Adenosine Deaminase in the Diagnosis of Tuberculous Pleural Effusions: A Report of 218 Patients and Review of the Literature

doi:10.1378/chest.99.2.355

Chest

Volume 99, Issue 2, February 1991, Pages 355-357

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The activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied. According to the etiology of exudative pleural effusions, the patients were divided into the following five groups: (1) tuberculosis; (2) lung cancer; (3) pneumonias; (4) miscellaneous; and (5) idiopathic. Patients with pleural tuberculosis presented significantly higher ADA activity than patients with nontuberculous pleural effusions (p<0.0001). The results indicated that in a population with a relatively high prevalence of tuberculosis, the analysis of ADA levels in pleural effusions constitutes a useful marker for the diagnosis which, in addition, can be made quickly and cheaply. Additionally, a comprehensive review of the literature on the role of ADA in the diagnosis of tuberculous pleural effusions is presented.

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PATIENTS AND METHODS

Two hundred and eighteen patients with the diagnosis of exudative pleural effusion (protein content greater than 30 g/L) were admitted to our Institute in a period of four years. There were 154 men and 64 women with a total mean age of 52 years (SD, 22.6). All patients were subjected to a pleural fluid aspirated and pleural biopsies, with the exception of those having parapneumonic effusions who had a diagnosis based on a history consistent with pneumonia and appropriate response to a course of

RESULTS

Two or more ADA measurements were performed for each sample with a difference of less than 5 percent between them. The ADA levels obtained in the different studied groups are shown in Figure 1. The ADA mean for the total population was 67.5 IU/L (SD 56). Tuberculous effusions presented a mean of 123.25 IU/L (SD 39.4), whereas nontuberculous fluids showed a mean of 30.36 IU/L (SD 26.4) (p<0.0001; Student's t test). Using 70 IU/L as a cut-off value, the ADA test exhibited a sensitivity of 98

DISCUSSION

Pleural effusions are common in clinical practice and they often constitute difficult diagnostic problems.

In spite of careful evaulation, the etiology of the effusions cannot be established in about 20 percent of patients.¹^,¹⁷^,¹⁸ Pleural fluid cultures to detect the presence of Mycobacterium tuberculosis are positive in only 20 to 30 percent of patients with tuberculous pleurisy,¹⁷ and biopsy of the parietal pleura shows typical epithelioid granulomas in 50 to 80 percent of patients with this

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Cited by (104)

Adenosine deaminase is a useful biomarker to diagnose pleural tuberculosis in low to medium prevalence settings
2016, Diagnostic Microbiology and Infectious Disease
Citation Excerpt :
It is likely that this scenario could avoid unnecessary costs. ADA activity is known to be also increased in empyema (Banales et al., 1991; Chen et al., 2004; Porcel et al., 2010; Valdes et al., 1996; Zaric et al., 2008). Patients with empyema had clear distinct clinical features with presence of frank pus in the pleural cavity, and may be easily distinguished from pTB, so ADA test should not be used in this situation.
Adenosine deaminase (ADA) activity measurement in pleural fluid is a relevant test to diagnose pleural tuberculosis (pTB) in high tuberculosis prevalence settings. We investigated the diagnostic utility of pleural ADA using a retrospective analysis of patients admitted with newly diagnosed pleural effusion without identified etiology between 2001 and 2008 in Paris suburb, a low to medium tuberculosis prevalence area. 104 adults (mean age 55 years; 34 with pTB, 70 with other diagnoses) were analyzed. Median follow-up was 15.6 months. Mean [interquartile range] pleural ADA was 119 U/L [IQR: 83–143] in pTB and 24 U/L [IQR: 15–31] in non-tuberculous effusions (P < 0.001). With an optimal pleural ADA cut-off value of 41.5 U/L for pTB diagnosis, sensitivity and specificity were 97.1% and 92.9%, while positive and negative predictive values were 86.8% and 98.5%, respectively. We conclude that pleural ADA activity could be integrated in the diagnostic procedures of pTB in low to medium tuberculosis prevalence settings.
Factors influencing pleural adenosine deaminase level in patients with tuberculous pleurisy
2014, American Journal of the Medical Sciences
Adenosine deaminase (ADA) activity is useful for diagnosing tuberculous (TB) pleurisy in regions with a high prevalence of tuberculosis. However, some cases of TB pleural effusion show decreased ADA activity. Therefore, we evaluated factors influencing pleural ADA levels in patients with TB pleurisy.
We retrospectively evaluated 182 patients with TB pleural effusion who were admitted to Gyeongsang National University Hospital from January 2004 to September 2008. Patients were dichotomized into 2 groups: a low-ADA (< 40 IU/L) group (n = 22) and a high-ADA (≥ 40 IU/L) group (n = 160). Age, sex, ADA level of pleural effusion, smoking status, history of tuberculosis and comorbid diseases were evaluated in each group.
The median age of the patients was 50.5 years, with a male to female ratio of 1.72:1. Patients with a low-ADA level were significantly older than those with a high ADA level (66.9 ± 12.0 versus 49.4 ± 21.2 years, P < 0.001). A history of tuberculosis and hypertension was more common in the low-ADA group than in the high-ADA group (31.8% versus 15.0%, P = 0.049 and 36.4% versus 16.9%, P = 0.03, respectively). A multivariate analysis revealed that older age and current smoking were predictive of TB pleurisy with a low ADA level (odds ratios, 1.053 and 4.848; P = 0.002 and 0.028, respectively).
Physicians should be careful when interpreting pleural ADA levels in elderly patients and/or current smokers for the diagnosis of TB pleurisy.
Differential diagnosis of tuberculous and malignant pleurisy using pleural fluid adenosine deaminase and interferon gamma in Taiwan
2011, Journal of Microbiology, Immunology and Infection
Citation Excerpt :
This discrepancy can be attributed, in part, to the use of different methods. With the most frequently reported colorimetric ADA assay, described by Giusti and Galanti,16 the reported cutoff value for ADA varies from 40 IU/L to 60 IU/L.5,27,29,30,32–34 Our cutoff value of 30 IU/L was lower than this range, although this may be because of the ethnicity of our study population. The cutoff values for IFN-γ vary from 60 pg/mL to 240 pg/mL, based on an enzyme-linked immunosorbent assay.35–37
Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n = 24) and malignant (n = 42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p < 0.001 for both). For differentiating the two effusions, results for ADA versus IFN-γ were: sensitivity, 70.8% versus 91.7%; specificity, 95.2% versus 97.6%; positive predictive value, 89.5% versus 96.7%; and negative predictive value, 85.1% versus 95.3%. IFN-γ allows precise diagnosis of pleural tuberculosis, but ADA is easier to use, has a low cost, and results are quickly available. Our study confirms previous studies and extends the usefulness of these diagnostic methods to a wider group of clinical laboratories by showing the reliability of standardized relatively inexpensive commercial kits. We recommend that initial ADA screening be used in conjunction with IFN-γ measurements for differential diagnosis of tuberculous pleurisy.
Enzyme-linked immunospot assay for interferon-gamma in the diagnosis of tuberculous pleurisy
2009, Clinical Microbiology and Infection
Patients presenting with pleural effusion of undetermined aetiology were prospectively enrolled, and an enzyme-linked immunospot (ELISPOT) assay on pleural fluid and peripheral blood was performed. Forty patients were studied, including 19 with culture- or biopsy-confirmed (n = 15) or clinically compatible (n = 4) tuberculous pleurisy, and 21 with pleural effusions due to non-tuberculous causes. The sensitivity, specificity and positive and negative predictive values of the assay were 94.7%, 85.7%, 85.7% and 94.7%, respectively, on pleural fluid, and 77.8%, 90.5%, 87.5% and 82.6%, respectively, on blood. Antigen-specific, interferon-gamma-secreting T-cells were concentrated eight to ten times in pleural fluid as compared with blood. Among the seven patients not suitable for pleural biopsy and three patients whose biopsy results were non-diagnostic, nine had positive ELISPOT result with pleural fluid. The ELISPOT assay for interferon-gamma can accurately diagnose tuberculous pleurisy and is helpful for patients not suitable for pleural biopsy and those whose biopsy results are non-diagnostic.
Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: A meta-analysis
2008, Respiratory Medicine
Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of adenosine deaminase (ADA) in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a meta-analysis to determine the accuracy of ADA measurements in the diagnosis of tuberculous pleurisy.
After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of ADA concentration in the diagnosis of pleural effusion were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.
Sixty-three studies met our inclusion criteria. The summary estimates for ADA in the diagnosis of tuberculous pleurisy in the studies included were sensitivity 0.92 (95% confidence interval 0.90–0.93), specificity 0.90 (95% confidence interval 0.89–0.91), positive likelihood ratio 9.03 (95% confidence interval 7.19–11.35), negative likelihood ratio 0.10 (95% confidence interval 0.07–0.14), and diagnostic odds ratio 110.08 (95% confidence interval 69.96–173.20).
ADA determination is a relative sensitive and specific test for the diagnosis of tuberculous pleurisy. Measurement of ADA in pleural effusion is thus likely to be a useful diagnostic tool for tuberculous pleurisy. The results of ADA assays should be interpreted in parallel with clinical findings and the results of conventional tests.
Pleural fluid neopterin levels in tuberculous pleurisy
2007, Clinical Biochemistry
Neopterin is produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It is regarded as a biochemical marker of cell-mediated immune response. This study was designed to assess the diagnostic value of pleural fluid neopterin levels in tuberculous pleurisy in comparison with adenosine deaminase activity.
Pleural fluid adenosine deaminase (ADA) activity and neopterin levels were measured in 16 patients with tuberculous pleurisy (TP) and 19 patients with malignant pleurisy (MP). ADA activity was determined by a colorimetric method, whereas neopterin levels were determined by a reversed-phase liquid chromatography technique. All values were given as median (min–max).
The mean age was 45.43 ± 20.39 years in the TP group and 60.42 ± 11.02 years in the MP group (p = 0.026). The median pleural fluid ADA activity was 51.75 U/L (3.50–62.40 U/L) in the TP group and was 2.30 U/L (1–8.20 U/L) in the MP group. The difference was statistically significant (p < 0.001). The median pleural fluid neopterin levels were 13.15 nmol/L (1.86–59.50 nmol/L) and 2.44 nmol/L (0.92–27.60 nmol/L) in the TP group and the MP group, respectively (p = 0.021). In order to evaluate the diagnostic value of pleural fluid neopterin concentrations, receiver-operating-characteristic curve analysis was performed.
Pleural fluid neopterin concentration is significantly higher in TP when compared to MP, however when compared, its clinical use as a diagnostic marker is not valuable as ADA.

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: This study was supported in part by the Canadian International Development Agency.

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Chest

Clinical InvestigationsAdenosine Deaminase in the Diagnosis of Tuberculous Pleural Effusions: A Report of 218 Patients and Review of the Literature

Section snippets

PATIENTS AND METHODS

RESULTS

DISCUSSION

Clin Chest Med

Chest

Chest

Tubercle

Tubercle

Clin Biochem

Chest

Chest

Tuberculous pleural diseases

Chest

Clinical Investigations
Adenosine Deaminase in the Diagnosis of Tuberculous Pleural Effusions: A Report of 218 Patients and Review of the Literature