Combination Of Bronchodilators Research Articles

New opportunities for prevention of exacerbations of chronic obstructive pulmonary disease. Russian Respiratory Society Expert Opinion

Combination therapy with long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) can reduce symptoms of chronic obstructive pulmonary disease (COPD) and the risk of future exacerbations. To date, the only fixed combination of long-acting bronchodilators, indacaterol/glycopyrronium, has demonstrated a significant reduction in dyspnea and in the risk of moderate and severe exacerbations of COPD in clinical trials when compared with the combination of salmeterol/fluticasone. Addition of inhaled steroids (ICS) to long-acting bronchodilators is recommended for patients with recurrent COPD exacerbations, especially in those with asthma-COPD overlap syndrome or history of elevated blood or sputum eosinophil levels. It is recommended to consider phenotype-specific therapy including roflumilast, N-acetylcysteine, and macrolides, in patients who continue to exacerbate despite being treated with LABA/LAMA or LABA/LAMA/ICS combinations. Withdrawal of inhaled corticosteroids is possible in patients with the low risk of exacerbation and in those with severe adverse events during ICS treatment. ICS should be withdrawn in a single step in patients with no repeated exacerbations during 12 months and with moderate bronchial obstruction (FEV1 ≥ 50% predicted). Stepwise withdrawal of ICS during 3 month with continuous dual bronchodilator therapy is recommended in COPD patients with severe bronchial obstruction (FEV1 ˂ 50% predicted) without frequent exacerbations in the previous year.

Approaches to drug therapy for COPD in Russia: a proposed therapeutic algorithm.

Until recently, there have been few clinical algorithms for the management of patients with COPD. Current evidence-based clinical management guidelines can appear to be complex, and they lack clear step-by-step instructions. For these reasons, we chose to create a simple and practical clinical algorithm for the management of patients with COPD, which would be applicable to real-world clinical practice, and which was based on clinical symptoms and spirometric parameters that would take into account the pathophysiological heterogeneity of COPD. This optimized algorithm has two main fields, one for nonspecialist treatment by primary care and general physicians and the other for treatment by specialized pulmonologists. Patients with COPD are treated with long-acting bronchodilators and short-acting drugs on a demand basis. If the forced expiratory volume in one second (FEV1) is ≥50% of predicted and symptoms are mild, treatment with a single long-acting muscarinic antagonist or long-acting beta-agonist is proposed. When FEV1 is <50% of predicted and/or the COPD assessment test score is ≥10, the use of combined bronchodilators is advised. If there is no response to treatment after three months, referral to a pulmonary specialist is recommended for pathophysiological endotyping: 1) eosinophilic endotype with peripheral blood or sputum eosinophilia >3%; 2) neutrophilic endotype with peripheral blood neutrophilia >60% or green sputum; or 3) pauci-granulocytic endotype. It is hoped that this simple, optimized, step-by-step algorithm will help to individualize the treatment of COPD in real-world clinical practice. This algorithm has yet to be evaluated prospectively or by comparison with other COPD management algorithms, including its effects on patient treatment outcomes. However, it is hoped that this algorithm may be useful in daily clinical practice for physicians treating patients with COPD in Russia.

LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis.

BackgroundRandomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments. The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.MethodsThis systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only). Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.ResultsEighteen studies (23 trials) were eligible (N=20,185). LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively). LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively). LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]). Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]). LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).ConclusionThe greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD. These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.

Umeclidinium/vilanterol as step-up therapy from tiotropium in patients with moderate COPD: a randomized, parallel-group, 12-week study.

IntroductionPatients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).MethodsIn this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%–70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks. Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0–3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs).ResultsCompared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45–131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27–72]; P<0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2–0.0]; P≤0.05). More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21–2.64]; P≤0.01). Improvements in SGRQ and CAT scores were similar between treatments. The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).ConclusionUMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.

MAXIMAL BRONCHODILATION WITH STARTING THERAPY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE: AN INFLUENCE ON THE COURSE OF THE DISEASE

Progressive airflow limitation is a principal sign of chronic obstructive pulmonary disease (COPD) which leads to pulmonary hyperinflation, progressive exertional breathlessness, reducing physical activity in daily life, deconditioning and significant decrease in quality of life. This phenomenon is noted in early stage of COPD. The earliest disruption of this 'vicious circle' is thought to result in better clinical outcome. Current combined bronchodilator therapy, such as a fixed combination of tiotropium/olodaterol, can significantly improve clinical status, dyspnea, physical limitation, deconditioning and quality of life of the patients due to improvement in bronchial obstruction and pulmonary hyperinflation. Therefore, the most promising approach today and in the nearest future is to start the optimal combined dual bronchodilator therapy at earlier stage of the disease.

Dual bronchodilation in COPD: lung function and patient-reported outcomes - a review.

Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol–glycopyrronium once daily, eight for umeclidinium–vilanterol once daily, three for tiotropium–olodaterol once daily, and two for aclidinium–formoterol twice daily). Results from these studies demonstrated that the LAMA–LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA–LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the FDCs were similar to placebo. Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA–LAMA combinations.

Efficiency and safety of roflumilast combined with long-acting bronchodilators on moderate-to-severe stable chronic obstructive pulmonary disease patients: a meta-analysis.

Roflumilast, a phosphodiesterase-4 inhibitor recommended by clinical guideline, is always being used in combination with at least one long-acting bronchodilator in patients with stable chronic obstructive pulmonary disease (COPD). However, there are few evidences about whether the combination of roflumilast and long-acting bronchodilators is safer and more effective in patients with moderate-to-very severe stable COPD. In our study, we investigate the effect and safety of roflumilast combined with long-acting bronchodilators on moderate-to-severe stable COPD patients. Several databases were adopted in February 5th 2016, so as to identify relevant randomized controlled trial (RCT). Studies indicated that the patients in the experimental group had to receive roflumilast and concomitant treatment with long-acting bronchodilators, and the patients in the control group had to receive placebo and concomitant treatment with long-acting bronchodilators. The primary outcome was COPD exacerbations and the secondary outcome was adverse events. The relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Total 5,746 patients were involved in all six trials. Roflumilast combined with long-acting bronchodilators could lead to significant reduction in exacerbations of COPD (RR, 0.77; 95% CI, 0.69 to 0.86; P<0.00001; I2=0%), and cause some adverse events such as: back pains, headache, diarrhea, nausea, weight loss, insomnia and decreased appetite. According to the subgroup analysis, the test for finding subgroup difference between roflumilast combined with long-acting bronchodilators and roflumilast combined with ICS and long-acting bronchodilators showed no significance in reducing exacerbations. Roflumilast combined with long-acting bronchodilators is a better option for moderate-to-severe COPD patients than exclusive use of long-acting bronchodilators in reducing exacerbations. However, it can cause some side effects. Further study needs consider well enough of the benefits and adverse events caused by roflumilast combined with long-acting bronchodilators.

Cost-effectiveness and budget impact of the fixed-dose dual bronchodilator combination tiotropium-olodaterol for patients with COPD in the Netherlands.

PurposeThe fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components. Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown. The aim of this study was to assess the cost–utility and budget impact of tiotropium–olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.Patients and methodsA cost–utility study was performed, using an individual-level Markov model. To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium–olodaterol TOnado trial. In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium–olodaterol FDC was compared with tiotropium. Cost–utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis. The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%). Both univariate and probabilistic sensitivity analyses were performed. Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.ResultsAs a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium–olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY. Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY. Results were robust in univariate and probabilistic sensitivity analyses. Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence. Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.ConclusionTiotropium–olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds.

Combination of asthma and chronic obstructive pulmonary disease: features of etiology, pathogenesis, diagnosis, pharmacotherapy

Bronchial asthma and chronic obstructive pulmonary disease are the most common obstructive diseases of the respiratory system. 230 million people suffer from chronic obstructive pulmonary disease, from bronchial asthma - 300 million people worldwide. Annually 200-300 people in Europe and 2.74 million of world population die from chronic obstructive pulmonary disease, from asthma - 250 thousand people a year. The social and economic significance of these diseases determine the need for in-depth study of their combination in the same patient. Each disease has its own phenotypes, but in 10-20% of patients, there are symptoms of both chronic obstructive pulmonary disease and asthma. In spite of clear diagnostic criteria, in some cases it is difficult to distinguish these diseases. Morphological basis of these diseases is a chronic inflammation in the bronchial tree that causes damage to the epithelial continuity that initiates bronchoconstrictive reaction and leads to irreversible airway obstruction attributable for both severe bronchial obstruction and chronic obstructive pulmonary disease. However, the treatment strategy of bronchial asthma and chronic obstructive pulmonary disease has significant differences, it is important to have a clear diagnostic criteria to distinguish different phenotypes, including those of combined phenotype of asthma and chronic obstructive pulmonary disease. Rational starting therapy of asthma and chronic obstructive pulmonary disease overlap syndrome includes drugs acting on the pathogenic mechanisms of both diseases, and is a combination of inhaled corticosteroids with combined bronchodilator therapy - long-acting β2-agonists and long-acting anticholinergics.

Efficacy of Indacaterol/Glycopyrronium in Patients with COPD Who Have Increased Dyspnea with Daily Activities.

Introduction: The Global initiative for chronic Obstructive Lung Disease (GOLD) recommends treating patients with chronic obstructive pulmonary disease (COPD) based on a combined assessment of symptom severity and airflow limitation and/or exacerbation risk. According to GOLD, patients with mild-to-moderate airflow limitation and distressing symptoms such as dyspnea should be treated with a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). If symptoms persist on monotherapy, GOLD recommends a combination of bronchodilators (LABA/LAMA). Methods: We performed a post-hoc analysis of data from two 26-week, prospective clinical trials to investigate the effect of treating patients with moderate-to-severe dyspnea with the once-daily LABA/LAMA combination indacaterol/glycopyrronium (IND/GLY) 110/50 µg compared with placebo, once-daily tiotropium 18 µg, and twice-daily salmeterol/fluticasone propionate (SFC) 50/500 µg. In this analysis, a Baseline Dyspnea Index (BDI) score ≤7 was used to identify dyspneic patients. Results: In dyspneic patients, IND/GLY significantly improved Transition Dyspnea Index (TDI) total scores compared with tiotropium (0.59 units; p<0.05) and SFC (0.97 units; p<0.05), and significantly increased the likelihood of a patient achieving a 1-unit improvement in TDI compared with tiotropium (odds ratio [OR] 1.87; p<0.05). IND/GLY also significantly improved trough forced expiratory volume in 1 second (FEV1) compared with tiotropium and SFC (p<0.001 and p<0.0001, respectively), and significantly reduced rescue medication use compared with tiotropium (p<0.001). Conclusions: Our analysis indicates that IND/GLY provides additional improvements in dyspnea and lung function compared with tiotropium and SFC in dyspneic patients.

The clinical relevance of the emphysema-hyperinflated phenotype in COPD

The classification of chronic pulmonary obstructive disease (COPD) into clinical and pathophysiological subsets is not new, but increasing data is available on the relation of these different phenotypes to clinically meaningful outcomes. This review focuses on the “emphysema-hyperinflation” (EH) phenotype, which is characterised by a prominent loss of lung elastic recoil and hyperinflation burden that translates into marked exercise intolerance and a heightened sense of dyspnoea. Although no single genetic profile has been associated with the EH phenotype, recent data have shown that certain single nucleotide polymorphisms, such as DNAH5, appear to have an effect on the preferential development of hyperinflation in smokers. Static and dynamic hyperinflation are hallmarks of the EH phenotype, and abnormal increases in resting lung function indices such as total lung capacity (TLC), functional residual capacity (FRC) and inspiratory to TLC ratio (IC/TLC) seem more associated with the clinical EH phenotype than others markers of gas trapping. An increased level of dyspnoea on exertion and exercise intolerance are also characteristic of the EH presentation and are likely related in part to critical mechanical constraints imposed on tidal volume expansion in situations where ventilatory demands are increased, but also possibly on cardiac and hemodynamic anomalies related to emphysema and hyperinflation. Importantly, the clinical relevance of the EH phenotype is underlined by the finding that indices of hyperinflation such as IC/TLC and residual volume (RV) can be used as independent predictors of mortality in patients with COPD. Treatment of patients with the EH phenotype should primarily focus on smoking cessation and maximal bronchodilator therapy. New long-acting combined bronchodilators options provide clinicians with safe and effective ways to address the hyperinflation issue in this population. Pulmonary rehabilitation also has a positive impact on exercise tolerance, quality of life and hyperinflation, and should be routinely considered in patients with EH presentation that remain symptomatic despite optimal treatment, whereas as lung volume reduction techniques should be reserved for highly selected patients.

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

Comparative efficacy of combination bronchodilator therapies in COPD: a network meta-analysis.

BackgroundSeveral new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable. This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers.MethodsA systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers. Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George’s Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework.ResultsA systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks. The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: −14.2, 42.3]), SGRQ total score (0.18 [−1.28, 1.63]), TDI focal score (−0.30 [−0.73, 0.13]), and rescue medication use (0.02 [−0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [−25.3, 159.4]), SGRQ total score (−0.11 [−1.84, 1.61]), and TDI focal score (0.58 [−0.33, 1.50]); and compared with formoterol plus TIO 18 μg on SGRQ total score (−0.68 [−1.77, 0.39]). Results at week 12 were consistent with week 24 outcomes. Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.ConclusionUMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints.

New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives.

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80–90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.

Aclidinium bromide/formoterol fixed-dose combination therapy for COPD: the evidence to date.

The quest for the right combination of bronchodilators with different mechanisms of action such as long-acting muscarinic antagonists and long-acting β-agonists in the management of stable moderate-to-severe chronic obstructive pulmonary disease (COPD) is a topic of intense research activity currently, given the rising morbidity and mortality due to this disease. The fixed-dose combination of aclidinium bromide and formoterol fumarate in a single inhaler seems to offer superior advantages over either drugs given alone or as separate inhalers concurrently. Since the fixed-dose combination needs to be given twice daily, it is likely to achieve control of symptoms most crucial to the quality of life in COPD, namely, the morning hours. This is reflected in significant trough FEV1 (forced expiratory volume in 1 second) improvements after the dose. This paper reviews the various studies related to this combination put in the perspective of its safety and efficacy and potential benefits over other therapeutic options. However, there is a dearth of data on the long-term safety and efficacy in terms of improvement in lung function. This combination could emerge as an excellent option in the management of stable COPD if data on exacerbation rates and patient-reported outcomes become available from longer-term studies. Moreover, we need some more studies to define the ideal phenotype of COPD best suited for the use of this combination.

Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study

BackgroundQVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD. The QUANTIFY...

Management of asthma in resource-limited settings: role of low-cost corticosteroid/β-agonist combination inhaler.

The management of asthma requires medicines that are effective in relaxing airway smooth muscles and in reducing airway inflammation. Rapid-acting β₂ agonist is a bronchodilator that provides quick symptom relief in patients with asthma. However, it does not effectively address the underlying problem of airway inflammation. Excess use of inhaled bronchodilators alone for symptom relief may result in delay in seeking health care, which in turn may result in delayed use of anti-inflammatory agents. Inhaled corticosteroid (ICS) is critical in the treatment of airway inflammation; it reduces the risk of life-threatening asthma attacks and the need for hospitalisation. ICS is underused, however, and a substantial proportion of patients with persistent asthma in resource-limited settings have no access to affordable ICS for long-term treatment. International guidelines recommend the use of rapid-acting β-agonists as needed as rescue treatment when symptoms occur. Studies have shown that the use of both ICS and rapid-acting β-agonist as needed for symptom relief might be a better option. The combination of ICS and rapid-acting bronchodilator in a single inhaler is currently too expensive and is not affordable for the poor. Although ICS and short-acting β₂ agonist (SABA) for rescue treatment can be obtained to a certain extent by using separate ICS and SABA inhalers, the first step is to ensure access to affordable, quality-assured essential asthma medicine in resource-limited settings.

Diagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines.

The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD). The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD. This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD. It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers. The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations. The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient. The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma–COPD overlap syndrome (ACOS). These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions. For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol–ipratropium) is recommended in patients with less symptoms. If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended. For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide–formoterol, beclomethasone dipropionate–formoterol, fluticasone propionate–salmeterol or fluticasone furoate–vilanterol) is recommended as a first choice. Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium–indacaterol or umeclidinium–vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic. If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast. ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD. Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD. Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both).

Influence of COPD Assessment Text (CAT) evaluation and rehabilitation education guidance on the respiratory and motor functions of COPD patients.

The study aimed to evaluate the influence of the COPD Assessment Test (CAT) evaluation and rehabilitation education guidance on the respiratory and motor functions of patients with chronic obstructive pulmonary disease (COPD). Forty-five patients with COPD admitted from Nov. 2012 to Nov. 2013 were treated with combined bronchodilators and inhaled corticosteroids. Thirty-five patients admitted from Nov. 2012 to Nov. 2013 and classified as a study group received rehabilitation education guidance on the basis of the treatment of the control group to compare the quality-of-life-scale score, dyspnea index score, and motor function of the two groups of patients after 48 weeks of treatment. After treatment, the CAT score of both groups of patients was significantly lowered. After 48 weeks of treatment, the respiratory function of both groups was significantly improved, but the Medical Research Council (MRC) scale for the study group after treatment was significantly lower than that for the control group. After 48 weeks of rehabilitation exercises, the 6-minute walk test (6MWT) for patients with COPD was significantly prolonged, but the test results were significantly higher for the study group after treatment than for the control group. After receiving CAT rehabilitation education, COPD patients had significantly improved life quality and significantly enhanced exercise tolerance. The treatment mode may be gradually introduced in future clinic and nursing work.

Current optimization of combined therapy for chronic obstructive pulmonary disease

Testing the new combined bronchodilator Anoro Ellipta in different clinical trials gives to its high clinical efficacy and safety in chronic obstructive pulmonary disease. The drug contains the molecules of sustained-release selective β2-adrenergic receptor agonist (vilanterol) and a muscarinic cholinergic receptor antagonist (umeclidinium bromide). The bronchodilating mechanisms of umeclidinium bromide are in the competitive inhibition of the binding of acetylcholine with muscarinic acetylcholine receptors of airway smooth muscles whereas in those of vilanterol are in that with the stimulation of intracellular adenylate cyclase. On days 1 and 24 after inhalation of the first dose of vilanterol and umeclidinium bromide, there was a significant increase in the forced expiratory volume in one second as compared to placebo. No clinical effects on QT interval on an electrocardiogram and cardiac rhythm were found. The benefits of an inhalation device (Ellipta) are its innovation design ensuring the effective delivery of an aerosol dose into the airway, convenience, and simplicity.