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1.  Effect of Prolonged Incubation Time on Results of the QuantiFERON TB Gold In-Tube Assay for Diagnosis of Latent Tuberculosis Infection 
Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.
PMCID: PMC3889582  PMID: 23825190
2.  18F-FDG Positron-Emission Tomography/Computed Tomography Findings of Radiographic Lesions Suggesting Old Healed Tuberculosis 
Journal of Korean Medical Science  2014;29(3):386-391.
The presence of radiographic lesions suggesting old healed tuberculosis (TB) is one of the strongest risk factors for the subsequent development of active TB. We elucidated the metabolic activity of radiographic lesions suggesting old healed TB using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). This cross-sectional study included 63 participants with radiographic lesions suggesting old healed TB and with available 18F-FDG PET/CT scans. The maximum standardized uptake value (SUVmax) measured in the lesions, the clinical characteristics, results of the tuberculin skin test (TST) and interferon-γ release assay (IGRA) were analyzed. The SUVmax in old healed TB was 1.5 or higher among nine (14.3%) participants. Age (adjusted odds ratio [aOR], 1.23; 95% CI, 1.03-1.46), history of previous TB (aOR, 60.43; 95% CI, 1.71-2131.65), and extent of the lesions (aOR, 1.34; 95% CI, 1.02-1.75) were associated with higher SUVmax. The positive rates for the TST and IGRA were not different between groups with and without increased FDG uptake. Increased FDG uptake on 18F-FDG PET/CT was observed in a subset of patients with radiographic lesions suggesting old healed TB. Given that the factors associated with increased FDG uptake are known risk factors for TB development, the possibility exists that participants with old healed TB lesions with higher SUV on 18F-FDG PET/CT scans might be at higher risk for active TB.
Graphical Abstract
PMCID: PMC3945134  PMID: 24616588
Positron-Emission Tomography; Tomography, X-Ray Computed; Tuberculosis, Pulmonary; Latent Tuberculosis; Interferon-gamma Release Tests
3.  Impact of outdoor air pollution on the incidence of tuberculosis in the Seoul metropolitan area, South Korea 
Although indoor air pollution is a well-known risk factor for tuberculosis (TB), the possible link between outdoor air pollution and TB development has not been examined fully. We assessed the impact of outdoor air pollution on TB development in the Seoul metropolitan area, South Korea.
The mean concentrations of ambient particulate matter (PM) with an aerodynamic diameter ≤ 10 µm (PM10), O3, CO, NO2, and SO2 levels in Seoul, between January 1, 1997 and December 31, 2006, were determined. Furthermore, their association with the risk of developing TB after adjusting for socioeconomic status, between January 1, 2002 and December 31, 2006, was investigated.
Between January 1, 2002 and December 31, 2006, a total of 41,185 TB cases were reported in Seoul. Concentrations of PM10, O3, CO, and NO2 were not associated with TB incidence in males or females. However, the interquartile increase in SO2 concentration was associated with a 7% increment in TB incidence (relative risk [RR], 1.07; 95% credible interval [CrI], 1.03 to 1.12) in males but not in females (RR, 1.02; 95% CrI, 0.98 to 1.07).
Long-term exposure to ambient SO2 increased the risk of TB in males.
PMCID: PMC3956988  PMID: 24648801
Air pollution; Tuberculosis; Sulfur dioxide
4.  Clinical characteristics and treatment responses of patients who developed tuberculosis following use of a tumor necrosis factor-α inhibitor 
Individuals being treated with tumor necrosis factor (TNF)-α inhibitors are at increased risk of developing tuberculosis (TB). We determined the clinical characteristics and treatment response of patients who developed TB after using TNF-α inhibitors.
Patients with TB detected within 12 months of the initiation of TNF-α inhibitor treatment were included, if seen from January 1, 2000 to August 31, 2011. We retrospectively reviewed the clinical records, results of bacteriological examinations, and radiographs of the included patients and the response to anti-TB treatment.
We indentified seven cases of TB in 457 patients treated with TNF-α inhibitors during the study period. TB developed a median of 123 days (range, 48 to 331) after the first dose of TNF-α inhibitor. Pulmonary TB, including TB pleuritis, was diagnosed in three patients and extrapulmonary TB in four. Favorable treatment outcomes were achieved in six of seven patients.
Among the TNF-α inhibitor users who contracted TB, extrapulmonary sites were common and the treatment response was satisfactory.
PMCID: PMC3604607  PMID: 23525649
Tumor necrosis factor-alpha; Tuberculosis; Mycobacterium
5.  Positive Tuberculin Skin Test or Interferon-Gamma Release Assay in Patients with Radiographic Lesion Suggesting Old Healed Tuberculosis 
Journal of Korean Medical Science  2012;27(7):761-766.
Radiographic lesions suggesting old healed tuberculosis (TB) is considered a risk factor for the subsequent development of active TB. The aim of this study was to estimate the positive rates of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in persons with old healed TB. Participants with lesions suggesting old healed TB on chest images and controls without such lesions were prospectively enrolled between January 1, 2010, and January 31, 2011. TST and the QuantiFERON-TB Gold In-Tube test (QFT-GIT) were performed. In total, 193 participants with old healed TB and 126 controls were recruited. The rates of positive TST and QFT-GIT among patients with old healed TB were 54.6% and 77.7%, respectively. The rates of positive TST and QFT-GIT among patients without old healed TB were 38.9% and 61.9%. Sixteen percent of participants with old healed TB showed negative results by both TST and QFT-GIT. The positive rate of TST waned among participants with old healed TB who were older than 60 yr, whereas QFT-GIT positivity was unaffected by age. The positive rates of TST and IGRA among participants with radiographic lesions suggesting old healed TB was higher than without those lesions. In addition, IGRA may be more accurate than TST for the detection of latent TB infection, especially in populations of individuals older than 60 yr.
PMCID: PMC3390724  PMID: 22787371
Radiology and Other Imaging; Tuberculosis; Pulmonary
6.  Bacterial Yield from Quantitative Cultures of Bronchoalveolar Lavage Fluid in Patients with Pneumonia on Antimicrobial Therapy 
Early diagnosis and appropriate antimicrobial choice are crucial when managing pneumonia patients, and quantitative culture of bronchoalveolar lavage (BAL) fluid is considered a useful method for identifying pneumonia pathogens. We evaluated the quantitative yield of BAL fluid bacterial cultures in patients being treated with antimicrobials and attempted to identify factors predictive of positive BAL cultures.
Patients over 18 years old and whose BAL fluid was subjected to quantitative culture to identify the organism causative of pneumonia between January 1, 2005, and December 31, 2009, were included. We reviewed the results of BAL fluid bacterial cultures and the clinical records, laboratory tests, and radiographic findings of the patients.
BAL was performed on 340 patients with pneumonia. A positive BAL culture, defined as isolation of more than 104 colony forming units/mL bacteria, was documented in 18 (5.29%) patients. Of these, 9 bacteria isolated from 10 patients were classified as probable pathogens. The most frequently isolated bacteria were methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. No independent predictive factor for positive BAL cultures was identified.
The yield of quantitative BAL fluid bacterial culture in patients already on antimicrobials was low. Clinicians should be cautious when performing a BAL culture in patients with pneumonia who are already on antimicrobials.
PMCID: PMC3372799  PMID: 22707887
Bronchoalveolar lavage; Pneumonia; Antimicrobials
7.  Retrospective Comparison of Levofloxacin and Moxifloxacin on Multidrug-Resistant Tuberculosis Treatment Outcomes 
To compare the effect of levofloxacin and moxifloxacin on treatment outcomes among patients with multidrug-resistant tuberculosis (MDR-TB).
A retrospective analysis of 171 patients with MDR-TB receiving either levofloxacin or moxifloxacin was performed. Treatment responses were categorized into treatment success (cured and treatment completed) or adverse treatment outcome (death, failure, and relapsed).
The median age of the patients was 42.0 years. Approximately 56% of the patients were male. Seventeen patients had extensively drug-resistant tuberculosis, and 20 had a surgical resection. A total of 123 patients (71.9%) received levofloxacin for a median 594 days, and 48 patients (28.1%) received moxifloxacin for a median 673 days. Other baseline demographic, clinical, and radiographic characteristics were similar between the two groups. The moxifloxacin group had a significantly higher number of resistant drugs (p < 0.001) and a higher incidence of resistance to ofloxacin (p = 0.005) in the drug sensitivity test. The treatment success rate was 78.9% in the levofloxacin group and 83.3% in the moxifloxacin group (p = 0.42). Adverse reactions occurred at similar rates in the groups (p = 0.44). Patients in the moxifloxacin group were not more likely to have treatment success than those in the levofloxacin group (adjusted odds ratio, 0.76; 95% confidence interval, 0.24 to 2.43; p = 0.65).
Both levofloxacin and moxifloxacin showed equivalent efficacy for treating MDR-TB.
PMCID: PMC3110847  PMID: 21716591
Levofloxacin; Moxifloxacin; Tuberculosis, multidrug-resistant; Quinolones; Tuberculosis
8.  Incidence and Risk Factors of Steroid-induced Diabetes in Patients with Respiratory Disease 
Journal of Korean Medical Science  2011;26(2):264-267.
Glucocorticoids are effective for treating several respiratory diseases. However, they can cause hyperglycemia. This study determined the incidence and risk factors of steroidinduced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks between January 2003 and December 2008. Patients whose initial random glucose level exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose was 4,965 mg, and the median duration of steroid treatment was 193 days. S-DM was diagnosed in 34 (14.7%) of 231 patients. Multivariate logistic regression identified older age (odds ratio 1.05, 95% confidence interval 1.02-1.09) as a risk factor for S-DM. S-DM is frequent among patients with respiratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of S-DM, especially among elderly patients.
PMCID: PMC3031012  PMID: 21286019
Diabetes; Glucocorticoids; Hyperglycemia; Respiration Disorders; Steroids
9.  Impact of Parenchymal Tuberculosis Sequelae on Mediastinal Lymph Node Staging in Patients with Lung Cancer 
Because tuberculous (TB) involvement of mediastinal lymph nodes (LN) could cause false positive results in nodal staging of lung cancer, we examined the accuracy of nodal staging in lung cancer patients with radiographic sequelae of healed TB. A total of 54 lung cancer patients with radiographic TB sequelae in the lung parenchyma ipsilateral to the resected lung, who had undergone at least ipsilateral 4- and 7-lymph node dissection after both chest computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT were included for the analysis. The median age of 54 subjects was 66 yr and 48 were males. Calcified nodules and fibrotic changes were the most common forms of healed parenchymal pulmonary TB. Enlarged mediastinal lymph nodes (short diameter > 1 cm) were identified in 21 patients and positive mediastinal lymph nodes were identified using FDG-PET/CT in 19 patients. The overall sensitivity and specificity for mediastinal node metastasis were 60.0% and 69.2% with CT and 46.7% and 69.2% with FDG-PET/CT, respectively. In conclusion, the accuracy of nodal staging using CT or FDG-PET/CT might be low in lung cancer patients with parenchymal TB sequelae, because of inactive TB lymph nodes without viable TB bacilli.
PMCID: PMC3012852  PMID: 21218032
Latent Tuberculosis; Lung Neoplasms; Mediastinum; Tuberculosis; Lymph Node
10.  Sequential Bilateral Lung Resection in a Patient with Mycobacterium Abscessus Lung Disease Refractory to Medical Treatment 
Yonsei Medical Journal  2009;51(1):141-144.
Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions.
PMCID: PMC2799965  PMID: 20046529
Atypical mycobacteria; surgery; therapeutics
11.  Prevalence and Its Predictors of Extrapulmonary Involvement in Patients with Pulmonary Tuberculosis 
Journal of Korean Medical Science  2009;24(2):237-241.
Extrapulmonary organ involvement in human immunodefiaency virus (HIV)-infected patients with pulmonary tuberculosis (TB) is reported to be 26%, however, the clinical predictors of extrapulmonary involvement in pulmonary TB patients has not been reported yet. We tried to determine the clinical predictors of presence of extrapulmonary involvement in patients with pulmonary TB. Cross-sectional study was performed including all adult patients with culture-proven pulmonary TB diagnosed between January 1, 2004 and July 30, 2006, at a tertiary referral hospital in South Korea. The presence of extra-pulmonary TB involvement was diagnosed based on bacteriological, pathological, or clinical evidence. Among 320 patients with a culture-proven pulmonary TB, 40 had extrapulmonary involvement. Patients with bilateral lung involvement were more likely to have extrapulmonary involvement, with an adjusted odds ratio (OR) of 4.21 (95% confidence interval [CI], 1.82-9.72), while patients older than 60 yr (adjusted OR, 0.27; 95% CI, 0.08-0.89), patients with cavitary lesions (adjusted OR, 0.37; 95% CI, 0.16-0.84), and with higher levels of serum albumin (adjusted OR, 0.45; 95% CI, 0.25-0.78) had less frequent involvement. Clinicians should be aware of the possibility of extrapulmonary involvement in TB patients with bilateral lung involvement without cavity formation or lower levels of serum albumin.
PMCID: PMC2672122  PMID: 19399264
Tuberculosis; Tuberculosis, Miliary; Diagnosis
12.  The Incidence and Clinical Implication of Sputum with Positive Acid-Fast Bacilli Smear But Negative in Mycobacterial Culture in a Tertiary Referral Hospital in South Korea 
Journal of Korean Medical Science  2008;23(5):767-771.
Although it is not rare to find sputum that is positive acid-fast bacilli (AFB) smear but subsequent culture fails to isolate mycobacteria in clinical practice, the incidence and clinical implication of those sputa from new patients has not been clearly elucidated. The aim of this study was to determine the incidence and clinical implication of sputum with positive AFB smear but negative in mycobacterial culture. All sputa that were positive AFB smear requested during diagnostic work up for new patients visiting Seoul National University Hospital from 1 January 2005 through 31 December 2006 were included. Sputa producing a positive AFB smear but negative mycobacterial culture were classified into one of four categories: laboratory failure to isolate mycobacteria, false positive AFB smear, pathogen may show a positive AFB smear other than mycobacteria, and indeterminate results. Out of 447 sputa with a positive AFB smear, 29 (6.5%) failed to culture any organism. Among these 29 sputa, 18 were caused by laboratory failure to isolate mycobacteria, six were false positive smears, and five indeterminate. Although most sputum with a positive AFB smear but negative culture could be classified as a laboratory failure, clinicians should consider the possibility of false positive AFB smear.
PMCID: PMC2580011  PMID: 18955779
Tuberculosis; Diagnosis; Hospital Laboratories, Hospital
13.  Lack of Association between Matrix Metalloproteinase 8 Promoter Polymorphism and Bronchiectasis in Koreans 
Journal of Korean Medical Science  2007;22(4):667-671.
The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex-matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans.
PMCID: PMC2693817  PMID: 17728507
Bronchiectasis; Genetic Predisposition to Disease; Koreans; Matrix-metalloproteinase; Neutrophil Collagenase; Single Nucleotide Polymorphism
14.  The Interval Between Initiation of Anti-tuberculosis Treatment in Patients with Culture-positive Pulmonary Tuberculosis and Receipt of Drug-susceptibility Test Results 
Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media.
PMCID: PMC2693564  PMID: 17297247
Tuberculosis; Microbial Sensitivity Tests; Treatment
15.  The Prevalence and Evolution of Anemia Associated with Tuberculosis 
Journal of Korean Medical Science  2006;21(6):1028-1032.
Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (≤65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8±113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment.
PMCID: PMC2721923  PMID: 17179681
Tuberculosis; Anemia; Treatment; Treatment Outcome
16.  Prevalence and Global Initiative for Chronic Obstructive Lung Disease Group Distribution of Chronic Obstructive Pulmonary Disease Detected by Preoperative Pulmonary Function Test 
PLoS ONE  2015;10(1):e0115787.
Despite being a major public health problem, chronic obstructive pulmonary disease (COPD) remains underdiagnosed, and only 2.4% COPD patients are aware of their disease in Korea. The objective of this study was to estimate the prevalence of COPD detected by spirometry performed as a preoperative screening test and to determine the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group distribution and self-awareness of COPD.
We reviewed the medical records of adults (age, ≥40 years) who had undergone spirometry during preoperative screening between April and August 2013 at a tertiary hospital in Korea. COPD was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio of <0.7. We analyzed self-administered COPD questionnaires for the assessment of the frequency of acute exacerbation over the previous year and dyspnea severity using the modified Medical Research Council dyspnea scale and COPD assessment test.
Among 3029 patients aged >40 years who had undergone spirometry as a preoperative screening test, 474 (15.6%; 404 men; median age, 70 years; range, 44–93 years) were diagnosed with COPD. Only 26 (5.5%) patients reported previous diagnosis of COPD (2.1%), emphysema (0.8%), or chronic bronchitis (2.5%). The GOLD group distribution was as follows: 63.3% in group A, 31.2% in group B, 1.7% in group C, and 3.8% in group D.
The prevalence of COPD diagnosed by preoperative spirometry was 15.6%, and only 5.5% patients were aware of their disease. Approximately one-third of the COPD patients belonged to GOLD groups B, C, and D, which require regular treatment.
PMCID: PMC4308080  PMID: 25625286
17.  Frequency and clinical implications of the isolation of rare nontuberculous mycobacteria 
To date, more than 125 species of nontuberculous mycobacteria (NTM) have been identified. In this study, we investigated the frequency and clinical implication of the rarely isolated NTM from respiratory specimens.
Patients with NTM isolated from their respiratory specimens between July 1, 2010 and June 31, 2012 were screened for inclusion. Rare NTM were defined as those NTM not falling within the group of eight NTM species commonly identified at our institution: Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, M. fortuitum, M. kansasii, M. gordonae, and M. peregrinum. Clinical, radiographic and microbiological data from patients with rare NTM were reviewed and analyzed.
During the study period, 73 rare NTM were isolated from the respiratory specimens of 68 patients. Among these, M. conceptionense was the most common (nine patients, 12.3%). The median age of the 68 patients with rare NTM was 68 years, while 39 of the patients were male. Rare NTM were isolated only once in majority of patient (64 patients, 94.1%). Among the four patients from whom rare NTM were isolated two or more times, only two showed radiographic aggravation caused by rare NTM during the follow-up period.
Most of the rarely identified NTM species were isolated from respiratory specimens only once per patient, without concomitant clinical aggravation. Clinicians could therefore observe such patients closely without invasive work-ups or treatment, provided the patients do not have decreased host immunity towards mycobacteria.
PMCID: PMC4297383  PMID: 25572753
Nontuberculous mycobacteria; Clinical manifestation
18.  Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients 
BMC Pulmonary Medicine  2014;14(1):168.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.
The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.
The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.
The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.
PMCID: PMC4233073  PMID: 25358403
Pulmonary fibrosis; Immunohistochemical analysis; Usual interstitial pneumonia; mTOR; ZEB1; ROCK1; Survival
19.  Culture Conversion Rate at 2 Months of Treatment According to Diagnostic Methods among Patients with Culture-Positive Pulmonary Tuberculosis 
PLoS ONE  2014;9(8):e103768.
The culture-negative conversion rate of sputum after 2 months of treatment in patients with pulmonary tuberculosis (TB) is used as a reliable surrogate marker for relapse after completion of treatment. We hypothesized that culture conversion of sputum at 2 months of anti-TB treatment and the time to culture conversion are different among pulmonary TB patients who are diagnosed using different methods.
Culture-confirmed pulmonary TB patients who were diagnosed between 1 January, 2011 and 31 December, 2012 were classified into three groups based on the diagnostic method that prompted treatment initiation: positive acid-fast bacilli (AFB) staining of sputum (smear-positive group), negative AFB staining, but Mycobacterium tuberculosis was cultured from sputum (culture-positive group), and positive AFB staining, positive polymerase chain reaction (PCR) for M. tuberculosis, or culture of M. tuberculosis from a bronchoscopic specimen (bronchoscopy group). Rates of negative mycobacterial culture conversion at 2 months of anti-TB treatment and the time to negative culture conversion of sputum were compared among the three groups.
A total of 203 patients with culture-confirmed pulmonary TB were included in the final analysis. TB patients in the culture-positive group (94.1%) and the bronchoscopy group (97.6%) showed a higher culture conversion rate at 2 months of treatment than those in the smear-positive group (78.7%, P = 0.001). Additionally, the time to culture conversion was longer in the smear-positive group (median, 40 days) than in the culture-positive (median, 19 days; P = 0.009) and bronchoscopy groups (median, 29 days; P = 0.004).
The higher culture conversion rate at 2 months and the shorter time to culture conversion among pulmonary TB patients with a negative AFB smear suggests the feasibility of shortening treatment duration and isolation in these patients.
PMCID: PMC4126681  PMID: 25105410
20.  Dominant gain-of-function STAT1 mutations in FOXP3WT IPEX-like Syndrome 
Mutations in STAT1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles), to mild disseminated mycobacterial disease (hypomorphic alleles), to chronic mucocutaneous candidiasis (hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity and squamous cell cancers.
To investigate the role of STAT1 gain of function mutations in phenotypes other than CMC.
We initially screened patients with chronic mucocutaneous candidiasis and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T cells. After our initial case identifications we explored two large cohorts of FOXP3WT IPEX-like patients for STAT1 mutations.
We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis, reminiscent of IPEX syndrome, all but one had a variety of mucosal and disseminated fungal infections. All patients lacked FOXP3 mutations but had uniallelic STAT1 mutations [c.629 G>T, p.R210I; c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M (2 patients)]. STAT1 phosphorylation in response to IFN-γ, IL-6 and IL-21 was increased and prolonged. CD4+ IL-17 producing T cells were diminished. All patients had a normal percentage of regulatory T cells in the CD4+ T cell compartment and their function was intact in the two patients tested. Patients with cells available for study had normal levels of IL-2-induced STAT5 phosphorylation..
Gain-of-function mutations in STAT1 can cause an IPEX-like syndrome with normal frequency and function of regulatory T cells.
PMCID: PMC3672257  PMID: 23534974
STAT1; IPEX; FOXP3; Treg; CMC; aneurysms
21.  Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer 
Journal of Korean Medical Science  2014;29(4):507-511.
Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 × 109/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.
Graphical Abstract
PMCID: PMC3991793  PMID: 24753697
Carcinoma Non-Small Cell Lung; Prognosis; Thrombocytosis; Fibrinogen
22.  Multivariate analysis of prognostic factors in patients with pulmonary actinomycosis 
There have been few studies of pulmonary actinomycosis, which is an uncommon anaerobic infection. Consequently, the optimal therapeutic regimen, appropriate duration of treatment, long-term prognosis, and factors predicting prognosis are not well established.
We retrospectively reviewed the medical records of histopathologically confirmed cases of pulmonary actinomycosis seen between November 2003 and December 2012.
The study included 68 patients with a mean age of 58.4 ± 11.6 years. Of the 68, initial surgery was performed in 15 patients (22.1%), while the remaining 53 (77.9%) received antibiotic therapy initially. In the initial antibiotic group, 45/53 (84.9%) were cured without relapse (median antibiotic duration 5.3 months). 5/53 (9.4%) patients were refractory medically (median antibiotic duration 9.7 months), and 3/53 (5.7%) experienced a recurrence (median time to relapse 35.3 months). In the initial surgery group, 14/15 (93.3%) were cured and treatment failure occurred in one (6.7%). In the multivariate analysis, the absence of an antibiotic response at 1 month was the only independent factor associated with a poor treatment outcome, with an adjusted odds ratio of 49.2 (95% CI, 3.34–724.30). There was no significant difference in treatment outcome based on the size of the parenchymal lesion, comorbidities, whether intravenous antibiotics were used, antibiotic therapy duration, or whether the initial treatment was surgical.
Antibiotic treatment with or without surgery was effective for treatment of pulmonary actinomycosis. Nevertheless, treatment failure or recurrence occurred in a considerable proportion of patients, especially those resistant to the initial antibiotic treatment.
PMCID: PMC3898383  PMID: 24400792
Actinomycosis; Anti-bacterial agents; Treatment outcome; Prognostic factors; Pulmonary
23.  Phenotypic, immunologic, and clinical characteristics of patients with nontuberculous mycobacterial lung disease in Korea 
BMC Infectious Diseases  2013;13:558.
This study aimed to elucidate the phenotypic, immunologic, and clinical characteristics of Korean patients with nontuberculous mycobacterial (NTM) lung disease and compare them with non-NTM bronchiectasis (BE) patients.
We prospectively recruited patients between 20 and 80 years of age who had nodular BE type NTM lung disease. Phenotypic, immunologic, and clinical characteristics were evaluated through physical examination, laboratory tests, pulmonary function tests, and radiographic examinations. Questionnaires were also answered. The results of the evaluations were compared with the results of non-NTM BE patients.
A total of 84 patients with NTM lung disease and 47 non-NTM BE patients participated in the study. Mycobacterium avium complex lung disease and M. abscessus lung disease were most common. Patients with NTM lung disease had lower body mass index than non-NTM BE patients. Scoliosis was observed more frequently in patients with NTM lung disease than in non-NTM BE patients.
Significant similarities were seen between Korean patients with NTM lung disease and patients from other countries. Differences in phenotypic and clinical characteristics between NTM lung disease and non-NTM BE patients suggest differences in the immunopathogenesis of NTM lung disease and non-NTM BE.
Trial registration information Registration number; NCT01616745
PMCID: PMC4222821  PMID: 24274658
Bronchiectasis; Clinical characteristics; Immunopathogenesis; Nontuberculous mycobacterial lung disease; Phenotype
24.  Diagnostic Accuracy and Turnaround Time of the Xpert MTB/RIF Assay in Routine Clinical Practice 
PLoS ONE  2013;8(10):e77456.
The Xpert MTB/RIF assay was introduced for timely and accurate detection of tuberculosis (TB). The aim of this study was to determine the diagnostic accuracy and turnaround time (TAT) of Xpert MTB/RIF assay in clinical practice in South Korea. We retrospectively reviewed the medical records of patients in whom Xpert MTB/RIF assay using sputum were requested. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of pulmonary tuberculosis (PTB) and detection of rifampicin resistance were calculated. In addition, TAT of Xpert MTB/RIF assay was compared with those of other tests. Total 681 patients in whom Xpert MTB/RIF assay was requested were included in the analysis. The sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay for diagnosis of PTB were 79.5% (124/156), 100.0% (505/505), 100.0% (124/124) and 94.0% (505/537), respectively. Those for the detection of rifampicin resistance were 57.1% (8/14), 100.0% (113/113), 100.0% (8/8) and 94.9% (113/119), respectively. The median TAT of Xpert MTB/RIF assay to the report of results and results confirmed by physicians in outpatient settings were 0 (0–1) and 6 (3–7) days, respectively. Median time to treatment after initial evaluation was 7 (4–9) days in patients with Xpert MTB/RIF assay, but was 21 (7–33.5) days in patients without Xpert MTB/RIF assay. Xpert MTB/RIF assay showed acceptable sensitivity and excellent specificity for the diagnosis of PTB and detection of rifampicin resistance in areas with intermediate TB burden. Additionally, the assay decreased time to the initiation of anti-TB drugs through shorter TAT.
PMCID: PMC3812224  PMID: 24204834
25.  A Case of Human Pulmonary Dirofilariasis in a 48-Year-Old Korean Man 
Dirofilariasis is a rare disease in humans. We report here a case of a 48-year-old male who was diagnosed with pulmonary dirofilariasis in Korea. On chest radiographs, a coin lesion of 1 cm in diameter was shown. Although it looked like a benign inflammatory nodule, malignancy could not be excluded. So, the nodule was resected by video-assisted thoracic surgery. Pathologically, chronic granulomatous inflammation composed of coagulation necrosis with rim of fibrous tissues and granulations was seen. In the center of the necrotic nodules, a degenerating parasitic organism was found. The parasite had prominent internal cuticular ridges and thick cuticle, a well-developed muscle layer, an intestinal tube, and uterine tubules. The parasite was diagnosed as an immature female worm of Dirofilaria immitis. This is the second reported case of human pulmonary dirofilariasis in Korea.
PMCID: PMC3857506  PMID: 24327784
Dirofilaria immitis; dirofilariasis; pulmonary dirofilariasis

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