Prevalence and Impact of Diabetes Mellitus Among Patients with Active Pulmonary Tuberculosis in South Korea.

OBJECTIVE: South Korea has an increasing prevalence of diabetes and a relatively high burden of tuberculosis. We aimed to determine the prevalence of diabetes in patients with active pulmonary tuberculosis (PTB) and examine the effect of diabetes on tuberculosis treatment outcomes. SETTING AND DESIGN: Data from patients ≥30 years diagnosed with and treated for PTB between January 2010 and December 2012 at Severance Hospital, a 2000-bed tertiary referral hospital in Seoul, South Korea, were analyzed and compared with data from a contemporaneous general population sample extracted from KNHANES V. RESULTS: Diabetes prevalence was 24.2% (252/1044) among patients with PTB and 11.6% (1700/14,655) among controls. Diabetes [odds ratios (OR) 2.56, 95% confidence interval (CI) 1.56-4.21, P < 0.001], male sex (OR 1.93, 95% CI 1.08-3.44, P = 0.027), and cavitary disease (OR 2.08, 95% CI 1.29-3.35, P = 0.003) were significant risk factors for 2-month culture positivity. Diabetes was the only factor associated with unsuccessful treatment outcomes (OR 1.67, 95% CI 1.03-2.70, P = 0.039). CONCLUSION: The prevalence of diabetes was markedly higher in patients with PTB than in a sample of the general South Korean population. Diabetes may delay sputum conversion and adversely affect treatment outcomes; detection and management of diabetes in patients with PTB is crucial.

Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury.

The Risk Factors and Characteristics of COPD Among Nonsmokers in Korea: An Analysis of KNHANES IV and V.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is increasing in prevalence and mortality. This study evaluated the prevalence, risk factors, characteristics, and health-related quality of life (HRQoL) of COPD among nonsmokers in Korea. METHODS: This was a population-based cross-sectional study using data obtained from the Fourth and Fifth Korean National Health and Nutrition Examination Survey, which was conducted from 2007 to 2011. RESULTS: A total of 15,063 participants completely answered the questionnaire and performed the spirometry. Among them, 59.6 % were nonsmokers and 40.4 % were smokers. The prevalence of nonsmoker COPD was 7.1 %. On multivariate analysis, age ≥65 years (OR, 2.93; 95 % CI, 2.44-3.51), male sex (OR, 2.98; 95 % CI, 2.40-3.71), living in rural area (OR, 1.26; 95 % CI, 1.05-1.51), lower body mass index (BMI) (<18.5 kg/m(2)) (OR, 3.00; 95 % CI, 1.78-5.01), self-reported asthma (OR, 2.72; 95 % CI, 2.05-3.60), and self-reported tuberculosis (OR, 4.73; 95 % CI, 3.63-6.17) showed a significantly higher risk of nonsmoker COPD. Analysis of nonsmoker and smoker COPD revealed that there are more females in nonsmoker COPD patients (73.9 vs. 6.9 %, P < 0.001). Nonsmoker COPD patients presented with impaired mobility, pain/discomfort, and anxiety/depression functions as well as a lower mean EuroQol Five-Dimension Questionnaire utility score, which showed HRQoL. CONCLUSIONS: The burden of nonsmoker COPD was considerable. Older age, male sex, lower BMI, self-reported asthma, and self-reported tuberculosis were risk factors for nonsmoker COPD and there were differences between nonsmoker and smoker COPD in terms of sex, comorbidities, and HRQoL.

Factors associated with the quality of life of Korean COPD patients as measured by the EQ-5D.

PURPOSE: This study evaluated the health-related quality of life measured using the EuroQol five-dimension questionnaire (EQ-5D) and the degree of airway obstruction in a Korean population using Korea National Health and Nutritional Examination Survey (KNHANES IV-V, 2007-2010) data. METHODS: A cross-sectional analysis examined 2356 subjects (1178 COPD patients, 1178 control subjects) aged ≥40 years and performed reliable spirometry as part of KNHANES IV-V. Baseline EQ-5D visual analog scale (VAS) and EQ-5D utility scores were obtained. A Tobit censored regression model was used to evaluate factors affecting EQ-5D in COPD patients. RESULTS: The EQ-5D VAS and EQ-5D utility scores were significantly different among the COPD severity groups (P < 0.05). The mean EQ-5D VAS scores for patients with mild, moderate, and severe COPD were 73.0 (SD 18.6), 70.8 (19.1), and 60.9 (23.4), respectively. The mean utility scores were 0.90 (0.14) for patients with mild COPD, 0.89 (0.14) for patients with moderate COPD, and 0.84 (0.15) for patients with severe COPD. Factors influencing the EQ-5D utility score in patients with COPD were age, gender, household income, education level, severe airflow obstruction, and comorbidities. CONCLUSIONS: The EQ-5D score could be a useful instrument for evaluating the quality of life of COPD patients in Korea. In Korean COPD patients, the main determinants of EQ-5D scores include older age, female gender, lower household income, lower education level, severe airflow obstruction, and many comorbid diseases.

Relationship of vitamin D status with lung function and exercise capacity in COPD.

BACKGROUND AND OBJECTIVE: The relationship between blood vitamin D level and clinical parameters in patients with chronic obstructive pulmonary disease (COPD) has been reported with conflicting results. We explored the effects of vitamin D on clinical characteristics of patients with COPD in Korea. METHODS: The study population comprised 193 patients with COPD from Korean Obstructive Lung Disease Cohort. The plasma level of 25-OH vitamin D3 (25-OH-VitD3) was measured every year along with various clinical parameters such as lung function, 6-min walking (6MW) distance, quality of life, exacerbations and emphysema index. Generalized estimating equations and linear mixed model were used for statistical analysis. RESULTS: Of the 193 patients, 12 (6.2%), 28 (14.5%) and 153 (79.3%) were categorized into normal, insufficiency and deficiency groups. Clustered analysis showed that the plasma 25-OH-VitD3 level was associated with the post-bronchodilator ratio of force expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) (estimated = 0.001; P = 0.022). The vitamin D deficiency group showed lower FEV1 (estimated = -0.129, P = 0.043), FEV1 % predicted (estimated = -4.994, P = 0.029) and FEV1 /FVC ratio (estimated = -0.048, P = 0.001) than did the non-deficiency group. The 6MW distance tended to be shorter in deficiency group (estimated = -17.26, P = 0.069) than in non-deficiency group. Quality of life, exacerbation and emphysema index were not associated with plasma 25-OH-VitD3 level. CONCLUSIONS: We demonstrated a high prevalence of vitamin D deficiency in Korean patients with COPD and a significant relationship between vitamin D deficiency and airflow limitation. The exercise capacity tended to be decreased in the vitamin D deficiency group.

Inhibition of mTORC1 induces loss of E-cadherin through AKT/GSK-3ß signaling-mediated upregulation of E-cadherin repressor complexes in non-small cell lung cancer cells.

BACKGROUND: mTOR, which can form mTOR Complex 1 (mTORC1) or mTOR Complex 2 (mTORC2) depending on its binding partners, is frequently deregulated in the pulmonary neoplastic conditions and interstitial lung diseases of the patients treated with rapalogs. In this study, we investigated the relationship between mTOR signaling and epithelial mesenchymal transition (EMT) by dissecting mTOR pathways. METHODS: Components of mTOR signaling pathway were silenced by shRNA in a panel of non-small cell lung cancer cell lines and protein expression of epithelial and mesenchymal markers were evaluated by immunoblotting and immunocytochemistry. mRNA level of the E-cadherin repressor complexes were evaluated by qRT-PCR. RESULTS: IGF-1 treatment decreased expression of the E-cadherin and rapamycin increased its expression, suggesting hyperactivation of mTOR signaling relates to the loss of E-cadherin. Genetic ablation of rapamycin-insensitive companion of mTOR (Rictor), a component of mTORC2, did not influence E-cadherin expression, whereas genetic ablation of regulatory-associated protein of mTOR (Raptor), a component of mTORC1, led to a decrease in E-cadherin expression at the mRNA level. Increased phosphorylation of AKT at Ser473 and GSK-3ß at Ser9 were observed in the Raptor-silenced NSCLC cells. Of the E-cadherin repressor complexes tested, Snail, Zeb2, and Twist1 mRNAs were elevated in raptor-silenced A549 cells, and Zeb2 and Twist1 mRNAs were elevated in Raptor-silenced H2009 cells. These findings were recapitulated by treatment with the GSK-3ß inhibitor, LiCl. Raptor knockdown A549 cells showed increased expression of N-cadherin and vimentin with mesenchymal phenotypic changes. CONCLUSIONS: In conclusion, selective inhibition of mTORC1 leads to hyperactivation of the AKT/GSK-3ß pathway, inducing E-cadherin repressor complexes and EMT. These findings imply the existence of a feedback inhibition loop of mTORC1 onto mTORC2 that plays a role in the homeostasis of E-cadherin expression and EMT, requiring caution in the clinical use of rapalog and selective mTORC1 inhibitors.

Factors associated with quality of life measured by EQ-5D in patients with nontuberculous mycobacterial pulmonary disease.

PURPOSE: The impact of pulmonary nontuberculous mycobacterial (pNTM) disease on health-related quality of life (HRQoL) has not received significant attention in the literature. In this study, we compared the HRQoL in patients with pNTM disease and healthy subjects and identified influencing factors using EuroQol 5D (EQ-5D) data. METHODS: The present study used an age- and sex-matched case-control analysis from a cohort of 85 pNTM patients and 340 participants from a national survey. Baseline EQ-5D utility scores and EQ-5D visual analog scale (VAS) scores were measured in both groups. In patients with pNTM disease, the factors affecting EQ-5D were identified using multiple linear regression analysis. RESULTS: While the median EQ-5D VAS scores were lower in pNTM patients than in the control subjects (pNTM, 70; control, 80; P < 0.001), the median EQ-5D utility scores were similar in two groups (both, 1.000, P = 0.878). Interestingly, the percentage of subjects reporting problems on the anxiety/depression dimension was higher for patients with pNTM disease (18.8 %) compared with the control subjects (11.5 %, P = 0.07). In multivariate analysis, increasing severity of forced expired volume in one second (FEV1) decline was associated with a significant decrease in EQ-5D scores of pNTM patients. CONCLUSIONS: This study suggested the EQ-5D may not be useful instrument in pNTM patients due to ceiling effect of EQ-5D and mild disease activity. Patients with pNTM disease tended to report more reduced health status and more problems with anxiety/depression than the healthy controls. Lung function, measured by FEV1, was independently associated with EQ-5D scores in patients with pNTM disease.

Prediction of methicillin-resistant Staphylococcus aureus in patients with non-nosocomial pneumonia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of not only hospital acquired pneumonia, but also non-nosocomial pneumonia. However, the risk factors for non-nosocomial MRSA pneumonia are not clearly defined. Our objective was to identify risk factors at admission that were associated with non-nosocomial MRSA pneumonia. METHODS: We evaluated 943 patients admitted to a university-affiliated hospital with culture-positive bacterial pneumonia developed outside the hospital from January 2008 to December 2011. We compared the clinical characteristics between MRSA and non-MRSA pneumonia, and identified risk factors associated with MRSA pneumonia. RESULTS: Of 943 patients, MRSA was identified in 78 (8.2%). Higher mortality was observed in MRSA than in non-MRSA patients (33.3% vs. 21.5%; P = 0.017). In a logistic regression analysis, MRSA pneumonia was observed more frequently in patients with a previous history of MRSA infection (OR = 6.05; P < 0.001), a PSI score ≥120 (OR = 2.40; P = 0.015), intravenous antibiotic treatment within 30 days of pneumonia (OR = 2.23; P = 0.018). By contrast, non-MRSA pneumonia was observed more often in patients with a single infiltrate on chest radiography (OR = 0.55; P = 0.029). CONCLUSIONS: Anti-MRSA antibiotics could be considered in hospitalized non-nosocomial patients with several risk factors identified herein. The presence or absence of these factors would provide useful guidance in selecting initial empirical antibiotics.

Increased prevalence of self-reported asthma among Korean adults: an analysis of KNHANES I and IV data.

BACKGROUND: Asthma is one of the most common chronic conditions. Knowing the longitudinal trends of prevalence is important in developing health service planning and in assessing the impact of the disease. However, there have been no studies that examined current asthma prevalence trends in Korea through the analysis of nationwide surveys. METHODS: Data were acquired from patients aged 20-59 years who participated in the First Korean National Health and Nutritional Examination Surveys (KNHANES), which was conducted in 1998, and in the second year of the Fourth KNHANES, which was conducted in 2008. To estimate the prevalence of asthma with age and gender standardization, we used data from the Population and Housing Census, which was conducted by Statistics Korea in 2005. RESULTS: The prevalence of physician-diagnosed asthma increased from 1998 to 2008 (1998: 0.7 %, 2008: 2.0 %). The prevalence of asthma medication usage also increased from 1998 to 2008 (1998: 0.3 %, 2008: 0.7 %); however, the prevalence of wheezing decreased between 1998 and 2008 (1998: 13.7 %, 2008: 6.3 %). A similar trend was observed after estimating the prevalence of asthma with age and gender standardization. Allergic rhinitis might be the reason for the increased prevalence of physician-diagnosed asthma, while the observed decrease in wheezing may be related to the decrease in smoking or the increase in the use of asthma medication. CONCLUSIONS: The present study showed that the prevalence of both self-reported physician-diagnosed asthma and asthma medication usage increased from 1998 to 2008 in Korea, despite a possible changing pattern of diagnosing asthma.

Mycobacterial infections in patients treated with tumor necrosis factor antagonists in South Korea.

BACKGROUND: The aims of this study were to determine the incidence of tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease in patients who were treated with tumor necrosis factor (TNF) antagonists in South Korea and to evaluate their clinical characteristics. METHODS: We surveyed all patients (N = 509) who were treated with TNF antagonists at Severance Hospital, South Korea, between January 2002 and December 2011. We reviewed the patients' medical records and collected microbiological, radiographic, and clinical data, including the type of TNF blocker(s) used and the results of tuberculin skin tests and interferon-gamma release assays. RESULTS: Rheumatoid arthritis (43.6 %) and ankylosing spondylitis (27.9 %) were the most common diseases in the patients treated with TNF antagonists. Patients received etanercept (33.4 %), infliximab (23.4 %), or adalimumab (13.2 %). The remaining patients received two or more TNF antagonists (30 %). Nine patients developed TB, and four patients developed NTM lung disease. After adjustment for age and sex, the standardized TB incidence ratio was 6.4 [95 % CI 3.1-11.7] compared with the general population. The estimated NTM incidence rate was 230.7 per 100,000 patients per year. CONCLUSIONS: Our results show that mycobacterial infections increase in patients treated with TNF antagonists. The identification of additional predictors of TB for the treatment of latent tuberculosis infection and the careful monitoring and timely diagnosis of NTM-related lung disease are needed for patients who receive long-term therapy with TNF antagonists.

TGF-ß1 T869C polymorphism may affect susceptibility to idiopathic pulmonary fibrosis and disease severity.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a key cytokine that plays a critical role in idiopathic pulmonary fibrosis (IPF). The genotypes of T869C polymorphism may be associated with the susceptibility to fibrotic lung disease. METHODS: We investigated a single-nucleotide polymorphism at exon 1 nucleotide position 29 (T â†’ C) of the TGF-ß1 gene. Eighty-five healthy controls and 85 subjects with surgically confirmed IPF were investigated using polymerase chain reaction and restriction enzyme fragment length polymorphism techniques. RESULTS: The IPF patients consisted of 55 men and 30 women. The mean age was 61 ± 8 years. Fifty-one (60 %) of the 85 IPF patients were smokers and 34 were nonsmokers. The distribution of genotypes between IPF patients and controls was significantly different (IPF: TT 43.5 % and TC or CC 56.5 %; controls: TT 27.1 % and TC or CC 72.9 %, p = 0.037). TT genotype was significantly associated with decreased PaO2 and increased D(A-a)O2 upon initial diagnosis (p = 0.006 and 0.009, respectively). There was a positive association between TT genotype and IPF development (odds ratio [OR] = 2.1, 95 % confidence interval [CI] = 1.1-4.0, p = 0.028). CONCLUSIONS: This study suggests that the TGF-ß1 gene T869C polymorphism may affect susceptibility to IPF in Koreans. Larger studies are required to confirm the genetic association of TGF-ß1 gene polymorphism and IPF.

Transglutaminase 2 expression predicts progression free survival in non-small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitor.

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-κB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-κB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-κB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-κB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.

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.

Distinct clinical features and outcomes in never-smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement.

BACKGROUND: The objectives of this study were to determine the proportions of major oncogenic alterations and to examine survival in genotype-specific subsets of never-smokers with nonsmall cell lung cancer (NSCLC). METHODS: The authors concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes and investigated anaplastic lymphoma kinase (ALK) gene rearrangements in samples from 229 never-smokers with NSCLC. ALK rearrangements were identified by fluorescent in situ hybridization and were confirmed by immunohistochemistry. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3 genes (WT/WT/WT) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic alterations were mutually exclusive. The median progression-free survival after treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3 months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox regression model, the adjusted hazard ratio for the risk of disease progression after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40-0.87; P = .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07-10.15; P < .001) for patients with ALK rearrangements, and 4.23 (95% CI, 1.65-10.8; P = .003) for patients with KRAS mutations. Overall survival also differed significantly among genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest comprehensive and concurrent analysis to date of 3 major oncogenic alterations in a cohort of East Asian never-smokers with NSCLC. Because survival outcomes differed among genotypes, and drugs that target specific alterations currently are available, genetic profiling to identify genotype-specific subsets can lead to successful treatment with appropriate kinase inhibitors.

Additional diagnostic value of tumor markers in cytological fluid for diagnosis of non-small-cell lung cancer.

BACKGROUND: Cytological fluid from a needle aspiration biopsy (NAB) is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21-1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC). METHODS: A total of 194 patients (M:F = 128:66, mean age 63.7 years) with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21-1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21-1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. RESULTS: Of 194 patients, 139 patients (71.6%) had NSCLC and 55 (28.4%) had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21-1: 95% versus 83.5%, p < 0.001, CEA: 92.1% versus 83.5%, p = 0.002, SCC: 91.4% versus 83.5%, p = 0.003). Accuracy improved significantly for NAB combined with cytological CYFRA 21-1 compared with NAB alone (95.9% versus 88.1%, p < 0.001). The area under curve (AUC) of NAB with cytological CYFRA 21-1 was significantly larger than for NAB alone (0.966 versus 0.917, p = 0.009). CONCLUSION: Of the tested tumor markers, cytological fluid measurements of CYFRA 21-1 improved the diagnostic performance of NAB for NSCLC.

Changing epidemiology of nontuberculous mycobacterial lung disease in South Korea.

OBJECTIVES: Pulmonary nontuberculous mycobacteria (NTM) are increasing worldwide, but data from regions with an intermediate tuberculosis (TB) burden are insufficient, and the reason for the changing epidemiology of NTM lung disease is unclear. We investigated the trends of NTM lung disease at a tertiary hospital in Korea and evaluated the contribution of liquid culture systems. METHODS: We conducted a retrospective observational study of mycobacterial cultures of respiratory specimens from 26,793 patients at Severance Hospital in South Korea from January 2006 to December 2010. RESULTS: The recovery percent of Mycobacterium tuberculosis isolates was 5.9% in 2006 and 7.1% in 2010, and the recovery percent of NTM isolates was 2.0% in 2006 and 6.3% in 2010. The annual percent of NTM isolation has increased steadily every year (p for trend < 0.001), and the proportion of patients from whom NTM was isolated increased from 21.4% in 2006 to 55.0% in 2010 (p for trend < 0.001). The incidence (per 100,000 inpatients and outpatients) of patients with NTM lung disease was 1.82 in 2006 and increased to 4.38 in 2010 (p < 0.001). Although the proportion of positive cultures in liquid medium only was higher for NTM than for M. tuberculosis (p < 0.001), the NTM recovery rate has increased in solid medium culture systems. CONCLUSIONS: The incidence of patients with NTM isolated from respiratory specimens and NTM lung disease increased from 2006 to 2010 in South Korea, a region with an intermediate TB burden.

Risk factors for occurrence and 30-day mortality for carbapenem-resistant Acinetobacter baumannii bacteremia in an intensive care unit.

To assess the risk factors for carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia and for 30-day mortality in patients with CRAB bacteremia in the intensive care unit (ICU), we conducted a retrospective study in the ICU at Severance Hospital in Korea from January 2008 to December 2009. Patients who acquired CRAB bacteremia in the ICU were enrolled as the case group and patients whose specimens of blood culture, sputum/endotracheal aspirate and urine revealed no AB were enrolled as controls. The case group comprised 106 patients and 205 patients were included as controls. Risk factors independently associated with CRAB bacteremia included prior chemotherapy or radiotherapy treatment (Odds ratio [OR], 3.6; P = 0.003), recent central venous catheter insertion (OR, 5.7; P < 0.001) or abdominal drainage insertion (OR, 21.9; P = 0.004), the number of antibiotics treated with (OR, 1.3; P = 0.016), and respiratory failure in the ICU (OR, 2.5; P = 0.035). The 30-day mortality was 79.8%. Renal failure during ICU stay was independently associated with 30-day mortality (OR, 3.7; P = 0.047). It is important to minimize invasive procedures, and to restrict excessive use of antibiotics, especially in immunocompromised patients, in order to prevent the development of CRAB bacteremia. Greater concern for CRAB bacteremia patients is needed when renal failure develops during ICU stay.

Healthcare-associated pneumonia among hospitalized patients in a Korean tertiary hospital.

BACKGROUND: Healthcare-associated pneumonia (HCAP) has more similarities to nosocomial pneumonia than to community-acquired pneumonia (CAP). However, there have only been a few epidemiological studies of HCAP in South Korea. We aimed to determine the differences between HCAP and CAP in terms of clinical features, pathogens, and outcomes, and to clarify approaches for initial antibiotic management. METHODS: We conducted a retrospective, observational study of 527 patients with HCAP or CAP who were hospitalized at Severance Hospital in South Korea between January and December 2008. RESULTS: Of these patients, 231 (43.8%) had HCAP, and 296 (56.2%) had CAP. Potentially drug-resistant (PDR) bacteria were more frequently isolated in HCAP than CAP (12.6% vs. 4.7%; P = 0.001), especially in the low-risk group of the PSI classes (41.2% vs. 13.9%; P = 0.027). In-hospital mortality was higher for HCAP than CAP patients (28.1% vs. 10.8%, P < 0.001), especially in the low-risk group of PSI classes (16.4% vs. 3.1%; P = 0.001). Moreover, tube feeding and prior hospitalization with antibiotic treatment within 90 days of pneumonia onset were significant risk factors for PDR pathogens, with odds ratios of 14.94 (95% CI 4.62-48.31; P < 0.001) and 2.68 (95% CI 1.32-5.46; P = 0.007), respectively. CONCLUSIONS: For HCAP patients with different backgrounds, various pathogens and antibiotic resistance of should be considered, and careful selection of patients requiring broad-spectrum antibiotics is important when physicians start initial antibiotic treatments.

Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis.

BACKGROUND: The immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis. METHODS: One hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer. RESULTS: Forty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without (p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI (p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure. CONCLUSIONS: DNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock.

Prognostic factors in small cell lung cancer: a new prognostic index in Korean patients.

OBJECTIVE: The aims of this study were to identify prognostic factors for overall survival (OS) in patients with small cell lung cancer (SCLC) and to construct a prognostic index on the basis of their expected OS. Long-term survivors were also given special attention. METHODS: We retrospectively analyzed 295 patients diagnosed with SCLC from January 2002 to September 2007 at the Severance Hospital, Seoul, Republic of Korea. Patient history was reviewed regarding both clinical and tumor-related markers, and treatment-related factors were also evaluated. RESULTS: There were 131 (44.4%) patients with limited disease (LD) and 164 (55.6%) with extensive disease (ED). Median follow-up lasted 9.4 months. Objective response to chemotherapy was 66.8%. The median survival time (MST) was 11.2 months in all patients, 20.4 months in LD patients, and 7.7 months in ED patients. The median progression-free survival was 9.4 months. Independent prognostic factors for overall survival (OS) were extent of disease, performance status, and CYFRA 21-1 level. We classified all patients into four groups based on the results of multivariate analysis using classification and regression tree analysis. Median survival times were 22.7, 13.7, 8.5, and 3.2 months, respectively. A total of 51 (17.3%) patients from the entire study population were evaluated for long-term survival, which was defined as survival >2 years. Their MST was 43.1 months, and extent of disease, performance status, and CYFRA 21-1 were independent prognostic factors for long-term survival. CONCLUSIONS: We confirmed the well-known prognosticators, disease extent and performance status, in our patients, but further identified CYFRA 21-1 as independent prognostic factor. A prognostic index was constructed to create four classifications of SCLC considering these variables.