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      International Journal of COPD (submit here)

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      Dual Bronchodilator in the Era of Triple Therapy

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          Abstract

          Pharmacological medications used for the treatment of COPD patients have increased significantly. Long-acting bronchodilators have been recognized as the mainstay of the treatment of stable COPD, while ICS are usually added in patients with COPD who experience exacerbations, despite bronchodilator treatment. In the latest years, several studies have been published showing the beneficial effect of adding ICS on dual bronchodilation in patients suffering from more severe disease comparing triple therapy with several therapeutic regiments including dual bronchodilation and providing a message that this triple therapy might be more appropriate for COPD patients. However, not all COPD patients have a desirable response to ICS treatment while long-term ICS use in COPD is associated with several side effects. In this report, we aimed to provide a review of the current knowledge on the importance of dual bronchodilation on COPD patients and to compare its use with triple therapy, by covering a wide spectrum of topics. Finally, we propose an algorithm on performing treatment step up from dual bronchodilation to triple therapy and step down from triple to double bronchodilation considering the current evidence.

          Most cited references93

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          Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019

          Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up. Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.
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            Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD

            The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid-LABA or LAMA-LABA), are uncertain.
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              Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease.

              Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                copd
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                28 October 2020
                2020
                : 15
                : 2695-2705
                Affiliations
                [1 ]2nd Respiratory Medicine Department, University of Athens, “Attikon” University Hospital , Athens, Greece
                [2 ]1st Respiratory Medicine Department, University of Athens, “Sotiria” Chest Hospital , Athens, Greece
                [3 ]PNOH Pulmonary Clinic, Metropolitan Hospital , Athens, Greece
                [4 ]Department of Respiratory Medicine, Medical School, Democritus University of Thrace , Alexandroupolis, Greece
                [5 ]Respiratory Medicine Department, Aristotle University of Thessaloniki, G Papanikolaou Hospital , Thessaloniki, Greece
                [6 ]5th Respiratory Medicine Department, Sotiria Chest Hospital , Athens, Greece
                [7 ]3rd Department of Medicine, Athens Medical School , Athens, Greece
                [8 ]Department of Thoracic Medicine, Faculty of Medicine, University of Crete , Crete, Greece
                Author notes
                Correspondence: Andriana I Papaioannou 2nd Respiratory Medicine Department, University of Athens, “Attikon” University Hospital , Chaidari, Athens, GreeceTel +302105831163 Email papaioannouandriana@gmail.com
                Author information
                http://orcid.org/0000-0001-9708-3241
                http://orcid.org/0000-0002-4278-9922
                http://orcid.org/0000-0003-0138-5582
                http://orcid.org/0000-0001-7121-6253
                http://orcid.org/0000-0003-4456-8987
                http://orcid.org/0000-0003-3002-9851
                Article
                273987
                10.2147/COPD.S273987
                7604249
                bcb89777-7539-4a3d-bf61-8b1b33103234
                © 2020 Papaioannou et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 30 July 2020
                : 23 September 2020
                Page count
                Figures: 1, References: 94, Pages: 11
                Categories
                Review

                Respiratory medicine
                chronic obstructive pulmonary disease,dual bronchodilation,inhaled corticosteroids,triple therapy

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