Yeon-Mok Oh

Comparison of two commercial interferon-γ assays for diagnosing Mycobacterium tuberculosis infection

The clinical usefulness of ex vivo interferon-γ assays may largely depend on the assay format and epidemiological status of tuberculosis (TB) in the region studied. From July 2004 to June 2005 a prospective comparison study was undertaken at a tertiary referral hospital in South Korea. The results of tuberculin skin tests (TST) and the commercially available QuantiFERON-TB Gold (QFT-G) and T SPOT-TB (SPOT) assays were compared in an intermediate TB-burden country. Of the 224 participants studied, results from all three tests (TST, QFT-G, and SPOT) were available in 218; 87 with active TB and 131 at a low risk for TB. Using 10 mm as a cut-off for TST, SPOT sensitivity (96.6%) was significantly higher than that seen for TST (66.7%) and QFT-G (70.1%). QFT-G showed superior specificity over TST (91.6 versus 78.6%). Although the specificity of QFT-G was higher than that of SPOT (91.6 versus 84.7%), the difference was not statistically significant. Whilst some differences were found in the performance of the two commercialised interferon-γ assays, they seemed to be superior in their detection of Mycobacterium tuberculosis infection compared with tuberculin skin tests. The most appropriate choice of interferon-γ assay to use may depend on the clinical setting.

Prevalence of chronic obstructive pulmonary disease in Korea: The fourth Korean National Health and Nutrition Examination Survey, 2008

Background and objective:  Because the mortality and social burden associated with COPD is increasing, repeated surveys of the prevalence of COPD have been used to assess risk factors, detect potential patients, and establish early diagnoses and management protocols. We report the prevalence of spirometrically detected COPD in Korea in 2008, using data from the fourth Korean National Health and Nutrition Survey.

Outcomes in patients with Mycobacterium abscessus pulmonary disease treated with long-term injectable drugs.

BACKGROUND The ATS (American Thoracic Society) has recommended periodic administration of multidrug therapy, including a macrolide and one or more parenteral agents or a combination of parenteral agents, over 2-4 months, for treatment of Mycobacterium abscessus pulmonary disease. However, there is little hard evidence supporting these guidelines, and treatment outcomes have not yet been reported. METHODS We retrospectively evaluated 41 patients with M. abscessus pulmonary disease treated in accordance with ATS guidelines. These patients were treated empirically with multidrug regimens, including a macrolide and one (amikacin) or more (amikacin and cefoxitin or imipenem) parenteral agents, over several months. Treatment outcomes were defined as treatment success, failure, or default. RESULTS Seventeen (41.5%) patients were prescribed a macrolide and one parenteral agent, and 24 (58.5%) were prescribed a macrolide and two parenteral agents. The median duration of parenteral and total antibiotic treatment were 230 days (range, 60-601 days) and 511 days (range, 164-1249 days), respectively. The treatment success, failure, and default rates were 80.5% (33/41), 12.2% (5/41), and 7.3% (3/41), respectively. Four patients relapsed over 445 days (range, 0-1443 days) of follow-up. There were no significant differences in treatment success and relapse rates between the groups receiving one and two parenteral agents. Adverse reactions developed in 18 of 41 patients (43.9%). CONCLUSIONS Combination antibiotic therapy, including long-term (minimum 2-4 months) parenteral drugs, as recommended by the ATS, resulted in successful treatment outcomes in 80.5% of patients with M. abscessus lung disease in Korea.

Bone marrow cells repair cigarette smoke-induced emphysema in rats

The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

Texture-based quantification of pulmonary emphysema on high-resolution computed tomography: comparison with density-based quantification and correlation with pulmonary function test.

Purpose:To develop a system for texture-based quantification of emphysema on high-resolution computed tomography (HRCT) and to compare it with density-based quantification in correlation with pulmonary function test (PFT). Materials and Methods:Two hundred sixty-one circular regions of interest (ROI) with 16-pixel diameter [66 ROIs representing typical area of normal lung; 69 representing bronchiolitis obliterans (BO); 64, mild emphysema (ME); and 62, severe emphysema (SE)] were used to train the automated classification system based on the Support Vector Machine classifier and on variable texture and shape features. An automated quantification system was developed with a moving ROI in the lung area, which classified each pixel into 4 categories. To validate the system, the HRCT and standard-kernel-reconstructed volumetric CT data of 39 consecutive patients with emphysema were included. Using this system, the whole lung area was evaluated, and the area fractions of each class were calculated (normal lung%, BO%, ME%, SE%, respectively). The emphysema index (EI) of texture-based quantification was defined as follows: (0.3 × ME% + SE%) (TEI). EIs from density-based quantification with a threshold of −950 Hounsfield Units, were measured on both HRCT (DEI_HR_2D) and on volumetric CT (DEI_standard_3D). The agreement between TEI, DEI_HR_2D, and DEI_standard_3D was assessed using interclass correlation coefficients (ICC). Correlation of the results on the TEI with the PFT results was compared with the results of the DEI_standard_3D and the DEI_HR_2D with Spearmans correlation test. To evaluate the contribution of each texture-based quantification lesion (BO%, ME%, SE%) on PFT, multiple linear regression analysis was performed. Results:The calculated TEI (19.71% ± 17.98%) was well correlated with the DEI_standard_3D (19.42% ± 14.30%) (ICC = 0.95), whereas the ICC with DEI_HR_2D (37.22% ± 9.42%) was 0.43. TEI showed better correlation with PFT than DEI_standard_3D or DEI_HR_2D did [R = 0.71 vs. 0.67 vs. 0.61 for forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC); 0.54 vs. 0.50 vs. 0.43 for diffusing capacity (DLco), respectively]. Multiple linear regression analysis revealed that the BO% and SE% areas were independent determinants of FEV1/FVC, whereas the ME% and the SE% were determinants of DLco. Conclusion:Texture-based quantification of emphysema using an automated system showed better correlation with the PFT results than density-based quantification. Separate quantification of the BO, ME, and SE areas showed a different contribution of each component to the FEV1/FVC and the DLco. The proposed system can be successfully used for detailed regional and global evaluation of lung lesions on HRCT scanning for emphysema.

Xenon ventilation imaging using dual-energy computed tomography in asthmatics: initial experience.

Purpose:To assess the feasibility of xenon ventilation computed tomography (CT) for evaluating ventilation abnormality in asthmatics. Materials and Methods:Twenty-two, stable asthmatics (M:F = 10:12; mean age, 57.6) were included. Single-phase, whole-thorax, dual-energy CT was performed using dual-source CT (Somatom Definition, Siemens) after subjects had inhaled 30% xenon for 90 seconds. Parameters include 512 × 512 matrix; 14 × 1.2 mm collimation; 40/140 eff. mAs at 140/80 kV; 0.45 pitch; and 0.33 seconds rotation time. On the color-coded xenon map, the extent of the ventilation defect was visually assessed using a 5-point scale in each lobe (0, absent defect; 1, 0%–25%; 2, 25%–50%; 3, 50%–75%; and 4, 75%–100%), which was defined as defect score. On the weighted average image, airway wall dimensions were measured at 4 segmental bronchi in both upper and lower lobes. Patients were classified into a defect group and a defect-free group based on the presence of defects shown on the xenon map. Pulmonary function test parameters and airway wall dimensions were compared in those 2 groups. Correlation analyses between the defect score, pulmonary function test, and airway wall dimensions were performed. Results:Sixteen asthmatics showed peripheral ventilation defects on the xenon map (defect score, 6.6 ± 4.2). The defect group had a significantly lower forced expiratory volume in 1 second (FEV1) and thicker airway wall than that of the defect-free group (P = 0.04 and 0.02, respectively). The defect score correlated negatively with a ratio of FEV1 and forced vital capacity (FEV1/FVC) (r = −0.44, P = 0.04) and corrected diffusing capacity (r = −0.76, P = 0.04) and correlated positively with total lung capacity, functional residual volume, and residual volume (r = 0.90, P = 0.005; r= 0.99, P < 0.001; r = 0.88, P = 0.008, respectively). Conclusions:The ventilation defects appeared on xenon ventilation CT in asthmatics with more severe airflow limitation and airway wall thickening. The extent of the ventilation defects showed correlations with parameters of pulmonary function test.

Medical utilization and cost in patients with overlap syndrome of chronic obstructive pulmonary disease and asthma.

Abstract Background: Little information is available regarding medical utilization and cost in patients with overlap syndrome of chronic obstructive pulmonary disease (COPD) and asthma. The purpose of this study is to analyze medical utilization and cost in patients with overlap syndrome and to compare them to COPD patients without asthma. Methods: Using the 2009 Korean National Health Insurance (NHI) database, COPD patients were identified. Medical utilization and costs were also analyzed. Results: Of a total of 185,147 patients identified with COPD, 101,004 patients were classified with overlap syndrome of COPD and asthma and 84,143 patients with COPD without asthma. In 2009, the percentages of emergency room visits, admissions, and intensive care unit admissions were 14.6%, 30.5%, and 0.5%, respectively, in the patients with overlap syndrome group and 5.0%, 14.1%, and 0.2%, respectively, in the COPD patients without asthma group (p < 0.05 for all comparisons). The cost of medical utilization was 790 ± 71 US dollars per person and 3,373 ± 4,628 dollars per person for outpatient and inpatient services, respectively, in the patients with overlap syndrome and 413 ± 512 and 3,010 ± 5,013, respectively, in the COPD patients without asthma (p < 0.05 for all comparisons). Multiple linear regression showed that age, sex, overlap syndrome, hospitalization in the last year, low socioeconomic status, and type of hospital use were significant factors affecting medical utilization and cost. Conclusions: In patients with overlap syndrome, both medical utilization and cost were higher than in COPD patients without asthma.

Quantitatively assessed dynamic contrast-enhanced magnetic resonance imaging in patients with chronic obstructive pulmonary disease: correlation of perfusion parameters with pulmonary function test and quantitative computed tomography.

Objectives:The purpose of this study is to evaluate the correlation of the perfusion parameters of 3-dimensional, contrast-enhanced magnetic resonance (MR) imaging (3D CEMRI) with pulmonary function test (PFT) and quantitative computed tomography (CT) parameters in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods:In 14 patients with COPD, 3D CEMRI was performed. From the signal intensity-time curves, pulmonary blood flow (PBF), pulmonary blood volume (PBV), and mean transit time of each pixel was calculated. From the volumetric CT data, the quantitative parameters including the volume fraction of the lung below −950 Housefield Units (V−950) and mean lung density were assessed. The correlation between the MR perfusion parameters and the parameters from quantitative CT and PFT was assessed using Spearman correlation analysis. The correspondence of the regional impairment of perfusion on MR perfusion maps to the areas of emphysema on quantitative CT maps in each patient was assessed qualitatively using a 4-class visual scoring method by 2 readers. Results:All 3D CEMRI examinations were successfully completed and MR perfusion parameters were obtained in all patients. The Spearman correlation test showed that PBF positively correlated with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (R = 0.49, P = 0.044), PBV positively correlated with FEV1/FVC (R = 0.69, P = 0.006) and negatively correlated with V−950 (R = −0.61, P = 0.020), and mean transit time positively correlated with FEV1 (R = 0.63, P = 0.017) and FEV1/FVC (R = 0.76, P = 0.002). The areas of perfusion impairment on PBF and PBV maps were relatively well correlated with the areas of emphysema on CT maps [very good or good: PBF 71.5% (reader 1) and 64.3% (reader 2) of the patients, &kgr; = 0.47 (P < 0.001); PBV 78.6% (reader 1) and 78.6% (reader 2) of the patients, &kgr; = 0.89 (P < 0.001)]. Conclusions:This study shows that the deterioration of perfusion parameters measured on MR in patients with COPD, correlates with worsening of airflow limitation on PFT and emphysema index on CT. Regional heterogeneity of emphysema on CT matches with the decreased perfusion on MR.

Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype☆

RATIONALE Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder in which a number of different pathological processes lead to recognition of patient subgroups that may have individual characteristics and distinct responses to treatment. OBJECTIVES We tested the hypothesis that responses of lung function to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid might differ among patients with various COPD subtypes. METHODS We classified 165 COPD patients into four subtypes according to the severity of emphysema and airflow obstruction: emphysema-dominant, obstruction-dominant, mild-mixed, and severe-mixed. The emphysema-dominant subtype was defined by an emphysema index on computed tomography of more than 20% and FEV(1) more than 45% of the predicted value. The obstruction-dominant subtype had an emphysema index < or = 20% and FEV(1) < or = 45%, the mild-mixed subtype had an emphysema index < or = 20% and FEV(1) > 45%, and the severe-mixed subtype had an emphysema index > 20% and FEV(1) < or = 45%. Patients were recruited prospectively and treated with 3 months of combined inhalation of long-acting beta-agonist and corticosteroid. RESULTS After 3 months of combined inhalation of long-acting beta-agonist and corticosteroid, obstruction-dominant subtype patients showed a greater FEV(1) increase and more marked dyspnea improvement than did the emphysema-dominant subgroup. The mixed-subtype patients (both subgroups) also showed significant improvement in FEV(1) compared with the emphysema-dominant subgroup. Emphysema-dominant subtype patients showed no improvement in FEV(1) or dyspnea after the 3-month treatment period. CONCLUSION The responses to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid differed according to COPD subtype.

Aspergillus galactomannan antigen assay in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis

OBJECTIVES A recently developed bronchoalveolar lavage (BAL) galactomannan (GM) assay shows promising results. We evaluated the diagnostic performance of this assay and analyzed risk factors for false-positive results. METHODS A prospective cohort study was performed in a tertiary hospital over a 9-month period. We reviewed all adult patients who underwent GM assays of BAL. Patients were categorized with proven, probable, or possible invasive pulmonary aspergillosis (IPA) according to revised EORTC/MSG definitions. Each patient with a false-positive BAL GM result was matched with three patients with true-negative BAL GM result, and the risk factors for false-positive BAL GM results were determined. RESULTS Of 359 enrolled patients, 22 (6%) were diagnosed with IPA (1 proven, 17 probable, and 4 possible). Of the 22 patients with IPA, 17 (77%) had already received antifungal agents before the BAL GM assay was conducted. At an index cutoff value of ≥0.5, the BAL GM assay had a sensitivity of 64% (95% CI 41%-83%) and a specificity of 89% (95% CI 85%-92%). However, at an index cutoff value of ≥0.2, the BAL GM assay had a sensitivity of 86% (95% CI 65%-97%) and a specificity of 74% (95% CI 69%-79%). Of the 52 patients with positive BAL GM assay (≥0.5), 25 (7%) were false-positives. Univariate and multivariate analysis revealed that treatment with piperacillin-tazobactam or ampicillin-sulbactam was associated with false-positive BAL GM results. CONCLUSIONS The BAL GM assay appears promising for the diagnosis of IPA. However, treatment with certain antibiotics may interfere with the results of the BAL GM assay.