Chronic intermittent hypoxia induces liver fibrosis in mice with diet-induced obesity via TLR4/MyD88/MAPK/NF-kB signaling pathways.

Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model. Inflammatory and oxidative stress markers, TLR4, MyD88, Toll/interleukin-1-receptor-domain-containing adaptor-inducing interferon-ß (TRIF), I-κB, NF-κB, p38 MAPK, c-JNK, and ERK activation, were measured in the serum and liver. As a result, α1(I)-collagen mRNA was significantly higher in DIO mice exposed to CIH than in the control groups. CIH mice exhibited liver fibrosis and significantly higher protein expression of TLR4, MyD88, phosphorylated (phospho-) I-κB, and phospho-ERK1/2 activation in the liver, and higher expression of NF-κB than that in the controls. TRIF, p38 MAPK, and JNK activation did not differ significantly between groups. We conclude that CIH in DIO mice leads to liver fibrosis via TLR4/MyD88/MAPK/NF-kB signaling pathways.

The apoptotic effect of simvastatin via the upregulation of BIM in nonsmall cell lung cancer cells.

PURPOSE: Statins are known to have pleiotropic effects that induce cell death in certain cancer cells. BIM is a member of the bcl-2 gene family, which promotes apoptotic cell death. This study investigated the hypothesis that simvastatin has pro-apoptotic effects in epidermal growth factor receptor (EGFR)-mutated lung cancer cell lines via the upregulation of the expression of the BIM protein. MATERIALS AND METHODS: The cytotoxic effects of simvastatin on gefitinib-sensitive (HCC827, E716-A750del) and -resistant (H1975, T790M + L858R) nonsmall cell lung cancer (NSCLC) cells were compared. Cell proliferation and expression of apoptosis-related and EGFR downstream signaling proteins were evaluated. Expression of BIM was compared in H1975 cells after treatment with simvastatin or gefitinib. SiRNA-mediated BIM depletion was performed to confirm whether the cytotoxicity of simvastatin was mediated by the expression of BIM. RESULTS: H1975 cells showed significantly reduced viability compared with HCC827 cells after treatment with simvastatin (2 µM) for 48 hours. In simvastatin-treated H1975 cells, expression of pro-apoptotic proteins was increased and the phosphorylation of ERK 1/2 (p-ERK 1/2) was reduced. Expression of BIM was suppressed by gefitinib (1 µM) treatment in H1975 cells, but it was significantly increased by treatment with simvastatin. BIM depletion by siRNA transfection enhanced the viability of H1975 cells that received simvastatin treatment and increased their expression of anti-apoptotic proteins. CONCLUSIONS: Simvastatin restored the expression of BIM to induce apoptotic cell death in NSCLC cells harboring an EGFR-resistant mutation. Our study suggests the potential utility of simvastatin as a BIM-targeted treatment for NSCLC.

Validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale.

BACKGROUND/AIMS: This study evaluated the validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale (WSWS-K) for use in clinical practice and research on Korean smokers. METHODS: The Wisconsin Smoking Withdrawal Scale was translated into Korean and then back-translated into English. The authors reviewed the translation and back-translation and approved the final questionnaire draft. The validity and reliability of the WSWS-K were evaluated based on data collected from 300 participants. Construct validity was evaluated with a confirmatory factor analysis. Criterion-related validity was assessed by examining the relationships between the subscales of the WSWS-K and the matched items of the Korean version of the Minnesota Nicotine Withdrawal Scale (MNWS-K). RESULTS: The participants were predominantly male (93.6%) and the mean age was 59.23 ± 15.19 years. The confirmatory factor analysis revealed that fit indices (namely, the goodness-of-fit index, adjusted goodness-of-fit index, comparative fit index, and the normed fit index) exceeded or approached 0.9. Cronbach's alpha for the entire scale was 0.87. The total score of the WSWS-K had a statistically significant positive correlation with that of the MNWS-K (Pearson's correlation coefficient, 0.768; p < 0.01). Additionally, we performed linear regression between the WSWS-K and MNWS-K scores after adjusting for age, gender, comorbidity, and smoking history. After this adjustment, the p value of the WSWS- K was < 0.001. CONCLUSION: The WSWS-K had satisfactory validity and reliability. The WSWS- K can be used with acceptable validity and reliability in research and clinical evaluation of Korean smokers.

Inhibitory effects of anti-immunoglobulin E antibodies on airway remodeling in a murine model of chronic asthma.

BACKGROUND: Airway remodeling is one of the cardinal features of asthma and is thought to play a pivotal role in refractory or persistent asthma. Immunoglobulin E (IgE) has a major effect on the pathogenesis of asthma. The aim of this study was to investigate the effects of anti-IgE antibody not only on airway inflammation and bronchial hyperresponsiveness, but also on airway remodeling in a murine model of chronic asthma. METHODS: The authors developed a mouse model of chronic asthma in which ovalbumin (OVA)-sensitized female BALB/c-mice were exposed to intranasal OVA administration twice a week for 3 months. Anti-IgE antibodies were administered intravenously starting on the 38th day and once a month thereafter for 3 months during the intranasal OVA challenge. RESULTS: Mice that were chronically exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR) to methacholine and showed increased levels of collagen, hydroxyproline, and alpha-smooth muscle actin, as compared with control mice. Treatment with anti-IgE antibody inhibited the development of AHR, eosinophilic inflammation, and airway remodeling. Moreover, anti-IgE antibody treatment reduced the levels of interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluids, although it did not affect the levels of IL-10, transforming growth factor-beta, and activin A. CONCLUSION: These results suggest that anti-IgE antibody treatment modulates the airway inflammation and remodeling associated with chronic allergen challenge. The inhibition of inflammation may be related to the regulation of Th2 cytokines. However, the mechanisms underlying the blocking of airway remodeling by anti-IgE antibody remain to be elucidated.

Obstructive fibrinous tracheal pseudomembrane after tracheal intubation: a case report.

Obstructive fibrinous tracheal pseudomembrane is a rare, but potentially fatal complication associated with endotracheal intubation. It has been known that the formation of tracheal pseudomembrane is related with intracuff pressure during endotracheal intubation or infectious cause. But in the patient described in this case, pseudomembrane formation in the trachea was associated with subglottic epithelial trauma or caustic injuries to the trachea caused by aspirated gastric contents during intubation rather than tracheal ischemia due to high cuff pressure. We report a patient with obstructive fibrinous tracheal pseudomembrane after endotracheal intubation who presented with dyspnea and stridor and was treated successfully with mechanical removal using rigid bronchoscopy.

Effects of elastase inhibitor on the epithelial cell apoptosis in bleomycin-induced pulmonary fibrosis.

Alveolar epithelial cell injury and apoptosis is consistent findings in human idiopathic pulmonary fibrosis (IPF). Epithelial cell apoptosis is known to be induced by leukocyte elastase in vitro. The authors hypothesized that synthetic neutrophil elastase inhibitor, sivelestat (ONO-5046), can inhibit the bleomycin-induced pulmonary fibrosis in rats by blocking the apoptotic pathways in epithelial cells. Adult rats were injected with intratracheal bleomycin. Sivelestat was given for 13 days intraperitoneally after bleomycin treatments. Similar experiments were carried out in which A549 cells, a human alveolar type II epithelial cell line, were treated with bleomycin or neutrophil elastase. In rats, sivelestat decreased neutrophil counts and the cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage (BAL) fluid of bleomycin-treated rats. Sivelestat also decreased the bleomycin-induced lung inflammatory cell apoptosis by decreasing caspase-3 and -9 activities. In A549 cells, sivelestat decreased the elastase-induced epithelial cell apoptosis but not the bleomycin-induced epithelial cell apoptosis. Similarly, sivelestat inhibited the elastase-induced cell death but not the bleomycin-induced cell death in MTT assays. Sivelestat also inhibited the elastase-induced caspase-3 and -9 activities and cytochrome c release from the mitochondria but did not inhibit the bleomycin-induced caspase activities in A549 cells. In conclusion, bleomycin caused the lung inflammatory cell apoptosis through the caspase-9 and -3 pathways in rats. Sivelestat inhibited pulmonary fibrosis by blocking these mitochondria-mediated apoptotic pathways in bleomycin-treated rats and in elastase-treated A549 cells. These findings suggest that sivelestat can suppress the bleomycin-induced pulmonary fibrosis by blocking neutrophil chemotaxis and by inhibiting the neutrophil elastase-induced lung cell apoptosis in rats.

Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies.

INTRODUCTION: Neutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied. METHODS: We studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery. RESULTS: Compared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76). CONCLUSIONS: Patients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.

Erdheim-Chester disease with lung involvement mimicking pulmonary lymphangitic carcinomatosis.

Erdheim-Chester disease (ECD) is a rare proliferative non-Langerhans cell histiocytosis of multiple organs with unknown etiology. Around 20% of ECD cases are reported to be associated with lung involvement and there are very few cases manifested solely by nonspecific respiratory symptoms. A 50-year-old woman presented with dry cough and dyspnea for 2 weeks. Chest computed tomography (CT) revealed diffuse interlobular septal and fissural thickening with perilymphatic and subpleural nodular opacities, suggesting pulmonary lymphangitic spread of metastatic carcinoma. Bone scintigraphy and positron emission tomography/CT showed multiple skeletal and lymph node involvement. The patient underwent surgical lung biopsy and the pathologic feature was consistent with ECD. We describe this case to emphasize that ECD should be included in the differential diagnosis of cases suspected to have lymphangitic lung carcinomatosis. Moreover, the findings of positron emission tomography/CT scan, which showed hot uptakes in the affected areas, are also described.

Clinical implications of discrepant results between genotypic MTBDRplus and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients.

BACKGROUND: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype-phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF). METHODS: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDRplus test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital. RESULTS: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrug-resistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti-TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF. CONCLUSIONS: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy.

The relationship between sleep disturbance and health status in patients with COPD.

Introduction: The detection of insomnia in patients with COPD is assumed to be significantly lower than the actual prevalence. In this study, we investigated the prevalence of insomnia and the relationship between insomnia and health status in patients with COPD using two fairly simple and straightforward questionnaires: COPD assessment test (CAT) and insomnia severity index (ISI). Patients and methods: A cross-sectional study was conducted using data from patients undergoing treatment for COPD at St Paul's Hospital, The Catholic University of Korea, between December 2015 and August 2016. Patients were classified into three groups according to the ISI score: a "clinical insomnia" group (ISI≥15), a "subthreshold insomnia" group (ISI 8-15), and a "non-insomnia" group (ISI<8). Clinical parameters including past medical history, pulmonary function tests, and questionnaire data were collected and analyzed. Results: A total of 192 patients were recruited, of which 25.0% were found to have clinical insomnia (ISI≥8). Insomnia severity was related to all CAT component items except for cough, and patients with higher CAT scores generally had more severe insomnia. Logistic regression analysis revealed that CAT score was significantly associated with insomnia in these patients (odds ratio, 1.23; 95% CI, 1.13-1.34; p<0.0001). CAT score was also a significant predictor of insomnia (area under receiver operating characteristic curve, 0.779; p<0.001). The optimal predictive cutoff value was a CAT score >14, giving a sensitivity and specificity of 66.7% and 71.5%, respectively. Conclusion: CAT score was closely related to insomnia severity in patients with COPD. The use of CAT scores to assess for the presence and severity of insomnia in these patients may allow for better detection and management and improve clinical practice.

Combination of carboplatin and intermittent normobaric hyperoxia synergistically suppresses benzo[a]pyrene-induced lung cancer.

BACKGROUND/AIMS: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. METHODS: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. RESULTS: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. CONCLUSIONS: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.

Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways.

BACKGROUND: Nitric oxide (NO) is generally increased during inflammatory airway diseases. This increased NO stimulates the secretion of mucin from the goblet cell and submucosal glands but the mechanism is still unknown precisely. In this study, we investigated potential signaling pathways involving protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in the NO-induced MUC5AC mucin gene and protein expression in A549 cells. METHODS: Nitric oxide was donated to the A549 cells by NOR-1. MUC5AC mucin levels were assayed by enzyme-linked immunosorbent assay (ELISA). MUC5AC promoter activity was determined by measuring luciferase activity after the lysing the transfected cells. Activation of PKC isoforms were measured by assessing the distribution of the enzyme between cytosolic and membrane fractions using immunoblotting. Immunoblotting experiments using a monoclonal antibody specific to PKC isoforms were performed in the cytosol and membrane fractions from A549 cells. Western blot analysis for pERK and p38 were performed using the corresponding antibodies from the cell lysates after donating NO to the A549 cells by NOR-1. RESULTS: The transcriptional activity of MUC5AC promoter was maximal at the concentration of 0.1 mM NOR-1 for 1 hour incubation in transfected A549 cells. (+/-)-(E)-methyl-2-((E)-hydroxyimino)-5-nitro-6-methoxy-3-hexenamide (NOR-1) markedly displaced the protein kinase C (PKC)alpha and PKCdelta from the cytosol to the membrane. Furthermore, the PKC-alpha,betainhibitors, GO6976 (10 nM) and PKCdelta inhibitors, rottlerin (4 muM) inhibited the NOR-1 induced migration of PKCalpha and PKCdelta respectively. NOR-1 also markedly increased the MUC5AC promoter activity and mRNA expression, mucin synthesis and ERK1/2 phosphorylation. The PKC inhibitors also inhibited the NOR-1 induced MUC5AC mRNA and MUC5AC protein synthesis by inhibiting the activation of PKCalpha and PKCdelta with ERK1/2 pathways. CONCLUSION: Exogenous NO induced the MUC5AC mucin gene and protein through the PKCalpha and PKCdelta-ERK pathways in A549 cells. Inhibition of PKC attenuated NO-mediated MUC5AC mucin synthesis. In view of this findings, PKC inhibitors might be useful in the treatment of bronchial asthma and chronic bronchitis patients where NO and mucus are increased in the bronchial airways.

Demographic Changes in Intensive Care Units in Korea over the Last Decade and Outcomes of Elderly Patients: A Single-Center Retrospective Study.

BACKGROUND: Aging is a significant issue worldwide, and Korea is one of the most rapidly aging countries. Along with the demographic transition, the age structure of intensive care unit (ICU) patients changes as well. METHODS: The aim of this study was to analyze the change in age distribution of the ICU patients over the last 10 years and its effect on clinical outcomes. Single-center, retrospective analysis of all patients aged ≥18 years admitted to either the medical or surgical ICU at St. Paul's Hospital, The Catholic University of Korea, between January 2005 and December 2014 was conducted. For clinical outcome, in-hospital mortality, duration of ICU stay, and hospital stay were analyzed. Cost analysis was performed to show the economic burden of each age strata. RESULTS: A total of 10,366 ICU patients were admitted to the chosen ICUs during the study period. The proportion of elderly patients aged ≥65 years increased from 47.9% in 2005 to 63.7% in 2014, and the proportion of the very elderly patients aged ≥80 years increased from 12.8% to 20.7%. However, this increased proportion of elderly patients did not lead to increased in-hospital mortality. The percent of ICU treatment days attributable to elderly patients increased from 51.1% in year 2005 to 64.0% in 2014. The elderly ICU patients were associated with higher in-hospital mortality compared to younger age groups. CONCLUSIONS: The proportion of elderly patients admitted to ICUs increased over the last decade. However, overall in-hospital mortality has not increased during the same period.

Factors Related to the Diagnostic Yield of Flexible Bronchoscopy without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions.

BACKGROUND: We aimed to analyze the factors predicting the diagnostic performance of flexible bronchoscopy without guidance in peripheral lung lesions that are endoscopically invisible. METHODS: This was a retrospective study conducted in St. Paul's Hospital, The Catholic University of Korea, between January 2007 and March 2013. We included all patients who received bronchoscopy during this period. The analyzed variables were age, sex, the etiology of the lesion, lesion size, distance from the pleura, and presence of the bronchus sign. We used multiple logistic regression analysis to identify the significant independent factors associated with diagnostic yield. RESULTS: We included 151 patients in this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for malignant disease and 78.1% for benign disease. The benign lung lesions (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors influencing the yield of flexible bronchoscopy by univariate analysis. In a multivariate logistic regression analysis, the exposed type of bronchus sign and benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95; 95% confidence interval [CI], 7.56-103.32; p<0.001 and OR, 4.91; 95% CI, 1.76-13.72; p=0.002). CONCLUSION: The presence of the exposed type of bronchus sign and benign lung lesions are determining factors of the diagnostic yield in flexible bronchoscopy in evaluating peripheral lesions that are not endoscopically visible.

Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer.

PURPOSE: To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. RESULTS: In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. CONCLUSION: Dyspnea could be a significant prognostic factor in patients with NSCLC.

Epidemiology of chronic thromboembolic pulmonary hypertension in Korea: results from the Korean registry.

BACKGROUND/AIMS: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is difficult for numerous reasons and is related with a poor prognosis. In Korea, the incidence of CTEPH and its clinical features are unknown. Thus, in this study, we evaluated the clinical characteristics and outcomes of CTEPH in a Korean cohort. METHODS: This study included South Korean patients diagnosed with CTEPH between September 2008 and October 2011. Baseline characteristics, treatments and outcomes were analyzed. RESULTS: A total of 134 patients were included in this study with 76 females (56.7%). Their median age was 58.3 ± 15.9 years and dyspnea (112 patients, 83.5%) was the most common presenting symptom. Sixty-three patients (47%) had a history of acute pulmonary embolism or deep vein thrombosis, and six (4.5%) had pulmonary tuberculosis. In total, 28 patients (21%) underwent pulmonary thromboendarterectomy (PTE), and 99 patients had medical therapy. During the study period, 18 patients (13.4%) died. In a multivariate analysis, higher hemoglobin (relative risk [RR], 1.516; 95% confidence interval [CI], 1.053 to 2.184; p = 0.025) and lower total cholesterol levels (RR, 0.982; 95% CI, 0.965 to 0.999; p = 0.037) were associated with increased mortality. CONCLUSIONS: This was the first national cohort study of Korean patients with CTEPH. Accurate diagnosis, characterization and distributions of CTEPH are imperative for prompt treatment in patients, particularly those undergoing PTE.

Efficacy of team-based financial incentives for smoking cessation in the workplace.

Worksite smoking cessation programs offer accessibility of the target population, availability of occupational health support, and the potential for peer pressure and peer support. The purpose of this study was to identify the efficacy of the financial incentives given to various teams in the workplace. St. Paul's Hospital's employees were enrolled. Each team of employees consisted of smoking participants and non-smoking fellow workers from the same department. The financial incentive of 50000 won (about $45) was rewarded to the team for each successful participant-not to individual members-after the first week and then after one month. If the smokers in the team remained abstinent for a longer time period, the team was given an incentive of 100000 won for each successful participant after 3 and 6 months. A total 28 smoking participants and 6 teams were enrolled. Self-reported abstinence rates validated by urinary cotinine test at 3, 6, and 12 months after the initial cessation were 61%, 54%, and 50%, respectively. Smokers with high nicotine dependence scores or those who began participation 1 month after enrollment initiation had a lower abstinence rate at 3 months, but not at 6 and 12 months. Participants who succeeded at smoking cessation at 12 months were more likely to be older and have a longer smoking duration history. The financial incentives given to teams could be promising and effective to improve long-term rates of smoking cessation. This approach could use peer pressure and peer support in the workplace over a longer period.

Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin.

Although carboplatin is one of the standard chemotherapeutic agents for non-small cell lung cancer (NSCLC), it has limited therapeutic efficacy due to activation of a survival signaling pathway and the induction of multidrug resistance. Curcumin, a natural compound isolated from the plant Curcuma longa, is known to sensitize tumors to different chemotherapeutic agents. The aim of this study is to evaluate whether curcumin can chemosensitize lung cancer cells to carboplatin and to analyze the signaling pathway underlying this synergism. We investigated the synergistic effect of both agents on cell proliferation, apoptosis, invasion, migration, and expression of related signaling proteins using the human NSCLC cell line, A549. A549 cell was treated with different concentrations of curcumin and carboplatin alone and in combination. Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. Matrix metalloproteinase (MMP)-2 and MMP-9 were more efficiently downregulated by co-treatment than by each treatment alone. mRNA and protein expression of caspase-3 and caspase-9 and proapoptotic genes was increased in cells treated with a combination of curcumin and carboplatin, whereas expression of the antiapoptotic Bcl-2 gene was suppressed. Co-treatment of both agents substantially suppressed NF-κB activation and increased expression of p53. Phosphorylation of Akt, a protein upstream of NF-κB, was reduced, resulting in inhibition of the degradation of inhibitor of κB(IκBα), whereas the activity of extracellular signal-regulated kinase (ERK1/2) was enhanced. Our study demonstrated that the synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-κB via inhibition of the Akt/IKKα pathway and enhanced ERK1/2 activity. Based on this mechanism, curcumin has potential as a chemosensitizer for carboplatin in the treatment of patients with NSCLC.

Serious Complications after Self-expandable Metallic Stent Insertion in a Patient with Malignant Lymphoma.

An 18-year-old woman was evaluated for a chronic productive cough and dyspnea. She was subsequently diagnosed with mediastinal non-Hodgkin lymphoma (NHL). A covered self-expandable metallic stent (SEMS) was implanted to relieve narrowing in for both main bronchi. The NHL went into complete remission after six chemotherapy cycles, but atelectasis developed in the left lower lobe 18 months after SEMS insertion. The left main bronchus was completely occluded by granulation tissue. However, the right main bronchus and intermedius bronchus were patent. Granulation tissue was observed adjacent to the SEMS. The granulation tissue and the SEMS were excised, and a silicone stent was successfully implanted using a rigid bronchoscope. SEMS is advantageous owing to its easy implantation, but there are considerable potential complications such as severe reactive granulation, stent rupture, and ventilation failure in serious cases. Therefore, SEMS should be avoided whenever possible in patients with benign airway disease. This case highlights that SEMS implantation should be avoided even in malignant airway obstruction cases if the underlying malignancy is curable.

Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD.

BACKGROUND: Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD. PATIENTS AND METHODS: In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed. RESULTS: Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20-6.48, P=0.018) compared with carriers in the dominant model. CONCLUSION: Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD.