• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.506-515
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• 2003

Background : A decreased level of serum arginine vasopressin(AVP) and an increased sensitivity to an exogenous AVP is expected in patients with septic shock who often require a high infusion rate of catecholamines. The goal of the study was to determine whether an exogenous AVP infusion to the patients with septic shock would achieve a significant decrement in infusion rate of catecholamine vasopressors while maintaining hemodynamic stability and adequate urine output. Method : Eight patients with septic shock who require a high infusion rate of norepinephrine had received a trial of 4-hour AVP infusion with simultaneous titration of norepinephrine. Hemodynamic parameters and urine output were monitored during the AVP infusion and the monitoring continued up to 4 hours after the AVP infusion had stopped. Results : Mean arterial pressure showed no significant changes during the study period(p=0.197). Norepinephrine infusion rate significantly decreased with concurrent AVP administration(p=0.001). However, beneficial effects had disappeared after the AVP infusion was stopped. In addition, hourly urine output showed no significant changes throughout the trials(p=0.093). Conclusion : Concurrent AVP infusion achieved the catecholamine vasopressor sparing effect in the septic shock patients, but there was no evidence of the improvement of renal function. Further study may be indicated to determine whether AVP infusion would provide an organ-protective effect to the septic shock patients.

• 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.54 no.4
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• pp.395-402
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• 2003

Background : Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for osteoporosis, which has implications for mobility and even mortality. The goal of this pilot study was to evaluate bone mineral density (BMD) and risk factors for osteoporosis in a limited number of men with COPD. Methods : We checked BMD, $FEV_1$(% of predicted) and investigated risk factors for osteoporosis in 44 male patients with COPD who visited our hospital from January to August 2002. Results : Mean(${\pm}$) age was $69{\pm}9$ yrs, body mass index(BMI) $21{\pm}3kg/m^2$, $FEV_1$ $50{\pm}18%$ of predicted, lumbar spine T-score $-3.0{\pm}1.2$, lumbar spine Z-score $-2.0{\pm}1.2$, and lumbar spine BMD $0.76{\pm}0.13g/cm^2$. Osteoporosis(T-score below -2.5) was present in 27 patients(61.4%) and osteopenia(T-score between -1 and -2.5) in 17(38.6%). None of the patients had normal BMD. There was no relationship between BMD and $FEV_1$(% of predicted). There were significant differences in smoking, alcohol consumption, exercise, cumulative steroid dose, BMI and BMD among the three groups according to $FEV_1$(% of predicted) (group1 : ${\geq}65%$, group2 : 50-64%, group3 : ${\leq}49%$), except age. However, there were no significant differences in these variables between the osteopenia and osteoporosis groups, except BMI. Linear Regression(Stepwise) analysis showed that lumbar BMD was correlated with BMI & exercise. Conclusion : BMD is significantly reduced in men with COPD. There was no relationship between BMD and pulmonary function.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.374-379
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• 2005

Background : The single-breath carbon monoxide diffusion capacity (DLCO) and the per unit alveolar volume (KCO; $D_LCO/VA$) gave discordant values when there was an abnormal alveolar volume (VA). However, the clinical significance of the discordant values in patients with airflow limitation has not been examined. This study investigated the $D_LCO$ and KCO changes after improving the airflow limitation. Methods : The baseline $D_LCO$ and KCO with lung volume were measured in patients with an airflow obstruction. The effective alveolar volume was measured using the single-breath $CH_4$ dilution method. The patients divided into two groups according to the baseline values: (1) increased KCO in comparison with the $D_LCO$ (high discordance) (2) decreased or not increased KCO in comparison with the $D_LCO$ (low discordance). The diffusion capacity and lung volume were measured after treatment. Results : There was no significant difference in the baseline lung volumes including the $FEV_1$ and FVC between the two groups. The $FEV_1$ and FVC were significantly increased in the high discordance group compared with the low discordance group after treating the airflow limitation. The $D_LCO$ and alveolar volume were significant higher in the high discordance group compared with the low discordance group while the TLC was not. Conclusion : The discordance between the $D_LCO$ and KCO could be translated into an airflow reversibility in patients with an airflow limitation.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.15-21
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• 2003

Background : There are many risk factors for osteoporosis in patients with chronic obstructive pulmonary disease(COPD). These include smoking, a low body mass index, insufficient exercise, and the use of glucocortcoids. However, there is lack of data on the incidence of osteoporosis according to the different glucocorticoid administration methods in patients with COPD. This study compared the incidence of osteoporosis according to the different administration methods of glucocorticoid. Methods : A matched case-controlled study (gender, age, cumulative steroid dose and pack-years of smoking) was conducted. Forty-five patients with documented COPD for at least a 3 year duration and a cumulative glucocorticoid dose above 1,000 mg were enrolled in study. The patients were classified into the following three groups. First, fifteen patients received continuous inhaled glucocorticoid with intermittent oral steroids but had no admission history due to an acute exacerbation(Group I). Secondly, fifteen patients received a multiple course of oral steroids with additional inhaled glucocorticoid but had no admission history due to their acute exacerbation(Group II). Lastly, fifteen patients received intermittent oral or inhaled glucocorticoids and had an admission history due to the acute exacerbation with intravenous steroid treatment for at least 2 weeks per year(Group III). The enrolled patients had apulmonary function test and bone densitometry performed at the lumbar spine and femoral neck. Results : The patients from Group III had significantly high incidence of osteoporosis in the lumbar and femoral neck compared to Group I and Group II (p<0.01). Conclusion : The incidence of osteoporosis in patients with COPD appears to be strongly affected by the method of steroid administration. This result suggests that intravenous steroid administration is strongly associated with the risk of osteoporosis.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.11-18
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• 2007

Background: Patients with chronic obstructive pulmonary disease (COPD) have often been reported to suffer from depression and anxiety possibly due to the exacerbation, hospitalization and mortality of COPD. However,scarce data are available in Korea. This study assessed degree of depression and anxiety, and evaluated the factors associated with depressive symptoms in COPD. Methods: The cross-sectional data on the lung function measurements, smoking behavior, body mass index (BMI), age, gender, depressive symptoms using Beck Depression Inventory (BDI) and anxiety using the State-Trait Anxiety Inventory (STAI) were evaluated in 72 outpatients with COPD and 50 controls without underling lung diseases from September, 2005 to October, 2006 in the Ewha medical center. Results: 1) The age, body mass index (BMI) and serum albumin levels were similar in the patients and controls. The BDI scores (16(0-37) vs. 12(1-30), p=0.001) and the prevalence of depression (36% vs. 6%, p<0.0001) were higher in the COPD patients than in the controls. In the COPD group, the prevalence of depression increased with increasing GOLD stage (p=0.008). The prevalence was 18%(4/22), in mild cases, 30%(6/20) in moderate cases, 52%(13/25) in severe cases and 60%(3/5) in very severe cases. 2) The SAI and TAI scores were higher in the COPD patients (44(20-67) and 47(20-66)) than in the healthy controls (39(26-65) and 44(33-90)). There were a significant correlation between the depression and anxiety scores (p<0.001). 3) A lower BMI, lower postbronchodilator $FEV_1$, current smoking behavior and severity of COPD were univariately associated with the depressive group in COPD, 4) while multivariate logistic analysis revealed only the severe-to-very severe group (OR 3.9, 95% CI 1.2 to 12.9) to be independently associated with depressive symptoms. Conclusion: COPD is strongly associated with depression and anxiety. Therfore, screening for psychological problems in COPD patients is essential, particularly in patients with severe-to-very severe COPD.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.944-955
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• 2000

Background : In patients with chronic obstructive pulmonary disease(COPD), several factors have been associated with a poor prognosis. These include old age, low $FEV_1$ low diffusing capacity, high alveolar-arterial oxygen pressure difference, and finally cor pulmonale. This study was done to investigate if the ECG signs suggesting cor pulmonale were independent prognostic factors in patients with COPD. Method : We analyzed ECG, pulmonary function data and arterial blood gas values in 61 patients who were admitted through the emergency department with an acute exacerbation of COPD. The ECG signs reflecting cor pulmonale were right strial overloading(RAO), right bundle branch block, right ventricular hypertrophy and low-voltage QRS. The 61 patients were divided into 2 groups ; group I with no ECG signs(n=36) and group II with one or more ECG signs(n=25) suggesting cor, pulmonale. Results : Poor, prognostic factors by univariate analysis were low $FEV_1$, $FEV_1$ % pred., VC % pred., DLco, DLco % pred., $PaO_2$ and $SaO_2$ high $PaCO_2$ presence of ECG signs reflecting cor pulmonale, presence of mental status change, use of mechanical ventilator, and long term use of glucocorticoid. A multivariate analysis indicated that age(risk ratio=1.13, 95% confidence interval 1.05-1.23), DLco % pred. (risk ratio=0,97. 95% confidence interval 0.94-0.99), $PaO_2$ (risk ratio=0.95, 95% confidence interval 0.90-0.99) and RAO(risk ratio=5.27, 95% confidence interval 1.40-19.85) were independent prognostic factors of survival. There was a significant difference in survival between the patients with and without RAO(p=0.038). The survival rates at 1, 2, and 5 years were 94.5%. 81.4%, and 50.0% in patients without RAO and 82.4%, 70.6%, and 27.5% in patients with RAO, respectively. Conclusion : These results suggest that the presence of ECG signs reflecting cor pulmonale is a predictor of survival and that RAO of these ECG signs is a significant independent predictor of survival in patients with COPD.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.746-753
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• 1998

Background : Cigarette smoking is closely related to both lung cancer and chronic obstructive pulmonary disease. The incidence of lung cancer is higher in patients with obstructive ventilatory impairment than in patients without obstructive ventilatory impairment regardless of smoking. So, obstructive ventilatory impairment is suspected as an independent risk factor of lung cancer. Methods: For the evaluation of the role of obstructive ventilatory impairment as a risk factor of lung cancer, a total of 73 cases comprising 47 cases of malignant and 26 benign solitary pulmonary nodule were analyzed retrospectively. A comparative study of analysis of forced expiratory volume curves and frequencies of obstructive ventilatory impairment were made between cases with malignant and benign nodules. Results: In comparison of vital capacity and parameters derived from forced expiratory volume curve between two groups. VC, FVC and $FEV_1$ were not significantly different. whereas $FEV_1/FVC%$ and FEF 25-75% showed a significant decrease in the cases with malignant nodule. The frequency of obstructive ventilatory impairment determined by pulmonary function test was significantly higher in the cases with malignant nodule(23.4%) than in benign nodule(3.8%). When the risk for lung cancer was examined by the presence or absence of obstructive ventilatory impairment using the logistic regression analysis, the unadjusted relative risk for the lung cancer of obstructive ventilatory impairment was 17.17. When the effect of smoking and age were considered, the relative risk was to 8.13. Conclusion: These findings suggest that an obstructive ventilatory impairment is a risk factor of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.298-308
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• 1997

Background : Portable devices for measuring peak expiratory flow(PEF) are now of proved value in the diagnosis and management of asthma and many lightweight PEF meters have become available. However, it is necessary to determine whether peak expiratory flow rate(PEFR) measurements measured with peak flowmeters is accurate and reproducible for clinical application. The aim of the present study is to define accuracy, agreement, and precision of mini-Wright peak flow meter(MPFM) against standard pneumotachygraph. Methods : The lung function tests by standard pneumotachygraph and PEFR measurement by MPFM were performed in a random order for 2 hours in 22 normal and 17 asthmatic subjects and also were performed for 3 successive days in 22 normals. Results : The PEFR measured with MPFM was significantly related to the PEFR and $FEV_1$ measured with standard pneumotachygraph in normal and asthmatics(for PEFR, r = 0.92 ; p < 0.001 ; for $FEV_1$, r = 0.78 ; p < 0.001). The accuracy of MPFM was within 100(limits of accuracy recommeded by NAEP) in all the subjects or 22 normal, mean difference from standard pneumotachygraph being 16.5L/min(percentage of difference being 2.90%) or 10.6L/min(percentage of difference being 1.75%), respectively. According to the method proposed by Bland and Altman, the 95% limits of the distribution of differences between MPFM and standard pneumotachygraph after correction of PEFR using our regression equation were +38.2 and -71.5L/min in all the subjects or 20.49~+9.49L/min in 22 normal and was similar to the intraindividual agreements for 3 successive days in normal. There was no statistically significant difference of PEFR measured with MPFM and standard pneumotachygraph among three days(p > 0.05) and the coefficient of variation($2.4{\pm}1.2%$) of PEFR measured with MPFM was significantly lower than that($5.2{\pm}3.5%$) with standard pneumotachygraph in normal (p < 0.05). Conclusion : This results suggest that the MPFM was as accurate and reproducible as standard pneumotachygraph for monitoring of PEFR in the asthmatic subjects.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.304-310
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• 1999

Background: IFN-$\gamma$ plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN-$\gamma$ caused by a defective IFN-$\gamma$ receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN-$\gamma$ in the development of chronic refractory tuberculosis. Methods: The LPS-induced TNF-$\alpha$ production with or without IFN-$\gamma$ priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN-$\gamma$ receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN-$\gamma$ is related to IFN-$\gamma$ receptor deficiency or not. Results: The ratio of TNF-$\alpha$ produced in response to stimulation with INF-$\gamma$ and LPS to LPS alone was $13.5{\pm}7.6$ in controls, $10.8{\pm}6.4$ in recently diagnosed tuberculosis patients and $6.7{\pm}3.9$ in chronic refractory tuberculosis patients. The priming effect of IFN-$\gamma$ significantly decreased in chronic refractory tuberculosis patients compared with that in controls(p=0.002). However, IFN-$\gamma$ receptor deficiency was detected in one of chronic refractory tuberculosis patients. Conclusion: The decrease of the priming effect of IFN-$\gamma$ may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN-$\gamma$ receptor deficiency.