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Communications to the Editor |

Diagnosing Pleural TuberculosisDiagnosing Pleural Tuberculosis FREE TO VIEW

Anete Trajman, MD, PhD; Morrys C. Kaisermann, MD, MSc; Afranio L. Kritski, MD, PhD; Rosa Dea Sperhacke, PhD; Maria Lucia Rossetti, PhD
Author and Funding Information

Affiliations: Gama Filho University, Rio de Janeiro, Brazil,  Federal University of Rio de Janeiro, Rio de Janeiro, Brazil,  Centro de Desenvolvimento Científico e Tecnológico, Rio Grande do Sul, Brazil,  School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

Correspondence to: Anete Trajman, MD, PhD, Rua Macedo Sobrinho 74/203, Humaitá, 22271-080 Rìo de Janeiro, Brazil; e-mail: atrajman@centroin.com.br



Chest. 2004;125(6):2366-2367. doi:10.1378/chest.125.6.2366
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To the Editor:

The diagnosis of pleural tuberculosis (pTB) remains a challenge. New inexpensive, safe, and fast methods are needed. Lima and colleagues (September 2003)1 have studied 45 patients with pleural effusion using polymerase chain reaction (PCR) and adenosine deaminase (ADA) detection, and have found a very low sensitivity for pleural fluid PCR (31.3%) in 16 patients with pTB. When combining PCR and ADA results, the sensitivity increased to 87.5%, but specificity dropped from 96.6 to 72.4%. Among pTB patients, only nine had a confirmed diagnosis by any other laboratory method. The authors concluded that the use of both methods is a useful approach to the diagnosis of pTB. However, it is difficult to make firm recommendations based on small samples.

Our preliminary (unpublished) results in a series of 90 patients, also from Brazil, in the state with the country’s highest tuberculosis incidence rate (Rio de Janeiro), indicate that PCR and ADA have sensitivities of 80% and 84.6%, respectively, which are much higher than those reported by Lima et al.1 Specificity was 84% and 96%, respectively. The only false-positive case of ADA was a patient with empyema, which has distinct clinical features and can thus be easily distinguished from pTB. The best accuracy was achieved using an ADA cutoff of 34.6 U/L, as determined by a receiver operating characteristic curve. When combined, PCR increased ADA sensitivity to 92.3% at the expense of specificity, which dropped to 80%. Therefore, in our hands, PCR appears to add cost to the diagnostic approach of pTB without offering a significant advantage over ADA alone. ADA activity detection in pleural fluid alone is a very useful tool for the diagnosis of pTB, and its combination with PCR is not presently warranted in low-income countries with a high prevalence of tuberculosis.

Lima, DM, Colares, KJB, Fonseca, BAL (2003) Combined use of the polymerase chain reaction and detection of adenosine deaminase activity on pleural fluid improves the rate of diagnosis of pleural tuberculosis.Chest124,909-914. [CrossRef] [PubMed]
 

Diagnosing Pleural Tuberculosis

To the Editor:

Pleural tuberculosis (pTB) is the most common extrapulmonary manifestation of tuberculosis but, as mentioned by Trajman et al, remains a challenge, even to physicians working in areas of high prevalence of tuberculosis. Several approaches have been taken aiming at the improvement of the rate of pTB diagnosis but, singly, none of them has achieved a “gold standard” status. It is always necessary to use more than one technique to reach a correct diagnosis of pTB. This is the most important conclusion of our article, as we have shown that the association of polymerase chain reaction (PCR) and adenosine deaminase activity (ADA) measurements dramatically improves the rate of pTB diagnosis.

Trajman et al questioned this finding, arguing that it is difficult to make firm recommendations based on such small samples as that presented on our article. They also argue that their PCR assay presents a higher sensitivity than the one reported on our article. However, it is impossible to compare both results since we do not know how their samples were collected and what was the protocol used on their assays. Our study included patients consecutively attended in our hospital with a possible diagnosis of pTB based solely on clinical grounds, and this fact may be responsible for the low yield of our PCR. As shown in our article, we encountered a variety of diseases presenting with similar clinical findings as pTB, such as empyema, lymphoma, etc. However, we do not know anything about their samples. Isn’t there a selection bias on their sampling that could explain the better performance of their PCR? It is also known that the prevalence of tuberculosis will influence the parameters of any test devised to improve its diagnosis, in particular, the positive predictive value. Their better results might be related to their higher prevalence of pTB on their cohort.

Another interesting point to comment is their high specificity of the ADA measurements. I do not know how to explain their results since ADA measurements are known to be very sensitive but associated with a low specificity. That was also one of the findings of our study, and our lower sensitivity and specificity may be related to a higher cut-off point used in our study. It is important to point out that our results are in agreement with several other studies12 done in other countries with different prevalence of tuberculosis. Finally, it is a known fact that PCR protocols may vary from laboratory to laboratory and heavily depends on the DNA extraction methods. We cannot exclude that we have used a different DNA extraction method that could be responsible for the better yield of their PCR assays.

In conclusion, our study had a small sample size but the reason is associated to the prevalence of pTB in our region. Also, it was prospectively done and well controlled, while the information on the data collection of their study is not available. Finally, even though PCR might add cost to the pTB diagnosis, the cost is irrelevant if the correct diagnosis is reached, as it was the case in our study. This means a cut in the cost of hospitalization to perform several other diagnostic tests, and probably, to the lower incidence of adverse effects of the medications against tuberculosis in those non-pTB patients that were put on drugs due to a false-positive ADA measurement. We still believe that our data are sufficiently good to warrant the worldwide use of a combination of PCR and ADA measurement for the pTB diagnosis independently of the medical resources offered by a particular country.

References
Querol, JM, Mínguez, J, García-Sánchez, E, et al Rapid diagnosis of pleural tuberculosis by polymerase chain reaction.Am J Respir Crit Care Med1995;152,1977-1985. [PubMed]
 
De Wit, D, Maartens, G, Steyn, L A comparative study of the polymerase chain reaction and conventional procedures for tuberculous pleural effusions.Tuber Lung Dis1992;73,262-267. [CrossRef] [PubMed]
 

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References

Lima, DM, Colares, KJB, Fonseca, BAL (2003) Combined use of the polymerase chain reaction and detection of adenosine deaminase activity on pleural fluid improves the rate of diagnosis of pleural tuberculosis.Chest124,909-914. [CrossRef] [PubMed]
 
Querol, JM, Mínguez, J, García-Sánchez, E, et al Rapid diagnosis of pleural tuberculosis by polymerase chain reaction.Am J Respir Crit Care Med1995;152,1977-1985. [PubMed]
 
De Wit, D, Maartens, G, Steyn, L A comparative study of the polymerase chain reaction and conventional procedures for tuberculous pleural effusions.Tuber Lung Dis1992;73,262-267. [CrossRef] [PubMed]
 
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