+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Persistent Systemic Inflammation is Associated with Poor Clinical Outcomes in COPD: A Novel Phenotype

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).

          Methods and Findings

          Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p<0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.


          Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

          Related collections

          Most cited references 45

          • Record: found
          • Abstract: found
          • Article: not found

          Points of control in inflammation.

           Carl Nathan (2015)
          Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.
            • Record: found
            • Abstract: found
            • Article: not found

            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.
              • Record: found
              • Abstract: not found
              • Article: not found

              The global burden of disease, 1990-2020.


                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                18 May 2012
                : 7
                : 5
                [1 ]Thorax Institute, Hospital Clinic, Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona and Centro de investigación en red de enfermedades respiratorias (CIBERES), Barcelona, Spain
                [2 ]Fundación Investigación Sanitaria Illes Balears (FISIB), Palma de Mallorca, Spain
                [3 ]GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America
                [4 ]University of Nebraska Medical Center, Omaha, Nebraska, United States of America
                [5 ]University of Edinburgh, Edinburgh, UK
                [6 ]GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America
                [7 ]Respiratory Section, Hvidovre Hospital/University of Copenhagen, Denmark
                [8 ]Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
                [9 ]University of Cambridge, Cambridge, UK
                [10 ]University of Liverpool, Liverpool, UK
                [11 ]University of Maastricht, Maastricht, The Netherlands
                [12 ]Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
                [13 ]University of British Columbia, Vancouver, Canada
                [14 ]University of Bergen, Bergen, Norway
                Clinica Universidad de Navarra, Spain
                Author notes

                Conceived and designed the experiments: AA LDE SIR WM RT-S BEM JV DAL PMAC EW CC JCY EKS HOC PB RJM BC. Performed the experiments: AA SIR WM JV DAL PMAC EW EKS HOC PB BC. Analyzed the data: AA LDE SIR WM RT-S BEM JV DAL PMAC EW CC JCY EKS HOC PB RJM BC. Wrote the paper: AA LDE SIR WM RT-S BEM JV DAL PMAC EW CC JCY EKS HOC PB RJM BC.

                Agustí et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 10
                Research Article
                Anatomy and Physiology
                Immune Physiology
                Immune System
                Clinical Immunology
                Diagnostic Medicine
                General Pathology
                Biomarker Epidemiology
                Chronic Obstructive Pulmonary Diseases



                Comment on this article