scholarly journals LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis

2020 ◽  
Vol 14 ◽  
pp. 175346662093719
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chi-Hsien Huang ◽  
Yi-Ping Hsiang ◽  
Chau-Chyun Sheu ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Similar Efficacy ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
History Of ◽  
Long Acting

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

scholarly journals Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

2015 ◽  
Vol 24 (137) ◽  
pp. 451-461 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Clive Page ◽  
Josè Jardim ◽  
Alexander G. Chuchalin ◽  
...  
Keyword(s):  
Relative Risk ◽  
Airway Obstruction ◽  
Chronic Bronchitis ◽  
Meta Analysis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Regular Treatment ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
High Doses

In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a meta-analysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (≤600 mg per day) and high (>600 mg per day) doses of NAC.The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n=1933; placebo or controls n=2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66–0.84; p<0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68–0.82; p=0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89–0.97; p=0.40; high doses relative risk 1.11, 95% CI 0.89–1.39; p=0.58).The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ≥1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient.

Real-Life Clinical and Functional Effects of Fluticasone Furoate/Umeclidinium/Vilanterol-Combined Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease

Respiration ◽  
2020 ◽  
pp. 1-8
Author(s):  
Corrado Pelaia ◽  
Giada Procopio ◽  
Maria Rosaria Deodato ◽  
Olivia Florio ◽  
Angelantonio Maglio ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Triple Therapy ◽  
Real Life ◽  
Chronic Obstructive ◽  
Fluticasone Furoate ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
Inhaled Therapy ◽  
Long Acting

<b><i>Background:</i></b> Triple therapy consisting of a drug association including an inhaled corticosteroid, a long-acting muscarinic receptor antagonist and a long-acting β<sub>2</sub>-adrenergic agonist, delivered via a single device, can be a valuable treatment for chronic obstructive pulmonary disease (COPD) patients experiencing frequent disease exacerbations. <b><i>Objectives:</i></b> The aim of this real-life, single-center, observational study was to evaluate, in 44 COPD patients with recurrent exacerbations, the effects of the triple inhaled therapy combining fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI). <b><i>Methods:</i></b> Within such a therapeutic context, several clinical and lung functional parameters were considered at baseline and after 24 weeks of treatment with combined inhaled triple therapy. <b><i>Results:</i></b> With respect to baseline, after 24 weeks of treatment with FF/UMEC/VI, significant changes were recorded with regard to Modified British Medical Research Council (<i>p</i> &#x3c; 0.0001) and COPD Assessment Test (<i>p</i> &#x3c; 0.0001) scores, COPD exacerbations (<i>p</i> &#x3c; 0.001), forced expiratory volume in the first second (<i>p</i> &#x3c; 0.001), residual volume (<i>p</i> &#x3c; 0.01), forced mid-expiratory flow between 25 and 75% of FVC (<i>p</i> &#x3c; 0.0001), inspiratory capacity (<i>p</i> &#x3c; 0.01), forced vital capacity (<i>p</i> &#x3c; 0.05), and peak expiratory flow (<i>p</i> &#x3c; 0.0001). Moreover, in a subgroup of 28 patients, a significant increase of diffusion lung capacity (<i>p</i> &#x3c; 0.01) was also detected. <b><i>Conclusions:</i></b> In conclusion, our real-life results suggest that triple inhaled therapy with FF/UMEC/VI, when given to COPD patients with frequent exacerbations, is able to positively impact on dyspnea and global health status as well as to significantly decrease COPD exacerbations and improve airflow limitation and lung hyperinflation.

scholarly journals Major comorbidities lead to the risk of adverse cardiovascular events in chronic obstructive pulmonary disease patients using inhaled long-acting bronchodilators: a case-control study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yen-Fu Chen ◽  
Yi-Ching Cheng ◽  
Chien-Hong Chou ◽  
Chung-Yu Chen ◽  
Chong-Jen Yu
Keyword(s):  
Cardiovascular Events ◽  
Case Control Study ◽  
Case Control ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
History Of ◽  
Long Acting ◽  
Control Study ◽  
Related Mortality

Abstract Background While inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies. This study investigates the risk of adverse events associated with the use of inhaled bronchodilators in COPD patients with multimorbidity. Methods A case-control study was conducted between January 2015 and December 2017, and patients with spirometry-confirmed diagnosis of COPD (N = 1565) using inhaled long-acting bronchodilators were enrolled. Medical records were reviewed and clinical data, including age, gender, smoking status, major comorbidities, lung function stage, history of exacerbations, bronchodilator regimens, and treatment duration were analyzed. Major adverse cardiovascular events occurring during long-acting bronchodilator use were recorded. Results The most common comorbidities were cardiovascular disease (CVD) (53.6%) and chronic kidney disease (CKD) (25.8%). We observed that CVD (odds ratio [OR], 5.77), CKD (OR, 2.02) and history of frequent exacerbations (OR, 2.37) were independent risk factors for cardiovascular events, regardless of the type of bronchodilators use. Moreover, COPD patients with both CKD and CVD had higher risk (6.32-fold) of adverse cardiovascular effects than those with neither comorbidity. Eighty-seven of 1565 (5.56%) COPD patients died during this study period. Of them, 21.8% (19/87) were cardiovascular-related and 73.6% (64/87) patients were respiratory-related mortality. Among COPD patients using long-acting bronchodilators, CKD was the only risk factor to predict cardiovascular events and cardiovascular-related mortality (OR, 4.87; 95% confidence interval [CI], 1.75–13.55]. Conclusions COPD patients had higher risk of cardiovascular events were associated with their CVD and/or CKD comorbidities and history of frequent exacerbations, rather than associated with their use of inhaled bronchodilators.

scholarly journals Comparison of Effectiveness Using Different Dual Bronchodilator Agents in Chronic Obstructive Pulmonary Disease Treatment

2021 ◽  
Vol 10 (12) ◽  
pp. 2649
Author(s):  
Shih-Lung Cheng
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Combination Therapy ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Bronchodilator Agents ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Dose Combination ◽  
Long Acting

The effectiveness and safety of fixed dual long-acting bronchodilators for chronic obstructive pulmonary disease (COPD) patients have been well established; however, there is a paucity of clinical effectiveness comparison in patients with COPD treatment. The aim of the current study was to compare the effectiveness of three once-daily dual bronchodilator agents in patients with COPD. Patients with diagnosed COPD and treated with a long-acting beta-agonist (LABA) + long-acting muscarinic antagonist (LAMA) fixed-dose combination therapy (UME/VIL (umeclidinium and vilanterol inhalation powder), IND/GLY (indacaterol and glycopyrronium), and TIO/OLO (tiotropium and olodaterol)) were enrolled in this retrospective study over a period of 12 months. Effectiveness assessments were evaluated using a COPD assessment test (CAT) and lung function parameters. Besides, times for acute exacerbation were also assessed. The enrolled patients’ number was 177 in IND/GLY, 176 in UME/VIL and 183 in TIO/OLO. Lung function measurements with FEV1 had significantly improved for patients using TIO/OLO (98.7 mL) compared to those of IND/GLY (65.2 mL) and UME/VIL (64.4 mL) (p < 0.001). CAT scores were also significantly decreased in patients treated with TIO/OLO (CAT down 5.6) than those with IND/GLY (3.8) and UME/VIL (3.9) (p = 0.03). Acute exacerbation was also reduced in patients using TIO/OLO (4.9%) compared with those using IND/GLY (10.2%) and UME/VIL (11.9%) (p = 0.01). Significant improvement in pulmonary function, symptoms were demonstrated after 12 months of LABA/LAMA fixed-dose combination therapy with three different treatment options. TIO/OLO demonstrated higher therapeutic effects compared with UME/VIL or IND/GLY. Determining clinical relevance will require a well-designed randomized controlled trial.

scholarly journals Risk of Cardiovascular Events Associated with Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Jing ◽  
Yufeng Li ◽  
Jianying Xu
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
Combination Group ◽  
Chronic Obstructive ◽  
Control Groups ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Long Acting ◽  
And Control

Background. The cardiovascular (CV) safety of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) is controversial because different studies have suggested that ICSs either increase or reduce the risk of CV events in COPD patients. In this meta-analysis, we assess the CV safety of ICS therapy in COPD. Methods. A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials of ICS treatment for COPD that include at least 4 weeks of follow-up was performed. A random-effects model was used to evaluate the effects of ICS treatment on CV events. CV events were documented in each trial, and the relative risk (RR) and 95% confidence intervals (CIs) for ICSs were estimated. Results. Thirty-one trials were included in this meta-analysis. The risk of CV events was not different between ICS-treated and control groups (RR: 0.99; 95% CI: 0.93 to 1.06; P=0.801). In a subgroup analysis, there were no significant differences in CV events between an ICS combined with long-acting β2 agonist (LABA) (ICS + LABA) group and an LABA-only group (RR: 1.00; 95% CI: 0.90 to 1.10; P=0.930), as well as between a combination group (ICS + LABA) and a long-acting muscarinic antagonist (LAMA) combined with LABA (LAMA + LABA) group (RR: 0.78; 95% CI: 0.39 to 1.55; P=0.473). In addition, there was no difference in the risk of CV events between ICS treatment and control groups (RR: 0.99; 95% CI: 0.90 to 1.09; P=0.872). Conclusions. These results demonstrate that ICSs do not increase the risk of CV events in COPD patients.

scholarly journals A randomized controlled trial of long-acting muscarinic antagonist and long-acting β2 agonist fixed-dose combinations in patients with chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masato Muraki ◽  
Yuki Kunita ◽  
Ken Shirahase ◽  
Ryo Yamazaki ◽  
Soichiro Hanada ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Questionnaire Survey ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Muscarinic Antagonist ◽  
Copd Patients ◽  
Long Acting ◽  
Β2 Agonist

Abstract Background In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting β2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs—glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)—in patients with COPD. Methods We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC). Results No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported. Conclusions The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported. Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).

scholarly journals Inhaled corticosteroids in COPD: friend or foe?

2018 ◽  
Vol 52 (6) ◽  
pp. 1801219 ◽  
Author(s):  
Alvar Agusti ◽  
Leonardo M. Fabbri ◽  
Dave Singh ◽  
Jørgen Vestbo ◽  
Bartolome Celli ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Lower Body ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Clinical Benefits ◽  
History Of ◽  
Bronchodilator Treatment ◽  
Long Acting ◽  
Blood Eosinophils

The efficacy, safety and positioning of inhaled corticosteroids (ICS) in the treatment of patients with chronic obstructive pulmonary disease (COPD) is much debated, since it can result in clear clinical benefits in some patients (“friend”) but can be ineffective or even associated with undesired side effects,e.g.pneumonia, in others (“foe”). After critically reviewing the evidence for and against ICS treatment in patients with COPD, we propose that: 1) ICS should not be used as a single, stand-alone therapy in COPD; 2) patients most likely to benefit from the addition of ICS to long-acting bronchodilators include those with history of multiple or severe exacerbations despite appropriate maintenance bronchodilator use, particularly if blood eosinophils are >300 cells·µL−1, and those with a history of and/or concomitant asthma; and 3) the risk of pneumonia in COPD patients using ICS is higher in those with older age, lower body mass index (BMI), greater overall fragility, receiving higher ICS doses and those with blood eosinophils <100 cells·µL−1. All these factors must be carefully considered and balanced in any individual COPD patient before adding ICS to her/his maintenance bronchodilator treatment. Further research is needed to clarify some of these issues and firmly establish these recommendations.

scholarly journals Possibilities and limitations of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease

2018 ◽  
Vol 28 (5) ◽  
pp. 602-612
Author(s):  
I. V. Leshchenko
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
History Of ◽  
Long Acting ◽  
Exacerbation Of Copd

Combinations of inhaled corticosteroids (ICS) and long-acting bronchodilators are recommended for those patients with chronic obstructive pulmonary disease (COPD) who did not improve significantly with regular long-acting bronchodilators. ICS are known to increase the risk of pneumonia in elderly patients (over 55 years), current smokers, patients with acute exacerbation of COPD, patients with history of previous pneumonia, patients with body mass index < 25 kg/m2, and patients with dyspnea or severe airflow limitation. The risk-benefit ratio should be considered before initiating the treatment with ICS in COPD patients, particularly in patients with the risk factors of adverse events associated with ICS.

scholarly journals Inhaled glucocorticosteroids in treatment of chronic obstructive pulmonary disease/

2018 ◽  
Vol 96 (3) ◽  
pp. 257-261
Author(s):  
Anna G. Romanovskikh ◽  
Yu. G. Belotserkovskaya ◽  
I. P. Smirnov
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Efficacy And Safety ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Long Acting ◽  
Β2 Agonists

Chronic obstructive pulmonary disease (COPD) is an urgent problem of modern healthcare. One of the most frequent approaches to the therapy of the COPD remains the appointment of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) in fixed-dose combinations. At the same time, the role and place of fixed-dose combinations (ICS/LABA) in COPD therapy is currently being actively discussed. The presented article describes the efficacy and safety of fixed-dose combinations (ICS/LABA) in COPD patients, modern approaches to the appointment of ICS/LABA.

scholarly journals Stable Clinical Course of Chronic Obstructive Pulmonary Disease Patients in the Era of Double Bronchodilator Therapy: A Single Referral Center Experience

2020 ◽  
Vol 9 (8) ◽  
pp. 2547
Author(s):  
Sun Hye Shin ◽  
Noeul Kang ◽  
Juhee Cho ◽  
Yeonseok Choi ◽  
Hyun Kyu Cho ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Clinical Course ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Treatment Change ◽  
Obstructive Pulmonary Disease ◽  
Bronchodilator Therapy ◽  
Copd Patients ◽  
Clinical Benefits ◽  
Long Acting

Despite clinical benefits of long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) double bronchodilator therapy, there has been limited evidence for treatment change from LAMA/LABA to inhaled corticosteroid (ICS)-containing therapy. This study aimed to assess the rate of ICS-containing therapy from LAMA/LABA and investigate the factors associated with ICS addition. Between October 2015 and March 2019, consecutive patients prescribed with a LAMA/LABA fixed-dose combinations (FDCs) therapy without ICS were retrospectively identified from a single-referral hospital. The primary outcome was addition of ICS. During LAMA/LABA FDCs therapy (median, 12.4 months), 47 (17.7%) out of 266 patients had ICS addition. Most patients maintained bronchodilators without addition of ICS at 12 (86.5%) or 24 (76.8%) months. Patients with dyspnea (mMRC ≥ 2) at baseline, previous ICS use, and exacerbation in the previous year were at a higher risk of ICS addition. Especially, exacerbation in the previous year and dyspnea were associated with the development of frequent exacerbations during LAMA/LABA FDCs therapy, which might have led to ICS addition. Double bronchodilator therapy could be well-maintained in stable COPD patients. However, patients with exacerbation in the previous year, dyspnea, and previous ICS use should be closely approached and monitored with initiation of LAMA/LABA FDCs therapy without ICS.

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