Significance of Alpha-2-Macroglobulin, Alpha-1-Acid Glycoprotein, and C-Reactive Protein in Pleural Effusion Differentiation

Abstract

Background: The differentiation between exudates and transudates is fundamental when investigating the cause of pleural effusions. Acute-phase proteins could be potentially useful markers in this discrimination. Objective: The present study was designed to evaluate whether the acute-phase proteins: α₂-macroglobulin (AMG), α₁-acid glycoprotein (AAG) and C-reactive protein (CRP) are useful in investigating the pleural effusions. Methods: We prospectively measured the concentrations of the above proteins in the serum and pleural fluid of 84 consecutive patients with various diseases using a nephelometric assay. Results: Pleural effusion AMG, AAG and CRP were all significantly elevated in the group of patients with exudates compared to patients with transudates (p < 0.001, p < 0.001 and p < 0.01, respectively). An AAG value >63 mg/dl in a pleural effusion is predictive of an exudate with a sensitivity of 90% and a specificity 85%. Similarly, an AMG value >44 mg/dl in a pleural effusion is predictive of an exudate with a sensitivity and a specificity of 90% and 60%, respectively. Moreover, pleural AAG was significantly higher in cancerous exudates than in exudates and transudates of all other cause taken together (p < 0.001). Finally, to differentiate the same pleural effusion, the cut-off value of 1.0 mg/dl of pleural CRP has a sensitivity and a specificity of 74% and 74%, respectively. Conclusions: We conclude that both AAG and AMG concentrations in pleural effusions have a high sensitivity and are therefore useful parameters in distinguishing exudates from transudates, but the latter is inferior due to its unacceptably low specificity.

C-Reactive Protein in Lymphocytic Pleural Effusions: A Diagnostic Aid in Tuberculous Pleuritis

“…Previous studies on CRP in pleural fluid concluded that this parameter may differentiate transudates from exudates, but with worse results than those of classical tests [23,24,25]. In one study [23], the authors found that CRP levels were significantly higher in parapneumonic and tuberculous effusions, and our group [14] reported previously that in pleural exudates a CRP <20 mg/l suggests a malignant origin, whereas a level >45 mg/l virtually ruled out this possibility.…”

Diagnostic Work-Up of Pleural Effusions

“…There are a number of studies on various novel markers, such as acute phase proteins [55], oncogenes [56], cytokines involved in inflammation [57, 58], and matrix metalloproteinases [59], in the differential diagnosis between transudates and exudates and/or between malignant and benign pleural effusions. Although some may be adequate markers for pleural effusion differentiation, they are not as sensitive, specific, or cost- and time-efficient as the easily available standard tests [60].…”

Pleural Interleukin-1β in Differentiating Transudates and Exudates: Comparative Analysis with Other Biochemical Parameters

“…Several tumor markers and biochemical parameters have been proposed in an effort to improve the differential diagnosis of pleural effusion [12, 13, 14, 15, 16]. Some of them, such as cholesterol levels, seem to reflect the etiology of pleural infusions [13, 14, 15, 16, 17]. …”