Revisiting Light's criteria: a validated blood-free triple combination matches diagnostic accuracy in over 7000...

Light's criteria remain the standard for distinguishing exudative from transudative pleural effusions, but require serum sampling and lack specificity. We assessed whether a pleural fluid-only approach could match the diagnostic accuracy.

We analysed 7280 diagnostic thoracenteses from a single centre, divided into derivation (n=5000) and validation (n=2280) cohorts. We compared Light's criteria with a triple (protein >3 g·dL^-1, lactate dehydrogenase (LDH) >250 IU·L^-1 or cholesterol >55 mg·dL^-1) and a double (LDH >250 IU·L^-1 or cholesterol >55 mg·dL^-1) combination using sensitivity, specificity, likelihood ratios and area under the curve (AUC). AUCs were assessed using the DeLong method with multiple imputations from a mixed model. McNemar's test examined discordant classifications.

The triple combination showed no significant AUC difference versus Light's criteria in either cohort and had equivalent sensitivity (99% versus 98% in derivation; both 98% in validation). In the derivation cohort, McNemar's test showed a small but statistically significant excess of false negative exudates with the triple combination (p<0.001), whereas no significant difference was found in the validation cohort (p=0.241). The triple combination correctly reclassified 19-20% of transudates misclassified by Light's criteria, while the reverse occurred in 11-14%. The double combination yielded the highest AUCs but missed more exudates, limiting its clinical safety.

A pleural fluid-only triple combination matches Light's criteria in diagnostic accuracy, avoids serum sampling and improves specificity with minimal sensitivity loss in one cohort. This approach may be a practical alternative for the initial classification of pleural effusion when blood sampling is unavailable or undesirable.