Affiliations: Hospital Ramón y Cajal Madrid, Spain,
PGIMER Chandigarh, India
Correspondence to: David Jiménez, MD, Respiratory Department, Hospital Ramón y Cajal, Ctra Colmenar Km 9, 100 Madrid, Spain 28034
We read with interest the article by Nagesh and colleagues (June 2001).1 They report serious doubts on the usefulness of adenosine deaminase (ADA) levels in the detection of tuberculous pleurisy. They also recommend polymerase chain reaction (PCR) as the method of choice for the diagnosis of tuberculous pleural effusions.
We would like to question that only 1 of 20 patients with pleural tuberculosis had the diagnosis on the basis of pleural biopsy, and only 4 of 20 patients (20%) on basis of acid-fast bacilli-positive results in the pleura or positive biopsy. The results from our own group2and others3 show that the diagnosis of tuberculosis is now established in 90 to 95% of patients with tuberculous pleuritis with the studies that we perform (stain, culture, and histology). Forty-five percent of the tuberculosis cases in the study by Nagesh and colleagues1 were diagnosed presumptively, and this could have biased the yield of PCR and ADA.
We also question that there were no parapneumonic effusions in the control group. Pneumonia is the second cause of pleural effusion in most series.4–5 It is possible that some of these parapneumonic effusions were misclassified as tuberculous effusions.
Nagesh and colleagues1 estimated ADA by the method of Giusti. In a meta-analysis performed by Bañales et al,6 ADA was analyzed with the Blake-Berman method. The sensitivity found was 99%, and the specificity was 89%. In 1999, Pérez-Rodríguez et al2 published a series of 103 cases with analyses of ADA and ADA isoenzymes. Sensitivity was 100% and specificity 95.6%. PCR offers a very disparate performance,7–8 probably due to scant number of mycobacteria in the fluid, the low number of neutrophils, and the lack of repetitiveness of the test.7
In conclusion, we think that the methods employed in the diagnosis and the distribution of etiologies, as well as the estimation of ADA by the Giusti method, can explain the results of Nagesh and colleagues.1 The experience of our group supports the ADA estimation as the biochemical method of choice for the diagnosis of pleural tuberculosis. Future improvements in the technique of detection of mycobacterial DNA by PCR and reduction in cost could justify its routine use.
Thanks for your letter along with comments of Dr. Perez-Rodriguez regarding our article published in CHEST (June 2001).1 After going through the contents of the letter, I found them to be just the view of one group who might have done work on adenosine deaminase (ADA) using some other and possibly more sensitive technique, and they might have had better results with their method. We do not have any objection to their claim that ADA might give better sensitivity. But as per our experience and the method used as mentioned in our article, we found it to be less sensitive and of limited usefulness. We have emphasized the usefulness of polymerase chain reaction (PCR) as an adjunct to the other routine techniques for detection of mycobacterium in pleural fluids. The pleural effusion is basically a hypersensitivity reaction to some infection or cancer and not characteristic of Mycobacterium tuberculosis infection. The number of bacilli in the pleural fluid is very low, and so the conventional methods of detection of mycobacteria are often ineffective. PCR, however, can be very sensitive and also specific if used carefully and meticulously as an adjunct to other clinical findings and laboratory investigations.
ADA is an enzyme involved in purine catabolism and is found in many cells but particularly in lymphocytes, where its concentration is inversely related to the degree of differentiation and can be raised in many other conditions like rheumatoid disease, chronic lymphatic leukemia, and undifferentiated lymphoma. False-positive results can be seen in these conditions. Moreover, neutrophils contribute to the high level of ADA found in empyema fluid. Serious doubts about the usefulness of ADA levels in the detection of the tuberculous pleurisy have also been raised by other workers.2–3 At the same time, many workers have shown high sensitivity of this marker, as we noted in our article.1
Become a CHEST member and receive a FREE subscription as a benefit of membership.
Individuals can purchase this article on ScienceDirect.
Individuals can purchase a subscription to the journal.
Individuals can purchase a subscription to the journal or buy individual articles.
Learn more about membership or Purchase a Full Subscription.
Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited:
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.