Myung-Goo Lee

Clinical Efficacy of Direct DNA Sequencing Analysis on Sputum Specimens for Early Detection of Drug-Resistant Mycobacterium tuberculosis in a Clinical Setting

BACKGROUNDnEarly detection of drug-resistant Mycobacterium tuberculosis is important for the control and prevention of disease transmission. However, conventional drug susceptibility tests for drug-resistant M tuberculosis take at least 3 to 8 weeks. Here, we report the clinical efficacy of direct DNA sequencing analysis for detecting drug-resistant TB on sputum specimens in a clinical setting.nnnMETHODSnA total of 113 sputum specimens from 111 patients, who were suspected of having drug-resistant TB by clinicians, were used for DNA sequencing of katG, rpoB, embB, and pncA genes for isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) resistance, respectively, and the results were compared with drug susceptibility tests. The optimization of antituberculosis drugs according to the results of DNA sequencing and the treatment outcomes of the patients were also analyzed.nnnRESULTSnTurnaround time of the direct DNA sequencing analysis was 3.8 +/- 1.8 days. We found mutations related to drug resistance in 30 clinical specimens for katG, 39 for rpoB, 13 for embB, and 24 for pncA. The sensitivity and specificity of the assay were 63.6% and 94.6% for INH, 96.2 and 93.9% for RIF, 69.2% and 97.5% for EMB, and 100% and 92.6% for PZA, respectively. Of the patients with RIF resistance, including multidrug-resistant TB by the assay, 92.5% of the patients with initial first-line antituberculosis drugs were changed to second-line antituberculosis drugs, and treatment was successful in 61.9% of these cases.nnnCONCLUSIONnDirect DNA sequencing analysis of clinical sputum specimens is a rapid and useful method for the detection and treatment of drug-resistant TB.

The association between airflow obstruction and radiologic change by tuberculosis

INTRODUCTIONnCigarette smoking is the most commonly encountered risk factor for chronic obstructive pulmonary disease (COPD). However, it is not the only one and there is consistent evidence from epidemiologic studies that nonsmokers may develop chronic airflow limitation. A history of tuberculosis has recently been found to be associated with airflow obstruction in adults older than 40 years. The aim of this study was to evaluate the association between the radiologic changes by tuberculosis and airflow obstruction in a population based sample.nnnMETHODSnA nationwide COPD prevalence survey was conducted. We compared the prevalence of airflow obstruction according to the presence of the radiologic change by the tuberculosis.nnnRESULTSnWe analyzed 1,384 subjects who participated in the nationwide Korean COPD survey. All subjects were older than 40 years and took the spirometry and simple chest radiography. We defined the airflow obstruction as FEV1/FVC <0.7. A total of 149 (10.8%) subjects showed airflow obstruction. A total of 167 (12.1%) subjects showed radiologic change by tuberculosis. Among these 167 subjects, 44 (26.3%) had airflow obstruction. For the subjects without radiologic change by tuberculosis, the prevalence of airflow obstruction was only 8.6%. The unadjusted odds ratio for airflow obstruction according to the radiologic change was 3.788 (95% CI: 2.544-5.642).nnnCONCLUSIONSnThe radiologic change by tuberculosis was associated with airflow obstruction.

COPD Patients with Exertional Desaturation Are at a Higher Risk of Rapid Decline in Lung Function

Purpose A recent study demonstrated that exertional desaturation is a predictor of rapid decline in lung function in patients with chronic obstructive pulmonary disease (COPD); however, the study was limited by its method used to detect exertional desaturation. The main purpose of this study was to explore whether exertional desaturation assessed using nadir oxygen saturation (SpO2) during the 6-minute walk test (6MWT) can predict rapid lung function decline in patients with COPD. Materials and Methods A retrospective analysis was performed on 57 patients with moderate to very severe COPD who underwent the 6MWT. Exertional desaturation was defined as a nadir SpO2 of <90% during the 6MWT. Rapid decline was defined as an annual rate of decline in forced expiratory volume in 1 second (FEV1) ≥50 mL. Patients were divided into rapid decliner (n=26) and non-rapid decliner (n=31) groups. Results A statistically significant difference in exertional desaturation was observed between rapid decliners and non-rapid decliners (17 vs. 8, p=0.003). No differences were found between the groups for age, smoking status, BODE index, and FEV1. Multivariate analysis showed that exertional desaturation was a significant independent predictor of rapid decline in patients with COPD (relative risk, 6.8; 95% CI, 1.8 to 25.4; p=0.004). Conclusion This study supports that exertional desaturation is a predictor of rapid lung function decline in male patients with COPD.

Identification of 10 Candidate Biomarkers Distinguishing Tuberculous and Malignant Pleural Fluid by Proteomic Methods

Purpose Pleural effusion, an accumulation of fluid in the pleural space, usually occurs in patients when the rate of fluid formation exceeds the rate of fluid removal. The differential diagnosis of tuberculous pleurisy and malignant pleural effusion is a difficult task in high tuberculous prevalence areas. The aim of the present study was to identify novel biomarkers for the diagnosis of pleural fluid using proteomics technology. Materials and Methods We used samples from five patients with transudative pleural effusions for internal standard, five patients with tuberculous pleurisy, and the same numbers of patients having malignant effusions were enrolled in the study. We analyzed the proteins in pleural fluid from patients using a technique that combined two-dimensional liquid-phase electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. Results We identified a total of 10 proteins with statistical significance. Among 10 proteins, trasthyretin, haptoglobin, metastasis-associated protein 1, t-complex protein 1, and fibroblast growth factor-binding protein 1 were related with malignant pleural effusions and human ceruloplasmin, lysozyme precursor, gelsolin, clusterin C complement lysis inhibitor, and peroxirexdoxin 3 were expressed several times or more in tuberculous pleural effusions. Conclusion Highly expressed proteins in malignant pleural effusion were associated with carcinogenesis and cell growth, and proteins associated with tuberculous pleural effusion played a role in the response to inflammation and fibrosis. These findings will aid in the development of novel diagnostic tools for tuberculous pleurisy and malignant pleural effusion of lung cancer.

Application of a New Spirometric Reference Equation and Its Impact on the Staging of Korean Chronic Obstructive Pulmonary Disease Patients

Purpose A new spirometric reference equation was recently developed from the first national chronic obstructive pulmonary disease (COPD) survey in Korea. However, Morris equation has been preferred for evaluating spirometric values instead. The objective of this study was to evaluate changes in severity staging in Korean COPD patients by adopting the newly developed Korean equation. Materials and Methods We evaluated the spirometric data of 441 COPD patients. The presence of airflow limitation was defined as an observed post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) less than 0.7, and the severity of airflow limitation was assessed according to GOLD stages. Spirometric values were reassessed using the new Korean equation, Morris equation and other reference equations. Results The severity of airflow limitation was differently graded in 143 (32.4%) patients after application of the new Korean equation when compared with Morris equation. All 143 patients were reallocated into more severe stages (49 at mild stage, 65 at moderate stage, and 29 at severe stage were changed to moderate, severe and very severe stages, respectively). Stages according to other reference equations were changed in 18.6-49.4% of the patients. Conclusion These results indicate that equations from different ethnic groups do not sufficiently reflect the airflow limitation of Korean COPD patients. The Korean reference equation should be used for Korean COPD patients in order to administer proper treatment.