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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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      Comparison of the Clinical Outcomes Between Nebulized and Systemic Corticosteroids in the Treatment of Acute Exacerbation of COPD in China (CONTAIN Study): A Post Hoc Analysis

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          Abstract

          Background and Objective

          Although corticosteroids have been widely used in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), few studies have evaluated the effectiveness of nebulized corticosteroids (NCS), systemic corticosteroids (SCS), and NCS plus SCS in the management of AECOPD in China. This study aimed to evaluate the effectiveness of NCS, SCS, and NCS plus SCS in Chinese patients with AECOPD.

          Patients and Methods

          This was a real-world study of AECOPD patients at 43 sites from January to September 2014. During hospitalization, patients treated with nebulized budesonide (NCS group, n=1091), SCS (SCS group, n=709), or both (NCS+SCS group, n=1846) were included. Propensity score matching (PSM) and subgroup analyses were performed. The primary outcomes were the length of hospital stay, mortality, and change in arterial blood gases from baseline.

          Results

          Multivariable analysis showed that the three treatments at the same severity of AECOPD were not significantly different regarding intubation rates, rates of pneumonia improvement at discharge, rates of new-onset pneumonia in hospital, and mortality. Following PSM, NCS+SCS was associated with greater length of hospital stay than both NCS and SCS (in patients without respiratory failure [RF, P<0.001] and with type I RF [ P=0.022]), and more hospitalization costs than the other two treatments (in patients without RF [ P<0.001]).

          Conclusion

          NCS is effective for patients with AECOPD, which may be an alternative treatment option. Further clinical trials are urgently needed to better understand the efficacy of NCS, SCS, and NCS+SCS in AECOPD management in China.

          Most cited references24

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          Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers.

          Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively. The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
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            Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial.

            Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and ≤ 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.
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              Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits

              Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden. Their diagnosis, assessment and management remain suboptimal and unchanged for decades. Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically. This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes. This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations.
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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
                30 September 2020
                2020
                : 15
                : 2343-2353
                Affiliations
                [1 ]Department of Respiratory Medicine, Peking University Third Hospital , Beijing, People’s Republic of China
                [2 ]Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai, People’s Republic of China
                [3 ]Department of Respiratory and Critical Care Medicine, Baogang Hospital, Third Affiliated Hospital of Inner Mongolia Medical College, Third School of Clinical Medicine, Inner Mongolia Regional Medical Center , Baotou, People’s Republic of China
                [4 ]Department of Respiratory Medicine, Shanghai Songjiang District Central Hospital , Shanghai, People’s Republic of China
                [5 ]Department of Respiratory Medicine, Shanghai Fengxian District Central Hospital , Shanghai, People’s Republic of China
                [6 ]State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University , Guangzhou, People’s Republic of China
                [7 ]Department of Respiratory Medicine, Hebei Provincial People’s Hospital , Shijiazhuang, People’s Republic of China
                Author notes
                Correspondence: Jin-fu Xu Email jfxucn@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-7511-661X
                http://orcid.org/0000-0002-8039-8973
                Article
                255475
                10.2147/COPD.S255475
                7533224
                f428b53b-1205-4097-8fe0-4ca68ce1dd8c
                © 2020 Chen 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
                : 03 April 2020
                : 18 August 2020
                Page count
                Figures: 3, Tables: 12, References: 30, Pages: 11
                Funding
                Funded by: AstraZeneca, China;
                Funded by: National Natural Science Fund for Distinguished Young Scholars to JFX;
                Funded by: Shanghai Leading Talent Program;
                Funded by: Project of the Shanghai Hospital Development Center;
                Funded by: National Key R&D Program of China;
                This study was funded by AstraZeneca, China. The study was also supported by National Natural Science Fund for Distinguished Young Scholars to JFX (81925001), Shanghai Leading Talent Program (No. 2016036 to JFX), the Project of the Shanghai Hospital Development Center (16CR3036A to JFX), and National Key R&D Program of China (No.2018YFC1311900) to JPZ. AECOPD NIS provided all clinical data, which was analyzed by CONTAIN members. AECOPD NIS was conducted by a large team of investigators (see details in the Appendix 2 collaborators list).
                Categories
                Original Research

                Respiratory medicine
                acute exacerbation,chronic obstructive pulmonary disease,clinical outcomes,corticosteroids

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