Long-acting Anticholinergic Bronchodilator Research Articles

Effective Following: A Counterpart to Leadership

Effective Following: A Counterpart to Leadership

Elderly age group patients with COPD continuing to smoke -a problem that cannot be ignored

IntroductionAccording to the WHO, 30.9% of the adult population of the Russian Federation are active smokers. From 30% to 43% of smoking patients with COPD are not able to give up nicotine despite the diagnosis and deterioration of health. Most of the publications related to the treatment of COPD do not distinguish smoking patients into a separate group. The purpose of this study is a comparative analysis of the effectiveness of LAMA (Tiotropium bromide and Glycopyrronium bromide) and LABA \\ LAMA (Olodaterol + tiotropium and Indacaterol + Glycopyrronium bromide). Materials and methodsThe study involved 102 patients with a high degree of nicotine addiction and irreversible bronchial obstruction. All the patients were submitted to the treatment of nicotine addiction syndrome on the basis of Otkrytie Medical Center LLC. All the patients continue to receive bronchodilatory therapy. Respondents were divided into two groups: patients who quit smoking and patients who continued to smoke. In turn, each group was divided into two subgroups depending on the drugs being taken - LAMA and LAMA / LABA. As comparison criteria, we selected the dynamics of FEV1 and the dynamics of CAT. ResultsAs a result of the analysis of the obtained data FEV1 increase was detected in both study groups, regardless of the treatment regimen. FEV1 increase within the group of smoking patients was lower than of those who quit smoking - 11% and 22% respectively (p < .05). CAT dynamics showed a downward trend in both groups. However, the patients who quit smoking demon-strated greater reduction of symptoms during therapy than the smoking patients — -10 and − 1 points respectively (p < .05). No statis-tically significant difference was found either on CAT (p = .31) or spirometry - FEV1 (p = .22) for the LAMA and LAMA / LABA subgroups. Combined therapy (LAMA / LABA) applied to the group of patients who quit smoking found to be more effective than monotherapy (LAMA) both in terms of spirometry (an increase in FEV1 came to 26% and 13% respectively (p < .05)), and the de-gree of reduction of the symptoms (CAT) - -11 and − 5 respectively (p < .05). ConclusionWhile maintaining nicotine status, long-acting anticholinergic (LAMA) and combined long-acting bronchodila-tors produce a moderate and comparable effect. Therefore, when choosing the tactics of COPD treatment, it is necessary to take into consideration the current nicotine status of the patient as well as the nicotine addiction degree.

A rational approach to the treatment of bronchial asthma in children: what can we do to control the disease?

Bronchial asthma is the most common among chronic bronchopulmonary diseases with heterogeneity in symptom profiles. Despite the delivery of baseline anti-inflammatory iGCS therapy, including the subsequent staged addition of other controlling treatment methods, symptoms of the disease persist in 40% of patients. Lack of asthma control results in high morbidity, mortality and treatment costs, which justifies the search for new therapeutic options to improve control and reduce the risk of future exacerbations. Tiotropium, a long-acting anticholinergic bronchodilator, can be a good alternative in the therapeutic treatment of poorly controlled asthma in both adults and children. Several clinical studies showed the efficacy and safety of Tiotropium Respimat Soft Mist Inhaler at a dose of 5 mg in various asthma treatment options in children at 6 years old and over, who do not achieve asthma control with iGCS monotherapy at medium/high doses or with iGCS/LABA combination at medium/high doses. All asthma studies in children were conducted using Respimat Soft Mist Inhalers that generate an aerosol with a larger number of small particles, which ensures effective drug distribution and deposition in the lungs. The aerosol cloud velocity at the nozzle outlet of the inhaler is just 0.8 m/s, and the time period over which the aerosol is released is extended to 1.5 s. Moving slowly, aerosol particles more often avoid colliding with the posterior pharyngeal wall and tongue, which reduces the drug deposition in the oral cavity, significantly increasing the amount of active substance delivered to the air ways. 55% of the dose of tiotropium bromide is released in the form of particles with an optimal aerodynamic diameter, which guarantees a high level of lung deposition - 52% of the ex-valve dose.

Legal demands of the tiotropium bromide for treatment of chronic obstructive pulmonary disease and their financial impact for the State of Paraná, Brazil.

ABSTRACTObjective To analyze the legal demands of tiotropium bromide to treat chronic obstructive pulmonary disease.Methods We included secondary data from the pharmaceutical care management systems made available by the Paraná State Drug Center.Results Public interest civil action and ordinary procedures, among others, were the most common used by the patients to obtain the medicine. Two Health Centers in Paraná (Londrina and Umuarama) concentrated more than 50% of the actions. The most common specialty of physicians who prescribed (33.8%) was pulmonology. There is a small financial impact of tiotropium bromide on general costs with medicines of the Paraná State Drug Center. However, a significant individual financial impact was observed because one unit of the medicine represents 38% of the Brazilian minimum wage.Conclusion Our study highlights the need of incorporating this medicine in the class of long-acting anticholinergic bronchodilator in the Brazilian public health system.

Efficacy and safety of tiotropium in school-age children with moderate-to-severe symptomatic asthma: A systematic review.

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® in children aged 6-11years with moderate-to-severe symptomatic asthma. Randomized, placebo-controlled trials were included. Primary outcomes were peak forced expiratory volume in 1s measured within 3h post-dosing) [FEV1 (0-3h) ] and trough FEV1 measured at the end of the dosing interval. Three studies (more than 900 patients) were selected. Tiotropium was associated with significant improvements in FEV1 peak (mean change from baseline) by 102mL (P<.0001) and trough by 82mL (P<.0001) compared with placebo. Tiotropium 5μg dose presented a trend (statistically non-significant) toward a greater bronchodilation in comparison with 2.5μg dose. Tiotropium significantly increased the rate of the Asthma Control Questionnaire (ACQ-7) responders compared with placebo (82.2% vs 75.4%, number needed to treat for benefit [NNTB]=15) and significantly decreased the number of patients with at least one exacerbation in comparison with placebo (29.1% vs. 39.8%, with a NNTB of 10). There were no significant differences in rescue medication use, withdrawals, and adverse events. OD tiotropium Respimat® is efficacious and well tolerated as an add-on to inhaled corticosteroids plus one or more controller medications in school-age symptomatic asthmatics.

Safety and tolerability of once-daily tiotropium Respimat® as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: A pooled safety analysis

BackgroundTiotropium, 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. ObjectiveTo 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. MethodsData 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. ResultsOf 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%. ConclusionTiotropium 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.

Tiotropium for the treatment of asthma: a drug safety evaluation

ABSTRACTIntroduction: 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.Areas covered: 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.Expert opinion: 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.

The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids (ICS). The objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat (5 μg or 2.5 μg), compared with placebo Respimat, as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma. A phase III, double-blind, placebo-controlled trial was conducted (NCT01316380). Adults with symptomatic asthma receiving low- to medium-dose ICS (200-400 μg budesonide or equivalent dose) and a pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥60% and ≤90% of predicted normal were randomized to 12 weeks of treatment with once-daily tiotropium Respimat 5 μg or 2.5 μg, or placebo Respimat, as add-on therapy to ICS. The primary endpoint was peak FEV1(0-3h) response. In total, 464 patients were randomized (61% female; mean age 43 years; mean baseline FEV1 78% of predicted normal). After 12 weeks, both tiotropium Respimat doses were superior to placebo (adjusted mean difference from placebo: 5μg, 128 mL; 2.5 μg, 159 mL; both P < .001). Both doses of tiotropium Respimat were also superior to placebo with regard to the secondary endpoints of adjusted mean trough FEV1 and FEV1 area under the curve(0-3h) responses, and the other endpoints of morning and evening peak expiratory flow. Adverse events were comparable across the treatment groups. Once-daily tiotropium Respimat add-on therapy to low- to medium-dose ICS in adults with symptomatic asthma is an efficacious bronchodilator, and its safety and tolerability are comparable with those of placebo Respimat.

Practical guidance on the recognition of uncontrolled asthma and its management.

To highlight the significance of asthma in primary care and offer a practitioner-friendly interpretation of the asthma guidelines for the busy provider, while introducing new treatment options currently in clinical trials, such as the once-daily long-acting anticholinergic bronchodilator tiotropium Respimat. Articles with relevant adult data published between 2004 and 2015 were identified via PubMed. Additional references were obtained by reviewing bibliographies from selected articles. In the United States, uncontrolled or symptomatic asthma is common, with rates of 46%-78% in primary care. Uncontrolled asthma has a substantial impact on patients' quality of life and represents a significant healthcare burden. Nurse practitioners can improve patients' asthma control through education, monitoring, assessment, and treatment. Although asthma management guidelines are readily available, the authors recognize that nurse practitioners see patients with multiple comorbidities, all of which have treatment guidelines of their own. Nurse practitioners have a compelling opportunity as frontline caregivers and patient educators to recognize and assess uncontrolled asthma, along with determining the steps necessary to help patients gain and maintain symptom control.

Strategies for reducing the risk of cardiovascular disease in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is frequently accompanied by multimorbidities in affected patients. Even though the majority of these comorbidities are also related to advanced age and cigarette smoke, also COPD itself has significant impact on insurgence, or worsening of these conditions. As a consequence, COPD is regarded as a complex disease with pulmonary and extra-pulmonary involvement. According to current guidelines for the management of COPD patients, the comprehensive treatment of this condition should target respiratory symptoms as well as comorbidities. Cardiovascular disease is one of the most frequent comorbidities in COPD patients and there are several strategies for reducing the risk of cardiovascular disease in COPD patients. These include smoking cessation, pharmacologic prevention of cardiovascular disease, and the treatment of COPD. Beta-blockers for the prevention of cardiovascular disease have been traditionally limited in COPD patients, albeit current evidence supporting their efficacy and safety in these patients. With regard to COPD medications, corticosteroids are generally not recommended, except for exacerbations, while long-acting beta2-agonists have demonstrated an acceptable profile of cardiovascular safety. Long-acting anticholinergic bronchodilators, in particular tiotropium in the mist inhaler formulation, have been associated with an increased risk of major cardiovascular events and mortality. Data on this issue remain, however, controversial. Glycopyrronium, a recently introduced anticholinergic, demonstrated. a rapid and sustained relief of respiratory symptoms with a favorable safety profile and no increase in cardiovascular risk, in monotherapy and in combination with a long-acting beta2-agonist in a comprehensive trial program indicating a valid option for COPD patients with CV comorbidities.

Tiotropium respimat® add-on therapy reduces airflow obstruction in patients with symptomatic moderate asthma, independent of TH2 inflammatory status

S A T U R D A Y 16 Tiotropium Respimat Add-On Therapy Reduces Airflow Obstruction In Patients With Symptomatic Moderate Asthma, Independent Of TH2 Inflammatory Status Dr. Thomas B. Casale, MD, FAAAAI, Dr. Eric Donn Bateman, MD, Prof. Ronald Dahl, MD, Dr. Emilio Pizzichini, Dr. Mark L. Vandewalker, MD, Dr. Johann Christian Virchow, Dr. Michael Engel, MD, Dr. Petra Moroni-Zentgraf, Dr. Hendrik Schmidt, Huib A. M. Kerstjens; Univeristy Of South Florida Morsani College Of Medicine, Tampa, FL, University of Cape Town Lung Institute, Cape Town, South Africa, Odense University Hospital, Odense, Denmark, NUPAIVA (Asthma Research Centre), Universidade Federal de Santa Catarina, Florian opolis, Brazil, Clinical Research of the Ozarks, Columbia, MO, University Clinic Rostock, Rostock, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. RATIONALE: In patients with symptomatic asthma receiving ICS or ICS+LABA, Phase III studies have demonstrated improved lung function with tiotropium Respimat , a once-daily long-acting anticholinergic bronchodilator. The efficacy of some treatments (e.g. ICS and omalizumab) appears higher in TH2-high phenotypes, but no specific treatments are available that work equally well in both TH2-high and TH2-low phenotypes. We explored whether TH2 biomarker status influenced responses to tiotropium in patients with moderate symptomatic asthma. METHODS: In two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group trials (NCT01172808/NCT01172821), patients with moderate symptomatic asthma, using medium-dose ICS (400-800 mg budesonide equivalent), were administered once-daily tiotropium Respimat 5 mg or 2.5 mg, placebo, or salmeterol (active comparator without inferential analysis). Co-primary endpoints included peak and trough FEV1 response (difference from baseline) at 24 weeks. Pre-planned analyses (pooled population) were performed in TH2-low and TH2-high subgroups defined at baseline as total serum IgE 430 mg/L or blood eosinophils 0.6310/L. RESULTS: Of 1545 patients in the full analysis set who received tiotropium or placebo, 915/1455 were reported with IgE >430 mg/L and 300/1461 with an eosinophil count of >0.6310/L. Peak FEV1 improved with tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and eosinophil count (p<0.0001 both doses). Trough FEV1 also improved with tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and eosinophil count (p<0.005 both doses). CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS reduces airflow obstruction in patients withmoderate symptomatic asthma, independent of TH2 phenotype, and thus may potentially provide an important therapeutic option.

P230 Once-daily Tiotropium Respimat(R) Improves Lung Function In Patients With Severe Symptomatic Asthma Independent Of Leukotriene Modifier Use

Background Once-daily tiotropium Respimat®, a long-acting anticholinergic bronchodilator, has been shown in a Phase III programme to improve lung function and reduce severe exacerbation risk in patients with severe asthma who remain symptomatic despite using inhaled corticosteroids (ICS) + long-acting β2-agonist (LABA). Use of pre-trial leukotriene receptor antagonists (LTRAs) was not restricted; we analysed whether pre-screening LTRA use affected tiotropium Respimat® efficacy. Methods In two Phase III, replicate, randomised, double-blind, placebo-controlled, parallel-group trials (PrimoTinA-asthma®: [NCT00772538][1], [NCT00776984][2]), symptomatic patients received high-dose ICS + LABA and once-daily tiotropium 5 µg or placebo (both delivered via the Respimat® SoftMist™ inhaler). LTRAs were permitted during run-in and treatment. Co-primary end points were peak and trough forced expiratory volume in 1 second (FEV1) responses (difference from baseline) at 24 weeks. Subgroups were defined by pre-screening LTRA use: ‘Yes’/‘No’. Results Of 912 randomised patients, 205 reported pre-screening LTRA use, 200 reported LTRA use during the treatment period and 187 had efficacy data at Week 24. Baseline characteristics were comparable between groups. Mean body mass index in LTRA ‘Yes’/‘No’ groups was 27.8 kg/m2 and 28.3 kg/m2, respectively. Mean% predicted FEV1 at baseline was 56% in both groups. Lung function responses improved independent of LTRA use: peak FEV1 was 99 ± 50 mL (p = 0.049) in the LTRA ‘Yes’ group and 113 ± 28 mL (p < 0.001) in the LTRA ‘No’ group (peak FEV1 improvements independent of concomitant LTRA use [interaction p value=0.6742]). Trough FEV1 (difference from placebo) was 90 ± 46 mL (p = 0.052) in the LTRA ‘Yes’ group and 93 ± 25 mL (p < 0.001) in the LTRA ‘No’ group (trough FEV1 improvements independent of concomitant LTRA use [interaction p value = 0.5218]). Conclusion Once-daily tiotropium Respimat® added to ICS + LABA improves lung function in patients with severe symptomatic asthma, independent of initial LTRA use. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00772538&atom=%2Fthoraxjnl%2F69%2FSuppl_2%2FA178.1.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00776984&atom=%2Fthoraxjnl%2F69%2FSuppl_2%2FA178.1.atom

P229 Once-daily Tiotropium Respimat(R) As Add-on To At Least Medium- To High-dose Ics, With Or Without Laba, Improves Lung Function In Patients With Symptomatic Asthma, Independent Of Allergic Status

Background A substantial number of patients have symptomatic asthma despite treatment according to guidelines. Several studies have confirmed that tiotropium Respimat ® , a once-daily long-acting anticholinergic bronchodilator, improves lung function in symptomatic patients receiving at least medium-dose inhaled corticosteroids (ICS) + long-acting β 2 -agonist (LABA) (Kerstjens et al . NEJM 2012;367:1198–207; Bateman et al . JACI 2011;128:315–22). Here we examine whether the atopic and/or allergic status of patients in these trials influenced their response to tiotropium Respimat ® . Method Two 48-week trials of tiotropium Respimat ® 5 µg (PrimoTinA-asthma ® : NCT00776984, NCT00772538) in patients (n = 912) on high-dose ICS + LABA; two 24-week trials of tiotropium Respimat ® 5 µg and 2.5 µg (MezzoTinA-asthma ® : NCT01172808, NCT01172821) in patients (n = 2100) on moderate-dose ICS. Pre-planned analyses (pooled populations) were performed in two subgroups defined at baseline as total serum immunoglobulin E (IgE) ≤ or >430 μg/L or blood eosinophils ≤ or >0.6×10 9 /L or clinical judgement of allergic status (‘No’ or ‘Yes’). All tiotropium doses were delivered via the Respimat ® SoftMist™ inhaler. Results Tiotropium Respimat ® 5 µg or 2.5 µg improved peak and trough forced expiratory volume in 1 second versus placebo (Table) independent of IgE, eosinophil count and clinical judgement. Conclusion Once-daily tiotropium Respimat ® as add-on to ICS or ICS + LABA in patients with moderate to severe symptomatic asthma reduces airflow obstruction, apparently independent of their atopic and/or allergic status.

Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?

Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease. Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of ‘cholinergic tone’. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce. Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.

Tiotropium as add-on to inhaled corticosteroids significantly improves asthma control as reflected by the ACQ responder rate

Background: Despite current medications, there remains an unmet need for asthma control in patients with moderate asthma receiving at least ICS. We analysed ACQ (asthma control questionnaire) data in patients treated with once-daily long-acting anticholinergic bronchodilator tiotropium who had symptomatic asthma despite treatment with medium-dose ICS (400 – 800 µg budesonide equivalent).

Once-Daily Tiotropium Respimat® Improves Lung Function In Patients With Severe Symptomatic Asthma Independent Of Leukotriene Modifier Use

Once-daily tiotropium Respimat®, a long-acting anticholinergic bronchodilator, has been shown in a Phase III program to improve lung function and reduce severe exacerbation risk in severe asthma patients who remain symptomatic despite using ICS+LABA. Use of pre-trial leukotriene receptor antagonists (LTRAs) was not restricted; we analyzed whether pre-screening LTRA use affected tiotropium Respimat® efficacy.

Aclidinium Bromide: Clinical Benefit in Patients with Moderate to Severe COPD.

Background and Aim:Long-acting bronchodilators are the mainstay of pharmacological treatment for patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the safety and efficacy of inhaled aclidinium bromide, a novel long-acting anticholinergic bronchodilator, for the treatment of COPD.Method:This systematic review explored the efficacy and safety of aclidinium bromide in comparison with placebo and other long-acting bronchodilators for treatment of moderate to severe COPD. Randomised controlled trials were identified through systematic searches of different databases of published trials.Results:Ten trials (3.922 participants) were included. Aclidinium bromide appears to be a safe and well-tolerated long-acting anti-cholinergic bronchodilator with a relatively fast onset of action. Compared with other long-acting bronchodilators, including tiotropium bromide, aclidinium bromide leads to at least similar clinically important improvements in level of FEV1, health status, use of rescue medication, and day-time dyspnea scores in patients suffering from moderate to severe COPD. With twice-daily dosing, aclidinium bromide may have clinically important effect on night-time symptom scores in COPD patients, but further studies are needed in order to permit valid conclusions with regard to this point. The effect of aclidinium bromide on exercise tolerance, as assessed by exercise endurance time, and dynamic hyperinflation in patients with moderate to severe COPD seems to be at least comparable to other long-acting bronchodilators, incl. tiotropium bromide and indacaterol. Aclidinium bromide might reduce the rate of exacerbations in COPD patients, but conclusions must await further long-term controlled trials.Conclusion:Aclidinium bromide has effects on relevant COPD outcome measures, including level of FEV1, similar to other long-acting bronchodilators, and therefore seems to have the potential for a significant role in the future management of moderate to severe COPD.

Chronic obstructive pulmonary disease: a slowly progressive cardiovascular disease masked by its pulmonary effects?

Chronic obstructive pulmonary disease: a slowly progressive cardiovascular disease masked by its pulmonary effects?

Effects of tiotropium and formoterol on quiet breathing pattern assessed by optoelectronic plethysmography in COPD patients: a pilot study

Chronic obstructive pulmonary disease (COPD) is a disease characterized by an airflow limitation that is not fully reversible. β(2)-agonists and anticholinergics represent the most effective therapeutic options. Optoelectronic plethysmography (OEP) is a novel technology, which provides noninvasive steady-state measurements of chest wall kinematics, together with the assessment of the relative contribution of all different thoracic and abdominal compartments to tidal volume. The aim of this pilot study was to investigate the changes in quiet breathing due to different long-acting bronchodilators (namely, formoterol and tiotropium) administered to COPD patients of different severity. Eight moderate-to-severe COPD patients were studied according to a randomized crossover design. All subjects received both the long-acting bronchodilators: formoterol (long-acting β(2)-agonist, 24 µg) and tiotropium (long-acting anticholinergic bronchodilator, 18 µg). The effect of bronchodilators on quiet breathing was evaluated by means of OEP at base conditions, and 2 and 7 hours after inhalation. Both bronchodilators caused changes in the quiet breathing pattern in COPD patients that had previously reported only negligible changes in FEV(1) (ΔFEV(1) = 2.6% after salbutamol). The main changes were observed in increased ventilation per minute, inspiratory and expiratory flow, and decreased breath-by-breath variability. Formoterol induced its main effects during the first 2 hours after inhalation, while tiotropium caused improvements between 2 and 7 hours. Even though a greater cohort of COPD patients is needed in order to confirm the present results, this pilot study reports a novel piece of evidence concerning the effects of bronchodilators on quiet breathing pattern in severe and very severe COPD patients.

Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study

BackgroundMany patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results.MethodsWe performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy.ResultsAnalyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: −17.3–69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77–21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups.ConclusionsOur study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration.