Maranhão BHF, Junior CTDS, Barillo JL, Souza JBS, Silva PS, Stirbulov R. Total adenosine deaminase cases as an inflammatory biomarker of pleural effusion syndrome. World J Clin Cases 2025; 13(19): 101850 [DOI: 10.12998/wjcc.v13.i19.101850]
Corresponding Author of This Article
Cyro Teixeira da Silva Junior, MD, PhD, Full Professor, Medical Clinics, Federal Fluminense University, 13 Conceição Avenue, State of Rio de Janeiro, Niteroi 24020080, Rio de Janeiro, Brazil. ctsilvajunior@predialnet.com.br
Research Domain of This Article
Respiratory System
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bernardo Henrique Ferraz Maranhão, Department of Specialized Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270004, State of Rio de Janeiro, Brazil
Cyro Teixeira da Silva Junior, Medical Clinics, Federal Fluminense University, Niteroi 24020080, Rio de Janeiro, Brazil
Jorge Luiz Barillo, Department of Thoracic Surgery, General Hospital Santa Teresa, Petropolis 25680-003, Rio de Janeiro, Brazil
Joeber Bernardo Soares Souza, Medical Clinics, Antonio Pedro University Hospital, Niteroi 24020-080, Rio de Janeiro, Brazil
Patricia Siqueira Silva, Professor Mazzini Bueno Tuberculosis Research and Assistance Center, Federal Fluminense University, Niteroi 24020-080, Rio de Janeiro, Brazil
Roberto Stirbulov, Department of Clinics, Rua Baronesa de Itu, São Paulo 1231001, São Paulo, Brazil
Author contributions: Maranhão BHF and Stirbulov R executed the idea and planned, organized, and supervised the study; Souza JBS, Barillo JL, and Silva PS were responsible for data collection; da Silva Junior CT wrote the earlier and final drafts of the manuscript and was responsible for statistical analysis and interpretation of the results. All authors have read and approved the manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of the Faculty of Medicine, Federal Fluminense University (number 48946121.9.0000.5243).
Informed consent statement: Written informed consent was obtained from all participants before the study.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest regarding the content of this article. Funding The authors received no financial support for the research, authorship, or publication of this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement- checklist of items.
Data sharing statement:sharing statement: The corresponding author can provide datasets that support the conclusions of this study upon request. The original datasets are not accessible to the general public because they contain data that may jeopardize the privacy of research participants.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cyro Teixeira da Silva Junior, MD, PhD, Full Professor, Medical Clinics, Federal Fluminense University, 13 Conceição Avenue, State of Rio de Janeiro, Niteroi 24020080, Rio de Janeiro, Brazil. ctsilvajunior@predialnet.com.br
Received: September 28, 2024 Revised: November 4, 2024 Accepted: March 4, 2025 Published online: July 6, 2025 Processing time: 171 Days and 17.7 Hours
Abstract
BACKGROUND
Although inflammatory diseases commonly affect the pleura and pleural space, their mechanisms of action remain unclear. The presence of several mediators emphasizes the concept of pleural inflammation. Adenosine deaminase (ADA) is an inflammatory mediator detected at increased levels in the pleural fluid.
AIM
To determine the role of total pleural ADA (P-ADA) levels in the diagnosis of pleural inflammatory diseases.
METHODS
157 patients with inflammatory pleural effusion (exudates, n = 124, 79%) and non-inflammatory pleural effusion (transudates, n = 33, 21%) were included in this observational retrospective cohort study. The P-ADA assay was tested using a kinetic technique. The performance of the model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The ideal cutoff value for P-ADA in pleural inflammation was determined using the Youden index in the ROC curve.
RESULTS
The transudates included congestive heart failure (n = 26), cirrhosis of the liver with ascites (n = 3), chronic renal failure (n = 3), and low total protein levels (n = 1). The exudate cases included tuberculosis (n = 44), adenocarcinoma (n = 37), simple parapneumonic effusions (n = 15), complicated parapneumonic effusions/empyema (n = 8), lymphoma (n = 7), and other diseases (n = 13). The optimal cutoff value of P-ADA was ≥ 9.00 U/L. The diagnostic parameters as sensitivity, specificity, positive and negative predictive values, positive and negative likelihood values, odds ratio, and accuracy were 77.69 (95%CI: 69.22-84.75); 68.75 (95%CI: 49.99-83.88); 90.38 and 44.90 (95%CI: 83.03-95.29; 30.67-59.77); 2.48 and 0.32 (95%CI: 2.21-11.2; 0.27-0.51); 7.65 (95%CI: 0.78-18.34), and 75.82 (95%CI: 68.24-82.37), respectively (χ² = 29.51, P = 0.00001). An AUC value of 0.8107 (95%CI: 0.7174-0.8754; P = 0.0000) was clinically useful. The Hosmer-Lemeshow test showed excellent discrimination.
CONCLUSION
P-ADA biomarker has high diagnostic performance for pleural inflammatory exudates.
Core Tip: Non-specialists find it difficult to diagnose pleural effusions. Although diagnosing the syndrome through imaging is simple, determining the cause is more difficult. To treat pleural disease as soon as possible, it is crucial to determine whether it is inflammatory. To our knowledge, this study is the first in Brazil and the world to establish a reference value with strict statistical criteria to classify inflammatory pleural effusion syndrome.