• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.309-318
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• 2002

Background : Usual interstitial pneumonia (UIP) is a fatal progressive fibrotic disorder of the lung with unknown etiology and characterized by a poor response to conventional immunosuppressive therapy. The histologic hallmark of UIP is parchy distribution of subpleural fibrosis and fibroblastic foci(FBF) with interposed normal appearing lung. Because FBF is a collection of actively proliferating myofibroblasts, it can be a marker of activity and prognosis of UIP. However, there were contradictory reports about the correlation between the degree of FBF and survival. Therefore we performed this study to investigate the value of FBF as prognostic marker of UIP. Methods : This was a retrospective study on the 46 patients(M:F=33:13, mean age:$59{\pm}12$ years) with UIP diagnosed by the surgical lung biopsy at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the ATS/ERS classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) by the experienced pathologists who did not know the clinical findings were compared to the clinical data and the follow up course. Results : Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. At the univariate analysis, FVC, $D_Lco$, smoking history and the grade of FBF were significantly related to the survial. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking. However the multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. Conclusion : These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.826-835
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• 1999

Background : The $\beta_2$ adrenergic receptor ($\beta_2$ AR) polymorphisms occurring at amino acid position 16 (Arg to Gly), 27 (Gln to Glu), 34 (Val to Met), and 164 (Thr to Ile) are known to be functionally relevant and also disease-modifying in subjects with asthma. However the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for allergic disease remains to be established. Methods : 109 patients with bronchial asthma and 42 healthy person were included. Serum total IgE, allergen specific IgE, and skin prick test were performed to all of the subjects. $\beta_2$ AR polymorphisms were checked by mutated allele specific amplification (MASA) method. Results : The results were as follows. The frequencies of $\beta_2$ AR polymorphisms in asthmatic patients and healthy person were not statistically different(p>0.05). There was no association between $\beta_2$ AR polymorphisms of amino acid position 16, 27, 34 and the existence of atopy among asthmatic patients(p>0.05). Between asthmatic patients with or without elevated IgE level and $\beta_2$ AR polymorphisms of amino acid position 16, 27, 34, there was no statistically significant association(p>0.05). Conclusion : There was no difference in frequency of the $\beta_2$ AR polymorphism between asthmatic patients and healthy person. In the bronchial asthma, association of $\beta_2$ AR polymorphism and atopy/serum total IgE was not found.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.409-415
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• 2001

Background : Multidrug-resistant tuberculosis(MDR-TB) in patients is mainly caused by acquired drug resistance. However, a small proportion of MDR-TB is caused by initial drug resistance(IDR), which may be somewhat different from acquired drug resistance. This study analyzed the clinical characteristics of IDR in MDR -TB patients to use the results as basic data in managing the disease. Methods : A retrospective study of 30 IDR cases in MDR-TB patients from Jan. 1995 to Dec. 1998 was performed. In order to analyze the clinical characteristics, the age, sex, family history, duration of negative conversion, number of resistant drugs, treatment regimens, duration of treatment, extent of disease and cavitary lesion on the chest X-ray was examined. In order to analyze the level of improvement, the extent of the disease and cavitary lesion on the chest X-ray, tested by Wilcoxon signed rank sum test, and the disease free interval rate of 1-year and 4-year was examined using the Kaplan-Meier method. Results : The mean age of the patients was 46.6 years and the sex ratio 1:1. Six(20%) patients had a family history. The mean negative conversion of the sputum AFB stain was 2.6 months. The number of resistant drugs was 7.6 and the number of used drugs 3.6. Twenty-three(67%) patients were treated for less than 12months and 28(93%) patients were treated with first-line drugs. The extent of the disease and the cavitary lesion on the chest X-ray improved after treatment(p<.05). Among 13 patients who were followed up for 22.6 months, 2(15%) patients relapsed and the disease free interval rate of I-year and 4-year was 85%. Conclusion: It is recommended that the duration of treatment of IDR in MDR-TB with first-line drugs be 9-12 months even if the extent of disease and cavitary lesion on the chest X-ray improves.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.401-408
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• 2001

Background : Perfusion scans are accurate predictors of postoperative lung function. There are few previous studies aimed at predicting the postoperative exercise capacity using the perfusion scanning and those that did reported contradictory results. Method : We prospectively studied the preoperative spirometric, exercise tests and perfusion scans from in 49 consecutive patients who were admitted to Inha University Hospital with surgically resectable lung cancer from Jan. 1998 to Jun. 1999 29 patients who had any condition affecting the lung function and exercise capacity, or refused a surgical resection or a follow-up study were excluded. Spirometric and exercise tests were performed 6 months after operation in 20 patients. Results : The predicted postoperative $FEV_1$, FVC and TLC correlated well with the following corresponding postoperative values : $r_s$ and p value, 0.809 and 0.000 for the $FEV_1$ 0.895 and 0.000 for the FVC ; 0.741 and 0.006 for the TLC, respectively. The measured postoperative exercise values were slightly higher than the postoperative exercise values predicted, $VO_{2max}$ and $Wr_{max}$, were as 112% of $VO_{2max}$ predicted and 119% of $WR_{max}$ predicted. The change in $FEV_1$, FVC and TLC had a weak correlation with the change in $VO_{2max}$ and $WR_{max}$. Conclusion : The perfusion scan was a useful tool for predicting the postoperative exercise capacity. However, they had a tendency to underestimate the exercise capacity, especially in the patients who had a pneumonectomy. A weak correlation between the change in lung function and exercise capacity was observed.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.196-204
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• 2001

Background : Bronchial asthma is characterized by a reversible airway obstruction, airway hyperresponsiveness, and eosinophilic airway inflammation. The bronchodilator response(BDR) after short acting beta agonist inhalation and PC20 with methacholine inhalation are frequently used for diagnosing bronchial asthma. However, the relationship between the presence of a bronchodilator response and the degree of airway hyperresponsiveness is uncertain. Therefore, the availability of a eosinophil cationic protein (ECP) and a correlation ECP with a bronchodilator response and airway hyperresponsiveness was investigated. Method : A total 71 patients with a moderate to severe degree of bronchial asthma were enrolled and divided into two groups. 31 patients with a positive bronchodilator response and 38 patients with a negative bronchodilator response were evaluated. In both groups, the serum ECP, peripheral blood eosinophil counts, and total IgE level were measured and the methacholine bronchial provocation test was examined. Results : There were no differences observed in age, sex, atopy, and baseline spirometry in both groups. The peripheral eosinophil counts showed no difference in both groups, but the ECP level in group 1 (bronchodilator responder group) was higher than in group 2(non-bronchodilator responder group) ($22.4{\pm}20.7$ vs $14.2{\pm}10.4$, mean$\pm$SD). The PC20 in group 1 was significantly lower than in group 2 ($1.14{\pm}1.68$ vs $66{\pm}2.98$). There was a significant positive correlation between the BDR and ECP, and a negative correlation between the bronchial hyperresponsiveness and ECP. Conclusion : The bronchodilator response significantly correlated with the bronchial hyperresponsiveness and serum ECP in the moderate to severe asthma patients. Hence, the positive bronchodilator response is probably related with active bronchial inflammation and may be used as a valuable index in treatment, course and prognosis of bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.570-578
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• 2003

Background : Ambient particles during Asian dust events are usually sized less than $10{\mu}m$, known to be associated with the adverse effects on the general populations. But, there has been no considerable evidence linking these particles to the adverse effects on airways. The objectives of this study was to investigate the possible adverse effects of Asian dust events on respiratory function and symptoms in subjects with bronchial asthma. Patients and Methods : From march to June 2002, Asthmatic patients who were diagnosed with bronchial challenge test or bronchodilator response were enrolled. We divided them into three groups; mild, moderate, and severe, according to the severity. Subjects with other organ insufficiency such as heart, kidney, liver, and malignancy were excluded. All patients completed twice daily diaries and recorded peak flow rate, respiratory symptom, and daily activity. Daily and hourly mean pollutant levels of particulate matter < $10{\mu}m$ in diameter($PM_{10}$), nitrogen dioxide($NO_2$), sulphur dioxide($SO_2$), ozone($O_3$) and carbon monoxide(CO) were measured at the 10 different monitoring sites. Results : Dust events occured 14 times during the study period. Daily averages of 4 air pollutant were measured with an increased level of $PM_{10}$, decreased level of $NO_2$ and $SO_2$, and no change in CO during dust days compared to those during control days. An increase in $PM_{10}$ concentration was associated with an increase of subjects with PEF variability of >20% (p<0.05), night time symptom(p<0.05), and a decrease in mean PEF (p<0.05), which were calculated by the longitudinal data analysis. Otherwise, there was no association between $PM_{10}$ level and bronchodialtor inhaler, and daytime respiratory symptoms. Conclusion : This study shows evidence that ambient air pollution, especially $PM_{10}$, during Asian dust events, could be one of the many aggravating factors at least in patients with airway diseases. This data can be used as a primary source to set up a new policy on air environmental control and to evaluate the safety of air pollution index. We also expect that this research will help identify precise components of dust, which are more linked to the adverse effects.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.488-498
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• 2003

Background : Activation of the transcription factor NF-${\kappa}B$ has been shown to protect cells from tumor necrosis factor-alpha, chemotherapy, and radiation-induced apoptosis. NF-${\kappa}B$-dependent cIAP expression is a major antiapoptotic mechanism for that. NF-${\kappa}B$ activation and cIAP expression in A549 lung cancer cells which is relatively resistant to radiation-induced cell death were investigated for the mechanism of radioresistance. Materials and methods : We used A549 lung cancer cells and Clinac 1800C linear accelerator for radiation. Cell viability test was done by MTT assay. NF-${\kappa}B$ activation was tested by luciferase reporter gene assay, Western blot for $I{\kappa}B{\alpha}$ degradation, and electromobility shift assay. For blocking ${\kappa}B$, MG132 and transfection of $I{\kappa}B{\alpha}$-superrepressor plasmid construct were used. cIAP expression was analyzed by RT-PCR and cIAP2 promoter activity was performed using luciferase assay system. Results : MTT assay showed that cytotoxicity even 48 hr after radiation in A549 cells were less than 20%. Luciferas assay demonstrated weak NF-${\kappa}B$ activation of $1.6{\pm}0.2$ fold compared to PMA-induced $3.4{\pm}0.9$ fold. Radiation-induced $I{\kappa}B{\alpha}$ degradation was observed in Western blot and NF-${\kappa}B$ DNA binding was confirmed by EMSA. However, blocking NF-${\kappa}B$ using MG132 and $I{\kappa}B{\alpha}$-superrepressor transfection did not show any sensitizing effect for radiation-induced cell death. The result of RT-PCR for cIAP1 & 2 expression was negative induction while TNF-${\alpha}$ showed strong expression for cIAP1 & 2. The cIAP2 promoter activity also did not show any change compared to positive control with TNF-${\alpha}$. Conclusion : We conclude that activation of NF-${\kappa}B$ does not determine the intrinsic radiosensitivity of cancer cells, at least for the cell lines tested in this study.

• 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.403-414
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• 2003

Background : Proteasome inhibitors can promote either cell survival or programmed cell death, depending on both the specific type and proliferative status of the cell. However, it is not well known whether inhibition of proteasome activity is related to apoptosis in lung cancer cells. In addition, the exact mechanisms responsible for apoptosis induced by proteasome inhibition are not well understood. In the present study, we have examined the effect of proteasome inhibition on lung cancer cells and tried to test the mechanisms that may be associated with the apoptosis of these cells. Methods : We examined the effect of proteasome inhibition with MG132 or PS-341 on cell survival in A549 and NCI-H157 lung cancer cells using MTT assay, and analyzed the cleavage of PARP by Western blot analysis to find evidence of apoptosis. Next, we evaluated the activation of caspase 3 by Western blot analysis and the activity of JNK by immunocomplex kinase assay. We also examined the changes in anti-apoptotic pathways like ERK and cIAP1 by Western blot analysis after inhibition of proteasome function. Results : We demonstrated that MG132 reduced cell survival by inducing apoptosis in A549 and NCI-H157 cells. Proteasome inhibition with MG132 or PS-341 was associated with activation of caspase 3 and JNK, reduced expression of activated ERK, and downregulation of cIAP1. Conclusion : Apoptosis induced by proteasome inhibition may be associated with the activation of pro-apoptotic pathways like caspase 3 and JNK and the inactivation of anti-apoptotic pathways in lung cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.473-479
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• 2005

Background : A pulmonary embolism often presents with nonspecific symptoms and signs. However, a delayed diagnosis can result in catastrophic outcome. The majority of preventable deaths associated with a pulmonary embolism can be ascribed to a missed diagnosis rather than to the failure of existing treatments. Therefore, accurate and rapid diagnostic methods are essential for the management of a pulmonary embolism. The recent generation of multidetector-row spiral CT scanners appears to outperform other imaging modalities in detecting a central and peripheral pulmonary embolism. However, there are some variations in the interpretations of the findings between observers. This study examined the inter-observer differences of the diagnoses in patients with a pulmonary embolism. Method : 64 patients who were diagnosed with a pulmonary embolism either clinically or with spiral chest CT from 2002 to 2004, were included. Two thoracic radiologists interpreted the multidetector-row spiral CT in terms of the diagnosis of a pulmonary embolism and the location of the thrombus independently. Among 64 patients, 14 patients were excluded because there was no evidence of a pulmonary embolism or there was different interpretation of the pulmonary embolism between radiologists. A clinical diagnosis was based on "Rules for predicting the probability of embolism". Results : The mean score of the patients according to the Wells method was $3.91{\pm}0.30$ (0-9). The accordance of the radiologists was 95% in the main, 85% in the lobar, 91.2% in the segmental, and 96% in the sub-segmental pulmonary arteries. After excluding the negative interpretation from both radiologists, their agreement was 76.2%(${\kappa}.$ 0.83) in the main, 57.6%(${\kappa}.$ 0.63) in the lobar, 51.5%(${\kappa}.$ 0.63) in the segmental, and 34.6%(${\kappa}.$ 0.49) in the sub-segmental pulmonary arteries. Conclusion : Chest CT has been recently applied to patients suspected of having a pulmonary embolism. It was found that spiral CT is a rapid test for diagnosing a thrombus, and there was reliable accordance between the observers from the area of the large pulmonary arteries. However, there was a lack of agreement between the observers in diagnosing thrombi located distal to the sub-segmental arteries.