Adenosine deaminase (ADA) isoenzyme analysis in pleural effusions: diagnostic role, and relevance to the origin of increased ADA in tuberculous pleurisy

Abstract

The rise in adenosine deaminase (ADA) activity in the pleural fluid of tuberculous pleurisy patients, though used for diagnosis, is of unknown origin. In this work, we determined ADA activity and the activities of 2'-deoxyadenosine deaminase and ADA-2 in 350 patients. We also considered whether the results throw light on the origin of high pleural fluid ADA in tuberculous pleurisy and estimated the diagnostic efficiency of 2'-deoxyadenosine deaminase, ADA-2 and total ADA activities with and without the inclusion of the 2'-deoxyadenosine deaminase/ADA activity ratio in a combined criterion.The 350 pleural effusions were classified by previously established criteria as transudates (60 males/18 females) or as tuberculous (49 males/27 females), neoplastic (50 males/39 females), parapneumonic (36 males/19 females), empyematous (11 males/ 3 females), or miscellaneous (25 males/13 females) exudates. Total ADA, ADA-2 and 2'-deoxyadenosine deaminase activities were, respectively, 127.5±2.9, 103±29.5 and 42.8±14 U·L -1 in tuberculous exudates. With diagnostic thresholds of 47, 40 and 22 U·L -1 respectively, the sensitivities of ADA, ADA-2 and 2'-deoxyadenosine deaminase for tuberculosis were 100, 100 and 95%; their specificities 91, 96 and 92%; and their efficiencies 93, 97 and 93%, respectively. One hundred and one effusions (all 76 tuberculous, 12 neoplastic, 4 parapneumonic and 9 empyematous exudates) had total ADA levels >47 U·L -1 ; of these, 8 neoplastic, 1 parapneumonic and all the tuberculous exudates had a 2'-deoxyadenosine deaminase/ADA activity ratio <0.49. The criterion of simultaneously having ADA >47 U·L -1 , ADA-2 >40 U·L -1 and a 2'-deoxyadenosine deaminase/ADA activity ratio <0.49 was satisfied by all the tuberculous effusions but only eight others (all neoplastic) (sensitivity 100%, specificity 97%, efficiency 98%).We conclude that: 1) high total ADA activity in tuberculous pleural effusions is due mainly to an increase in ADA-2, and, therefore, originated from the only known source monocytes and macrophages; 2) ADA-2 was a more efficient diagnostic marker of tuberculous pleurisy than total ADA activity, although the difference was not statistically significant; and 3) among effusions with high total ADA the 2'-deoxyadenosine deaminase/ADA activity ratio differentiates tuberculous effusions from empyemas and parapneumonic effusions, but fails to discriminate well between tuberculous and neoplastic effusions.

High pleural fluid adenosine deaminase levels: A valuable tool for rapid diagnosis of pleural TB in a middle-income country with a high TB/HIV burden

“…They consisted mainly of malignancies, parapneumonias and congestive cardiac failure. Most of the malignancies were due to bronchial cancer, which is in agreement with Zemlin et al [10] Valdés et al [17] found that parapneumonic effusions were the most frequent reason for a high FADA, followed by carcinomas (with pleural metastatic lesions) and lymphomas.…”

Diagnostic value of adenosine deaminase in tuberculous pleural effusion: a meta-analysis

“…23 Recently, it has been suggested that the test performance of ADA isoenzymes is superior to ADA, yielding lower false negative and false positive ¢ndings. 40,48,50 Finally, limitations of our study should be noted. First, misclassi¢cation bias can occur.…”

Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of adult tuberculous pleural effusion in Hong Kong

“…Excluding patients with an early diagnosis of nontuberculous disease, notably malignancy and nontuberculous infection, may also help improve the utility of pfADA for TBPE. 5,9,[23][24][25][26] Diagnostic test accuracy depends on sensitivity and specificity, which are relatively stable, and pre-test probability that can be enhanced by selecting appropriate patients. In this study, we aimed to optimise its utility by increasing the pretest probability, and establish a local diagnostic pfADA cut-off value for adult TBPE.…”