• Tuberculosis and Respiratory Diseases
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• v.76 no.4
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• pp.153-159
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• 2014

Tuberculous pleurisy is the most common form of extrapulmonary tuberculosis in Korea. Tuberculous pleurisy presents a diagnostic and therapeutic problem due to the limitations of traditional diagnostic tools. There have been many clinical research works during the past decade. Recent studies have provided new insight into the tuberculous pleurisy, which have a large impact on clinical practice. This review is a general overview of tuberculous pleurisy with a focus on recent findings on the diagnosis and management.

• 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.61 no.6
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• pp.526-532
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• 2006

Backgroud: Traditionally, tuberculous pleurisy has been known to largely develop as primary tuberculosis. However, as the incidence of tuberculosis decrease, recent studies have shown reactivation tuberculosis has become the main cause of tuberculous pleurisy. Methods: 141 cases of tuberculous pleurisy, between January 2003 and February 2006, at the Dankook university hospital. were retrospectively studied. The patients were divided into primary and reactivation tuberculosis. based on the history and radiological characteristics, and the clinical, radiological characteristics at the time of diagnosis and residual pleural thickening after 6 month of chemotherapy were compared between the two groups. Results: 1. Of the 141 tuberculous pleurisy cases, in 135 it was possible to differentiate between primary and reactivation tuberculosis. 2. Of the 135 tuberculous pleurisy cases, 38 (28%) showed a primary tuberculosis pattern, and 98 (72%) showed a reactivation tuberculosis pattern. 3. There were no significant differences between primary and reactivation tuberculosis in relation to age, sex, duration of symptom, amount of pleural effusion, pleural fluid WBC, lymphocyte count, and level of protein, LDH and ADA at the time of diagnosis 4. 124 patients were followed for 6 months after diagnosis of tuberculous pleurisy, and there was no significant difference in the residual pleural thickening between primary and reactivation tuberculosis. Conclusion: In South Korea, a reactivation disease is currently a more common cause of tuberculous pleurisy than a primary disease. There was no difference in the clinical characteristics between primary and reactivation tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.135-143
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• 1994

Background: The cell mediated immunity has an important role in the pathogenesis of tuberculosis. sIL-2R has been known as a sensitive marker of T lymphocyte activation Elevated serum levels of sIL-2R have been found in patients with lymphoproliferative disorders, organ transplantation, autoimmune diseases, and various granulomatous diseases. Elevated levels of sIL-2R have been also found in the serum and pleural fluid of the patients with tuberculosis. To evaluate the diagnostic value of sIL-2R in the differentiation of tuberculous pleurisy and nontuberculous pleurisy. We measured the level of sIL-2R in the sera and pleural fluids of 12 patients with tuberculous pleurisy and 32 patients with nontuberculous pleurisy. Method: Samples of pleural fluid and serum were centrifuged at 2500 rpm for 10 min to remove cell pellets. Soluble IL-2R was measured with a sandwitch enzyme immunoassay using the Cellfree(r) Interleukin-2 Receptor Test kit(T-cell science,Inc. Cambridge, MA). Results: The results obtained were as follows: 1) The sIL-2R level in pleural fluid of the patients with tuberculous pleurisy was higher than that of patients with nontuberculous pleurisy(P<0.005). 2) When the sIL-2R level above 5,000 u/ml in pleural fluid was used as the cut-off value to diagnose tuberculous pleurisy, it had a sensitivity of 84.6% and a specificity of 90.9%. 3) The sIL-2R level in the sera of the patients with tuberculous pleurisy was higher than that of patients with bacterial pleural effusions and normal control group(P<0.05) and there was no difference of levels compared with malignant pleural effusions and transudative pleural effusions(P>0.05). 4) In patients with tuberculous pleurisy, the mean concentration of sIL-2R in pleural fluid was higher than that in serum(P<0.005). Conclusion: These findings suggest that the measurement of elevated levels of pleural fluid sIL-2R in tuberculous pleurisy may be useful in the differential diagnosis between patients with tuberculous pleurisy and nontuberculous pleurisy.

• Biomedical Science Letters
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• v.13 no.4
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• pp.325-332
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• 2007

Cell-mediated immune response (CMI) is a major immune protective mechanism against tuberculosis (TB) infection. Among several components involved in CMI, recent studies suggest that CD8+ T cells are important in controlling TB infection. In our previous report, we defined four Mycobacterium tuberculosis (MTB) derived epiotpe peptides specific for HLA-A*0201-restricted CD8+ T cells. These four peptides are $PstAl_{75-83}$, $ThyA_{30-38}$, $RpoB_{127-135}$ and $85B_{15-23}$. In this study, these epitope peptides specific CD8+ T cell responses in tuberculous pleurisy were investigated using ex vivo $IFN-\gamma$ elispot assay and intracellular $IFN-\gamma$ staining method. As a result, we observed these epitope peptide specific CD8+ T cell responses are induced in all three patients with tuberculous pleurisy suggesting that CD8+ T cells are involved in protective immune mechanism against MTB infection in tuberculous pleurisy. However, the CMI to mitogens and MTB antigens from pleural fluids of patients with tuberculous pleurisy does not seem to correlate with that from peripheral blood, although the sample size is too small to make any conclusion. In sum, the MHC I restricted CD8+ T cell responses seem to be induced efficiently in the pleural fluids, at the site of TB infection, in which the CMI is actively induced. In addition, these experiments suggest that MHC I restricted CD8+ T cell mediated immune responses are also involved in protective mechanism against MTB infection in extra-pulmonary TB.

• Tuberculosis and Respiratory Diseases
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• v.73 no.3
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• pp.143-150
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• 2012

Background: The release of interferon-gamma (IFN-${\gamma}$) by T lymphocytes increases after rechallenge with Mycobacterium tuberculosis antigen, especially, at a localized site of tuberculosis (TB) infection. We aimed to compare the clincial efficacy of two commercial IFN-${\gamma}$ release assays from pleural fluid for the diagnosis in tuberculous pleurisy. Methods: We performed T-SPOT.TB and QuantiFERON-TB Gold tests simultaneously on pleural fluid and peripheral blood samples from patients with pleural effusion, in South Korea, an area with intermediate TB burden. Results: Thirty-six patients were enrolled prospectively, and tuberculous pleurisy was found in 21 patients. Both the numbers of IFN-${\gamma}$ secreting T cells and the concentration of IFN-${\gamma}$ were greater in the pleural tuberculous group, comparing with the non-tuberculous group. Moreover, in the tuberculous group, there was a significant difference in IFN-${\gamma}$ producing spot-forming cells using the T-SPOT.TB method between pleural fluid and peripheral blood. The receiver operating characteristic (ROC) curve, was the greatest for pleural fluid T-SPOT.TB test, followed by peripheral blood T-SPOT.TB test, peripheral blood QuantiFERON-TB Gold test, and pleural fluid QuantiFERON-TB Gold test (area under the ROC curve of 0.956, 0.890, 0.743, and 0.721, respectively). The T-SPOT.TB assay produced less indeterminate results than did QuantiFERON-TB Gold assay in both pleural fluid and peripheral blood. Conclusion: These findings suggest that the pleural fluid T-SPOT.TB test could be the most useful test among the IFN-${\gamma}$ release assays for diagnosing tuberculous pleurisy in an area with an intermediate prevalence of TB infection.

• Journal of Chest Surgery
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• v.30 no.8
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• pp.793-802
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• 1997

A clinical analysis was performed on 52 cases of tuberculous pleurisy experienced in the department of thoracic and cardiovascular surgery and department of medicine, Chosun University Hospital during a period from Jan. 1994 to Dec. 1995. Among them, male was 39 cases, female was 13 cases, with age ranged from 7 to 73 years. The common symptoms were chest pain 75%, dyspnea 59.6%, cough 55.8%. The most common diagnostic tool was pleural biopsy. The protein levels in the tuberculous pleural effusion were 0.9∼6.5 gmojo, and ratios of effusion protein to serum protein were 0.48 ∼ 1.06. The glucose levels in the tuberculous pleural effusion were 37∼ 112 mg%. The LDH levels in the tuberculous pleural effusion were 80 ∼ 2440 unitlml, and ratios of tuberculous p eural effusion LDH to serum LDH were 0.48 ∼ 1.03. The ADA levels in the tuberculous pleural effusion were 24-63 lU/L. The common surgical methods of treatment in the tuberculous pleurisy were closed thoracostomy in 18 cases(66.7%), and thoracentesis in 5 cases(18.5%). This study compares the clinical results of group A and group B. There were no significant differences for age and sex, lag period from initial symptoms to admission, diagnostic method, and protein, pH, LDH, glucose, ADA levels in tuberculous pleural effusion. Authors noted that the discharge after admission on the tuberculous pleurisy was more faster in patients with surgical treatment than in patients with only medical treatment. (Korean J Thorac Cardiovasc Surg 1997;30:793-802)

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.301-310
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• 1998

Background: Cell mediated immune response mediated by interaction between CD4+ T lymphocytes and macrophagies is thought to play an important role in tuberculous pleurisy. This interaction is dependent on the interplay of various cytokines. The immunologic response of tuberculous pleurisy is thought to depend on the balance between helper T cell(Th1) cytokine Interleukin-12, Interferon gamma and Th2 cytokine IL-4, IL-10. To understand immunologic mechanism in tuberculous pleurisy and evaluate diagnostic value of these cytokines, the concentrations of Th1 cytokine IL-12, IFN -$\gamma$ and Th2 cytokine IL-10 were measured in tuberculous pleurisy and malignant pleural effusion group. Material and Methods: The concentrations of IL-10, IL-12 and IFN-$\gamma$ were measured by ELISA method in pleural fluids and serums of 20 patients with tuberculous pleurisy and 20 patients with malignant pleural effusion ADA activities were measured by spetrophotomery in pleural fluids of both groups. Results: In tuberculous pleurisy, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL and $420.4{\pm}285.9$ pg/mL. These were significantly higher than that of serum, $21.2{\pm}60.9$ pg/mL, 194.5 pg/mL, $30.1{\pm}18.3$ pg/mL respectively(p< 0.01). In malignant pleural effusion, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL and $30.5{\pm}54.8$ pg/mL respectively. Compared with that of serum ($43.4{\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL), only IL-10 was significantly higher (p<0.001), but IL-12, IFN-$\gamma$ were not significant. In tuberculous pleural effusion compared with malignant pleural effusion, the concentration of IL-12, IFN-$\gamma$, ADA were significantly higher (p=value 0.046, <0.001, <0.001), but IL-10 was not significant. For differential diagnosis of tuberculous pleurisy from malignant pleural effusion, using cut-off value of IL-12, IFN-$\gamma$, ADA as 300 pg/mL. 100 pg/mL, 45 U/L, the sensitivity/specificity were 60%/70%, 90%/87.5%, 85%/90% respectively. Conclusion: In tuberculous pleurisy, IL-10, IL-12 and IFN-$\gamma$ were selectively concentrated highly in pleural space than serum. Compared with malignant pleural effusion, IL-12 and IFN-$\gamma$ were significantly higher, but IL-10 were not in tuberculous pleural effusion. The results suggest that Th1 pathway contributes to immune resistant mechanism in tuberculous pleurisy. IFN-$\gamma$ and ADA revealed useful methods of differential diagnosis in tuberculous pleurisy from malignant pleural effusion.

• 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.3
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• pp.434-439
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• 1996

Although the incidence of pulmonary tuberculosis is declining, the number of extrapulmonary tuberculosis has remained constant. Tuberculous Lymphadenitis accounts for over 50% of total inflammatory lymphadenitis and the most common site is cervical lymph node. We report a case of single cervical tuberculous cold abscess associated with multiloculated and septated tuberculous pleurisy. Intracavitary urokinase instillation via percutaneous catheter is indicated in loculated and septated pleural effusion. And our result was satisfactory without complication.