Use of Plasma Biomarkers at Exacerbation of Chronic Obstructive Pulmonary Disease

• Published in: American journal of respiratory and critical care medicine Vol. 174; no. 8; pp. 867 - 874
• Main Authors: Hurst, John R, Donaldson, Gavin C, Perera, Wayomi R, Wilkinson, Tom M. A, Bilello, John A, Hagan, Gerry W, Vessey, Rupert S, Wedzicha, Jadwiga A
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.10.2006; American Lung Association; American Thoracic Society
• Subjects: Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers - blood; C-Reactive Protein - metabolism; Chronic obstructive pulmonary disease, asthma; Follow-Up Studies; Humans; Intensive care medicine; Medical sciences; Pneumology; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Severity of Illness Index; Lung disease; Intensive care; Respiratory disease; Chronic disease; Bronchus disease; Inflammation; Obstructive pulmonary disease; Resuscitation; chronic obstructive pulmonary disease; exacerbation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200604-506OC

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