Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease.

The most classic treatment recommended in the current chronic obstructive pulmonary disease (COPD) guidelines is glucocorticoid and ß2 receptor agonist combination, such as salmeterol xinafoate and fluticasone propionate (Sal/Flu), causing many adverse reactions due to hormones. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating chronic inflammation, contributing to its structure is similar to steroidal anti-inflammatory drugs. In this study, we successfully established COPD rat model by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction, as characterized by lung function decline. We discovered that salmeterol xinafoate/MgIG combination could alleviated lung inflammation infiltration, airway wall thickness (AWT) and the secretion of bronchial mucin MUC5AC of COPD rats more than salmeterol xinafoate, MgIG, or salmeterol xinafoate and fluticasone propionate treatment did, as well as reduced inflammatory cells (white blood cells, neutrophils and lymphocytes) accumulation in bronchoalveolar lavage fluid and decreased TNF-α, IL-6 and IL-1ß production in the serum of COPD rats. Finally, we found that Moreover, the mechanism involved might be related to the suppression of JAK/STAT signaling pathway. Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone propionate for the clinical treatment of patients with COPD.

Comparative Efficacy of Umeclidinium/Vilanterol Versus Other Bronchodilators for the Treatment of Chronic Obstructive Pulmonary Disease: A Network Meta-Analysis.

INTRODUCTION: Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD. METHODS: A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV1), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented. RESULTS: The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV1 versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 µg, glycopyrronium 50 µg, glycopyrronium 18 µg, tiotropium 18 µg and salmeterol 50 µg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation. CONCLUSION: UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV1 at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.

Bronchodilators are medicines that open the airways, allowing patients with chronic obstructive pulmonary disease (COPD) to breathe more easily. There are two different types of bronchodilators, namely long-acting muscarinic antagonists (LAMAs) and long-acting ß₂-agonists (LABAs), which can be used on their own or combined (LAMA/LABAs). Only a few clinical trials have compared different LAMA/LABA combinations with each other, so it is unclear which LAMA/LABA combination provides the greatest benefits for patients.In this study, we used network meta-analysis to compare a LAMA/LABA combination medicine called umeclidinium and vilanterol (UMEC/VI) with other LAMAs and LABAs used alone or in combination to treat patients with COPD. Network meta-analysis is a way of comparing two or more medicines by analysing data from many studies. We systematically searched for evidence from clinical trials in adult patients with COPD that were at least 8 weeks long and that compared LAMA/LABA combinations with a LAMA, a LABA, or another LAMA/LABA combination. We analysed data from 49 clinical trials that met these criteria.We found that patients treated with UMEC/VI had better lung function than patients treated with alternative LAMA/LABA combinations or bronchodilators used on their own. Patients treated with UMEC/VI had better quality of life than those receiving some other treatments, but not all. All the medicines we compared had similar side effects.Our results suggest that treating patients with COPD with UMEC/VI might improve their lung function and quality of life more than alternative bronchodilators.

[Systematic review and Meta-analysis on efficacy and safety of Liujunzi Decoction combined with Western medicine for stable chronic obstructive pulmonary disease].

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

Systematic review and Meta-analysis on efficacy and safety of Liujunzi Decoction combined with Western medicine for stable chronic obstructive pulmonary disease / 中国中药杂志

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

A retrospective study of Yiqibushenhuoxue decoction for the treatment of chronic obstructive pulmonary disease.

This retrospective study aimed to investigate the effect and safety of Yiqibushenhuoxue decoction (YQBSHXD) for the treatment of chronic obstructive pulmonary disease (COPD).This study involved 120 cases of patients with COPD. These cases were assigned to an intervention group and a control group equally, 60 subjects each group. Patients in both groups underwent Salmeterol. In addition, the cases in the intervention group also received YQBSHXD. All cases received a total of 12 weeks treatment. The primary outcome of lung function was measured by forced expiratory volume in 1 second (FEV1), and FEV1/forced vital capacity (FVC). The secondary outcomes included severity of dyspnea on exertion, evaluated by 6-minute walk test (6MWT) with measurement of 6-minute walk distance (6MWD); and quality of life, assessed by the St. George's Respiratory Questionnaire (SGRQ). In addition, adverse events (AEs) were also recorded in this study. All outcome measurements were assessed before and after 12-week treatment.After 12-week treatment, cases in the intervention group underwent YQBSHXD did not show better outcome in lung function improvement, measured by the FEV1 (P = .11), and FEV1/FVC (P = .15), compared with those in the control group. However, YQBSHXD may help to alleviate the severity of dyspnea on exertion, as measured by 6MWD (P = .03), and to improve the quality of life, as assessed by the SGRQ (P < .01). Additionally, no significant differences in AEs were detected between the 2 groups.The results of this study showed that YQBSHXD may help to manage COPD after 12-week treatment, although the lung function has not been improved.

Characteristics and health care resource use of subjects with COPD in the year before initiating LAMA monotherapy or LAMA+LABA combination therapy: A U.S. database study.

PURPOSE: To characterize subjects with chronic obstructive pulmonary disease (COPD) newly initiated on long-acting muscarinic antagonists (LAMA) or dual LAMA/long-acting ß2-adrenergic agonist (LABA) therapy. DESIGN: This pilot/preliminary analysis was a retrospective crosssectional study of subjects with COPD from the Optum Impact National Managed Care Benchmark Database. METHODOLOGY: Subjects with at least one LAMA prescription in the index period (July 2008-June 2009) were included and stratified by treatment. Data were collected in the year before the index date and included comorbidities, medication use, COPD-related costs, health care resource use, and exacerbations. RESULTS: Of 5,311 eligible subjects, 2,057 initiated LAMA therapy (LAMA cohort) and 191 initiated LAMA+LABA therapy (LAMA+LABA cohort). The Charlson comorbidity index was slightly lower in the LAMA+LABA cohort than the LAMA cohort (mean±SD: 0.63±1.13 vs. 0.66±1.28), but the number of prescriptions was higher (mean±SD: 42.9±23.2 vs. 30.5±27.2). The LAMA+LABA cohort had higher short-acting inhaled ß2 agonist (56.0% vs. 35.7%), oral corticosteroid (37.7% vs. 32.6%), and home oxygen therapy use (14.1% vs. 3.2%) than the LAMA cohort. Total medical costs were greater in the LAMA+LABA cohort than the LAMA cohort (mean±SD: $3,320.40±4085.9 vs. $1,226.20±3602.9), although emergency department ($11.00±66.8 vs. $30.70±259.2) and outpatient visit ($39.60±163.1 vs. $41.70±424.3) costs were lower. Resource use and exacerbation incidence were similar between cohorts. CONCLUSION: In this first look, subjects with COPD initiating LAMA or LAMA+LABA therapy exhibited different clinical and resource use characteristics in the year before treatment. Subjects receiving LAMA+LABA were older, with higher COPD co-medication use, more prescriptions, and associated higher pharmacy costs compared with subjects initiating LAMA. These differences may reflect a higher severity of COPD in those starting LABA+LAMA treatment.

When Two Drugs Are Better than Three: Re-Modulating the Therapeutic Plan of a Chronic Obstructive Pulmonary Disease Patient.

We present the case of a 77-year-old man diagnosed with chronic obstructive pulmonary disease (COPD) stage D with emphysema phenotype and treated with triple therapy (salmeterol, fluticasone propionate, and tiotropium) for 1 year without relevant improvements in exertional dyspnea and disease impact. After switching to combination therapy with a long-acting ß2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (indacaterol/glycopyrronium), we observed, in a 3-month period, a substantial reduction of the modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT) scores. Moreover, the patient reported a reduction of dynamic hyperinflation and an improvement of ventilatory response to exercise.

Chinese Herbal Medicine and Salmeterol and Fluticasone Propionate for Chronic Obstructive Pulmonary Disease: Systematic Review and Network Meta-Analysis.

Among Chinese populations worldwide, Chinese herbal medicines (CHMs) are often used as an adjunct to pharmacotherapy in managing chronic obstructive pulmonary disease (COPD). However, the relative performance among different CHM is unknown.The aim of this study was to evaluate comparative effectiveness of different CHM when used with salmeterol and fluticasone propionate (SFP), compared with SFP alone.This study is a systematic review of randomized controlled trials (RCTs) with network meta-analyses (NMAs).Eight electronic databases were searched. Data from RCTs were extracted for random effect pairwise meta-analyses. Pooled relative risk (RR) with 95% confidence interval (CI) was used to quantify the impact of CHM and SFP on forced expiratory volume in 1 second (FEV1), St George's Respiratory Questionnaire (SGRQ) scoring, and 6-Minute Walk Test (6MWT). NMA was used to explore the most effective CHM when used with SFP.Eleven RCTs (n = 925) assessing 11 different CHM were included. Result from pairwise meta-analyses indicated favorable, clinically relevant benefit of CHM and SFP on FEV1 [7 studies, pooled weighted mean difference (WMD) = 0.20 L, 95% CI: 0.06-0.34 L], SGRQ scoring (5 studies, pooled WMD = -4.99, 95% CI: -7.73 to -2.24), and 6MWT (3 studies, pooled WMD = 32.84 m, 95% CI: 18.26-47.42). Results from NMA showed no differences on the comparative effectiveness among CHM formulations for improving FEV1. For SGRQ, NMA suggested that Runfeijianpibushen decoction and Renshenbufei pills performed best. Use of CHM on top of SFP can provide clinically relevant benefit for COPD patients on FEV1 and SGRQ. Additional use of Runfeijianpibushen decoction and Renshenbufei pills showed better effect on improving SGRQ.Use of CHM and SFP may provide clinically relevant benefit for COPD patients on FEV1, SGRQ, and 6MWT. Use of different CHM formulae included in this NMA showed similar effect for increasing FEV1, while the additional use of Runfeijianpibushen formula and Renshenbufei Pills showed better effect on improving SGRQ. Well conducted, adequately powered trials are needed to confirm their effectiveness in the future.

Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting bronchodilators, comprising long-acting beta2-agonists (LABA) and long-acting anti-muscarinic agents (LAMA, principally tiotropium), are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and LABAs for the treatment of COPD are unclear. OBJECTIVES: To compare the relative effects on markers of quality of life, exacerbations, symptoms, lung function and serious adverse events in people with COPD randomised to LABA plus tiotropium versus tiotropium alone; or LABA plus tiotropium versus LABA alone. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials and ClinicalTrials.gov up to July 2015. SELECTION CRITERIA: We included parallel-group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to LABA against tiotropium or LABA alone for people with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. MAIN RESULTS: This review included 10 trials on 10,894 participants, mostly recruiting participants with moderate or severe COPD. All of the trials compared tiotropium in addition to LABA to tiotropium alone, and four trials additionally compared LAMA plus LABA with LABA alone. Four studies used the LABA olodaterol, three used indacaterol, two used formoterol, and one used salmeterol.Compared to tiotropium alone, treatment with tiotropium plus LABA resulted in a slightly larger improvement in mean health-related quality of life (St George's Respiratory Questionnaire (SGRQ) (mean difference (MD) -1.34, 95% confidence interval (CI) -1.87 to -0.80; 6709 participants; 5 studies). The MD was smaller than the four units that is considered clinically important, but a responder analysis indicated that 7% more participants receiving tiotropium plus LABA had a noticeable benefit (greater than four units) from treatment in comparison to tiotropium alone. In the control arm in one study, which was tiotropium alone, the SGRQ improved by falling 4.5 units from baseline and with tiotropium plus LABA the improvement was a fall of a further 1.3 units (on average). Most of the data came from studies using olodaterol. High withdrawal rates in the trials increased the uncertainty in this result, and the GRADE assessment for this outcome was therefore moderate. There were no significant differences in the other primary outcomes (hospital admission or mortality).The secondary outcome of pre-bronchodilator forced expiratory volume in one second (FEV1) showed a small mean increase with the addition of LABA over the control arm (MD 0.06, 95% CI 0.05 to 0.07; 9573 participants; 10 studies), which showed a change from baseline ranging from 0.03 L to 0.13 L with tiotropium alone. None of the other secondary outcomes (exacerbations, symptom scores, serious adverse events, and withdrawals) showed any statistically significant differences between the groups. There was moderate heterogeneity for both exacerbations and withdrawals.This review included data on four LABAs: two administered twice daily (salmeterol, formoterol) and two once daily (indacaterol, olodaterol). The results were largely from studies of olodaterol and there was insufficient information to assess whether the other LABAs were equivalent to olodaterol or each other.Comparing LABA plus tiotropium treatment with LABA alone, there was a small but significant improvement in SGRQ (MD -1.25, 95% CI -2.14 to -0.37; 3378 participants; 4 studies). The data came mostly from studies using olodaterol and, although the difference was smaller than four units, this still represented an increase of 10 people with a clinically important improvement for 100 treated. There was also an improvement in FEV1 (MD 0.07, 95% CI 0.06 to 0.09; 3513 participants; 4 studies), and in addition an improvement in exacerbation rates (odds ratio (OR) 0.80, 95% CI 0.69 to 0.93; 3514 participants; 3 studies). AUTHORS' CONCLUSIONS: The results from this review indicated a small mean improvement in health-related quality of life and FEV1 for participants on a combination of tiotropium and LABA compared to either agent alone, and this translated into a small increase in the number of responders on combination treatment. In addition, adding tiotropium to LABA reduced exacerbations, although adding LABA to tiotropium did not. Hospital admission and mortality were not altered by adding LABA to tiotropium, although there may not be enough data. While it is possible that this is affected by higher attrition in the tiotropium group, one would expect that participants withdrawn from the study would have had less favourable outcomes; this means that the expected direction of attrition bias would be to reduce the estimated benefit of the combination treatment. The results were largely from studies of olodaterol and there was insufficient information to assess whether the other LABAs were equivalent to olodaterol or each other.