Anticholinergic Bronchodilator Research Articles

Effective Following: A Counterpart to Leadership

Effective Following: A Counterpart to Leadership

Use of aerosol therapy in patients under mechanical ventilation in the ICU

Aerosol therapy is a form of drug administration that favors a rapid and easy absorption of the same in the respiratory tract; thus favoring great advantages in improving the health status of patients who are subjected to mechanical ventilation in the ICU. The most commonly used drugs are beta-agonist and anticholinergic bronchodilators. The use of this therapy should be used more frequently in these patients, but factors specific to the individual and the drug should be considered for its application; its use in patients with covid-19 should also be considered.

Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BackgroundTiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes.MethodsIn a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium–placebo or placebo–tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 μg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set.Results90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72–1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23–92 mL; p=0.002). Adverse events were similar under both treatments.ConclusionsTiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Safety, Tolerability and Pharmacokinetics of Bencycloquidium Bromide, a Novel Inhaled Anticholinergic Bronchodilator, in Healthy Subjects: Results from Phase I Studies

BackgroundBencycloquidium bromide (BCQB) is a novel inhaled anticholinergic bronchodilator with high selectivity for muscarinic M3 receptor. BCQB's potential utility of for therapy in Chronic obstructive pulmonary disease (COPD) has been indicated in pre-clinical studies. PurposeTo investigate the initial safety, tolerability and pharmacokinetics of BCQB delivered via pressurised Metered Dose Inhaler (pMDI) in healthy subjects. MethodsThis study consisted of single-ascending-dose (SAD), multiple-ascending-dose (MAD) tolerability study periods, and single- plus multiple-dose pharmacokinetic study periods. Randomized, double-blind, placebo-controlled, dose-escalating tolerability and pharmacokinetic studies were conducted. Seventy-two healthy subjects were assigned 3:1 (BCQB: placebo) to 7 single-dose cohorts (125, 250, 500, 750, 1125, 1500 and 2000 μg) and 2 multiple-dose cohorts (1500 μg/d and 2000 μg/d). In the pharmacokinetic periods, 12 subjects were allocated three-way crossover to receive single dose of 250, 750 or 2000 μg BCQB, respectively. Subsequently, the same 12 subjects received multiple dose of 750 μg/d and 1000 μg/d for 7 days. Pharmacokinetic, safety and tolerability assessments were performed. ResultsBCQB administered by inhalation was well tolerated, especially with favorable cardiovascular safety profile. BCQB was rapidly absorbed into plasma after inhalation through pMDI, with peak concentrations achieved within 5 to 10 minutes. Repeated inhalation caused certain degree of accumulation with the accumulation ratio RCmax 2.50, RAUC 3.49 for 3 times-a-day and RCmax 2.23, RAUC 3.44 for 4 times-a-day, respectively. Twice-a-day or even once-a-day dosage could be suggested in phase II study. Sex didn't affect the pharmacokinetics of BCQB and dose adjustments based on sex is not anticipated in clinical use. Approximately 4% of the BCQB dose excreted unchanged in urine and liver metabolism is the main biotransformation route of BCQB in human. ConclusionsThe results of our study provided the initial safety, tolerability and pharmacokinetic profiles of BCQB inhalation, and could enable further clinical development in COPD patients.

Comparison of Combined Nebulization of Salbutamol-Ipratropium Bromide with Salbutamol Alone in Children with Mild and Moderate Acute Asthma

ntroduction: The β2 agonists are potent bronchodilators but their repeated and high doses are related to adrenergic side effects. While ipratropium bromide, an anticholinergic bronchodilator has less adverse effects.
 Objective: To compare the efficacy of combined nebulization of salbutamol-ipratropium bromide with salbutamol alone in children with mild and moderate acute asthma.
 Materials and Methods: This randomised control trial was done on 80 children aged 5 to 12 years who presented with mild to moderate acute asthma in the emergency department of Children Hospital of Pakistan Institute of Medical Sciences (PIMS) from July 2014 to June 2016 and randomized into 2 groups. In the experimental group each child received 2 nebulizations of combined salbutamol (5mg) and ipratropium Bromide (0.25mg) at presentation and 20 minutes later. Similarly, each child of the control group received 2 nebulizations of 5mg Salbutamol and 2 ml of Normal saline. Asthma clinical score (ACS) was assessed at baseline and then after every 20 minutes up to one hour after the presentation.
 Results: In the experimental group, the mean + SD ACS at presentation and 60 minutes were 3.50±1.8 and 3.45±1.7 respectively with mean + SD change in ACS of 0.05 ± 0.1. In the control group, the mean + SD ACS at presentation and 60 minutes were 3.70 ± 1.2 and 3.60 ± 1.9, respectively with mean + SD change in ACS of 0.1 ± 0.7. This difference in mean + SD change in ACS between 2 groups was not statistically significant (P=0.6560).
 Conclusion: There is no statistically significant benefit of adding ipratropium bromide with salbutamol nebulization as compared to salbutamol alone for the management of children with mild to moderate asthma attacks.

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.

Anticholinergics aggravate the imbalance of the autonomic nervous system in stable chronic obstructive pulmonary disease

BackgroundInhaled anticholinergics, recommended as first-line maintenance treatment for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), has been demonstrated to be associated with an increased risk of cardiovascular diseases. Nevertheless, why COPD patients using inhaled anticholinergics have this higher risk remains unknown. One of mechanisms may be an autonomic imbalance because anticholinergics yield reduced vagal nervous activity. To test our hypothesis, we studied heart rate recovery (HRR) after exercise, recognized as a marker of cardiac autonomic function, in COPD patients using and not using inhaled anticholinergics.MethodsSixty patients with COPD were involved in this study (mean FEV1 = 1.57 ± 0.42 L), including 24 patients who had received tiotropium for more than 1 year and 36 patients not using tiotropium as a control group. A maximal cardiopulmonary exercise test was performed. HRR was defined as the difference between peak exercise and at 1-min recovery heart rate.ResultsHRR was significantly lower in patients using tiotropium than in the controls (16 ± 6 vs 22 ± 8 beats/min, respectively, p < 0.05). Multivariate regression analysis revealed that tiotropium use and peak VCO2 were independent predictors of HRR in these COPD patients.ConclusionsThese findings suggest that anticholinergics bronchodilators reduce HRR after exercise in COPD patients. This has the potential to aggravate autonomic nervous imbalance. Therefore, we recommend that COPD patients taking anticholinergic bronchodilators should be considered for monitoring of cardiac function and prescribers should be alert for cardiovascular events that may arise from autonomic nervous imbalance.

Clinical Pharmacology of Bronchodilator Medications.

Obstructive lung diseases, including asthma and COPD, are characterized by air-flow limitation. Bronchodilator therapy can often decrease symptoms of air-flow obstruction by relaxing airway smooth muscle (bronchodilation), decreasing dyspnea, and improving quality of life. In this review, we discuss the pharmacology of the β agonist and anticholinergic bronchodilators and their use, particularly in asthma and COPD. Expanding knowledge of receptor subtypes and G-protein signaling, agonist and antagonist specificity, and drug delivery have led to the introduction of safer medications with fewer off-target effects, medications with longer duration of action that may improve adherence, and more effective and efficient aerosol delivery devices.

The Impact of Bronchodilator Therapy on Systolic Heart Failure with Concomitant Mild to Moderate COPD.

In older adults, chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure with reduced ejection fraction (HFrEF), and the high prevalence of this combination suggests that customized treatment is highly necessary in patients with COPD and HFrEF. To investigate whether the treatment of COPD with tiotropium, an anticholinergic bronchodilator, reduces the severity of heart failure in patients with HFrEF complicated by mild to moderate COPD, forty consecutive participants were randomly divided into two groups and enrolled in a crossover design study. Group A inhaled 18 μg tiotropium daily for 28 days and underwent observation for another 28 days. Group B completed the 28-day observation period first and then received tiotropium inhalation therapy for 28 days. Pulmonary and cardiac functions were measured on days 1, 29, and 56. In both groups, 28 days of tiotropium inhalation therapy substantially improved the left ventricular ejection fraction (from 36.3 ± 2.4% to 41.8 ± 5.9%, p < 0.01, in group A; from 35.7 ± 3.8% to 41.6 ± 3.8%, p < 0.01, in group B) and plasma brain natriuretic peptide levels (from 374 ± 94 to 263 ± 92 pg/mL, p < 0.01, in group A; from 358 ± 110 to 246 ± 101 pg/mL, p < 0.01, in group B). Tiotropium inhalation therapy improves pulmonary function as well as cardiac function, and reduces the severity of heart failure in patients with compensated HFrEF with concomitant mild to moderate COPD.

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.

Ipratropium is ‘luminally recycled’ by an inter-play between apical uptake and efflux transporters in Calu-3 bronchial epithelial cell layers

The mechanism by which quaternized anticholinergic bronchodilators permeate the airway epithelium remains controversial to date. In order to elucidate the role of drug transporters, ipratropium bidirectional transport as well as accumulation and release studies were performed in layers of the broncho-epithelial cell line Calu-3 grown at an air-liquid interface, in presence or absence of a range of transporter inhibitors. Unexpectedly, a higher transepithelial permeability was observed in the secretory direction, with an apparent efflux ratio of > 4. Concentration-dependent and inhibitor studies demonstrated the drug intracellular uptake was carrier-mediated. Interestingly, monitoring drug release post cell loading revealed the presence of an efficient efflux system on the apical side of the cell layers. Acting in concert, apical transporters seem to promote the ‘luminal recycling’ of the drug and hence, limit its transcellular transport. The data are in agreement with an apical Organic Cation Transporter (OCT) being involved in this process but also suggest the participation of unknown uptake and efflux transporters sensitive to probenecid. This study suggests the absorption of ipratropium across the pulmonary barrier is primarily governed by paracellular passive diffusion but transporters might play a significant role in controlling the drug local concentrations in the lungs.

Tiotropium bromide exerts anti-inflammatory effects during resistive breathing, an experimental model of severe airway obstruction.

IntroductionResistive breathing (RB), a hallmark of obstructive airway diseases, is characterized by strenuous contractions of the inspiratory muscles that impose increased mechanical stress on the lung. RB is shown to induce pulmonary inflammation in previous healthy animals. Tiotropium bromide, an anticholinergic bronchodilator, is also shown to exert anti-inflammatory effects. The effect of tiotropium on RB-induced pulmonary inflammation is unknown.MethodsAdult rats were anesthetized, tracheostomized and breathed spontaneously through a two-way non-rebreathing valve. Resistances were connected to the inspiratory and/or expiratory port, to produce inspiratory resistive breathing (IRB) of 40% or 50% Pi/Pi,max (40% and 50% IRB), expiratory resistive breathing (ERB) of 60% Pe/Pe,max (60% ERB) or combined resistive breathing (CRB) of both 40% Pi/Pi,max and 60% Pe/Pe,max (40%/60% CRB). Tiotropium aerosol was inhaled prior to RB. After 6 h of RB, mechanical parameters of the respiratory system were measured and bronchoalveolar lavage (BAL) was performed. IL-1β and IL-6 protein levels were measured in lung tissue. Lung injury was estimated histologically.ResultsIn all, 40% and 50% IRB increased macrophage and neutrophil counts in BAL and raised IL-1β and IL-6 lung levels, tissue elasticity, BAL total protein levels and lung injury score. Tiotropium attenuated BAL neutrophil number, IL-1β, IL-6 levels and lung injury score increase at both 40% and 50% IRB. The increase in macrophage count and protein in BAL was only reversed at 40% IRB, while tissue elasticity was not affected. In all, 60% ERB raised BAL neutrophil count and total protein and reduced macrophage count. IL-1β and IL-6 levels and lung injury score were increased. Tiotropium attenuated these alterations, except for the decrease in macrophage count and the increase in total protein level. In all, 40%/60% CRB increased macrophage and neutrophil count in BAL, IL-1β and IL-6 levels, tissue elasticity, total protein in BAL and histological injury score. Tiotropium attenuated the aforementioned alterations.ConclusionTiotropium inhalation attenuates RB-induced pulmonary inflammation.

Anticholinergic drugs in asthma therapy

Current guidelines recommend a stepwise approach for pharmacological therapy aimed to achieve and maintain asthma control. Despite these recommendations, at least 50% of patients continue to be uncontrolled with risk of asthma exacerbations that can often be serious and are associated with deterioration of quality of life. In recent years, the interest in anticholinergic bronchodilators, which have been primarily used in the treatment of chronic obstructive pulmonary disease, has increased patients with uncontrolled asthma. This review analyzes the mechanisms for the proposed clinical use of anticholinergic bronchodilators as an adjunctive therapy in asthma. Based on existing and recent evidence, the use of anticholinergic bronchodilators, particularly long-acting muscarinic antagonists (LAMAs), plays an important role as add-on therapy in patients uncontrolled on existing therapies. In particular, the use of anticholinergics in asthma may have a role in patients intolerant to long-acting β2 agonist, in patients with certain pharmacogenetic profiles and in those patients with asthma symptoms mostly at night. Data from clinical trials and from real-life confirm the safety and efficacy of LAMAs, especially tiotropium, in patients who remain uncontrolled despite the use of inhaled corticosteroid therapy.

Deficiency of CPEB2-Confined Choline Acetyltransferase Expression in the Dorsal Motor Nucleus of Vagus Causes Hyperactivated Parasympathetic Signaling-Associated Bronchoconstriction.

This study first generated and characterized cpeb2 gene-deficient mice. CPEB2-knock-out (KO) mice are born alive but most die within 3 d after birth showing no overt defects in anatomy. We found that the KO neonates showed severe apnea and altered respiratory pattern. Such respiratory defects could be recapitulated in mice with pan-neuron-specific or cholinergic neuron-specific ablation of the cpeb2 gene. Further investigation revealed that cholinergic transmission in the KO dorsal motor nucleus of vagus was overactivated because KO mice lack CPEB2-suppressed translation of the rate-limiting enzyme in the production of acetylcholine (i.e., choline acetyltransferase). Consequently, increased parasympathetic signaling leads to hyperactivated bronchoconstriction and abnormal respiration in the KO neonates.

KOAH tedavisinde yeni bronkodilatörler ve kombinasyonları

Bronchodilator drugs are widely used therapeutic agents for treatment of asthma and chronic obstructive pulmonary disease (COPD). In order to mantain bronchodilation, both sympathetic system (particularly beta-2 receptors) activation and parasympathetic system inhibition (antimuscarinic effect) mechanisms are utilized. Over 20 years, there were no significant changes in bronchodilator therapy in obstructive pulmonary diseases. In recent years, however, after the development of new ultra long acting bronchodilator drugs, a single dose inhaler treatments per day in the treatment of stable COPD became a current issue. In this review, with the guidence of the current literature, the effects of new beta-2 agonists and anticholinergic bronchodilators will be discussed.

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.

1E25 気管支拡張剤が酸素輸送効率に与える影響に関する理論的検討

It is well known that beta-adrenergic agonist bronchodilators result in transient decreases in PaO2 levels in spite of bronchodilation. On the other hand, anticholinergic bronchodilators have been shown to have no effects on arterial blood gases. We hypothesized that the bronchodilation might alter oxygen transport from the trachea to alveoli, because the oxygen transport in the airway is governed by convection rather than diffusion. We constructed a 4D finite element lung model in which one subacinus (= the airspace supplied air by one last respiratory bronchiole) and its entire airway was included. Other lung regions were modeled as cubic sets whose side lengths were equal to their air-supplying bronchi. The lung model was moved during two seconds so that the air went into the lung from the tracheal upper open end at a constant flow rate at upright posture. By Solving incompressible Navier-Stokes equation and oxygen diffusion equation simultaneously, oxygen concentration distribution within the airway was computed. The small-airway dilation reduced oxygen concentration by 40% in average. Meanwhile, the large-airway dilation little changed it. This was because the air velocity at periphery was decrease by the small-airway dilatation, and oxygen transport there was performed only by diffusion. These results have indicated that the small-airway dilation itself decreases the arterial blood oxygen level.