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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      A Framework For Step Down Or Therapeutic Re-Organization For Withdrawal Of Inhaled Corticosteroids In Selected Patients With COPD: A Proposal For COPD Management

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          Abstract

          While chronic obstructive pulmonary disease (COPD) continues to be a major cause of morbidity and mortality, pharmacological therapy has a definite benefit on symptoms as well as the frequency and severity of exacerbations, and general health. The most recent Global Initiative for Obstructive Lung Disease (GOLD) guidelines recommend triple therapy (long-acting beta2 agonists [LABA] + long-acting muscarinic antagonists [LAMA] + inhaled corticosteroids [ICS]) only for patients with exacerbations, elevated eosinophils, and without control using a LABA/LAMA or ICS/LABA combination. Long-term monotherapy with ICS is not currently recommended, but may be considered in association with LABAs in patients with a history of exacerbations and elevated eosinophils in spite of appropriate treatment with long-acting bronchodilators. However, long-term use of ICS in combination therapy has been associated with adverse effects, even if widely used in routine management for decades. The available evidence suggests that ICS can be rationally discontinued in patients with stable disease and is not likely to have unfavorable effects on lung function, overall health, or be associated with a greater risk of exacerbations. Indeed, it is widely accepted that ICS therapy should be limited to a small proportion of patients after careful assessment of the individual risk-benefit profile. Unfortunately, however, there are no international recommendations that provide specific guidance or a protocol for withdrawal of ICS. Herein, the available evidence on the use of ICS is reviewed and an easy to use tool is proposed that can provide clinicians with a simple management scheme to guide the most appropriate therapy for management of COPD and use of ICS. In management of COPD, a highly personalized approach is advocated so that the most appropriate therapy for each individual patient can be selected.

          Most cited references32

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          Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial

          Blood eosinophil counts might predict response to inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. We used data from the WISDOM trial to assess whether patients with COPD with higher blood eosinophil counts would be more likely to have exacerbations if ICS treatment was withdrawn.
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            Blood eosinophils as a marker of response to inhaled corticosteroids in COPD.

            Identification of a biomarker that predicts response to inhaled corticosteroids (ICS) would help evaluate the risk/benefit profile of ICS in chronic obstructive pulmonary disease (COPD) and guide treatment.The ISOLDE study randomised 751 patients (mean post-bronchodilator forced expiratory volume in 1 s (FEV1) 1.4 L: 50% predicted normal) to fluticasone propionate 500 μg twice daily or placebo for 3 years, finding no difference in FEV1 rate of decline between treatments (p=0.16) and a significant reduction in median exacerbation rate with fluticasone propionate versus placebo (p=0.026). We re-analysed ISOLDE results by baseline blood eosinophil count to investigate whether eosinophil level predicts ICS benefit.Patients with eosinophils <2% (n=456) had a similar rate of post-bronchodilator FEV1 decline with fluticasone propionate as placebo (-2.9 mL·year(-1); p=0.688). With eosinophils ≥2% (n=214), the rate of decline decreased by 33.9 mL·year(-1) with fluticasone propionate versus placebo (p=0.003). Exacerbation rate reduction on ICS for fluticasone propionate versus placebo was higher in the eosinophil <2% group compared with the ≥2% group; time-to-first moderate/severe exacerbation was not different between treatments in either group.A baseline blood eosinophil count of ≥2% identifies a group of COPD patients with slower rates of decline in FEV1 when treated with ICS: prospective testing of this hypothesis is now warranted.
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              Airway eosinophilia in chronic bronchitis during exacerbations.

              To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.
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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
                23 September 2019
                2019
                : 14
                : 2185-2193
                Affiliations
                [1 ]Respiratory Unit, Azienda Ospedaliera Universitaria Integrata , Verona, Italy
                [2 ]Department of Internal Medicine, Respiratory Diseases and Allergy Clinic, University of Genova, Azienda Policlinico IRCCS San Martino , Genoa, Italy
                [3 ]Department of Medical Sciences, University of Ferrara , Ferrara, Italy
                [4 ]Department of Health Sciences, Università degli Studi di Milano, Respiratory Unit, Papa Giovanni XXIII Hospital , Bergamo, Italy
                [5 ]Department of Health Sciences, Università degli Studi di Milano,Pulmonary Unit, Luigi Sacco University Hospital, ASST Fatebenefratelli , Milan, Italy
                Author notes
                Correspondence: Claudio Micheletto Respiratory Unit, Azienda Ospedaliera Universitaria Integrata , Piazzale Stefani 1, Verona37122, ItalyTel +39 045 8122248 Email claudio.micheletto@univr.it
                Author information
                http://orcid.org/0000-0002-2731-5809
                http://orcid.org/0000-0002-1743-0504
                Article
                216059
                10.2147/COPD.S216059
                6765263
                bd5b57cb-38f3-41e8-a48f-3fcfa816cbf8
                © 2019 Micheletto 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
                : 17 May 2019
                : 09 August 2019
                Page count
                Figures: 2, References: 54, Pages: 9
                Categories
                Review

                Respiratory medicine
                copd,exacerbation,inhaled corticosteroids,laba,lama,deprescribing
                Respiratory medicine
                copd, exacerbation, inhaled corticosteroids, laba, lama, deprescribing

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