This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200604-506OCv1 174/8/867    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hurst, J. R. Articles by Wedzicha, J. A. Search for Related Content PubMed PubMed Citation Articles by Hurst, J. R. Articles by Wedzicha, J. A.

Use of Plasma Biomarkers at Exacerbation of Chronic Obstructive Pulmonary Disease

Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, London; GlaxoSmithKline Research and Development, Greenford, Middlesex, United Kingdom; and GlaxoSmithKline Research and Development, Upper Merion, Pennsylvania, and Research Triangle Park, North Carolina

Correspondence and requests for reprints should be addressed to Jadwiga A. Wedzicha, M.D., Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. E-mail: j.a.wedzicha{at}medsch.ucl.ac.uk

Impact: This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events.

Rationale: The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers.

Objective: To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity.

Methods: We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD.

Measurements and Main Results: To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66–0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82–0.93; p < 0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic–neutrophilic pathways.

Conclusions: Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.

Key Words: chronic obstructive pulmonary disease • exacerbation • inflammation

This article has been cited by other articles:

				W. T. McNicholas Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea: Overlaps in Pathophysiology, Systemic Inflammation, and Cardiovascular Disease Am. J. Respir. Crit. Care Med., October 15, 2009; 180(8): 692 - 700. [Abstract] [Full Text] [PDF]

				D. D. Sin and J. Vestbo Biomarkers in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, September 15, 2009; 6(6): 543 - 545. [Abstract] [Full Text] [PDF]

				D. A. Lomas, E. K. Silverman, L. D. Edwards, N. W. Locantore, B. E. Miller, D. H. Horstman, R. Tal-Singer, and on behalf of the Evaluation of COPD Longitudinally Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD Eur. Respir. J., July 1, 2009; 34(1): 95 - 102. [Abstract] [Full Text] [PDF]

				A. Lacoma, C. Prat, F. Andreo, and J. Dominguez Biomarkers in the management of COPD Eur. Respir. Rev., June 1, 2009; 18(112): 96 - 104. [Abstract] [Full Text] [PDF]

				D. A. Ngan, S. V. Vickerman, D. J. Granville, S. F. P. Man, and D. D. Sin The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease Therapeutic Advances in Respiratory Disease, June 1, 2009; 3(3): 113 - 129. [Abstract] [PDF]

				P. J. Barnes and B. R. Celli Systemic manifestations and comorbidities of COPD Eur. Respir. J., May 1, 2009; 33(5): 1165 - 1185. [Abstract] [Full Text] [PDF]

				S. F. P. Man, L. Xing, J. E. Connett, N. R. Anthonisen, R. A. Wise, D. P. Tashkin, X. Zhang, R. Vessey, T. G. Walker, B. R. Celli, et al. Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD? Eur. Respir. J., December 1, 2008; 32(6): 1451 - 1457. [Abstract] [Full Text] [PDF]

				Z. L. Borrill, K. Roy, and D. Singh Exhaled breath condensate biomarkers in COPD Eur. Respir. J., August 1, 2008; 32(2): 472 - 486. [Abstract] [Full Text] [PDF]

				D. Stolz, M. Christ-Crain, N. G. Morgenthaler, D. Miedinger, J. Leuppi, C. Muller, R. Bingisser, J. Struck, B. Muller, and M. Tamm Plasma Pro-Adrenomedullin But Not Plasma Pro-Endothelin Predicts Survival in Exacerbations of COPD Chest, August 1, 2008; 134(2): 263 - 272. [Abstract] [Full Text] [PDF]

				D. D. Sin and S. F. P. Man Biomarkers in COPD: Are We There Yet? Chest, June 1, 2008; 133(6): 1296 - 1298. [Full Text] [PDF]

				J. P. de Torres, V. Pinto-Plata, C. Casanova, H. Mullerova, E. Cordoba-Lanus, M. Muros de Fuentes, A. Aguirre-Jaime, and B. R. Celli C-Reactive Protein Levels and Survival in Patients With Moderate to Very Severe COPD Chest, June 1, 2008; 133(6): 1336 - 1343. [Abstract] [Full Text] [PDF]

				N. MacIntyre and Y. C. Huang Acute Exacerbations and Respiratory Failure in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2008; 5(4): 530 - 535. [Abstract] [Full Text] [PDF]

				M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers Eur. Respir. J., February 1, 2008; 31(2): 416 - 469. [Abstract] [Full Text] [PDF]

				S. Bozinovski, A. Hutchinson, M. Thompson, L. MacGregor, J. Black, E. Giannakis, A.-S. Karlsson, R. Silvestrini, D. Smallwood, R. Vlahos, et al. Serum Amyloid A Is a Biomarker of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., February 1, 2008; 177(3): 269 - 278. [Abstract] [Full Text] [PDF]

				M. K. Han, V. V. McLaughlin, G. J. Criner, and F. J. Martinez Pulmonary Diseases and the Heart Circulation, December 18, 2007; 116(25): 2992 - 3005. [Abstract] [Full Text] [PDF]

				J. A. Wedzicha and J. R. Hurst Structural and Functional Co-conspirators in Chronic Obstructive Pulmonary Disease Exacerbations Proceedings of the ATS, December 1, 2007; 4(8): 602 - 605. [Abstract] [Full Text] [PDF]

				E. F. M. Wouters, K. H. Groenewegen, M. A. Dentener, and J. H. J. Vernooy Systemic Inflammation in Chronic Obstructive Pulmonary Disease: The Role of Exacerbations Proceedings of the ATS, December 1, 2007; 4(8): 626 - 634. [Abstract] [Full Text] [PDF]

				F. J. Martinez Pathogen-directed Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, December 1, 2007; 4(8): 647 - 658. [Abstract] [Full Text] [PDF]

				G. Viegi, F. Pistelli, D. L. Sherrill, S. Maio, S. Baldacci, and L. Carrozzi Definition, epidemiology and natural history of COPD Eur. Respir. J., November 1, 2007; 30(5): 993 - 1013. [Abstract] [Full Text] [PDF]

				J. R. Hurst, G. Hagan, J. A. Wedzicha, and F. Frost Mechanism of Statin-Associated Mortality Reduction in COPD Chest, October 1, 2007; 132(4): 1409 - 1410. [Full Text] [PDF]

				V. Pinto-Plata, J. Toso, K. Lee, D. Park, J. Bilello, H. Mullerova, M. M De Souza, R. Vessey, and B. Celli Profiling serum biomarkers in patients with COPD: associations with clinical parameters Thorax, July 1, 2007; 62(7): 595 - 601. [Abstract] [Full Text] [PDF]

				K. F. Rabe, B. Beghe, F. Luppi, and L. M. Fabbri Update in Chronic Obstructive Pulmonary Disease 2006 Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1222 - 1232. [Full Text] [PDF]

				B. R. Celli and P. J. Barnes Exacerbations of chronic obstructive pulmonary disease Eur. Respir. J., June 1, 2007; 29(6): 1224 - 1238. [Abstract] [Full Text] [PDF]

				D. Stolz, M. Christ-Crain, N. G. Morgenthaler, J. Leuppi, D. Miedinger, R. Bingisser, C. Muller, J. Struck, B. Muller, and M. Tamm Copeptin, C-Reactive Protein, and Procalcitonin as Prognostic Biomarkers in Acute Exacerbation of COPD Chest, April 1, 2007; 131(4): 1058 - 1067. [Abstract] [Full Text] [PDF]

				M. N. Hylkema, P. J. Sterk, W. I. de Boer, and D. S. Postma Tobacco use in relation to COPD and asthma Eur. Respir. J., March 1, 2007; 29(3): 438 - 445. [Abstract] [Full Text] [PDF]

				J R Hurst and J A Wedzicha What is (and what is not) a COPD exacerbation: thoughts from the new GOLD guidelines Thorax, March 1, 2007; 62(3): 198 - 199. [Full Text] [PDF]

				B. Muller and M. Tamm Biomarkers in acute exacerbation of chronic obstructive pulmonary disease: among the blind, the one-eyed is king. Am. J. Respir. Crit. Care Med., October 15, 2006; 174(8): 848 - 849. [Full Text] [PDF]