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      C-reactive protein correlates with tissue oxygen availability in patients with stable COPD

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          Abstract

          Background

          Arterial oxygen tension, oxygen delivery to tissue, and systemic inflammation are recognized as pivotal factors in the progression of chronic obstructive pulmonary disease (COPD). However, interconnections between systemic inflammation and tissue oxygen availability are scantly investigated. Tissue oxygen availability depends on arterial PaO 2, oxygen concentration, hemoglobin oxygen affinity (P 50), and hemoglobin oxygen binding capacity ( ceHb). As the integrated changes of those indices are summarized by oxygen extraction tension (PaO 2x), the objective of this study was to explore the association between C-reactive protein (CRP) blood levels and either PaO 2x or each of its determinants, in stable COPD.

          Materials and methods

          Blood CRP and oxygen status of arterial blood were measured at rest while breathing room air in 44 moderate to severe stable COPD patients. PaO 2x was calculated along the shape of oxygen binding curve as the oxygen tension resulting from removal of 2.3 mmol of oxygen per liter of blood. Multiple linear regression analysis was performed with PaO 2, ceHb, and P 50 as independent variables, and CRP as the dependent variable, adjusting for age and sex. The analysis was repeated using PaO 2x as a sole independent variable.

          Results

          Multiple linear regression analysis indicated that ceHb, PaO 2, and P 50, were significant and independent predictors of CRP (R 2 = 0.52, p < 0.0001). PaO 2x alone was an even stronger predictor of CRP (R 2 = 0.62, p < 0.0001).

          Conclusions

          These findings indicate that physiological determinants of tissue oxygen availability are independently associated with CRP blood levels. Thus, improvement of tissue oxygen availability is a central therapeutic option to modulate the severity of systemic inflammatory processes in patients with COPD.

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          Most cited references 31

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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.

           ,  Suzanne Hurd,  P Calverley (2001)
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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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              HIF-1: mediator of physiological and pathophysiological responses to hypoxia.

              All organisms can sense O(2) concentration and respond to hypoxia with adaptive changes in gene expression. The large body size of mammals necessitates the development of multiple complex physiological systems to ensure adequate O(2) delivery to all cells under normal conditions. The transcriptional regulator hypoxia-inducible factor 1 (HIF-1) is an essential mediator of O(2) homeostasis. HIF-1 is required for the establishment of key physiological systems during development and their subsequent utilization in fetal and postnatal life. HIF-1 also appears to play a key role in the pathophysiology of cancer, cardiovascular disease, and chronic lung disease, which represent the major causes of mortality among industrialized societies. Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                December 2008
                December 2008
                : 3
                : 4
                : 745-751
                Affiliations
                [1 ] Department of Pneumology and Biomedical Engineering, Scientific Institute of Montescano, Salvatore Maugeri Foundation IRCCS, Pavia, Italy
                [2 ] Respiratory Pathophysiology Unit, Clinical Medicine Department, “La Sapienza” University, Rome, Italy
                Author notes
                Correspondence: Baldi Simonetta, U.O di Riabilitazione Specialistica – Pneumologia Riabilitativa, Istituto Scientifico di Montescano, Fondazione Salvatore Maugeri IRCCS, Via per Montescano, 31, 27040 Montescano (Pavia) Italy, Tel +39 0385 247227, Fax +39 0385 61386, Email simonetta.baldi@ 123456fsm.it
                Article
                copd-3-745
                2650602
                19281089
                © 2008 Dove Medical Press Limited. All rights reserved
                Categories
                Original Research

                Respiratory medicine

                systemic inflammation, copd, oxygen extractivity, c-reactive protein

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