, and FEV(1)=1.55l (53.0% predicted). Improvements at 12 weeks with tiotropium were observed for the primary endpoint FEV(1) area under the curve (AUC) from 0 to 6h (difference=186+/-24 ml, p<0.001) and for morning pre-dose FEV(1) (difference=98+/-23 ml, p<0.001). Significant differences in favor of tiotropium were observed for pre-dose FVC (difference=128+/-34 ml, p<0.001) and FVC AUC 0-6h (difference=232+/-35 ml, p<0.001). Compared to baseline, the mean weekly number of daily puffs of prn salbutamol was reduced by 0.05+/-0.12 puffs/day in the placebo group and by 0.50+/-0.12 puffs/day in the tiotropium group at week 12 (p<0.05).. Patients with COPD and concomitant asthma achieve spirometric improvements with tiotropium along with symptomatic benefit as seen by reduced need for rescue medication.

Topics: Asthma; Bronchodilator Agents; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Spirometry; Tiotropium Bromide; Treatment Outcome

We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0-69.0)l/min [p<0.05]; and RAW of 0.98 (0.14-1.8)cm H(2)O/l/s [p<0.05]. Adding salmeterol/tiotropium produced similar improvements in PEF and RAW, but also improved FEV(1) by 0.17 (0.01-0.32)l [p<0.05]; FVC 0.24 (0.05-0.43)l [p<0.05] and reduced exhaled NO by 2.86 (0.12-5.6)ppb [p<0.05]. RV and TLC were not altered by either treatment; there were no significant changes in symptoms or quality of life compared with baseline. Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life.

Topics: Adult; Aged; Albuterol; Androstadienes; Asthma; Breath Tests; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Plethysmography, Whole Body; Quality of Life; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity

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.

Topics: Adult; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Cholinergic Antagonists; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Male; Methacholine Chloride; Scopolamine Derivatives; Time Factors; Tiotropium Bromide

An important proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, such as tiotropium bromide has been recommended for this subgroup of patients. The purpose of this study was to assess the cost-effectiveness of tiotropium as add-on therapies to ICS + LABA for children and adolescents with uncontrolled allergic asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYS of two interventions including standard therapy (ICS + LABA), and add-on therapy with tiotropium, were calculated over a time horizon from 6 to 18 years. Probability sensitivity analyses were conducted.. For a patient with severe asthma, our Markov model showed that compared to standard therapy, add-on therapy with tiotropium was associated with higher treatment costs and QALY. The incremental cost-effectiveness ratio estimated was US$2,017 in the probabilistic model after Monte-Carlo simulation. Our base-case results were robust to variations in all assumptions and parameters. The incremental net monetary benefit of US$327 with a 95% credible interval of US$396 to US425.. Add-on therapy with tiotropium was cost-effective when added to usual care in children and adolescents with severe asthma who remained uncontrolled despite treatment with medium or high-dose ICS/LABA. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Child; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Tiotropium Bromide

The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma.. The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP. Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (. These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP

Topics: Animals; Asthma; Histone Deacetylase 2; Humans; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred C57BL; NF-kappa B; Tiotropium Bromide

In patients with uncontrolled asthma, despite management with high doses of inhaled corticosteroids, the additional use of omalizumab and tiotropium is recommended. Omalizumab is an expensive medication and doubts arise as to whether the benefit of this drug outweighs the additional expense of the drug. The purpose of this study was to assess the cost-effectiveness of tiotropium versus omalizumab as add-on therapies to ICS + LABA for patients with uncontrolled allergic asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life years (QALYs) of patients with uncontrolled allergic asthma in Colombia. Total costs and QALYs of three interventions including standard therapy (ICS + LABA), add-on therapy with tiotropium, and add-on therapy with omalizumab, were calculated over a 10-year time horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. The model showed that tiotropium was associated with lower cost than standard therapy and omalizumab (US$5590 vs. US$5693 vs. U$18,154 average annual cost per patient), and higher QALYs (11.8 vs. 11.3 vs. 11.9) average per patient), showing dominance respect to standard therapy. The probability that tiotropium provides a more cost-effective use of resources compared with standard therapy exceeds 99% for willingness-to-pay threshold.. Add-on therapy with tiotropium was a cost-effective alternative to omalizumab and standard therapy for uncontrolled allergic asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Humans; Omalizumab; Tiotropium Bromide

Topics: Administration, Inhalation; Allergens; Asthma; Bronchial Provocation Tests; Double-Blind Method; Humans; Inflammation; Tiotropium Bromide

Mucociliary clearance (MCC) is an essential defense mechanism in airway epithelia for removing pathogens from the respiratory tract. Impaired ciliary functions and MCC have been demonstrated in asthma and chronic obstructive pulmonary disease (COPD). Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators, which are used for treating asthma and COPD; however, the effects of LAMAs on ciliary function remain unclear. This study aimed to identify the effects of LAMAs on airway ciliary functions.. Wild-type BALB/c mice were treated with daily intranasal administrations of glycopyrronium for 7 days, and tracheal samples were collected. Cilia-driven flow and ciliary activity, including ciliary beat frequency (CBF), ciliary beating amplitude, effective stroke velocity, recovery stroke velocity and the ratio of effective stroke velocity to recovery stroke velocity, were analyzed by imaging techniques. Using in vitro murine models, tracheal tissues were transiently cultured in media with/without LAMAs, glycopyrronium or tiotropium, for 60 min. Cilia-driven flow and ciliary activity were then analyzed. Well-differentiated normal human bronchial epithelial (NHBE) cells were treated with glycopyrronium, tiotropium, or vehicle for 60 min, and CBF was evaluated. Several mechanistic analyses were performed.. Intranasal glycopyrronium administration for 7 days significantly increased cilia-driven flow and ciliary activity in murine airway epithelium. In the murine tracheal organ culture models, treatment with glycopyrronium or tiotropium for 60 min significantly increased cilia-driven flow and ciliary activity in airway epithelium. Further, we confirmed that 60-min treatment with glycopyrronium or tiotropium directly increased CBF in well-differentiated NHBE cells. In the mechanistic analyses, neither treatment with glycopyrronium nor tiotropium affected intracellular calcium ion concentrations in well-differentiated NHBE cells. Glycopyrronium did not increase protein kinase A activity in well-differentiated NHBE cells. Moreover, glycopyrronium had no effect on extracellular adenosine triphosphate concentration.. LAMAs exert a direct effect on airway epithelium to enhance ciliary function, which may improve impaired MCC in asthma and COPD. Further investigations are warranted to elucidate the underlying mechanisms of the effects of LAMAs on the promotion of airway ciliary function.

Topics: Animals; Asthma; Epithelium; Glycopyrrolate; Humans; Mice; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Stroke; Tiotropium Bromide; Trachea

Long-acting muscarinic antagonists (LAMA) are used for long-term treatment of bronchial asthma in adults. Its use in the management of pediatric bronchial asthma, however, is currently not approved in Japan. Nonetheless, there have been a few reports of its use in children, particularly in cases of severe bronchial asthma or those without atopic disease that are refractory to existing treatment protocols. We report the progress of LAMA in infantile asthma patients.. Three out of four patients had LAMA introduced at 3 to 5 years of age after being diagnosed with asthma at 1 to 3 years old. Three patients had non-IgE-related asthma and an underlying disease, such as Apert and Noonan syndrome, while one patient had severe IgE-related asthma without a pre-existing disease. In all cases, conventional long-term medications such as medium to high-dose inhaled corticosteroids and long-acting beta-agonists, were given. However, severe bronchial asthma persisted, with some patients having uncontrolled secretions. Since uncontrolled severe-persistent bronchial asthma results in repeated hospitalization and intensive care unit admission, we introduced LAMA, specifically 2.5μg/day of tiotropium (Tio). After the introducing Tio, none of the patients had an acute exacerbation that required hospitalization and the frequency of wheezing was reduced. LAMA was administered for up to 19 months, with no adverse events.. The results of this series suggest that LAMA is an effective and safe option for uncontrolled infantile asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchodilator Agents; Child; Child, Preschool; Humans; Infant; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Tiotropium Bromide

A Markov cohort state transition model (focusing on exacerbations) was used to investigate the cost-effectiveness of medium- or high-dose BDP/FF/G vs medium- or high-dose BDP/FF, and high-dose BDP/FF/G vs high-dose BDP/FF + tiotropium. The model analysed cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER), and was developed from the England National Health Service perspective (2020 costs). Uncertainty of the inputs was estimated using one-way and probabilistic sensitivity analyses.. Both medium- and high-dose BDP/FF/G were cost-effective vs BDP/FF, with ICERs of £12,224 and £15,587 per QALY gained. High-dose BDP/FF/G was dominant vs BDP/FF + tiotropium, as it was both cheaper and gained QALYs. Sensitivity analyses were consistent with the base model: medium- and high-dose BDP/FF/G had 94.3% and 88.3% likelihoods to be cost-effective vs BDP/FF; high-dose BDP/FF/G had 100% likelihood to be a dominant strategy vs BDP/FF + tiotropium.. Both medium- and high-dose BDP/FF/G were cost-effective vs medium- and high-dose BDP/FF in adults with asthma that was uncontrolled by ICS/LABA. In addition, high-dose BDP/FF/G was a dominating strategy to high-dose BDP/FF + tiotropium.. GOV: NCT02676076 and NCT02676089.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Nebulizers and Vaporizers; State Medicine; Tiotropium Bromide

Topics: Asthma; Birth Cohort; Child; Humans; Immunization Programs; Respiratory Sounds; Tiotropium Bromide

The first NHLBI Clinical Trials Research Network was the Asthma Clinical Research Network (ACRN 1), which was born in 1993 to perform multiple controlled clinical trials for asthma: "… dispassionately examine new & existing therapies for asthma" and "… rapidly communicate findings to medical community," and therefore, to perform clinical trials drug companies could not or would not do. Among the many areas studied by the ACRN and its successor networks, through 2019, was how to effectively and safely use long-acting beta-agonists and to find novel alternatives for them. In its Tiotropium Add-On Trial (TALC) trial, the ACRN demonstrated that tiotropium as add on-therapy to inhaled corticosteroids (ICS) was effective and non-inferior to long-acting beta-agonist add on-therapy. During the lifetime of the clinical trial networks (1993-2020), 71 manuscripts including 25 major clinical trials were published, many which have laid the groundwork for precision approaches for asthma therapy and the now ongoing PrecISE Asthma Network.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Drug Therapy, Combination; Humans; National Heart, Lung, and Blood Institute (U.S.); Patient Care; Precision Medicine; Talc; Tiotropium Bromide; United States

Despite the availability of various treatment options, a large proportion of patients with asthma have uncontrolled asthma in the United States. Consequently, the economic burden of suboptimal asthma control is anticipated to substantially grow in the next 20 years, adversely impacting patients' quality of life. Therefore, there is an urgent need for effective treatments to achieve and maintain asthma control. The Global Initiative for Asthma recommends tiotropium as a controller medication for patients with asthma aged ≥6 years, based on evidence from several randomized controlled trials. However, more real-world data on the effectiveness of tiotropium are required to establish a broad picture of its use in everyday clinical practice.. All 3 patients were prescribed tiotropium, irrespective of their age. Tiotropium improved lung function and quality of life, as indicated by the forced expiratory volume in 1 s/forced vital capacity ratio and the Asthma Control Test score. Furthermore, the addition of tiotropium reduced the use of rescue medication.. Hence, the results from these case reports highlight that tiotropium could be an effective and safe add-on treatment option for patients across a range of age groups with uncontrolled or fixed obstructive asthma receiving prior ICS or ICS + LABA and/or LTRA therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Quality of Life; Tiotropium Bromide

Asthma is a heterogeneous disease characterized by airway inflammation resulting from complex interactions between multiple hosts as well as environmental factors. As a chronic respiratory condition, asthma exerts a significant impact on patients and the healthcare system. Per the Global Initiative for Asthma (GINA), inhaled corticosteroids (ICS) with/without long-acting beta

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Physicians, Primary Care; Tiotropium Bromide

Tiotropium has the potential to alleviate asthmatic symptoms caused by the aging of lungs. However, few studies have focused on specific treatments for elderly patients with asthma.. To estimate the cost-effectiveness of adding tiotropium to inhaled corticosteroids and long-acting beta-agonists in elderly patients with severe asthma using real-world data.. Phase I was a retrospective cohort study using the National Health Insurance claims data to measure clinical and economic outcomes. In phase II, a Markov model was constructed to evaluate cost-effectiveness from Korean health care system perspective, based on phase I, including 2 health states, and an asthma exacerbation event. We estimated cost given in 2018 US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Subgroup analyses for patients with poorly controlled symptoms (frequent short-acting beta-agonist users; frequent exacerbators) were performed.. In elderly patients with severe asthma, the incremental cost and effectiveness in the tiotropium group compared with the inhaled corticosteroid and long-acting beta-agonist group were $2281 and 0.038 QALYs, respectively. The incremental cost-effectiveness ratio was $60,074/QALY, indicating that the addition of tiotropium is not a cost-effective alternative. Meanwhile, 2 subgroups with poorly controlled symptoms showed that adding tiotropium is a cost-effective alternative (frequent short-acting beta-agonist users $4078/QALY; frequent exacerbators $8332/QALY).. Tiotropium shows a higher cost-effectiveness profile when applied to elderly patients with uncontrolled symptoms. These results using real-world evidence provide information beyond the clinical outcomes reported by randomized controlled trials, providing a complementary ground in establishing the reimbursement criteria of tiotropium for elderly patients with severe asthma.

Topics: Adrenal Cortex Hormones; Aged; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Humans; Retrospective Studies; Tiotropium Bromide

A variety of dual-combination maintenance inhalers are used to treat asthma and chronic obstructive pulmonary disease (COPD). Understanding patient preferences for treatment attributes may help select an optimal treatment from the patient perspective.. Patient preferences for maintenance inhaler device and medication attributes were elicited through a discrete choice experiment and used in benefit-risk assessments to calculate predicted choice probabilities (PrCPs) for 14 dual-combination maintenance inhalers in four treatment classes: lower- and higher-dose inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) inhalers for asthma, and ICS/LABA and long-acting muscarinic antagonist (LAMA)/LABA inhalers for COPD.. For all treatment classes, reduced exacerbations and faster onset of action were the most important attributes. For all classes, patients were willing to tolerate an extra yearly exacerbation to decrease the medication's onset of action from 30 to 5 min. For patients with asthma using lower-dose ICS/LABA (n = 497), budesonide/formoterol fumarate dihydrate (80 μg/4.5 μg) pressurized metered-dose inhaler (pMDI) had the highest PrCP (28.4%), and for those using a higher-dose ICS/LABA (n = 285), PrCPs were highest for mometasone furoate/formoterol fumarate dihydrate (200 μg/5 μg) pMDI (27.0%) and budesonide/formoterol fumarate dihydrate (160 μg/4.5 μg) pMDI (26.9%). For patients with COPD using an ICS/LABA (n = 574), budesonide/formoterol fumarate dihydrate (160 μg/4.5 μg) pMDI had the highest PrCP (56.6%), and for those using a LAMA/LABA inhaler (n = 217), tiotropium/olodaterol (2.5 μg/2.5 μg) soft mist inhaler had the highest PrCP (42.3%).. Patient preference data for maintenance inhaler attributes can be used to identify a preference order of inhalers in different treatment classes.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Benzoxazines; Budesonide; Delayed-Action Preparations; Disease Progression; Drug Combinations; Drug Therapy, Combination; Formoterol Fumarate; Maintenance Chemotherapy; Nebulizers and Vaporizers; Patient Preference; Patient-Centered Care; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Tiotropium Bromide

Topics: Aged; Asthma; Cost-Benefit Analysis; Humans; Patients; Social Determinants of Health; Tiotropium Bromide

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Child; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Tiotropium Bromide

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.

Topics: Aged; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Formoterol Fumarate; Glycopyrrolate; Humans; Indans; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Radiographic Image Enhancement; Radiography, Thoracic; Spirometry; Tiotropium Bromide; Treatment Outcome

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Humans; Seasons; Tiotropium Bromide

Data are limited on the differential response to long-acting bronchodilators in older versus younger adults with asthma.. To determine whether the response to tiotropium Respimat differed in older versus younger patients with asthma.. Post hoc analyses of 4 randomized, double-blind, placebo-controlled studies in adults with asthma were carried out. Two studies compared tiotropium Respimat 5 μg once daily with placebo, both added to high-dose inhaled corticosteroid (ICS) plus long-acting β. Across the age categories, treatment-by-age subgroup interaction P values for trough FEV. Once-daily tiotropium Respimat add-on to ICS or ICS/long-acting β

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchodilator Agents; Double-Blind Method; Humans; Middle Aged; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome

Topics: Asthma; Formoterol Fumarate; Humans; Tiotropium Bromide

Topics: Asthma; Bronchodilator Agents; Cholinergic Antagonists; Humans; Ipratropium; Tiotropium Bromide

We previously demonstrated increased expression of programmed cell death 5 (PDCD5) in asthmatic patients and ovalbumin-induced allergic asthma. International guidelines (GINA 2019) have included the use of tiotropium bromide for chronic treatment of the most severe and frequently exacerbated asthma in patients ≥6 years old, who do not have good response to inhaled corticosteroids.. To explore the role of tiotropium and its effect on PDCD5 level in a mouse model of chronic asthma.. We divided 12 female mice into 2 groups: untreated asthma (. Tiotropium treatment significantly reduced airway inflammation and remodeling in asthmatic mice and intensified the lung function. PDCD5 level was reduced with tiotropium (. Tiotropium treatment may alleviate the pathological changes with asthma by regulating apoptosis.

Topics: Animals; Apoptosis Regulatory Proteins; Asthma; Caspase 3; Cholinergic Antagonists; Disease Models, Animal; Female; Lung; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Receptor, Muscarinic M3; Tiotropium Bromide

In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium Respimat. Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Female; Forced Expiratory Volume; Humans; Japan; Lung; Male; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Smoking; Tiotropium Bromide; Treatment Outcome

Topics: Asthma; Eosinophils; Humans; Mometasone Furoate; Sputum; Tiotropium Bromide

Asthma is a common yet complex airway disorder, comprising diverse phenotypes and pathophysiology. According to the Australian Institute of Health and Welfare, asthma affects 11% of the Australian population. Despite the availability of effective therapies and a national medicines subsidy scheme, a significant burden of disease still exists in Australia, with high mortality by international standards.. This article discusses the challenges in managing patients with difficult-to-treat and severe asthma in primary care, how to distinguish between difficult-to-treat and severe asthma, when to refer, and the role of biologic therapy.. Asthma that remains uncontrolled despite treatment with high-dose preventive therapies is not only challenging for clinicians but also imposes long-term, debilitating burdens on patients' quality of life. Recent advances in evidence-based guidelines for severe asthma, increasing evidence about phenotypic patterns and asthma biomarkers, and the availability of targeted biologic therapies offer hope for improving patient outcomes.

Topics: Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Australia; Humans; Medication Adherence; Metered Dose Inhalers; Omalizumab; Patient Education as Topic; Tiotropium Bromide; Treatment Failure

Topics: Asthma; Bronchodilator Agents; Child; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Asthma; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Respiratory Function Tests; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Tiotropium Bromide

The long-acting muscarinic antagonist tiotropium received an indication for the treatment of asthma from the FDA in 2015.. This paper summarizes much of the published findings on tiotropium and asthma and explores the heterogeneity of the asthma population vis-à-vis recent changes in guidelines for management of COPD. The accompanying case study provides an illustration of how tiotropium might be added to a patient's regimen appropriately.. Tiotropium has been shown in many studies to be beneficial to patients with asthma as an add-on medication. It should be considered as an agent by the clinician managing patients with both allergic and non-allergic asthma.

Topics: Administration, Inhalation; Asthma; Cholinergic Agents; Dyspnea; Female; Guidelines as Topic; Humans; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Tiotropium Bromide

Topics: Adolescent; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Humans; Scopolamine Derivatives; Tiotropium Bromide

Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Humans; Tiotropium Bromide

Tiotropium is a long acting muscarinic antagonist (LAMA), licensed as triple therapy with inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). There may be a synergistic benefit between LAMA and LABA as a consequence of receptor cross-talk, which in turn could modify beta-2 receptor downregulation and associated tolerance induced by LABA.. We hypothesize this mechanism may result in a reduction of airway hyperresponsiveness (AHR) when using triple therapy.. We evaluated 14 non-smoking asthmatics using an open-label, randomized crossover design. ICS with Indacaterol and Tiotropium (IND/TIO) vs ICS with Indacaterol (IND) over 4 weeks with challenge performed after first and last doses at trough.. Our data suggest that concomitant tiotropium does not modify the bronchoprotective tolerance induced by Indacaterol, in turn suggesting that cross-talk may not be clinically relevant when using triple therapy. This study was registered on clinicaltrials.gov as NCT02039011.

Topics: Adult; Aged; Asthma; Biomarkers; Bronchial Hyperreactivity; Drug Therapy, Combination; Female; Humans; Indans; Male; Middle Aged; Muscarinic Antagonists; Quinolones; Respiratory Function Tests; Tiotropium Bromide; Treatment Outcome

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. Female C57BL/6J mice were sensitized intranasally (i.n.) with 1 μg of house dust mite (HDM) extract followed by a challenge regime (5 consecutive days 10 μg HDM extract i.n.) after one week. Mice were exposed to a secondary challenge five weeks after sensitization and were treated i.n. with different concentrations of tiotropium or olodaterol (1, 10 and 100 μg/kg) or a combination thereof (10 μg/kg each) prior to and during the secondary challenge period. Three days after the last challenge, bronchoalveolar lavage (BAL) fluid and lung tissue were collected for flow cytometry and histologic analysis, respectively. Secondary challenge with HDM extract strongly induced allergic airway disease reflected by inflammatory cell infiltration and goblet cell metaplasia. Treatment with tiotropium, but not with olodaterol reduced tissue inflammation and goblet cell metaplasia in a dose-dependent manner. The combination of tiotropium and olodaterol was more effective in significantly reducing tissue inflammation compared to tiotropium treatment alone, and also led to a decrease in BAL cell counts. These data suggest that in a model of relapsing allergic airway disease tiotropium directly prevents exacerbations by reducing inflammation and mucus production in the airways. In addition, the combination of tiotropium and olodaterol exerts synergistic effects.

Topics: Allergens; Animals; Asthma; Benzoxazines; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Female; Flow Cytometry; Goblet Cells; Inflammation; Mice; Mice, Inbred C57BL; Pyroglyphidae; Tiotropium Bromide

Anticholinergic therapy has long been a cornerstone of management of chronic obstructive pulmonary disease (COPD) but has not been included in treatment guidelines for asthma. In September 2015, tiotropium bromide was approved for use in adults with asthma; the indication has since been expanded to children ages 6 years and older. This article discusses appropriate patient selection and dosing, and the role of tiotropium bromide in asthma management.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Child; Cholinergic Antagonists; Disease Management; Female; Humans; Male; Patient Selection; Tiotropium Bromide; Young Adult

Severe asthma poses significant disease-related and economic burdens in the United States. Challenges in practice include how to define "severe asthma" for a given patient, knowing which are the right tests to perform and when, and having a better understanding of a patient's asthma phenotype. Furthermore, current guidelines do not address a clear, practical approach to treatment that is based on a patient's asthma phenotype.. To develop a consensus on the definition of severe asthma, the role of biomarkers and phenotyping severe asthma, and the use of newer biologic therapies and bronchial thermoplasty to help guide practicing clinicians.. A roundtable meeting was convened with a panel of severe asthma experts to discuss areas in practice that are not adequately addressed by current guidelines, specifically phenotype-guided treatment.. We describe a consensus on the definition of severe asthma, asthma phenotyping with the use of available biomarkers, and guiding principles for newer biologic therapies and bronchial thermoplasty.. To optimize therapy and improve outcomes such as daily symptoms, quality of life, exacerbations, and hospitalizations, a clear picture of a patient's asthma phenotype is needed to guide therapy. Determining asthma phenotypes is the foundation of precision medicine for this persistent, often difficult-to-treat disease.

Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Bronchial Thermoplasty; Humans; Omalizumab; Phenotype; Quality of Life; Severity of Illness Index; Tiotropium Bromide

Topics: Asthma; Australia; Bronchodilator Agents; Dietary Proteins; Enterocolitis; Epigenesis, Genetic; Food Hypersensitivity; Genetic Predisposition to Disease; Humans; Tiotropium Bromide; Urticaria

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Humans; Scopolamine Derivatives; Tiotropium Bromide

Topics: Asthma; Bronchodilator Agents; Humans; Tiotropium Bromide

Some patients with asthma have poorly controlled disease despite the use of high-dose inhaled corticosteroids (ICS), long-acting β2 agonists (LABAs) and antileukotrienes. The aim of the study was to assess the effectiveness of tiotropium as an add-on therapy to the standard treatment with high-dose ICS/LABA on asthma control and lung function in patients with severe asthma.. Of the 633 asthmatic patients, 64 (10.1%) patients with severe asthma who were add-on treated at least for 3 months were evaluated. Number of exacerbations, emergency department visits, hospitalizations and lung functions of patients belonging to 12 months before starting add-on treatment were compared with those of 12 months after starting add-on treatment.. The mean duration of add-on tiotropium treatment was 8.3 ± 0.5 months. For patients with severe asthma that was poorly controlled with standard combination therapy, tiotropium improved asthma control in 42.2%, decreased the number of emergency department visits in 46.9% and decreased the number of hospitalizations in 50.0% of them. The mean baseline forced expiratory volume in 1 s before add-on tiotropium was 57.5 ± 1.9% and forced vital capacity was 74.3 ± 15.6%. However, after 12 months of add-on tiotropium treatment, these rates became 65.5 ± 1.9% and 82.5 ± 15.1%, respectively. The addition of tiotropium significantly improved the percentages of the number of emergency department visits, the number of hospitalizations (P < 0.05).. Our study has suggested that, for patients with poorly controlled asthma despite of the use of ICS/LABA, the addition of tiotropium to standard care may be beneficial.

Topics: Administration, Inhalation; Adult; Aged; Airway Obstruction; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Prednisone; Retrospective Studies; Theophylline; Tiotropium Bromide; Treatment Outcome

Anticholinergic drug products are not part of the current treatment paradigm for asthma, despite their widespread availability for chronic obstructive pulmonary disease (COPD) and interest in their use for asthma. Published study results, mostly of short duration and primarily with ipratropium and tiotropium, have revealed inconsistent efficacy results. Consequently, the role of inhaled anticholinergic drugs in the treatment of asthma has been unclear. This commentary discusses and comments on data from five clinical trials in adults that were submitted by Boehringer Ingelheim to the U.S. Food and Drug Administration to support approval of tiotropium delivered by the Respimat device (Spiriva Respimat) for the treatment of asthma. These trials provided substantial evidence that supported the approval of Spiriva Respimat at a recommended dose of 2.5 μg once daily for asthma. Notably, in trials that evaluated two doses of tiotropium, 2.5 μg and 5 μg (the dose approved for COPD), pulmonary function measures for Spiriva Respimat 2.5 μg once daily were better overall than those obtained for the 5-μg once-daily dose, thus justifying selection of the lower dose for asthma. Spiriva Respimat represents the first new class of drug approved by the U.S. Food and Drug Administration for the treatment of asthma in more than a decade. The availability of Spiriva Respimat for asthma along with other novel therapies currently under development has the potential to impact asthma treatment guidelines.

Topics: Adult; Asthma; Bronchodilator Agents; Disease Progression; Drug Approval; Forced Expiratory Volume; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; United States; United States Food and Drug Administration; Vital Capacity

The long-acting anticholinergic tiotropium has recently been registered for the treatment of asthma, and its use is associated with a reduction in exacerbation frequency. Anti-inflammatory and anti-remodeling effects of tiotropium have been demonstrated in in vitro and in vivo models. Because tiotropium treatment is used in combination with inhaled corticosteroids, potential additive effects between the two would be clinically relevant. Therefore, the aim of this study was to investigate additive effects between tiotropium and ciclesonide on airway inflammation and remodeling in guinea pig models of asthma.. Guinea pigs (n = 3-8/group) were sensitized and challenged with ovalbumin in an acute (single challenge) and a chronic model (12 weekly challenges) of allergic asthma. Animals were treated with vehicle, nebulized tiotropium (0.01-0.3 mM) and/or intranasally instilled ciclesonide (0.001-1 mg/kg) before each challenge. Bronchoalveolar lavage fluid and lungs were collected for analysis of airway inflammation and remodeling.. Tiotropium and ciclesonide treatment, alone or in combination, did not inhibit airway inflammation in the acute asthma model. In a dose-finding study, low doses of tiotropium and ciclesonide inhibited airway eosinophilia and airway smooth muscle thickening in the chronic asthma model. Threshold doses of 0.01 mM tiotropium (nebulizer concentration) and 0.01 mg/kg ciclesonide were selected to investigate potential additive effects between both drugs. At these doses, tiotropium and ciclesonide did not inhibit airway eosinophilia or airway smooth muscle thickening when administered alone, but significantly inhibited these allergen-induced responses when administered in combination.. Combined treatment with low doses of tiotropium and ciclesonide inhibits airway inflammation and remodeling in a guinea pig model of chronic asthma, suggesting that combined treatment with anticholinergics and corticosteroids may have anti-inflammatory and anti-remodeling activity in allergic airway diseases. Since tiotropium is registered as a therapy for asthma added on to corticosteroid treatment, these beneficial effects of the combination therapy may be clinically relevant.

Topics: Administration, Inhalation; Airway Remodeling; Animals; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Guinea Pigs; Male; Ovalbumin; Pregnenediones; Tiotropium Bromide; Treatment Outcome

Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications.. 2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA.. In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95% CI 0.31, 1.00], p = 0.05).. Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma.. ClinicalTrials.gov NCT00608764, first received 1/28/2008.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Asthma; Bronchodilator Agents; Cohort Studies; Comorbidity; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Logistic Models; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Factors; Sex Factors; Tiotropium Bromide

Topics: Administration, Inhalation; Adolescent; Asthma; Child; Clinical Trials as Topic; Forced Expiratory Volume; Humans; Tiotropium Bromide

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Allergens; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Bronchial Thermoplasty; Bronchodilator Agents; Environmental Exposure; Eosinophilia; Humans; Practice Guidelines as Topic; Prenatal Care; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tiotropium Bromide; Vitamin D; Vitamins

Topics: Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Female; Humans; Male; Salmeterol Xinafoate; Tiotropium Bromide

Topics: Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Female; Humans; Male; Salmeterol Xinafoate; Tiotropium Bromide

Topics: Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Female; Humans; Male; Salmeterol Xinafoate; Tiotropium Bromide

Bronchial asthma is becoming increasingly prevalent worldwide. Although first-line therapy with inhaled corticosteroids (ICS) with or without long-acting β2 agonists (LABA) has significantly improved the clinical outcomes of asthma, they cannot provide all asthmatics with good control and thus alternatives or add-on drugs are required. Tiotropium is a long-acting muscarinic antagonist that has been used to treat chronic obstructive pulmonary disease and it has been approved for treating asthma in some countries. This agent has similar bronchodilatory effects to those of LABA and might also have anti-inflammatory and anti-remodeling effects.. Some pivotal clinical trials have found tiotropium effective as an add-on medication for low-to-medium doses of ICS for treating symptomatic asthma and asthma that remains uncontrolled despite ICS plus LABA therapy.. Whether or not tiotropium has anti-inflammatory and anti-remodeling effects in humans with asthma is an important issue. Predictors that would identify patients who would derive the maximal potential benefit from treatment with tiotropium in addition to their current therapy are also needed. Although the cardiovascular toxicity of tiotropium is less remarkable in asthma than in chronic obstructive pulmonary disease, longer and larger studies are still needed to confirm the safety of tiotropium for treating asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Diagnosis, Differential; Health Care Costs; Humans; Patient Compliance; Poland; Tiotropium Bromide

Topics: Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Female; Humans; Male; Salmeterol Xinafoate; Tiotropium Bromide

To assess, using a standard observational tool, the ability of patients to demonstrate and maintain proper inhaled medication administration techniques following pharmacist education.. Six-month observational study.. Patients' homes or adult day health center.. Patients in a Program for All-inclusive Care for the Elderly (PACE) prescribed one or more inhaled medications used at least once daily.. Instruction by on-site clinical pharmacist.. Hickey's Pharmacies Inhaler Technique assessment (score range: 0-20, higher better).. Forty-two patients were evaluated at baseline, taught proper techniques for using inhaled medications, assessed immediately following the education, and re-assessed 4-6 weeks later. The mean pre-assessment score was 14 (SD 4.5, range 0-20), the initial post-assessment score increased to 18 (SD 3, range 10-20). The second post-assessment (4-6 weeks later) score mean was 17.7 (SD 3, range 10-20). Both follow-up scores were significantly improved from baseline (p < 0.05). Multivariable analysis indicated the strongest predictors of second post-training score were: score after initial pharmacist training and being subscribed to auto-refill. These characteristics predicted ∼70% of the variance in the second score (p < 0.001).. These results indicate that education by a pharmacist combined with an auto-refill program can improve and sustain appropriate inhaler use by community-dwelling elders in a PACE program. The improved score was maintained 4-6 weeks later indicating a sustained benefit of medication administration education. Optimal inhaler use ensures optimal dosing and supports appropriate inhaler treatment in lieu of oral agents.

Topics: Administration, Inhalation; Adult Day Care Centers; Age Factors; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Drug Delivery Systems; Female; Fluticasone-Salmeterol Drug Combination; Humans; Independent Living; Male; Middle Aged; Nebulizers and Vaporizers; Outcome Assessment, Health Care; Patient Education as Topic; Pharmacists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Tiotropium solution for inhalation (Spiriva Respimat - Boehringer Ingelheim) is the first long-acting muscarinic antagonist to be marketed in the UK for the management of asthma. It is licensed as add-on maintenance bronchodilator treatment in adults with asthma who are using an inhaled corticosteroid (≥800μg budesonide/day or equivalent) and a long-acting beta2 agonist, and who have had one or more severe exacerbations in the previous year. This corresponds to use at step 4 of both the British asthma guideline and the Global Initiative for Asthma (GINA) strategy for the treatment of asthma in adults. Here we consider the evidence for tiotropium in the management of asthma and whether it offers any advantages over existing therapeutic options at step 4.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Delayed-Action Preparations; Humans; Muscarinic Antagonists; Practice Guidelines as Topic; Tiotropium Bromide

Inhaled corticosteroid/long-acting β2-agonist combinations and/or long-acting muscarinic antagonists are recommended first-line therapies for preventing chronic obstructive pulmonary disease (COPD) exacerbation. Comparative effectiveness of budesonide/formoterol combination (BFC, an inhaled corticosteroid/long-acting β2-agonist combination) vs tiotropium (long-acting muscarinic antagonist) in the US has not yet been studied.. Using US claims data from the HealthCore Integrated Research Environment, COPD patients (with or without comorbid asthma) ≥40 years old initiating BFC or tiotropium between March 1, 2009 and February 28, 2012 and at risk for exacerbation were identified and followed for 12 months. Patients were propensity score matched on demographics and COPD disease severity indicators. The primary outcome was time to first COPD exacerbation. Secondary outcomes included COPD exacerbation rate, health care resource utilization, and costs.. The Cox proportional hazards model for time to first exacerbation yielded a hazard ratio (HR) of 0.78 (95% CI =[0.70, 0.87], P<0.001), indicating a 22% reduction in risk of COPD exacerbation associated with initiation of BFC versus tiotropium. A post hoc sensitivity analysis found similar effects in those who had a prior asthma diagnosis (HR =0.72 [0.61, 0.86]) and those who did not (HR =0.83 [0.72, 0.96]). BFC initiation was associated with lower COPD-related health care resource utilization and costs ($4,084 per patient-year compared with $5,656 for tiotropium patients, P<0.001).. In COPD patients new to controller therapies, initiating treatment with BFC was associated with improvements in health and economic outcomes compared with tiotropium.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Asthma; Bronchodilator Agents; Budesonide; Comorbidity; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Hospitalization; Humans; Insurance Claim Reporting; Male; Middle Aged; Muscarinic Antagonists; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Negative binomial model has been increasingly used to model the count data in recent clinical trials. It is frequently chosen over Poisson model in cases of overdispersed count data that are commonly seen in clinical trials. One of the challenges of applying negative binomial model in clinical trial design is the sample size estimation. In practice, simulation methods have been frequently used for sample size estimation. In this paper, an explicit formula is developed to calculate sample size based on the negative binomial model. Depending on different approaches to estimate the variance under null hypothesis, three variations of the sample size formula are proposed and discussed. Important characteristics of the formula include its accuracy and its ability to explicitly incorporate dispersion parameter and exposure time. The performance of the formula with each variation is assessed using simulations.

Topics: Asthma; Clinical Trials as Topic; Computer Simulation; Humans; Likelihood Functions; Models, Statistical; Sample Size; Scopolamine Derivatives; Tiotropium Bromide

Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway remodeling and lung damage. We tested the efficacy of tiotropium bromide, a selective long-acting, muscarinic receptor antagonist as an adjunct therapy in relapses of allergic asthma in mice. We compared the effectiveness of local intranasal administration of tiotropium and dexamethasone in acute and relapsing allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent bronchodilator, we tested higher doses to determine effectiveness on inflammation and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during disease initiation and 88% at relapse compared to vehicle alone. Both drugs were comparable in their capacity to suppress airway and parenchymal inflammation and mucus hypersecretion, though tiotropium was better than dexamethasone at reducing mucus secretion during disease relapse. Despite treatment with either drug, serum antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study indicates that tiotropium at higher doses than required for bronchodilation, effectively suppresses inflammation and mucus hypersecretion in the lungs and airways of mice during the initiation and relapse of asthma. Tiotropium is currently not approved for use in asthma. Clinical studies have to demonstrate the efficacy of tiotropium in this respiratory disease.

Topics: Airway Remodeling; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Eosinophils; Female; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred BALB C; Mucus; Recurrence; Scopolamine Derivatives; Tiotropium Bromide

Mesenchymal cells (fibroblasts) of the airway wall respond to cholinergic stimulation by releasing pro-inflammatory and chemotactic cytokines and may thus contribute to chronic inflammation of the lung. Here, we studied the anti-inflammatory potential of olodaterol, a long acting β2-adrenergic receptor agonist, and tiotropium, a long-acting muscarinic receptor antagonist, and whether they interact at the level of the cyclic AMP dependent signaling pathway. Pulmonary fibroblasts of asthmatic (n = 9) and non-asthmatic (n = 8) subjects were stimulated with the muscarinic receptor agonist carbachol and interleukin-1β (IL-1 beta) in presence or absence of tiotropium or olodaterol alone, or their combination. We also measured cAMP levels and phosphorylation of the cAMP response element binding protein (CREB). As single components, carbachol, olodaterol and tiotropium did not affect IL-6 and IL-8 release. Carbachol concentration-dependently enhanced the production of IL-1β-induced IL-6 and IL-8, which was blocked by the simultaneous addition of tiotropium. The combination of olodaterol plus tiotropium further reduced IL-6 and IL-8 release. Olodaterol induced cAMP and the phosphorylation of CREB, an effect counteracted by carbachol, but rescued by tiotropium. We conclude that olodaterol plus tiotropium cooperate to decrease the inflammatory response in pulmonary fibroblasts in vitro.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Inflammatory Agents; Asthma; Benzoxazines; Bronchodilator Agents; Carbachol; Cyclic AMP; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fibroblasts; Humans; In Vitro Techniques; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Muscarinic Antagonists; Phosphorylation; Scopolamine Derivatives; Signal Transduction; Tiotropium Bromide

Topics: Adolescent; Asthma; Bronchodilator Agents; Child; Chronic Disease; Cough; Female; Humans; Male; Scopolamine Derivatives; Tiotropium Bromide

Topics: Asthma; Humans; Scopolamine Derivatives; Tiotropium Bromide

Topics: Asthma; Bronchodilator Agents; Glucocorticoids; Humans; Scopolamine Derivatives; Tiotropium Bromide

A considerable proportion of patients with asthma remain uncontrolled or symptomatic despite treatment with a high dose of inhaled glucocorticosteroids (ICSs) and long-acting β2-agonists (LABAs). Tiotropium Respimat(®) added to usual care improves lung function, asthma control, and the frequency of non-severe and severe exacerbations, in a population of adult asthma patients who are uncontrolled despite treatment with ICS/LABA.. This study estimated the cost effectiveness of tiotropium therapy as add-on to usual care in asthma patients that are uncontrolled despite treatment with ICS/LABA combination from the perspective of the UK National Health Service (NHS).. A Markov model was developed which considers levels of asthma control and exacerbations. The model analysed cost and quality-adjusted life-years (QALYs); sensitivity and scenario analyses were also conducted to test the robustness of the base case outcomes. All costs are given at 2012 prices.. The model found that in this category of asthma with unmet need, add-on tiotropium therapy generated an incremental 0.24 QALYs and £5,238 costs over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of £21,906 per QALY gained. Sensitivity analysis suggested that findings were most dependent on the costs of managing uncontrolled asthma and the cost of treatment with tiotropium.. In this modelled analysis of two clinical trials, tiotropium was found to be cost effective when added to usual care in patients who remain uncontrolled despite treatment with high-dose ICS/LABA. Further research should investigate the long-term treatment effectiveness of tiotropium.

Topics: Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Markov Chains; Quality-Adjusted Life Years; Respiratory Therapy; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Topics: Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Asthma; Benzyl Alcohols; Biological Products; Chlorobenzenes; Cytokines; Drug Approval; Germany; Humans; Immunoglobulin E; Off-Label Use; Omalizumab; Physician's Role; Rhinitis, Allergic, Perennial; Scopolamine Derivatives; Tiotropium Bromide

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Ethanolamines; Forecasting; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Muscarinic Antagonists; Pregnadienediols; Pregnenediones; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

To review the literature evaluating the efficacy and steroid-sparing effect of tiotropium for inadequately controlled persistent asthma in adults.. Information was obtained through a search of MEDLINE/PubMed (1966-October 2012), using the terms asthma and tiotropium. A further review of reference citations was performed to identify other relevant articles.. English-language case reports and clinical trials were reviewed. Publications evaluating the efficacy and steroid-sparing effect of tiotropium in adults with inadequately controlled persistent asthma were included in the review. One case report and 5 clinical trials met our criteria.. The ultimate goal for asthma management is to maintain disease control by preventing acute exacerbations while avoiding adverse medication effects. Inhaled corticosteroids (ICS) are part of all preferred maintenance regimens for persistent asthma. Unfortunately, persistent asthma remains inadequately controlled in some patients and concerns about serious adverse effects with long-term high-dose ICS treatment exist. Interest in the use of tiotropium to control asthma symptoms and reduce steroid requirements in inadequately controlled persistent asthma is emerging. Results of several trials indicate that tiotropium improves pulmonary function markers and reduces corticosteroid requirements. Moreover, the largest and longest published trial not only showed improvements in pulmonary function tests but also a reduction in corticosteroid use and an increase in the time to first exacerbation.. Although tiotropium use in treatment of persistent asthma appears to be promising, more robust clinical trials are needed to assess whether improved pulmonary function tests as well as a decrease in asthma exacerbations and corticosteroid requirements translate into improvements in quality of life. Additionally, the optimal patient population, long-term efficacy, and safety of tiotropium when delivered by various methods need to be determined before it can be recommended over current alternative asthma therapies.

Topics: Administration, Inhalation; Adult; Animals; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Glucocorticoids; Humans; Quality of Life; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide

Asthma is characterized by reversible bronchoconstriction and airway hyperreactivity. Although M(3) muscarinic receptors mediate bronchoconstriction, non-selective muscarinic receptor antagonists are not currently recommended for chronic control of asthma. We tested whether selective blockade of M(3) receptors, at the time of antigen challenge, blocks subsequent development of airway hyperreactivity in antigen-challenged guinea-pigs.. Ovalbumin-sensitized guinea-pigs were pretreated with 1 µg·kg(-1) of a kinetically selective M(3) receptor antagonist, tiotropium, or 1 mg·kg(-1) of a non-selective muscarinic receptor antagonist, atropine, and challenged with inhaled ovalbumin. Animals were anaesthetized, paralyzed, ventilated and vagotomized 24 h later. We measured vagally mediated bronchoconstriction and i.v. ACh-induced bronchoconstriction.. Electrical stimulation of both vagus nerves induced frequency-dependent bronchoconstriction in sensitized animals that was significantly increased after antigen challenge. Antigen-induced hyperreactivity was completely blocked by tiotropium pretreatment but only partially blocked by atropine pretreatment. Surprisingly, although tiotropium blocked bronchoconstriction induced by i.v. ACh, it did not inhibit vagally-induced bronchoconstriction in sensitized controls, suggesting that tiotropium does not block hyperreactivity by blocking receptors for vagally released ACh. Rather, tiotropium may have worked through an anti-inflammatory mechanism, since it inhibited eosinophil accumulation in the lungs and around nerves.. These data confirm that testing M(3) receptor blockade with exogenous ACh does not predict vagal blockade. Our data also suggest that selective blockade of M(3) receptors may be effective in asthma via mechanisms that are separate from inhibition of bronchoconstriction.

Topics: Acetylcholine; Animals; Asthma; Atropine; Bronchial Hyperreactivity; Bronchoconstriction; Disease Models, Animal; Eosinophils; Female; Guinea Pigs; Inflammation; Ovalbumin; Receptor, Muscarinic M3; Scopolamine Derivatives; Tiotropium Bromide; Vagus Nerve

Long-term therapy with systemic corticosteroids is not recommended in the treatment of chronic obstructive pulmonary disease (COPD). However, experience demonstrates that some patients receive low dose therapy. Our objective was to describe the demographic, physiologic and radiologic characteristics of COPD patients treated with chronic systemic corticosteroids. We analyzed COPD subjects with GOLD I-IV disease in the COPDGene® study. Subjects were divided into 2 groups based on whether they reported using chronic oral steroids or not; 1264 subjects were included. Fifty-eight (4.5%) reported chronic systemic corticosteroid use. There were no differences in age, race, co-morbid conditions (other than asthma), or body mass index between the groups. There was a greater proportion of GOLD III (41% vs. 26%) and IV (41% vs. 13%) subjects in the group using chronic systemic corticosteroids. This group used more respiratory medications, required more oxygen (2.31 ± 0.21 vs. 0.59 ± 0.05 L/min; p < 0.0001), and walked less distance (245.4 ± 17.4 vs. 367.2 ± 3.9 meters; p < 0.0001). They reported more total (1.7 ± 0.16 vs. 0.62 ± 0.03; p < 0.0001) and severe exacerbations per year (0.41 ± 0.05 vs. 0.18 ± 0.01; p < 0.0001). BODE (5.0 ± 0.3 vs. 2.6 ± 0.1; p < 0.0001), MMRC (3.31 ± 0.19 vs. 1.90 ± 0.04; p < 0.0001) and SGRQ scores (54.9 ± 2.9 vs 53.3 ± 0.6; p < 0.0001) were higher. They also had a higher percentage of emphysema (22.4 ± 1.9 vs. 14.0 ± 0.4;%, p = <0.0001) on CT scan. COPD patients that report using chronic systemic corticosteroids have more severe clinical, physiologic, and radiographic disease.

Topics: Administration, Oral; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hypersensitivity; Male; Middle Aged; Multidetector Computed Tomography; Nebulizers and Vaporizers; Oxygen; Oxygen Inhalation Therapy; Prednisone; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Quality of Life; Scopolamine Derivatives; Severity of Illness Index; Smoking; Spirometry; Theophylline; Tiotropium Bromide; United States; Walking

Recent evidence suggests that acetylcholine acting through muscarinic receptors may play an inhibitory role in the mechanisms that drive the structural changes in the airways called airway remodeling. The novel anticholinergic drug tiotropium bromide, which selectively antagonizes muscarinic receptors, especially the M3 subtype, and is long acting, could be beneficial in attenuating airway remodeling in chronic asthma.. To investigate the effect of tiotropium bromide on parameters of airway remodeling, including smooth muscle hypertrophy and peribronchial thickening, in a mouse model of chronic asthma.. To develop the murine models of acute and chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 1 and 3 months, respectively. The effect of tiotropium bromide (0.1mM in 50 μL of phosphate-buffered saline) on pulmonary inflammation and remodeling was evaluated. The expression of muscarinic receptors M2 and M3 was analyzed.. In the chronic asthma model, the tiotropium-treated group significantly decreased smooth muscle thickening and peribronchial collagen deposition. As for pulmonary inflammation, the chronic asthma model had a reduction of inflammatory cells and T(H)2 cytokines by tiotropium bromide, but the effects in the asthma acute model were reversed. In the chronic asthma model, expression of the M3 receptor was inhibited and that of the M2 receptor was elevated by the administration of tiotropium bromide.. This study suggests that tiotropium bromide might have an inhibitory effect on airway remodeling in a murine model of chronic asthma. Differential effects on muscarinic receptor subtypes may explain why tiotropium bromide has different effects on acute and chronic asthma.

Topics: Acetylcholine; Acute Disease; Airway Remodeling; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cholinergic Antagonists; Chronic Disease; Cytokines; Disease Models, Animal; Eosinophils; Female; Macrophages; Mice; Mice, Inbred BALB C; Muscle, Smooth; Neutrophils; Ovalbumin; Pneumonia; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Scopolamine Derivatives; Th2 Cells; Tiotropium Bromide

Topics: Asthma; Bronchodilator Agents; Female; Humans; Male; Scopolamine Derivatives; Tiotropium Bromide

Topics: Asthma; Drug Therapy, Combination; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Smoking; Tiotropium Bromide

Chronic obstructive pulmonary disease (COPD) management was investigated in two sub-studies of the BEACH (Bettering the Evaluation and Care of Health) program at 5711 general practitioner-patient encounters in February to March 2010 and April to May 2011.

Topics: Aged; Albuterol; Asthma; Australia; Bronchodilator Agents; Comorbidity; Female; General Practice; Humans; Male; Middle Aged; Prevalence; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Airway Remodeling; Asthma; Bronchodilator Agents; Humans; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

This study investigated the effects of tiotropium bromide on chronic asthma patients with persistent obstructive ventilatory impairment (FEV1/FVC%<70%) like COPD.. Twenty-four patients (14 males, 10 females, mean age 64.3±10.7 years old) were enrolled. They were all treated with a high dose inhaled steroids and a long-acting β2-agonist. All patients had bronchial reversibility, normal diffusing capacity (DLCO) and no low attenuation areas in HRCT. This study examined the FEV1 at baseline and after inhalation of short-acting bronchodilators (400 μg salbutamol and 40 μg ipratropium, 15 minutes and 30 minutes after, respectively). Eleven patients agreed to take an additional treatment with tiotropium, and received 18 μg of tiotropium per daily for one year. The usual treatments were continued for 7 patients that did not agree to take tiotropium and for 6 patients who were ineligible for tiotropium due to co-morbidities. The FVC, FEV1, FEV1/FVC%, V50, and IC were compared between the two groups after one year.. FEV1 and V50 were significantly elevated after one year in the tiotropium-treated patients in comparison to those in the 13 subjects that did not receive tiotropium bromide, after adjusting for age, smoking and the values determined on enrollment. There was a positive correlation between the change of FEV1 30 min after ipratropium inhalation (short-term effect) and FEV1 one year after tiotropium inhalation (long-term effect).. Combination treatment with tiotropium, high dose steroids and long-acting β2 agonist inhalation provides improvement in the expiratory flow limitations of asthma patients with persistent obstructive ventilatory impairment.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Drug Therapy, Combination; Female; Humans; Ipratropium; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiration Disorders; Scopolamine Derivatives; Steroids; Tiotropium Bromide

Topics: Asthma; Cholinergic Antagonists; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Asthma; Bronchodilator Agents; False Positive Reactions; Forced Expiratory Volume; Humans; Obesity; Scopolamine Derivatives; Tiotropium Bromide; Vital Capacity

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Drug Therapy, Combination; Glucocorticoids; Humans; Ipratropium; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Despite the fact that bronchioles are involved in asthma, there have been limited asthmatic cases showing marked centrilobular opacities on computed tomography (CT) chest scans. Systemic corticosteroids have been administered in such cases, but the efficacy of extra-fine particle inhaled corticosteroids has not been assessed.. A previously healthy 64-year-old man presented with a four-month history of productive cough and progressive dyspnea despite a combination therapy with inhaled salmeterol (50 μg bid) and fluticasone (500 μg bid), sustained-release theophylline, and pranlukast because of suspicion of asthma. Physical examination revealed wheezing at the end of forced expiration. High resolution CT chest scan showed diffuse centrilobular opacities, bronchiectatic changes, and bronchial wall thickening. Transbronchial lung biopsy, bronchoalveolar lavage fluid, and transbronchial biopsy all showed predominant eosinophil infiltrates, suggesting that eosinophilic inflammation across the entire airway tree caused the abnormal CT findings. Alveolar fraction of exhaled nitric oxide level, a non-invasive marker of eosinophilic peripheral airway inflammation, was also elevated. Because he refused systemic corticosteroids, inhaled ciclesonide (400 μg bid) and inhaled tiotropium were added on to his current medication under careful observation. His symptoms, pulmonary function and CT findings promptly improved, and he had fully recovered at follow-up.. Extra-fine particle inhaled corticosteroids could be an alternative approach in centrilobular opacities caused by eosinophilic peripheral airway inflammation.

Topics: Anti-Allergic Agents; Asthma; Eosinophils; Humans; Inhalation; Lung; Male; Middle Aged; Nitric Oxide; Pregnenediones; Pulmonary Alveoli; Scopolamine Derivatives; Tiotropium Bromide; Tomography, X-Ray Computed

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Formoterol Fumarate; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pregnenediones; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Excipients; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Acetates; Administration, Inhalation; Adult; Airway Obstruction; Asthma; Atherosclerosis; Bronchodilator Agents; Bronchoscopy; Child; Cyclopropanes; Glucocorticoids; Humans; Hyperthermia, Induced; Leukotriene Antagonists; Quinolines; Scopolamine Derivatives; Sulfides; Tiotropium Bromide

Tiotropium bromide, a long acting muscarinic receptor inhibitor, is a potent agent for patients with bronchial asthma as well as chronic obstructive pulmonary disease.. The aim of this study was to evaluate whether tiotropium bromide can inhibit allergen-induced acute and chronic airway inflammation, T helper (Th)2 cytokine production, and airway remodelling in a murine model of asthma.. Balb/c mice were sensitized and challenged acutely or chronically to ovalbumin (OVA). The impact of tiotropium bromide was assessed using these mice models by histologic, morphometric, and molecular techniques. Moreover, the effect of tiotropium bromide on Th2 cytokine production from purified human peripheral blood mononuclear cells (PBMCs) was assessed.. Treatment with tiotropium bromide significantly reduced airway inflammation and the Th2 cytokine production in bronchoalveolar lavage fluid (BALF) in both acute and chronic models of asthma. The levels of TGF-beta1 were also reduced by tiotropium bromide in BALF in a chronic model. The goblet cell metaplasia, thickness of airway smooth muscle, and airway fibrosis were all significantly decreased in tiotropium bromide-treated mice. Moreover, airway hyperresponsiveness (AHR) to serotonin was significantly abrogated by tiotropium bromide in a chronic model. Th2 cytokine production from spleen cells isolated from OVA-sensitized mice was also significantly inhibited by tiotropium bromide and 4-diphenylacetoxy-N-methylpiperidine methiodide, which is a selective antagonist to the M3 receptor. Finally, treatment with tiotropium bromide inhibited the Th2 cytokine production from PBMCs.. These results indicate that tiotropium bromide can inhibit Th2 cytokine production and airway inflammation, and thus may reduce airway remodelling and AHR in a murine model of asthma.

Topics: Airway Remodeling; Animals; Asthma; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Cytokines; Disease Models, Animal; Female; Humans; Leukocytes, Mononuclear; Mice; Mice, Inbred BALB C; Pneumonia; Scopolamine Derivatives; Th2 Cells; Tiotropium Bromide

Topics: Administration, Inhalation; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Cholinergic Antagonists; Comparative Effectiveness Research; Cross-Over Studies; Drug Industry; Drug Therapy, Combination; Glucocorticoids; Humans; Placebos; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Topics: Administration, Inhalation; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Cholinergic Antagonists; Drug Therapy, Combination; Glucocorticoids; Humans; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach.. A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 microg was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics.. Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele-dominant model] was significantly associated with response to tiotropium.. As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium.

Topics: Aged; Alleles; Asthma; Bronchodilator Agents; Female; Genetic Predisposition to Disease; Genotype; Humans; Logistic Models; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Muscarinic M1; Receptors, Adrenergic, beta-2; Receptors, Muscarinic; Scopolamine Derivatives; Tiotropium Bromide

Topics: Aged; Asthma; Bronchodilator Agents; Cohort Studies; Drug Therapy, Combination; Eosinophils; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Scopolamine Derivatives; Sputum; Tiotropium Bromide

To report a case of confirmed beta(16) Arg/Arg polymorphism (Arg/Arg) in a patient with uncontrolled asthma.. A 49-year-old black female presented to the emergency department with acute shortness of breath with subsequent intubation. After extubation, she reported multiple hospitalizations for asthma with one prior intubation, adherence to asthma medications, and very frequent use of her short-acting beta(2)-agonist (SABA). Because of her asthma history, self-reported adherence, and race, she was tested for beta(2)-adrenoreceptor genotype, which revealed Arg/Arg. Based on these findings, beta(2)-agonists were discontinued and tiotropium (maintenance) and ipratropium (primary rescue) were initiated as part of her asthma regimen. Application of the Naranjo probability scale revealed probable causality between uncontrolled asthma in our patient and SABA use. The patient is followed in our outpatient pulmonary clinic and, at time of writing, had not been admitted to our hospital for asthma-related events.. Approximately 15% of Americans with asthma are Arg/Arg, with an increased prevalence in black and Asian populations. It is hypothesized that changes in the degree of sensitivity or desensitization to the bronchodilator effect of beta(2)-agonists may occur in these individuals. Data exist, although they are conflicting, suggesting that inhaled beta(2)-agonists may worsen clinical outcomes. Trials have reported declines in peak expiratory flow rates plus increases in asthma symptoms and exacerbations when SABAs have been used regularly in patients with Arg/Arg. Studies evaluating long-acting beta(2)-agonists (LABAs) have inconsistent results. Preliminary data suggest that anticholinergics may serve as a beneficial primary rescue medication instead of beta(2)-agonists in patients with Arg/Arg.. Clinicians should be aware of factors (eg, race and polymorphisms) that may predict unfavorable outcomes with regular SABA and possibly LABA use. Patients with poor asthma control despite adherence to asthma therapy may benefit from beta(2)-adrenoreceptor genotyping and, possibly, from anticholinergics.

Topics: Adrenergic beta-Agonists; Arginine; Asthma; Bronchodilator Agents; Female; Humans; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Scopolamine Derivatives; Tiotropium Bromide

Patients with respiratory failure are often unable to inhale powdered aerosol medications such as long-acting beta agonists and long-acting anticholinergics, which are important treatments for chronic obstructive pulmonary disease and asthma.. To explore delivery of aerosolized powder medications via tracheostomy tube.. We designed interfaces to connect the HandiHaler and Aerolizer devices to tracheostomy tubes, and to connect the HandiHaler to a manual resuscitator bag. With these interfaces, in 23 patients, we assessed the clinical ease/difficulty of delivery and delivery time of the first 3 administrations of powder-aerosol long-acting beta agonists and long-acting anticholinergics from the HandiHaler and the Aerolizer.. The powder aerosols were readily delivered to all the patients. Nineteen of the 23 patients (83%) were able to inhale the medication on their own. In the 4 patients who were unable to effectively inhale the medication on their own, bag-assist was successful. The aerosol delivery time was usually < 3 min.. With a proper interface, powdered long-acting beta agonists and long-acting anticholinergics can be easily delivered via tracheostomy tube, even if the patient cannot inhale on his or her own. Further studies are needed to assess particle size, dose delivery, and clinical efficacy with these interfaces and device modifications.

Topics: Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Drug Delivery Systems; Ethanolamines; Formoterol Fumarate; Humans; Intubation, Intratracheal; Middle Aged; Nebulizers and Vaporizers; Powders; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Tracheostomy

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.. 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.. 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.. 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.

Topics: Animals; Asthma; Bronchi; Cell Count; Cholinergic Antagonists; Contractile Proteins; Disease Models, Animal; Guinea Pigs; Male; Muscle, Smooth; Ovalbumin; Scopolamine Derivatives; Tiotropium Bromide; Trachea

Long acting inhaled bronchodilators - beta agonists and anti-cholinergic--can improve symptoms, enhance quality of life, increase exercise ability, and reduce exacerbation rates in patients with COPD. PHARMAC needs to change policy so that these patients have easy access to this effective group of drugs.

Topics: Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Drug Approval; Ethanolamines; Formoterol Fumarate; Humans; National Health Programs; New Zealand; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Drug Approval; Drug Evaluation; Humans; National Health Programs; New Zealand; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Topics: Adult; Animals; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Disease Models, Animal; Dogs; Humans; Ipratropium; Lung Diseases, Obstructive; Muscarinic Antagonists; Scopolamine Derivatives; Time Factors; Tiotropium Bromide