• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.7-14
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• 1992

Background: Cognitive deficit by hypoxia and/or hypercapnia is one of neuropsychological impairments frequently observed in patients with chronic obstructive pulmonary disease (COPD). The degree of cognitive deficit is variable among patients with similar level of hypoxia and/or hypercapnia, although a cause of this individual difference is well not known. COPD can be divided into two characteristic clinical entities including predominant emphysema and predominant bronchitis. This study was designed to evaluate the individual difference in cognitive deficit respond to hypoxia and/or hypercapnia in patients with COPD. Method: Sixteen patients with COPD (9 emphysema-dominant and 7 bronchitis-dominant) participated in this study. On admission arterial blood gas analysis and trail-making B (TMB) test for the evaluation of cognitive function were done in all patients. Mean TMB scores and the correlations between TMB scores and arterial blood gases were compared between two clinical groups. Results: 1) Mean TMB scores and arterial blood gases between two clinical groups were not different. 2) There was a tendency to be higher TMB score in hypoxemia, acidemia, and hypercapnia. However these findings were not statistically significant. 3) In emphysema-dominant group, $PaCO_2$ was mostly well correlated with TMB score (r=0.693). 4) In bronchitis-dominant group, arterial pH was mostly well correlated with TMB score (r=-0.526). Conclusion: Our data suggest that the individual difference in cognitive deficit respond to hypoxia and/or hypercapnia in patients with COPD may be dependent on their clinical entities, and arterial blood gases mostly well correlated with cognitive function that may be different according to their clinical entities.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.172-183
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• 1999

Background: Nitric oxide is a short-lived effector molecule derived from L-arginine by the nitric oxide synthase(NOS). Nitric oxide plays a role in a number of physiologic and pathophysiologic functions including host defense, edema formation, and regulation of smooth muscle tone. Some kinds of cells including macrophage are known to produce large quantities of nitric oxide in response to inflammatory stimuli such as interleukin-$1\beta$(IL-$1\beta$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), interferon-$\gamma$(IFN-$\gamma$) and lipopolysaccharide(LPS). Reactive oxygen species are also known to be important in the pathogenesis of acute cell and tissue injury such as acute lung injury model Methods: Using the RA W264.7 cells, we have examined the ability of oxidant hydrogen peroxide($H_2O_2$) to stimulate nitric oxide production and inducible NOS mRNA expression. Also, we have examined the effects of NOS inhibitors and antioxidants on $H_2O_2$ induced nitric oxide production. Results: Stimulation of RAW264.7 cells with combinations of 100 ng/ml IL-$1\beta$, 100 ng/ml TNF-$\alpha$, and 100 U/ml IFN-$\gamma$ or 100 U/ml IFN-$\gamma$ and $1{\mu}g/ml$ LPS induced the synthesis of nitric oxide as measured by the oxidation products nitrite($NO_2^-$) and nitrate($NO_3^-$). Addition of $250 {\mu}M-2$ mM $H_2O_2$ to the cytokines significantly augmented the synthesis of $NO_2^-$ and $NO_3^-$(p<0.05). When cells were incubated with increasing concentrations of $H_2O_2$ in the presence of IL-$1\beta$, TNF-$\alpha$ and IFN-$\gamma$ at constant level, the synthesis of $NO_2^-$ and $NO_3^-$ was dose-dependently increased(p<0.05). $N^G$-nitro-L-arginine methyl ester(L-NAME), dose dependently, significantly inhibited the formation of $NO_2^-$ and $NO_3^-$ in cells stimulated with LPS, IFN-$\gamma$ and $H_2O_2$ at constant level(p<0.05). Catalase significantly inhibited the $H_2O_2$-induced augmentation of cytokine-induced $NO_2^-$ and $NO_3^-$ formation(p<0.05). But, boiled catalase did not produce a significant inhibition in comparison with the native enzyme. Another antioxidant 2-mercaptoethanol and orthophenanthroline dose-dependently suppressed $NO_2^-$ and $NO_3^-$ synthesis(p<0.05). Northern blotting demonstrated that H:02 synergistically stimulated the cytokine-induced iNOS mRNA expression in RA W264.7. Conclusion: These results suggest that $H_2O_2$ contributes to inflammatory process by augmenting the iNOS expression and nitric oxide synthesis induced by cytokines.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.195-208
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• 1999

Background: Pulmonary infiltrate in immunocompromised hosts has many infectious and non-infectios etiologies. To evaluate the diagnostic yield and therapeutic implication of two invasive diagnostic methods, such as bronchoscopy and surgical lung biopsy, we performed retrospective analysis of these patients. Methods: All immunocompromised patients admitted to Samsung Medical Center from October 1995 to August 1998 who underwent bronchoscopy and/or surgical lung biopsy for the diagnosis of pulmonary infiltrates were included in this study. Confirmative diagnostic yield, the rate of changed therapeutic plan and patients' survival were investigated. Results: Seventy-five episodes of pulmonary infiltrates developed in 70 patients(M : F=46 : 24, median age 51). Underlying diseases of patients were hematologic malignancy(n=30), organ transplantation(n=11), solid tumor(n= 12), connective tissue disease(n=6) and others. Confirmative diagnosis was made in total 53 cases (70.7%), of which 70.2% had infectious etiology. Diagnostic yields of bronchoscopy, bronchoalveolar lavage(BAL), transbronchiallung biopsy(TBLB) and surgical lung biopsy were 35.0%(21/60), 31.4%(16/51), 25.0%(9/36) and 80.0%(20/25). Therapeutic plan was changed in 40%(24/60) of patients after bronchoscopy and in 36%(9/25) of patients after surgical lung biopsy. More patients survived (84.4% vs 60.5%, p=0.024) when therapeutic plan was changed after invasive diagnostic study. Conclusion: Bronchoscopy and surgical lung biopsy are helpful for the therapeutic implication of pulmonary infiltrates in immunocompromised hosts. Large-scale prospective case-control study may further clarify their limitation and usefulness.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.168-179
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• 2004

Background : The statistical analysis is an essential procedure ensuring that the results of researches are based on evidences rather than opinion. The purpose of this study is to evaluate which statistical techniques are used and whether these statistical methods are used appropriately or not in the journal of Tuberculosis and Respiratory Diseases. Materials and Methods : We reviewed 185 articles reported in the journal of Tuberculosis and Respiratory Diseases in 1999. We evaluated the validity of used statistical methods based upon the checklist that was developed on the basis of the guideline for statistical reporting in articles for medical journals by International Committee of Medical Journal Editors. Results : Among 185 articles, original articles and case reports were 110 (59.5%) and 61 (33.0%) respectively. In 112 articles excluding case reports and reviews, statistical techniques were used in 107 articles (95.5%). In 94 articles (83.9%) descriptive and inferential methods were used, while in 13 (11.6%) articles only descriptive methods were used. With the types of inferential statistical techniques, comparison of means was most commonly used (64/94, 68.1%), followed by contingency table (43/94, 45.7%) and correlation or regression (18/94, 19.1%). Among the articles in which descriptive methods were used, 83.2% (89/107) showed inappropriate central tendency and dispersion. In the articles in which inferential methods were used, improper methods were applied in 88.8% (79/89) and the most frequent misuse of statistical methods was inappropriate use of parametric methods (35/89, 39.3%). Only 14 articles (13.1%) were satisfactory in utilization of statistical methodology. Conclusion : Most of the statistical errors found in the journal were misuses of statistical methods related to basic statistics. This study suggests that researchers should be more careful when they describe and apply statistical methods and more extensive statistical refereeing system would be needed.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.606-612
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• 2005

Background : It has been reported that nontuberculosis mycobacterium(NTM) isolates account for approximately 10% of patients with a positive Acid-Fast Bacilli(AFB) smear. Therefore, it is necessary to consider NTM pulmonary disease when such a positive test is encountered. The aim of this study was to evaluate the etiologies and clinical characteristics of patients with NTM pulmonary disease who had been treated at a national tuberculosis hospital. Methods : The NTM isolates were recovered from the sputum or bronchial washing specimens submitted to a clinical laboratory of National Masan TB Hospital from August 2002 to July 2003. All samples were identified using a polymerase chain reaction-restriction fragment length polymorphism analysis method, which amplifies the rpoB gene. The patients were diagnosed with NTM disease according to the American Thoracic Society diagnostic criteria. Results : One hundred NTM isolates were recovered from 57 patients. Of the 100 isolates, M. avium complex(MAC) was the most common species, which was found 55%(n=55) of patients, followed by M. abscessus(n=25), and M. fortuitum( n=9). 26(45.6%) patients had NTM disease. Twenty-six (45.6%) patients had NTM disease according to The American Thoracic Society classification. The main organisms involved in NTM disease were MAC(n=19, 73.1%) and M. abscessus(n=5, 19.2%). The pathogenic potential was 67.9% in M. intracellulare and 41.7% in M. abscessus. The predictive factors related to NTM disease were a positive sputum smear (OR 6.4, p=0.02) and the isolation of either MAC or M. abscessus(OR 6.9, p=0.007). Fifteen patients(57.7%) were cured. There were no significant factors associated with the treatment success. Conclusion : There was a relatively high proportion of NTM disease in NTM isolates and the common species were MAC and M. abscessus. The predictive factors for NTM disease were a positive sputum smear and the isolation of either MAC or M. abscessus.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.39-46
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• 2005

Background : Even though it has been suggested that low-colony, scotochromogen nontuberculous mycobacteria (NTM) are usually contaminants and not true pathogens, evidence for this hypothesis has not been provided. This study investigated the colony characteristics, organism identification, and clinical significance of low-colony scotochromogen. Methods : The laboratory cultured 6,898 respiratory clinical specimens for an examination of mycobacteria over a three-month period. A low-colony count was arbitrarily defined as ${\leq}20$ colonies. This study analyzed the recovery rate of the mycobacteria, the number of colonies and their gross characteristics, and their clinical significance. PCR-restriction fragment length polymorphism analysis was carried out to identify the NTM species. NTM pulmonary disease was defined according to the American Thoracic Society. Results : A total of 6,898 respiratory specimens for mycobacterium were cultured. Of these, 263 (3.8%) grew NTM, and 382 (5.5%) grew M. tuberculosis. Of the 263 cultured NTM specimens, 124 (47.1%) were scotochromogens. The smear-positive rate was significantly lower in these scotochromogens (4.8%) than in the non-scotochromogens (23.7%) (p<0.05). The most common isolates were M. gordonae (83/102, 81.4%) in the scotochromogens, and MAC (52/121, 43.0%) in the non-scotochromogens. Even though three out of 113 patients with a low-colony scotochromogen has been diagnosed with NTM pulmonary disease, the isolated scotochromogen was not considered to be the cause of the NTM disease but was just a contaminant. Conclusion : In this study, the most common isolate of a low-colony count scotochromogen was M. gordonae, which appeared to be contaminants and not true pathogens. Greater efforts in the quality control of a mycobacterium laboratory are needed in cases where there is a high recovery rate of low-colony count scotochromogen.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.210-218
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• 2003

Background : Sex specific cross sectional reference values for the lung function indices usually employ a linear model with a term for age and height. The purpose of this study was to determine the effects of the body mass index (BMI), the fat percentage of the body mass and the fat-free mass index (FFMI) on the forced expiratory volume curve. Methods : Between January 2000 and December 2001, a total of 300 subjects, 150 men and 150 women (mean age : $45{\pm}13$ years), with a normal lung function were enrolled in the study sample. This study measured the $FEV_1$, FVC and $FEF_{25-75%}$ from the forced expiratory volume curve by a spirometer and the body composition by a bioelectrical impedance method in all subjects. Multiple regression analysis was used in order to examine the effects of the body composition on the parameters derived from the forced expiratory volume curve. Results : After adjusting for age, the BMI and Fat percentage improved the descriptions of the FVC (p<0.05, $r^2=0.491$) and $FEV_1$ (p<0.05, $r^2=0.654$) in women. In contrast, the FFMI contributed significantly to the FVC (p<0.05, $r^2=0.432$) and $FEV_1$ (p<0.05, $r^2=0.567$) in men. The $FEF_{25-75%}$ correlated with the fat percentage in women (p<0.05, $r^2=0.337$). Conclusion : These results suggest that the BMI, the fat percentage and the FFMI are significant determinants of the forced expiratory volume curve. The plmonary function test, when considering the BMI, the fat percentage and the FFMI, might be useful in clinical applications.

• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.199-209
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• 2003

Background : Unexplained weight loss, which commonly occurs in patients with chronic obstructive pulmonary disease(COPD), is important because weight loss is an independent risk factor of mortality and morbidity in these patients. Leptin is known to play an important role in regulating body weight. In addition, the tumor necrosis factor($TNF-{\alpha}$) might also play a potential role in the weight loss experienced in chronic wasting disease. The aim of this study was to determine the influence of plasma leptin and the circulating $TNF-{\alpha}$ system to the difference in the body compositions in patients with COPD. Methods : Spirometry, body composition analysis and the plasma concentrations of leptin, $TNF-{\alpha}$ and a soluble TNF receptor (STNF-R55, -R75) were measured in 31 patients with chronic bronchitis and 10 patients with emphysema. The COPD subtype was classified by the transfer coefficient of carbon monoxide, DLco/VA. Results : The circulating levels of leptin were significantly lower in those patients with emphysema($108.5{\pm}39.37pg/ml$) than those with chronic bronchitis($180.9{\pm}57.7pg/ml$). The circulating levels of sTNF-R55 were significantly higher in the emphysema patients($920.4{\pm}116.4pg/ml$) than in those with chronic bronchitis($803.2{\pm}80.8pg/ml$). There was no relationship between the circulating leptin levels and the activated TNF system in patients with chronic bronchitis and emphysema. However, the circulating leptin levels correlated well with the BMI and fat mass in both patient groups. Conclusion : These results suggest that the weight loss noted in emphysema patients may be associated with the activation of the $TNF-{\alpha}$ system rather than the plasma leptin level.

• Tuberculosis and Respiratory Diseases
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• v.71 no.2
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• pp.120-125
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• 2011

Background: Although the prevalence of pulmonary tuberculosis has progressively decreased all over the world, drug-resistant tuberculosis is major obstacle in treating tuberculosis. This study was performed to examine the current prevalence and risk factors of drug resistant tuberculosis in a single tertiary hospital in Busan, Korea. Methods: We enrolled 367 patients with active pulmonary tuberculosis on a retrospective basis who had undergone mycobacterium culture and drug sensitivity tests between January 2005 and December 2009. We analyzed all clinical and radiographic parameters to find predictors related to drug resistant tuberculosis. Results: At least one incident of drug resistance was found in 75 (20.4%) patients. Isoniazid (18.8%) was the most frequent resistant drug, followed by rifampin (10.9%), ethambutol (7.1%), streptomycin (4.9%), and fluoroquinolone (2.7%). Resistance to second-line drugs was found in 37 (10.1%) patients. Multidrug resistance and extensively drug resistance was evident in 39 (10.6%) and 4 (1.1%) patients, respectively. Using multiple logistic regression analysis, history of previous treatment including relapse (odd ratio [OR], 11.3; 95% confidence interval [CI], 4.92~26.08; p<0.01), treatment failure (OR, 24.1; 95% CI, 5.65~102.79; p<0.01) and an age of below 46 years-old (OR, 3.8; 95% CI, 1.62~8.65; p<0.01) were found to be independent predictors of multidrug resistant tuberculosis. Conclusion: We found that the prevalence of drug resistant tuberculosis was considerably high. A careful consideration for possible drug resistant tuberculosis is warranted in patients with a history of previous treatment or for younger patients.