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      External Validation Of The Updated ADO Score In COPD Patients From The Birmingham COPD Cohort

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          Abstract

          Background

          Reviews suggest that the ADO score is the most discriminatory prognostic score for predicting mortality among chronic obstructive pulmonary disease (COPD) patients, but a full evaluation and external validation within primary care settings is critical before implementation.

          Objectives

          To validate the ADO score in prevalent and screen-detected primary care COPD cases at 3 years and at shorter time periods.

          Patients and methods

          One thousand eight hundred and ninety-two COPD cases were recruited between 2012 and 2014 from 71 United Kingdom general practices as part of the Birmingham COPD Cohort study. Cases were either on the practice COPD register or screen-detected. We validated the ADO score for predicting 3-year mortality with 1-year and 2-year mortality as secondary endpoints using discrimination (area-under-the-curve (AUC)) and calibration plots.

          Results

          One hundred and fifty-four deaths occurred within 3 years. The ADO score was discriminatory for predicting 3-year mortality (AUC= 0.74; 95% CI: 0.69–0.79). Similar performance was found for 1- (AUC= 0.73; 0.66–0.80) and 2-year mortality (0.72; 0.67–0.76). The ADO score showed reasonable calibration for predicting 3-year mortality (calibration slope 0.95; 0.70–1.19) but over-predicted in cases with higher predicted risks of mortality at 1 (0.79; 0.45–1.13) and 2-year (0.79; 0.57–1.01) mortality.

          Discussion

          The ADO score showed promising discrimination in predicting 3-year mortality in a primary care population including screen-detected cases. It may need to be recalibrated if it is used to provide risk predictions for 1- or 2-year mortality since, in these time-periods, over-prediction was evident, especially in cases with higher predicted mortality risks.

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          Most cited references 22

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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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            Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine.

            Chronic obstructive pulmonary disease (COPD) is a complex disease at the clinical, cellular, and molecular levels. However, its diagnosis, assessment, and therapeutic management are based almost exclusively on the severity of airflow limitation. A better understanding of the multiple dimensions of COPD and its relationship to other diseases is very relevant and of high current interest. Recent theoretical (scale-free networks), technological (high-throughput technology, biocomputing), and analytical improvements (systems biology) provide tools capable of addressing the complexity of COPD. The information obtained from the integrated use of those techniques will be eventually incorporated into routine clinical practice. This review summarizes our current knowledge in this area and offers an insight into the elements needed to progress toward an integrated, multilevel view of COPD based on the novel scientific strategy of systems biology and its potential clinical derivative, P4 medicine (Personalized, Predictive, Preventive, and Participatory).
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              "GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"

              Background The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. Methods In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. Results Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. Conclusions GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.
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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
                24 October 2019
                2019
                : 14
                : 2395-2407
                Affiliations
                [1 ]Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham , Birmingham, UK
                [2 ]Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+ , Maastricht, the Netherlands
                [3 ]Ciro , Horn, the Netherlands
                [4 ]Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+ , Maastricht, The Netherlands
                [5 ]Utrecht Institute for Pharmaceutical Sciences Utrecht University , Utrecht, The Netherlands
                [6 ]NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham , Birmingham, UK
                [7 ]Clinical Trials Unit, Warwick Medical School, University of Warwick , Coventry, UK
                Author notes
                Correspondence: Rachel E Jordan Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham , Edgbaston, Birmingham, UKTel +44 0121 414 6775 Email r.e.jordan@bham.ac.uk
                Article
                212381
                10.2147/COPD.S212381
                6818100
                © 2019 Keene et al.

                This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 3, Tables: 2, References: 35, Pages: 13
                Categories
                Original Research

                Respiratory medicine

                pulmonary disease, chronic obstructive, mortality, prognosis, validation studies

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