Pleural protein capillary electrophoresis for the separation of transudates and exudates.

To the Editor: Categorization of pleural effusions as transudates or exudates assists diagnostic and therapeutics decisions. To meet the criteria of Light et al. (1 ) for exudates, an effusion must have at least one of the following: a ratio of pleural fluid (PF) protein to serum protein .0.5, a ratio of PF to serum lactic dehydrogenase (LD) .0.6, and PF LD more than two-thirds the upper limit of normal for serum LD. Numerous studies have examined the diagnostic accuracy of these criteria, which misdiagnose 10–30% of transudates as exudates (2, 3). Recently in this Journal, Chen and Lam (4 ) reported that qualitative protein zone electrophoresis is more sensitive (100% vs 95%) and specific (50% vs 38%) than the criteria of Light et al. (1 ) in a study of 51 patient samples (8 transudates and 43 exudates). Moreover, when quantitative analysis was performed, the PF a2globulin:albumin ratio at the best cutoff point (0.28) showed a sensitivity and specificity of 85% and 80%, respectively. To determine whether protein capillary electrophoresis rather than protein zone electrophoresis meets the accuracy of the criteria of Light et al. (1 ), we prospectively studied 116 adult patients with pleural effusions over a 1-year period. On the basis of predetermined clinical criteria (2–4), there were 29 transudates (25 heart failure, 3 liver cirrhosis, 1 hypoalbuminemia) and 87 exudates (30 malignant, 26 parapneumonic, 19 tuberculous, and 12 miscellaneous). LD and protein in both PF and serum were measured on a selective discrete multichannel analyzer (Hitachi 917). Protein capillary electrophoresis of PF was performed with a Paragon CZE 2000 (Beckman). By the Student t-test, no differences were found between transudates and exudates in the mean percentages of PF a1-, b-, and g-globulin fractions. In contrast, albumin, a2globulins, and the a2-globulin:albumin ratio were significantly different between transudates and exudates. We therefore used a nonparametric ROC analysis (SPSS 9.0 statistical software) where test thresholds were selected for the highest overall diagnostic accuracy. Table 1 shows the diagnostic accuracy of the different tests for identifying exudative pleural effusions compared with the performance of the criteria of Light et al. (1 ). After we excluded PF albumin for its low accuracy, the confidence intervals suggest that no differences exist among the remaining tests. We analyzed the misclassified effusions for each test. Three malignant exudates were misclassified as transudates by the criteria of Light et al. (of which two were correctly classified by the alternative tests). There was a good explanation for two of the “transudates” cytologically confirmed to be malignant in the face of atelectasis and heart failure, but the third patient died prematurely, precluding evaluation of potential causes. Notably, 16 and 12 exudates were falsely classified by the PF a2globulins and the PF a2-globulin:albumin ratio, respectively, including 7 malignant effusions for which no alternative cause could be determined. Thus, we feel that these alternative criteria may provide clinicians false reassurance when evaluating patients with “transudative” effusions. To recommend new tests on the basis of their higher specificity compared with the criteria of Light et al. fails to recognize that multiple tests combined in “or” rules [e.g., the criteria of Light et al. (1 )] always have a higher sensitivity but lower specificity compared with noncombination single tests when each of the test components of the combination and the new single test have similar discriminative properties (5 ). We believe that the criteria of Light et al. (1 ) continue to be the most practical method of separating exudates from transudates.