• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.41-58
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• 2003

Background : The resurgence of tuberculosis and the widespread emergence of multidrug-resistant M. tuberculosis have emphasized the importance of rapid and accurate diagnostic procedures. Recently, the oligonucleotide chip has proven to be a useful tool in the rapid diagnosis of infectious diseases. The purpose of this study was to rapidly and accurately detect specific mutations in the rpoB, katG and rpsL genes associated with rifampin, isoniazid and streptomycin resistance in M. tuberculosis, respectively, using a single oligonucleotide chip. Method : For detection of drug-resistance, 7 wild-type and 13 mutant-type probes for rifampin, 2 wild-type and 3 mutant-type probes for isoniazid, and 2 wild-type and 2 mutant-type probes for streptomycin were designed and spotted onto glass slides. Fifty-five cultured samples of M. tuberculosis were amplified by PCR, and then underwent hybridization and scanning. Direct sequencing was done to verify the results from the oligonucleotide chip and to analyze the types of mutations. Result : Thirty-five cases out of 40 rifampin-resistant strains(~88%) had mutations in the rpoB gene. One case had a new mutation(D516F, GAC R TTC) and another known mutation together. Twenty cases out of 42 isoniazid-resistant strains(~50%) had mutations in the katG gene, while 7 cases out of 9 streptomycin-resistant strains(~78%) had mutations in the rpsL gene. From these results, the oligonucleotide chip was confirmed to be able to detect the most frequent mutations from the genes associated with rifampin, isoniazid and streptomycin resistance. The results proved that the drug-resistance detection probes were specific. When the results from the oligonucleotide chip and DNA sequencing were compared, the types of mutations were exactly matched. Conclusion : The diagnostic oligonucleotide chip with mutation specific probes for drug resistance is a very reliable and useful tool for the rapid and accurate diagnosis of drug resistance against rifampin, isoniazid and streptomycin in M. tuberculosis infections.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.427-432
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• 2008

Background: A paradoxical response is defined as the radiological and clinical worsening of a previous lesion or the development of new lesion after initial improvement during theprocess of antituberculous treatment. The related factors for the development of a paradoxical response in patients with tuberculous pleurisy are not certain. Methods: We selected patients with tuberculous pleurisy who had been treated for more than 4 months. The changes onthe serial chest X-ray findings before and after treatment were reviewed. Paradoxical responses were regarded as any worsening or development of new lesion at least 2 weeks after the initiation of treatment. The baseline clinical characteristics and laboratory findings of the peripheral blood and pleural fluid were compared between the patients with a paradoxical response and the patients without a paradoxical response. Results: Paradoxical responses appeared in sixteen patients (21%) among the 77 patients.It took a mean of 38.6 days after the treatment and the time to resolve the paradoxical response was a mean of 32.1 days. For the patients with a paradoxical response, the median age was younger (30.5 years vs 39.0 years, respectively) and the lymphocytic percentage of white blood cells in the pleural fluid was higher (82.1% vs 69.6%, respectively) than for the patients without a paradoxical response. Conclusion: The development of a paradoxical response during the treatment of patients with tuberculous pleurisy was not rare and this was related with the age of the patients and the percentage of lymphocytic white blood cells in the pleural fluid.

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.54-61
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• 2002

Background: Tracheal stenosis is an urgent but uncommon disease. Therefore, primary care clinicians have limited clinical experience. Animal models of a tracheal stenosis can be used conveniently for the learning, teaching, and developing new diagnostic and therapeutic modalities for tracheal stenosis. Recently, a canine model of a tracheal stenosis was developed using a Nd-YAG laser. To describe the methods and results of developed animal model, we performed this study. Methods : Six Mongrel dogs were generally anesthetized and the anterior 180 degree of tracheal cartilage of the animal was photo-coagulated using a Nd-YAG laser. The animals were bronchoscopically evaluated every week for 4 weeks and a pathologic evaluation was also made. Results : Two weeks after the laser coagulation, the trachea began to stenose and the stenosis progressed through 4 weeks. All animals suffered from shortness of breath, wheezing, and weight loss in the 3 weeks after the laser treatment, and two died of respiratory failure just before the fourth week. The gross pathologic findings showed the loss of cartilage and a dense fibrosis, which resulted in a fibrous stricture of the trachea. Microscopy also showed that the fibrous granulation tissue replaced destroyed cartilage. Conclusion : The canine model can assist in the understanding and development of new diagnostic and therapeutic modalities for tracheal stenosis.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.735-746
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• 1999

Background: As the prevalence of nontuberculous mycobacteriosis has been increasing rapidly, there has been recent advance in diagnostic methods and drug therapies for disease. Although the incidence of pulmonary disease caused by nontuberculous mycobacteria(NTM) has been increasing in Korea since 1990, detailed clinical description about the disease were very few. In this study we described the clinical manifestations, radiologic findings, and therapeutic outcomes of nontuberculous mycobacterial pulmonary disease. Methods: Medical records and radiologic findings were retrospectively reviewed in 27 patients who were fulfilled the diagnostic criteria of ATS guideline for NTM pulmonary disease between January of 1990 and August of 1998 in Seoul National University Hospital(SNUH). Results: Of the 27 patients, 15 were male. The mean age was 51.5 yr($\pm$11.9). Twenty patients(74.1%) had preexisting pulmonary diseases. Among them, 19 patients had previous pulmonary tuberculosis. Sixteen patients(59.2%) had cavitary lesions and the majority showed slow progression over 1 yr during follow up period on radiography. Susceptibility test to standard antituberculous drugs showed 100% resistance to INH, 72.2% to RMP, 81.5% to EMB, 92.6% to PZA. The average resistance rate to 2nd-line antituberculous drugs was 66.1%. Among twenty-one patients(77.8%) who received drug therapy over 6 months, 11 subjects were improved and 10 subjects were aggravated. Of six subjects(22.2%) without therapy, 5 patients were aggravated. Presence of cavity and less than 3 sensitive drugs in the regimen were indicators for adverse outcome. Conclusion : The nontuberculous mycobacterial pulmonary diseases in our hospital developed predominantly in older patients with preexistent pulmonary disease. The results of antituberculous drug therapy has been frustrating and disappointing. To improve treatment response, different susceptibility tests and drug regimens for different species of NTM should be performed. Also, diagnostic and therapeutic guidelines of Korea should be made in the recent future.

• Tuberculosis and Respiratory Diseases
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• v.53 no.1
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• pp.27-35
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• 2002

Background : The paradoxical response refers to an enlargement of old lesions or unexpected new ones during apparently adequate antituberculous therapy. This response has been reported in cases of intracranial tuberculoma, tuberculous lymphadenopathy, tuberculous pleurisy and pulmonary tuberculosis. However, there are few reports on its frequency and clinical characteristics. Materials and Methods : This study enrolled 205 patients who were treated with first line antituberculous agents for more than 6 months. We retrospectively studied 155 patients with pulmonary tuberculosis and 57 patients with pleural tuberculosis (7 patients had both) from July 1998 to March 2000. The patients were divided into the paradoxical response group and the non-paradoxical group. The clinical characteristics of the paradoxical response group and the non-paradoxical group. The clinical characteristics of the paradoxical group were investigated. Statistical analysis was done with an independent sample T-test and Chi-squared test. Results : 29 of the 205 patients(14.1%) had paradoxical response. Among the 29 patients, there were 19 pulmonary tuberculosis, 8 tuberculous pleurisy(2 patients had both). Paradoxical response appeared 32 days (mean 35 days in pulmonary tuberculosis, mean 25 days in tuberculous pleurisy) after the beginning of chemotherapy. The duration to regress less than half of initial chest lesion was 114 days in pulmonary tuberculosis and 124 days in tuberculous pleurisy, respectively. Most common clinical manifestation of paradoxical response patients was coughing in both pulmonary tuberculosis and tuberculous pleurisy. Male sex, high blood WBC count and high level of pleural fluid LDH were related with paradoxical response. Conclusion : These findings suggest that presponse usually appears 1 month and disappears within 4 months after the beginning of anti-tuberculous chemotherapy. Paradoxical response was relatively correlated with male sex, high blood WBC count and high level of pleural fluid LDH.

• Pediatric Infection and Vaccine
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• v.8 no.2
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• pp.175-180
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• 2001

Purpose : Recently in Korea since 1998, 2TU has been used instead of 5TU, which caused a confusion in interpreting tuberculin skin tests. We compared the tuberculin skin reaction to PPD(purified protein derivatives) 1TU, 2TU and 5TU. Methods : We studied tuberculin skin reaction to PPD 1TU, 2TU and 5TU on 92 infants who were vaccinated with percutaneous multiple puncture BCG vaccine(Tokyo 172 strain, Japan BCG Laboratory Co.) in neonatal period. Diameters of indurations were measured in millimeters 48~72 hours after the intradermal injection of PPD 1TU, 2TU and 5TU. Results : Among 92 infants(male : 56, female : 36), 1TU was used on 31 infants, 2TU on 31 infants and 5TU on 30 infants for tuberculin skin test. The mean diameter of induration for PPD 1TU, 2TU and 5TU were $5.7{\pm}4.2mm$, $7.1{\pm}3.7mm$, and $9.2{\pm}4.2mm$, respectively. There was no statistical difference in mean diameter of induration between 1TU and 2TU. However, when tested with 5TU, the diameter of induration was significantly larger than those of PPD 1TU and 2TU(P<0.05). Six subjects(19.4%) tested with 1TU, 9 subjects(29%) tested with 2TU and 16 subjects(53.3%) tested with 5TU had diameter of 10 mm or more. There was no statistical difference between 1TU and 2TU but for 5TU, number of subjects with diameter of 10 mm or more was significantly higher than PPD 1TU and 2TU(P<0.05). Number of subjects with induration diameter of 5 mm or more for 1TU, 2TU and 5TU was 19(61.3%), 22(71.0%) and 26(86.7%), respectively. However, there was no statistical difference. Conclusion : A new standard criteria for interpreting the tuberculin skin test with PPD 2TU should be established for clinical diagnosis of tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.51 no.1
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• pp.17-24
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• 2001

Background : Community-acquired pneumonia(CAP) remains a leading cause of morbidity and mortality worldwide. Recently, the evolution of drug-resistant microorganisms has become a serious problem in CAP management. Specific antimicrobial therapy is the cornerstone of CAP management. However, obtaining an accurate etiologic diagnosis clinically is not easy and empirical antimicrobial treatment is usually administered prior to the correct microbiologic diagnosis. In this study, the clinical usefulness of empirical CAP treatment was investigated. Methods : A total 35 cases were studied prospectively over a 16-month period in Mokpo Catholic Hospital from Dec. 1995 to Mar. 1997. The microbiologic diagnosis was made by sputum, blood culture, a specific serum antibody test and an immunologic study. Results : The causative organisms were isolated in 10 (30%) out of 33 cases: 8 cases and 1 case on the sputum culture and blood culture respectively, and 1 case by an indirect hemagglutinin test. 12 cases had underlying diseases: pulmonary tuberculosis 4, alcoholism 4, diabetes mellitus 3, and liver cirrhosis 1. Antimicrobial treatment was given empirically and all cases recovered. Conclusion : A definite microbiologic diagnosis before commencing the appropriate treatment in CAP is not straightforward. Empirical therapy according to a clinical assessment is important and helpful. However, every effort to make the correct etiologic diagnosis should be taken.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.129-136
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• 2006

Background: To interpret lung function tests, it is necessary to determine the lower limits of normal (LLN) and to derive a consensus on the interpretative algorithm. '0.7 of LLN for the $FEV_1$/FVC' was suggested by the COPD International Guideline (GOLD) for defining obstructive disease. A consensus on a new interpretative algorithm was recently achieved by ATS/ERS in 2005. We evaluated the accuracy of '0.7 of LLN for the $FEV_1$/FVC' for diagnosing obstructive diseases, and we also determined the effect of the new algorithm on diagnosing ventilatory defects. Methods: We obtained the age, gender, height, weight, $FEV_1$, FVC, and $FEV_1$/FVC from 7362 subjects who underwent spirometry in 2005 at the Asan Medical Center, Korea. For diagnosing obstructive diseases, the accuracy of '0.7 of LLN for the $FEV_1$/FVC' was evaluated in reference to the $5^{th}$ percentile of the LLN. By applying the new algorithm, we determined how many more subjects should have lung volumes testing performed. Evaluation of 1611 patients who had lung volumes testing performed as well as spirometry during the period showed how many more subjects were diagnosed with obstructive diseases according to the new algorithm. Results: 1) The sensitivity of '0.7 of LLN for the $FEV_1$/FVC' for diagnosing obstructive diseases increased according to age, but the specificity was decreased according to age; the positive predictive value decreased, but the negative predictive value increased. 2) By applying the new algorithm, 34.5% (2540/7362) more subjects should have lung volumes testing performed. 3) By applying the new algorithm, 13% (205/1611) more subjects were diagnosed with obstructive diseases; these subjects corresponded to 30% (205/681) of the subjects who had been diagnosed with restrictive diseases by the old interpretative algorithm. Conclusion: The sensitivity and specificity of '0.7 of LLN for the $FEV_1$/FVC' for diagnosing obstructive diseases changes according to age. By applying the new interpretative algorithm, it was shown that more subjects should have lung volumes testing performed, and there was a higher probability of being diagnosed with obstructive diseases.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1199-1213
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• 1998

Background : The number of immunocompromised hosts has been increasing steadily and a new pulmonary infiltrate in these patients is a potentially lethal condition which needs rapid diagnosis and treatment. In this study we sought to examine the clinical manifestations, radiologic findings, and therapeutic outcomes of pulmonary mycoses presenting as a new pulmonary infiltrate in immunocompromised hosts. Method : All cases presenting as a new pulmonary infiltrate in immunocompromised hosts and confirmed to be pulmonary mycoses by pathologic examination or by positive culture from a sterile site between October of 1996 and April of 1998 were included in the study and their chart and radiologic findings were retrospectively reviewed. Results : In all, 14 cases of pulmonary mycoses from 13 patients(male : female ratio = 8 : 5, median age 47 yr) were found. Twelve cases were diagnosed as aspergillosis while two were diagnosed as mucormycosis. Major risk factors for fungal infections were chemotherapy for hematologic malignancy(10 cases) and organ transplant recipients(4 cases). Three cases were receiving empirical amphotericin B at the time of appearance of new lung infiltrates. Cases in the hematologic malignancy group had more prominent symptoms : fever(9/10), cough(6/10), sputum(5/10), dyspnea(4/10), chest pain(5/10). Patients in the organ transplant group had minimal symptoms(p<0.05). On simple chest films, all of the cases presented as single or multiple nodules(6/14) or consolidations(8/14). High resolution computed tomograph showed peri-lesional ground glass opacities(14/14), pleural effusions(5/14), and cavitary changes(7/14). Definitive diagnostic methods were as follows : 10 cases underwent minithoracotomy, 2 underwent video-assisted thoracoscopic surgery, 1 underwent percutaneous needle aspiration and 1 case was diagnosed by culture of abscess fluid. All cases received treatment with amphotericin B with 1 case each being treated with liposomal amphotericin B and itraconazole due to renal toxicity. Lung lesion improved in 12 of 14 patient but 4 patients died before completing therapy. Conclusion : When a new lung infiltrate develops presenting either as a nodule or consolidation in a neutropenic patient with hematologic malignancy or in a transplant recipient, you should always consider pulmonary mycoses as one of the differential diagnosis. By performing aggressive work up and early treatment, we may improve prognosis of these patients.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.448-463
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• 2000

Background : Pulmonary infiltrate is a frequent cause of morbidity and mortality in patients with leukemia. It is often hard to obtain a reliable diagnosis by clinical and radiologic findings alone. The aim of this study was to evaluate diagnostic and therapeutic benefits of invasive procedures for new lung infiltrates in leukemia. Methods : Patients with leukemia who developed new lung infiltrates from December 1994 to March 1999 were included in this study. These patients were classified into the empirical group who received empirical therapy only and into the invasive group who underwent bronchoscopy or surgical lung biopsy for the diagnostic purpose of new lung infiltrates. A retrospective chart review was done to find the etiologies of new lung infiltrates, the yield of invasive procedures, outcome as well as predicting factors for survival. Results : 1) One hundred-two episodes of new lung infiltrates developed in 90 patients with leukemia. Invasive procedures were performed in 44 episodes while 58 episodes were treated with empirical therapy only. 2) Invasive procedures yielded a specific diagnosis in 72.7%(32/44), of which 78.1% had infectious etiology. Therapeutic plan was changed in 52.3%(23/44) of patients after invasive procedures. None of them showed procedure-related mortality. 3) The overall survival rate was 62.7%(64/102). Survival rate in the invasive group (79.5%) was significantly better than that in the empirical group (50.0%) (p=0.002). 4) Upon multivariate analysis, the performance of invasive procedures, no need for mechanical ventilation and achievement of complete remission of leukemia after induction chemotherapy were the independent predicting factors for survival in patients with leukemia and new lung infiltrates. Conclusion : Bronchoscopy and surgical lung biopsy are useful in the diagnosis of new lung infiltrates in patients with leukemia. However, survival benefits of invasive procedures should be considered together with disease status of leukemia and severity of respiratory compromise.