To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.
Forced Expiratory Volume ; Humans ; Medicine, Chinese Traditional ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Tiotropium Bromide ; Vital Capacity

BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.
Actins ; Aged ; Airway Remodeling ; Animals ; Asthma* ; Eosinophils ; Female ; Humans ; Hydroxyproline ; Interleukin-13 ; Interleukin-5 ; Interleukins ; Mice* ; Ovalbumin ; Ovum ; Pneumonia ; Receptors, Muscarinic* ; Tiotropium Bromide*

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

Bronchodilators provide improvements in lung function and reductions in symptoms and exacerbations, and are the mainstay of pharmacological management of chronic obstructive pulmonary disease (COPD). The Global Initiative for Chronic Obstructive Lung Disease strategy recommends the use of a combination of long-acting β₂-agonist/long-acting muscarinic antagonists (LABA/LAMA) as the first-line treatment option in the majority of symptomatic patients with COPD. This review provides an indirect comparison of available LABA/LAMA fixed-dose combinations (FDCs) through discussion of important efficacy and safety data from the key literature, with the objective of providing physicians with a framework for informed decision-making. LABA/LAMA FDCs provided greater benefits compared with placebo and similar or greater benefits compared with tiotropium and salmeterol/fluticasone in improving lung function, dyspnea, health-related quality of life, reducing rescue medication use and preventing exacerbations, although with some variability in efficacy between individual FDCs; further, tolerability profiles were comparable among LABA/LAMA FDCs. However, there is a disparity in the amount of evidence generated for different LABA/LAMA FDCs. Thus, this review shows that all LABA/LAMA FDCs may not be the same and that care should be taken when extrapolating individual treatment outcomes to the entire drug class. It is important that physicians consider the efficacy gradient that exists among LABA/LAMA FDCs, and factors such as inhaler devices and potential biomarkers, when choosing the optimal bronchodilator treatment for long-term management of patients with COPD.
Asian Continental Ancestry Group ; Biomarkers ; Bronchodilator Agents ; Disease Management ; Dyspnea ; Humans ; Korea ; Lung ; Muscarinic Antagonists* ; Nebulizers and Vaporizers ; Pulmonary Disease, Chronic Obstructive* ; Quality of Life ; 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

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as “severe” asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.
Adrenal Cortex Hormones ; Asthma ; Biological Products ; Comorbidity ; Humans ; Immunoglobulin E ; Interleukin-5 ; Nebulizers and Vaporizers ; Receptors, Leukotriene ; Tiotropium Bromide

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

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08–3.00 h, 0.03–0.10 h and 0.03–0.10 h, respectively) and were eliminated with mean half-lives of 9.29–10.44 h, 6.09–12.39 h and 0.25–47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250–750 µg and 50–150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.
Charcoal ; Fluticasone* ; Gastrointestinal Absorption ; Humans ; Inhalation* ; Lung Diseases, Obstructive ; Male ; Pharmacokinetics ; Plasma ; Pulmonary Disease, Chronic Obstructive ; Respiratory Tract Absorption ; Salmeterol Xinafoate* ; 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

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.