Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 µg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 µg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

A cross-sectional study of SARS-CoV-2 antibodies among healthcare workers in a tertiary care hospital in Taiwan: implications for protection against the Omicron variants.

BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.

Survival Comparison Between Open and Thoracoscopic Upfront Esophagectomy in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: The survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) after open or thoracoscopic upfront esophagectomy remained unclear. OBJECTIVE: The aim of this retrospective study was to compare overall survival between open and thoracoscopic esophagectomy for ESCC patients without neoadjuvant chemodatiotherapy (CRT). METHODS: The Taiwan Cancer Registry was investigated for ESCC cases from 2008 to 2016. We enrolled 2053 ESCC patients receiving open (n = 645) or thoracoscopic (n = 1408) upfront esophagectomy. One-to-two propensity score matching between the two groups was performed. Stage-specific survival was compared before and after propensity score matching. Univariate analysis and multivariate analysis were used to identify risk factors. RESULTS: After one-to-two propensity score matching, a total of 1299 ESCC patients with comparable clinic-pathologic features were identified. There were 433 patients in the open group and 866 patients in the thoracoscopic group. The 3-year overall survival of matched patients in the thoracoscopic group was better than that of matched patients in the open group (58.58% vs 47.62%, P = 0.0002). Stage-specific comparisons showed thoracoscopic esophagectomy is associated with better survival than open esophagectomy in patients with pathologic I/II ESCC. In multivariate analysis, surgical approach was still an independent prognostic factor before and after one-to-two propensity score matching. CONCLUSION: This propensity-matched study revealed that thoracoscopic esophagectomy could provide better survival than open esophagectomy in ESCC patients without neoadjuvant CRT.

Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study.

BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.

Survival Comparison Among Neoadjuvant Chemoradiotherapy Followed by Esophagectomy, Definitive Chemoradiotherapy, and Esophagectomy Alone for Esophageal Squamous Cell Carcinoma.

BACKGROUND: For patients with locoregional esophageal squamous cell carcinoma (ESCC), survival outcomes among neoadjuvant chemoradiotherapy followed by operation (nCRT-OP), definitive chemoradiotherapy (dCRT), and esophagectomy alone remain controversial. PATIENTS AND METHODS: Information from the 2008-2016 Taiwan Cancer Registry was used. A total of 7637 cT1b-4, N0/+, M0 ESCC patients receiving nCRT-OP (n = 1955), dCRT (n = 4122), or esophagectomy alone (n = 1560) were included. Propensity score matching was performed to balance clinical variables among the three groups. Stage-specific overall survival was compared before and after propensity score matching. Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Propensity score matching resulted in 1407 cases for comparison. The 5-year overall survival rates for matched patients treated via dCRT, nCRT-OP, and esophagectomy alone were 19.77%, 31.23%, and 30.52%, respectively (p < 0.001). On multivariable analysis, treatment modality was still an independent prognostic factor both before and after propensity score matching. nCRT-OP and esophagectomy alone were associated with significantly better overall survival than dCRT for locoregional ESCC patients. CONCLUSIONS: This propensity-matched study revealed that nCRT-OP and esophagectomy provided better survival than dCRT in cT1b-4, N0/+, M0 ESCC patients.

miR-145-5p Targets Sp1 in Non-Small Cell Lung Cancer Cells and Links to BMI1 Induced Pemetrexed Resistance and Epithelial-Mesenchymal Transition.

Pemetrexed is a folic acid inhibitor used as a second-line chemotherapeutic agent for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancers. However, prolonged treatment with pemetrexed may cause cancer cells to develop resistance. In this study, we found increased expressions of BMI1 (B Lymphoma Mo-MLV insertion region 1 homolog) and Sp1 and a decreased expression of miR-145-5p was found in pemetrexed-resistant A400 cells than in A549 cells. Direct Sp1 targeting activity of miR-145-5p was demonstrated by a luciferase based Sp1 3'-UTR reporter. Changed expression of miR-145-5p in A400 or A549 cells by transfection of miR-145-5p mimic or inhibitor affected the sensitivity of the cells to pemetrexed. On the other hand, the overexpression of Sp1 in A549 cells caused the decreased sensitivity to pemetrexed, induced cell migratory capability, and epithelial-mesenchymal transition (EMT) related transcription factors such as Snail Family Transcriptional Repressor 1 and Zinc Finger E-Box Binding Homeobox 1. In addition, the overexpression of BMI1 in the A549 cells resulted in an increase in Sp1 and a decrease in miR-145-5p accompanied by the elevations of cell proliferation and EMT transcription factors, which could be reduced by the overexpression of miR-145-5p or by treatment with the Sp1 inhibitor of mithramycin A. In conclusion, the results of this study suggest that the downregulation of miR-145-5p by BMI1 overexpression could lead to the enhanced expression of Sp1 to induce the EMT process in pemetrexed-resistant NSCLC cells. These results suggest that increasing miR-145-5p expression by delivering RNA drugs may serve as a sensitizing agent for pemetrexed-resistant NSCLC patients.

Update on guidelines for the treatment of COPD in Taiwan using evidence and GRADE system-based recommendations.

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.

Particulate matter of 2.5 µm or less in diameter disturbs the balance of TH17/regulatory T cells by targeting glutamate oxaloacetate transaminase 1 and hypoxia-inducible factor 1α in an asthma model.

BACKGROUND: Epidemiologic evidence suggests that exposure to particulate matter of 2.5 µm or less in diameter (PM2.5) aggravates asthma. OBJECTIVE: We sought to investigate the underlying mechanisms between PM2.5 exposure and asthma severity. METHODS: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4+ T cell-specific aryl hydrocarbon receptor (AhR)-null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of TH17/regulatory T (Treg) cells were investigated by using flow cytometry and quantitative RT-PCR. Mechanisms were investigated by using mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing, and glycolysis rates. RESULTS: PM2.5 impaired differentiation of Treg cells, promoted differentiation of TH17 cells, and aggravated asthma in an AhR-dependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of TH17 cells by upregulating hypoxia-inducible factor 1α expression and enhancing glycolysis through AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase 1 (Got1) expression through AhRs and accumulation of 2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase 2 activity, resulting in hypermethylation in the forkhead box P3 locus and impaired differentiation of Treg cells. A GOT1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of TH17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on TH17/Treg cell imbalance were noted in human T cells, and in a case-control design PAH exposure appeared to be a potential risk factor for asthma. CONCLUSIONS: The AhR-hypoxia-inducible factor 1α and AhR-GOT1 molecular pathways mediate pulmonary responses on exposure to PM2.5 through their ability to disturb the balance of TH17/Treg cells.

Comparison of Treatment Strategies for Patients With Clinical Stage T1-3/N2 Lung Cancer.

BACKGROUND: The therapeutic strategies for clinical stage T1-3N2 (cT1-3N2) lung cancer are controversial. For operable tumors, treatment can vary by center, region, and continent. This study aimed to identify the optimal therapeutic method and type of surgical strategy for cT1-3N2 lung cancer. METHODS: This retrospective evaluation analyzed the records of 17,954 patients with cT1-3N2 lung cancer treated in 2010 through 2015 from the SEER database. The effects of different therapeutic methods and types of surgical strategies on overall survival (OS) were assessed. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: The 5-year OS rates were 27.7% for patients with T1N2 disease, 21.8% for those with T2N2 disease, and 19.9% for T3N2 disease. Neoadjuvant therapy plus operation (OP) plus adjuvant therapy, and OP plus adjuvant therapy, provided better 5-year OS rates than OP alone or concurrent chemoradiotherapy (34.1%, 37.7%, 29.3%, and 16.1%, respectively). In the T1N2, T2N2, and T3N2 groups, lobectomy provided better 5-year OS than pneumonectomy, sublobectomy, and no surgery. Both univariate and multivariate analyses showed that young age, female sex, well-differentiated histologic grade, adenocarcinoma cell type, neoadjuvant and adjuvant therapy, lobectomy, and T1 stage were statistically associated with better 5-year OS rates. CONCLUSIONS: In cT1-3N2 lung cancer, multimodal treatments tended to provide better 5-year OS than OP alone or concurrent chemoradiotherapy. In addition, lobectomy was associated with better survival than other operative methods.

Comparison between COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores for evaluation of clinical symptoms, comorbidities and medical resources utilization in COPD patients.

BACKGROUND: The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed a new severity assessment system for emphasizing clinical symptom evaluation by COPD Assessment Test (CAT) or modified Medical Research Council (mMRC) dyspnea scores. The aim of the study was to evaluate the effectiveness of two scoring systems in evaluating COPD patients. METHODS: A population based cross-sectional study employing computer-assisted telephone interviewing system (CATI) for surveying the epidemiology of COPD in Taiwan. Among 6600 subjects recruited (age > 40), 404 subjects (6.1%) were diagnosed as COPD. The comorbidities, COPD-related symptoms, health care resources utilization were compared between CAT and mMRC. RESULTS: There were significant differences in all co-morbidities, symptom severity in favor of CAT as compared to mMRC. When comparing health care resources utilization, CAT and mMRC have equal effectiveness in evaluating patients with regular medical treatment. There were significant differences in emergency room visit and hospitalization in favor of mMRC. However, CAT was more effective in evaluating patients with ICU admission (P = 0.005). CONCLUSION: Compared with CAT and mMRC, there are individual benefits in the evaluation of clinical symptoms, co-morbidities and medical resources utilization for ER, hospitalization and ICU admission in COPD patients.

Long-acting ß2-adrenoreceptor agonists suppress type 1 interferon expression in human plasmacytoid dendritic cells via epigenetic regulation.

The combination of inhaled long-acting ß2-adrenoreceptor (LABA) and inhaled glucocorticoid (ICS) is a major therapy for asthma. However, the increased risk of infection is still a concern. Plasmacytoid dendritic cells (pDCs) are the predominant cells producing type 1 interferon (IFN) against infection. The effect of LABA/ICS on type 1 IFN expression in human pDCs is unknown. Circulating pDCs were isolated from healthy human subjects and were pretreated with glucocorticoid (GCS), LABA or a cAMP analog, and were stimulated with Toll-like receptor (TLR) agonist CpG (TLR9) or imiquimod (TLR7) in the presence of IL-3. The expression of type 1 IFN (IFN-α/ß) were measured by ELISA. The mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting and chromatin immunoprecipitation. GCS suppressed TLR-induced IFN-α expression, and LABA enhanced the suppressive effect. LABA alone also suppressed TLR-induced IFN-α/ß expression, and the effect was reversed by the ß2-adrenoreceptor antagonist ICI118551. Dibutyryl-cAMP, a cAMP analog, conferred a similar suppressive effect, and the effect was abrogated by the exchange protein directly activated by cAMP (Epac) inhibitor HJC0197 or intracellular free Ca2+ chelator BAPTA-AM. Formoterol suppressed TLR-induced phosphorylation of mitogen-activated protein kinase (MAPK)-p38/ERK. Formoterol suppressed interferon regulatory factor (IRF)-3/IRF-7 expression. Formoterol suppressed CpG-induced translocation of H3K4 specific methyltransferase WDR5 and suppressed H3K4 trimethylation in the IFNA and IFNB gene promoter region. LABA suppressed TLR7/9-induced type 1 IFNs production, at least partly, via the ß2-adrenoreceptor-cAMP-Epac-Ca2+, IRF-3/IRF-7, the MAPK-p38/ERK pathway, and epigenetic regulation by suppressing histone H3K4 trimethylation through inhibiting the translocation of WDR5 from cytoplasm to nucleus. LABA may interfere with anti-viral immunity.

The effects of asthma medications on reactive oxygen species production in human monocytes.

OBJECTIVE: Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promotes the production of reactive oxygen species (ROS) leading to airway inflammation, hyper-responsiveness, and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long-acting ß2 agonists (LABAs; salmeterol and formoterol), and a new extra-LABA (indacaterol). METHODS: The human monocyte cell line THP-1 cells were pre-treated with different concentrations of the asthma medications at different time points after hydrogen peroxide (H2O2) stimulation. H2O2 production was measured with DCFH-DA by flow cytometry. RESULTS: Montelukast, fluticasone, and salmeterol suppressed H2O2-induced ROS production. Indacaterol enhanced H2O2-induced ROS production. Budesonide and formoterol alone had no anti-ROS effects, but the combination of these two drugs significantly suppressed H2O2-induced ROS production. CONCLUSIONS: Different asthma medications have different anti-ROS effects on monocytes. The combination therapy with LABA and ICS seemed not to be the only choice for asthma control. Montelukast may also be a good supplemental treatment for the poorly controlled asthma because of its powerful anti-ROS effects. Our findings provide a novel therapeutic view in asthma.

High-frequency power of heart rate variability can predict the outcome of thoracic surgical patients with acute respiratory distress syndrome on admission to the intensive care unit: a prospective, single-centric, case-controlled study.

BACKGROUND: The morbidity and mortality of acute respiratory distress syndrome (ARDS) remains high, and the strategic focus of ARDS research has shifted toward identifying patients at high risk of mortality early in the course of illness. This study intended to identify the heart rate variability (HRV) measure that can predict the outcome of patients with ARDS on admission to the surgical intensive care unit (SICU). METHODS: Patients who had lung or esophageal cancer surgery were included either in the ARDS group (n = 21) if they developed ARDS after surgery or in the control group (n = 11) if they did not. The ARDS patients were further stratified into survivors and non-survivors subgroups according to their outcomes. HRV measures of the patients were used for statistical analysis. RESULTS: The mean RR interval (mRRI), high-frequency power (HFP) and product of low-/high-frequency power ratio tidal volume and tidal volume (LHR*VT) were significantly lower (p < 0.05), while the normalized HFP to VT ratio (nHFP/VT) was significantly higher in the ARDS patients (p = 0.011). The total power (TP), low-frequency power (LFP), HFP and HFP/VT were all significantly higher in the non-survived ARDS patients, whereas Richmond Agitation-Sedation Scale (RASS) was significantly lower in the non-survived ARDS patients. After adjustment for RASS, age and gender, firth logistic regression analysis identified the HFP, TP as the significant independent predictors of mortality for ARDS patients. CONCLUSIONS: The vagal modulation of thoracic surgical patients with ARDS was enhanced as compared to that of non-ARDS patients, and the non-survived ARDS patients had higher vagal activity than those of survived ARDS patients. The vagal modulation-related parameters such as TP and HFP were independent predictors of mortality in patients with ARDS on admission to the SICU, and the HFP was found to be the best predictor of mortality for those ARDS patients. Increased vagal modulation might be an indicator for poor prognosis in critically ill patients following thoracic surgery.

Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells.

Epidermal growth factor receptor (EGFR) mutations have been identified in approximately 55% of lung cancer patients in Taiwan. Gefitinib (Iressa) and Erlotinib (Tarceva) are the first-generation targeting drugs to patients with EGFR gene mutants a work by inhibiting tyrosine kinase activity. However, resistance in EGFR-mutated patients to first-generation tyrosine kinase inhibitor (TKI) therapy after 8-11 months of treatment has occurred. Betulinic acid (BetA) is a pentacyclic triterpenoid natural product derived from widespread plants. BetA has been reported to have a cytotoxic effect in several cancers. The purpose of this study is to investigate the effects and mechanisms of BetA on dampening EGFR TKI-resistance of lung cancer cells. Our study has demonstrated by MTT assay that combining BetA and an EGFR TKI increased the cytotoxicity against EGFR TKI-resistance lung cancer cells. Based on flow cytometry, combination treatments of BetA with an EGFR TKI enhanced Sub-G1 accumulation, induced apoptosis and induced mitochondrial membrane potential loss. Using western blotting, BetA and EGFR TKI combined treatments inhibited cell cycle related protein and triggered apoptosis- and autophagy- related protein expression. Taken together, our data suggests that a target therapy combining BetA with an EGFR TKI improves drug efficacy in EGFR TKI-resistant lung cancer cells.

Comparative efficacy and tolerability of beclomethasone/formoterol and fluticasone/salmeterol fixed combination in Taiwanese asthmatic patients.

BACKGROUND: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients. METHODS: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared. RESULTS: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group. CONCLUSION: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F.

Lobocrassin B Induces Apoptosis of Human Lung Cancer and Inhibits Tumor Xenograft Growth.

Lobocrassin B, a natural cembrane-type compound isolated from the soft coral Lobophytum crassum, has been shown to have significant biological effects, including anticancer activity. As the most common cause of cancer mortality worldwide, lung cancer remains a major concern threatening human health. In the current study, we conducted in vitro experiments to demonstrate the inhibiting effect of Lobocrassin B on CL1-5 and H520 human lung cancer cells growth and to explore the underlying mechanisms, as well as in nude mice bearing CL1-5 tumor xenografts. Lobocrassin B exerted cytotoxic effects on lung cancer cells, as shown by decreasing cell viability, and inducing apoptosis, oxidative stress and mitochondrial dysfunction. In addition, the increased level of Bax, cleaved caspase-3, -9 and -8, and the suppression of Bcl-2 were observed in the Lobocrassin B treated cells. Moreover, in vivo assays verified the significance of these results, revealing that Lobocrassin B inhibited CL1-5 tumor xenograft growth and that inhibitory effects were accompanied by a marked increase in tumor cell apoptosis. In conclusion, the results suggested that Lobocrassin B could be a potential anticancer compound for its propensity to inhibit growth and induce apoptosis in human lung cancer cells.

Left-Right Asymmetry in Spectral Characteristics of Lung Sounds Detected Using a Dual-Channel Auscultation System in Healthy Young Adults.

Though lung sounds auscultation is important for the diagnosis and monitoring of lung diseases, the spectral characteristics of lung sounds have not been fully understood. This study compared the spectral characteristics of lung sounds between the right and left lungs and between healthy male and female subjects using a dual-channel auscultation system. Forty-two subjects aged 18-22 years without smoking habits and any known pulmonary diseases participated in this study. The lung sounds were recorded from seven pairs of auscultation sites on the chest wall simultaneously. We found that in four out of seven auscultation pairs, the lung sounds from the left lung had a higher total power (PT) than those from the right lung. The PT of male subjects was higher than that of female ones in most auscultation pairs. The ratio of inspiration power to expiration power (RI/E) of lung sounds from the right lung was greater than that from the left lung at auscultation pairs on the anterior chest wall, while this phenomenon was reversed at auscultation pairs on the posterior chest wall in combined subjects, and similarly in both male and female subjects. Though the frequency corresponding to maximum power density of lung sounds (FMPD) from the left and right lungs was not significantly different, the frequency that equally divided the power spectrum of lung sounds (F50) from the left lung was significantly smaller than that from the right lung at auscultation site on the anterior and lateral chest walls, while it was significantly larger than that of from the right lung at auscultation site on the posterior chest walls. In conclusion, significant differences in the PT, FMPD, F50, and RI/E between the left and right lungs at some auscultation pairs were observed by using a dual-channel auscultation system in this study. Structural differences between the left and the right lungs, between the female and male subjects, and between anterior and posterior lungs might account for the observed differences in the spectral characteristics of lung sounds. The dual-channel auscultation system might be useful for future development of digital stethoscopes and power spectral analysis of lung sounds in patients with various kinds of cardiopulmonary diseases.

A Population-Based Cost Analysis of Thoracoscopic Versus Open Lobectomy in Primary Lung Cancer.

BACKGROUND: Thoracoscopic lobectomy for primary lung cancer has become increasingly popular worldwide due to several advantages over open lobectomy including reduced pain, reduced length of hospital stay, and comparable oncologic outcomes. The costs of thoracoscopic versus conventional open lobectomy have been compared in several studies with variable results. We compared the costs of thoracoscopic versus open lobectomy in lung cancer patients in Taiwan. METHODS: Patients who underwent lobectomy for primary lung cancer from the Taiwan National Health Insurance Research Database (NHIRD) between 2004 and 2010 were identified. Patient characteristics, operative data, and costs for each part of the hospitalization for surgery and 30 days of care after discharge were analyzed. RESULTS: A total of 5366 patients with complete clinical data who underwent either conventional open lobectomy (n = 3166, 59 %) or thoracoscopic lobectomy (n = 2200, 41 %) for primary lung cancer were identified from the database. Compared with open lobectomy, thoracoscopic lobectomy was associated with younger age, less comorbidity, shorter anesthesia times, and reduced lengths of hospital stay. Total hospital costs, operative costs, and other costs were significantly higher in the thoracoscopic group. The 30-day after discharge costs were significantly lower in the thoracoscopic group. CONCLUSIONS: Thoracoscopic lobectomy for primary lung cancer in Taiwan was associated with higher total hospital costs but lower 30 days after discharge costs than open lobectomy. These differences may have resulted from higher operative and instrument costs in the thoracoscopic group.

Chidamide alleviates TGF-ß-induced epithelial-mesenchymal transition in lung cancer cell lines.

Transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition is a critical process in the initiation of metastasis of various types of cancer. Chidamide is a class I histone deacetylase inhibitor with anti-tumor activity. This study investigated the effects of chidamide on TGF-ß-mediated suppression of E-cadherin expression in adenocarcinomic lung epithelial cells and the molecular mechanisms involved in these effects. Western blot analysis, confocal microscopy, Quantitative methyl-specific PCR and bisulfite sequencing were used to evaluate the effects of different treatments on chidamide ameliorating TGF-ß induced-E-cadherin loss. H3 acetylation binding to the promoter of E-cadherin was detected by chromatin immunoprecipitations (CHIP). We found that chidamide reduced the level of lung cancer cell migration observed using a Boyden chamber assay (as an indicator of metastatic potential). Chidamide inhibited TGF-ß-induced SMAD2 phosphorylation and attenuated TGF-ß-induced loss of E-cadherin expression in lung cancer cells by Western blotting and confocal microscopy, respectively. Quantitative methyl-specific PCR and bisulfite sequencing revealed that TGF-ß-enhanced E-cadherin promoter methylation was ameliorated in cells treated with chidamide. We demonstrated that histone H3 deacetylation within the E-cadherin promoter was required for TGF-ß-induced E-cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-ß suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF-ß-treated cells and inhibited lung cancer cell migration. These findings indicate that chidamide has a potential therapeutic use due to its capacity to prevent cancer cell metastasis.