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PurposeAs the aging of society progresses, the proportion of extremely older lung cancer patients has also increased; However, studies of these patients with non–small cell lung cancer are limited. Therefore, we investigated the initial treatment modalities and survival outcomes for patients aged 80 years or over.Materials and MethodsWe included a multicenter retrospective cohort from the Korean Association for Lung Cancer Registry, which surveys 10% of the newly diagnosed lung cancer patients across 52 hospitals in Korea. We analyzed and compared the 2014–2016 data of the non–small cell lung cancer patients aged ≥ 80 years and those aged < 80 years. ResultsOf the 6,576 patients reviewed, 780 patients were aged ≥ 80 years, and 5,796 patients were aged < 80 years. In the patients aged ≥ 80 years, surgery and radiation therapy resulted in longer patient survival among those with a resectable tumor (stage I–II) than the best supportive care (median survival, not reached [surgery] vs. 32.2 months [radiation therapy] vs. 11.43 months [best supportive care]). The duration of survival in patients with advanced-stage (IV) lung cancers was higher after chemotherapy than after the best supportive care (median survival, 8.63 months vs. 2.5 months). Patients with stage IV adenocarcinoma who received targeted therapy had better survival than those who did not (median survival, 9.0 months vs. 4.3 months).ConclusionEven in extremely older patients, active treatments, such as surgery, radiation therapy, and chemotherapy, can result in better survival outcomes than the best supportive care.

Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Copy number variation (CNV) in several genetic regions correlate with cancer susceptibility. Hence, this study evaluated the association between CNV and non-small cell lung cancer (NSCLC) in the peripheral blood. Methods: Blood samples of 150 patients with NSCLC and 150 normal controls were obtained from a bioresource center (Seoul, Korea). Through an epigenome-wide analysis using the MethylationEPIC BeadChip method, we extracted CNVs by using an SVS8 software-supplied multivariate method. We compared CNV frequencies between the NSCLC and controls, and then performed stratification analyses according to smoking status. Results: We acquired 979 CNVs, with 582 and 967 copy-number gains and losses, respectively. We identified five nominally significant associations (ACOT1, NAA60, GSDMD, HLA-DPA1, and SLC35B3 genes). Among the current smokers, the NSCLC group had more CNV losses and gains at the GSDMD gene in chromosome 8 ( P=0.02) and at the ACOT1 gene in chromosome 14 ( P=0.03) than the control group. It also had more CNV losses at the NAA60 gene in chromosome 16 ( P=0.03) among non-smokers. In the NSCLC group, current smokers had more CNV gains and losses at the ACOT1 gene in chromosome 14 ( P=0.003) and at HLA-DPA1 gene in chromosome 6 ( P=0.02), respectively, than non-smokers. Conclusion: Five nominally significant associations were found between the NSCLC and CNVs. CNVs are associated with the mechanism of lung cancer development. However, the role of CNVs in lung cancer development needs further investigation.

BACKGROUND: Recent advances in critical care and infection control have led to improved intensive care unit (ICU) survival rates. However, controversy exists regarding the benefits of ICU treatment for patients with lung cancer. In this study, we evaluated the clinical outcomes of patients from the Korean national database, who had been diagnosed with lung cancer and had received ICU treatment. METHODS: We investigated patients in Korea who had been newly diagnosed with lung cancer between January 1, 2008 and December 31, 2010. We classified these critically ill patients with lung cancer according to their lung cancer treatment pathways, with a specific focus on those who had undergone ICU treatment. RESULTS: We found that 31.3% of patients newly diagnosed with lung cancer had been admitted to the ICU for any reason, and 18.5% of patients with lung cancer were admitted to the ICU for reasons other than postoperative surgical lung cancer resection. The ICU mortality rate was 2.9% in patients admitted to the ICU for postoperative care and 47.5% in patients admitted for other reasons. Clinical cancer staging (HR, 7.02; 95% CI, 5.82–8.48; P

Microwave assisted thermal sterilization (MATS) is a novel microwave technology currently used in the commercial production of ready-to-eat meals. It combines surface heating of high-temperature circulation water with internal microwave heating in cavities. The heating pattern inside the food packages in a MATS process depends heavily on the electric field distribution formed by microwaves from the top and bottom windows of the microwave heating cavities. The purpose of this research was to study the effect of the electric field on 922 MHz microwave heating of ready-to-eat meals as they moved through the microwave chamber of a pilot-scale MATS system using the finite-difference time-domain (FDTD) method. A three-dimensional numerical simulation model was developed as a digital twin of the MATS process of food moving through the microwave chamber. The simulation showed that the electric field intensity of the MATS microwave cavity was greatest on the surface and side edge of the cavity and of the food. There was a strong similarity of the experimental heating pattern with that of the electric field distribution simulated by a computer model. The digital twin modeling approach can be used to design options for improving the heating uniformity and throughput of ready-to-eat meals in MATS industrial systems.

Background Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD. Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. Methods To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. Results Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219, P = 0.015). Conclusion Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD., Graphical Abstract

Tuberculosis (TB)-infected giant bullae are rare. A 55-year-old man was referred when an infected bulla did not respond to empirical treatment. Computed tomography showed a giant bulla in the right upper lobe with an air-fluid level and surrounding infiltrate. Sputum culture, acid-fast bacilli (AFB) stain, and polymerase chain reaction (PCR) for TB were negative. Percutaneous drainage of the bullous fluid was performed. AFB stain and PCR were positive in the drained fluid. The patient was given anti-TB drugs and later underwent obliteration of the pulmonary cavity using talc. To summarize, we report a patient with a TB-infected giant bulla that was treated successfully with anti-TB drugs and obliteration of the pulmonary cavity using talc.

This paper investigates the gas sensing characteristics of the MOSFET-type sensor having an inkjet-printed WS2 sensing layer. The drain current of the gas sensor increases when NO2 gas is injected into the test chamber since NO2 gas is an oxidizing gas that extracts electrons from the sensing layer. On the contrary, the drain current decreases when H2S gas is injected into the test chamber since H2S gas is a reducing gas that donates electrons to the sensing layer. In both cases, the change of the drain current increases as the gas concentration increases. However, for other gases (NH3 and CO2), the gas sensor has a small change of the drain current. The responses of the gas sensor to 10 ppm NO2, H2S, NH3, and CO2 gases are 15.20%, 7.18%, 1.66%, and 3.02%, respectively. Therefore, the WS2 sensor has a high selectivity for NO2 gas among the four target gases.

The food industry and the research community have shown interest in microwave pasteurization of packaged food products since the 1970s. Microwave heating offers possibilities of shorter processing time and better heating uniformity compared to conventional thermal processing using steam or hot water. It, thus, holds potential to deliver safe and higher quality foods. Factors that have hindered commercial applications of microwave pasteurization include engineering challenges in system design, relatively high costs for new equipment installation and operation, and un-familiarity with microwave heating systems. Consumer desire for convenience, food safety risks associated with e-commerce and home delivery of prepared meals, and regulatory requirements imposed by the Food Safety Modernization Act (FSMA) in the USA have generated great commercial interest in in-package pasteurization technologies. In this paper, we will review pathogens of concern in designing thermal pasteurization processes, regulatory guidelines for pasteurization, and advancements in microwave pasteurization system designs. We offer opinions as to how microwave assisted pasteurization will help the food deliver safe and high quality ready-to-eat meals to consumers through various distribution methods.

Background There are few studies on intensive care unit (ICU) patients in the Republic of Korea. We analyzed the characteristics and mortality changes of all ICU patients over the last 8 years. Methods This study used the cohort of the National Health Insurance Corporation, which provides medical care to all residents of the Republic of Korea. The cohort consists of patients aged 20 years or older between 2003 and 2010 with a history of ICU admission. We analyzed changes in sex, age, household income, number of hospital beds, emergency admissions, and reasons for admission using the Cochran-Armitage trend test. The adjusted hazard ratios (HRs) of mortality according to these variables and year of admission were calculated by Cox proportional hazards regression. Results The proportion of patients aged ≥70 years increased over that period, as did their average age (by 3.6 years). During the 8-year study period, the 3-year mortality rate was 32.91%-35.83%. The overall mortality was higher in males and older patients, in those with a lower household income and higher Charlson Comorbidity Index (CCI) score, those admitted to a hospital with a smaller number of beds, and those admitted via the emergency room. There was no significant change in crude mortality rate over the 8-year study period; however, the adjusted HR showed a decreasing trend. Conclusions Patients admitted to the ICU were older and had higher CCI score. Nevertheless, there was a temporal trend toward a decrease in the HR of long-term mortality.

In this paper, a Field-Effect-Transistor (FET)-type gas sensor using the composite of Na2CO3 and NaNO2 as the sensing material is investigated. The sensor has a floating gate (FG) passivated by an insulator stack and a control gate (CG), which are formed in an interdigitated form in a horizontal direction. The inkjet printing process forms the sensing material on the interdigitated FG and CG. Just before forming the sensing material, a (3-aminopropyl) triethoxysilane (APTES) monolayer is formed to prevent diffusion of Na+ ions contained in the sensing material through the insulator layer. The sensor can be electrically programmed like a typical memory device due to the FG, which makes the calibration of the sensor possible. CO2 gas sensing properties of the sensor are characterized at an operating temperature of 160 °C. The results indicate that the proposed sensor produces a reasonable and repeatable response to a certain concentration of CO2.

In this work, we demonstrate the pulse scheme to obtain stable humidity sensing characteristics in Si FET-type humidity sensor using MoS2 film as a sensing layer. To investigate the reaction between H2O molecules and MoS2 film, the transfer characteristics (ID-VCG) and transient drain current behaviors (ID-t) are measured in both pMOSFET and nMOSFET sensors by DC measurement. To verify the effect of the pulse scheme, the pulsed I–V (PIV) and the ID-t are measured as a parameter of relative humidity. The ID drift of the FET-type sensor is effectively eliminated by applying the pulse to the control-gate (CG) of the FET-type humidity sensor.

Oxygen (O2) sensors are needed for monitoring environment and human health. O2 sensing at low temperature is required, but studies are lacking. Here we report, for the first time, that the performance of a field effect transistor (FET)-type O2 sensor operating at 25 °C was improved greatly by a physisorption sensing mechanism. The sensing material was platinum-doped indium oxide (Pt-In2O3) nanoparticles formed by an inkjet printer. The FET-type sensor showed excellent repeatability under a physisorption mechanism and showed much better sensing performance than a resistor-type sensor fabricated on the same wafer at 25 °C. The sensitivity of the sensor increased with increasing Pt concentration up to ∼10% and decreased with further increasing Pt concentration. When the sensing temperature reached 140 °C, the sensing mechanism of the sensor changed from physisorption to chemisorption. Interestingly, the pulse pre-bias before the read bias affected chemisorption but had no effect on physisorption.

Various biomarkers have emerged as potential surrogates to represent various subgroups of chronic obstructive pulmonary disease (COPD), which manifest with different phenotypes. However, the biomarkers representing never-smokers with COPD have not yet been well elucidated. The aim of this study was to evaluate the associations of certain serum and radiological biomarkers with the presence of COPD in never-smokers. To explore the associations of serum and radiological biomarkers with the presence of COPD in never-smokers, we conducted a cross-sectional patient cohort study composed of never-smokers from the COPD in Dusty Areas (CODA) cohort, consisting of subjects living in dusty areas near cement plants in South Korea. Of the 131 never-smokers in the cohort, 77 (58.8%) had COPD. There were no significant differences in the number of subjects with high levels of inflammatory biomarkers (>90th percentile of never-smokers without COPD), including white blood cell count, total bilirubin, interleukin (IL)-6, IL-8, and C-reactive protein, or radiologic measurements (including emphysema index and mean wall area percentage) between never-smokers with COPD and those without COPD. However, the number of subjects with high uric acid was significantly higher in never-smokers with COPD than never-smokers without COPD (31.2% (24/77) vs. 11.1% (6/54); p = 0.013). In addition, multivariate analysis revealed that high uric acid was significantly associated with the presence of COPD in never-smokers (adjusted relative risk: 1.63; 95% confidence interval: 1.21, 2.18; p = 0.001). Our study suggests that high serum levels of uric acid might be a potential biomarker for assessing the presence of COPD in never-smokers.

The promotive effect of a pre-bias condition on the recovery speed of a field-effect transistor-type gas sensor, which has a horizontal control gate (CG) and floating gate (FG), is investigated in this letter. To verify the pre-bias effect in the recovery phase after the detection of H2S gas, a type of reducing gas, a 200-nm-thick layer of SnOx is deposited on top of the interdigitated CG and FG as a sensing material. A pulse measurement method is proposed to improve the recovery speed of the sensor for H2S gas sensing by applying a negative pre-bias condition to the CG before the read operation of the sensor. This method greatly accelerates the recovery and reduces the recovery time by 74% with a pre-bias of −3 V at 180° C. The mechanism is explained in terms of energy band theory. The pre-biasing method used with our gas sensor is beneficial for the continuous monitoring and for the rapid detection of various gases.

An efficient pre-bias method is proposed in the reading operation of a Field-Effect-Transistor(FET)-type gas sensor which utilizes flatband voltage change of the sensing material formed between the control-gate (CG) and floating-gate (FG) of the FET. The proposed method improves greatly recovery speed and shortens recovery time by more than 10 times at 180 °C, which can reduce the power consumed by heater. Since the polarity of the pre-bias affects response, sensing and recovery speeds, it is possible to identify the redox characteristics of the detected gas. To verify experimentally the pre-bias effect, we apply pulses for the pre-biasing and reading to the sensor with a sensing material of 200-nm-thick SnO x layer to detect NO 2 gas as an example. The mechanism is explained theoretically by energy band theory. The pre-biasing method is expected to open a new biasing scheme which improves significantly sensing characteristics, gas identification, and power dissipation.

Background It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients. Methods Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models. Results Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15–0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants. Conclusions Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0587-9) contains supplementary material, which is available to authorized users.

In this work, we propose Si FET-type gas sensors and barometric pressure sensors that can be efficiently integrated on the same substrate using CMOS process technology and report the measurement results. The gas sensor has a localized micro-heater capable of heating up to 124 °C with a power of 4 mW. NO 2 gas sensing is successfully achieved with this sensor. The barometric sensor has a built-in poly-Si temperature sensor that can simultaneously measure ambient temperature and atmospheric pressure. The measured atmospheric pressure varies with temperature, but with a designed neural network, accurate pressure can be obtained with an accuracy of 97.5 %.

The sensing characteristics of nitrogen dioxide (NO 2 ) gas in Si FET-type gas sensor using localized micro-heater are investigated. As the sensing material, a 12-nm-thick indium oxide (In 2 O 3 ) deposited by a radio frequency magnetron sputtering method is used. The NO 2 gas sensing characteristics are examined while varying the applied voltage of the micro-heater (V H ) and the concentration of the NO 2 gas at room temperature. The fabricated sensor shows excellent performance in detecting low concentration of NO 2 gas (25 ppb) and shows that it can improve the sensing characteristics using the pre-bias scheme while 2 V is applied to the micro-heater with 50 % of duty cycle which only consumes ~0.84 mW.

Lung cancer is the most common cancer and the leading cause of cancer-related morbidity and mortality worldwide. As early symptoms of lung cancer are minimal and non-specific, many patients are diagnosed at an advanced stage. Despite a concerted effort to diagnose lung cancer early, no biomarkers that can be used for lung cancer screening and prognosis prediction have been established so far. As global DNA demethylation and gene-specific promoter DNA methylation are present in lung cancer, DNA methylation biomarkers have become a major area of research as potential alternative diagnostic methods to detect lung cancer at an early stage. This review summarizes the emerging DNA methylation changes in lung cancer tumorigenesis, focusing on biomarkers for early detection and their potential clinical applications in lung cancer.

Gas sensors are commercialized and widely applied in various fields. Existing commercial sensors, however, have limitations in terms of power consumption. In this work, we propose a new design guideline of the FET-type gas sensor platform to significantly improve the power efficiency of the embedded poly-Si micro-heater. The fabricated sensors are capable of low power operation while maintaining high response and stability. To our knowledge, the embedded micro-heater of the proposed platform provides the best power efficiency (e.g. 300 ℃ at 1.63 mW) among reported gas sensors with external heaters. By adopting electrode metals with low thermal conductivity (Ti/TiN instead of Cr) in contact with the heater and an efficient heat insulating air gap design (increasing air gap length under the electrode from 0 μm to 28 μm), we can increase the heater temperature by 63 % at the same power consumption. Also, the proposed platform is more sensitive and advantageous for low-concentration gas detection compared to the reported FET-type platform using hot chuck that increases the temperature of the entire sensor.

This study was performed to evaluate the potential association between serum heavy metal levels and lung function in a cohort of chronic obstructive pulmonary disease (COPD) patients. We analyzed data from 152 subjects enrolled in a cohort study on COPD from 2012 to 2013 and living in a dusty area. In total, 152 subjects from the cohort study were enrolled; 111 were diagnosed with OLD. There was a significant association between post-bronchodilator FEV1 and serum mercury level after adjusting for age, gender and smoking status (p=0.03). Following the adjustment, a significantly higher prevalence of OLD was observed in subjects in the highest mercury concentration tertile (p=0.03). The risk of OLD was significantly higher for subjects in the higher mercury concentration (odds ratio, 3.62; 95% confidence interval: 1.29-10.18) than in those in the lowest tertile. In conclusion, serum mercury level may be a risk factor for reduced lung function and OLD.

Introduction and Objectives Although tobacco smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), more than one-fourth of COPD patients are non-smokers. In this cross-sectional study, the differences in COPD phenotypes between non-smokers and smokers in male subjects were investigated and were focused on structural lung changes using a quantitative assessment of computed tomography (CT) images. Methods They divided male participants with COPD, from a Korean cohort near a cement plant, into non-smokers and smokers by a cutoff of a 5 pack-year smoking history. Clinical characteristics, including age, body mass index (BMI), spirometry results, history of biomass smoke exposure, and CT measurements, were compared between the two groups. Emphysema index (EI) and mean wall area percentage (MWA %) were used to evaluate the structural lung changes on volumetric CT scans. Results The non-smoker group (n = 49) had younger patients and had a greater BMI than the smoker group (n = 113) (P

Background: Identifying markers for predicting the course and outcome of chronic obstructive pulmonary disease (COPD) remains important. The relative pulmonary artery enlargement to aorta ratio (PA-A ratio), which is measured using computed tomography (CT), is a reported predictor for COPD exacerbation and mortality. However, little is known about the implications of the PA-A ratio in patients with mild COPD. Methods: We investigated the utility of the PA-A ratio as a biomarker in patients with relatively mild COPD. A total of 131 patients with mild to moderate COPD [post-bronchodilator forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) 61.6±6.4, mean post-bronchodilator FEV1 83%±17.8% of predicted value] were selected from a Korean COPD cohort (from 2012 until the end of 2014) and analyzed retrospectively. We determined the correlation between the PA-A ratio and clinical parameters using a linear regression model. Results: The COPD assessment test (P=0.04), FEV1 (P=0.03), and a history of exacerbation in the last year (P=0.03) were significant factors in the univariate linear regression analysis. Post-bronchodilator FEV1 was most significantly associated with the PA-A ratio in the multivariate analysis (P=0.01). Conclusions: The PA-A ratio evaluated by CT imaging was independently correlated with a representative pulmonary function factor (FEV1) in patients with relatively mild COPD. The results suggest that the PA-A ratio may be an important biomarker for clinical outcome in patients with mild COPD.

The purpose of this study was to develop a convenient method to assist the food industry in developing process schedules for production of ready-to-eat meals using microwave assisted pasteurization system (MAPS). An analytical model was applied to estimate the temperature increase in the cold zone in packaged foods during heating in a 915 MHz single-mode microwave system. This model was validated in a pilot-scale four-cavity MAPS using mashed potato-gellan gum model food with different thicknesses (22 to 36 mm) and salt contents (0.0 to 1.0%). Mobile sensors were placed in the packages to measure temperature at the pre-determined cold spots. For 2.48 min of microwave heating with 5, 5, and 8.7 kW 915 MHz microwave powers, the highest temperature increase at the cold spot during microwave heating was 33.2 °C in the 22 mm thick model food with 0.6% salt content, whereas the lowest temperature increase was 10.3 °C in the 36 mm thick model food with 1.0% salt content. There was a deviation of 1.9 ± 1.2 °C between experimental and predicted data with an R2 of 0.89. A simplified chart was developed based on the validated analytical results to allow rapid prediction of temperature increases in MAPS as influenced by food dielectric properties and package thickness. Examples were used to illustrate how the chart could assist in process scheduling. The chart can help assess the heating rates of various pre-packaged food products in a specific industrial MAPS or guide product development for desired heating uniformity.

Background Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzymes play important roles in generating reactive oxygen species (ROS); in particular, NOX4 plays a distinct role in regulating lung inflammation and apoptosis. Methods We determined whether plasma NOX4 level can be used as a prognostic biomarker to guide weaning from mechanical ventilation and to predict mortality in intubated patients. Plasma levels of NOX4 were measured at days 1 (NOX4 D1) and 7 (NOX4 D7) after initiation of mechanical ventilation in 184 patients. Results With increase in day 7 NOX4 quartile, the success of weaning tended to decrease and 28-day mortality tended to increase. On multivariate logistic regression, Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) [odds ratio (OR): 1.10; 95% CI, 1.02-1.18], duration of mechanical ventilation (OR: 1.12; 95% CI: 1.06-1.18), and NOX4 D7 levels >18.2 ng/mL (OR: 4.40; 95% CI: 1.91-10.06) were independently associated with weaning failure. Also, Cox-hazard proportional model showed that NOX4 D7 level >18.2 ng/mL (hazard ratio [HR], 2.29; 95% CI, 1.26-4.16), APACHE II (HR: 1.07; 95% CI: 1.02-1.14), Sequential Organ Failure Assessment (SOFA) (HR: 1.10; 95% CI: 1.01-1.20) and coexisting cancer (HR: 1.99; 95% CI, 1.01-3.94), were independently associated with 28-day mortality. The longitudinal trend of NOX4 level varied according to the clinical outcomes. Conclusions An increased plasma NOX4 D7 level was associated with weaning failure and 28-day mortality in patients with mechanical ventilation. Our results suggest that NOX4-directed management may lead to improved outcomes in patients with mechanical ventilation.

Background Increased incidence of lung cancer in subjects with previous tuberculous infection was reported in epidemiologic data. NOX4 signaling contributes to tuberculous pleural fibrosis and lung cancer proliferation, respectively. The objective of this study was to investigate the role of NOX4 in tuberculous pleurisy-assisted tumorigenicity both in vitro and in vivo. Methods After pleural mesothelial cells from WT and NOX4 KO C57BL/6 mice were stimulated with Heat-Killed mycobacterium tuberculosis (HKMT) for 24 hour, cellular interactions between mesothelial cell and cancer cell were evaluated by using transwell invasion assay and wound healing assay. A murine model injected with cancer at 4 weeks after Mycobacterium bovis bacillus Calmette-Guérin (BCG) pleural infection were used to validate the contribution of tuberculous fibrosis to tumor invasion. Results HKMT -stimulated mesothelial cells induced enhanced invasion and migration potential of lung cancer cells in a NOX4-dependent manner. The inhibition of NOX4 signaling exerted a negative effect on the metastatic potential of lung cancer by tuberculous fibrosis in mice model. The expression of inflammatory cytokines like TNF-a, TGF-β and IL-6 was enhanced in the WT-BCG+CA than WT+PBS+CA and NOX4 KO+BCG+CA. The expression of P62 in lung tissue was higher in the WT-BCG+CA than WT+PBS+CA and NOX4 KO+BCG+CA. Discussions Our results suggest that NOX4 and autophagy signaling changed by tuberculous fibrosis could result enhanced tumorigenic potential. NOX4-P62 might seve as a target for the development of anti-tuberculous fibrosis and anti-cancer drugs. Citation Format: Yoonki Hong, Seong-Ji Woo, Youngmi Kim, Ji Young Hong. NOX4 P62 regulates tuberculous fibrosis promoted tumorigenic potential [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1247.

Background Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI). Methods In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay. Results Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1β in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15nil) and negatively with that of TB antigen-stimulated IL-32 (IL-32TB) in QFT-GIT supernatants. Although the IL-15nil and IL-15TB levels were higher in LTBI subjects than patients with active TB, the IL-32nil and IL-32TB levels were higher in the latter patients. A combination of the IL-15nil and IL-32TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964. Conclusions Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.

Background Although physical activity is known to be beneficial to lung function, few studies have been conducted to investigate the correlation between physical activity and lung function in dusty areas. Therefore, the purpose of this study is to investigate the correlation between physical activity and lung function in a Korean cohort including normal and COPD-diagnosed participants. Methods Data obtained from the COPD in dusty areas (CODA) cohort was analyzed for the following factors: lung function, symptoms, and information about physical activity. Information on physical activity was valuated using questionnaires, and participants were categorized into two groups: active and inactive. The evaluation of the mean lung function, modified Medical Research Council dyspnea grade scores, and COPD assessment test scores was done based on the participant physical activity using a general linear model after adjusting for age, sex, smoking status, pack-years, height, and weight. In addition, a stratification analysis was performed based on the smoking status and COPD. Results Physical activity had a correlation with high forced expiratory volume in 1 second (FEV₁) among CODA cohort (p=0.03). While the active group exhibited significantly higher FEV₁ compared to one exhibited by the inactive group among past smokers (p=0.02), no such correlation existed among current smokers. There was no significant difference observed in lung function after it was stratified by COPD. Conclusion This study established a positive correlation between regular physical activity in dusty areas and lung function in participants.

A poly-Si localized micro-heater for Si FET-type gas sensor is proposed. The gas sensor has an air gap under the heater to prevent the heat dissipation. It is verified that the heater temperature can be read by reading the heater resistance immediately after the heating pulse is turned on or off. A heater temperature of 112°C is achieved at a heat pulse bias of 2 V, which consumes ∼0.92 mW. The heating and cooling times of the heater are $\sim\ 200\mu\mathrm{s}$ and $\sim\ 100\mu\mathrm{s}$ , respectively. NO 2 and H 2 S sensing are successfully performed by using a pulse-driven micro-heater in the proposed gas sensor.

Yeon-Mok Oh,1,* Keu Sung Lee,2,* Yoonki Hong,3,* Sung Chul Hwang,2 Jae Yeol Kim,4 Deog Keom Kim,5 Kwang Ha Yoo,6 Ji-Hyun Lee,7 Tae-Hyung Kim,8 Seong Yong Lim,9 Chin Kook Rhee,10 Hyoung Kyu Yoon,11 Sang Yeub Lee,12 Yong Bum Park,13 Jin Hee Jung,14 Woo Jin Kim,3 Sang-Do Lee,1 Joo Hun Park2 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea; 3Department of Internal Medicine and Environmental Health Center, Kangwon National University, Kangwon National University Hospital, Chuncheon, Korea; 4Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 7Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 8Division of Pulmonology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea, Seoul, Korea; 11Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 12Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 13Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 14Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea *These authors contributed equally to this work Background: High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids. However, the prognostic role of blood eosinophil count remains underexplored. Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.Methods: Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital. The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%–5%), and low (

Background: Asian dust is known to have harmful effects on the respiratory system. Respiratory conditions are also influenced by environmental conditions regardless of the presence of pollutants. The same pollutant can have different effects on the airway when the air is dry compared with when it is humid. We investigated hospital visits for chronic obstructive pulmonary disease (COPD) and asthma in relation to the environmental conditions. Methods: We conducted a retrospective study using the Korean National Health Insurance Service claims database of patients who visited hospitals in Chuncheon between January 2006 and April 2012. Asian dust, haze, mist, and fog days were determined using reports from the Korea Meteorological Administration. Hospital visits for asthma or COPD on the index days were compared with the comparison days. We used two-way case-crossover techniques with one to two matching. Results: The mean hospital visits for asthma and COPD were 59.37 ± 34.01 and 10.04 ± 6.18 per day, respectively. Hospital visits for asthma significantly increased at lag0 and lag1 for Asian dust (relative risk [RR], 1.10; 95% confidence interval [CI], 1.01-1.19; p

Background Chronic obstructive pulmonary disease (COPD) is associated with poor prognosis and a high health care burden. The incidence of asthma and COPD overlap syndrome is increasing, and contributes to a high financial burden and poor prognosis. Objective To investigate clinical features of the overlap syndrome among Asian patients and to analyse its impact on hospitalisation due to respiratory problems or death compared to COPD alone. Design We performed a retrospective cohort analysis of 2933 COPD patients presenting at the Asan Medical Center from 1 January 2000 to 31 December 2009. Kaplan-Meier and Cox proportional hazard models were used to analyse the significance of clinical parameters, including age, sex, smoking history, body mass index (BMI), severity of airflow limitation, airway obstruction reversibility and overlap syndrome with hospitalisation due to respiratory problems or death. Results Overlap syndrome patients were older, included smaller proportions of males and of smokers and had lower forced expiratory volume in 1 s (FEV1) (% predicted). Shorter hospitalisation-free and survival periods were noted among overlap syndrome patients. Overlap syndrome was significantly associated with risk of hospitalisation due to respiratory problems after adjusting for age, smoking history, BMI, FEV1 (% predicted) and changes in FEV1 (P Conclusion Asthma and COPD overlap syndrome is associated with a higher risk of hospitalisation due to respiratory problems than COPD alone.

A mathematical model for predicting electromagnetic power dissipation within a rectangular dielectric slab heated by equal intensity 915 MHz plane waves from top and bottom was developed. A dimensionless parameter (J-T number) which is a combination of the loss factor (er″), dielectric constant (er′) and food thickness (L) was proposed. This unique number provided direct insight into the relationship between food dielectric properties, thickness, product temperature, and thermal lethality. For the validation tests, mashed potatoes, peas and rice samples with 0–2% salt content were processed in a pilot scale microwave assisted thermal sterilization (MATS) system. In each food, the combination of dielectric properties and thickness which gave J-T number of 1.8–2.2 at 100–121°C, provided the highest lethalities. MATS is a novel commercial technology being adapted in the food industry. A qualitative assessment of the combined effect of food properties on lethalities using this model will be helpful in process development for MATS systems.

Background Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). Methods Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. Results The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). Conclusion Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC., Graphical Abstract

Introduction: Although occupational exposure is an important risk factor for development of chronic obstructive pulmonary disease (COPD), it has been little known about the effects of occupations exposures for progression of COPD. Aims and Objectives: To determine the effect of history for occupational exposures on lung function decline in men with COPD. Methods: Subjects were selected from a Korean COPD cohort, prospectively designed observational study and underwent yearly post bronchodilator spirometry. They were included if they underwent the spirometry at least three times. History of occupational exposures was evaluated for metal, asbestos, fiber, cereal, drugs, paper dust, and chemicals. History of occupational exposures was assessed by two blinded experts for each case. The annual decline of FEV1 was analyzed by random-slope and random-intercept mixed linear regression. Results: A total 222 patients with COPD were included, and patients with occupational exposures were 49. The mean age was 65.2 (standard deviation: 7.5) years, the mean smoking amount was 46.3 (28.1) pack-years. There were no significant differences in years of age, smoking amount, quality of life, and emphysema extent on CT, according to the presence of occupation exposures. The annual decline rates in FEV1 (ml per year) were significantly different for groups without occupational exposures of -32.9±21.9 compared to groups with occupational exposures of -25.5±19.9 (p = 0.038). Conclusions: Occupational exposures in men with COPD were associated with slower decline of lung function.

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses. In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up. Methods We analyzed dusty areas cohort comprising 272 patients with COPD. The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline. The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data. The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups. Results PCA revealed that six independent components accounted for 77.3% of variance. Three distinct subgroups were identified through the cluster analysis. Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up. Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up. Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization. Conclusions Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes. These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD. Electronic supplementary material The online version of this article (10.1186/s12890-017-0553-9) contains supplementary material, which is available to authorized users.

Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases ventilation and therefore improves ventilation-perfusion (V/Q) mismatch. Materials and Methods All patients provided written informed consent to be included in this study, which was approved by the Institutional Review Board (2013-0368) of Asan Medical Center. The physiologic changes that occurred after BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced perfusion dual-energy computed tomography (CT). Patients with severe emphysema plus hyperinflation who did not respond to usual treatments were eligible. Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of life assessment, and dual-energy CT were performed at baseline and 3 months after BLVR. The effect of BLVR was assessed with repeated-measures analysis of variance. Results Twenty-one patients were enrolled in this study (median age, 68 years; mean forced expiratory volume in 1 second [FEV

Sensing characteristics of the SO2 gas are investigated using a horizontal floating-gate FET-type gas sensor. SO2 gas sensing characteristics of the resistor-type gas sensor, a conventional sensor, fabricated on the same wafer are also investigated and compared with the FET-type gas sensor. The 18-nm-thick WO3 deposited using a radio frequency magnetron sputtering method is used as the sensing material. The SO2 gas sensing characteristics are examined while varying the operating temperature, the concentration of the SO2 gas, and the pre-bias (Vpre). The sensing mechanism for detecting the SO2 gas in an FET-type gas sensor is examined. Both sensors are able to detect up to 10 ppm of SO2 gas, and the FET-type sensor shows significantly improved gas response by using the pre-bias scheme.

A new capacitive-type FET (CFET) gas sensor is proposed in this work and fabricated by using Si FET technology. Only five photomasks are used to prepare the CFET sensor and a ZnO thin film prepared by atomic layer deposition (ALD) is adopted as a sensing material. A diluted nitrogen dioxide (NO2) is used as a test gas and the sensing properties of the CFET gas sensor are measured at 180℃ by using pulse pre-bias method. It is verified that the response of the CFET sensor is significantly improved as the absolute value of the difference between pre-bias (Vpre) and gate read bias (VrCG) increases. However, the response is negligible when Vpre = VrCG. The drain current (ID) of the CFET gas sensor increases by 44.6% at a Vpre of −2 V while the ID decreases by 43.2% at a Vpre of 2 V under exposure to 0.5 ppm NO2 at a VrCG of 0 V at 180℃. The response and the recovery times are also investigated. The sensing mechanism is explained by using schematic energy band diagrams.

Although many patients with severe emphysema have benefited from bronchoscopic lung volume reduction (BLVR) worldwide, experience of BLVR in Asian emphysema patients is scarce. Between July 2012 and March 2013, seven patients with advanced heterogeneous emphysema underwent BLVR in the Asan Medical Center. They had severe dyspnea and poor lung function (Modified Medical Research Council dyspnea scale 3-4; median forced expiratory volume in 1 sec [FEV1], 0.59 L [19.0 % predicted]; median 6-min walk distance [6MWD], 195 m). Endobronchial valves were inserted into the target lobe which was most hyperinflated and least perfused, and had no collateral ventilation with other lobes. Six patients showed clinical improvement after 1 month. Of them, 2 patients improved to dyspnea scale 1 and 4 patients did to scale 2 (P = 0.026). The median FEV1 increased from 0.59 to 0.89 L (51%; P = 0.028) and the median 6MWD increased from 195 to 252 m (29.2%; P = 0.028). Two patients developed a pneumothorax (one requiring drainage) and one patient experienced slight hemoptysis; however, there were no other serious adverse events. BLVR is effective in Asian advanced emphysema patients, with noted clinical improvements in lung function and exercise capacity. Graphical Abstract Keywords: Emphysema, Individualized Medicine, Lung Volume Reduction, Patient Selection, Pulmonary Disease, Chronic Obstructive INTRODUCTION Chronic obstructive pulmonary disease (COPD) is characterized by a persistent airflow limitation, which is caused by a mixture of small airways disease (obstructive bronchiolitis) and parenchymal destruction (emphysema) (1). The current therapeutic options for COPD are smoking cessation and pharmacologic and non-pharmacologic therapies. Pharmacologic therapies include bronchodilators and corticosteroids, which aim to decrease airway resistance and airway inflammation. However, these treatments show limited effectiveness against the decreased elastic recoil and hyperinflation associated with emphysema (2). Lung volume reduction surgery (LVRS) is a surgical procedure in which selected areas of the hyperinflated lungs are resected, making respiratory muscles more effective pressure generators and increasing the elastic recoil pressure of the lungs (3, 4). LVRS has been proposed as a palliative treatment for patients with severe emphysema and was shown to improve lung function, exercise tolerance and quality of life in a subgroup of patients with upper lobe-dominant emphysema when compared to medical therapy alone (5). However, the substantial perioperative morbidity and mortality associated with LVRS has led to the development of lower risk and less invasive bronchoscopic techniques that have similar physiologic mechanisms to LVRS. Among them, endobronchial valves (EBVs) are the most widely used devices for bronchoscopic lung volume reduction (BLVR) and have shown promising results. EBVs are bronchial devices that incorporate a one-way valve that blocks the bronchial lumen leading to a targeted region of the emphysematous lung. EBVs have shown acceptable safety and efficacy when used as a unilateral treatment to improve lung function, exercise tolerance, and quality of life in patients with advanced emphysema (6, 7, 8). EBVs have been granted European Community (Communaute Europeenne [CE]) mark approval for use in BLVR and many patients worldwide have benefited from the procedure. However, the use of EBVs in BLVR in Asian emphysema patients has been minimal. In Korea, EBVs were first introduced and approved for BLVR by the Korean FDA in November 2011, with the first case performed in July 2012. The aim of this paper was to report the experience of the first Asian cases of EBV deployment in advanced emphysema patients treated with BLVR.