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      International Journal of COPD (submit here)

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      Inhaled corticosteroids, blood eosinophils, and FEV 1 decline in patients with COPD in a large UK primary health care setting

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          Abstract

          Background: Inhaled corticosteroid (ICS)-containing medications slow rate of decline of FEV 1. Blood eosinophil (EOS) levels are associated with the degree of exacerbation reduction with ICS.

          Purpose: We investigated whether FEV 1 decline differs between patients with and without ICS, stratified by blood EOS level.

          Patients and methods: The UK Clinical Practice Research Datalink (primary care records) and Hospital Episode Statistics (hospital records) were used to identify COPD patients aged 35 years or older, who were current or ex-smokers with ≥2 FEV 1 measurements ≥6 months apart. Prevalent ICS use and the nearest EOS count to start of follow-up were identified. Patients were classified at baseline as higher stratum EOS (≥150 cell/µL) on ICS; higher stratum EOS not on ICS; lower stratum EOS (<150 cells/µL) on ICS; and lower stratum EOS not on ICS. In addition, an incident ICS cohort was used to investigate the rate of FEV 1 change by EOS and incident ICS use. Mixed-effects linear regression was used to compare rates of FEV 1 change in mL/year.

          Results: A total of 26,675 COPD patients met our inclusion criteria (median age 69, 46% female). The median duration of follow up was 4.2 years. The rate of FEV 1 change in prevalent ICS users was slower than non-ICS users (−12.6 mL/year vs −21.1 mL/year; P =0.001). The rate of FEV 1 change was not significantly different when stratified by EOS level. The rate of FEV 1 change in incident ICS users increased (+4.2 mL/year) vs −21.2 mL/year loss in non-ICS users; P<0.001. In patients with high EOS, incident ICS patients showed an increase in FEV 1 (+12 mL/year) compared to non-ICS users whose FEV 1 decreased (−20.8 mL/year); P<0.001. No statistical difference was seen in low EOS patients. Incident ICS use is associated with an improvement in FEV 1 change, however, over time this association is lost.

          Conclusion: Regardless of blood EOS level, prevalent ICS use is associated with slower rates of FEV 1 decline in COPD.

          Most cited references13

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          The natural history of chronic airflow obstruction.

          A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
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            Effectiveness of Fluticasone Furoate-Vilanterol for COPD in Clinical Practice.

            Evidence for the management of chronic obstructive pulmonary disease (COPD) comes from closely monitored efficacy trials involving groups of patients who were selected on the basis of restricted entry criteria. There is a need for randomized trials to be conducted in conditions that are closer to usual clinical practice.
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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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                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 May 2019
                2019
                : 14
                : 1063-1073
                Affiliations
                [1 ]National Heart and Lung Institute, Imperial College London , London, UK
                [2 ]Respiratory Epidemiology, GlaxoSmithKline R&D , Uxbridge, UK
                [3 ]MRC Biostatistics Unit, University of Cambridge , Cambridge, UK
                Author notes
                Correspondence: Hannah R WhittakerNational Heart and Lung Institute, Imperial College , Emmanuel Kaye Building, London, UKEmail h.whitaker@ 123456imperial.ac.uk
                Article
                200919
                10.2147/COPD.S200919
                6536812
                31213788
                8220c19a-5ae7-4c6c-8527-bf935feba39c
                © 2019 Whittaker 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
                : 09 January 2019
                : 01 April 2019
                Page count
                Figures: 2, Tables: 6, References: 23, Pages: 11
                Categories
                Original Research

                Respiratory medicine
                copd,lung function,eosinophil,inhaled corticosteroids
                Respiratory medicine
                copd, lung function, eosinophil, inhaled corticosteroids

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