A novel diagnostic method for distinguishing parapneumonic effusion and empyema from other diseases by using the pleural lactate dehydrogenase to adenosine deaminase ratio and carcinoembryonic antigen levels

Our plain-English summary of A novel diagnostic method for distinguishing parapneumonic effusion and empyema from other diseases by using the pleural lactate dehydrogenase to adenosine deaminase ratio and carcinoembryonic antigen levels, by T. Saraya, K. Ohkuma, T. Koide, et al (Medicine, 2019).

The study

• Authors: T. Saraya, K. Ohkuma, T. Koide, H. Goto, H. Takizawa, R.W. Light
• Journal: Medicine
• Published: 2019;98(13):e15003
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural effusions are a common medical problem not only for pulmonologists but also for general physicians, often needing thoracentesis for a definite diagnosis. However, thoracentesis cannot always reveal malignant cells or microbiological evidence.In this context, we prospectively enrolled a total of 289 patients with pleural effusions due to diverse etiologies: parapneumonic effusion (PPE) (63), empyema (22), tuberculous pleural effusion (TBPE) (54), malignant pleural effusion (MPE) (140), or chronic renal failure (CRF)/congestive heart failure (CHF) (10). The MPE group consisted of lung cancer (adenocarcinoma, n = 90; squamous cell carcinoma, n = 5; small cell carcinoma, n = 4), malignant lymphoma (n = 17), malignant mesothelioma (n = 11), malignant melanoma (n = 3), and metastasis from other organs (n = 10).This study demonstrated that the pleural lactate dehydrogenase (LDH)to adenosine deaminase (ADA) ratios differed significantly between patients with CHF/CRF, MPE, TBPE, empyema, and PPE. We discovered a simple method to differentiate pleural diseases based on the pleural LDH to ADA ratio and carcinoembryonic antigen (CEA). A pleural LDH to ADA ratio greater than 15.5 and a pleural CEA level of less than 5 ng/mL is indicative of PPE or empyema rather than TBPE, MPE, or transudative pleural effusion (CRF, CHF).This method has a sensitivity of 62.0%, a specificity of 91.0%, and an area under the receiver operating characteristic curve of 0.765 (95% confidence interval [CI]: 0678-0.852, P < .001), odds ratio of 16.6 (95% CI: 7.28-37.8, P < .001), a positive likelihood ratio (LR) of 6.8, and a negative LR of 0.02.

In plain English

This prospective study at Kyorin University Hospital in Tokyo enrolled 289 adults with fluid around the lungs (pleural effusion) between November 2012 and November 2016. These included 63 with parapneumonic effusion (fluid linked to pneumonia), 22 with empyema (infected fluid), 54 with tuberculous effusion, 140 with malignant effusion and 10 with chronic renal failure or heart failure. The malignant group included 11 people with malignant mesothelioma. The study did not examine asbestos exposure. The authors measured the fluid's ratio of two enzymes, LDH to ADA, and a tumor marker, CEA. The ratio differed significantly between the groups. It was highest in empyema (median 50.0) and parapneumonic effusion (median 35.4) and lowest in tuberculous effusion (median 5.1). Combining a ratio above 15.5 with CEA below 5 ng/mL identified parapneumonic effusion or empyema with a sensitivity of 62% and a specificity of 91%. The authors concluded that this combination can be an effective diagnostic tool alongside Light's criteria. They said it needs confirmation in larger studies and noted their small number of patients.

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: Prospective observational diagnostic study
• Who was studied: 289 adult patients with pleural effusion at Kyorin University Hospital, Tokyo, November 2012 to November 2016. Groups: parapneumonic effusion 63, empyema 22, tuberculous pleural effusion 54, malignant pleural effusion 140 (including malignant mesothelioma n=11), chronic renal failure/heart failure 10.
• Exposure: No asbestos or other environmental exposure was studied. The study evaluated pleural fluid markers: the LDH to ADA ratio and CEA levels, plus the amount of fluid on chest X-ray.
• Main results:
  • The pleural LDH to ADA ratio differed significantly between groups: chronic heart failure/chronic renal failure median 13.0, malignant pleural effusion 21.6, tuberculous pleural effusion 5.1, empyema 50.0, parapneumonic effusion 35.4.
  • The LDH to ADA ratio distinguished the parapneumonic effusion/empyema groups from the other groups with an area under the curve of 0.783 (95% CI 0.724–0.842, P=.03).
  • At a threshold of 15.5, the LDH to ADA ratio discriminated parapneumonic effusion/empyema from other causes with a sensitivity of 87.1% and a specificity of 49.5% (odds ratio 6.6, 95% CI 3.3–13.2).
  • Pleural CEA discriminated malignant pleural effusion from other diseases (AUC 0.806). At an optimal cut-off of 5.3 ng/mL, sensitivity was 81.1%, specificity 75% and positive likelihood ratio 3.24.
  • Combining an LDH to ADA ratio above 15.5 with CEA below 5 ng/mL differentiated empyema/parapneumonic effusion from other diseases with a sensitivity of 62% and a specificity of 91%. The article prints a positive likelihood ratio of 6.8, a negative likelihood ratio of 0.02 and an odds ratio of 16.6 (95% CI 7.28–37.8, P<.001).
  • Severe pleural effusion on chest X-ray was significantly more common in malignant pleural effusion (24.5%), empyema (31.8%) and parapneumonic effusion (25.4%) than in tuberculous pleural effusion (9.1%).
  • Combining the LDH to ADA ratio with the amount of effusion on chest X-ray discriminated empyema/parapneumonic effusion from other diseases much less well.
• The authors' conclusion: The authors concluded that combining the pleural LDH to ADA ratio with CEA levels can be an effective diagnostic tool in addition to Light's criteria, and that the result needs confirmation in future studies with more cases.
• Limitations the authors state:
  • A relatively small number of patients were included.
  • Only 25.9% (n=14) of tuberculous pleural effusion cases were confirmed by pathological or microbiological tests.

Topics

Medical terms in this study, explained in our Lexicon: Empyema, Lactate Dehydrogenase (LDH), Carcinoembryonic Antigen (CEA), Pleural Effusion, Thoracentesis, Lung Cancer, Adenocarcinoma, Squamous Cell Carcinoma.

Related studies

• Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels — T. Saraya, K. Ohkuma, et al. (2022)
• Diagnostic value of biochemical ratios in the differential diagnosis of tuberculous and malignant pleural effusions — U. İlhan, Z. Güney, et al. (2026)
• Adenosine Deaminase in Pleural Effusion and Its Relationship with Clinical Parameters in Patients with Malignant Pleural Mesothelioma — Y. Nakajima, K. Kuribayashi, et al. (2020)
• Lung surfactant protein-A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma — N. Shijubo, Y. Honda, et al. (1995)
• Adenosine deaminase inhibitor EHNA exhibits a potent anticancer effect against malignant pleural mesothelioma — Y. Nakajima, T. Kanno, et al. (2015)
• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)

Browse more research in Medicine, or return to medical research.