• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.290-300
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• 1998

Background: CYFRA 21-1 is a tumor marker which measures a fragment of cytokeratin 19 expressed by epithelial cells in bronchus. It is known that cytokeratin 19 is abundant in squamous epithelial cell cancer of the lung. However, if the incidence of elevated serum CYFRA 21-1 level in patients with benign lung diseases or pulmonary tuberculosis with severe parenchymal damage is high the specificity of CYFRA 21-1 could be decreased. The purpose of this study is to investigate the changes of serum CYFRA 21-1 according to the degree of parenchymal damage and the usefulness of CYFRA 21-1 for diagnosing possibly combined lung cancer in patients with pulmonary tuberculosis. Method: We studied the changes of serum CYFRA 21-1 according to the sputum AFB stain, radiologic manifestation and history of treatment in 81 patients with pulmonary tuberculosis, and 20 healthy persons, 25 patients with lung cancer, as a control group. CYFRA 21-1 concentration in serum was quantified by the immunoradiometry assay(Centocor$^{(R)}$). Result: The results were as follow; Serum CYFRA 21-1 level was significantly lower in patients with pulmonary tuberculosis($1.54{\pm}1.19ng/mL$, p<0.01) as compared to patients with lung cancer($12.25{\pm}15.97ng/mL$), and was slightly higher than the level in heathy persons($0.90{\pm}0.49ng/mL$) but there was no significant difference. Serum CYFRA 21-1 level was below the cut-off value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis but it was above the cut-off value in 64 percent of patients with lung cancer. Serum CYFRA 21-1 level was significantly higher in the initial treatment group($1.91{\pm}1.55ng/mL$, p<0.05) as compared to the treatment. failure group ($0.92{\pm}0.30ng/mL$). According to the sputum AFB smear, serum CYFRA 21-1 level in patients with negative result was slightly higher than the level in patients with positive result but there was no significant difference. According to the radiologic manifestation, serum CYFRA 21-1 level was significantly higher in patients with infiltrative lesion ($2.15{\pm}1.63ng/mL$, p<0.01) as compared to patients with destructive lesion ($l.04{\pm}0.54ng/mL$). As the size of cavity or destructive lesion was larger, the level was significantly lower(p<0.05). Conclusion: As serum CYFRA 21-1 level was significantly higher in the initial treatment group and patients with infiltrative lesion, it suppose to be closely related with the degree of parenchymal damage of the lung of the pulmonary tuberculosis. However CYFRA 21-1 could be useful method for diagnosing lung cancer even in patients with pulmonary tuberculosis combined with lung cancer because of the fact that it was below the cutoff value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.226-233
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• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Tuberculosis and Respiratory Diseases
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• v.66 no.5
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• pp.358-364
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• 2009

Background: The appropriate empirical antimicrobial choice in the treatment of community-acquired pneumonia (CAP) should be advocated by community-based information on the etiologic pathogens, their susceptibility to antimicrobials, clinical characteristics and outcomes. Jeju is a geographically isolated and identical region in Korea. However, there is no regional reference on adult CAP available. This study investigated the etiologic agents and clinical outcomes of adult patients diagnosed with CAP in Jeju, Korea, to help guide the empirical antimicrobial choice. Methods: A prospective observational study for one year in a referral hospital in Jeju, Korea. Patients diagnosed with CAP were enrolled with their clinical characteristics. Microbiological evaluations to identify the etiologic agents in the adult patients with CAP were performed with blood culture, expectorated sputum smear and culture, antibody tests for mycoplasma, chlamydophila, and antigen tests for legionella and pneumococcus. The clinical outcomes of the initial empirical treatment were analyzed. Results: Two hundred and three patients with mean age of 64 and 79 females were enrolled. Ten microbials from 90 cases (44.3%) were isolated and multiple isolates were confirmed in 30. Among the microbial isolates, S. pneumoniae (36.3%) was the most common, followed by M. pneumoniae (23.0%), C. pneumoniae (17.0%), S. aureus (9.6%) and P. aeruginosa (5.9%). The initial treatment failure (23.8%) was related to the isolation of polymicrobial pathogens, elevated inflammatory markers, and the presence of pleural effusion. Among the 30 isolates of S. pneumoniae, 16 (53.3%) were not susceptible to penicillin, and 19 isolates (63.3%) to erythromycin and clarithromycin. However, 29 isolates (96.7%) were susceptible to levofloxacin and ceftriaxone. Conclusion: S. pneumoniae, M. pneumoniae, S. aureus, and P. aeruginosa are frequent etiologic agents of adult CAP in Jeju, Korea. The clinical characteristics and antibiotic resistance should be considered when determining the initial empirical antimicrobial choice. Respiratory quinolone or ceftriaxone is recommended as an empirical antimicrobiotic in the treatment of adult CAP in Jeju, Korea.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.13-19
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• 2009

Background: The interferon-gamma assay is reported to have high sensitivity and specificity for making the diagnosis of latent tuberculosis infection. The clinical usefulness of this essay for detecting active tuberculosis has not fully defined. We evaluated the diagnostic value of the commercial interferon-gamma assay kit (QuantiFERONTB GOLD) for patients with suspected tuberculosis. Methods: From January to August 2007, we recruited 52 patients with suspected tuberculosis infection. We performed chest X-ray, sputum smear, culture, PCR and the QuantiFERON-TB GOLD test. Pleural fluid analysis and pleural biopsy were also done for the patients with pleural effusion. Results: Of the 52 patients we studied, 30 patients had a positive QuantiFERON-TB GOLD test result. 35 patients were finally diagnosed with active tuberculosis: twenty-five with a positive QuantiFERON-TB GOLD test and 10 with a negative QuantiFERON-TB GOLD test. The sensitivity of the QuantiFERON-TB GOLD test was 71.4% and the specificity was 64.7%. The positive predictive value was 0.83 and the negative predictive value was 0.50. There was no significant difference of any of the clinical and laboratory characteristics between the two groups of patients except the C-reactive protein (CRP) level. The CRP level was 29.2${\pm}$27.3 mg/dL in the pulmonary tuberculosis patients with a positive QuantiFERON-TB GOLD test and 72.9${\pm}$67.9 mg/dL in the patients with a negative QuantiFERON-TB GOLD test (p<0.05). Conclusion: The sensitivity and specificity of the QuantiFERON-TB GOLD test were inadequate for making the diagnosis of active tuberculosis. We suggest that the QuantiFERON-TB GOLD test should not be used by itself to exclude the diagnosis of active tuberculosis. The relationship of the QuantiFERON-TB GOLD test and the CRP level in patients with TB would be further investigated.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.161-172
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• 2002

Background : To Investigate the association between bronchial anthracofibrosis (AF) and tuberculosis (TB), and the clinical utility of a polymerase chain reaction (PCR) on bronchial specimens for rapid diagno-sis of active pulmonary TB in patients with bronchial AF. Method : Thirty patients (25 women and 5 men ranging in age from 53 to 88), who were diagnosed with bronchial AF by a bronchoscopic exami-nation, were enrolled in this study. PCR targeting the IS6110 segment of Mycobacterium tuberculosis was performed on the bronchial wash fluid and anthracofibrotic bronchial tissue. The PCR results were compared with the bacteriological, histological, and clinical findings. Results : Eighteen of the 30 patients (60%) were associated with TB, nine of whom were confirmed as having active TB. The remaining 9 had a past history of TB. The sputum or bronchial aspirate AFB smear, culture, and histological findings were positive in 4 (13%), 9 (30%), and 5 (17%) patients, respectively. PCR of the AF tissue and bronchial wash fluid was positive in 5 (17%) and 11 (37%) of the 30 patients, respectively. PCR was more sensitive than the AFB smears for diagnosing pulmonary TB (22 % us 89 %, respectively, p<0.05). All 5 patients with positive AF tissue PCR results also had both histological findings and positive bronchial wash fluid PCR results. Of the 3 patients with positive PCR but negative bacteriological or histological results, 2 of these patients appeared to have active tuberculosis on a clinical basis. Conclusion: Although TB-PCR did not reveal an increased association between bronchial AF and TB compared with traditional methods, PCR on the bronchial wash fluid appears to be useful for the rapid diagnosis of pulmonary TB in patients with bronchial AF. TB-PCR on AF bronchial tissue itself did not yield additional benefits for diagnosing TB, which suggests that an AF lesion itself may not be an active or original site of the infection, but a secondary change of TB.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.169-178
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• 2000

Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.

• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.344-352
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• 2003

Background : The prevalence of multidrug resistant tuberculosis (MDR-TB), resistant to isoniazid (INH) and rifampin (RFP), was 5.3% worldwide in 1995 and its increment has raised important public health problems. Resistance to RFP, one of the key drugs in the treatment of tuberculosis, results in grim clinical outcome. Recently rapid detection of RFP-resistant mutations in rpoB gene based on PCR method has become available. This study evaluated the prevalence of RFP resistance in first diagnosed, treatment failure, and recurred patients using INNO-LiPA test, and compared the results of INNO-LiPA with those of conventional mycobacterial drug susceptibility test. Methods : Forty-six patients, who were diagnosed of pulmonary tuberculosis and had revealed positive sputum AFB smear, were enrolled in this study from 1998 to 2002. The cases were classified as one three groups; first diagnosed, treatment failure, or recurred. RFP resistance was studied using an INNO-LiPA Rif. TB kit and compared with that obtained from drug susceptibility based on M. tuberculosis culture study. Results : Twenty-one out of 46 patients were enrolled under first diagnosis of pulmonary tuberculosis, 17 under treatment failure with first line drugs, and 8 under recurrence. The positive and negative predictive values of INNO-LiPA test in diagnosis in RFP resistant tuberculosis compared with conventional mycobacterial drug susceptibility test were 85.7% and 76.0%, respectively. INNO-LiPA result revealed rpoB gene mutation in 20 (80.0%) out of 25 patients who were diagnosed as treatment failure or recurrence, but in only 4 (19.0%) out of 21 patients who were first diagnosed as pulmonary tuberculosis. Conclusion : This study showed that RFP resistance could be diagnosed rapidly and accurately using INNO-LiPA test and that this test might be helpful for choosing second line anti-mycobacterial drugs. It might be of great help in clinical diagnosis and decision when used in complimentarily with drug susceptibility test based on M. tuberculosis culture.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.760-773
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• 2000

Background : Hemoptysis is a common clinical symptom responsible for 11% of admission to the hospital chest service. In KOREA pulmonary tuberculosis is still the most common cause of hemoptysis and the incidence of hemoptysis due to neoplasia has increased. Bronchoscopy and high resonance CT are essential for diagnosis of the cause of hemoptysis. We studied the causes, diagnostic tools and treament treatment of hemoptysis Methods : We conducted a retrospective analysis of clinical profiles, radiologic and bronchoscopy findings and treatments of hemoptysis for 220 patients who were admitted to our hospital with hemoptysis between 1994 and 1998. Results : The mean age at diagnosis was 49.3 years and male to female ratio was 2.1 : 1. The main causes were active pulmonary pulmonary tuberculosis in 72 cases(32.7%), inactive pulmonary tuberculosis with sequlae in 69 cases(31.4%) lung cancer in 43 cases(19.5%), bronchiectasis in 10 cases(4.5%), and chronic bronchitis in 10 cases(4.5%). The mean amount of hemoptysis for 24hrs was 120cc. The mean duration of bleeding was 25 days. The number of cases with a past history of pulmonary tuberculosis were 128 cases, in which 24 were relapsed tuberculosis cases, 25 chronic tuberculosis cases, 69 inactive tuberculosis cases, and 10 lung cancer cases. High resonance CT was the most useful method for structural etiologic evaluation of hemoptysis developed in patients with inactive tuberculosis, bronchiectasis and aspergilloma. Sputum study and bronchofiberscopy were the confirmative diagnostic tools for active pulmonary tuberculosis and lung cancer. The treatments of hemoptysis medical in 152 cases(71.7%), bronchial arteη embolization in 39 cases(17.8%), and operation in 9 cases(4.0%). The mean following up duration was 22.4 months. The overall outcomes of hemoptysis were controlled in 77 cases(43.5%), rebleeding in 100 cases (56.5%) and expired in 9 cases (4.0%). The outcomes of hemoptysis in pulmonary tuberculosis were controlled in 21.6%, rebleeding in 78.4%, and expire in 14.7%. Conculsion : The most common cause of hemoptysis was related with pulmonary tuberculosis. HRCT was an important diagnostic tool in AFB smear negative active pulmonary tuberculosis and inactive tuberculosis with sequelae. Early, proper management of pulmonary tuberculosis is important for prevention of hemoptysis in Korea.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.248-260
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• 2004

Background : As an effective regimen for isoniazid (INH)-resistant pulmonary tuberculosis, several treatment regimens have been recommended by many experts. In Korea, a standard regimen has not been established for INH-resistant tuberculosis, and the treatment by individual physicians has been performed on an empirical bases. The purpose of the present study was to retrospectively describe the treatment characteristics and evaluate the treatment outcomes of patients with INH-resistant tuberculosis. Materials and Methods : Sixty of 69 patients reported to have INH-resistant tuberculosis from 1994 to 2001 were retrospectively analyzed. Exclusion criteria included: death from other causes, with the exceptions of tuberculosis and incomplete treatment, including a patient's transfer-out. Results : A previous tuberculosis history was found in 28 (46.7%) patients. The sputum smear for acid-fast bacilli was positive in 44 (73.3%) patients, and 30 (50.0%) had cavitary disease. Streptomycin resistance coexisted in 25.0% of isolates. INH was to be prescribed continuously, even after INH resistance was reported, in 86.0% of patients. The treatment regimens were diverse between the patients according to drug regimen composition and treatment duration. The most frequent prescribed regimen included rifampin, ethambutol and pyrazinamide, with and without INH, for the full 12-month term of treatment. Treatment failure occurred in 13 (21.7%) patients. Cavitary disease (p=0.005) and a treatment regimen with second-line drugs, excluding rifampin (p=0.015), were associated with treatment failure. One patient experienced a relapse. Conclusions : Standardized treatment guidelines will be needed in Korea to improve the treatment efficacy for INH-resistant tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.401-408
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• 2002

Background : Tuberculin skin test is a method to examine M. tuberculosis infection and has been used all over the world. But various factors make it difficult to understand testing results. In 2000, the American Thoracic Society recommended that skin test results should be decided by considering risk factors of the tested. In Korea, high tuberculosis infection rate and BCG vaccination rate make it difficult to differentiate current infection, past infection, and no infection by the skin test. This study was attempted to examine a negative predictive value of the skin test to understand how the skin test acts on deciding administration of anti-tuberculosis drug. Methods : From Mar. 1 to Jul. 31 in 2001, the test was performed for patients hospitalized in Department of Internal Medicine, Hallym University College of Medicine, Chunchon, Korea by administering Tuberculin PPD RT23 2 TU (0.1 ml)to them that has been currently used in Korea based on Mantoux method. They were decided to be infected with tuberculosis bacilli by following diagnostic standard: 1) tuberculosis bacilli was cultured in sputum by microbiological diagnostic standard or Acid-fast bacilli was proven on a microscopic examination or 2) tuberculosis bacilli was not proven in the aforesaid microbiological test by clinical diagnostic standard, while there was opinion or symptom suitable for tuberculosis by radiographic or histological standard so the doctor decided to apply the tuberculosis treatment. Results : In this study, total 210 patients except 20 patients (8.7%) among 230 hospitalized patients were evaluated. Their average age was 60±16.8 years, and male-female rate was 1.28 : 1 (male: 118, female: 92). Number of patient, who was diagnosed and decided as tuberculosis, was 53(25.2%). Pulmonary tuberculosis was found in 45 patients (84.9%); 22 patients were decided to be positive in the Acid-fast bacilli smear test by microbiological examination (culture positive: 13, culture negative: 9), and 23 patients were decided to be tuberculosis patients by clinical diagnosis standard. Tuberculosis pleuritis was found in 8 patients (15.1%); 4 patients were diagnosed and decided by histological standard, and 4 patients were decided and treated by clinical standard. In differentiating patients into 'Negative' and 'Positive' by the skin test standard of the American Thoracic Society, negative predictive value 92.3%, positive predictive value 47.3%, sensitivity and specificity were 83%, 68.8%, respectively. Conclusion : In hospitalized respiratory patients, there was high negative predictive vlaue 92.3% by tuberculin skin test, therefore skin test would be a important factor for deciding administration of anti-tuberculosis drug on negative skin test patient.