• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.17-23
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• 2007

Background: Many diagnostic approaches for defining the definitive cause of pleurisy should be included due to the large variety of diseases resulting in pleural effusion. Although ADA is a useful diagnostic tool for making a differential diagnosis of pleural effusion, particularly for tuberculous pleural effusion, a definitive diagnostic cut-off value remains problematic in Korea. It was hypothesized that ADA multiplied by the Lymphocyte/Neutrophil ratio(L/N ratio) might be more powerful for making a differential diagnosis of pleural effusion. Methods: One hundred and ninety patients, who underwent thoracentesis and treatment in Chung-Ang University Hospital from January, 2005 through to February 2006, were evaluated. The clinical characteristics, radiologic data and the examination of the pleural effusion were analyzed retrospectively. Results: 1. Among the 190 patients, 59 patients (31.1%) were diagnosed with tuberculous pleurisy, 45 patients(23.7%) with parapneumonic effusion, 42 patients(22.1%) with malignant effusions, 36 patients(18.9%) with transudate, and 8 patients(4.2%) with empyema. One hundred and twenty one patients were found to have an ADA activity of 1 to 39 IU/L(63.7%). Twenty-nine were found to have an ADA activity of 40 to 75 IU/L(15.3%) and 40 were found to have an ADA activity of 75 IU/L or greater(21.0%). 2. Among the patients with tuberculous pleurisy, 5(8%), 18(30%) and 36 patients(60%) had an ADA activity ranging from 1 to 39 IU/L, 40 to 75 IU/L, and 75 IU/L or greater, respectively. In those with an ADA activitiy 40 to 75 IU/L, 18 patients(62%) had tuberculous pleurisy, 9(31%) had parapneumonic effusion and empyema, and 1(3.4%) had a malignant effusion. 3. In those with an ADA activity of 40 to 75 IU/L, there was no significant difference between tuberculous pleurisy and non-tuberculous pleural effusion(tuberculous pleurisy : 61.3 ${\pm}$ 9.2 IU/L, non-tuberculous pleural effusion : 53.3${\pm}$10.5 IU/L). 4. The mean L/N ratio of those with tuberculous pleurisy was 39.1 ${\pm}$ 44.6, which was significantly higher than nontuberculous pleural effusion patients (p<0.05). The mean ADA x L/N ratio of the tuberculous pleurisy patients was 2,445.7 ${\pm}$ 2,818.5, which was significantly higher than the non-tuberculous pleural effusion patients (level p<0.05). 5. ROC analysis showed that the ADA x L/N ratio had a higher diagnostic value than the ADA alone in the group with an ADA between 40-75 IU/L. Conclusion: The ADA multiplied by the lymphocyte-to-neutrophil ratio might provide a more definitive diagnosis of tuberculous pleurisy.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.491-499
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• 1996

Background : Pleural effusion is a common disease in clinical practice but its effect on pulmonary function and altered pulmonary mechanics after removal of effusion are not still largely understood. Previous studies have shown that there is little or a relatively small improvement in pulmonary function and arterial blood oxygenation after therapeutic thoracentesis. The present study was designed to assess the effect on pulmonary function of pleural effusion and to test whether there was a significant improvement in pulmonary function and arterial oxygenation after thoracentesis and to observe long tenn effect after thoracentesis. Method : We examined flow-volume curve, body box and arterial blood gas analysis according to severity of effusion, present symptom, and symptom duration. Then, we measured changes of pulmonary function after thoracentesis and observed longterm effect after thoracentesis. Result: 1) Pleural effusion cause restrictive pulmonary insufficiency. Not only functional impairment of small airway but also large airway is provoked. 2) MMFR, FEV1, Raw, POz are earlier improved than FVC and TLC after thoracentesis and patients without complication have mild restrictive pulmonary insufficiency after longterm observation. 3) FVC, FEV1, & TLC are similarly restricted as severity of pleural effusion and po, is relatively decreased. 4) Cases with symptom duration 1 week or less and cases with dyspnea have more severe pulmonary insufficiency than others. 5) The flow volume curves show a relatively greater improvement in flow rates at large lung volumes than small airway. 6) Significant relationship is shown between first thoracentesis amount and changes of FEV1, FVC, TLC. Conclusion: Pleural effusion cause restrictive pulmonary insufficiency and not only functional impairment of small airway impairment but also large airway is provoked. Then, Pulmonary function is progressively improved after thoracentesis and remained mild restrictive pulmonary insufficiency after recovery.

• 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.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.56 no.2
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• pp.159-168
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• 2004

Background : In recent years, numerous human tumor specific antigens such as melanoma antigen gene(MAGE) that is recognized by autologous cytotoxic T lymphocytes have been identified. MAGE is expressed in many human malignancies in various organs, such as lung, breast, stomach, esophagus and leukemia. Therefore MAGE has been studied widely for tumor diagnosis and immunotherapy. But, so far there were no clinical studies evaluating the role of MAGE in pleural effusion. We investigated the expression of MAGE in the patients with exudative pleural effusion for it's diagnostic utility and the results were compared with those of cytologic examinations. Methods : Diagnostic thoracentesis was performed in 44 consecutive patients with exudative pleural effusion during 6 months. We examined the expression of MAGE and cytology with the obtained pleural effusion. Expression of MAGE was interpreted by means of a commercial kit using RT-PCR method. Enrolled patients were divided into two groups such as malignant and benign and we analyzed its' sensitivity and specificity. Results : There were no significant differences between two groups in age, sex, white blood cell counts in pleural fluid, pleural fluid/serum protein ratio and pleural fluid/serum LDH ratio. The sensitivity and specificity of MAGE were 72.2% and 96.2% respectively and the positive predictive value and negative predictive value of MAGE were also 92.9% and 83.3% respectively. The sensitivity and negative predictive value of cytologic examinations were 66.7% and 81.3% respectively. There were no significant differences between sensitivities of MAGE and cytologic examinations but false positive result of MAGE was found in 1 case of tuberculous pleurisy. Conclusion : MAGE is a sensitive and specific marker for the differential diagnosis between benign and malignant effusion in patients with exudative pleural effusion. And MAGE would provide the equal sensitivity compared with that of cytologic examination in patients with malignant pleural effusion if 5mL of the pleural fluid is examined.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.467-477
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• 2003

Background : Pleural effusions are generally divided into transudates and exudates. If it is exudative, more diagnostic tests are required in order to determine the cause of the local disease. A malignancy is a common and important cause of exudative pleural effusions. Because the pleural fluid cytology and pleural biopsy specimens do not provide a diagnosis in a high percentage of malignant effusions, several tumor markers have been examined. In order to overcome this limitation, this study hypothesized that C-reactive protein(CRP) and vascular endothelial growth factor(VEGF) measurements would be useful for differentiating trasudates from exudates and determining the differences between a benign and malignant effusion. Methods : Eighty consecutive patients with a pleural effusion (tuberculous 20, parapneumonic 20, malignant 20, transudative 20) were examined prospectively: 60 of them were classified according to Light's criteria as having an exudative fluid and 20 had a transudative fluid. The standard parameters of a pleural effusion were examined and the serum and pleural effusion VEGF levels were measured using enzyme linked immunosorbent assay(ELISA). CRP in the serum and pleural fluid was determined by a turbidimetric immunoassay. Results : The pleural CRP levels in the exudates were significantly higher than those in the transudates, $4.19{\pm}4.22mg/d{\ell}$ and $1.29{\pm}1.45mg/d{\ell}$, respectively. The VEGF levels in the pleural effusions were significantly elevated in the exudates compared to the transudate, $1,011{\pm}1,055pg/m{\ell}$ and $389{\pm}325pg/m{\ell}$, respectively. The VEGF ratio in the exudative effusion is significantly higher than a transudative effusions, $3.9{\pm}4.7$ and $1.6{\pm}0.9$, respectively. The pleural CRP levels in the patients with a benign effusion($4.15{\pm}4.20mg/d{\ell}$) were significantly higher than those in the malignant effusion($1.43{\pm}1.91mg/d{\ell}$). The VEGF ratio is significantly higher in malignant effusions($4.9{\pm}5.5$) than in benign effusions($2.8{\pm}3.6$). Conclusion : In conclusion, the CRP and VEGF levels in the serum and pleural effusion can distinguish between transudates and exudates. Moreover it can differentiate between benign and malignant pleural effusions.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.361-367
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• 2005

Background : Differential diagnosis of lymphocytic pleural effusion is difficult even with many laboratory findings. Nitric oxide(NO) level is higher in the sputum or exhaled breath of patients with active pulmonary tuberculosis than in those without tuberculosis. In addition, there are some reports about the increased level of NO metabolites in body fluids of cancer patients. However, there is no data on the NO levels in the pleural fluid of patients with tuberculous pleurisy. Method : The serum and pleural fluid NO in the patients with acute lymphocytic pleural effusion were analyzed. Results : Of total 27 patients, there were 14 males and average age of patients was 48 years. The final diagnosis was tuberculous pleurisy in 17 cases and malignant pleural effusion in 10. The pleural fluid NO level was $540.1{\pm}116.4{\mu}mol$ in the tuberculous pleurisy patients and $383.7{\pm}71.0{\mu}mol$ in the malignant pleural effusion patients. The serum NO level was $624.7{\pm}142.0{\mu}mol$ in tuberculous pleurisy patients and $394.4{\pm}90.4{\mu}mol$ in malignant pleural effusion patients. There was no significant difference in the serum and pleural fluid NO level between the two groups. The NO level in the pleural fluid showed a significant correlations with the pleural fluid neutrophil count, the pleural fluid/serum protein ratio, and pleural fluid/serum albumin ratio (p<0.05 in each). The protein concentration, leukocyte and lymphocyte count in the pleural fluid were significantly higher in the tuberculous pleurisy patients than the malignant pleural effusion patients (p<0.05 in each). Conclusion : NO is not a suitable marker for a differential diagnosis of lymphocytic pleural effusion. However, the NO level in the pleural fluid might be associated with the neutrophil recruitment and protein leakage in the pleural space.

• 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.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.109-113
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• 2007

Background: In non-small cell lung cancer (NSCLC), malignant pleural effusion is a frequently observed com-plication, and is an important negative prognostic factor. Although many studies concerned to diagnosis and treatment of malignant pleural effusion have been performed, prognostic factors of malignant pleural effusion have rarely been investigated. This study was performed to determine the prognostic factors of malignant pleural effusion n non-small cell lung cancer. Material and Method: We evaluated 33 NSCLC patients with malignant effusion treated between January 2002 and December 2003. We analyzed possible factors: gender, age, TNM Stage, fluid analysis (pH, CEA, LDH, glucose, albumin) and treatment modality. Median survival time of each factor was calculated by Kaplan-Meier method and difference of median survival time between groups of factor compared by log-rank test. The Cox proportional hazards regression model was used to confirm the significance of prognostic factor. Results: Of the 33 patients, 23 (69.7%) patients were adenocarcinoma. The median interval of the diagnosis of lung cancer and malignant effusion was 7.3 months ($25^{th}{\sim}75^{th}:\;3.9{\sim}11.8$), and the median survival time was 3.6 months (95% Confidence Interval: $1.14{\sim}5.99$). In the univariate analysis, using the log-rank test, those with an adenocarcinoma showed a relatively longer median survival time than those of a non-adenocarcinoma (4.067 vs. 1.867 months, p=0.067) without statistical significance. In the multivariate analysis, using the Cox regression, those with a non-adenocarcinoma showed a trend of high risk of cancer death than those with an adenocarcinoma without statistical significance (Relative risk; 2.754, 95% Cl: $0.988{\sim}7.672$, p=0.053). Conclusion: We could not find an independent prognostic factor of malignant pleural effusion in NSCLC. As there was a trend of high risk of cancer death according to histology, further study will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.363-368
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• 2014

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.