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      Blood Eosinophilia and Its Stability in Hospitalized COPD Exacerbations are Associated with Lower Risk of All-Cause Mortality

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          Abstract

          Purpose

          Peripheral blood eosinophilic counts are susceptible to many factors and have variability over time. There are limited studies on association of blood eosinophilia with long-term mortality of chronic obstructive pulmonary disease (COPD) patients and these results remain controversial. Our aims were to explore the association of blood eosinophilia at index hospitalization and stability of blood eosinophilia stability over 5 years with all-cause mortality of patients hospitalized for acute exacerbation of COPD (AECOPD).

          Patients and Methods

          Eight hundred twenty-nine patients hospitalized for AECOPD between 2013 and 2014 were included in this study and grouped into two groups according to blood eosinophil with 150 cells/μL used as the cutoff value to form eosinophilic and non-eosinophilic groups. Two hundred forty-one COPD inpatients with at least three blood eosinophils measured from different hospitalizations were used for analysis of longitudinally eosinophilic stability and divided into three groups according to the same cutoff value: predominantly (PE), intermittently (IE) and rarely (RE) eosinophilic groups. Cox regression analysis was used to determine the association of blood eosinophilia and all-cause mortality.

          Results

          In patients hospitalized for AECOPD, 261 (31.5%) at baseline and 41 (17%) based on at least three measurements of blood eosinophils had increased blood eosinophils. For all-cause mortality, eosinophilic COPD patients at index hospitalization had a lower all-cause mortality compared with non-eosinophilic COPD patients (hazard ratio 0.77, 95% confidence interval 0.6–0.99, P=0.04). In patients readmitted for AECOPD by longitudinal eosinophil stability, with the RE group used as reference, the PE group was associated with a lower all-cause mortality of AECOPD patients (hazard ratio 0.43, 95% confidence interval 0.22–0.85, P=0.016), compared to the IE group (hazard ratio 0.72, 95% confidence interval 0.47–1.11, P=0.133).

          Conclusion

          Patients with increased eosinophils (using eosinophil 150 cells/μL as a cutoff value), especially predominantly increased eosinophil levels based on multiple measurements, had a lower risk of all-cause mortality. Blood eosinophilia can be used as a biomarker in hospitalized COPD exacerbations for predicting the risk of all-cause mortality.

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          Most cited references 19

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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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            Predicting outcomes following hospitalization for acute exacerbations of COPD.

            Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a frequent cause of hospital admission and are associated with significant morbidity, mortality, high readmission rates and high resource utilization. More accurate prediction of survival and readmission in patients hospitalized with AECOPD should help to optimize clinical management and allocation of resources, including targeting of palliative care and strategies to reduce readmissions. We have reviewed the published retrospective and prospective studies in this field to identify the factors most likely to be of value in predicting in-hospital and post-discharge mortality, and readmission of patients hospitalized for AECOPD. The prognostic factors which appear most important vary with the particular outcome under consideration. In-hospital mortality is related most clearly to the patient's acute physiological state and to the development of acute comorbidity, while post-discharge mortality particularly reflects the severity of the underlying COPD, as well as specific comorbidities, especially cardiac disease. Important factors influencing the frequency of readmission include functional limitation and poor health-related quality of life. Large prospective studies which incorporate all the potentially relevant variables are required to refine prediction of the important outcomes of AECOPD and thus to inform clinical decision making, for example on escalation of care, facilitated discharge and provision of palliative care.
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              Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis.

              Inhaled corticosteroids are important in the management of chronic obstructive pulmonary disease (COPD), but can slightly increase the risk of pneumonia in patients with moderate-to-severe COPD. Patients with circulating eosinophil counts of 2% or more of blood leucocytes respond better to inhaled corticosteroids than do those with counts of less than 2% and it was therefore postulated that blood eosinophil count might also have an effect on the risk of pneumonia in patients with COPD. In this post-hoc meta-analysis, we investigate whether a 2% threshold can identify patients who differ in their risk of pneumonia, irrespective of inhaled corticosteroid treatment.
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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
                19 May 2020
                2020
                : 15
                : 1123-1134
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020, People’s Republic of China
                [2 ]Clinical Epidemiology and Tobacco Dependence Treatment Research Department, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020, People’s Republic of China
                Author notes
                Correspondence: Huan-Zhong Shi; Ying-Xiang Lin Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , 8 Gongti Nanlu, Chaoyang District, Beijing100020, People’s Republic of China Tel/Fax +86 10 65935208 Email shihuanzhong@sina.com; bjlin666@163.com
                [*]

                These authors contributed equally to this work

                Article
                245056
                10.2147/COPD.S245056
                7245431
                32547000
                © 2020 Zhang 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).

                Page count
                Figures: 3, Tables: 6, References: 27, Pages: 12
                Funding
                This work was supported by the National Key R&D Program of China (2016YFC1303900), the Beijing Municipal Administration of Hospitals’ Mission Plan, the People's Republic of China (No. SML20150301), Capital’s Funds for Health Improvement and Research (No. CFH2016-4-1062) and Chinese Medical Association Chronic Respiratory Disease Fund (No. CRD 08020440122).
                Categories
                Original Research

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