OBJECTIVETo evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma.

METHODSReports 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.

RESULTSFive 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).

CONCLUSIONSTiotropium 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.

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

Humans ; Pneumoconiosis ; complications ; drug therapy ; Pulmonary Disease, Chronic Obstructive ; complications ; drug therapy ; Tiotropium Bromide ; therapeutic use

OBJECTIVE: International institutes such as Global institute for Asthma(GINA), KAAACI(Republic of Korea), NHLBI(USA), BTS(UK) and JSA(Japan) have published guidelines for asthma treatment. The aim of this study was to compare the representatives' international guidelines of pharmacotherapy for pediatric asthma. METHODS: The recommendations related to pharmacotherapy for pediatric asthma were extracted from the latest representatives' international guidelines, and comprehensive comparisons were conducted. RESULTS: Major comparison outcomes between international guidelines were evaluated as follows: classification system on severity and pediatric age group, recommendation for inhaled corticosteroid dose, recommendation for pediatric age group of theophylline in mild asthma, and recommendation for pediatric age group of tiotropium in severe asthma. Clinical trials emphasized the adverse effects of theophylline, whereas tiotropium demonstrated beneficial actions for pediatric asthma. Therefore, theophylline was recommended for older patients with persistent asthma, and tiotropium was considered to be suitable for younger patients with severe asthma according to GINA guidelines. CONCLUSION: These findings address the requirement to harmonize international guidelines of pharmacotherapy in pediatric asthma. In addition, the findings suggest that KAAACI needs to update its pharmacotherapy guidelines of theophylline, tiotropium and other medicines recently approved.
Academies and Institutes ; Asthma* ; Classification ; Drug Therapy* ; Humans ; Pediatrics ; Theophylline ; Tiotropium Bromide

Despite a range of efficacious therapies for asthma, including inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA), a significant proportion of patients have poor asthma control and retain a risk of future worsening of their symptoms. Long-acting muscarinic antagonist (LAMA) bronchodilators offer a well-tolerated, efficacious, and cost-effective add-on to a patient's treatment. Of the LAMAs currently under investigation or available for the treatment of asthma, evidence from a comprehensive clinical trial program in adults and children shows that once-daily treatment with tiotropium provides benefits for patients with uncontrolled asthma despite the use of ICS and LABAs. Tiotropium is included in the Global Initiative for Asthma (GINA) strategy document as an add-on therapy option for patients at Step 4 or 5 with a history of asthma exacerbations. Tiotropium Respimat® has demonstrated safety and efficacy in patients with a range of disease severities, ages, and phenotypes. This review describes the evidence for the use of LAMA as add-on therapy for patients with asthma who remain uncontrolled despite the use of ICS and LABA treatments.
Adrenal Cortex Hormones ; Adult ; Asthma* ; Bronchodilator Agents ; Child ; Humans ; Muscarinic Antagonists* ; Phenotype ; Tiotropium Bromide

BACKGROUND: In Korea, patients with destroyed lung due to tuberculosis (TB) account for a significant portion of those affected by chronic pulmonary function impairment. The objective of our research was to evaluate the efficacy of inhaled tiotropium bromide in TB destroyed lung. METHODS: We compared the effectiveness of inhaled tiotropium bromide for 2 months between pre- and post-treatment pulmonary function tests performed on 29 patients with destroyed lung due to TB. RESULTS: The mean age of the total number of patients was 63+/-9 years, where 15 patients were male. The pre-treatment mean forced expiratory volume in 1 second (FEV1) was 1.02+/-0.31 L (44.1+/-16.0% predicted). The pre-treatment mean forced vital capacity (FVC) was 1.70+/-0.54 L (52.2+/-15.8% predicted). Overall, the change in FEV1% predicted over baseline with tiotropium was 19.5+/-19.1% (p<0.001). Twenty patients (72%) got better than a 10% increase in FEV1 over baseline with tiotropium, but one patient showed more than a 10% decrease in FEV1. Overall, the change in FVC% predicted over baseline with tiotropium was 18.5+/-19.9% (p<0.001). Seventeen patients (59%) experienced greater than a 10% increase in FVC over baseline with tiotropium; 12 (41%) patients had stable lung function. CONCLUSION: The inhaled tiotropium bromide therapy may lead to improve lung functions in patients with TB destroyed lung. However, the long-term effectiveness of this treatment still needs to be further assessed.
Forced Expiratory Volume ; Humans ; Korea ; Lung* ; Male ; Respiratory Function Tests ; Tuberculosis ; Vital Capacity ; Tiotropium Bromide

Asthma is a chronic respiratory disease characterized by reversible airway obstruction that is secondary to an allergic inflammation and excessive smooth muscle contraction. Cholinergic signals were known to contribute significantly to the pathophysiology of asthma. However, the use of anti-cholinergic agents in asthma has been justified only in acute asthma exacerbations, until tiotropium bromide, a long-acting anti-cholinergic agent was introduced. Recent reports showing a promising role of tiotropium in the treatment of asthma have aroused interest of the use of anti-cholinergic agent for the management of asthma. This report describes pharmacological characteristics, potential effects on inflammatory cells, and the current status of tiotropium in the treatment of asthma.
Airway Obstruction ; Asthma ; Bronchodilator Agents ; Cholinergic Antagonists ; Inflammation ; Muscle, Smooth ; Tiotropium Bromide

The prevention of and the controlling of symptoms, reductions in the frequency of exacerbations, and disease severity are central to the pharmacologic therapy of chronic obstructive pulmonary disease (COPD). COPD patients are inclined to be older, have more comorbidities, and use polypharmacy as a result. Long-acting inhaled muscarinic antagonists (LAMAs) is a preferred treatment modality. However, the cardiovascular (CV) safety of anti-cholinergics, including LAMA, has been an issue. In contrast, the results of the UPLIFT trial and a pooled analysis of data from 30 trials of tiotropium illustrates the association of tiotropium with reductions in the risk of all cause mortality, CV mortality and CV events. And, the UPLIFT trial provides clues regarding the additive advantages of tiotropium in COPD patients who already are using long-acting inhaled beta2 agonists and inhaled corticosteroids. Following the contribution of tiotropium as a first LAMA, new LAMAs such as aclidinium and glycopyrrolate (NVA-237) seem to be emerging.
Adrenal Cortex Hormones ; Cholinergic Antagonists ; Comorbidity ; Glycopyrrolate ; Humans ; Muscarinic Antagonists ; Polypharmacy ; Pulmonary Disease, Chronic Obstructive ; Scopolamine Derivatives ; Tiotropium Bromide

OBJECTIVE: The study aimed to evaluate efficacy of tiotropium as add-on therapy on top of standard regimens for uncontrolled asthma, specifically in terms of FEV1, morning and evening PEF, reduction in exacerbations, rescue medication use, and quality of life improvement.
METHODS: A search was done for eligible trials after which validity screen and data extraction was performed. Results were presented as mean differences, standard errors, and 95% confidence intervals, and graphically as forest plots. Estimates were pooled using the random effects model with I2 and Chi2 tests used to assess heterogeneity. Adverse events were reported as dichotomous variables.
RESULTS: Four studies were included totaling 1617 participants. The tiotropium group had statistically significant improvement in FEV1 (95% Cl, 0.14 [0.09, 0.19], p<0.00001), morning (95% Cl, 20.03 [11.71, 28.35], p<0.00001) with trend towards benefit in reduction of rescue medications (95% Cl, 0.12 [-0.17,0.4],p=0.42) and quality of life improvements (95% Cl, 0.1 [-0.05,0.25], p=0.20). Homogeneity (I2= 0%, Chi2= 0.47-3.22) was found across studies.
CONCLUSION: Tiotropium is associated with significant improvement in pulmonary function among patients with uncontrolled asthma, with possible benefit in reduction of rescue medications and quality of life improvement.

Human ; Male ; Female ; Adult ; Asthma ; Bronchodilator Agents ; Confidence Intervals ; Quality Of Life ; Respiratory Physiological Phenomena ; Scopolamine Derivatives ; Tiotropium Bromide ; Meta-analysis

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0–3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0–3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P< 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.
Adrenal Cortex Hormones ; Adult ; Asian Continental Ancestry Group ; Asthma ; China ; Forced Expiratory Volume ; Humans ; Salmeterol Xinafoate ; Tiotropium Bromide

Bronchodilator therapy is central to the management of chronic obstructive pulmonary disease and are recommended as the preferred treatment by the Global Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA) and long acting β₂ agonists (LABA) are both more effective than regular short-acting drugs but many patients remain symptomatic despite monotherapy with these drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit while minimizing dose-dependent side effects of long-acting bronchodilator therapy. The TOviTO programme has investigated the benefits of treatment with a combination of tiotropium and olodaterol administered via a single inhaler. Tiotropium+olodaterol 5/5 µg significantly improved forced expiratory volume in 1 second (FEV₁) area under the curve from 0 to 3 hours, trough FEV₁ health status and breathlessness versus the mono-components and placebo. Tiotropium+olodaterol 5/5 µg also increased endurance time and reduced dynamic hyperinflation during constant work rate cycle ergometry. On the basis of these and other studies the 2017 GOLD report recommends escalating to dual bronchodilator therapy in patients in groups B and C if they remain symptomatic or continue to have exacerbations and as initial therapy for patients in group D.
Dyspnea ; Ergometry ; Forced Expiratory Volume ; Humans ; Lung Diseases ; Lung Diseases, Obstructive ; Nebulizers and Vaporizers ; Pulmonary Disease, Chronic Obstructive ; Tiotropium Bromide