Chul Gyu Yoo

Genetic susceptibility to chronic obstructive pulmonary disease in Koreans : combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1

BACKGROUND Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10–20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD. METHODS The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers. RESULTS No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group. CONCLUSIONS Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.

Nodular Ground-Glass Opacities on Thin-section CT: Size Change during Follow-up and Pathological Results

Objective To evaluate the inter-group differences in growth and the pathological results of nodular ground-glass opacities (GGOs) according to their size and focal solid portions. Materials and Methods Ninety-six nodular GGOs in 55 individuals followed by CT for at least one month from an initial chest CT were included. Forty nodular GGOs in 30 individuals were pathologically confirmed to be: adenocarcinoma (n = 15), bronchioloalveolar carcinoma (BAC) (n = 11), atypical adenomatous hyperplasia (AAH) (n = 8), focal interstitial fibrosis (n = 5) and aspergillosis (n = 1). Lesions were categorized based on high-resolution CT findings: pure nodular GGO (PNGGO) ≤ 10 mm, PNGGO > 10 mm, mixed nodular GGO (MNGGO)≤ 10 mm, and MNGGO > 10 mm. In each group, the change in size during the follow-up period, the pathological results and the rate of malignancy were evaluated. Results Three MNGGO lesions, and none of the PNGGO, grew during the follow-up period. Resected PNGGOs ≤ 10 mm were AAH (n = 6), BAC (n = 5), and focal interstitial fibrosis (n = 1). Resected PNGGOs > 10 mm were focal interstitial fibrosis (n = 4), AAH (n = 2), BAC (n = 2), and adenocarcinoma (n = 2). Resected MNGGOs ≤ 10 mm were adenocarcinoma (n = 2), and BAC (n = 1). Resected MNGGOs > 10 mm were adenocarcinoma (n = 11), BAC (n = 3), and aspergillosis (n = 1). Conclusion Mixed nodular GGOs (MNGGOs) had the potential for growth; most were pathologically adenocarcinoma or BAC. By contrast, PNGGOs were stable for several months to years; most were AAH, BAC, or focal interstitial fibrosis.

Pulmonary lymphangioleiomyomatosis in Korea

BACKGROUND Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed. METHODS The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study. RESULTS All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (Tlco) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted Tlco/Va (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation. CONCLUSIONS As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.

Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer

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

Economic Burden and Epidemiology of Pneumonia in Korean Adults Aged over 50 Years

This study was performed to estimate the direct medical costs and epidemiology of pneumonia in adults of Korea. We conducted a multi-center, retrospective, observational study and collected data targeting for community-acquired pneumonia patients ( ≥ 50 yr) from 11 hospitals. Costs attributable to the treatment of pneumonia were estimated by reviewing resource utilization and epidemiology data (distribution of pathogen, hospital length of stay, overall outcome) were also collected. A total 693 patients were included; average 70.1 ( ± 10.5) aged, 57.3% male and average 1.16 CURB-65 (confusion, blood urea nitrogen, respiratory rate, blood pressure, age > 65 yr) scored. The pathogen was identified in the 32.9% (228 patients); Streptococcus pneumoniae accounted for 22.4% (51 patients) of identified pathogens. The hospital mortality was 3.2% (especially, for S. pneumoniae was 5.9%) and average length of stay was 9 days. The mean total cost for the treatment of pneumonia was US dollar (USD) 1,782 (SD: USD 1,501). Compared to the cost of all caused pneumonia, that of pneumococcal pneumonia was higher, USD 2,049 ( ± USD 1,919), but not statistically significant. Charge of hospitalization accounted the greatest part of total medical costs. The economic burden of pneumonia was high in Korea, and the prevention of pneumonia should be considered as effective strategy.

Bronchoscopic findings of endobronchial vascular lesions in patients with haemoptysis

Cases of endobronchial vascular lesions observed with bronchoscope are presented. These lesions tend to be diagnosed erroneously as true endobronchial tumours so that biopsies are tried frequently. Consequently, a catastrophic accident of massive bleeding can complicate the condition if endobronchial vascular lesions are injured during bronchoscopic biopsy or brushing. We present three types of endobronchial vascular lesion: tubular bulging type, mass‐like type and haemangioma type. Because bronchoscopic findings of submucosal tubular structure and visible pulsation are highly suggestive of endobronchial vascular lesion, there must be extreme caution to prevent fatal bleeding.

Multiple cystic lung disease.

A lung cyst is an air-filled lucent structure surrounded by a thin wall. The presence of multiple intrapulmonary cysts is defined as cystic lung disease. Although cystic lung disease is rare, incidental detection has increased significantly in recent years by screening using computed tomography. There are many conditions that can mimic lung cysts and cause cystic lung disease. Clinical, radiographic, and histologic findings are all necessary for a proper diagnosis, and multidisciplinary approaches are frequently required. The aim of this report is to review the causes and characteristics of cystic lung disease to better understand and improve treatment.

Bronchiolitis obliterans organizing pneumonia in Korea

Abstract An analysis of the clinical features in 23 cases of bronchiolitis obliterans organizing pneumonia (BOOP) in Korea is presented. Six were men and 17 were female, with a male‐tofemale ratio of 1:2.4. Idiopathic BOOP was present in 18 of these patients, connective tissue disease‐associated BOOP in five and all of them were females. The most frequent symptoms were dyspnoea and coughing in both groups; and crackles were the most prominent physical findings. Leukocytosis was observed in seven of the idiopathic BOOP group and all in the connective tissue disease‐associated BOOP group. In most cases, FVC, FEV1, diffusing capacity and arterial O2 pressure were reduced. In roentgenographic study, patchy air space consolidation was the major finding and subpleural predominance was observed in the majority of patients in both groups. Migration of lesions were identified in only two patients with idiopathic BOOP. Steroid treatment was effective in all of idiopathic BOOP. In contrast to previous reports, an analysis of the 23 Korean BOOP patients showed several interesting points. First, a female predominance was observed. Second, migration of lesion was rare. Third, it did not show any different prognosis in patients with reticular pattern on roentgenogram compared with patients with patchy air space consolidation on roentgenogram. Whether these differences were due to ethnic or environmental factors is to be determined.

The effects of transferring tumor suppressor gene p16INK4A to p16INK4A-deleted cancer cells.

Objectives p16 is known to be an important tumor suppressor gene and is also called MTS1(multiple tumor suppressive gene 1). Especially in the case of non-small cell lung cancer, it was not expressed in more than 70% of cell lines examined. To determine changes in cell-cycle related proteins and the tumorigenic effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines. Methods We transfected p16INK4A gene into lung cancer cell lines which do not express p16 protein. We evaluated the effect by clonogenic assay and observed the changes of cell-cycle related proteins. Results The newly-expressed p16 formed a complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G4T8 showed that, in the cell lines transfected with p16, tumorigenicity was significantly less than in the control. Conclusion These results suggest that the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which p16INK4A gene is inactivated.

Clinical Implication of Microscopic Anthracotic Pigment in Mediastinal Staging of Non-Small Cell Lung Cancer by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Microscopic anthracotic pigment (MAP) is frequently observed in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen in non-small cell lung cancer, but its clinical interpretation is not well-known. The aim of this study was to evaluate the clinical implication of MAP in mediastinal staging of non-small cell lung cancer. From May 2010 to July 2011, consecutive potentially operable non-small cell lung cancer patients who underwent EBUS-TBNA for mediastinal staging were recruited. Of the total 133 patients, 102 (76.7%) were male patients. Median age was 68 yr. Total 279 mediastinal lymph nodes were sampled by EBUS-TBNA; station 4R (100, 35.8%) and station 7 (86, 30.8%) were the most common sites. Malignant lymph nodes were 100 (35.8%). MAP was observed in 61 (21.7%) lymph nodes, and among them only 3 were malignant lymph nodes (P < 0.001). The lymph nodes with MAP were smaller (9.0 vs 10.8 mm, P = 0.001) and showed low standard uptake values on FDG-PET (4.4 vs 4.7, P = 0.256). In multivariate analysis, MAP was negatively associated with malignant lymph node (adjusted OR, 0.12; 95% CI, 0.03-0.42; P < 0.001). In potentially operable non-small cell lung cancer patients, MAP in endobronchial ultrasound-guided transbronchial needle aspiration specimens is strongly associated with benign mediastinal and hilar lymph nodes.