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      International Journal of COPD (submit here)

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      Smokers with COPD Show a Shift in Energy and Nitrogen Metabolism at Rest and During Exercise

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          Abstract

          Purpose

          There is an ongoing demand for easily accessible biomarkers that reflect the physiological and pathophysiological mechanisms of COPD. To test if an exercise challenge could help to identify clinically relevant metabolic biomarkers in COPD.

          Patients and Methods

          We performed two constant-load exercise challenges separated by 4 weeks including smokers with COPD (n=23/19) and sex- and age-matched healthy smokers (n=23/20). Two hours after a standardized meal venous blood samples were obtained before, 5 mins after the start, at the end of submaximal exercise, and following a recovery of 20 mins. Data analysis was performed using mixed- effects model, with the metabolite level as a function of disease, time point and interaction terms and using each individual's resting level as reference.

          Results

          Exercise duration was longer in healthy smokers but lactate levels were comparable between groups at all four time points. Glucose levels were increased in COPD. Glutamine was lower, while glutamate and arginine were higher in COPD. Branched-chain amino acids showed a stronger decline during exercise in healthy smokers. Carnitine and the acyl-carnitines C16 and C18:1 were increased in COPD. These metabolite levels and changes were reproducible in the second challenge.

          Conclusion

          Higher serum glucose, evidence for impaired utilization of amino acids during exercise and a shift of energy metabolism to enhanced consumption of lipids could be early signs for a developing metabolic syndrome in COPD. In COPD patients, deviations of energy and nitrogen metabolism are amplified by an exercise challenge.

          Most cited references31

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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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            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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              Metabolic regulation of inflammation

              The need for energy permeates every aspect of the life of immune cells, being especially important during periods of transition and differentiation such as during inflammation. In this Review, the authors provide an overview of the processes and pathways involved in immunometabolism.
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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
                06 January 2020
                2020
                : 15
                : 1-13
                Affiliations
                [1 ]Fraunhofer ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research , Hannover, Germany
                [2 ]Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research , Hannover, Germany
                [3 ]Department of Biomarker Development, Takeda Pharmaceuticals International GmbH , Zürich, Switzerland
                [4 ]Biocrates Life Sciences AG , Innsbruck, Austria
                [5 ]Research Group for Clinical Bioinformatics, Private University for Health Sciences, Medical Informatics and Technology , Hall in Tirol, Austria
                [6 ]sAnalytiCo Ltd , Belfast, Ireland
                [7 ]Department of Biochemistry, ALTANA , Konstanz, Germany
                Author notes
                Correspondence: Olaf Holz Department of Clinical Airway Research, Fraunhofer ITEM , Hannover30625, GermanyTel +49-511-5350-8141Fax +49-511-5350-8250 Email olaf.holz@item.fraunhofer.de
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-0665-7807
                http://orcid.org/0000-0002-0141-9116
                http://orcid.org/0000-0002-8947-5306
                http://orcid.org/0000-0003-2646-6186
                Article
                217474
                10.2147/COPD.S217474
                6956026
                0eb926c0-679f-4a3d-afdc-d52cf743c6b9
                © 2020 Holz 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
                : 28 May 2019
                : 21 November 2019
                Page count
                Figures: 5, Tables: 2, References: 44, Pages: 13
                Funding
                Fraunhofer has received a research grant for conducting the study from Nycomed GmbH. Nycomed employees participated in study design, and in data analysis (SR, CS). OH, DSD, JMH were supported by the German Center for Lung Research.
                Categories
                Original Research

                Respiratory medicine
                targeted metabolomics,biomarker,airway inflammation
                Respiratory medicine
                targeted metabolomics, biomarker, airway inflammation

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