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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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      FEV 1 is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease

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          Abstract

          Purpose

          Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations. However, it is unclear if forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) differ in predictive value.

          Patients and Methods

          Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV 1 %predicted, FVC %predicted, FEV 1/FVC). The four highest quintiles (Q2–Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.

          Results

          Compared to Q1 (<53.5% FEV 1 predicted), increasing FEV 1 quintiles (Q2 53.5–457.5% predicted, Q3 57.5–461.6% predicted, Q4 61.6–465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4–34%), 28% (13–40%), 23% (7–36%), and 30% (15–42%) risk reduction, respectively). In contrast, a significant risk reduction (21% (4–35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV 1 nor FVC was associated with cardiovascular risk. Increased FEV 1 and FEV 1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8–52%) risk increase).

          Conclusion

          Our results suggest that FEV 1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.

          Most cited references18

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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.

            Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.
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              Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial

              Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk.
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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
                20 May 2020
                2020
                : 15
                : 1135-1142
                Affiliations
                [1 ]Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester, UK
                [2 ]Division of Infection, Immunity & Respiratory Medicine, University of Manchester , Manchester, UK
                [3 ]Medical Department, Herlev and Gentofte Hospital , Herlev, Denmark
                [4 ]Section of Epidemiology, Department of Public Health, University of Copenhagen , Copenhagen, Denmark
                [5 ]Research & Development, GlaxoSmithKline , Middlesex, UK
                [6 ]University of Michigan Health System , Ann Arbor, MI, USA
                [7 ]University of Liverpool, Department of Medicine, Clinical Sciences Centre, University Hospital Aintree , Liverpool, UK
                [8 ]Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA, USA
                [9 ]Statistics & Programming, Veramed Ltd ., Twickenham, UK
                [10 ]Research & Development, GlaxoSmithKline , Research Triangle Park, NC, USA
                [11 ]Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine , New York, NY, USA
                [12 ]British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh , Edinburgh, UK
                Author notes
                Correspondence: Andras Bikov 2nd Floor ERC Building, Wythenshawe Hospital, Southmoor Road, ManchesterM23 9LT, UKTel +36203141599Fax +441612915730 Email andras.bikov@gmail.com
                Author information
                http://orcid.org/0000-0003-0401-0081
                http://orcid.org/0000-0003-1313-9725
                http://orcid.org/0000-0002-3391-2490
                http://orcid.org/0000-0002-2412-3182
                http://orcid.org/0000-0001-6355-6362
                Article
                242809
                10.2147/COPD.S242809
                7247606
                32547001
                6a81a109-2a0e-4d70-9e92-1fb1c1b652d7
                © 2020 Bikov 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
                : 18 December 2019
                : 20 April 2020
                Page count
                Figures: 1, Tables: 2, References: 29, Pages: 8
                Funding
                This study was funded by GlaxoSmithKline plc (HZC113782/NCT01313676).
                Categories
                Original Research

                Respiratory medicine
                airflow limitation,cardiovascular risk,exacerbation,lung function,lung volumes,death rate

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