Share This Article:

Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease: Results from the Cosmic Study

Full-Text HTML Download Download as PDF (Size:425KB) PP. 63-72
DOI: 10.4236/ojrd.2012.23010    2,891 Downloads   6,225 Views   Citations

ABSTRACT

Objective: The study aims to elucidate the association of host-related factors on systemic inflammation in COPD patients. Methods: In 295 clinically stable and optimally treated COPD patients from 39 outpatient centers, age, gender, and body composition (body mass index, BMI; fat-free mass index, FFMI; fat mass index, FMI) were related to inflammatory biomarkers: CRP, fibrinogen, TNFα, and its soluble receptors (s)TNFαR1 and sTNFαR2. Furthermore, forced expiratory volume in the first second (FEV1), BMI, FFMI, and FMI were stratified by quartiles to elucidate the influence on inflammatory biomarkers. Monovariate and multivariate regression analyses were performed for associations between inflammatory biomarkers. Results: Positive correlations were found for FFMI with sTNFαR1, FMI with CRP and age with TNFα, sTNFαR1 and sTNFαR2 (p < 0.01). FEV1 was not correlated with body composition and inflammatory markers. Mono- and multivariate analysis showed weak correlations between the acute phase markers and the TNFα system after correcting for multiple co-variants. Conclusions: This study highlights the modest role of age and body composition on levels of systemic inflammatory biomarkers in COPD. Results show the degree of airflow limitation does not affect systemic inflammation. Last, a weak relationship between acute phase markers and markers of the TNFα system is present in COPD.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Breyer, E. Rutten, M. Spruit, W. Hop, D. Postma and E. Wouters, "Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease: Results from the Cosmic Study," Open Journal of Respiratory Diseases, Vol. 2 No. 3, 2012, pp. 63-72. doi: 10.4236/ojrd.2012.23010.

References

[1] K. F. Rabe, et al., “Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary,” American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 6, 2007, pp. 532-555. doi:10.1164/rccm.200703-456SO
[2] W. Q. Gan, et al., “Association between Chronic Obstructive Pulmonary Disease and Systemic Inflammation: A Systematic Review and a Meta-Analysis,” Thorax, Vol. 59, No. 7, 2004, pp. 574-580. doi:10.1136/thx.2003.019588
[3] J. H. Vernooy, et al., “Local and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease: Soluble Tumor Necrosis Factor Receptors Are Increased in Sputum,” American Journal of Respiratory and Critical Care Medicine, Vol. 166, No. 9, 2002, pp. 1218-1224. doi:10.1164/rccm.2202023
[4] M. A. Spruit, et al., “Muscle Force during an Acute Exacerbation in Hospitalised Patients with COPD and Its Relationship with CXCL8 and IGF-I,” Thorax, Vol. 58, No. 9, 2003, pp. 752-756. doi:10.1136/thorax.58.9.752
[5] M. Dahl, et al., “Elevated Plasma Fibrinogen Associated with Reduced Pulmonary Function and Increased Risk of Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 164, No. 6, 2001, pp. 1008-1011.
[6] D. G. Yanbaeva, et al., “IL6 and CRP Haplotypes Are Associated with COPD Risk and Systemic Inflammation: A Case-Control Study,” BMC Medical Genetics, Vol. 10, 2009, p. 23. doi:10.1186/1471-2350-10-23
[7] D. D. Sin and S. F. Man, “Why Are Patients with Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases? The Potential Role of Systemic Inflammation in Chronic Obstructive Pulmonary Disease,” Circulation, Vol. 107, No. 11, 2003, pp. 1514-1519. doi:10.1161/01.CIR.0000056767.69054.B3
[8] M. Dahl, et al., “C-Reactive Protein as a Predictor of Prognosis in Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 175, No. 3, 2007, pp. 250-255. doi:10.1164/rccm.200605-713OC
[9] S. F. Man, et al., “C-Reactive Protein and Mortality in Mild to Moderate Chronic Obstructive Pulmonary Disease,” Thorax, Vol. 61, No. 10, 2006, pp. 849-853. doi:10.1136/thx.2006.059808
[10] K. H. Groenewegen, et al., “Increased Systemic Inflammation Is a Risk Factor for COPD Exacerbations,” Chest, Vol. 133, No. 2, 2008, pp. 350-357. doi:10.1378/chest.07-1342
[11] P. D. Wagner, “Possible Mechanisms Underlying the Development of Cachexia in COPD,” European Respiratory Journal, Vol. 31, No. 3, 2008, pp. 492-501. doi:10.1183/09031936.00074807
[12] L. G. Franciosi, et al., “Markers of Disease Severity in Chronic Obstructive Pulmonary Disease,” Pulmonary Pharmacology & Therapeutics, Vol. 19, No. 3, 2006, pp. 189199. doi:10.1016/j.pupt.2005.05.001
[13] M. K. Breyer, et al., “Highly Elevated C-Reactive Protein Levels in Obese Patients with COPD: A Fat Chance?” Clinical Nutrition, Vol. 28, No. 6, 2009, pp. 642-647. doi:10.1016/j.clnu.2009.05.005
[14] D. D. Sin and S. F. Man, “Impaired Lung Function and Serum Leptin in Men and Women with Normal Body Weight: A Population Based Study,” Thorax, Vol. 58, No. 8, 2003, pp. 695-698. doi:10.1136/thorax.58.8.695
[15] E. F. Wouters, E. C. Creutzberg and A. M. Schols, “Systemic Effects in COPD,” Chest, Vol. 121, No. 5, 2002, pp. 127S-130S. doi:10.1378/chest.121.5_suppl.127S
[16] E. F. Wouters, et al., “Withdrawal of Fluticasone Propionate from Combined Salmeterol/Fluticasone Treatment in Patients with COPD Causes Immediate and Sustained Disease Deterioration: A Randomised Controlled Trial,” Thorax, Vol. 60, No. 6, 2005, pp. 480-487. doi:10.1136/thx.2004.034280
[17] M. A. Vermeeren, et al., “Prevalence of Nutritional Depletion in a Large Out-Patient Population of Patients with COPD,” Respiratory Medicine, Vol. 100, No. 8, 2006, pp. 1349-1355. doi:10.1016/j.rmed.2005.11.023
[18] J. F. Leeuwenberg, M. A. Dentener and W. A. Buurman, “Lipopolysaccharide LPS-Mediated Soluble TNF Receptor Release and TNF Receptor Expression by Monocytes. Role of CD14, LPS Binding Protein, and Bactericidal/ Permeability-Increasing Protein,” Journal of Immunology, Vol. 152, No. 10, 1994, pp. 5070-5076.
[19] M. Cazzola, et al., “Outcomes for COPD Pharmacological Trials: From Lung Function to Biomarkers,” European Respiratory Journal, Vol. 31, No. 2, 2008, pp. 416469. doi:10.1183/09031936.00099306
[20] T. M. Eagan, et al., “Body Composition and Plasma Levels of Inflammatory Biomarkers in COPD,” European Respiratory Journal, Vol. 36, No. 5, 2010, pp. 1027-1033. doi:10.1183/09031936.00194209
[21] V. Pinto-Plata, et al., “Profiling Serum Biomarkers in Patients with COPD: Associations with Clinical Parameters,” Thorax, Vol. 62, No. 7, 2007, pp. 595-601. doi:10.1136/thx.2006.064428
[22] J. C. Hogg, et al., “The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease,” New England Journal of Medicine, Vol. 350, No. 26, 2004, pp. 2645-2653. doi:10.1056/NEJMoa032158
[23] D. Singh, et al., “Induced Sputum Genes Associated with Spirometric and Radiological Disease Severity in COPD Ex-Smokers,” Thorax, Vol. 66, No. 6, 2011, pp. 489-495. doi:10.1136/thx.2010.153767
[24] N. Takabatake, et al., “The Relationship between Chronic Hypoxemia and Activation of the Tumor Necrosis Factor-Alpha System in Patients with Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 161, No. 4, 2000, pp. 1179-1184.
[25] F. Licastro, et al., “Innate Immunity and Inflammation in Ageing: A Key for Understanding Age-Related Diseases,” Immunity and Ageing, Vol. 2, 2005, p. 8. doi:10.1186/1742-4933-2-8
[26] M. Provinciali, M. Cardelli and F. Marchegiani, “Inflammation, Chronic Obstructive Pulmonary Disease and Aging,” Current Opinion in Pulmonary Medicine, Vol. 17, No. 1, 2011, pp. S3-S10. doi:10.1097/01.mcp.0000410742.90463.1f
[27] H. Bruunsgaard and B. K. Pedersen, “Age-Related Inflammatory Cytokines and Disease,” Immunology and Allergy Clinics of North American, Vol. 23, No. 1, 2003, pp. 15-39. doi:10.1016/S0889-8561(02)00056-5
[28] A. R. Folsom, “Epidemiology of Fibrinogen,” European Heart Journal, Vol. 16, No. A, 1995, pp. 21-24.
[29] A. Fu and K. S. Nair, “Age Effect on Fibrinogen and Albumin Synthesis in Humans,” American Journal of Physiology, Vol. 275, No. 6, 1998, pp. E1023-E1030.
[30] M. K. Breyer, et al., “Gender Differences in the Adipose Secretome System in Chronic Obstructive Pulmonary Disease (COPD): A Pivotal Role of Leptin,” Respiratory Medicine, Vol. 105, No. 7, 2011, pp. 1046-1053. doi:10.1016/j.rmed.2011.02.001
[31] G. Fantuzzi, “Adipose Tissue, Adipokines, and Inflammation,” Journal of Allergy and Clinical Immunology, Vol. 115, No. 5, 2005, pp. 911-920. doi:10.1016/j.jaci.2005.02.023
[32] P. O. Bridevaux, et al., “Sex-Specific Effect of Body Weight Gain on Systemic Inflammation in Subjects with COPD: Results from the SAPALDIA Cohort Study 2,” European Respiratory Journal, Vol. 34, No. 2, 2009, pp. 332-339. doi:10.1183/09031936.00162608
[33] J. P. de Torres, et al., “Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study,” PLoS One, Vol. 6, No. 1, 2011, Article ID e16021. doi:10.1371/journal.pone.0016021
[34] J. Crofton and K. Bjartveit, “Smoking as a Risk Factor for Chronic Airways Disease,” Chest, Vol. 96, No. 3, 1989, pp. 307S-312S. doi:10.1378/chest.96.3.307S
[35] P. Boyle, “Cancer, Cigarette Smoking and Premature Death in Europe: A Review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996,” Lung Cancer, Vol. 17, No. 1, 1997, pp. 1-60. doi:10.1016/S0169-5002(97)00648-X
[36] A. Agusti, et al., “Characterisation of COPD Heterogeneity in the ECLIPSE Cohort,” Respiratory Research, Vol. 11, 2010, p. 122.
[37] W. B. Kannel, R. B. D’Agostino and A. J. Belanger, “Fibrinogen, Cigarette Smoking, and Risk of Cardiovascular Disease: Insights from the Framingham Study,” American Heart Journal, Vol. 113, No. 4, 1987, pp. 1006-1010. doi:10.1016/0002-8703(87)90063-9
[38] L. A. Bazzano, et al., “Relationship between Cigarette Smoking and Novel Risk Factors for Cardiovascular Disease in the United States,” Annals of Internal Medicine, Vol. 138, No. 11, 2003, pp. 891-897.
[39] J. Heinrich, et al., “Fibrinogen and Factor VII in the Prediction of Coronary Risk. Results from the PROCAM Study in Healthy Men,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 14, No. 1, 1994, pp. 54-59. doi:10.1161/01.ATV.14.1.54
[40] S. G. Wannamethee, et al., “Associations between Cigarette Smoking, Pipe/Cigar Smoking, and Smoking Cessation, and Haemostatic and Inflammatory Markers for Cardiovascular Disease,” European Heart Journal, Vol. 26, No. 17, 2005, pp. 1765-1773. doi:10.1093/eurheartj/ehi183
[41] P. H. Wirtz, et al., “Enhanced Glucocorticoid Sensitivity of Cytokine Release from Circulating Leukocytes Stimulated with Lipopolysaccharide in Healthy Male Smokers,” Brain, Behavior, and Immunity, Vol. 18, No. 6, 2004, pp. 536-543. doi:10.1016/j.bbi.2004.01.002
[42] M. L. Gander, et al., “Effect of the G-308A Polymorphism of the Tumor Necrosis Factor (TNF)-Alpha Gene Promoter Site on Plasma Levels of TNF-Alpha and CReactive Protein in Smokers: A Cross-Sectional Study,” BMC Cardiovascular Disorders, Vol. 4, No. , 2004, p. 17. doi:10.1186/1471-2261-4-17
[43] D. Stolz, et al., “Copeptin, C-Reactive Protein, and Procalcitonin as Prognostic Biomarkers in Acute Exacerbation of COPD,” Chest, Vol. 131, No. 4, 2007, pp. 10581067. doi:10.1378/chest.06-2336
[44] C. E. Bolton, et al., “Associated Loss of Fat-Free Mass and Bone Mineral Density in Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 170, No. 12, 2004, pp. 1286-1293. doi:10.1164/rccm.200406-754OC
[45] N. Takabatake, et al., “Circulating Leptin in Patients with Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 159, No. 4, 1999, pp. 1215-1219.
[46] S. Yende, et al., “Inflammatory Markers Are Associated with Ventilatory Limitation and Muscle Dysfunction in Obstructive Lung Disease in Well Functioning Elderly Subjects,” Thorax, Vol. 61, No. 1, 2006, pp. 10-16. doi:10.1136/thx.2004.034181
[47] K. Ito and P. J. Barnes, “COPD as a Disease of Accelerated Lung Aging,” Chest, Vol. 135, No. 1, 2009, pp. 173180. doi:10.1378/chest.08-1419
[48] A. A. Eid, et al., “Inflammatory Response and Body Composition in Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 164, No. 8, 2001, pp. 1414-1418.
[49] H. A. Van Helvoort, et al., “Exercise-Induced Systemic Effects in Muscle-Wasted Patients with COPD,” Medicine & Science in Sports & Exercise, Vol. 38, No. 9, 2006, pp. 1543-1552. doi:10.1249/01.mss.0000228331.13123.53
[50] H. van der Vaart, et al., “First Study of Infliximab Treatment in Patients with Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 4, 2005, pp. 465-469. doi:10.1164/rccm.200501-147OC
[51] M. J. Loza, et al., “Systemic Inflammatory Profile and Response to Anti-Tumor Necrosis Factor Therapy in Chronic Obstructive Pulmonary Disease,” Respiratory Research, Vol. 13, No. 1, 2012, p. 12. doi:10.1186/1465-9921-13-12
[52] U. Kolsum, et al., “The Repeatability of Interleukin-6, Tumor Necrosis Factor-Alpha, and C-Reactive Protein in COPD Patients over One Year,” International Journal of Chronic Obstructive Pulmonary Disease, Vol. 4, 2009, pp. 149-156. doi:10.2147/COPD.S5018
[53] B. K. Pedersen and H. Bruunsgaard, “Possible Beneficial Role of Exercise in Modulating Low-Grade Inflammation in the Elderly,” Scandinavian Journal of Medicine & Science in Sports, Vol. 13, No. 1, 2003, pp. 56-62. doi:10.1034/j.1600-0838.2003.20218.x

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.