Diagnostic value of biochemical ratios in the differential diagnosis of tuberculous and malignant pleural effusions

Our plain-English summary of Diagnostic value of biochemical ratios in the differential diagnosis of tuberculous and malignant pleural effusions, by U. İlhan, Z. Güney, A. Özçelik, et al (BMC Pulmonary Medicine, 2026).

The study

• Authors: U. İlhan, Z. Güney, A. Özçelik, H.S. Kaya, E. Cetinkaya, M. Çörtük
• Journal: BMC Pulmonary Medicine
• Published: 2026;26(1)
• Read it: PubMed · Publisher · Free full text

Abstract

Background And Objective: The differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in patients with pleural effusion (PE) continues to pose significant clinical challenges. While conventional pleural fluid cytology has limited sensitivity, invasive diagnostic procedures are often costly or inaccessible, particularly in resource-limited settings. In this study, we investigated the diagnostic contribution of ratios derived from pleural fluid adenosine deaminase (ADA), total protein, serum lactate dehydrogenase (S-LDH), and pleural effusion lactate dehydrogenase (PE-LDH) levels in patients with histopathological confirmed pleural effusion etiology. Specifically, the diagnostic performance of biochemical and hematological parameters, particularly the ADA/serum protein, S-LDH/ADA and PE-LDH/ADA ratios were evaluated for their ability to discriminate between TPE and MPE.

Methods: This retrospective cross-sectional study was conducted among patients who underwent diagnostic evaluation and treatment for pleural effusion at a tertiary referral hospital between 1 November 2014 and 1 November 2024. A total of 1,003 patients with pleural effusion (397 TPE and 606 MPE: 409 primary, 133 metastatic, and 64 mesothelioma) were included, whose etiologies were determined using a composite reference standard based on clinical, radiological, microbiological, and histopathological findings, with multidisciplinary team (MDT) evaluation applied in selected cases where appropriate. Receiver operating characteristic (ROC) curve analyses were performed to determine diagnostic accuracy, sensitivity, specificity, and optimal cut-off values.

Results: Patients with TPE were significantly younger than those with MPE (median age: 32 vs. 65 years, p < .001). Overall, 62.9% of the study population were male. ADA levels were significantly higher in the TPE group, whereas S-LDH levels were higher in the malignant effusion group. When ratio-based parameters were evaluated, the S-LDH/ADA ratio was markedly higher in patients with malignant pleural effusion and emerged as the most powerful discriminatory marker, with an area under the curve (AUC) of 0.938, sensitivity of 89.5%, and specificity of 91.3%. The ADA/serum protein ratio also demonstrated high diagnostic accuracy for differentiating TPE, with an AUC of 0.929, sensitivity of 89.9%, and specificity of 93.3%. In multivariate analysis, the S-LDH/ADA ratio, ADA/serum protein ratio, and PE-LDH/ADA ratio remained independently associated with diagnostic discrimination between TPE and MPE.

Conclusions: Biochemical ratios particularly the S-LDH/ADA and PE-ADA/serum protein ratios are reliable, minimally invasive diagnostic tools for distinguishing TPE from MPE. These ratios are especially useful in guiding clinical decision-making in settings where access to invasive diagnostic procedures is limited.

© 2026. The Author(s).

In plain English

This retrospective study, from a chest diseases hospital in Istanbul, Turkey, reviewed records of 1,003 adults with fluid around the lungs (pleural effusion) seen between 2014 and 2024. Of these, 397 had tuberculous effusion and 606 had malignant effusion (409 primary lung malignancy, 133 metastatic, 64 mesothelioma). The article does not discuss asbestos. The authors tested whether ratios of routine laboratory values could tell tuberculosis apart from cancer. The serum LDH to pleural ADA ratio gave an area under the curve of 0.938; at a cut-off of 11.14, sensitivity was 89.5% and specificity 91.3%. The ADA to serum protein ratio gave 0.929, with 89.95% sensitivity and 89.5% specificity at a cut-off of 0.305. In the mesothelioma group, pleural ADA was higher (median 12 U/L) than in the other cancer groups, and pleural glucose and pH were lower. The authors concluded that the ratios are reliable, minimally invasive tools. They cautioned that ADA was partly used to diagnose tuberculosis, which may have overstated accuracy, and that the mesothelioma group was small. Some figures differ between the article's text and its tables.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cross-sectional diagnostic accuracy study (ROC curve and logistic regression analyses) at a single center
• Who was studied: 1,003 adults with pleural effusion at a tertiary chest diseases hospital in Istanbul, Turkey, with records from November 2014 to November 2024. 397 had tuberculous pleural effusion and 606 had malignant pleural effusion: 409 primary lung malignancy, 133 metastatic malignancy, 64 mesothelioma.
• Exposure: Not an exposure study; asbestos is not mentioned. The tests examined were laboratory ratios: pleural ADA to serum protein, serum LDH to pleural ADA, and pleural LDH to pleural ADA, plus the neutrophil-to-lymphocyte ratio.
• Main results:
  • For tuberculous versus malignant effusion, the serum LDH to ADA ratio had an area under the curve of 0.938. At a cut-off of 11.14, sensitivity was 89.5% and specificity 91.3%.
  • The ADA to serum protein ratio had an area under the curve of 0.929 for distinguishing tuberculous effusions. At a cut-off of 0.305, sensitivity was 89.95% and specificity 89.5%.
  • The neutrophil-to-lymphocyte ratio showed limited diagnostic value: area under the curve 0.577, sensitivity 31.1%, specificity 84.7%.
  • Among the three cancer subgroups, pleural ADA was highest in the mesothelioma group (median 12 U/L).
  • Pleural glucose and pleural pH were significantly lower in patients with mesothelioma.
  • The mesothelioma group had the highest ADA to serum protein ratio (median 0.176) and significantly lower serum LDH to ADA and pleural LDH to ADA ratios.
  • In the multivariate model (tuberculous effusion against primary malignancy as reference), a higher ADA to serum protein ratio was associated with a higher likelihood of tuberculosis: adjusted OR 4.579, 95% CI 1.723 to 32.408.
  • In the same model, a higher serum LDH to pleural ADA ratio was associated with a lower probability of tuberculosis: adjusted OR 0.937, 95% CI 0.910 to 0.963.
• The authors' conclusion: The authors concluded that biochemical ratios, particularly the serum LDH to ADA and pleural ADA to serum protein ratios, are reliable, minimally invasive tools for distinguishing tuberculous from malignant pleural effusion.
• Limitations the authors state:
  • Pleural ADA was part of the reference standard used to diagnose tuberculosis and is also part of the tested ratios. This incorporation bias may have overestimated diagnostic performance.
  • ADA may also have indirectly influenced diagnoses made by multidisciplinary team evaluation.
  • The confidence interval for the ADA to serum protein ratio in the multivariate analysis was wide.
  • The mesothelioma subgroup was small (n = 64), which may limit statistical power.
  • The retrospective, single-center design may introduce bias and limit generalizability.
  • Differences between laboratories may affect how well the proposed cut-off values apply elsewhere.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Pleural Effusion, Fluid Cytology, Lactate Dehydrogenase (LDH), Etiology, Mesothelioma, Multidisciplinary Team, Multivariate Analysis.

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