Active Tuberculosis Incidence and Characteristics in Patients Treated with Tumor Necrosis Factor Antagonists According to Latent Tuberculosis Infection.

This study aimed to determine the incidence and characteristics of active tuberculosis (TB) in patients treated with tumor necrosis factor (TNF) antagonists according to baseline latent tuberculosis infection (LTBI). Data were retrospectively obtained from 702 patients aged ≥20 years treated with TNF antagonists between November 2005 and June 2016 at Severance Hospital, a tertiary referral hospital in Seoul, South Korea. The interferon-gamma release assay (IGRA) with or without a tuberculin skin test (TST) was used to diagnose LTBI. Of the total of 702 patients, LTBI was diagnosed in 255 (36.3%) patients. 23.9% (168/702) had positive IGRA results, and 32.2% (165/512) had positive TST results. Five patients developed active TB after LTBI treatment, and 6 developed TB despite baseline negative LTBI results. After adjustment for age and sex, the standardized TB incidence ratio was 6.01 (95% CI 1.94-14.04) in the LTBI group and 5.14 (95% CI 1.88-11.18) in the baseline negative LTBI group. Clinicians should be aware of the risk of active TB in patients treated with TNF antagonists despite baseline negative LTBI screening results. Regular monitoring and serial tests should be considered during long-term TNF antagonist therapy, especially in intermediate to high TB burden country.

MYC expression correlates with PD-L1 expression in non-small cell lung cancer.

Objectives Programmed death-ligand 1 (PD-L1) is a widely used biomarker for predicting immune checkpoint inhibitors, but is of limited usefulness in the prediction of drug response. MYC, a transcription factor that is overexpressed in cancers, is involved in preventing immune cells from attacking tumor cells through inducing PD-L1 expression. This study evaluated the relationship between MYC and PD-L1 expression in 84 non-small cell lung cancer (NSCLC) patients who underwent curative surgical resection. Materials and Methods The relationship between MYC and PD-L1 was investigated by introducing pcDNA3-cMYC into A549 and H1299 cells with low PD-L1 expression and siRNA against MYC into H60 and H2009 cells with high PD-L1 expression. Expression of PD-L1 in NSCLC tissues was analyzed by immunostaining using a PD-L1 (22C3) PharmDx protocol using the Dako Automated Link 48 platform and expression of MYC was determined using anti-c-MYC (Y69) (ab320720). Results Of 84 patients, PD-L1 was expressed in 14 (16.7%) and MYC was overexpressed in 30 (35.7%). We investigated the relationship between PD-L1 and MYC expression. There were 49 (58.3%) double-negative patients and 9 (10.7%) double-positive patients. Significant positive correlation was observed between PD-L1 and MYC expression (γ=0.210, P=0.029). Double-negative patients showed better disease free (31.1 vs. 7.1 months, P=0.011) and overall survival (56.1 vs. 14.4 months, P=0.032) than double-positive patients. Conclusion Taken together, MYC expression significantly correlated with PD-L1 expression in NSCLC. The usefulness of MYC expression as a surrogate marker of treatment response assessment is worth evaluating for immune checkpoint inhibitor therapy and special interest are required for the subgroup of NSCLC patients, whose tumor expresses PD-L1 and MYC double positive.

Risk factors for Pneumocystis jirovecii pneumonia (PJP) in kidney transplantation recipients.

Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised patients. The aim of this study was to evaluate risk factors for PJP in kidney transplantation recipients. We conducted a retrospective analysis of patient data from 500 consecutive kidney transplants performed at Severance Hospital between April 2011 and April 2014. Eighteen kidney transplantation recipients (3.6%) were diagnosed with PJP. In the univariate analysis, acute graft rejection, CMV infection, use of medication for diabetes mellitus, and lowest lymphocyte count were associated with PJP. Recipients who experienced acute graft rejection (odds ratio [OR] 11.81, 95% confidence interval [CI] 3.06-45.57, P < 0.001) or developed CMV infection (OR 5.42, 95% CI 1.69-17.39, P = 0.005) had high odds of PJP in multivariate analysis. In the acute graft rejection subgroup, patients treated with anti-thymocyte globulin (ATG) had significantly higher odds of PJP (OR 5.25, 95% CI 1.01-27.36, P = 0.006) than those who were not. Our data suggest that acute graft rejection and CMV infection may be risk factors for PJP in kidney transplant patients. The use of ATG for acute graft rejection may increase the risk of PJP.

The influence of protein provision in the early phase of intensive care on clinical outcomes for critically ill patients on mechanical ventilation.

BACKGROUND AND OBJECTIVES: Mechanically ventilated patients often face progressive and rapid losses of body mass and muscle because of hypermetabolism and increased protein catabolism. To investigate the impact of adequate nutritional provision during the early phase of intensive care unit (ICU) admission on the clinical outcomes in patients with medical illnesses receiving mechanical ventilation support. METHODS AND STUDY DESIGN: Two hundred and eleven mechanically ventilated patients admitted to a 30-bed medical ICU were included. Three groups, based on nutrition intake, were examined: adequate protein intake (aPI), n=34; insufficient protein intake/ adequate energy intake (iPI/aEI), n=25; insufficient protein and energy intake (iPI/iEI), n=152. RESULTS: Patients' mean age was 65±14 years; body mass index, 22±4; Acute Physiology and Chronic Health Evaluation II score, 24±7. The aPI group had significantly lower rates of in-ICU (14.7%) and in-hospital (23.5%) mortality than patients with insufficient protein intake: in-ICU mortality, iPI/aEI, 36%; iPI/iEI, 44.1% (p=0.006); in-hospital mortality, iPI/aEI, 56.0%; iPI/iEI, 52.0% (p=0.008). In the multivariate analysis, the hazard ratios (95% confidence intervals) for 60-day survival were 2.59 (1.02-6.59; p=0.046) and 2.88 (1.33-6.26; p=0.008) for the iPI/aEI and iPI/iEI groups, respectively. CONCLUSIONS: Despite possible selection bias owing to the retrospective nature of the study, achievement of >90% of target protein intake was associated with improved ICU outcomes in mechanically ventilated critically ill patients, based on real-world clinical circumstances.

Changes in the prevalence of COPD in Korea between 2001 and 2011 in the KNHANES data.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a serious public health problem. Understanding the longitudinal trend in prevalence is important for characterizing the burden of COPD and planning health services. METHODS: We analyzed the prevalence of airflow obstruction between 2001 and 2011 using data from Korean National Health and Nutritional Examination Surveys (2001, n = 2217; 2011, n = 3101). Participants >40 years of age with an FEV1/FVC <0.7 were defined as having COPD. We used data from the Population and Housing Census, which was conducted by Statistics Korea in 2010, to compare the prevalence of COPD after standardizing by age. RESULTS: The crude prevalence of COPD was not significantly different between 2001 and 2011 (2001, 13.0%; 2011, 13.2%), but the age-standardized prevalence of COPD decreased significantly over the 10-year period (2001, 15.7%; 2011, 12.4%). While significant decreases were observed for ex-smokers and current smokers, significant increases were noted for subjects who smoked <20 pack-years and those with a BMI ≤18.5 kg/m2. The prevalence of mild and severe COPD decreased (2001, mild 8.5%, severe 1.4%; 2011, mild 5.4%, severe 0.5%), while the prevalence of moderate COPD increased (2001, 5.7%; 2011, 6.4%) after age standardization. CONCLUSIONS: We report a reduction in the age-standardized prevalence of COPD in Korea from 2001 to 2011. Continued surveillance and early prevention are required because the socioeconomic burden of COPD remains substantial.

Value of Serum Cystatin C Measurement in the Diagnosis of Sepsis-Induced Kidney Injury and Prediction of Renal Function Recovery.

PURPOSE: Acute kidney injury (AKI) is common in critically ill patients. Serum cystatin C has emerged as a reliable marker of AKI. We sought to assess the value of serum cystatin C for early detection and prediction of renal function recovery in patients with sepsis. MATERIALS AND METHODS: Sepsis patients (113 AKI patients and 49 non-AKI patients) admitted to the intensive care unit (ICU) were included. Serum creatinine and cystatin C levels and glomerular filtration rate were measured on days 0, 1, 3, and 7. RESULTS: Serum cystatin C levels were significantly higher in AKI patients than in non-AKI patients at all time points. Multivariate analysis showed that only serum cystatin C levels on day 0 were associated with AKI development [odds ratio (OR)=19.30; 95% confidence interval (CI)= 2.58-144.50, p<0.001]. Linear mixed model analysis showed significant variation in cystatin C levels between the recovery and non-recovery groups over time (p=0.001). High levels of serum cystatin C at day 0 (OR=1.64; 95% CI=1.00-2.68, p=0.048) were associated with recovery of AKI. CONCLUSION: Serum cystatin C level was found to be associated with the development and worsening of AKI in ICU patients with sepsis.

ABT-737 Synergizes with Cisplatin Bypassing Aberration of Apoptotic Pathway in Non-small Cell Lung Cancer.

A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models. The synergism of this combination was evaluated by the Chou-Talalay Combination Index method. In vivo activity was evaluated by micro-CT. In NSCLC cells, there was a time and dose-dependent phosphorylation of SRC-JAK2-STAT3 by cisplatin, followed by increased expression of anti-apoptotic molecules. When the expression of the BCL-2 protein family members was evaluated in clinical samples, BCL-xL was most frequently overexpressed. Dominant negative STAT3 suppressed their expression, suggesting that STAT3 mediates cisplatin mediated overexpression of the anti-apoptotic molecules. ABT-737 displaced BCL-xL from mitochondria and induced oligomerization of BAK. ABT-737 itself showed cytotoxic effects and a combination of ABT-737 with cisplatin showed strong synergistic cytotoxicity. In a murine lung cancer model, co-treatment with ABT-737 and cisplatin induced significant tumor regression. These findings reveal a synergistic cytotoxic and anti-tumor activity of ABT-737 and cisplatin co-treatment in preclinical models, and suggest that clinical trials using this strategy may be beneficial in advanced NSCLC.

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.

A Pilot Study of the Effectiveness of Medical Emergency System Implementation at a Single Center in Korea.

BACKGROUND: An automatic alarm system was developed was developed for unexpected vital sign instability in admitted patients to reduce staffing needs and costs related to rapid response teams. This was a pilot study of the automatic alarm system, the medical emergency system (MES), and the aim of this study was to determine the effectiveness of the MES before expanding this system to all departments. METHODS: This retrospective, observational study compared the performance of patients admitted to the pulmonary department at a single center using patient data from three 3-month periods (before implementation of the MES, December 2013-February 2014; after implementation of the MES, December 2014-February 2015 and December 2015-February 2016). RESULTS: A total of 571 patients were admitted to the pulmonary department during the three observation periods. During this pilot study, the MES automatically issued 568 alarms for 415 admitted patients. There was no significant difference in the rate of cardiopulmonary resuscitation (CPR) before and after application of the MES. The mortality rate also did not change. However, it appeared that CPR was prevented in four patients admitted from the general ward to the intensive care unit (ICU) during MES implementation. The median length of hospital stay and median length of ICU stay were not significantly different before and after MES implementation. CONCLUSIONS: Although we did not find a significant improvement in outcomes upon MES implementation, the CPR rate and mortality rate did not increase despite increased comorbidities. This was a small pilot study and, based on these results, we believe that the MES may have significant effects in longer-term and larger-scale studies.

Implications of Plasma Renin Activity and Plasma Aldosterone Concentration in Critically Ill Patients with Septic Shock.

BACKGROUND: The renin-angiotensin-aldosterone system is closely associated with volume status and vascular tone in septic shock. The present study aimed to assess whether plasma renin activity (PRA) and plasma aldosterone concentration (PAC) measurements compared with conventional severity indicators are associated with mortality in patients with septic shock. METHODS: We evaluated 105 patients who were admitted for septic shock. Plasma levels of the biomarkers PRA and PAC, the PAC/PRA ratio, C-reactive protein (CRP) level, and cortisol level on days 1, 3, and 7 were serially measured. During the intensive care unit stay, relevant clinical information and laboratory results were recorded. RESULTS: Patients were divided into two groups according to 28-day mortality: survivors (n = 59) and non-survivors (n = 46). The survivor group showed lower PRA, PAC, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score than did the non-survivor group (all P < 0.05). The SOFA score was positively correlated with PRA (r = 0.373, P < 0.001) and PAC (r = 0.316, P = 0.001). According to receiver operating characteristic analysis, the areas under the curve of PRA and PAC to predict 28-day mortality were 0.69 (95% confidence interval [CI], 0.58 to 0.79; P = 0.001) and 0.67 (95% CI, 0.56 to 0.77; P = 0.003), respectively, similar to the APACHE II scores and SOFA scores. In particular, the group with PRA value ≥3.5 ng ml-1 h-1 on day 1 showed significantly greater mortality than did the group with PRA value <3.5 ng ml-1 h-1 (log-rank test, P < 0.001). According to multivariate analysis, SOFA score (hazard ratio, 1.11; 95% CI, 1.01 to 1.22), PRA value ≥3.5 ng ml-1 h-1 (hazard ratio, 3.25; 95% CI, 1.60 to 6.60), previous history of cancer (hazard ratio, 3.44; 95% CI, 1.72 to 6.90), and coronary arterial occlusive disease (hazard ratio, 2.99; 95% CI, 1.26 to 7.08) were predictors of 28-day mortality. CONCLUSIONS: Elevated PRA is a useful biomarker to stratify the risk of critically ill patients with septic shock and is a prognostic predictor of 28-day mortality.

Rare causes of hyperbilirubinemia after lung transplantation: our experience at a single center.

BACKGROUND: Lung transplantation is the last treatment option for end-stage lung disease, and the number of lung transplantations has been steadily increasing. Hyperbilirubinemia is a rare complication after lung transplantation. The aim of this study was to review rare causes of hyperbilirubinemia after lung transplantation at our center. METHODS: In this single-center study, we retrospectively reviewed the records of 116 consecutive lung transplantation patients who underwent lung transplantation at Severance Hospital and Gangnam Severance Hospital of Yonsei University College of Medicine in South Korea between December 22, 2010 and January 1, 2016. Hyperbilirubinemia was defined as a total bilirubin level exceeding 5 mg/dL for at least 3 days after lung transplantation. RESULTS: Hyperbilirubinemia occurred in 33 patients (28.4%) who received lung transplants at our institution. Twenty-four cases involved common causes such as drug toxicity, biliary tract stone, sepsis, and bleeding. However, rare causes of hyperbilirubinemia including hemophagocytic lymphohistiocytosis (HLH), thrombotic microangiopathy (TMA), and ischemic cholangiopathy were observed in 9 (7.8%) patients during the study period. All patients with hyperbilirubinemia due to a rare cause died despite aggressive treatment. CONCLUSION: Causes of hyperbilirubinemia after lung transplantation are varied, and the prognosis of patients with hyperbilirubinemia arising from rare causes was poor. Therefore, early evaluation and management of hyperbilirubinemia after lung transplantation is important to improve patient outcomes.

Clinical Implications of Sarcopenia on Decreased Bone Density in Men With COPD.

BACKGROUND: Sarcopenia and osteoporosis are systemic features of COPD. The present study investigated the association between sarcopenia and osteopenia/osteoporosis and the factors associated with low bone mineral density (BMD) in men with COPD. METHODS: Data from 777 men with COPD who underwent both pulmonary function test and dual-energy x-ray absorptiometry were extracted from the Korean National Health and Nutritional Examination Survey database between 2008 and 2011. Sarcopenia was assessed with the appendicular skeletal mass index (ASMI) and osteopenia/osteoporosis with the T-score. RESULTS: As the severity of airflow limitation increased, the prevalence of sarcopenia increased (Ptrend < .001). Additionally, as the degree of sarcopenia became severe, the prevalence of osteopenia/osteoporosis increased (Ptrend < .001), and a significant positive correlation was noted between appendicular skeletal muscle mass and BMD (ASMI/T-score: r = 0.408; P < .001). Sarcopenia was independently associated with an increased risk of low BMD in men with COPD (OR, 2.31; 95% CI, 1.53-3.46; P < .001). Old age and low fat mass were significantly associated with low BMD in both sarcopenic and non-sarcopenic participants. High serum hemoglobin and insulin levels were associated with a reduced risk of low BMD only in the sarcopenic participants, whereas exercise and dietary intake were associated with a reduced risk only in the non-sarcopenic participants. CONCLUSIONS: Sarcopenia is closely correlated with osteopenia/osteoporosis in men with COPD. Moreover, different factors are associated with low BMD according to the presence/absence of sarcopenia in that population.

Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions.

OBJECTIVES: Disruption in the stability of respiratory microbiota is known to be associated with many chronic respiratory diseases. However, only few studies have examined microbiomes in lung cancer. Therefore, we characterized and compared the microbiomes of patients with lung cancer and those with benign mass-like lesions. MATERIALS AND METHODS: Bronchoalveolar fluid was collected prospectively to evaluate lung masses in patients who had undergone bronchoscopies from May to September 2015. Twenty-eight patients (20 male, 8 female) were enrolled: 20 diagnosed with lung cancer and 8 diagnosed with benign diseases. Samples were analysed by 16S rRNA-based next-generation sequencing. RESULTS: The participants' mean age was 64±11years. Bacterial operational taxonomic units were classified into 26 phyla, 44 classes, 81 orders, 153 families, 288 genera, and 797 species. The relative abundance of two phyla (Firmicutes and TM7) was significantly increased in patients with lung cancer (p=0.037 and 0.035, respectively). Furthermore, two genera (Veillonella and Megasphaera) were relatively more abundant in lung cancer patients (p=0.003 and 0.022, respectively). The area under the curve of a combination of these two genera used to predict lung cancer was 0.888 (sensitivity=95.0%, specificity=75.0% and sensitivity=70.0%, specificity=100.0%; p=0.002). CONCLUSION: The results indicate that differences exist in the bacterial communities of patients with lung cancer and those with benign mass-like lesions. The genera Veillonella and Megasphaera showed the potential to serve as biomarkers to predict lung cancer. Thus, the lung microbiota may change the environment in patients with lung cancer.

Association of serum ferritin levels with smoking and lung function in the Korean adult population: analysis of the fourth and fifth Korean National Health and Nutrition Examination Survey.

BACKGROUND: Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. MATERIALS AND METHODS: Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study. RESULTS: The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. CONCLUSION: Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher levels of serum ferritin were associated with enhanced spirometric results in a representative sample of the general Korean adult population. Future prospective studies will be needed to clarify the causality between serum ferritin and lung functions and their role in COPD morbidity.

Cut-off value of FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction in a Korean population.

BACKGROUND: Forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) has been proposed as an alternative to FEV1/forced vital capacity (FVC) for detecting airway obstruction. A fixed cut-off value for FEV1/FEV6 in a Korean population is lacking. We investigated a fixed cut-off for FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction. MATERIALS AND METHODS: We used data obtained in the 5 years of the Fifth and Sixth Korean National Health and Nutrition Examination Survey. A total of 14,978 participants aged ≥40 years who underwent spirometry adequately were the study cohort. "Airway obstruction" was a fixed cut-off FEV1/FVC <70% according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. We also used European Respiratory Society/Global Lung Initiative 2012 equations for the FEV1/FVC lower limit of normal. RESULTS: Among the 14,978 participants (43.5% male, 56.5% female; mean age: 56.9 years for men and 57.0 years for women), 14.0% had obstructive lung function according to a fixed cut-off FEV1/FVC <70%. Optimal FEV1/FEV6 cut-off for predicting FEV1/FVC <70% was 75% using receiver operating characteristic curve analyses (area under receiver operating characteristic curve =0.989, 95% confidence interval 0.987-0.990). This fixed cut-off of FEV1/FEV6 showed 93.8% sensitivity, 94.8% specificity, 74.7% positive predictive value, 98.9% negative predictive value, and 0.8 Cohen's kappa coefficient. When compared with FEV1/FVC < lower limit of normal, FEV1/FEV6 <75% tended to over-diagnose airflow limitation (just like a fixed cut-off of FEV1/FVC <70%). When grouped according to age and FEV1 (%), FEV1/FEV6 <75% diagnosed more airway obstruction in older participants and mild-moderate stages compared with FEV1/FVC <70%. CONCLUSION: A valid fixed cut-off for detecting airway obstruction in a Korean population is FEV1/FEV6 of 75%, but should be used with caution in older individuals and those with mild-moderate airway obstruction.

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.

Functional and Prognostic Implications of the Main Pulmonary Artery Diameter to Aorta Diameter Ratio from Chest Computed Tomography in Korean COPD Patients.

BACKGROUND: The ratio of the diameter of the main pulmonary artery (mPA) to the diameter of the aorta (Ao) on chest computed tomography is associated with diverse clinical conditions. Herein, we determined the functional and prognostic implications of the mPA/Ao ratio in Korean chronic obstructive pulmonary disease (COPD) patients. METHODS: The study population comprised 226 chronic obstructive pulmonary disease patients from the Korean Obstructive Lung Disease cohort who underwent chest computed tomography. We analyzed the relationships between the clinical characteristics, including pulmonary function, echocardiography findings, St. George's Respiratory Questionnaire, 6-minute walking (6MW) distance, and exacerbation with the mPA, Ao, and mPA/Ao ratio. RESULTS: The mean age was 65.8 years, and 219 (96.9%) patients were male. The mean FEV1% predicted and FEV1/FVC ratio were 61.2% and 47.3%, respectively. The mean mPA and Ao were 23.7 and 36.4 mm, respectively, and the mPA/Ao ratio was 0.66. The mPA/Ao ratio correlated negatively with the 6MW distance (G = -0.133, P = 0.025) and positively with the right ventricular pressure (G = 0.323, P = 0.001). After adjustment for potential confounders, the mPA/Ao ratio was significantly associated with 6MW distance (ß = -107.7, P = 0.017). Moreover, an mPA/Ao ratio >0.8 was a significant predictor of exacerbation at the 1-year (odds ratio 2.12, 95% confidence interval 1.27-3.52) and 3-year follow-ups (odds ratio 2.04, 95% confidence interval 1.42-2.90). CONCLUSIONS: The mPA/Ao ratio is an independent predictor of exercise capacity and an mPA/Ao ratio >0.8 is a significant risk factor of COPD exacerbation.

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.

Risk factors for tuberculosis after gastrectomy in gastric cancer.

AIM: To examine incidence of tuberculosis (TB) in gastrectomy patients and investigate the risk factors for developing TB after gastrectomy in patients with gastric cancer. METHODS: A retrospective cohort study of gastrectomy patients with gastric cancer was performed at a university-affiliated hospital in Seoul, South Korea between January 2007 and December 2009. We reviewed patient medical records and collected data associated with the risk of TB, surgery, and gastric cancer. Standardized incidence ratios (SIRs) of TB were calculated to compare the incidence of TB in gastrectomy patients with that in the general Korean population, and risk factors for TB after gastrectomies were analyzed. RESULTS: Among the 1776 gastrectomy patients, 0.9% (16/1776) developed post-gastrectomy TB, with an incidence of 223.7 cases per 100000 patients per year. The overall incidence of TB in gastrectomy patients, adjusted by sex and age, was significantly higher than that in the general population (SIR = 2.22, 95%CI: 1.27-3.60). Previous TB infection [odds ratio (OR) = 7.1, P < 0.001], lower body mass index (BMI) (kg/m(2); OR = 1.21, P = 0.043) and gastrectomy extent (total gastrectomy vs subtotal gastrectomy) (OR = 3.48, P = 0.017) were significant risk factors for TB after gastrectomy in a multivariate analysis. CONCLUSION: TB incidence after gastrectomy is higher than that in the general population. Previous TB infection, lower BMI, and total gastrectomy are risk factors for TB after gastrectomy in patients with gastric cancer.

Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease

Abstract Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p < 0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p = 0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p = 0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.