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      Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis

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          Abstract

          Background

          Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.

          Methods

          We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.

          Results

          Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74–0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52–0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44–0.78). No association was found in four out of five observational studies.

          Conclusion

          This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a “real world” COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

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          Most cited references20

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          Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies.

          Findings from previous studies showed that mepolizumab significantly reduces the rate of exacerbations in patients with severe eosinophilic asthma. To assess the relationship between baseline blood eosinophil counts and efficacy of mepolizumab we did a secondary analysis of data from two studies, stratifying patients by different baseline blood eosinophil thresholds.
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            • Record: found
            • Abstract: found
            • Article: not found

            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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              • Record: found
              • Abstract: found
              • Article: not found

              Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials.

              The peripheral blood eosinophil count might help identify those patients with chronic obstructive pulmonary disease (COPD) who will experience fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc analyses have proposed eosinophil cutoffs that are both arbitrary and limited in evaluating complex interactions of treatment response. We modelled eosinophil count as a continuous variable to determine the characteristics that determine both exacerbation risk and clinical response to ICS in patients with COPD.
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                Author and article information

                Contributors
                timothy.harries@kcl.ac.uk
                victoria.rowland@kcl.ac.uk
                chris.corrigan@kcl.ac.uk
                iain.marshall@kcl.ac.uk
                lucy.mcdonnell@kcl.ac.uk
                vibhore.prasad@kcl.ac.uk
                peter.1.schofield@kcl.ac.uk
                david.armstrong@kcl.ac.uk
                patrick.white@kcl.ac.uk
                Journal
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                3 January 2020
                3 January 2020
                2020
                : 21
                : 3
                Affiliations
                [1 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Public Health and Primary Care, School of Population Health & Environmental Sciences, , King’s College London, ; 3rd floor Addison House, Guys Campus, London, SE1 1UL UK
                [2 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Asthma Allergy & Respiratory Science, , King’s College London, ; London, UK
                Author information
                http://orcid.org/0000-0002-3891-9157
                Article
                1268
                10.1186/s12931-019-1268-7
                6942335
                31900184
                14cd6a5d-85a0-45b1-a24b-eb9494e263fb
                © The Author(s). 2020

                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
                : 28 September 2019
                : 23 December 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Award ID: DRF-2015-08-091
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Respiratory medicine
                pulmonary disease, chronic obstructive,eosinophils,inhaled corticosteroids,randomised controlled trials,observational studies

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