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      COPD and stroke: are systemic inflammation and oxidative stress the missing links?

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          Abstract

          Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress.

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          Most cited references128

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          Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

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            Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis.

            Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular diseases, osteoporosis, and muscle wasting. Systemic inflammation may be involved in the pathogenesis of these disorders. A study was undertaken to determine whether systemic inflammation is present in stable COPD. A systematic review was conducted of studies which reported on the relationship between COPD, forced expiratory volume in 1 second (FEV(1)) or forced vital capacity (FVC), and levels of various systemic inflammatory markers: C-reactive protein (CRP), fibrinogen, leucocytes, tumour necrosis factor-alpha (TNF-alpha), and interleukins 6 and 8. Where possible the results were pooled together to produce a summary estimate using a random or fixed effects model. Fourteen original studies were identified. Overall, the standardised mean difference in the CRP level between COPD and control subjects was 0.53 units (95% confidence interval (CI) 0.34 to 0.72). The standardised mean difference in the fibrinogen level was 0.47 units (95% CI 0.29 to 0.65). Circulating leucocytes were also higher in COPD than in control subjects (standardised mean difference 0.44 units (95% CI 0.20 to 0.67)), as were serum TNF-alpha levels (standardised mean difference 0.59 units (95% CI 0.29 to 0.89)). Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.
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              Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.

              Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.
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                Author and article information

                Journal
                Clin Sci (Lond)
                Clin. Sci
                ppclinsci
                CS
                Clinical Science (London, England : 1979)
                Portland Press Ltd.
                0143-5221
                1470-8736
                23 May 2016
                1 July 2016
                : 130
                : 13 ( displayID: 13 )
                : 1039-1050
                Affiliations
                [* ]School of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC 3083, Australia
                []Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia
                []Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia
                Author notes
                [1]

                These authors contributed equally.

                Correspondence: Ross Vlahos (email ross.vlahos@ 123456rmit.edu.au ).
                Article
                CS20160043
                10.1042/CS20160043
                4876483
                27215677
                fd94d49f-9f62-4de2-be3e-70349467c8ab
                © 2016 The Author(s)

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY-NC-ND).

                History
                : 18 January 2016
                : 19 February 2016
                : 7 March 2016
                Page count
                Figures: 1, References: 177, Pages: 12
                Categories
                Review Articles
                Review Article
                S47
                S46
                S40

                Medicine
                cardiovascular disease,chronic obstructive pulmonary disease (copd),comorbidities,oxidative stress,stroke,systemic inflammation

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