• Tuberculosis and Respiratory Diseases
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• v.83 no.2
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• pp.141-146
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• 2020

Background: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). Methods: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected. Conclusion: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

• Tuberculosis and Respiratory Diseases
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• v.72 no.5
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• pp.409-415
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• 2012

Background: The isolation of non-tuberculous mycobacteria (NTM) has been increasing in South Korea. To date, however, the cause of this increase has not been determined, and it remains unclear whether the use of liquid media has contributed to this increase. The aim of this study was to evaluate the factors associated with NTM isolation and the impact of liquid media on NTM culture. Methods: Mycobacterial smear/culture results of respiratory specimens (sputum and bronchial aspirates), obtained during the years 2002, 2005, and 2010, were retrieved and analyzed retrospectively. Results: During the years 2002, 2005, and 2010, 83,096 sputum specimens were collected from 31,104 patients, and were cultured for mycobacteria, using solid media only in the 2002 and 2005 specimens and both solid and liquid media in the 2010. Of these, 3,516 (4.2%) specimens were smear-positive for acid-fast bacilli (AFB). The annual rate of NTM among positive culture specimens increased from 21% in 2002 to 57.8% in 2010 (p<0.001), as did the proportion of NTM, among AFB smear- and culture-positive specimens, from 12.2% in 2002 to 45.2% in 2010 (p<0.001). In 2010, the NTM culture rate was higher in the liquid than in the solid media (13.9% vs. 8.4%, p<0.001). The NTM rate among AFB-positive specimens was higher in patients aged >50 than ${\leq}$50 years. Conclusion: The rate of NTM isolation has steadily been increasing at the hospital in South Korea, likely due in part to the use of liquid media for the culture.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.173-182
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• 2002

Background : Nontuberculous mycobacteria (NTM) have usually been considered to be contaminants of colonizers when isolated from respiratory specimens in Korea, where there is a high prevalence of tuberculosis and a low rate of HIV infections. Therefore, there has been few studies on the clinical significance of NTM species in immunocompetent patients were investigated. Methods : Thirty-five NTM isolates, for which species identification was requested by the treating physicians during 1999 at the Asan Medical Center, were retrospectively analyzed. They were identified to the species level by mycolic acid analysis using high-performance liquid chromatography. The medical records of the patients with the NTM isolates were reviewed to identify those patients who met the American Thoracic Society (ATS)'s criteria for mycobacterial pulmonary infection. Their antimicrobial susceptibility data were compared with the clinical outcomes. Results : The NTM were identified as M. intracellulare (6 isolates), M. avium (5), M. abscessus (5), M. gordonae (5), M. terrae complex (4), M. szulgai (2), M. kansasii (2), M. fortuitum (2), M. peregrinum (1), M. mucogenicum (1), M. celatum (1), and M. chelonae (1). All 35 patients showed clinical symptoms and signs of chronic lung disease, but none had a HIV infections; 16 (45.7%) patients were found to be compatible with a NTM pulmonary infection according to the ATS criteria, 5 and 4 cases were affected with M. intracellulare and M. abscessus, respectively; 8 patients had a history of pulmonary tuberculosis. 13 patients received antimycobacterial therapy for an average of 21 months and 9 patients were treated with second-line drugs. Only 4 patients had improved radiologically. Conclusion : A NTM should be considered a potential pathogen of pulmonary infections in immunocompetent patients with chronic pulmonary diseases. Most NTM infections were left untreated for a prolonged period and showed a poor outcome as a result, M. intracellulare and M. abscessus were the two most frequent causes of NTM pulmonary infections in this study. Species identification and antimycobacterial susceptibility tests based on the species are needed for the optimum management of a NTM pulmonary infection in patients.

• Tuberculosis and Respiratory Diseases
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• v.54 no.3
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• pp.283-294
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• 2003

Introduction : Rapidly growing nontuberculous mycobacteria (RGM) can produce numerous types of manifestations including a pulmonary infection. Managing a pulmonary infection due to RGM is unusually difficult to treat because the organism is invariably resistant to traditional antituberculous drugs and has a varying susceptibility to other antibiotics. The experiences of treatments for a RGM pulmonary infection with various antibiotics are also limited. This study evaluated the clinical manifestations, treatment, and the therapeutic outcomes of a RGM pulmonary infection. Subjects and method : Fifty-four cases with RGM from respiratory specimens were identified between November of 1996 and September of 2002 in the Asan medical center. The medical records and radiographic findings in 20 patients who fulfilled the diagnostic criteria of nontuberculous mycobacteria (NTM) pulmonary disease by ATS guidelines. The clinical, laboratory, and radiological parameters between subgroups. Results : Of the 20 patients, 15 were female. The mean age was 57.7 yrs (${\pm}7.5$), and all of the patients had a history of pulmonary tuberculosis. Most (90%) had an underlying lung disease. The majority of the isolates (80%) were M. abscessus. Chest radiography showed bilateral involvement in 80% of the patients. Bronchiectasis and multiple nodules were the main findings. Cavitation was present in 35% of the patients. Even though 70 % of the patients received antituberculous drugs prior to the correct diagnosis, all of the patients eventually received antibiotics. A mean of 3.5 antibiotics were given for an average of 439 days(${\pm}168$). After completing treatment, nine patients showed improvement after a mean 591(${\pm}311$) days of treatment, whereas the antibiotic treatment was unsuccessful in 2 patients. Conclusion : Many patients with a RGM pulmonary infection show an atypical pattern of radiological findings (bronchiectasis and multiple centrilobular nodules). It is very important to differentiate between M. tuberculosis and NTM and to identify the causative organisms among the NTM because a misdiagnosis can lead to an inappropriate and prolonged treatment. Combined antibiotic treatment yielded promising results, and is recommended for treating patients with a RGM pulmonary infection.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.22-32
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• 2003

Background : Sputum smears for acid-fast bacilli(AFB) examined microscopically is the most important diagnostic test for pulmonary tuberculosis. However, the AFB observed on the smear may represent either M. tuberculosis or nontuberculous mycobacteria (NTM). This study examined the recovery rate of NTM from the AFB smear-positive sputum specimens in a tertiary hospital in Korea. Materials and Methods : This study analyzed the results for the 1,889 AFB smear-positive and culture-positive sputum specimens collected from 844 patients from July, 1997 to December, 2001. Results : The 1,889 sputum specimens collected from 844 patients tested positive on both microscopy and culture during the 4.5 years. The NTM were recovered from 10.3% (195/1,889) of the smear-positive sputum specimens and 11.0% (93/844) of patients with smear-positive sputum. The NTM were isolated more than two times in 44.1% (41/93) of the patients from whom the NTM was recovered. Trends of the recovery rate of the NTM from the AFB smear-positive sputum specimens were increasing from 6.5%(17/262) in the latter half of 1997 to 17.8%(36/202) in the latter half of 2001 (p<0.001, test for trend). Conclusions : These results suggest that some patients with AFB smear-positive sputum have NTM pulmonary disease rather than pulmonary tuberculosis in Korea.

• Tuberculosis and Respiratory Diseases
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• v.69 no.3
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• pp.201-206
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• 2010

Nontuberculous mycobacterial (NTM) diseases are increasing worldwide. However NTM lung disease in organ transplant recipients has been rarely reported. Here, we report 2 cases of NTM lung disease in heart transplant recipients. A 37-year-old man, who had undergone a heart transplant one year previous, was admitted to hospital due to a cough. Chest CT scan showed multiple centrilobular nodules in both lower lungs. In his sputum, M. abscessus was repeatedly identified by rpoB gene analysis. The patient improved after treatment with clarithromycin, imipenem, and amikacin. An additional patient, a 53-year-old woman who had undergone a heart transplant 4 years prior and who suffered from bronchiectasis, was admitted because of purulent sputum. The patient's chest CT scan revealed aggravated bronchiectasis; M. intracellulare was isolated repeatedly in her sputum. Treatment was successfully completed with clarithromycin, ethambutol, and ciprofloxacin. NTM lung disease should be considered as a potential opportunistic infection in organ transplant recipients.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.275-283
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• 2012

Background: Healthy individuals who develop nontuberculous mycobacteria (NTM) lung disease are likely to have specific susceptibility factors which can lead to a NTM infection. The aim of the present study was to investigate the mechanism underlying innate immune responses, including the role of mitogen-activated protein kinase (MAPK), in Mycobacterium abscessus lung disease. Methods: Extracellular signal-regulated kinase (ERK1/2) and p38 MAPK expression in monocytes from peripheral blood mononuclear cells were measured by Western blot analysis after stimulation by Mycobacterium avium in five patients with M. abscessus lung disease and seven healthy controls. A M. avium-induced cytokine assay was performed after inhibition of ERK1/2 and p38 MAPK pathways. Results: Mycobacterium avium induced p38 and ERK1/2 expression in monocytes from healthy controls and subsequently upregulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 production. In monocytes from patients with M. abscessus lung disease, however, induction of p38 and ERK1/2 expression, and the production of TNF-${\alpha}$, IL-6, and IL-10 were significantly lower. Conclusion: Decreased activity of MAPK and cytokine secretion in monocytes from patients with M. abscessus lung disease may provide an explanation regarding host susceptibility to these uncommon infections.

• 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.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.2
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• pp.83-89
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• 2015

Although Mycobacterium tuberculosis complex strains remain responsible for the majority of diseases caused by mycobacterial infections worldwide, the increase in HIV (human immuno deficiency virus) infections has allowed for the emergence of other non-tuberculous mycobacteria as clinically significant pathogens. M. tuberculosis was detected by two-tube nested polymerase chain reaction (PCR) and non-tuberculous mycobacteria was detected by PCR-restriction fragment length polymorphism (RFLP) with Msp I. Result of niacin test is equal to result of two-tube nested PCR after culture for M. tuberculosis. In this study, acid fast bacilli stain (AFB. stain) >2+ case, Detection of Mycobacteria is similar to result before culture and after culture. AFB. stain <1+ case, result of mycobacteria is distinguished. Conclusionly, these results suggest that identification of mycobacteria must go side by side both culture and PCR for more fast and accuracy.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.242-249
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• 2004

Background : Because of the low sensitivity of sputum smear and culture, diagnosis of nontuberculous mycobacterium (NTM) pulmonary disease, especially in patients with bronchiectasis, is often difficult. We investigated the usefulness of bronchoscopy for the diagnosis of NTM pulmonary disease including M. avium complex (MAC) and M. abscessus in patients with bronchiectasis and multiple pulmonary nodules on chest computed tomography (CT). Methods : We reviewed 48 cases of patients who were performed bronchoscopic bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) under suspect of NTM pulmonary disease based on CT findings of bronchiectasis and multiple nodules from April 2002 to June 2003. Results : Twenty five of the 48 patients (54%; 12 MAC, 14 M. abscessus) were diagnosed as NTM pulmonary disease on the basis of the American Thoracic Society diagnostic criteria for NTM pulmonary disease. Sixteen of the 21 patients (76%; 5 MAC, 11 M. abscessus) with 3 or more positive sputum cultures of NTM were confirmed tissue invasion by TBLB. Five of the 24 patients (21%; 4 MAC, 1 M. abscessus) who could not be diagnosed with sputum cultures were diagnosed by bronchoscopic BAL and TBLB. Conclusion : Bronchoscopy is helpful for the diagnosis of NTM pulmonary disease and confirmation of tissue invasion by NTM, not only MAC but also M. abscessus, in patients with bronchiectasis and multiple nodules on chest CT scan.