• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.560-569
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• 2003

Background : A large number of pollutants such as sulfur dioxide, nitric oxide, carbon monoxide, particulate matter, and ozone influence on the body. These pollutants put a burden on the lung and the sequelae resulting from the oxidative stress are thought to contribute to the development of fibrotic lung disease, emphysema, chronic bronchitis and lung cancer. Also, carbon monoxide generated from the incomplete combustion of carbon-containing compounds is an important component of air pollution caused by traffic exhaust fumes and has the toxic effect of tissue hypoxia and produce various systemic and neurologic complications. The objective of this study is to compare the difference of pulmonary function and serum carboxyhemoglobin(CO-Hb) level between the traffic policemen and clerk policemen. Method : Three hundred and twenty-nine of traffic policemen, and one hundred and thirty clerk policemen were included between 2001 May and 2002 August. The policemen who took part in this study were asked to fill out a questionnaire which included questions on age, smoking, drinking, years of working, work-related symptoms and past medical history. The serum CO-Hb level was measured by using carboxyoximeter. Pulmonary function test was done by using automated spirometer. Additional tests, such as elecrocardiogram, urinalysis, chest radiography, blood chemistry, and CBC, were also done. Results : $FEV_1(%)$ was $97.1{\pm}0.85%$, and $105.7{\pm}1.21%$(p<0.05). FVC(%) was $94.6{\pm}0.67%$, and $102.1{\pm}1.09%$, respectively(p<0.05). Serum CO-Hb level was $2.4{\pm}0.06%$, and $1.8{\pm}0.08%$(p<0.05). After correction of confounding factors (age, smoking), significant variables were FVC(%), $FEV_1(%)$ and serum CO-Hb level(%)(p<0.05). Conclusion : Long exposure to air pollution may influence the pulmonary function and serum CO-Hb level. But, further prospective cohort study will be needed to elucidate detailed influences of specific pollutants on pulmonary function and serum carboxyhemoglobin level.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.367-377
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• 2003

Background : It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). Methods : HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. Results : Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. Conclusion : HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.

• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.589-596
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• 2003

Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patients in the our nation with high incidence of tuberculoma. We could not exclude whether the SPN was benign or malignant by the change of the size at chest radiograph and findings of chest CT. Recently, positron emission tomography(PET) have been tried as the differential diagnostic method of SPN. We evaluated the efficacy of PET for differentiating malignant from benign SPN and the relationship between standardized uptake values(SUV) of PET and serum glucose. Method : Between January 2001 and July 2002, sixty-one patients with pulmonary nodule were examined by the chest CT and PET. The SPN has been finally diagnosed by the transthorasic needle aspiration and biopsy, bronchoscopic biopsy, and open lung biopsy. Results : Forty eight patients had a malignant nodule(23 squamous cell lung carcinoma, 16 adenocarcinoma, 9 small cell lung cancer) and thirteen patients had a benign nodule(3 tuberculoma, 9 inflammatory granuloma, 1 cryptococcosis). The mean size of malignant and benign nodule was 40.6 mm and 20.0 mm, respectively. All malignant nodules showed a marked increase in 18 fluorodeoxyglucose (FDG) uptake. Mean SUV of malignant was $9.52{\pm}5.20$ and benign nodule was $1.61{\pm}3.60$. There were false positive cases with an increase in 18-FDG uptake (2 tuberculoma, 1 inflammatory granuloma). The SUV of malignant nodule in diabetes patients has no difference in non diabetes patients($9.10{\pm}4.51$ vs $9.65{\pm}5.46$). The sensitivity and specificity of the PET scan for SPN were 100%, 77%, respectively. The positive and negative predictive values were 94% and 100%. Conclusion : PET scanning showed highly accurate result in differentiating the malignant and benign SPN. There were no significant differences between the SUV and serum glucose in the patients with lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.597-611
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• 2003

Background : Loss of the short arm of chromosome 16 is a frequent event in various cancers, which suggests the presence of tumor suppressor gene(s) there. To map precise tumor suppressor loci on the chromosome arm for further positional cloning efforts, we tested 23 primary small cell lung cancers. Method : The DNAs extracted from paraffin embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Twenty polymorphic microsatellite markers located in the short arm of chromosome 16 were used in the microsatellite analysis. Results : We found that six (26.1%) of 23 tumors exhibited LOH in at least one of tested microsatellite markers. Two (8.7%) of 6 tumors exhibiting LOH lost a larger area in chromosome 16p. LOH was observed in five common deleted regions at 16p. Among those areas, LOH between D16S668 and D16S749 was most frequent (21.1%). LOH was also observed at four other regions, between D16S3024 and D16S748, D16S405, D16S420, and D16S753. Six of 23 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.3% (15 of 460) of the loci tested. Conclusion : Our data demonstrated that at least five tumor suppressor loci might exist in the short arm of chromosome 16 and that they may play an important role in small cell lung cancer tumorigenesis.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.18-24
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• 2005

Background : Endobronchial tuberculosis often complicates bronchostenosis, which can cause dyspnea due to an airway obstruction, and can be misdiagnosed as bronchial asthma or lung cancer. This study investigated the possible correlation between the $interferon-{\gamma}$($IFN-{\gamma}$) and transforming growth $factor-{\beta}$($TGF-{\beta}$) levels in the serum and bronchial washing fluid and the treatment results in endobronchial tuberculosis patients. Methods : Sixteen patients, who were diagnosed as endobronchial tuberculosis using bronchoscopy, and 10 healthy control subjects were enrolled in this study. The $IFN-{\gamma}$ and $TGF-{\beta}$ levels were measured in the serum and bronchial washing fluid of 16 endobronchial tuberculosis patients before and after treatment using the ELISA method. The endobronchial tuberculosis patients were divided into those who showed bronchial fibrostenosis after treatment and those who did not. Results : The $IFN-{\gamma}$ and $TGF-{\beta}$ levels in the bronchial washing fluid in endobronchial tuberculosis patients were elevated comparing to the control (p<0.05). After treatment, 7 of the 16 endobronchial tuberculosis patients showed bronchial fibrostenosis and the other 9 cases healed without this sequela. In the patients with fibrostenosis after treatment, the initial serum $TGF-{\beta}$ level was lower than the patients without fibrostenosis after treatment (p<0.05). Moreover, the serum $TGF-{\beta}$ level after treatment further decreased comparing to the patients without fibrostenosis after treatment(p<0.05). Conclusion : Elevated $IFN-{\gamma}$ and $TGF-{\beta}$ levels in the bronchial washing fluid in endobronchial tuberculosis patients are believed to be related to the pathogenesis of endobronchial tuberculosis. The decreased initial serum $TGF-{\beta}$ level and the change in the serum $TGF-{\beta}$ level after treatment are believed to be involved in bronchial fibrostenosis during the course of the disease.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.11-17
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• 2005

Background : Interferon-gamma ($IFN-{\gamma}$) is essential in the immune response to mycobacterial infections, and a complete or partial deficiency in the $IFN-{\gamma}$ receptor 1 ($IFN{\gamma}R1$) or the $IFN-{\gamma}$ receptor 2 ($IFN{\gamma}R2$) have been reported to confer susceptibility to a disseminated infection with nontuberculous mycobacteria. However, similar mutations in the $IFN-{\gamma}$ receptor have not been specifically examined in the patients with clinical tuberculosis. Methods : This study searched for mutations in the $IFN-{\gamma}$ receptor gene that resulted in a partial $IFN-{\gamma}$ receptor deficiency in six patients with disseminated tuberculosis. The previously identified $IFN{\gamma}R1$ and $IFN{\gamma}R2$ coding regions were sequenced after amplification. Results : There was no partial $IFN{\gamma}R1$ deficiency including a homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and a hotspot for small deletions (818delT, 818del4, 818insA) found in any of the patients. In addition, a partial $IFN{\gamma}R2$ deficiency of the homozygous missense mutation (R114C) was not found in any of the patients. Conclusion : Genetic defects causing a partial $IFN-{\gamma}$ receptor deficiency were not identified in our patients with disseminated tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.72-75
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• 2006

Background : This report reviews our experience with persistent air leaks in the peumothorax that were not considered candidates for surgical treatment in order to evaluate the efficacy and risks of the OK-432 plus autoblood or OK-432 pleurodesis. Material & Methods : From March 2004 to July 2005, 8 consecutive patients who had an air leak in the pneumothorax over 5 days and had been treated with OK-432 plus autoblood or OK-432 pleurodesis. The patients were not considered candidates for surgical treatments because the chest CT findings revealed severe chronic lung disease with multiple bullae and/or bullous changes. A prolonged air leak with/without dead space was treated with either OK-432 plus autoblood or OK-432 pleurodesis. The efficacy and side effects of OK-432 pleurodesis were assessed by determining the duration of the air leak, the number of pleurodesis, the patients' symptoms, measurements of the white blood cell count and the c-reactive protein level. Results : All of eight patients were male and the mean age was $72.4{\pm}8.5$. The mean number of pleurodesis was $1.9{\pm}1.1$ and the mean duration of the air leak was $4.6{\pm}4.6days$ after pleurodesis. Side effects after pleurodesis were encountered in 7 patients, which included a chilling sensation in 7 cases, chest pain in 5 cases, headache in 3 cases, local heat sensation in 2 cases, and fever in 1 case. Leukocytosis was observed in 6 patients, and the mean of WBC count and CRP were $14500{\pm}2100$ and $21.9{\pm}11.4mg/dL$, respectively. Conclusion : Either OK-432 plus autoblood or OK-432 pleurodesis has acceptable side effects, and can be considered a treatment option for persistent air leaks in the pneumothorax that are not candidates for surgical treatment.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.65-71
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• 2006

Background : Hemoptysis, when massive and untreated, has a mortality rate of over 50 percents, is considered as one of most dreaded of all respiratory emergencies and can have a variety of underlying causes. Bronchial artery embolization (BAE) has become an established procedure in the management of massive and recurrent hemoptysis, and its efficacy is widely documented thereafter by number of articles. However, the long-term success rate of BAE is known to be unfavorable. Risk factors influencing that control failure are inevitably needed. Materials and methods : Seventy-five patients underwent bronchial artery embolization due to massive hemoptysis in Severance Hospital from Jan. 2000 to Jan. 2005. Nine patients' data were not available and could not be contacted with. Finally 66 patients' (48 males, 18 females) medical records were analyzed retrospectively during a mean follow up period of 20.4 months (ranging from 1 month to 54 months). Results : Among 66 patients whose data were available, 23(34.9%) patients had recurrent major hemoptysis. Patients' age, sex, underlying disease, previous intervention history, and number of feeding vessels had no statistical validity as risk factors of recurred major hemoptysis. But bilaterality of lesion, amount of hemoptysis, and pleural thickening were revealed as meaningful factors for predicting relapse (p = 0.008, 0.018, and 0.001, respectively). Conclusion : According to our series, patients presenting with larger amount of hemoptysis, pleural thickening of chest radiography and bilateral lesion are associated with increased risk of major hemoptysis in patients treated with BAE.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.406-412
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• 2005

Background : Recently, two commercialized whole-blood assays, $QuantiFERON^{(R)}-TB$ Gold (QFT) and T $SPOT-TB^{(R)}$ (SPOT), which measure the $IFN-{\gamma}$ released in the whole blood after being incubation with mycobacterial antigens, were approved for the diagnosis of a latent tuberculosis infection (LTBI). However, there is data on whether or not the previously used PPD skin tests (TST) have any influence on the diagnostic ability of these ex-vivo $IFN-{\gamma}$ assays. Methods : Forty-six 15 year-old students who did not appear to be infected with Mycobacterium tuberculosis were enrolled in this study. The peripheral blood was collected and used for two $IFN-{\gamma}$ assays. The $IFN-{\gamma}$ assays and TST were performed at the baseline ($1^{st}$). The TST was repeated two months later ($2^{nd}$), and the $IFN-{\gamma}$ assays were repeated two ($2^{nd}$) and four months ($3^{rd}$) later only in those subjects who had negative results at the baseline in both the $IFN-{\gamma}$ assays and TST. An induration size > 10 mm was considered to be positive in the TST. Results : The mean TST value was $3.1{\pm}5.4mm$ (range: 0-20). Of the 46 subjects examined, 13 subjects (28.3%) showed positive results in the two-step TST. Nine (19.6%) were SPOT-positive and only one (2.2%) was QFT-positive. The $2^{nd}$ and $3^{rd}$ QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The $2^{nd}$ SPOT was performed in 23 subjects and only one (4.3%) showed a weak-positive result. Conclusion : Even though there were some discrepancies in the results of the two ex-vivo $IFN-{\gamma}$ assays, it appears that their results were not influenced by a previous TST carried out in two or four months earlier.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.44-48
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• 2006

Background : Isoniazid (INH) is one of the most effective anti-tuberculosis (TB) drugs. In Korea, the dose of INH normally used in patients over 50 kg is 400 mg/day, which differs from the dose recommended by other countries. Indeed, the metabolism of INH shows ethnic variations, and Koreans are predominantly rapid acetylators. However, two reports suggested 300 mg of INH might be sufficient to reach an ideal peak level in Korean patients over 50 kg. Therefore, the aim of this study was to compare the effectiveness and adverse reactions between INH 300 mg and 400 mg in Korean TB patients. Method : Patients who were culture-positive, susceptible to all 1st-line drugs, initially on HREZ, and weighed over 50 kg were selected from patients with pulmonary TB between April 2003 and March 2005. The treatment results and adverse reactions in the INH 300 mg and 400 mg group were compared. Since April 2004, most TB patients at Asan Medical Center were administered INH 300 mg irrespective of the body weight. Results : The study included 123 patients in the 300 mg INH group and 128 in the 400 mg INH group. There were no significant differences between the groups in terms of age, gender, weight, history of TB treatment, initial smear strength, and frequency of cavitary lesions. There was no difference in the treatment duration between the groups. One hundred eleven (90%) patients in the INH 300 mg group and 102 (80%) in the INH 400 mg group completed treatment (p>0.05). There were no differences in the frequency of modification of the initial regimen between groups due to any adverse reactions (300 mg : 9.0%, 400 mg : 13.7%) and hepatotoxicity (300 mg : 2.7% ; 400 mg : 7.8%). Conclusion : Considering treatment results and adverse reactions of two groups, 300mg of INH may be sufficient for treating Korean TB patients. Further studies comparing the frequency of relapse will be needed.