• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.530-541
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• 2002

Background : Pleural fluid adenosine deaminase (ADA) activity can be helpful in a differntial diagnosis of an exudative pleural effusion because it is increased in a tuberculous pleural effusion. The ADA activity is determined mainly by the lymphocyte function. Age-associated immune decline is characterized by a decrease in T-lymphocyte function. For that reason, the pleural fluid ADA level would be lower in older patients with exudative pleural effusion. This study focused on the influence of age on the pleural fluid ADA activity in patients with exudative pleural effusion. Methods : A total of 81 patients with exudative pleural effusion were enrolled in this study. In all patients, the pleural fluid ADA activity was measured using an automated kinetic method. Results : The mean age of the patients was $52.7{\pm}21.2$ years. In all patients with exudative pleural effusion, the pleural fluid ADA activity revealed a significant difference between young patients (under 65 years of age) and old patients (p<0.05), and showed a negative correlation with age (r=-0.325, p<0.05). In the 60 patients with a tuberculous pleural effusion, the pleural fluid ADA activity revealed a significant difference between the young and older patients : $103.5{\pm}36.9$ IU/L in young patients Vs. $72.2{\pm}31.6$ IU/L in old patients (p<0.05), and showed a negative correlation with age (r=-0.384, p<0.05). In the 21 patients with non-tuberculous exudative pleural effusion, the pleural fluid ADA activity of the young patients and old patients was similar : $23.7{\pm}15.3$ IU/L in young patients Vs. $16.1{\pm}10.2$ IU/L in old patients (p>0.05), and did not show any correlation with age (r=-0.263, p>0.05). The diagnostic cutoff value of pleural fluid ADA activity for tuberculous pleural effusion was lower in the older patients (25.9 IU/L) than in the younger patients (49.1 IU/L) or all patients (38.4 IU/L) with exudative pleural effusion. Conclusion : Tuberculous pleural effusion is an important possibility to consider in older patients with a clinical suspicion of a tuberculous pleural effusion, although no marked increase in the pleural fluid ADA activity is usually detected. For a diagnosis of a tuberculous pleural effusion in old patients, the cutoff for the pleural fluid ADA activity should be set lower.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.669-675
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• 2000

Background: Tuberculous pleurisy is the leading cause of pleural effusion in Korea. And differential diagnosis of tuberculous pleurisy with other cause is clinically very important. Traditional diagnostic methods such as routine analysis of pleural fluid, staining for acid-fast bacilli or pleural biopsy have major inherent limitaion. This study was designed to evaluate the significance of pleural fluid polymerase chain reaction(PCR) and adenosine deaminase (ADA) activity in early diagnosis of tuberculous pleurisy. Material and Method: Between March 1996 and July 1997, 198 patients with pleural effusion reviewed retrospectively. The study group included 112 cases with tuberculous effusion and 86 cases with non-tuberculous effusions, whose diagnoses were confirmed by pleural biopsy, microbiological methods, or cytology. We compared the results of PCR and pleural fluid levels of ADA between tuberculous and non-tuberculous effusions. Result: Mean age was 47.54$\pm$19.52 years(range 2 to 85 years). The positive rate of PCR was significantly higher in tuberculous group than non-tuberculous group(p<0.05). The sensitivty, specificity, positive predictive value(PPV), and negative predictive value(NPV) for PCR were 31.7, 90.9, 83.0, and 48.8%, respectively. Mean ADA activity was significantly higher in tuberculous group than non-tuberculous group(83.2 U/L vs 49.8 U/L)(p<0.05). With diagnostic thresholds of 40 U/L, the sensitivity, specificity, PPV, and NPV of ADA for tuberculosis were 75.9, 70.9, 77.3, and 69.3% respectively. At a level of 70 U/L, the sensitivity, specificity, PPV, and NPV of ADA for tuberculosis were 70.1, 75.9, 82.9, and 60.3% respectively. Conclusion: PCR is very highly specific, but less sensitive methods in diagnosis of tuberculous pleurisy. But ADA level of pleural fluid has acceptable sensitivity and specificity in diagnosis of tuberculous pleurisy. ADA activity is more useful test in the evaluation of pleural effusions.

• Tuberculosis and Respiratory Diseases
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• v.52 no.6
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• pp.608-615
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• 2002

Background : ADA is an enzyme found in most cells, and is involved in purine metabolism, but its chief role concerns the proliferation and differentiation of lymphocytes, especially T-lymphocytes. For that reason ADA has been looked on as a marker of cell-mediate immunity, which is the key mechanism of the tuberculous pleural effusion. Thus, the pleural fluid ADA activity is increased in the tuberculous pleural effusion. Age associated immune decline is characterized by decreases in both B and T-lymphocyte function and the former may be largely a result of the latter. Therefore, the pleural fluid ADA activity would be lower in old rather than in young, patients with tuberculous pleural effusion. We studied the relationship between age, and pleural fluid ADA activity, in patients with tuberculous pleural effusion. Materials and Methods : In the 46 patients with tuberculous pleural effusion enroll in this study, the pleural fluid ADA activities were measured by means of an automated kinetic method. Results : The mean age of the patients was $53.0{\pm}22.0$ years, with a male to female ratio of 30:16. The patients were divided into two groups, young patients, regarded as < 65 and old regarded as ${\geq}65$ years with 28 and 18 patients, respectively. The pleural fluid ADA activity in both groups show significant differences : $99.4{\pm}22.6$ IU/L(young patients) Vs. $75.8{\pm}30.9$ IU/L(old patients)(p<0.05), but a negative correlation with age (r=-0.311, p<0.05). Conclusion : Although pleural fluid ADA activity was not adequately increased, tuberculous pleural effusion, in older patients, would have to be considered clinically suspicious tuberculous pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.388-396
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• 1998

Background: Etiologic diagnosis of pleural effusion is usually made by clinical characteristics, pleural fluid analysis and pleural biopsy. But, despite careful diagnostic study, the cause of pleural effusion cannot be found in about 20 percent of patients, especially in loculated pleural effusions. Tuberculous pleurisy is one of the most common cause of pleural effusion in Korea. But, pleural fluid culture for Mycobacterium tuberculosis are positive in only 20 to 30 percent of patients and typical pleural biopsy finding in less than 50 percent of patients with this disease. In recent studies, adenosine deaminse(ADA) and its isoenzymes were proposed to be a useful diagnostic tool for differential diagnosis of pleural effusion. We investigated the pattern of ADA and its iscenzyme activities in various cause of pleural effusions to evaluate the diagnostic value of measuring ADA and its isoenzymes. Method: We measured total ADA and its isoenzyme activities in pleural fluid and serum from 54 patients with pleural effusion(25 tuberculous pleural effusion, 10 parapneumonic effusion, 14 malignant pleural effusion, 5 transudative pleural effusion), including 5 loculated tuberculous pleural effusions and 6 loculated parapneumonic effusions. Total ADA activity was measured by the spectrophotometric method and ADA2 isoenzyme activity was measured with same method using EHNA, potent inhibitor of ADA1 isoenzyme activity. Result: Total ADA activity of tuberculous pleural effusion was higher than malignant pleural effusion(p<0.01), but no significant difference was found between tuberculous pleural effusion and parapneumonic effusion(tuberculous pleural effusion: $148.9{\pm}89.9IU/L$, parapneumonic effusion: $129.0{\pm}119.4IU/L$, malignant pleural effusion: $48.7 {\pm}39.7IU/L$). Percentage of ADA2 activity to total ADA activity(ADA2%) of pleural effusion of tuberculous pleurisy was higher than parapneumonic effusion(p<0.05). but no significant difference was found between tuberculous pleural effusion and malignant pleural effusion(tuberculous pleural effusion: $57.2{\pm}10.7%$, parapneumonic effusion: $35.9{\pm}17.8%$, malignant pleural effusion: $60.7{\pm}4.1%$). In loculated pleural effusion, ADA2% of tuberculous pleural effusion was higher than parapneumonic effusion(tuberculous pleural effusion: $53.3{\pm}3.9%$, parapneumonic effusion: $27.8{\pm}7.9%$). Conclusion: Measurement of ADA isoenzyme activity is useful for differentiating tuberculous pleural effusion from parapneumonic effusion, especially in loculated pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.35-42
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• 1993

Background: In order to establish the etiology of the pleural effusion, routine analysis of the fluid, bacteriologic studies, cytologic tests and pleural biopsies are currently being employed. However, even with the above mentioned tests, the exact causes cannot be determined in approximately 10-20% of cases. The purpose of our study is to determine the diagnostic value of measuring ADA activity and CEA simultaneously in various pleural fluids which their etiologies have confirmed Methods: We have studied 61 cases of tuberculous pleural effusions, 17 cases of suspected tuberculous pleural effusions, 17 cases of malignant pleural effusions, 22 cases of suspected malignant pleural effusions, and 7 cases of parapneumonic pleural effusions. We have measured the ADA activity and CEA level simultaneously in pleural fluid samples in each cases. Results: 1) The ADA activity in tuberculous pleural effusion was significantly higher than that in malignant effusion. 2) The CEA level in malignant pleural effusion was significantly higher than that in tuberculous effusion. 3) With the cut-off values of the pleural fluid ADA activity more than 40 U/L and the CEA level less than 12 ng/mL, the sensitivity was 86.9%, and the specificity was 100% in the diagnosis of tuberculous effusion. With the cut-off values of the pleural fluid CEA level more than 12 g/mL and the ADA activity less than 40 U/L, the sensitivity was 76.5%, and the specificity was 100% in the diagnosis of malignant effusion. Conclusion: It is suggested that the combined assay of pleural fluid ADA activity and CEA level is very useful in the differential diagnosis of tuberculous and malignant pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.595-600
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• 1999

Background: The estimation of ADA activity in pleural fluid has been proved useful tool in the diagnosis of tuberculous pleural effusions. However, there is controversy about its usefulness when estimated in bronchial washing fluid in the patients with pulmonary tuberculosis. This study aims at evaluating the usefulness of measuring ADA activity in bronchial washing fluid of tuberculous patients as biochemical marker in the early diagnosis of the disease. Methods: We examined the difference of ADA activity in bronchial washing fluid among the group I(tuberculosis group), group II(lung cancer group) and group III(control group). Results: There was significantly higher bronchial washing fluid ADA level in tuberculosis group compared to the lung cancer and control groups(p<0.01). Conclusion: These results suggest that bronchial washing fluid ADA activities seem to be a useful tool in the diagnosis of pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.838-845
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• 1995

The determination of ADA(adenosine deaminase) activity in pleural fluid is useful in differental diagnosis of pleural effusion. The conventional method of determining ADA activity used by Giusti was influenced by contamination of ammonia. Additionally, because Giusti's method was mannual method a determining the ADA activities in sample, was not easily automated. In 1993, Oosthuizen HM with collegues developed simple kinetic method for determining ADA activity. It was reliable and suiable method for automation. In this study, we have measured ADA activity in 162 patients with various pleural effusion by Hitachi 747 autoanalyser using the Oosthuizen kinetic method for the purpuse of determination of new diagnostic cut-off value for the tuberculous effusion and evaluation of the correlation between the conventional method and new automated method. This new method of an enzymatic reaction involves 2, 6-dichlorophenolindophenol dye(DICP), adenosine, xanthine oxidase(XO), and nucleoside phosphorylase(NP). The results were as follows: 1) The mean pleural ADA activity of the tuberculous effusion was $52.53{\pm}16.43\;U/L$ and significantly higher than that of other groups(p<0.001). If the diagnostic cut-off value of pleural ADA activity for tuberculous effusion is above 30 U/L, the sensitivity is 96% and the specificity is 90%. 2) The mean pleural to serum ADA activity ratio of the tuberculous effusion was $2.29{\pm}0.96$ and it was also significantly higher than that of other pleural groups(p<0.001). If the diagnostic cut-off value of pleural to serum ADA activity ratio is 1.5, the sensitivity is 80% and the specificity is 88% in the diagnosis of tuberculous pleural effusion. 3) The new kinetic method is correlates well to Giuisti's conventional method(r=0.971). In conclusion, the new kinetic method described is easily automated and seems to be suitable for the routine determination of ADA activity.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.280-289
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• 1998

Background: It is sometimes difficult to differentiate tuberculous pleural effusion from malignant pleural effusion by clinical symptoms, signs, by routine tests of pleural fluid, and by pathologic studies. And recently, it was discovered that cytokines such as IL-2, IFN-$\gamma$, TNF-$\alpha$ are elevated in tuberculous pleural fluid, and there have been several attempts to diagnose tuberculous pleural effusion by using these immunological mediators. There are several studies regarding the diagnostic value of IFN-$\gamma$, and there are two studies in Korea. But the diagnostic values of IFN-$\gamma$ in these studies were slightly lower than those in other countries. To compare the diagnostic value of IFN-$\gamma$ with those of CEA and ADA, and to determine the sensitivity and specificity of IFN-$\gamma$ in Korean, we mesured IFN-$\gamma$, CEA level and ADA activity in pleural effusions. Methods: ADA activity, IFN-$\gamma$ level and CEA level as well as cell count, differential count, and biochemical assays such as protein content and lactate dehydrogenase were measured in 40 cases of tuberculous pleuritis and 42 cases of malignant pleural effusion. Results: Tuberculous pleural fluid showed higher levels of IFN-$\gamma$ and ADA ($832.6{\pm}357.2$ pg/ml and $82.5{\pm}25.9$ U/L, respectively) than those of malignant pleural effusion ($2.6{\pm}8.0$ pg/ml and $19.2{\pm}10.9$ U/L, respectively) (p<0.01). Malignant pleural effusions showed higher median value (102.2 ng/ml) than tubercalous pleural effusions (1.8 ng/ml) (p<0.01). The sensitivities of IFN-$\gamma$, ADA, CEA were 0.97, 0.87, 0.67 and the specificities of IFN-$\gamma$, ADA, CEA were 1.0, 0.97, 1.0, respectively. There was no significant correlation between ADA activity and IFN-$\gamma$ level. Conclusion: This study showed that IFN-$\gamma$ test would be a very useful clinical test for differential diagnosis of tuberculous pleuritis and malignant pleural effusion because it is very sensitive and specific, although it is an expensive test.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.456-462
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• 2006

Background: Differential diagnosis is very important in patients with pleural effusions. A few studies on the etiologies of massive pleural effusions have been reported, but these were conducted in different decades and locations. In the present study, the etiologic spectrum of massive pleural effusions in Korea, were evaluated through an investigation at one university hospital. Methods: Retrospective chart reviews were performed in patients having undergone thoracentesis between July 2002 and July 2005. Pleural effusions were deemed to be massive if they occurred in two thirds or more of one hemithorax. The etiologies of massive pleural effusions, pleural fluid findings, serum laboratory findings, and sputum and pleural fluid cytologies were compared. Results: Of 298 pleural effusions cases, 41 (13.8%) had massive pleural effusions. The most frequent causes of massive pleural effusions were malignancy (19; 46.3%) followed by tuberculosis (15; 36.6%), parapneumonic effusion (4; 9.8%) and transudate (3; 7.3%). Compared with massive benign effusions, patients with massive malignant pleural effusions were more likely to have lower adenosine deaminase (ADA) activity, a higher amylase level and higher RBC count in their pleural fluids. Also, compared with non-tuberculosis effusions, patients with massive tuberculous pleural effusions were more likely to have lower RBC and neutrophil counts, but a higher lymphocyte count, adenosine deaminase (ADA) activity and protein level. Conclusion: The most common etiologies of massive pleural effusions in Korea are malignancy and tuberculosis. A high ADA content favors a tuberculous condition, while bloody effusions with a relatively lower ADA content. favors malignancy. The proportion of tuberculosis in massive pleural effusions was higher than in previous reports.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.437-443
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• 2009

Background: The aim of this study was to consider the significance of pleural fluid adenosine deaminase (ADA) activity combined with lymphocyte/neutrophil (L/N) ratio in the diagnosis of tuberculous pleurisy (TBpl) in a region of intermediate prevalence of tuberculosis (TB). Methods: We collected data from 388 patients with exudative pleural effusions. The final diagnoses were compared to the results from our diagnostic method using pleural fluid ADA and L/N ratio. Results: 108 patients had a final diagnosis of TBpl; 102 cases had high levels of ADA ($\geq$40 IU/L). When we considered ADA $\geq$40 IU/L as a diagnostic criterion, the sensitivity was 94.4%, specificity 87.5%, and posttest posttest probability 74.5%. However, when we considered ADA $\geq$40 IU/L combined with the L/N ratio $\geq$0.75 as a diagnostic criterion, the specificity and post-test probability were rose to 97.5% and 93%, respectively. The other causes of high ADA and L/N ratios were lymphoma and metastatic carcinoma, but mass-like lesions were found on the chest radiographs or CT scans. Conclusion: To evaluate the causes of exudative pleural effusions in a region of intermediate prevalence of tuberculosis, we recommend measuring the pleural fluid ADA and L/N ratio first. If the result is high and malignancies are not suspected, it may be diagnostic of TBpl.