Combination Of Long-acting Bronchodilators Research Articles

Modern possibilities of correction of broncho-obstructive syndrome in chronic heart failure of ischemic origin in combination with chronic obstructive pulmonary disease: simple randomized parallel group study

AIM: To evaluate the efficacy and safety of complex basic therapy for chronic heart failure (CHF) of ischemic origin in combination with chronic obstructive pulmonary disease (COPD) with the inclusion of prolonged bronchodilators.
 MATERIALS AND METHODS: The study included 67 patients (50 men and 17 women) with CHF IIIII functional class (FC) with left ventricular ejection fraction (LVEF) of 45% in combination with moderate-to-severe COPD (GOLD). The patients were divided into three groups: group 1 (n=30) received formoterol as part of therapy, group 2 (n=19) received aclidinium, and group 3 (n=18) received a fixed combination of aclidinum and formoterol. The basic therapy for CHF included nebivolol, losartan, eplerenone, diuretics, low-dose glucocorticosteroids, nitrates, and cardiac glycosides (if necessary). The clinical condition of patients, intracardiac hemodynamics, was indicated using echocardiography, a 6-min walking test (6MWT), bifunctional 24-h monitoring of blood pressure and heart rate, and spirometry. Quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire, St. Georges Respiratory Questionnaire, and Modified Medical Research Council dyspnea scale.
 RESULTS: After 6 months of therapy, the clinical and instrumental parameters and quality of life improved in all groups. At the end of the observation period, the average FC of CHF and dyspnea severity decreased by 17.5, 18.2, 20.1 20.5, 24.2, and 28.1%, respectively. The increase in exercise tolerance was 22.1, 22.6, and 29.2%. An improvement in intracardiac hemodynamics was noted. The LVEF increased by 17.1, 20.5, and 24.6%, and the myocardial mass index decreased by 8.7, 14.2, and 17.4%. The total peripheral vascular resistance, degree of pulmonary hypertension, and duration and frequency of painless myocardial ischemia significantly decreased. The best results were obtained in group 3 using nebivolol, reninangiotensinaldosterone system antagonists, and a combination of long-acting bronchodilators. Therapy was well tolerated by all study groups, with no serious adverse side effects.
 CONCLUSION: The inclusion of nebivolol and losartan in basic therapy, while taking long-acting bronchodilators, improves the clinical and functional states of patients and quality of life, and slows down disease progression. When used in a fixed combination, the use of aclidinium and formoterol improves spirometry to a greater extent.

Bronchodilator therapy in patients with chronic obstructive pulmonary disease: what should be considered in clinical practice when choosing a dosing regimen?

The use of long-acting bronchodilators is central to the chronic obstructive pulmonary disease (COPD) therapy. One of the goals of bronchodilation is to reduce the morning COPD symptoms that are associated with a more severe disease and an increased risk of exacerbations.The aim of the study was to evaluate the clinical efficacy of switching COPD patients with severe morning symptoms who received combinations of long-acting bronchodilators QD to a fixed-dose combination of aclidinium bromide (AB) and formoterol fumarate (FF) BID.Methods. We examined COPD patients treated with combinations of long-acting β2-agonists and M-anticholinergics (but not AB and FF), who continued to complain of severe symptoms in the morning despite the treatment. After examination, the patients were switched to the fixed-dose combination of AB 0.4 mg and FF 0.012 mg (AB/FF) BID in the form of a metered-dose powder inhaler. The patients were examined at baseline and at 6-month follow-up.Results. Of the 115 included COPD patients, 90 completed the study. After 6 months of treatment, they showed a significant decrease in the intensity of cough, sputum amount, severity of distant wheezing, and shortness of breath in the morning (–0.88, –0.38, –0.29, –0.58 on a 4-point scale, the mean score –0.44; p < 0.001). The result of the COPD Assessment test decreased from 28 (24; 34) to 24 (20; 28) (p = 0.011), the distance of a 6-minute walk increased from 319 ± 72 to 354 ± 67 m (p < 0.001). The fixed-dose combination of AB/FF did not cause serious adverse events.Conclusion. The fixed-dose AB/FF combination in COPD patients resulted in a significant clinical improvement and was well tolerated. The AB/FF combination with twice daily dosing regimen is advisable for the patients with morning symptoms persisting despite therapy with other combinations of long-acting bronchodilators with once daily dosing regimen.

Features and significance of the early bronchodilatation effect of the first dose of a long-acting bronchodilator alone and in fixed combination in the treatment of chronic obstructive pulmonary disease

The early bronchodilatory effects of the first dose of long-acting anticholinergics (glycopyrronium and tiotropium) were compared with those of a fixed double combination of long-acting bronchodilators of various classes (indacaterol/glycopyrronium) in patients with stable chronic obstructive pulmonary disease. The possibility of using the results of an early bronchodilatory response to predict their effectiveness in the basic therapy of chronic obstructive pulmonary disease is evaluated. A total of 176 patients with chronic obstructive pulmonary disease were examined. The patients were randomized into three groups. The first group (n = 66) took glycopyrronium, the second group (n = 60) received a combination of indacaterol/glycopyrronium, and the third group (n = 50, control) took tiotropium. Broncholytic tests with the listed drugs were evaluated. The early bronchodilatory effect of the first dose of 110/50 mcg indacaterol/glycopyrronium was manifested by significant bronchodilation (p 0.001) from 30 min, reached its maximum value 60 min after drug intake, and persisted after a 28-day course of treatment. The combination of indacaterol/glycopyrronium provided rapid and prolonged bronchodilation in patients with stable chronic obstructive pulmonary disease, demonstrating advantages over the isolated use of glycopyrronium and tiotropium. Maximization of bronchodilation by the sequential use of glycopyrronium and salbutamol leads to an increase in the volume of forced exhalation in the first second on the 90th min, comparable with the results of indacaterol/glycopyrronium on the 60th min after drug intake, which indicates the clinical feasibility of maximizing bronchodilation with drugs both separately and in combination. Based on a direct positive correlation between the initial value of the forced expiratory volume in the first second and the value on day 28 of indacaterol/glycopyrronium therapy, an equation for predicting the individual effectiveness of the drug during treatment is derived.

Cost-effectiveness of the fixed-dose combination tiotropium/olodaterol versus tiotropium monotherapy or a fixed-dose combination of long-acting β2-agonist/inhaled corticosteroid for COPD in Finland, Sweden and the Netherlands: a model-based study

ObjectivesChronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single...

Approaches to the treatment of exacerbation of chronic obstructive pulmonary disease with comorbid hypertension

Aim. Аnalysis of the efficacy and safety of complex therapy including fixed-dose combinations of long-acting bronchodilators (FCLB) in comorbid patients with an exacerbation of chronic obstructive pulmonary disease (COPD) of the spirometry grades III – IV and hypertension.Methods. A total of 232 patients with an exacerbation of COPD of the spirometry grades III – IV were examined. 174 (75%) patients were diagnosed with the third grade (GOLD III), 58 (25%) – with the fourth spirometry grade (GOLD IV). In the GOLD III group, a moderate exacerbation was diagnosed in 22 (12.6%), severe — in 152 (87.4%). In the GOLD IV group, a moderate exacerbation was diagnosed in 5 (8.5%), severe — in 53 (91.5%), respectively. The patients were divided into 4 groups. Group 1 included 50 patients with an exacerbation of COPD of the spirometry grades III – IV without hypertension; Group 2 – 56 patients with an exacerbation of COPD and concomitant hypertension; Group 3 – 64 patients with an exacerbation of COPD without hypertension, who received FCLB in addition to standard therapy from the 3rd day of hospitalization; Group 4 – 62 patients with an exacerbation of COPD of the spirometry grades III – IV and concomitant hypertension who received FCLB in addition to standard therapy from the 3rd day of hospitalization. The examination included clinical and instrumental methods: the changes in the clinical signs and symptoms, the dyspnea index (according to the mМRS scale), the saturation of hemoglobin with oxygen (SaO2), spirometry, heart rate variability, the frequency and nature of arrhythmias, and systolic and diastolic blood pressure (BP).Results. A sympathicotonic disorder of the autonomic balance was revealed in patients with exacerbation of COPD of the spirometry grades III – IV. This tendency intensified in the patients with concomitant hypertension, which indicated an additional negative effect of comorbid hypertension on the studied parameters. Aggravation of sympathicotonia could be a trigger for an increase in ectopic rhythm disturbances, including high-grade ventricular extrasystoles. In the groups with concomitant hypertension, rhythm disturbances were more frequent (p < 0.05). The inclusion of FCLB in the complex therapy of exacerbation of COPD of the spirometry grades III – IV made it possible to improve the condition of patients significantly: to reduce the dyspnea index on the mМRS scale, increase SaО2 and FEV1 (p < 0.05), achieve clinical improvement in COPD faster and shorten the hospitalization period. As a result of the rapid and effective relief of exacerbation of COPD, the influence of pathogenic factors on the cardiovascular system in the examined patients decreased. The addition of FCLB to the treatment COPD with and without comorbid hypertension did not have a negative effect on heart rate variability, did not aggravate rhythm disturbances, and did not destabilize the BP.Conclusion. The positive clinical effects of the inclusion of FCLB in the complex therapy of exacerbation of COPD of the spirometry grades III – IV in patients with comorbid hypertension led to a decrease in shortness of breath, an improvement in respiratory functions, a decrease in tissue hypoxia and eliminated possible adverse events of this group of drugs.

Early bronchodilatory response to the first dose of indacaterol/glycopyrronium as an additional individual predictor of their effectiveness in the treatment of chronic obstructive pulmonary disease

The effectiveness of the early bronchodilatory response of the first dose of a fixed double combination of long-acting bronchodilators of various classes indacaterol/glycopyrronium and long-acting anticholinergics glycopyrronium and Tiotropium in patients suffering from stable chronic obstructive pulmonary disease is compared. It was found that in all patients included in the study and suffering from chronic obstructive pulmonary disease, changes in functional respiratory indicators were accompanied by positive and comparable dynamics of clinical signs: a decrease in the severity of shortness of breath, the impact of the disease on the quality of life and increased tolerance to physical activity. It was found that the combination of indacaterol/glycopyrronium provides rapid, pronounced and prolonged bronchodilation in patients suffering from chronic obstructive pulmonary disease compared to the separate use of glycopyrronium and Tiotropium. Consistent use of glycopyrronium and salbutamol leads to maximum bronchodilation, which makes it advisable to separate the use of prolonged bronchodilators when initiating therapy for chronic obstructive pulmonary disease. Therefore, there is a clinical feasibility of taking not only fixed combinations of bronchodilators of different classes, but also their consistent use. The results of an early bronchodilatory response to the first dose of indacaterol/glycopyrronium can be used as an additional individual predictor of their effectiveness in the treatment of chronic obstructive pulmonary disease.

PRS30 Cost-Effectiveness of the Fixed-Dose Combination Tiotropium+Olodaterol Versus Tiotropium and Laba/Ics in Finland, Sweden and the Netherlands

Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for COPD patients that have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-effectiveness of the fixed dose combination of the bronchodilators tiotropium and olodaterol (TIO+OLO) versus two comparators (tiotropium monotherapy (TIO) and long-acting beta agonist/ inhaled corticosteroid (LABA/ICS) combinations) in three different countries: Finland (FI), Sweden (SE) and The Netherlands (NL). A previously published COPD patient-level discrete event simulation model was used to estimate effects and costs for 2,000 patients receiving either TIO+OLO, TIO monotherapy or LABA/ICS. Efficacy data for TIO+OLO versus TIO were obtained from a post-hoc analysis of the TONADO and DYNAGITO trials, while efficacy versus LABA/ICS was obtained from a Cochrane review. Treatment effects modelled included impact on FEV1, total and severe exacerbations, and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained from each of the three countries. The main outcomes were the lifetime quality-adjusted life-years (QALYs) and costs. Analyses adhered to the recommendations in the Finnish, Swedish and Dutch pharmacoeconomic guidelines. Treatment with TIO+OLO resulted in a gain in discounted QALYs of 0.09 (FI/SE) to 0.11 (NL) versus TIO and 0.23 (FI/SE) to 0.28 (NL) versus LABA/ICS. The incremental cost-effectiveness ratio of TIO+OLO in Finland was €11,300/QALY versus TIO and dominant versus LABA/ICS (payer perspective). For Sweden the ratios were €4,600/QALY and dominant, respectively (societal perspective). For The Netherlands the ratios were €14,400 and €9,200, respectively (societal perspective). TIO+OLO is a cost-effective option versus TIO in all three countries. Compared with LABA/ICS, TIO+OLO is cost-effective in the Netherlands and dominant in Sweden and Finland.

Efficacy and safety of beta-blockers and prolonged bronchodilators in patients with heart failure with coronary artery disease and moderate to severe COPD

Abstract Purpose To compare clinical efficacy and safety of various treatment regimens with the inclusion of beta-blockers, RAAS antagonists (ACE inhibitors or ARBs), prolonged bronchodilators (LABA, LAMA) in heart failure patients with CAD and COPD. Methods 385 patients (292 men and 93 women), aged 66.3±4.1 years, with CHF classes II to III (NYHA) combined with moderate to severe COPD (GOLD) and with LVEF less than 45% were randomized into nine groups: enalapril + LAMA (control group), nebivolol + enalapril + LAMA, nebivolol + losartan + LAMA, nebivolol + losartan + LABA, nebivolol + losartan + LAMA/LABA, carvedilol + enalapril + LAMA, carvedilol + losartan + LAMA, carvedilol + losartan + LABA, carvedilol + losartan + LAMA/LABA. Patients of all groups received complex CHF treatment comprising diuretics, nitrates, cardiac glycosides (if necessary). Clinical examination, TTE, 6-minute walk test (6MWT), 24-hour electrocardiogram and blood pressure monitoring, respiratory function test were assessed at baseline and after 6 months of treatment. The quality of life was evaluated by MYHFQ, SGRQ and mMRC scale. Results After 6 months of therapy the improvement of clinical condition and quality of life were marked in all groups. At the end of observation period there was a significant improvement of patients clinical condition, quality of life, reduction of mean CHF FC and dyspnea severity, increase of exercise tolerance, slowing of progression of CHF and COPD, improvement of the parameters of intracardiac hemodynamics, structural and functional parameters of the left and right heart (a decrease in the size of the atria, LV volumes and internal dimension at end-diastole and end-systole, cardiac index, LVMMI, an increase of LVEF, a significant decrease in systemic vascular resistance and the pulmonary hypertension grade, significant improvement in systolic and diastolic function of the ventricles, regression of pathological remodeling of the heart, reduction of heart rate, duration and frequency of myocardial ischemia episodes (including its “silent” form). The best results were obtained in groups using a beta-blocker (nebivolol or carvedilol), a RAAS antagonist, and a combination of long-acting bronchodilators (indacaterol and tiotropium) – group 5 and 9. It is worth noting that beta-blockers, LABA and LAMA were well tolerated in all observation groups and serious adverse events were absent. Conclusions The appointment of 3-generation beta-blockers to patients with CHF on the background of CAD and COPD can significantly increase the effectiveness of treatment and does not cause a deterioration in spirometry in patients with such cardiopulmonary pathology. In our opinion, the most important point in the appointment of beta blockers to patients with moderate to severe COPD is low start dose and slow titration of the dose at the beginning of the therapy. It is advisable to include in the complex therapy of such patients a combination of LABA and LAMA as a basic bronchodilator support. Funding Acknowledgement Type of funding source: None

2019 Year in Review: Aerosol Therapy.

Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and long-acting muscarinic antagonists. A combination of aclidinium bromide and formoterol fumarate was approved in the United States. The combination was superior to its components alone, as well as tiotropium and a salmeterol-fluticasone combination. Increased risk of an asthma exacerbation was reported in children exposed to electronic nicotine delivery systems. A smart inhaler capable of recording inspiratory flow was approved in the United States. The use of as-needed budesonide-formoterol was reported to be superior to scheduled budesonide and as-needed terbutaline for the treatment of adults with mild-to-moderate asthma. A survey among teens with asthma and their caregivers revealed a disagreement in the number of inhaled controller medications the teen was taking. Treatment with inhaled hypertonic saline resulted in a decreased lung clearance index in infants and preschool children with cystic fibrosis. Surgical masks were well tolerated and significantly decreased the burden of aerosolized bacteria generated by coughing in adults with cystic fibrosis. Inhaled liposomal amikacin in addition to guideline-based therapy was reported to be superior to guideline-based therapy alone in achieving negative sputum cultures in adult subjects with Mycobacterium avium complex pulmonary disease. During 2019, lung injury associated to e-cigarette or vaping was reported, including 60 casualties.

Fixed-Dose Combinations of Long-Acting Bronchodilators for the Management of COPD: Global and Asian Perspectives.

Maintenance bronchodilator therapy with long-acting β-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) is the cornerstone treatment for patients with stable chronic obstructive pulmonary disease (COPD). Fixed-dose combinations (FDCs) of LABA/LAMA are recommended for the majority of symptomatic COPD patients by global guidelines; regional guidelines such as the Japanese and Korean guidelines also provide similar recommendations for the use of LABA/LAMA FDCs. This review comprehensively describes the latest clinical evidence from key studies on the efficacy and safety of four approved LABA/LAMA fixed-dose combinations: indacaterol/glycopyrronium, vilanterol/umeclidinium, formoterol/aclidinium, and olodaterol/tiotropium. Additionally, in this review we describe the rationale behind the use of LABA/LAMA FDC therapy, key findings from the preclinical and clinical trial evaluation of respective LABA and LAMA monocomponents, and the efficacy and safety of LABA/LAMA FDCs. Special emphasis is placed on the clinical evidence for the monocomponents and LABA/LAMA FDCs from the Asian population. This detailed overview of the efficacy and safety of LABA/LAMA FDCs in global and Asian COPD patients is envisaged to provide a better understanding of the benefits of these therapies and to inform healthcare providers and patients on their appropriate use.Funding: Novartis Pharma K.K.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-0893-3) contains supplementary material, which is available to authorized users.

Protocol for a systematic literature review and network meta-analysis of the clinical benefit of inhaled maintenance therapies in chronic obstructive pulmonary disease

IntroductionChronic obstructive pulmonary disease (COPD) exacerbations progress the course of disease and impair lung function. Inhaled maintenance therapy reduces exacerbations. It is not yet established which inhaled therapy combination is...

Effects of baseline symptom burden on treatment response in COPD.

RationaleIn symptomatic patients with COPD, the decision whether to initiate maintenance treatment with a single agent or a combination of long-acting bronchodilators remains unclear.ObjectiveTo investigate whether baseline symptomatic status influences response to tiotropium/olodaterol treatment.Materials and methodsPost hoc analysis of the randomized OTEMTO® studies (NCT01964352; NCT02006732), in which patients with moderate-to-severe COPD received placebo, tiotropium 5 µg, tiotropium/olodaterol 2.5/5 µg, or tiotropium/olodaterol 5/5 µg once daily for 12 weeks via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Impact of baseline symptomatic status (modified Medical Research Council [mMRC] score) on response to treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, or placebo at Week 12 was assessed by St George’s Respiratory Questionnaire (SGRQ) total score and response rate, transition dyspnea index (TDI) focal score and response rate, and trough forced expiratory volume in 1 second response.ResultsTiotropium/olodaterol improved SGRQ total scores and response rates compared with placebo and tiotropium for patients with baseline mMRC scores 0–1 and ≥2. For tiotropium/olodaterol vs tiotropium, greater improvements were observed for patients with mMRC ≥2 (SGRQ score adjusted mean treatment difference −3.44 [95% CI: −5.43, −1.46]; P=0.0007; SGRQ response rate ORs 2.09 [95% CI: 1.41, 3.10]; P=0.0002). Dyspnea, measured by TDI score, was consistently improved with tiotropium/olodaterol vs placebo for patients with mMRC scores 0–1 and ≥2 (adjusted mean treatment difference 1.63 [95% CI: 1.06, 2.20]; P<0.0001 and 1.60 [95% CI: 1.09, 2.10]; P<0.0001, respectively). In patients with mMRC scores 0–1 and ≥2, tiotropium/olodaterol consistently improved TDI response rate and lung function vs placebo and tiotropium.ConclusionsPatients with COPD with more severe baseline dyspnea appear to derive greater health status benefit with tiotropium/olodaterol compared with tiotropium alone.

New possibilities of pharmacotherapy for chronic obstructive pulmonary disease

The use of bronchodilators (DB) remains up to the present day the leading therapeutic strategy for the treatment of chronic obstructive pulmonary disease (COPD), in which case administration of fixed-dose combinations of long-acting bronchodilators seem the most promising. At the same time, the issues of anti-inflammatory therapy of COPD are also actively discussed, first of which is feasibility for the wide use of fixed-dose combinations of inhaled glucocorticosteroids (IHGC) with long-acting β2-agonists (LABA). Recent years are characterized by the launch of a significant number of new BDs, anti-inflammatory drugs and their combinations to the pharmaceutical market. The article considers the role and place of new drugs in the treatment of COPD having a stable course.

PRS49 - COST-EFFECTIVENESS OF THE FIXED-DOSE COMBINATION TIOTROPIUM + OLODATEROL VERSUS TIOTROPIUM BASED ON THE DYNAGITO TRIAL RESULTS IN FRANCE

Combinations of long-acting bronchodilators are recommended to reduce the rate of chronic obstructive pulmonary disease (COPD) exacerbations. Evidence from a recent head-to-head trial, DYNAGITO, suggests that the fixed dose combination tiotropium+olodaterol (TIO+OLO) produces a reduction in the risk of exacerbating compared with tiotropium monotherapy (TIO). This study assessed the cost-effectiveness of TIO+OLO versus TIO in the French setting. A recently developed COPD patient-level simulation model was used to estimate the lifetime effects and costs for 15,000 patients receiving either TIO+OLO or TIO by applying the difference in annual exacerbation rate as observed in the DYNAGITO trial. The unit costs for treatment medication, COPD maintenance treatment, COPD exacerbations (moderate and severe) and pneumonias were obtained from relevant sources in France. The main outcomes were the annual exacerbation rate, quality-adjusted life-years (QALYs) and lifetime costs. Analyses were performed from a societal perspective. Patients receiving TIO+OLO benefitted from QALYs gain as compared to those treated with TIO: on average + 0.042 QALYs per patient over lifetime (PSA: 0.043 (95% UI: -0.015; 0.102)). The higher treatment medication costs for TIO+OLO versus TIO (+€1,640) were not completely compensated by the reduction in exacerbation costs (-€1,540), but the resulting difference in total costs between TIO + OLO versus TIO was small +€123 (PSA: €131 (95% UI: -€1021; €1026). The base case cost-effectiveness ratio (ICER) of TIO+OLO vs OLO was €2,900 per QALY. This finding was consistent across all sensitivity analyses conducted. On the basis of the results of the DYNAGITO trial, TIO+OLO is cost-effective versus TIO in COPD patients in France with a low cost per QALY.

Comorbidities, mortality, and management of chronic obstructive pulmonary disease patients who required admissions to public hospitals in Hong Kong - computerized data collection and analysis.

BackgroundCOPD is a common cause for hospital admission. Conventional studies of the epidemiology of COPD involved large patient number and immense resources and were difficult to be repeated. The present study aimed at assessing the utilization of a computerized data management system in the collection and analysis of the epidemiological and clinical data of a large COPD cohort in Hong Kong (HK).Patients and methodsIt was a computerized, multicenter, retrospective review of the characteristics of patients discharged from medical departments of the 16 participating hospitals with the primary discharge diagnosis of COPD in 1 year (2012). Comparison was made between the different subgroups in the use of medications, ventilatory support, and other health care resources. The mortality of the subjects in different subgroups was traced up to December 31, 2014. The top 10 causes of death were analyzed.ResultsIn total, 9,776 subjects (82.6% men, mean age = 78 years) were identified. Of the 1,918 subjects with lung function coding, 85 (4.4%), 488 (25.5%), 808 (42.1%), and 537 (28.0%) subjects had the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 2, 3, and 4 classes, respectively. Patients with higher GOLD classes had higher number of hospital admissions, longer hospital stay, increased usage of noninvasive mechanical ventilation (NIV), combinations of long-acting bronchodilators, and higher mortality. Of the 9,776 subjects, 2,278 (23.3%) received NIV, but invasive mechanical ventilation was uncommon (134 of 9,776 subjects [1.4%]); 4,427 (45.3%) subjects had died by the end of 2014. The top causes of death were COPD, pneumonia, lung cancer, and other malignancies.ConclusionPatients admitted to hospitals for COPD in HK had significant comorbidities, mortality, and imposed heavy burden on health care resources. It is possible to collect and analyze data of a large COPD cohort through a computerized system. Suboptimal coding of lung function results was observed, and underutilization of long-acting bronchodilators was common.

Pharmacoeconomic assessment of dual bronchodilation therapy in patients with COPD

This study was aimed at clinical and economic assessment of feasibility of inclusion glycopyrronium bromide/indacaterol fixed combination in the State Program for providing necessary drugs to patients. Methods. This retrospective study was based on previously published clinical data. Change of economic burden was assessed using budget impact analysis. Cost-efficacy was assessed using cost minimization analysis and lost opportunities analysis. Results. Switching COPD patients from free combination of long-acting bronchodilators (LABD) to glycopyrronium bromide/indacaterol fixed combination has led to 20.44% decrease in the economic burden. The 3-year cost reduction of COPD therapy has reached RUB 2,416 bln. Conclusion. The results demonstrated higher cost-efficacy of glycopyrronium bromide/indacaterol fixed combination compared to the standard therapy of COPD. Inclusion of glycopyrronium bromide/indacaterol combination into the State Program for providing necessary drugs to COPD patients could be rational and ecomonically feasible.

Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial

Combinations of long-acting bronchodilators are recommended to reduce the rate of chronic obstructive pulmonary disease (COPD) exacerbations. It is unclear whether combining olodaterol, a long-acting beta-agonist, with tiotropium, a long-acting anti-muscarinic, reduces the rate of exacerbations compared with tiotropium alone. This 52-week, double-blind, randomised, parallel-group, active-controlled trial randomly assigned (1:1) patients with COPD with a history of exacerbations using a randomised block design to receive tiotropium-olodaterol 5 μg-5 μg or tiotropium 5 μg once daily. Patients using inhaled corticosteroids continued this therapy. Treatment was masked to patients, investigators, and those involved in analysing the data. The primary endpoint was the rate of moderate and severe COPD exacerbations from the first dose of medication until 1 day after last drug administration. The primary analysis included all randomly assigned patients who received any dose of study medication but were not from a site excluded due to on-site protocol violations. The trial is registered with ClinicalTrials.gov, number NCT02296138. Overall, 9009 patients were screened from 818 centres in 51 countries. We recruited 7880 patients between Jan 22, 2015 and March 7, 2016 (mean age 66·4 years [SD 8·5], 5626 [71%] were men, mean FEV1 percent predicted 44·5% [SD 27·7]): 3939 received tiotropium-olodaterol and 3941 tiotropium. The rate of moderate and severe exacerbations was lower with tiotropium-olodaterol than tiotropium (rate ratio [RR] 0·93, 99% CI 0·85-1·02; p=0·0498), not meeting the targeted 0·01 significance level. The proportion of patients reporting adverse events was similar between treatments. Combining tiotropium and olodaterol did not reduce exacerbation rate as much as expected compared with tiotropium alone. Boehringer Ingelheim International GmbH.

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.

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).

P237 Comparison of COPD exacerbations with once-daily QVA149 versus twice-daily salmeterol/fluticasone combination: the ILLUMINATE study

IntroductionExacerbations are the most frequent cause of hospitalisation and death among patients with COPD. Combinations of long-acting bronchodilators maximise bronchodilation and may reduce the risk of exacerbations. QVA149, a once-daily...