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      Evaluation of exacerbations and blood eosinophils in UK and US COPD populations

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          Abstract

          Background

          Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β 2-agonist and long-acting muscarinic antagonist).

          Methods

          In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.

          Results

          Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included. Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL. Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year. In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability. Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.

          Conclusion

          A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions. A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.

          Electronic supplementary material

          The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users.

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          Most cited references15

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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 and Exacerbations in Chronic Obstructive Pulmonary Disease. The Copenhagen General Population Study.

            Whether high blood eosinophils are associated with chronic obstructive pulmonary disease (COPD) exacerbations among individuals with COPD in the general population is largely unknown.
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              Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

              Background Eosinophilic airway inflammation in COPD is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However there is no consistent blood eosinophil level that has been used to define the increased exacerbation risk. Objective To investigate blood eosinophil levels associated with exacerbation risk in COPD Methods Blood eosinophil counts and exacerbation risk were analyzed in moderate-to-severe COPD subjects, using two independent studies of former and current smokers with longitudinal data. The COPDGene study was analyzed for discovery (n=1553) and the ECLIPSE study was analyzed for validation (n=1895). A subset of the ECLIPSE subjects were used to assess the stability of blood eosinophil counts over time. Results COPD exacerbation risk increased with higher eosinophil counts. An eosinophil threshold of ≥300 cells/μL showed adjusted incidence rate ratios (IRR) for exacerbations of 1.32 in COPDGene (95% confidence interval (CI) 1.10–1.63). The cutoff of ≥300 cells/μL was validated for prospective risk of exacerbation in ECLIPSE with adjusted IRR of 1.22 (95% CI 1.06–1.41) using 3 year follow up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count ≥300 cells/μL was driven by subjects with a history of frequent exacerbations in both COPDGene and ECLIPSE. Conclusions Patients with moderate to severe COPD and blood eosinophil count ≥ 300 cells/μL had an increased risk exacerbations in the COPDGene Study which was prospectively validated in the ECLIPSE Study.
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                Author and article information

                Contributors
                +49 6421 586 6451 , vogelmei@med.uni-marburg.de
                ktkostikas@gmail.com
                jenny.fang@novartis.com
                hengfeng.tian@novartis.com
                bethan.jones@pharmatelligence.co.uk
                chris.morgan@pharmatelligence.co.uk
                robert.fogel@novartis.com
                florian.gutzwiller@novartis.com
                hui.cao@novartis.com
                Journal
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                7 August 2019
                7 August 2019
                2019
                : 20
                : 178
                Affiliations
                [1 ]ISNI 0000 0004 1936 9756, GRID grid.10253.35, Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, , Philipps-University Marburg, Member of the German Center for Lung Research (DZL), ; 35043 Marburg, Germany
                [2 ]ISNI 0000 0001 2108 7481, GRID grid.9594.1, Respiratory Medicine Department, , University of Ioannina School of Medicine, ; Ioannina, Greece
                [3 ]ISNI 0000 0004 0439 2056, GRID grid.418424.f, Novartis Pharmaceuticals Corporation, ; East Hanover, NJ USA
                [4 ]KMK Consulting Inc, Morristown, NJ USA
                [5 ]Pharmatelligence, Cardiff, UK
                [6 ]ISNI 0000 0001 1515 9979, GRID grid.419481.1, Novartis Pharma AG, ; Basel, Switzerland
                Article
                1130
                10.1186/s12931-019-1130-y
                6686508
                31391053
                aa8322ef-a7df-4c11-a6b0-f6548ca02b3a
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 March 2019
                : 8 July 2019
                Funding
                Funded by: Novartis Pharma AG
                Award ID: N/A
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Respiratory medicine
                copd,triple therapy,eosinophil,exacerbation
                Respiratory medicine
                copd, triple therapy, eosinophil, exacerbation

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