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      International Journal of COPD (submit here)

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      Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease

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          Abstract

          Introduction

          Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations.

          Methods

          Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators.

          Results

          A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators.

          Conclusion

          Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

          Most cited references35

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Chronic obstructive pulmonary disease

            Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.
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              Severe exacerbations and BODE index: two independent risk factors for death in male COPD patients.

              1) To determine whether severe exacerbation of COPD is a BODE index independent risk factor for death; 2) whether the combined application of exacerbations and BODE (e-BODE index), offers greater predictive capacity than BODE alone or can simplify the model, by replacing the exercise capacity (BODEx index). A prospective study was made of a cohort of COPD patients. In addition to calculation of the BODE index we register frequency of exacerbations. An analysis was made of all-cause mortality, evaluating the predictive capacity of the exacerbations after adjusting for the BODE. These variables were also used to construct two new indexes: e-BODE and BODEx. The study included 185 patients with a mean age of 71+/-9 years, and FEV(1)% 47+/-17%. Severe exacerbation appeared as an independent adverse prognostic variable of BODE index. For each new exacerbation the adjusted mortality risk increased 1.14-fold (95% CI: 1.04-1.25). However, the e-BODE index (C statistic: 0.77, 95% CI: 0.67-0.86) didn't improve prognostic capacity of BODE index (C statistic: 0.75, 95% CI: 0.66-0.84) (p=NS). An interesting finding was that BODEx index (C statistic: 0.74, 95% CI: 0.65-0.83) had similar prognostic capacity than BODE index. Severe exacerbations of COPD imply an increased mortality risk that is independent of baseline severity of the disease as measured by the BODE index. The combined application of both parameters (e-BODE index) didn't improve the predictive capacity, but on replacing exacerbation with exercise capacity the multidimensional grading system is simplified without loss of predictive capacity.
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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
                31 March 2020
                2020
                : 15
                : 681-690
                Affiliations
                [1 ]Pneumology Department, Hospital Universitari Vall d´Hebron/Vall d’Hebron Institut de Recerca (VHIR) , Barcelona, Spain
                [2 ]Medicine Department, Autonomous University of Barcelona (UAB) , Barcelona, Spain
                [3 ]Respiratory Unit, AOU Sassari , Sassari, Italy
                [4 ]Department of Pulmonary Diseases, University Medical Centre Ljubljana , Ljubljana, Slovenia
                [5 ]Department of Pulmonary Diseases, Medical Faculty, Medical University of Sofia , Sofia, Bulgaria
                [6 ]CIBER de Enfermedades Respiratorias (CIBERES) , Barcelona, Spain
                Author notes
                Correspondence: Marc Miravitlles Pneumology Department, Hospital Universitari Vall d´Hebron , P. Vall d’Hebron 119-129, Barcelona08035, SpainTel +34 934893000Fax +34 93 274 82 08 Email marcm@separ.es
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-4067-0466
                http://orcid.org/0000-0003-0297-7600
                http://orcid.org/0000-0002-9643-1934
                http://orcid.org/0000-0002-5896-9717
                http://orcid.org/0000-0003-2702-0311
                http://orcid.org/0000-0003-1457-8025
                http://orcid.org/0000-0002-9850-9520
                Article
                240720
                10.2147/COPD.S240720
                7127861
                32280207
                6bccb793-a2de-4477-8d39-0f48a88f8023
                © 2020 Nuñez 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
                : 01 December 2019
                : 10 March 2020
                Page count
                Figures: 2, Tables: 4, References: 48, Pages: 10
                Funding
                This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
                Categories
                Original Research

                Respiratory medicine
                copd,blood cells,biomarkers,exacerbation,phenotypes
                Respiratory medicine
                copd, blood cells, biomarkers, exacerbation, phenotypes

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