• 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.54 no.1
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• pp.80-90
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• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.410-415
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• 1993

Background: The lung abscess predominantly occurs on a dependent region, because its major predisposing factor is aspiration. However, a lung abscess appeared on a nondependent region occasionally. Traditionally bronchoscopy has been performed in patients with lung abscess on a nondependent region for evaluating the endobronchial obstruction such as bronchogenic carcinoma. But the clinical characteristics and necessities of bronchoscopy in patients with lung abscess located at nondependent region have not been discussed previously. Thus, we investigated the underlying etiologies and the necessities of bronchoscpy in patients with lung abscess in a nondependent region. Method: Fifteen patients with cavitary lesion on a nondependent location have been studied retrospectively by reviewing their clinical records, chest PAs, computerized tomograms, and bronchoscopic findings. Results: 1) Most patients were older than 30 years except one, and their mean age was 51 years. The ratio of male to female was 6.5:1. 2) The underlying etiologies were bacterial infections in 13 cases, and tuberculous infection in two cases. However, bronchogenic carcinoma was not found as its etiology. 3) Among thirteen bacterial lung abcess, tweleve cases located at right middle lobe. 4) The findings of bronchoscopy were non-speicifc mucosal change in 8 cases and segmental obstructions in 2 cases. There were no malignant evidences in the finings of cytology and bronchscopic biopsy. 5) Among thirteen bacterial lung abcess, eleven patients showed good clinical reponse to antibiotic therapy. Conclusion: The necessity of early bronchoscopy may need to be re-evaluated in the lung abscess on a nondependent region, unless evidences of bronchial obstruction or bronchogenic carcinoma exist. The pulmonary tuberculosis shoud be regarded as the underlying etiology of the nondependent lung abscess.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.805-812
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• 1998

Background: Among the variety of opportunistic infections, pneumonia comprises the major morbidity in immunocompromised patients. Pneumocystis carnii pneumonia (PCP) and cytomegalovirus (CMV) pneumonia are common infectious illness of immunocompromised hosts. Although there are many reports regarding to the co-infection of PCP and CMV diagnosed by bronchoalveolar lavage (BAL) fluid examination, the effects of CMV co-infection on the outcome of PCP is still controversial. The purpose of this investigation is to evaluate the effects of CMV detected by BAL fluid examination on the clinical course of PCP in the immunocompromised patients other than human immunodeficiency virus infection. Method: Ten patients with PCP were enrolled and retrospective analysis of their medical records were done. HIV infected persons were excluded. The PCP was diagnosed by BAL fluid examination with Calcofluor-White staining. CMV was detected in BAL fluid by Shell-vial culture system. Chest radiographic findings were reviewed. We used Fisher's exact test and Mann-Whitney U test for statistical analysis of data. Results: The underlying disorders of patients were idiopathic pulmonary fibrosis (n=1), renal transplantation (n=4), necrotizing vasculitis (n=l), systemic lupus erythematosus (n=1), brain tumor (n=1), chronic myelogenous leukemia (n=1), unidentified (n=1). There were no difference in clinical course, APACHE III score, arterial blood gas analysis, white blood cell count, lymphocyte count, serum albumin concentration, chest radiographic findings and mortality between patients with PCP alone (n=4) and those with CMV co-infection (n=6). Univariate analysis regarding to the factors that associated with mortality of PCP were revealed that the application of mechanical ventilation (p=0.028), the level of APACHE III score (p=0.018) and serum albumin concentration (p=0.048) were related to the mortality of patients with PCP. Conclusion: The clinical course of PCP patients co-infected by CMV were not different from PCP only patients. Instead, accompanied respiratory failure, high APACHE III score and poor nutritional status were associated with poor outcome of PCP.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.410-419
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• 1996

Background : Spontaneous pneumothorax have been managed with a variety of methods. The technique most frequently used is chest tube drainage. Small caliber catheters were first used in the management of pneumothorax complicating the percutaneous needle aspiration lung biopsy, and the try to treat spontaneous pneumothorax also has been reported. However, the value of small caliber catheters in spontaneous pneumothorax has not been fully evaluated. So, we tried to elucidate the efficacy of 8 French catheter in the management of spontaneous pneumothorax. Method : From January, 1990, to April, 1994, 44 patients with spontaneous pneumothorax treated at Chung-Ang university hospital were reviewed. The patients were sub-divide into 8 French catheter insertion group (n=21) and chest tube insertion group (n=23). We compared the presence of underlying lung disease, the extent of the collapse, the duration of indwelling catheter and complication between two groups. Results : 1) The duration of indwelling showed no significant difference between 8 French catheter group and chest tube. But, complication after insertion as subcutaneous emphysema was developed in only chest tube group. (p<0.05) 2) In the primary spontaneous pneumothorax, all case of the pneumothorax of which size was less than 50% showed complete healing with 8 French catheter insertion. Whereas the success rate in patients with large pneumothorax (more than 50%) was tended to be dependent on the age. 3) In the patients with secondary spontaneous pneumothorax who were managed with 8 French catheter, the success rate was trended to be high if the underlying disease of pneumothorax was not COPD and if the patient was young. Conclusion : These results show that 8 French catheter insertion probably was effective in the pneumothorax less than 50%, the primary spontaneous pneumothorax, young age or secondary pneumothorax not associated with COPD.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.401-408
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• 1997

Background : Pulmonary sequestration is a rare congenital malformation, which is manifested by formation of nonfunctioning lung tissue lacking normal communication with the tracheobronchial tree. The preoperative diagnostic rate has been relatively low, and without consideration of pulmonary sequestration, unexpected bleeding from aberrant vessels may be a serious problem during the operation. The purpose of our study is to describe the clinical features of pulmonary sequestration based on a review of 15 cases treated by operation. Method : Fifteen patients with pulmonary sequestration who had undergone surgical treatment from 1991 through May 1996 at Yongdong Severance Hospital and Severance Hospital were reviewed retrospectively. Results : The mean age of the patients was 22.5 years (range 5~57), and male to female ratio was 9 : 6. Clinical presentations varied from recurrent respiratory infections such as fever, cough, and sputum or chest pain to no symptom. The chest simple X-rays showed multicystic shadow(10/15) and solid mass-like shadow(5/15). The chest CT scans, done in twelve cases, showed multicystic lesion with or without lung infiltration(8/12), solid mass-like lesion(4/12), The chest MRIs, done in three cases, revealed the aberrant arteries originating from descending aorta(2/3). Aortograms, done in four cases, showed the aberrant arteries originating from descending thoracic aorta(2/4), abdominal aorta(I/4), and intercostal artery(1/4). and the venous returns were via the pulmonary veins. Pulmonary sequestration was considered preoperatively in six patients of fifteen. Other preliminary diagnosis were lung tumor(3/15), lung abscess(21/15), bronchiectasis(2/15), and mediastinal tumor(2/15). In the operative findings, twelve cases were of intralobar type and three cases of extralobar type. The left lower lobe was most often affected(9/15) and one extralobar sequestration was in the pericardium. The aberrant arteries originated from descending thoracic aorta(6/15), abdominal aorta(1/15), internal thoracic arteries (2/15), intercostal artery(1/15), pericardiophrenic artery(1/15), but in four cases, the origins could not be defined. There was no mortality or complication postoperatively. Conclusion : In our study, preoperative diagnostic rate was relatively low, and clinical features were similar to previous reports. Preoperative vigorous diagnostic approach including aortography is strongly advocated not only for its diagnostic value, but also for accurate localization of the aberrant vessels, which is major concern to surgical procedure.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.205-211
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• 2009

Background: Serum procalcitonin level has been considered prognostic during sepsis and septic shock. We investigated the significance of procalcitonin in critically ill patients with respiratory infections. Methods: The patients who had radiographically diagnosed diffuse lung infiltrations were enrolled on a prospective basis. Bronchoalveolar lavage (BAL) fluid for the purpose of quantitative cultures (${\geq}10^4$ cfu/mL) was obtained from all patients. Serum procalcitonin levels determined by PCT-Q kit were measured on BAL day and classified as follows; <0.5 ng/mL, 0.5~2.0 ng/mL, 2.0~10.0 ng/mL and >10.0 ng/mL. We analyzed the patient's characteristics according to outcome; favorable or unfavorable, defined as death. Results: Patients from the following categories were included: medical 17 (47.2%), surgical 9 (25%), and burned 10 (27.8%). APACHE II scores on admission to intensive care unit were 11.5${\pm}$6.89 and 11 (30.6%) had unfavorable outcomes. A procalcitonin level ${\geq}$0.5 ng/mL was in 17 (47.2%) of all. On univariate analysis, the frequencies of burn injury, mechanical ventilation, multiple organ failure, and a procalcitonin level ${\geq}$0.5 ng/mL were more often increased in patients with unfavorable outcomes than in those with favorable outcomes (p<.05). Also, a higher procalcitonin range and ventilator-associated pneumonia (VAP) were more closely associated with an unfavorable outcome (p<.05). However in multivariate analysis, a strong predictor of unfavorable outcome was burn injury (p<.05). A procalcitonin level ${\geq}$0.5 ng/mL was more sensitive in predicting VAP than unfavorable outcome. Conclusion: A higher procalcitonin level seems to be associated with VAP, but further study is required to know that procalcitonin would be a prognostic marker in critically ill patients with respiratory infections.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.194-199
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• 2008

Background: Early identification of pathogens can improve the prognosis of patients with ventilator associated pneumonia (VAP). In the present study, we evaluated the feasibility of performing multiplex PCR for endotracheal aspirates to detect three important pathogens (P. aeruginosa, K. pneumoniae and MRSA) in patients with VAP. Methods: The endotracheal aspirates of 24 patients were collected within 24 hours of the diagnosis of VAP for performing multiplex PCR. Forward and reverse primers were designed to target the specific site of each pathogen (the oprL gene for P. aeruginosa, 16S rRNA for K. pneumoniae and the mec gene for MRSA). We analyzed the clinical data of the VAP patients, including the culture reports for the endotracheal aspirates. Results: Twenty-four patients (M:F=18:6, mean age=$70{\pm}11$) with VAP were enrolled. Pathogens were isolated from 11 patients (P. aeruginosa in 2, K. pneumoniae in 1, MRSA in 2, other enteric Gram negative bacilli in 3, S. pneumoniae in 2 and mixed infection in 1). Multiplex PCR detected three cases of P.aeruginosa (2 cases coincided with the culture reports) and four cases of K. pneumoniae (1 matched with the culture report). PCR detected two MRSA cases, which did not coincide with the culture reports. Conclusion: Multiplex PCR of the endotracheal aspirate showed some ability to detect Gram negative bacilli, although caution is required when interpreting the results.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.455-464
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• 1995

Background: Considering that both humoral and cell mediated immunities play an important role for human tuberculosis infection, enzyme-linked immunosorbent assay(ELISA) measurement of immunoglobulin G (IgG) antibody to mycobacterial antigens can be used for the serologic diagnosis of tuberculous pleural effusion. Method: We measured absorbance values of IgG antibodies to purified-protein-derivative (PPD) and lipoarabinomannan-B (LAM-B) in the pleural fluid (PF) and the serum in 40 tuberculous (TPE) and 19 nontuberculous pleural effusions (NTPE). Results: 1) The IgG antibodies to PPD and LAM-B were significantly (P<0.0005) higher in the PF and the serum of TPE compared to NTPE. 2) The IgG antibodies to PPD and LAM-B in the serum were higher than that in PF. 3) Significant correlations were found between pleural and serum IgG antibodies to PPD and LAM-B. 4) With a cutoff value for IgG antibody to PPD in the PF of 0.091, sensitivity was 55.0% and specificity 94.7% in the diagnosis of TPE. 5) With a cutoff value for IgG antibody to LAM-B in the PF of 0.337, sensitivity was 50.0% and specificity 94.7% in the diagnosis of TPE. 6) The seropositive rates in TPE were not related to PPD skin test status, the amount of PF and coexisting active pulmonary tuberculosis. Conclusion: The assay of IgG antibodies to PPD and LAM-B might be useful for the diagnosis of TPE. Our study suggests the mechanism of passive transfer of IgG antibodies to PPD and LAM-B from the serum to the PF through pleural tissue.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.470-478
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• 1997

Background : Phagocytosis is probably the first step for mycobacteria to be virulent in host because virulent strains are more readily phagocytosed by macrophage than attenuated strains. According to the traditional concept, multi-drug resistant strains have been regarded as less virulent. However, this concept has been challenged, since recent studies(reported) showed that the degree of virulence and drug-resistance is not related. The purpose of this study is to evaluate whether the phagocytic activity of M.tuberculosis by peripheral blood mononuclear cells(PBMC) is different according to drug-resistance or host factor. To evaluate this, we estimated the difference of phagocytic activity of drug-resistant and drug-sensitive M.tuberculosis and also estimated the phagocytic activity of PBMC from intractable tuberculosis patients and healthy controls. Methods : PBMC from ten intractable tuberculosis patients and twelve healthy control, and three different strains of heat-killed M.tuberculosis, ie, ADS(all drug sensitive), MDR(multi-drug resistant), and ADR(all drug resistant) were used. After incubation of various strains of M.tuberculosis with PBMC, the phagocytic activity was evaluated by estimating proportion of PBMC which have phagocytosed M.tuberculosis. Results : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains(Percentage of PBMC phagocytosed M.tuberculosis in healthy control : ADS : $32.3{\pm}2.9%$, ADR : $49.6{\pm}3.4%$, p = 0.0022, Percentage of PBMC phagocytosed M.tuberculosis in intractable tuberculosis patients : ADS : $34.9{\pm}3.6%$, ADR : $50.7{\pm}4.5%$, p = 0.0069). However, there was no difference in phagocytic activity of PBMC from healthy control and intractable tuberculosis patients. Conclusion : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains and host factors does not seems to influence the phagocytosis of M.tuberculosis.