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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.

Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥ 291cells/μL), and serum tryptase (≤ 1448 pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥ 25 pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP potentially played the pathogenic role across different asthma phenotypes. TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.

Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04–10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29–80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04–4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02–11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02–11.65)], oral atenolol [RR = 0.51 (95% CI 0.20–1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03–25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08–10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma.Trial registration: PROSPERO CRD42020190540.

Shih-Lung Cheng,1,2 Hsu Hui Wang,1 Ching-Hsiung Lin3–5 1Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, 2Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan, 3Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, 4Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, 5School of Medicine, Chung Shan Medical University, Taichung, Taiwan Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder encompassing different phenotypes with different responses to treatment. The present 1-year, two-center hospital-based study investigated whether the plasma immunoglobulin E (IgE) level and/or eosinophil cell count could be used as biomarkers to stratify patients with COPD according to predicted responses to inhaled corticosteroids (ICS)-based therapy. Methods: A hospital-data based cohort study of COPD patients treated at two territory hospital centers was conducted for 1 year. Allergic biomarkers, including blood eosinophil counts and IgE levels, were assessed at baseline. Lung function parameters, including forced expiratory volume in 1second (FEV1), forced vital capacity (FVC), and the COPD Assessment Test (CAT), were also evaluated. The frequencies of acute exacerbation (AE) and pneumonia were also measured. Eosinophilia and a high IgE level were defined as >3% and 173 IU/mL, respectively. Results: A total of 304 patients were included. Among patients with eosinophilia and high IgE levels, ICS-based therapy was associated with significant improvements in FEV1, FVC, and CAT scores, compared with bronchodilator (BD) therapy (P≤0.042). ICS-based therapy was also associated with a significantly lower incidence of AE vs BD-based therapy (11.7% vs 24.1%; P

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015&ndash, 4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022&ndash, 2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250&ndash, 2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

Asthma is a leading allergic disease worldwide, demonstrating an ever‑increasing prevalence over the past two decades. Asthma is characterized by allergen‑associated airway hyperresponsiveness (AHR) that primarily results from T helper 2 (Th2) cell inflammation, in which dendritic cells (DCs) serve an important role in determining T cell development after encountering an antigen. Atractylodin (ATL), a polyethene alkyne extracted from Atractylodis rhizoma (also known as Cangzhu), has proven effective in treating digestive disorders, rheumatic disease and influenza. In addition, ATL was discovered to alleviate mouse collagen‑induced arthritis via regulating DC maturation. The present study aimed to investigate the effect of ATL on asthma given that DCs serve an essential role in Th2‑mediated inflammation in asthma. Mouse model of asthma was induced by ovalbumin (OVA). OVA‑induced airway hyperresponsiveness (AHR) and inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected. The production of IgE and IgG1 in serum and cytokines in BALF were detected by ELISA. The effects of ATL on dendritic cells maturation and T cell expansion were detected by flow cytometry analysis and 3H‑thymidine incorporation. Using a model of OVA‑induced asthma, it was demonstrated that ATL ameliorated AHR and decreased the levels of IL‑4, IL‑5 and IL‑13 in bronchoalveolar lavage fluid (BALF), and OVA‑specific IgE and IgG1 in the serum. OVA‑stimulated splenocytes were used to demonstrated that ATL decreased cell expansion and the production of IL‑4, IL‑5 and IL‑13 in the culture medium. In order to determine the cellular mechanism of ATL in asthma, splenic DCs were isolated and it was subsequently observed that ATL downregulated the expression levels of CD40 and CD80. Furthermore, OVA‑stimulated CD4+ T cells were co‑cultured with splenic DCs, which revealed that ATL‑treated splenic DCs led to impaired cellular proliferation and the production of IL‑4, IL‑5 and IL‑13 in OVA‑stimulated T cells. In conclusion, these results indicated that ATL may suppress antigen‑specific Th2 responses in an OVA‑induced allergic asthma model via regulating DCs. Therefore, ATL may exhibit therapeutic potential in the management of asthma and other allergic diseases presenting with Th2 inflammation.

Sheng-Hao Lin,1,2 Diahn-Warng Perng,3,4 Ching-Pei Chen,5,6 Woei-Horng Chai,1 Chin-Shui Yeh,1 Chew-Teng Kor,7 Shih-Lung Cheng,8,9 Jeremy JW Chen,2,* Ching-Hsiung Lin1,10,11,* 1Department of Internal Medicine, Division of Chest Medicine, Changhua Christian Hospital, Changhua, 2Institute of Biomedical Sciences, National Chung Hsing University, Taichung, 3Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, 4School of Medicine, National Yang-Ming University, Taipei, 5Department of Internal Medicine, Division of Cardiology, Changhua Christian Hospital, 6Department of Beauty Science and Graduate Institute of Beauty Science Technology, Chien-Kuo Technology University, 7Department of Internal Medicine, Internal Medicine Research Center, Changhua Christian Hospital, Changhua, 8Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, 9Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli City, Taoyuan, 10Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, 11School of Medicine, Chung Shan Medical University, Taichung, Taiwan *These authors contributed equally tothiswork Background and objective: COPD patients with community-acquired pneumonia (CAP) have worse clinical outcomes, as compared to those without COPD. Cardiovascular disease (CVD) is a common comorbidity for COPD patients. Whether COPD with comorbid CVD will increase the risk of CAP is not well investigated. The incidence and factors associated with CAP in COPD patients with and without CVD were analyzed. Methods: The medical records of patients with newly diagnosed COPD between 2007 and 2010 were reviewed. The patients’ characteristics, medical history of CVD, occurrence of CAP, and type of medication were recorded. Kaplan–Meier curves were used to assess the differences in cumulative incidence of CAP. Cox’s proportional hazards regression model was used to determine the adjusted hazard ratios with 95% confidence intervals in relation to factors associated with CAP in COPD patients with and without CVD. Results: Among 2,440 patients, 475 patients (19.5%) developed CAP during the follow-up period. COPD patients who developed CAP were significantly older, had lower forced expiratory volume in 1 second, frequent severe exacerbation and comorbid CVD, as well as received inhaled corticosteroid (ICS)-containing therapy than those without CAP. The cumulative incidence of CAP was higher in COPD patients with CVD compared to those without CVD. Patients who received ICS-containing therapy had significantly increased risk of developing CAP compared to those who did not. Conclusion: For patients with COPD, comorbid CVD is an independent risk factor for developingCAP. ICS-containing therapy may increase the risk of CAP among COPDpatients. Keywords: chronic obstructive pulmonary disease, COPD, community-acquired pneumonia, cardiovascular disease, inhaled corticosteroids, CAP, CVD

Background There is a lack of large, prospective, randomized studies comparing thoracoscopic and open lobectomy in terms of long-term survival in the setting of NSCLC. Additionally, large case series evaluating the issue are limited. Until now, whether thoracoscopic lobectomy entails a long-term survival benefit compared with open lobectomy not been determined. Methods Data were obtained from the National Health Insurance Research Database published in Taiwan. We included patients treated with open lobectomy or thoracoscopic lobectomy. In this retrospective review, the clinicopathologic characteristics of 5222 patients with lung cancer during the period 2004–2010 were analyzed. Patients were stratified according to clinical stage. Overall survival (OS) was compared between patients treated with open and those treated with thoracoscopic lobectomy and was also compared between patients in the three different clinical stages. Propensity-matching analysis and multivariate analysis were performed. Results Open lobectomy was performed on 3058 patients (58.6%) and thoracoscopic lobectomy on 2164 (41.4%). Propensity matching produced 1848 patients in each group. The 1-year, 3-year, and 5-year OS rates for propensity-matched patients treated with open lobectomy were 93.4%, 79.3%, and 65.5%, respectively. The 1-year, 3-year, and 5-year OS rates for propensity-matched patients treated with thoracoscopic lobectomy were 94.1%, 80.9%, and 68.7%, respectively. The difference was not statistically significant. In multivariate analysis, surgical resection (open versus thoracoscopic) was not an independent prognostic factor. Conclusions This propensity-matched study suggests that open and thoracoscopic lobectomy are associated with similar long-term survival in the setting of lung cancer. Thoracoscopic lobectomy is an acceptable surgical treatment of lung cancer.

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

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.

Shih-Lung Cheng,1,2 Ming-Cheng Chan,3 Chin-Chou Wang,4 Ching-Hsiung Lin,5 Hao-Chien Wang,6 Jeng-Yuan Hsu,3 Liang-Wen Hang,7,8 Chee-Jen Chang,9 Diahn-Warng Perng,10,* Chong-Jen Yu6,* On behalf of the Taiwan COPD Consortium 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, 2Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li City, Taoyuan County, 3Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 4Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 5Division of Chest Medicine, Changhua Christian Hospital, Changhua City, Changhua County, 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, 7Department of Pulmonary and Critical Care Medicine, Sleep Medicine Center, China Medical University Hospital, 8Department of Respiratory Therapy, College of Health Care, China Medical University, Taichung, 9Biostatistical Center for Clinical Research, Chang Gung Memorial Hospital, Linkou Branch, Guishan Township, Taoyuan County, 10Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Objectives: To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.Methods: We conducted a random cross-sectional national survey of adults older than40years in Taiwan. Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health. Subjects with diagnosed COPD were subdivided by smoking status. Subjects who fulfilled the case definition of COPD and smoked were designated as “possible COPD”. Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits. Data from these groups were analyzed and compared.Results: Of the6,600participants who completed the survey,404(6.1%) fulfilled the epidemiological case definition of COPD:137with diagnosed COPD and267possible COPD. The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%). Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32vs12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01). The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR]1.15,95% confidence interval [CI]1.04–1.26), higher modified Medical Research Council Breathlessness Scale scores (OR1.97,95% CI1.11–3.51), and having more than one comorbidity (OR5.19,95% CI1.05–25.61).Conclusion: With estimated prevalence of6.1% in the general population, COPD in Taiwan has been underdiagnosed. Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD. There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms. Keywords: Asia, COPD, epidemiology, health care utilization, risk factors

The prognosis of esophageal squamous cell carcinoma is poor. In order to find out appropriate treatment for each group of patients, we aim to examine the prognostic factors influencing survival for esophageal cancer patients in Taiwan. Data were obtained from the Taiwan Society of Cancer Registry. There were 14,394 esophageal cancer patients analyzed between 2008 and 2014 in this retrospective review. The impact of the clinicopathologic factors on overall survival was assessed. The following clinic‐pathologic factors were included to analyses: age, sex, tumor location, tumor length, histologic grade, clinical T, clinical N, clinical M, clinical stage, and all therapeutic methods within 3 months after diagnosis. The 5‐year survival rate was 16.8%, with a median survival of 343 days. The distribution of patients by their clinical stage is as follows: stage 0 (n = 162; 1.1%); stage I (n = 964; 6.7%); stage II (n = 2392; 16.6%); stage III (n = 6636; 46.1%); and stage IV (n = 3661; 25.4%). In the multivariate analysis, age, sex, tumor location, tumor length, clinical T, clinical N, clinical M, and treatment remained independent prognostic factors. Our data indicated that age, sex, tumor location, tumor length, clinical T, clinical N, clinical M, and treatment remained independent prognostic factors. Patients who could receive surgery had significantly better outcomes.

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. Keywords: COPD, GOLD guideline, CAT, mMRC

Objectives IFN-γ takes part in immunologic responses to cancer and its interactions with chemotherapy have also been described. Our previous study had showed an association between phytohemagglutinin (PHA)-stimulated IFN-γ (PSIG) response and overall survival in patients with advanced non-small-cell lung cancer (NSCLC). Here, we aimed to evaluate the correlation between PSIG and chemotherapy responses. Materials and methods From January 2011 to August 2012, 340 newly diagnosed patients with lung cancer were enrolled in a prospective latent tuberculosis observational study. Patients with advanced NSCLC who were treated with chemotherapy were included in this analysis. An IFN-γ release assay (IGRA) was used to evaluate pre-treatment PSIG levels. Patients were grouped into low and high PHA response groups according to their PSIG levels. Their demographic characteristics, tumor responses, and survival rates were investigated. Results Eighty-four patients were enrolled. The chemotherapy response rates in the high and low PHA response groups were 45.2% and 35.7% (p = 0.190), respectively. The disease control rate in the high PHA response group was 76.2%, versus 52.4% in the low PHA response group (p = 0. 023). In multivariate analysis, PHA response was an independent predictor of disease control (odds ratio = 3.017, 95% confidence interval = 1.115–8.165). The Kaplan-Meier method demonstrated both longer progression-free survival (p = 0.008) and overall survival (p = 0.003) in the high PHA response group. Conclusions A higher pre-treatment PSIG response, obtained using the IGRA, was associated with better disease control rate and survival among patients with advanced NSCLC treated with chemotherapy.

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. Keywords: Asthma, Combination therapy, Inhaled corticosteroid, Long acting beta2-agonist, Pulmonary hyperinflation

SummaryWe evaluated the predictive value of the COPD assessment test (CAT™) for exacerbation in the following six months or time to first exacerbation among COPD patients with previous exacerbations.COPD outpatients with a history of exacerbation from 19 hospitals completed the CAT questionnaire and spirometry over six months. Exacerbation events were prospectively collected using a structured questionnaire.The baseline CAT score categorised into four groups (0–9, 10–19, 20–29, and 30–40) showed strong prediction for time to first exacerbation and modest prediction for any exacerbation or moderate-severe exacerbation (AUC 0.83, 0.64, and 0.63 respectively). In multivariate analyses, the categorised CAT score independently predicted all three outcomes (p = 0.001 or p 24, 14, 9, and 5 weeks and the adjusted RR was 1.00, 1.30, 1.37, and 1.50 in the category of 0–9, 10–19, 20–29, and 30–40 respectively. Exacerbation history (≥2 vs. 1 event in the past year) was related to time to first exacerbation (adjusted HR 1.35; p = 0.023) and any exacerbation during the study period (adjusted RR 1.15; p = 0.016).The results of this study support the use of the CAT as a simple tool to assist in the identification of patients at increased risk of exacerbations. This could facilitate timely and cost-effective implementation of preventive interventions, and improve health resource allocation.Trial registrationClinicaltrials.gov: NCT01254032.

ObjectiveTo investigate the association between diabetes and latent tuberculosis infections (LTBI) in high TB incidence areas.DesignCommunity-based comparison study.SettingOutpatient diabetes clinics at 4 hospitals and 13 health centres in urban and rural townships. A community-based screening programme was used to recruit non-diabetic participants.ParticipantsA total of 2948 patients with diabetes aged older than 40 years were recruited, and 453 non-diabetic participants from the community were enrolled.Primary and secondary outcome measuresThe interferon-gamma release assay (IGRA) and the tuberculin skin test were used to detect LTBI. The IGRA result was used as a surrogate of LTBI in logistic regression analysis.ResultsDiabetes was significantly associated with LTBI (adjusted OR (aOR)=1.59; 95% CI 1.11 to 2.28) and age correlated positively with LTBI. Many subjects with diabetes also had additional risk factors (current smokers (aOR=1.28; 95% CI 0.95 to 1.71), comorbid chronic kidney disease (aOR=1.26; 95% CI 1.03 to 1.55) and history of TB (aOR=2.08; 95% CI 1.19 to 3.63)). The presence of BCG scar was protective (aOR=0.66; 95% CI 0.51 to 0.85). Duration of diabetes and poor glycaemic control were unrelated to the risk of LTBI.ConclusionThere was a moderately increased risk of LTBI in patients with diabetes from this high TB incidence area. This finding suggests LTBI screening for the diabetics be combined with other risk factors and comorbidities of TB to better identify high-risk groups and improve the efficacy of targeted screening for LTBI.

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.

Background and Objectives Complete surgical resection is recommended for early stage lung cancer, and adjuvant chemotherapy is given for stage IB to IIIA disease. No studies have examined the best timing to administer chemotherapy after surgery in lung cancer. This study was to investigate the optimal timing of adjuvant chemotherapy after surgical resection. Methods Data collected from the Taiwan National Health Insurance Research Database between January, 2004 and December, 2010 were retrospectively analyzed. Patients with stage IB to IIIA lung cancer underwent complete surgical resection and adjuvant chemotherapy were included. A total of 1522 patients were included. The patients were divided into 4 groups according to the interval between surgery and chemotherapy: group 1, < 30 days; group 2, 30–45 days; group 3, 46–60 days; group 4 > 60 days. Univariate and multivariate regression analyses were used to identify prognostic factors for overall survival. Results The numbers of patients in groups 1, 2, 3, and 4 were 153, 161, 290, and 818, respectively. The 5-year survival rate was 41% in group 1, 48% in group 2, 50% in group 3, and 35% in group 4 (p

Shih-Lung Cheng,1,2 Ching-Hsiung Lin3–5 1Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, 2Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli, Taoyuan City, 3Department of Internal Medicine, Division of Chest Medicine, Changhua Christian Hospital, Changhua, 4Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, 5School of Medicine, Chung Shan Medical University, Taichung City, Taiwan Background: Blood eosinophil counts have been documented as a good biomarker for patients with chronic obstructive pulmonary disease (COPD) using inhaled corticosteroid (ICS) therapy. However, the effectiveness and safety of prescribing high or medium dose of ICS for patients with different eosinophil counts are unknown.Methods: A post hoc analysis of a previous prospective randomized study was performed for COPD patients using higher dose (HD: Fluticasone 1,000 µg/day) or medium dose (MD: Fluticasone 500 µg/day) of ICS combined with Salmeterol (100 µg/day). Patients were classified into two groups: those with high eosinophil counts (HE ≥3%) and those with low eosinophil counts (LE

Liang-Wen Hang,1,2 Jeng-Yuan Hsu,3 Chee-Jen Chang,4 Hao-Chien Wang,5,6 Shih-Lung Cheng,7,8 Ching-Hsiung Lin,9 Ming-Cheng Chan,3 Chin-Chou Wang,10 Diahn-Warng Perng,11 Chong-Jen Yu5,6 On behalf of the Taiwan COPD Consortium 1Department of Respiratory Therapy, College of Health Care, China Medical University, 2Sleep Medicine Center, Department of Pulmonary and Critical Care Medicine, China Medical University Hospital, 3Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 4Biostatistical Center for Clinical Research, Chang Gung Memorial Hospital, Linkou Branch, Guishan Township, Taoyuan County, 5Department of Internal Medicine, National Taiwan University Hospital, 6Department of Internal Medicine, National Taiwan University, College of Medicine, Taipei, 7Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, 8Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li City, Taoyuan County, 9Division of Chest Medicine, Changhua Christian Hospital, Changhua City, Changhua County, 10Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 11Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Background and objectives: COPD and obstructive sleep apnea (OSA) share similar pathological processes and cardiovascular sequelae. Coexisting OSA in COPD – “overlap syndrome” – has worse prognosis than either condition alone, and appropriate treatment improves survival. Our objectives were to ascertain the frequency at which COPD coexists with the risk of OSA in Taiwan and to compare the risk factors, COPD symptoms, and life quality metrics between COPD subgroups with versus without risk of OSA. Methods: We conducted a random cross-sectional national telephone survey of adults >40years old in Taiwan. Participants fulfilling an epidemiological case definition of COPD completed a questionnaire to assess COPD symptoms and OSA risk, comorbidities, and performance of daily activities. Data from COPD cohorts with and without risk of OSA were analyzed and compared. Results: Of 6,600 interviews completed, 404 subjects fit the epidemiological case definition of COPD – an overall prevalence of 6.1% in this national sample. Data on OSA risk were available for 292 of this COPD cohort, of whom 29.5% were at risk of OSA. Compared to those without risk of OSA, those with risk of OSA were significantly more likely to have hypertension or cardiovascular disease and diabetes, had significantly higher body mass index and COPD Assessment Test scores, and reported impaired work performance and leisure activities. Conclusion: Among adults in Taiwan who fulfill epidemiologic criteria for COPD, 29.5% have coexisting risk of OSA. Comorbid hypertension or cardiovascular disease and diabetes are common and significantly more prevalent among the COPD population at risk of OSA than those who are not. OSA screening is warranted in patients with COPD with those risk factors that are more prevalent in COPD with risk of OSA than without, to target early interventions to reduce adverse cardiovascular sequelae from overlap syndrome. Keywords: cardiovascular risk, COPD, coexistent, obstructive sleep apnea, OSA, overlap syndrome

To fill a void in the literature, we performed a literature search and subsequently reviewed randomized controlled trials (RCTs) in the field of obesity surgery that were published over the past 40 years. All RCTs published in the English between January 1972 and December 2011 were identified through a literature search using the PubMed database. The following search terms were used: "bariatric surgery", "obesity surgery", and "weight reducing surgery". Studies of basic science and anesthesia-related pain management were excluded. The extracted trials were divided into four groups: comparisons of different interventions, intraoperative surgical techniques, preoperative evaluation, and postoperative care. The literature search produced 753 manuscripts, of which 168 met the eligibility criteria. Among 168 papers, 32 % compared different interventions, 48 % assessed intraoperative surgical techniques, 18 % assessed postoperative care, and the remaining 2 % assessed preoperative evaluation. The RCTs were published in 47 different journals, most commonly in Obesity Surgery (28.6 %) and the Annals of Surgery (11.9 %). Trials were conducted in 25 different countries, with the greatest contribution from the USA (35.1 %). There was a progressive increase in published trials from 1972 to 2011, with 119 RCTs (70.8 %) being published over the last decade. A trend for an increasing number of published RCTs in the field of bariatric surgery was observed over the recent years. Although data from large, adequately powered, long-term RCTs are still lacking, any surgical intervention appears to be more effective than medical care for the treatment of morbid obesity.

Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50~60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12–3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.

Soluble Fas ligand (sFasL) is abundant in effusions of tuberculous (TB) pleurisy; however, its diagnostic value has not been scrutinized. We collected pleural effusions from 79 patients, including 23 with TB pleurisy and 56 without TB, and measured sFasL, adenosine deaminase (ADA), and interferon-γ (IFN-γ) concentrations of each specimen. The median of the sFasL concentration of the TB group was 57.3 pg/mL, which was significantly higher than that of the non-TB group (27.4 pg/mL) (P < 0.001). When cutoff value was 39.85 pg/mL, the sensitivity and specificity of sFasL were 95.7% and 80.4%, respectively. The area under the receiver operating characteristic curve for sFasL was not significantly different from those of ADA and IFN-γ. Soluble FasL concentrations of TB patients were significantly higher than those of parapneumonic effusion subgroup (P = 0.039). In conclusion, pleural effusion sFasL is another good diagnostic marker for TB pleurisy.

Tianhua (TH-R) is extracted from Trichosanthes kirilowii Maxim (Cucurbitaceae) containing trichosanthin, a traditional Chinese medicine, which has been locally reported to have good anticancer effects in vivo in both animal and human models. However, there have been several reports that trichosanthin has an anticancer effect involving apoptosis.To investigate other anticancer effects of TH-R, various tumorigenesis parameters were verified.Telomerase activity, anti-apoptosis, anti-migration and immunomodulatory activity were estimated by telomeric repeat amplification protocol assay (TRAP), flow cytometry, Boyden chamber assay and ELISA assay, respectively.In our studies, we are the first to find that TH-R had a cytotoxic effect on lung cancer cells in MTS assays; it could change the cell cycle distribution of human lung cancer cells (A549 cell line) and induce apoptosis. Further anti-telomerase effects in human lung adenocarcinoma A549 cells using the TRAP assay were noted. TH-R also had an aggregation effect on peripheral blood lymphocytes, but no effect on stimulating peripheral lymphocytes to produce human interferon-γ(IFN-γ). TH-R could inhibit the migration, or metastatic ability, of A549 cells by Boyden chamber assay. In the oral feeding therapy of an in vivo mouse model, there was an initial inhibition of A549 cancer cell growth, but no statistical difference after one month of therapy.It has been proven that medicinal herbs such as Tianhua have positive effects against cancer through preventing or inhibiting the process of lung tumorigenesis.

To evaluate the clinical benefits and disadvantages of adding metoclopramide to tramadol for patient-controlled analgesia (PCA).Forty adult patients, undergoing elective arthroplasties, were recruited into this prospective, randomized, double-blind study. During general anesthesia all patients received 2.5 mg x kg(-1) of tramadol as a loading dose at the beginning of wound closure. In the postanesthesia care unit (PACU) patients were randomly allocated to receive PCA containing either 20 mg tramadol + 1 mg metoclopramide per millilitre (n = 20, Group T+M) or tramadol 20 mg per millilitre (n = 20, Group T). The PCA setup was 1 mL/bolus with a lockout interval of five minutes. A blinded investigator assessed the vital signs, visual analogue scale, and severity of postoperative nausea and/or vomiting in the PACU. The PCA demand and delivery, overall satisfaction rate and adverse effects were recorded in the PACU and on postoperative days one and two.Nausea/vomiting scores were more severe (1.7 +/- 1.0 vs 0.2 +/- 0.5, 2.3 +/- 1.2 vs 0.6 +/- 0.6, 1.9 +/- 0.9 vs 0.2 +/- 0.5, at 12 hr, 18 hr, 24 hr, respectively, P0.05) and more frequent (7/20 vs 1/20, 5/20 vs 0/20 for nausea and vomiting respectively, P0.05) on postoperative day one in Group T compared to Group T+M. However, the incidence of sedation was higher in Group T+M (7/20 vs 1/20, P0.05).The incidence and severity of nausea/vomiting decreased if metoclopramide was added to tramadol for PCA. An increased incidence of sedation was noticed with this drug combination.

The efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real-life effectiveness are seldom reported.This multicenter trial enrolled steroid-naïve, symptomatic asthmatics with baseline exhaled nitric oxide (eNO) of ≥ 40 ppb. There were 120 eligible patients who were randomized and received a dose of inhaled budesonide/formoterol 320/9 μg (lower dose budesonide/formoterol), 640/18 μg (higher dose budesonide/formoterol (HDBF)), or terbutaline (TERB) 1 mg. Inflammatory cells and mediators in induced sputum, eNO and lung function were measured at baseline and 6 h (acute phase). Subsequently, all patients used BFMRT as real-life practice for 24 weeks (maintenance phase).In the acute phase, the degree of post-treatment reduction in total eosinophil counts, interleukin-8 and matrix metalloproteinase-9 in induced sputum were significantly greater in group HDBF (vs TERB, P0.05). The increase in forced expiratory volume in first second (FEV1 ) in group HDBF was significantly higher (vs LDBF and TERB, P0.05) 3 h after dosing. In the maintenance phase, significant improvement of asthma control (presented by eNO, FEV1 and a five-item asthma control questionnaire) in real-life settings was observed at 4 weeks and sustained to the end of study. The rate of patients who followed scheduled visits declined over time (87% at week 4 and 42% at week 24).Budesonide/formoterol as reliever exerts acute, dose-related anti-inflammatory effects and FEV1 improvement in symptomatic asthmatics. BFMRT is effective in asthma control. However, the decrease in long-term follow-up rate remains an issue to overcome in real-life settings.

Objectives Lung cancer and tuberculosis (TB) share common risk factors and are associated with high morbidity and mortality. Coexistence of lung cancer and TB were reported in previous studies, with uncertain pathogenesis. The association between lung cancer and latent TB infection (LTBI) remains to be explored. Methods Newly diagnosed, treatment-naive lung cancer patients were prospectively enrolled from four referral medical centers in Taiwan. The presence of LTBI was determined by QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic characteristics and cancer-related factors associated with LTBI were investigated. The survival status was also analyzed according to the status of LTBI. Results A total of 340 lung cancer patients were enrolled, including 96 (28.2%) LTBI, 214 (62.9%) non-LTBI, and 30 (8.8%) QFT-GIT results-indeterminate cases. Non-adenocarcinoma cases had higher proportion of LTBI than those of adenocarcinoma, especially in patients with younger age. In multivariate analysis, COPD (OR 2.41, 95% CI 1.25–4.64), fibrocalcified lesions on chest radiogram (OR 2.73, 95% CI 1.45–5.11), and main tumor located in typical TB areas (OR 2.02, 95% CI 1.15–3.55) were independent clinical predictors for LTBI. Kaplan–Meier survival analysis demonstrated patients with indeterminate QFT-GIT results had significantly higher 1-year all-cause mortality than those with LTBI ( p p =0.003). In multivariate analysis, independent predictors for 1-year all-cause mortality included BMI p =0.033), advanced stage of lung cancer (RR 7.76, 95% CI 1.90–31.78, p =0.004), and indeterminate QFT-GIT results (RR 2.40, 95% CI 1.27–4.54, p =0.007). Conclusions More than one-quarter of newly diagnosed lung cancer patients in Taiwan have LTBI. The independent predictors for LTBI include COPD, fibrocalcified lesions on chest radiogram, and main tumor located in typical TB areas. The survival rate is comparable between LTBI and non-LTBI cases. However, indeterminate QFT-GIT result was an independent predictor for all-cause mortality in lung cancer patients.

BACKGROUND Thoracoscopic lobectomy is a safe and effective procedure; however, the ways by which to incorporate this technically demanding procedure into residency training is still unknown. We reported on the outcomes of thoracoscopic lobectomies performed by a single thoracic resident, who was simultaneously undergoing training for both open and thoracoscopic lobectomies. PATIENTS AND METHODS Between January 2010, and May 2011, data from 87 consecutive thoracoscopic lobectomies that were performed by a trainee surgeon (B.-Y.W.) were prospectively obtained. Data were grouped into the first 30 and subsequent 57 cases. Patient characteristics, operative data, complications, and surgical pathology were analyzed. RESULTS The mean operating time in group 2 was significantly lower compared with group 1 (264.0 ± 45.9 min in group 1 vs. 197.5 ± 57.7 min in group 2; p

To compared the clinical efficacy of tramadol and morphine using a patient-controlled analgesia (PCA) delivery system.In a prospective, randomized, double blind study, we evaluated 80 adult patients scheduled for elective hip or knee arthroplasty with general inhalational anesthesia. When patients complained of pain in the recovery room, patients were randomized to receive either tramadol or morphine by titration in 30 min to achieve analgesia (VASor =4). Equivalent volumes containing either 30 mg x ml(-1) tramadol or 1 mg x ml(-1) morphine were used for PCA with a lockout interval of 10 min. The patients were followed six-hourly for 48 hr for VAS, satisfaction rate, analgesic dose, and side effects.Patients obtained adequate analgesia with either drug. More patients had very good satisfaction scores in the morphine group in the recovery room (43% vs. 23%, P0.05) and at 24 hr (40% vs. 20%, P0.05) than those in the tramadol group. More nausea was evident in the tramadol group (48% vs. 11% in recovery room and 28% vs. 12% in 24 hr, P0.05) than in the morphine group. Vomiting was also more (28% vs. 5% in recovery room, 15% vs. 3% in 24 hr, P0.05). Morphine produced more sleepiness (45% vs. 23% in recovery room, P0.05 and 35% vs. 15% in 24 hr, P0.05).Tramadol PCA can provide effective analgesia following major orthopedic surgery provided sufficiently high doses are given for loading and by patient demand. However, the incidence of nausea/vomiting is also higher causing decreased satisfaction.

Background Type 2 diabetes mellitus (DM) is a common medical disorder and a leading cause of morbidity and mortality worldwide. We investigated whether chronic obstructive pulmonary disease (COPD) was the risk factor for type 2 diabetes in an Asian population. Materials and methods From Taiwan's National Health Insurance Research Database, we collected data from 16 088 patients, including 8044 COPD patients and 8044 age- and gender- matched control subjects. Cox proportional hazard regression was performed to evaluate independent risk factors for type 2 diabetes in all patients and identify risk factors in patients with COPD. Results During the 5·5-year follow-up, patients with COPD were found to have a significantly higher rate of incident type 2 diabetes than the control group (P

Introduction: Lung cancer is the leading cause of cancer death in Taiwan. This study investigated the prognostic factors affecting survival of patients with lung cancer in Taiwan. Methods: Data were obtained from the National Health Insurance Research Database published in Taiwan. Clinicopathologic profiles and prognostic factors of 33,919 lung cancer patients were analyzed between 2002 and 2008 in this retrospective review. The impact of the clinicopathologic factors on overall survival was assessed. Results: Nearly two thirds of the patients were men. The 5-year survival rate was 15.9%, with a median survival of 13.2 months. The clinical staging of the patients included stage I (n = 4254; 12.5%), stage II (n = 1140; 3.4%), stage III (n = 10,161; 30.0%), and stage IV (n = 18,364; 54.1%). In the multivariate analysis, age more than 65 years, sex, cell type, histologic grade, and primary tumor location were identified as independent prognostic factors. Conclusion: In additional to tumor-nodes-metastasis (TNM) staging system, patient sex and age, tumor location, cell type, and differentiation were independent prognostic factors. We recommend incorporation of these factors to subclassify lung cancer patients.

Inhaled corticosteroids (ICSs) are widely used in asthma control. Ciclesonide (CIC) is an ICS with on-site lung activation for potent anti-inflammatory activity. This study aimed to compare the clinical benefit of CIC with budesonide (BUD) in step-down therapy. A total of 150 patients with mild-to-moderate asthma well controlled by a combination of ICS and long-acting β2-agonist were randomised to receive either CIC 320 μg (n=75) once daily or 2 inhalations of BUD 200 μg (n=75) twice daily for 12 weeks. The forced expiratory volume in 1s (FEV1), maximum mid-expiratory flow (MMEF) and asthma control test (ACT) scores were measured. Ranked stratification of patients and physicians was assessed. Drug adherence was significantly higher in the CIC group than in the BUD group (76.0% vs. 58.7%, P=0.03). The FEV1 and MMEF remained stable throughout the 12-week CIC treatment. In the BUD group, FEV1 significantly decreased at weeks 4 and 12. MMEF had a higher value in the CIC group than in the BUD group. Both patients and physicians ranked CIC over BUD. CIC is more effective and has better drug adherence than BUD as step-down treatment when asthma is well controlled by combination therapy. Ciclesonide is more effective than budesonide in people seeking to reduce their asthma medications. Best-practice guidelines suggest that patients can take just one drug once they achieve reasonable asthma control for at least 3 months. This is known as step-down therapy. Researchers in Taiwan, led by Chun-Hua Wang and Han-Pin Kuo of Chang Gung Memorial Hospital, randomised 150 individuals with mild to moderate asthma well controlled by a combination of corticosteroid and β2 agonist to receive either ciclesonide or budesonide, both inhaled corticosteroid drugs. The study found that participants on a once-daily regimen of ciclesonide maintained a stable pulmonary function throughout the 12-week trial, whereas those receiving two doses of budesonide per day had smaller lung volumes. More research is needed to determine whether the benefit of ciclesonide is attributable to treatment compliance or drug efficacy.

Aim Colorectal cancer (CRC) is the second commonest cause of cancer death in Taiwan. Although numerous genes have been associated with tumorigenesis in colorectal cancer, only a few have been validated and used as biomarkers for predicting clinical outcome. The aim of this study was to analyse the association of APC gene mutation and miR-21 expression with clinical outcome in CRC patients. Method In total, 195 colorectal cancer patients were enrolled in a single medical centre between 2003 and 2007. APC gene mutation and expression of APC and miR-21 were analysed by direct DNA sequencing and real-time reverse transcription polymerase chain reaction. The primary outcome included 5-year overall survival and univariate (Kaplan–Meier) and multivariate (Cox regression) analyses of prognostic factors. Results The results showed that 66 (33.8%) of 195 tumour tissues contained an APC mutation. The predominant APC gene variations were deletion mutations (50.0%). APC gene expression was low in CRC and negatively correlated with miR-21 expression and gene mutation. In advanced-stage cancer, patients with APC mutation/high miR-21 had poorer overall survival rates than those with APC mutation/low miR-21, APC wild-type/high miR-21 and APC wild-type/low miR-21. Conclusion In Taiwan, downregulation of the APC gene in CRC correlated with gene mutation and miR-21 upregulation. APC mutation and miR-21 expression could be used to predict the clinical outcome of CRC, especially in patients with advanced disease.

The optimal treatment modality for locoregional esophageal squamous-cell carcinoma (ESCC) is still undetermined. This study investigated the treatment modalities affecting survival of patients with ESCC in Taiwan. Data on 6202 patients who underwent treatment for locoregional esophageal squamous-cell carcinoma during 2008 to 2012 in Taiwan were collected from the Taiwan Cancer Registry. Patients were stratified by clinical stage. The major treatment approaches included definitive chemoradiotherapy, preoperative chemoradiation followed by esophagectomy, esophagectomy followed by adjuvant therapy, and esophagectomy alone. The impact of different treatment modalities on overall survival was analyzed. The majority of patients had stage III disease (n = 4091; 65.96%), followed by stage II (n = 1582, 25.51%) and stage I cancer (n = 529, 8.53%). The 3-year overall survival rates were 60.65% for patients with stage I disease, 36.21% for those with stage II cancer, and 21.39% for patients with stage III carcinoma. Surgery alone was associated with significantly better overall survival than the other treatment modalities for patients with stage I disease (P = 0.029) and was associated with significantly worse overall survival for patients with stage III cancer (P

Summary Background REACH-B [Risk Estimation for Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B] scoring system was developed to predict the risk of HCC in noncirrhotic chronic hepatitis B (CHB) patients. Aim To evaluate the discriminatory performance of REACH-B scoring system in classifying anti-viral treatment eligibility of CHB patients according to the 2012 Asian Pacific Association for the Study of the Liver (APASL) treatment guideline. Methods A total of 904 noncirrhotic CHB were enrolled. Patients' age, gender, liver biochemistry, HBeAg status and HBV DNA levels were recorded. Results The minimum REACH-B risk score for patients to be eligible for anti-viral treatment was 7 for HBeAg-positive and 6 for HBeAg-negative patients. Among them, increasing REACH-B score was not significantly associated with eligibility for treatment [adjusted odds ratio (OR): 1.210, 95% confidence interval (CI): 0.979–1.494, P = 0.078] in HBeAg-positive patients, as shown by logistic regression analysis after adjusting for gender. In HBeAg-negative patients, REACH-B score significantly predicted the treatment eligibility (adjusted OR: 1.783, 95% CI: 1.607–1.979, P

SummaryBackground Measuring fractional exhaled nitric oxide (FeNO) is a simple and non-invasive method for assessing airway inflammation. IL-17 plays an important role in T cell-dependent inflammatory response that occurs in allergic asthma, it could act as a potent activator of inducible nitric oxide synthase (iNOS) to amplify FeNO levels. Objectives To evaluate the differences in the CD4+IL-17A+ T cell counts, serum IL-17 levels, and FeNO levels in children with mild intermittent to moderate to severe persistent asthma classified by using the Global Initiative for Asthma (GINA). Methods One hundred and twenty asthmatic children divided into the mild intermittent (n = 42), mild persistent (n = 42), and moderate to severe persistent (n = 36) groups, and 20 healthy controls were recruited for the study. Information obtained at visits included the assessment of asthma severity according to GINA guidelines and C-ACT, lung function parameters, FeNO levels, CD4+IL-17A+ T cells counts from PBMCs, iNOS production by sputum cells and serum IL-17 levels. Results Serum IL-17 and FeNO levels were significantly higher in mild to severe persistent asthmatic patients than in intermittent asthmatics or healthy controls (P

Genotypes of Mycobacterium tuberculosis (MTB) are related to the geographic origin of the patients and population migration. The relationship between genotypes of MTB and clinical presentations has mainly focused on transmission of multi-drug resistant MTB strain in population. This study aimed to investigate the molecular epidemiology and dynamic change of MTB genotypes in Taiwan, and their association with clinical presentation among patients with pulmonary tuberculosis. A multi-center, two-year study which enrolled 516 patients with 516 MTB isolates was conducted, including: (1) 254 isolates from northern Taiwan; (2) 38 isolates from mid-western Taiwan; (3) 211 isolates from southern Taiwan; and (4) 13 isolates from the east coast of Taiwan. The isolates were genotyped with spoligotyping and standardized 12-loci-MIRU-VNTR method. The results showed Beijing/Beijing-like family was the major genotype of MTB in the northern (58%), eastern (53%), and southern (33%) regions. The second most widely spread lineage were the EAI-Manila (20% in the west and south) and Haarlem family (13–27% in the south, west, and east). According to the cluster analysis of 12-MIRU-VNTR genotypes, there were differences in distribution of MTB genotype between the northern and southern regions, and a temporal relationship between isolation year and 12-MIRU-VNTR genotype especially in loci 26 and 39 might exist. Furthermore, some patients with cavity lesions on chest films were associated with a cluster of Beijing family MTB strains, which can be defined by cluster analysis of 12-MIRU-VNTR genotype. However, the results of 12-loci-MIRU-VNTR genotyping in a longitudinal study should be interpreted with caution due to its short term instability. Further investigations of different molecular methodologies are necessary.

Background The radiological manifestations of lower lung field (LLF) tuberculosis (LLFTB) are similar to those of LLF pneumonia (LLFP), making diagnosis challenging. The aim of this study was to determine if there are differences in the clinical manifestations of LLFTB and LLFP in patients with unilateral LLF opacities. Methods We performed a retrospective review of patient records to identify those with unilateral LLF opacities who were subsequently diagnosed with LLFTB or LLFP. We compared demographics, clinical manifestations, hematological data, and radiographic findings between the groups of patients. Results We identified 22 and 72 patients diagnosed with LLFTB and LLFP, respectively. Multivariate analysis revealed that age (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.99–1.11, P =0.072), lack of fever>38°C (OR=9.04, 95% CI=1.69–48.40, P =0.001), duration of symptoms≥7 days (OR=4.57, 95% CI=1.09–19.26, P =0.038), and the lack of air bronchograms upon radiography (OR=12.08, 95% CI=1.98–73.64, P =0.007) were significant predictors of LLFTB in patients with LLF opacities. We used these predictors to construct a mathematical model for predicting LLFTB in patients with LLF opacities. Conclusions Our findings suggest that older age, prolonged duration of symptoms, lack of fever>38°C, and the absence of air bronchograms are more common in patients with LLFTB than patients with LLFP. These findings may help clinicians differentiate between LLFTB and LLFP and thus initiate timely and appropriate treatment.

Polyomavirus type BK (BKV) nephropathy is increasingly a significant cause of graft dysfunction and even failure. Early diagnosis followed by reduction of immunosuppression has been associated with an improved prognosis. We screened 250 patients with the urine qualitative polymerase chain reaction (PCR) for BKV DNA. We followed with blood BKV PCR if the urine screen was positive and then reduced immunosuppression in viremic patients. One hundred ninety-nine patients (80%) had no viuria; 43 (17%) viuria; and 8 (3%) both viuria and viremia. Graft biopsy performed in three patients (1%) with viremia and impaired graft function all revealed BKV nephropathy. After 6 months of follow-up, seven out of eight viremic patients (88%) had negative repeat blood PCR and stabilized graft function. An early diagnosis of BKV infection with reduction of immunosuppression may reverse viremia and retard progression of BKV nephropathy. BKV screening by PCR assays should be considered in kidney transplant recipients, especially those with impaired graft function.

Background: To clarify clinical arguments regarding nutrition support in patients with long-term mechanical ventilation, we investigated the effects of hypercaloric feeding on nutrition status and carbon dioxide production. Methods: Twenty-eight mechanically ventilated, clinically stable patients with nasogastric tube feeding were recruited and randomly divided into the control and hypercaloric groups, which were provided with 1.2- and 1.8-fold of resting energy expenditure (REE), respectively. The arterial and venous blood samples were collected, the anthropometric measurements were determined, the serum concentrations of nutrition-related proteins were measured, and the parameters on the ventilator and indirect calorimeter were recorded on weeks 0, 2, and 4. Results: There were no significant changes in anthropometric measurements, blood gas tensions, and REE between the control and hypercaloric groups during the experimental period (mixed model with repeated measures analysis, p

Negative pressure pulmonary oedema (NPPE) is a well-recognized but rare complication secondary to upper airway obstruction such as laryngeal spasm during emergence from general anaesthesia. Cauterization of the second and third thoracic sympathetic ganglia is a treatment for hyperhidrosis of the hands. We report a case of NPPE induced by direct suctioning of the endotracheal tube adapter during thoracic sympathetic ganglionectomy without recognized upper airway obstruction.A 19-yr-old otherwise healthy, non-smoking man was scheduled for elective bilateral chest endoscopic ablation of the second and third thoracic sympathetic ganglion for hyperhidrosis of the hands under general anaesthesia. To view and cauterize the ganglion with the endoscope, the surgeon requested cessation of positive pressure ventilation. As the surgeon could not satisfactorily visualize the target ganglia, he requested brief application of wall suction via the ETT tube adapter. A pressure of -100 mmHg was generated which lasted for three to four seconds. The goal was to reduce further the lung volume by increasing the pneumothorax produced by the endoscope. The patient developed negative pressure pulmonary oedema without upper airway obstruction.This case demonstrated that intrathoracic negative pressure generated by direct ETT adapter suctioning may produce pulmonary oedema similar to that induced by laryngeal spasm during the emergence of general anaesthesia.

Objective Tuberculosis continues to be a major global health problem. We wanted to investigate whether Type 2 diabetes was a risk factor for tuberculosis in an Asian population. Methods From Taiwan’s National Health Insurance Research Database, we collected data from 31,237 female patients with type 2 diabetes and 92,642 female controls and 32,493 male patients with type 2 diabetes and 96,977 male controls. Cox proportional hazard regression was performed to evaluate independent risk factors for tuberculosis in all patients and to identify risk factors in patients with type 2 diabetes. Results During the study period, both female (standardized incidence ratio (SIR): 1.40, p

Figure 1: (A) Chest radiography revealed a 1.5-cm radio-opaque density at the level of the T4-5 vertebrae. (B and C) Chest computed tomography demonstrated bilateral neck subcutaneous emphysema and pneumomediastinum with a tubular structure, 15 cm in length, in the cervical and upper thoracic oesophagus. (D) The upper posterior mediastinal pleura were opened, and a ballpoint pen was found between oesophagus and vertebral body.

BACKGROUND: Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy. METHODS: This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated. RESULTS: A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03-1.05), malignancy (RR = 2.42, 95%CI: 1.77-3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12-2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47-0.84), fever (RR = 1.45, 95%CI: 1.09-1.94), and anorexia (RR = 1.49, 95%CI: 1.07-2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p

We describe a method of single-port thoracoscopic rib resection using a Gigli saw. Rib resection is typically performed with a large skin incision and soft tissue dissection. Some authors have described a thoracoscopic approach for rib resection from the inner side of the chest wall instead of the outside to decrease pain and improve quality of life. A 41-year-old Chinese male received single-port thoracoscopic rib resection with satisfactory recovery. We present the technique, which may expand the indications of single-port thoracoscopic procedures.