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BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

The clinical implications of airflow limitation severity and blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and prolonged mechanical ventilation (PMV) are unknown. Thus, this study aimed to identify whether or not these two indicators were significantly associated with short-term in-respiratory care center (RCC) treatment outcomes in this population. Of all participants (n = 181) in this retrospective cross-sectional study, 41.4%, 40.9%, 8.3%, and 52.5% had prolonged RCC admission (RCC length of stay >21 days), failed weaning, death, and any adverse outcomes of interest, respectively. Compared to participants without any adverse outcomes of interest, moderate (the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II) and/or severe (GOLD III) airflow limitation were significantly associated with short-term in-RCC adverse outcomes in terms of failed weaning (for III versus I, OR = 15.06, p = 0.003) and having any adverse outcomes of interest (for II versus I, OR = 17.66, p = 0.002; for III versus I, OR = 37.07, p = 0.000) though the severity of airflow limitation did not have associations with prolonged RCC admission and death after adjustment. Meanwhile, blood eosinophilia defined by various cut-off values was not associated with any adverse outcomes. The findings have significant clinical implications and are useful in the management of patients with COPD and PMV.

Meng-Jer Hsieh,1,2 Shu-Yi Huang,1 Tsung-Ming Yang,1 Chi-Wei Tao,3 Shih-Lung Cheng,4 Chao-Hsien Lee,5 Ping-Hung Kuo,6 Yao-Kuang Wu,7,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Ming-Shian Lin,12 Chin-Chou Wang,13 Yu-Feng Wei,14 Ying-Huang Tsai1,2 1Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang-Gung Medical foundation, Chiayi, Taiwan; 2Department of Respiratory Therapy, School of Medicine, Chang-Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 8School of Medicine, Tzu Chi University, Hualien, Taiwan; 9Department of pulmonary and critical care medicine, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 11Division of Chest Medicine, Taichung Veterans General Hospital, Taiwan; 12Dpartment of Internal Medicine, Ditmanson Medical Foundation, Chia-Yi Cristian Hospital, Chia-Yi, Taiwan; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang-Gung Medical Foundation, Kaohsiung, Taiwan; 14Department of Internal Medicine E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Background: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methods: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.Results: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.Conclusion: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. Keywords: chronic obstructive pulmonary disease, GOLD guidelines, inhaled corticosteroids, long-acting bronchodilators

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

ObjectivesThe clinical implications of blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission are still unknown. Thus, this study aimed to compare the features of such patients with and without blood eosinophilia.DesignThis was a retrospective case–control study.SettingAn ICU of a medical centre in central Taiwan.ParticipantsA total of 262 patients with COPD and CAP requiring IMV and ICU admission.ResultsOf all participants (n=262), 32 (12.2%) had an eosinophil percentage (EP) >2% and 169 (64.5%) had an absolute eosinophil count (AEC) >300 cells/µL. Regardless of whether 2% or 300 cells/µL was used as a cut-off value, the eosinophilia group were slightly older (years) (82.9±5.4 vs 78.1±9.1, p=0.000 and 79.2±8.4 vs 77.6±9.6, p=0.246, respectively), and had a higher forced expiratory volume in 1 s/forced vital capacity (%) (56.0±8.0 vs 51.3±11.6, p=0.005 and 53.1±11.2 vs 49.5±11.2, p=0.013, respectively), less severe spirometric classification (p=0.008 and p=0.001, respectively), and lower white cell count 109/L (8.8±3.2 vs 11.1±4.9, p=0.009 and 10.3±4.4 vs 11.8±5.3, p=0.017, respectively) than the non-eosinophilia group. The bacteriology of endotracheal aspirates showed thatPseudomonas aeruginosaand other gram-negative bacilli were the most common organisms in all study groups. Participants with an EP >2% had a shorter ICU length of stay (OR=12.13, p=0.001) than those with an EP ≤2%, while an AEC >300 cells/µL was not associated with any in-ICUoutcomes.ConclusionsThe results of this study have significant clinical implications and should be considered when making treatment decisions for the management of patients with COPD and CAP requiring IMV and ICU admission.

Background and objectives The clinical implications of the discordance between the risk of exacerbations and the level of airflow limitation in patients with chronic obstructive pulmonary disease (COPD) are still unknown. This study aimed to clarify the clinical significance of such discordance in the management of COPD by exploring its characteristics and risk factors. Methods In this retrospective, cross-sectional study, participating physicians completed a detailed patient record form for each participating outpatient with COPD. The data, collected by the Taiwan Obstructive Lung Disease consortium, were managed and analyzed. Results Of the enrolled participants, 316 (41.7%) had an inconsistency between the risk of exacerbations and the severity of airflow limitation. Univariate analysis showed that more severe airflow limitation (p = 0.000), higher COPD assessment test (CAT) scores (p = 0.003) and modified Medical Research Council (mMRC) scales (p = 0.008), and the presence of at least one (p = 0.000) or two (p = 0.003) co-morbidities were significantly associated with such inconsistency. More severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3 and 4 classification; odds ratio (OR) = 27.09, p = 0.000 and OR = 25.15, p = 0.000, respectively) and the presence of at least one co-morbidity (OR = 2.01, p = 0.001) were still associated with the inconsistency in multivariate logistic regression analysis. Furthermore, the presence of wheezing (OR = 3.90, p = 0.000) and at least two co-morbidities (OR = 5.43, p = 0.005) were independent risk factors for an inconsistency of a high risk of exacerbations / GOLD 1 or 2 and the CAT score≧10 (OR = 1.58, p = 0.007), mMRC scale 2-4 (OR = 1.53, p = 0.017), and the presence of at least one co-morbidity (OR = 2.55, p = 0.000) for an inconsistency of a low risk of exacerbations / GOLD 3 or 4. Conclusions The patients with COPD and an inconsistency between the risk of exacerbations and level of airflow limitation had unique clinical characteristics and risk factors for this inconsistency. Management of these patients should include more detailed evaluations.

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

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

Background/Purpose: Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP. Methods: A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476. Results: A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (−3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (−8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05). Conclusion: Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476. Keywords: Clinical outcome, Community-acquired pneumonia, Levofloxacin, Nemonoxacin, Randomized controlled trial, Safety

Fractional exhaled nitric oxide (FeNO) measurement is an important noninvasive tool for evaluating eosinophilic inflammation of the airways. However, measurement of online FeNO in elderly people may not be possible if they are unable to perform the expiratory maneuver. The offline FeNO test is an alternative method that obviates the need for the expiratory maneuver. Adult asthma patients were enrolled and assigned to one of two age groups: group 1, aged >65 years old (n = 29), and group 2, control group, aged 20-65 years old (n = 27). Online and offline FeNO measurements were performed for all patients. There were no significant differences in pulmonary function parameters (forced expiratory volume in 1 second [FEV1], percentage of predicted FEV1, and FEV1/forced vital capacity [FVC]) between the two groups but group 1 had significantly lower Asthma Control Test scores. There was a high correlation between online and offline FeNO levels (r = 0.908; p < 0.001). There was significantly higher mean FeNO level, regardless of online or offline measurements, in patients with poorly controlled asthma. Offline FeNO measurement was found to be a simple and convenient method of measuring FeNO in elderly patients and can be used as an objective guide for further management of eosinophilic inflammatory airway disease in this population.

Background Sleep disturbance is a common complaint in patients with chronic obstructive lung disease (COPD). However, the factors resulting in sleep disturbance remain unclear. This retrospective, observational, multicenter study aimed to identify the factors associated with sleep disturbance in patients with COPD. Methods The study was a retrospective, observational, and multicenter research. Data including age, sex, body mass index, smoking status, COPD inhaler prescribed, clinical symptoms, pulmonary function tests, medical history of comorbidities, and questionnaires were collected. Parameters including demographics, symptoms, medication, severity, functional classification, and comorbidities were correlated with sleep quality scores. Results Among 377 patients with COPD, 200 (53 %) patients experienced poor sleep quality (Pittsburg Sleep Quality Index scores > 5). A significant difference in sleep quality, as measured by PSQI scores, was noted between groups based on the 2011 Global Initiatives for Chronic Obstructive Lung Disease (GOLD) classification system. The most common sleep disturbances included “getting up to use the bathroom” (70.3 %), “wake up at night or early morning” (40.3 %), and “cough and snore loudly at night” (15.9 %). The use of inhaled corticosteroids, the presence of wheezing, COPD Assessment Test (CAT) scores, and Modified Medical Research Council (mMRC) dyspnea scale scores positively correlated with poor sleep quality (odds ratio: 1.51, 1.66, 1.09, and 1.30, respectively). Upon multivariate analysis, the CAT score was an independent factor for poor sleep quality in these patients. With the exception of sleep problem items, based on the CAT questionnaire, phlegm was significantly higher in COPD patients with poor sleep quality. Conclusions Poor sleep quality is common among patients with COPD and symptoms including wheeze, phlegm, and inhaled corticosteroid use may contribute to poor sleep quality. The CAT score is a good indicator of poor sleep quality in patients with COPD.

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

Wan-Chun Huang,1 Ying-Huang Tsai,2 Yu-Feng Wei,3 Ping-Hung Kuo,4 Chi-Wei Tao,5 Shih-Lung Cheng,6 Chao-Hsien Lee,7 Yao-Kuang Wu,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Chin-Chou Wang,12 Ming-Shian Lin1,131Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 2Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 3Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, 4Department of Internal Medicine, National Taiwan University Hospital, 5Department of Internal Medicine, Cheng-Hsin General Hospital, 6Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, 7Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, 9Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 11Division of Chest Medicine, Taichung Veterans Genera Hospital, Taichung, 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 13Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan, Republic of ChinaBackground: COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.Methods: The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.Results: Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P

The aim of this study was to determine the usefulness of cancer antigen 125 (CA-125) serum levels in patients with tuberculosis (TB) with and without tuberculous serositis. A total of 64 TB patients with a mean age of 58.17 ± 19.05 years were enrolled in this observational case series study. All patients underwent blood sampling for the measurement of CA-125 serum levels before treatment. If the CA-125 serum levels were found to be elevated, the patients underwent blood sampling in the initial treatment phase, continuation treatment phase, and every 6 months thereafter for 2 years. The treatment outcomes of the pulmonary TB group were evaluated using chest radiography and sputum examinations, and those of the tuberculous serositis group were evaluated on the basis of the amounts of fluid determined by ultrasound. All patients in the tuberculous serositis group and 45% of the patients in the pulmonary TB group had elevated CA-125 serum levels before treatment. The pretreatment mean CA-125 serum level was significantly higher in the tuberculous serositis group than in the pulmonary TB group. CA-125 serum levels decreased along with improvement in anti-TB treatment outcomes in both the groups. In conclusion, the CA-125 serum levels in combination with clinical responses, chest radiography, and sputum examinations, can offer better monitoring of therapeutic responses in anti-TB treatment.

Background/Purpose: The fractional concentration of exhaled nitric oxide (FE(subscript NO)) has been reported to be elevated in asthma and many other lung diseases. The present study investigated reference values and determinants of FE(subscript NO) in a Taiwanese non-smoking, healthy adult population. Methods: We used a chemiluminescence analyzer according to American Thoracic Society/European Respiratory Society recommendations to measure FE(subscript NO) values in 356 adults who received a health check-up and a detailed respiratory questionnaire at Taichung Veterans General Hospital, Taiwan. Among the volunteers, 249 fulfilled our definition of healthy adults: no history of smoking or physician-diagnosed asthma; no recent upper airway infection; no chronic respiratory symptoms; and no allergic rhinitis and urticaria. Results: Among the 249 non-smoking and non-asthmatic adults, the mean (5(superscript th) to 95(superscript th) percentile reference range) FE(subscript NO) was 27.9 (12.5-58.0) parts per billion. In multivariate regression analyses, age and lung function (forced vital capacity or forced expiratory volume in 1 second) were associated positively with FE(subscript NO) values. Sex, height, weight, and ambient NO values were not associated significantly with FE(subscript NO) values. Conclusion: Age and lung function were predictors of FE(subscript NO) in this population, and these factors should be considered for clinical applications of FE(subscript NO) measurements.

Background Pulmonary hypertension (PH) is an overlooked cardiovascular morbidity in patients undergoing haemodialysis. Inflammation has been demonstrated to play a significant role with certain types of PH in non-uraemic patients, but studies analysing the mechanisms in dialyzed patients with PH are rare. Hence, we investigated systemic and local inflammation biomarkers associated with PH in uraemia patients to elucidate the potential mechanism. Methods A cross-sectional study was conducted in which 97 haemodialysis patients were initially evaluated in our hospital. Twelve inflammatory cytokines were measured using a cytometric beads assay in patients with and without PH. FE(NO) (fractional exhaled nitric oxide) was checked by a chemiluminescence analyser in patients with and without PH as well as by normal controls. Results Thirty-nine eligible patients were enrolled. Compared to patients without PH (group A), patients with PH (group B) had significantly higher serum levels of hs-CRP, IL-1beta, TNF-alpha and IL-6. FE(NO) was also measured. Though the pre-dialysis FE(NO) levels were elevated in both groups; group B patients had significantly higher pre-dialysis FE(NO) levels than group A patients (39.9 +/- 16.7 versus 31.8 +/- 10.3, P = 0.045). The post-dialysis FE(NO) levels returned to normal in group A while the remaining were significantly higher in group B (30.3 +/- 10.3 versus 20.1 +/- 10.9, P = 0.003). Conclusions Our study revealed that dialyzed patients with PH had a significantly higher level of airway FE(NO) as well as serum levels of acute phase reactive protein and cytokines, including IL-1beta, TNF-alpha and IL-6. A chronic inflammation might play an important role in the pathogenesis of PH in patients undergoing haemodialysis.

Background and objective: ARDS is life-threatening acute respiratory failure, and pneumonia is one of the most common causes of direct ARDS. Procalcitonin (PCT) has been evaluated for its utility in determining the aetiology of community-acquired pneumonia (CAP), choice of antibiotics and prediction of outcome. This study evaluated the role of PCT in predicting the outcome of patients with ARDS caused by severe CAP. Methods: This was a prospective observational study conducted from September 2002 to December 2003. The plasma PCT was analysed at baseline, 24 and 72 h after enrolment and measured by ELISA. Results: Of the 22 patients with ARDS caused by CAP and enrolled in the study, 17 (77.3%) were alive 14 days after admission and five (22.7%) had died. The survivors had lower APACHE II scores (22.2 ± 4.6 vs 30.6 ± 9.6, P = 0.031), pneumonia severity index (141.9 ± 2.2 vs 195.6 ± 23.8, P = 0.005) and lower plasma PCT at baseline (9.83 ± 3.54 vs 106.70 ± 67.86, P = 0.004), at 24 h (10.51 ± 5.39 vs 81.32 ± 57.68, P = 0.014) and at 72 h (2.03 ± 0.76 vs 19.57 ± 6.67, P = 0.005). Conclusion: PCT analysed within 72 h of the onset of ARDS predicted mortality of patients with ARDS caused by severe CAP.

Background/purpose To evaluate the roles of plasma sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) and C-reactive protein (CRP) in predicting treatment response in patients with community-acquired pneumonia (CAP). Methods Patients with CAP were enrolled prospectively at a medical center in central Taiwan from September 1, 2004 to July 31, 2005. They were treated according to the guidelines proposed by the American Thoracic Society. Patients were noted as nonresponsive to initial treatment if they had one of the following: persistent fever for more than 3 days, progression on chest radiograph, switching to other antibiotics, or need of mechanical ventilation and/or chest tube drainage. Results Fifty-eight patients (43 males/15 females; mean age, 67 ± 21 years) with CAP were enrolled. Twelve (12/58, 21%) were nonresponsive. In the response group, CRP was reduced up to 58% from day 1 to day 3 (from 18.8 to 7.8 mg/dL), whereas sTREM-1 was reduced by only 15% (from 32.8 to 28.1 pg/mL). In the nonresponse group, CRP still declined 20% (from 22.2 to 17.7 mg/dL), whereas sTREM-1 was persistently high (from 61.7 to 63.7 pg/mL). Using multivariate logistic regression analysis, both CRP ( p = 0.006) and sTREM-1 ( p = 0.046) on day 3 predicted treatment response significantly, but CRP on day 3 had stronger statistic power. Conclusion Both CRP and sTREM-1 on day 3 could be useful in predicting nonresponsive CAP patients. Differential trends between sTREM-1 and CRP in nonresponsive CAP suggest that sTREM-1 could be an adjuvant biomarker to CRP in predicting CAP patients without response to empiric treatment. [ J Formos Med Assoc 2007;106(3):187-195]

Yu-Feng Wei,1 Ping-Hung Kuo,2 Ying-Huang Tsai,3 Chi-Wei Tao,4 Shih-Lung Cheng,5,13 Chao-Hsien Lee,6 Yao-Kuang Wu,7 Ning-Hung Chen,8 Wu-Huei Hsu,9 Jeng-Yuan Hsu,10 Ming-Shian Lin,11 Chin-Chou Wang12 1Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 5Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan; 8Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University and China Medical University Hospital, Taichung, Taiwan; 10Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 13Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan Background and objective: The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice. The aim of this study was to explore the factors associated with the use of ICS in these patients. Methods: The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan. Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients. Results: Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively). The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients. Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14–4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24–2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40–2.96; P

BackgroundGender, smoking history, adenocarcinoma histology, performance status, and East Asian ethnicity were predictive factors of gefitinib response in previous analysis. However, these factors tend to be correlated with each other; it is not clear whether gender, smoking history, and adenocarcinoma histology were all independent predictors for response in East Asian populations.MethodsTumor response, survival and predictive factors of gefitinib response of advanced non-small cell lung cancer patients treated between May of 2002 and November of 2004 were collected retrospectively from three medical centers in Taiwan. Univariate and multivariate logistic regression models were used to test potential predictive factors associated with response to gefitinib. Overall survivals between groups with different predictive factors were compared by log-rank tests. Multivariate analyses were performed to identify factors that independently predict for survival.ResultsA total of 428 patients were analyzed. The median follow-up duration for living patients was 19.5 months (range, 10.2–39.9). Objective tumor response was observed in 114 patients (26.6%, 95% confidence interval [CI]: 22.4%–30.8%) and disease stabilization in 129 patients (30.2%). Response rate was statistically significant higher in adenocarcinoma, good performance status, and chemonaive patients in multivariate analysis. The median survival was 7.4 months (95% CI: 5.8–9.0) and 1-year survival was 34.3% (95% CI: 29.0%–38.0%). Significant independent predictive factors associated with longer survival in multivariate analysis were good performance status (p < 0.001) and responsiveness to gefitinib (p < 0.001). In 286 chemotherapy-treated patients, the response rate was 22.7%. Median and 1-year survival was 7.9 months and 36.7%, respectively. Good performance status was predictive of tumor response (p < 0.001) and better survival (p < 0.001) in multivariate analysis. Response to gefitinib was predictive of better survival (p < 0.001).ConclusionsGender and smoking status were not, but good performance status (PS), no previous chemotherapy, and adenocarcinoma histology were independent predictive factors in multivariate analysis for gefitinib response in Taiwanese advanced non-small cell lung cancer population. In patients previously treated with chemotherapy, only good PS was an independent predictor for tumor response in multivariate analysis.

Background The relationship between bacterial etiology and serum cytokine levels in patients with severe community-acquired pneumonia (CAP) without response to initial empiric treatment remains unclear. This study investigated the bacterial etiology, outcomes, and bronchoalveolar and systemic cytokines (interleukin [IL]-1β, IL-8, IL-10) in these patients. Methods This hospital-based study enrolled 47 consecutive patients without response to initial empiric treatment and requiring mechanical ventilation due to severe CAP between July 1, 2000 and October 31, 2001, in a respiratory intensive care unit of a 1200-bed teaching hospital in central Taiwan. Bronchoalveolar lavage (BAL) was performed within 3 days after hospitalization. BAL fluid was processed for quantitative bacterial cultures. Blood samples were taken just before BAL, and the levels of both BAL and serum cytokines were measured. Results The most common pathogens isolated were Pseudomonas aeruginosa (22.5%) and Klebsiella pneumoniae (25%). Patients with a K. pneumoniae isolate ( w = 10) had significantly higher levels of IL-1β in BAL fluid and significantly higher levels of IL-10 in serum and BAL fluid than patients with other etiologies. Non-survivors had higher levels of serum IL-8 (p = 0.001), serum IL-10 (p 0.001) and BAL IL-10 (p = 0.039) than survivors. Marked increases in local and systemic cytokine expression (IL-8 and IL-10) were noted in rapidly fatal cases. Conclusion P. aeruginosa and K. pneumoniae are the most common causes of CAP requiring mechanical ventilation in Taiwan. Cytokine patterns in the BAL fluid and serum of patients with severe CAP due to K. pneumoniae showed significant elevations compared to other pathogens. Bronchoalveolar and systemic cytokine levels (especially IL-10) predicted mortality. These findings suggest the need for a clinical trial to determine how immunomodulating therapy might affect cytokine profiles and clinical outcome.

Background/PurposeTo compare the efficacy and safety of tiotropium and ipratropium in patients with chronic obstructive pulmonary disease (COPD) in Taiwan.MethodsThis double-blind, randomized, placebo-controlled, parallel group study was conducted at six hospitals in Taiwan. COPD patients aged ≥ 40 years, with a forced expiratory volume in 1 second (FEV1) ≤65% of predicted and FEV1/forced vital capacity (FVC) ≤ 70% were enrolled. After a 2-week screening/baseline period, 132 patients were randomized to receive 4 weeks of treatment with either tiotropium 18 μg once daily from a dry powder inhaler (HandiHaler(r)) or two puffs of ipratropium 20 μg four times daily from a metered dose inhaler. The primary outcome was the change in trough FEV1 from baseline to week 4. The secondary outcome measures were trough FVC response, FEV1 and FVC responses at 2 hours postinhalation.ResultsAfter 4 weeks, trough FEV1 had increased by 61.7 + 25.3 mL for tiotropium but decreased by 16.4 + 27.9 mL for ipratropium. The difference between groups was significant (p

Advanced non-small-cell lung cancer (NSCLC) patients with poor performance status (PS) are less likely to respond to chemotherapy, or to have an improvement in survival, but more likely to experience toxicity. We retrospectively evaluated the efficacy and tolerability of gefitinib in patients with advanced NSCLC and very poor PS in Taiwan. Patients with stage IIIB, IV NSCLC with an Eastern Cooperative Oncology Group (ECOG) PS of 3-4 received oral gefitinib 250 mg once daily. Totally, 52 patients were included (25 men, 27 women). Forty-three patients (82.7%) were in a PS of 3. Tumor response rate was 25.0% (13/52). Tumor response rate to gefitinib was highest in chemonaive patients 38.1% (8/21) vs. failed 1 chemotherapy regimen 13.3% (2/15) vs. failed 2 or more chemotherapy regimens 18.8% (3/16), p = 0.015. The median overall survival was 2.5 months (response group 9.1 months, stable disease 3.1 months, and progressive group 0.8 month, p < 0.001). Adverse events, mainly skin reactions and diarrhea, were generally mild (grade 1 or 2) except paronychia and acne. Thus, gefitinib has clinically antitumor activity and good tolerability in Taiwan patients with advanced NSCLC and very poor performance status, with a higher response rate than that seen Europe or in European heritage Americans. Chemonaive patients responded better than patients with prior chemotherapy. Formal clinical trials are warranted to evaluate the role of gefitinib in this situation.

The study was carried out on elderly nursing home residents in Taiwan. We assessed whether the serial QuantiFERON-TB Gold (QFT-G) assay and serial tuberculin skin test (TST) were reliable tools to predict or exclude the development of active tuberculosis (TB).This prospective observational cohort study involved non-bacillus Calmette-Guérin-vaccinated 259 elderly nursing home residents free of active TB at baseline. Of these, 147 were eligible for follow up. Participants underwent serial QFT-G and TST at baseline and 2-year follow up, and were monitored for active TB over 5 years. Agreement between QFT-G and TST, incidence rate ratio, positive predictive value, and negative predictive value for progression to active TB were measured.During 5-year follow up, three participants developed active TB. The agreement between these two tests was 54.13% (ĸ = 0.167, P = 0.001). The incidence rate ratio was 15.8 (P = 0.016) for the QFT-G-conversion group compared with the TST-positive group at baseline. Positive predictive value for QFT-G conversion groups was 25%. Negative predictive value was 100% for the TST-negative group at baseline.In the elderly nursing home residents, QFT-G conversion is a more reliable tool to predict the development of active TB. Meanwhile, TST is a valuable tool for predicting the chance of not developing active TB.

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.

BackgroundDifferent end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms.ObjectivesWe aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance.MethodsPatients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis.ResultsThe mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (−11.0 ± 7.8 vs. −3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70.ConclusionsWe propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.

Fourteen patients, with abnormalities on their chest radiographs found over a period ofor = 4 weeks and diagnosed as chronic pulmonary infections in the follow-up, underwent ultrasound-guided fine-needle aspiration biopsy (US-guided FNAB). Six patients also underwent color Doppler ultrasound examination before needle aspiration biopsy. Nine patients had a confirmed diagnosis [tuberculosis (n = 1), cryptococcosis (n = 3), actinomycosis (n = 2), and aspergillosis (n = 1)] or a suggestive diagnosis [caseating granulomatous inflammation (n = 1) and caseous necrosis (n = 1)] made after US-guided FNAB. The remaining 5 patients were finally diagnosed by US-guided large-bore cutting biopsy (n = 1, tuberculosis) and surgical resection [aspergillosis and organized pneumonia (n = 1), mucormycosis and organized pneumonia (n = 1), penicillium infection and organized pneumonia (n = 1), and cryptococcosis (n = 1)]. In 8 patients receiving gray scale US examination only, complications developed in 2 patients after US-guided FNAB [minimal pneumothorax (n = 1) and hemoptysis (n = 1)]. Of the 6 patients who also underwent color Doppler US examination, 4 had detectable blood vessels within the lesion. Thus, the site for US-guided FNAB was changed in 2 patients to prevent injury to prominent blood vessels. There were no complications observed following color Doppler US examination. We conclude that US-guided FNAB is useful for diagnosing chronic pulmonary infections, and color Doppler US is valuable for preventing injury to blood vessels.

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.

The Asthma Insight and Management (AIM) survey was conducted in North America, Europe, the Asia-Pacific region and Latin America to characterize patients' insights, attitudes and perceptions about their asthma and its treatment. We report findings from the Asia-Pacific survey.Asthma patients (≥12 years) from Australia, China, Hong Kong, India, Malaysia, Singapore, South Korea, Taiwan and Thailand were surveyed. Patients answered 53 questions exploring general health, diagnosis/history, symptoms, exacerbations, patient burden, disease management, medications/treatments and patient's attitudes. The Global Initiative for Asthma guidelines were used to assess asthma control. The survey was conducted by random digit telephone dialling (Australia, China and Hong Kong) or by random face-to-face interviews (India, Malaysia, Singapore, South Korea, Taiwan and Thailand).There were 80 761 households screened. Data from 3630 patients were collected. Wide disparity existed between objective measures of control and patient perception. Reported exacerbations during the previous year ranged from 19% (Hong Kong) to 67% (India). Reported unscheduled urgent/emergency visits to a doctor's office/hospital/clinic in the previous year ranged from 15% (Hong Kong) to 46% (Taiwan). Patients who reported having controlled asthma in the previous month ranged from 27% (South Korea) to 84% (Taiwan). Substantial functional and emotional limitations due to asthma were identified by 13% (South Korea) to 78% (India) of patients.Asthma has a profound impact on patients' well-being despite the availability of effective treatments and evidence-based management guidelines. Substantial differences across the surveyed countries exist, suggesting unmet, country-specific cultural and educational needs. A large proportion of asthma patients overestimate their level of control.

Supplemental Digital Content is available in the text, The use of validated patient-reported outcome (PRO) instruments for the treatment outcome measure of laryngopharyngeal reflux (LPR) is crucial given the lack of objective markers. However, current symptom-based PRO instruments can only partially capture the impact of LPR. The GERD Analyzer (GERDyzer), an existing disease-specific PRO instrument, which measures multidimensional health-related quality of life (HRQL) affected by the illness rather than by any specific symptoms, has been validated in patients with erosive gastroesophageal reflux disease (GERD). Following the U.S. Food and Drug Administration PRO guidance, we cross-culturally adapted the GERDyzer instrument into Chinese, and examined the qualitative and quantitative psychometric properties of the Chinese version GERDyzer in pH-test-proven LPR patients. The GERDyzer comprises 10 dimensions of HRQL, including general well-being, pain/discomfort, physical health, diet, energy, activities, leisure activities, social life, mood, and sleep. To examine the content validity, we recruited 26 pH-test-proven LPR participants to conduct 4 focus group meetings for direct patient input on clinical manifestations and HRQL impacts. We also tested the quantitative psychometric properties, including reliability, validity, and responsiveness in 100 pH-test-proven LPR patients. Saturation of concept elicitation was achieved from the 4 focus groups, and a strong conceptual match was evident between the GERDyzer contents and responses from the focus group participants. Cognitive debriefing assessment showed that the Chinese version GERDyzer was adequate for use by patients as it demonstrated linguistic validation and cultural harmonization. Quantitative psychometric properties showed evidence of high internal consistency (Cronbach α: 0.96), good to excellent test-retest reliability (intraclass correlation coefficient: 0.84–0.98). Confirmatory factor analysis supported a 2-factor structure. Convergent validity was confirmed by moderate correlation assessments referencing the Reflux Symptoms Index and the Reflux Questionnaire. The discriminant validity was supported by the ability to discriminate moderate-to-severe disease from mild disease. The responsiveness was also high in participants with and without typical GERD symptoms (effect sizes 1.20 and 1.21, respectively). In conclusion, the Chinese version GERDyzer instrument is a reliable, valid, and responsive instrument for assessing HRQL in Taiwanese patients with LPR.

Objectives/Hypothesis Factors predicting the efficacy of proton pump inhibitors (PPIs) in patients with suspected laryngopharyngeal reflux (LPR) are unclear. PPI treatment in patients without concomitant esophageal syndrome remains controversial. We investigated whether composite pH can predict PPI treatment response for LPR with or without concomitant typical reflux syndrome (CTRS). Study Design Prospective, open-label therapeutic cohort study. Methods Patients with LPR in a tertiary center divided by presence (n = 65) and absence (n = 42) of CTRS underwent 24-hour esophagopharyngeal pH test and took esomeprazole (40 mg, twice daily) for 12 weeks. Positive composite pH was defined as the presence of 1) excessive pharyngeal acid reflux, and/or 2) excessive distal esophageal acid reflux. A responder was defined as a patient with ≥50% reduction in primary laryngeal symptoms. The change in reflux symptoms was determined using the reflux symptom index (RSI) questionnaire. Logistic regression and mixed model were used to evaluate the predictability of the composite pH parameter. Results After 8 and 12 weeks of treatment, participants with positive composite pH were 10.3-fold (95% confidence interval [CI], 1.7–61.5; P = .01) and 7.9-fold (95% CI, 1.4–44.8; P = .02) more likely to respond, respectively, than participants with negative composite pH among patients without CTRS. However, no difference was found in those with CTRS. Weekly repeated measures of RSI yielded similar findings. Conclusions In patients with suspected LPR without CTRS, a composite pH parameter, which incorporates pharyngeal and distal esophageal acid reflux, may predict response to esomeprazole therapy. Level of Evidence 2b

The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used. This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC. This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed. Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT⩾10/mMRC 0–1 subgroup had more wheezing than CAT

Accurate assessment of control is an integral part of asthma management. We investigated the relationship between control status derived from the Global Initiative for Asthma (GINA), the Asthma Control Test (ACT) and urgent health-care utilization.Asthma Insights and Reality in Asia-Pacific Phase 2 (AIRIAP 2) was a cross-sectional, community-based survey of 4805 subjects with asthma from urban centres across Asia. A symptom control index was derived from the AIRIAP 2 questionnaire using the GINA control criteria for day- and night-time symptoms, need for rescue medication, activity limitation and exacerbations; lung function was excluded. The main outcomes were asthma control, based on these GINA criteria and the ACT, and the relationship between control and self-reported urgent health-care utilization (hospitalization, emergency room visits or other unscheduled urgent visits) related to asthma over the previous 12months.Each of the symptom criteria was significantly associated with urgent health-care utilization, with odds ratios (ORs) ranging from 2.25 (95% confidence interval (CI): 1.94-2.61) for daytime symptoms to 2.57 (95% CI: 2.29-2.90) for nocturnal awakening. Similarly, control status was significantly associated with urgent health-care utilization, with ORs of 0.19 (95% CI: 0.13-0.28), 0.70 (95% CI: 0.65-0.76) and 1.00 for controlled, partly controlled and uncontrolled, respectively. The optimal ACT cut-off score for identifying uncontrolled asthma was ≤19 for subjects aged ≥12years. Urgent health-care utilization was reported by 57.2% versus 28.7% of patients scoring ≤19 versus19 (P0.001).The GINA control classification and the ACT are valid symptom-based measures that are significantly associated with urgent health-care utilization.

Background. Chronic obstructive pulmonary disease (COPD) is a common disease in the elderly population and is characterized by airway inflammation. Whether it is a progressive condition resulting from allergic inflammation or a distinct condition involving a pathogen-induced reaction remains unclear. Objectives. To determine the role of allergic inflammation in the pathogenesis of elderly COPD. Methods. A total of 63 elderly adults (21 mite-allergic COPD patients, 29 non-allergic COPD patients, and 13 normal controls) were recruited in this study. The serum-specific IgE for mites, level of interleukin-5 (IL-5), IL-8, leptin, adiponectin, regulated upon activation normal T cell expressed and secreted (RANTES), growth-related oncogene-α (GRO-α), vitamin E, and glutathione (GSH) were determined. Results. The serum levels of GRO-α in patients with COPD were higher in comparison to normal controls (105.8 ± 32.7 vs. 7.5 ± 7.5 pg/mL, p = .021). Compared to patients with non-allergic COPD, patients with mite allergies had a higher serum level of IL-8 (63.2 ± 12.6 vs. 35.0 ± 8.2 pg/mL, p = .022). Although both IL-5 and RANTES levels were increased in COPD patients, there were no significant differences between allergic and non-allergic COPD. There were also no differences in serum levels of leptin, adiponectin, vitamin E, and GSH between COPD patients and normal controls. Conclusions. The increased serum levels of GRO-α indicate that it may have potential as a candidate biomarker for elderly COPD patients. There was no difference of eosinophils-related chemokines in allergic and non-allergic COPD. These results indicated that both adipokines and eosinophil-related chemokines only play trivial roles in the pathogenesis of COPD.

Organophosphates and carbamates are potent cholinesterase inhibitors that are widely used as insecticides in agriculture. Pneumonia is a frequent complication of cholinesterase inhibitor poisoning (CIP) and a risk factor for death. The aim of this retrospective study was to assess the risk factors for pneumonia in patients with CIP.The medical records of 155 patients, who were treated for CIP in a 1300-bed medical centre in central Taiwan, from January 2002 to December 2004, were retrospectively analysed. Pneumonia was diagnosed by a new or persistent infiltrate on CXR, as well as clinical symptoms. Demographic data, comorbidities, acute respiratory failure and in-hospital mortality were also recorded.Of the 155 patients, 31 (20%) died and 92 (59.4%) developed acute respiratory failure. Thirty-four patients (21.9%) were diagnosed with early onset pneumonia during hospitalization. Acute respiratory failure (OR 12.10, 95% CI: 2.55-57.45), underlying cardiovascular disease (OR 3.02, 95% CI: 1.02-8.91), undergoing gastric lavage at peripheral hospitals (OR 6.23, 95% CI: 1.52-25.98) and development of respiratory failure at the study centre after gastric lavage (OR 3.43, 95% CI: 1.17-10.0) were predictive factors for early onset pneumonia. Cardiopulmonary resuscitation (OR 23.58, 95% CI: 6.03-92.29), early onset pneumonia (OR 7.45, 95% CI: 2.02-27.5) and lower Glasgow coma score (OR 1.26, 95% CI: 1.08-1.48) were predictive factors for mortality.Pneumonia was a significant risk factor for death in patients with CIP. In addition to aggressive management of patients with CIP who develop respiratory failure, careful respiratory evaluation before and after gastric lavage would help to decrease the incidence of early onset pneumonia in patients with CIP.

Impalpable osteolytic lesions may be detected and diagnosed by ultrasonography and sonographically guided needle aspiration biopsy. Eleven cases with bone destruction found on chest radiographs were proved to be malignant by sonographically guided needle aspiration biopsy. The bony lesions were all hypoechoic and could be demonstrated easily. No complications or discomfort occurred after needle aspiration. Bony lesions can be detected by ultrasonography only when pathologic changes have occurred. Ultrasonography and sonographically guided needle aspiration biopsy provide a simple, convenient, and non-invasive method for detecting and diagnosing impalpable osteolytic lesions.

Background/Purpose Acute respiratory distress syndrome (ARDS) is a serious disorder of intensive care unit patients. We evaluated the safety of continuous prone position ventilation (PRONE) and its effects on oxygenation and plasma cytokine concentrations in patients with ARDS caused by severe community-acquired pneumonia (CAP). Methods This was a prospective observational clinical study conducted in a respiratory intensive care unit of a 1200-bed medical center in central Taiwan. Twenty-two patients with severe CAP and ARDS were included. They were treated by traditional supine ventilation (SUPINE, n = 11) or PRONE (n = 11) if they met the criteria for ARDS. Patients in the PRONE group were ventilated in prone position continuously for at least 72 hours. Plasma cytokines were collected and analyzed at baseline, 24 hours and 72 hours after enrolment. Serial PaO2/FiO2 and complications were evaluated. Results Complications associated with PRONE were minor and self-limited. PRONE had higher PaO2/FiO2 ratio than SUPINE did at 48 hours after enrolment. The levels of plasma IL-6 concentration declined significantly with time in the PRONE group (p = 0.011). The levels of plasma IL-6 concentration at enrolment, 24 hours and 72 hours after enrolment also predicted the 14th day mortality of all patients. Conclusion PRONE was a safe and effective maneuver for improving oxygenation in patients with severe CAP and ARDS. PRONE also influenced IL-6 expression in patients with severe CAP.

Background and objective: The triggering receptor expressed on myeloid cell-1 (TREM-1) is a newly discovered molecule that is associated with the inflammatory response to microorganisms. We investigated the role of surface and soluble TREM-1 in differentiating different disease entities in pleural effusion formation. Methods: Sixty-seven patients with pleural effusion due to transudate (14), malignancy (15), tuberculous pleuritis (16), para-pneumonic effusion (10) and empyaema (12) were included in this study. Surface TREM-1 was measured by flow cytometry and was expressed as mean fluorescence intensity and soluble TREM-1 was measured by ELISA and expressed as pg/mL. Results are given as mean levels ± SEM. Results: Surface TREM-1 was measured in 24 patients and the levels were highest in para-pneumonic effusion (30.0 ± 8.4) and lowest in malignant pleural effusion (5.2 ± 1.1) and tuberculous pleuritis (5.2 ± 2.4). Soluble TREM-1 was highest in effusions of infectious aetiology (para-pneumonic effusion (979.4 ± 229.6) and empyaema (1712.6 ± 299.5)) and lowest in non-infectious effusions (transudate (81.2 ± 4.5 pg/mL) and malignancy (111.3 ± 20.7). At a cut-off value of 114 pg/mL, soluble TREM-1 yielded a sensitivity of 87.5% and a specificity of 89.7% in differentiating non-infectious effusion from tuberculous pleuritis. At a cut-off value of 374 pg/mL, sTREM-1 yielded a sensitivity of 93.8% and a specificity of 90.9 in differentiating tuberculous pleuritis from bacterial pleural effusion. Conclusion: Soluble and surface TREM-1 are valuable markers in establishing the aetiology of pleural effusions.

Objective This study investigated the trends in incidence and mortality of out-of-hospital cardiac arrest (OHCA), as well as factors associated with OHCA outcomes in Taiwan. Methods Our study included OHCA patients requiring cardiopulmonary resuscitation (CPR) upon arrival at the hospital. We used national time-series data on annual OHCA incidence rates and mortality rates from 2000 to 2012, and individual demographic and clinical data for all OHCA patients requiring mechanical ventilation (MV) care from March of 2010 to September of 2011. Analytic techniques included the time-series regression and the logistic regression. Results There were 117,787 OHCAs in total. The overall incidence rate during the 13 years was 51.1 per 100,000 persons, and the secular trend indicates a sharp increase in the early 2000s and a decrease afterwards. The trend in mortality was also curvilinear, revealing a substantial increase in the early 2000s, a subsequent steep decline and finally a modest increase. Both the 30-day and 180-day mortality rates had a long-term decreasing trend over the period (p

The aim of this study was to evaluate the characteristics of asthma in patients with different ages of disease onset.Five hundred and four asthmatic patients (303 males and 201 females) were divided into five groups based on age of onset (group I, age of onset15 years old; group II, 15-24 years old; group III, 25-44 years old; group IV, 45-64 years old; and group V,64 years old). The relationship between age of onset and the characteristics of asthma, including lung function, reversibility, atopic status and the incidence of coexistent allergic rhinitis was assessed. Multivariate analysis, adjusted for the duration of disease, gender, educational level, smoking status, and degree of previous inhaled corticosteroid treatment, was performed.Thirty per cent of the patients developed asthma before they were 14 years old (group I), and the percentages of those developing asthma at other ages of onset were: group II, 12%; group III, 29%; group IV, 21% and group V, 8%. In all, 57.6% of the asthmatic patients had coexistent allergic rhinitis; younger patients tended to have this comorbidity. The pulmonary function of older onset asthma patients was worse than that of early onset patients. The multivariate analysis showed that there was a positive correlation between the reduction of pulmonary function and duration of the disease (P0.001), but there was no relationship between pulmonary function and gender (P = 0.502), educational level (P = 0.734), smoking pack-years (P = 0.902), or degree of use of inhaled corticosteroid treatment (P = 0.586).Asthma is a heterogeneous disease with a wide variety of presentations. This study provides information about the disease characteristics and their relationship with age of onset. Further study is necessary to determine why these differences exist.

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p0.01; for PI, all por =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p0.05 for RI and PI), and even a significant difference from SCC (p0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.

Background: Traditional pleurodesis for malignant pleural effusion is performed by large-bore chest tube insertion with the instillation of sclerosing agents after the compressed lung re-expansion and pleural fluid drainage of 100-150 ml/day. This study was carried out to evaluate the possibility of rapid sclerotherapy for malignant pleural effusions by insertion of a small-bore Elecath tube (12-French) under ultrasound guidance and intrapleural injection of bleomycin 60 IU. Methods: Twenty-six patients, with 28 cytopathologically proven malignant pleural effusions (two patients had bilateral pleural effusions) and receiving the insertion of the Elecath tube for drainage, were included in our series. This rapid and short-term sclerosing method was performed and completed by intrapleural injection of bleomycin when the pleural effusion had been clearly drained by the small-bore Elecath tube and the compressed lung had fully re-expanded on follow-up chest radiographs. Results: Twenty patients with 22 pleural effusions underwent the intrapleural injection of bleomycin, with the results of pleurodesis being complete response 41% (9/22), partial response 36% (8/22) and failure 23% (5/22). Interestingly, among the 17 successful procedures of pleurodesis (complete response and partial response), 71% (12) procedures could be completed within 2 days (seven within one day and five within 2 days). The remaining unsuccessful procedures carried out on six patients without the injection of bleomycin were due to a non-re-expanded lung (n =3) and inadequate drainage (n =3); of these, four patients also received the large-bore chest tube insertion after the removal of the Elecath tube, but the compressed lung still could not re-expand. The complications of the bleomycin injection were fever [77% (17/22)], vomiting [14°,10 (3/22)] and hiccup [5% (1/22)]. Conclusion: The method of rapid sclerotherapy for malignant pleural effusions by small-bore Elecath tube is promising, with a success rate achieving 77%, usually within 2 days.

Background Chronic cough related to eosinophilic inflammation has become an important cause of cough in recent years. Although fractional exhaled nitrogen oxide (FeNO) measurement is an important monitoring tool, its lack of reference level may limit its usefulness. This study aimed to determine the optimal FeNO level to guide inhaled corticosteroid (ICS) management in patients with chronic cough. Methods This retrospective study reviewed the medical records of patients with chronic cough for more than 8 weeks. Based on the selection criteria, data were recalculated to determine the optimal cut-off value of FeNO for initiating ICS treatment in such patients. Results The medical records of 81 eligible patients were reviewed. Cough improved completely in 38 (Group A) of 44 patients who were treated with ICS but not in the other six patients (Group B). In the 37 patients without ICS treatment, cough improved in 32 (Group C) by specific treatment aimed at the possible causes of the cough, whereas the remaining five (Group D) had persistent cough. The patients were further subdivided into Category 1 (all patients in Group A) and Category 2 (all patients in Groups B and C). Receiver operating characteristic analysis showed that an FeNO of 33.9 ppb was the best cut-off value for using ICS (sensitivity 94.7%, specificity 76.3%) in patients with chronic cough. In fourteen of 15 patients with bronchial hyperresponsiveness (BHR) or borderline BHR, the FeNO values were equal or higher than 33.9 ppb. Obstructive ventilatory impairment was only seen in two patients. Conclusion Using FeNO measurement as a rapid, noninvasive diagnostic tool for patients with chronic cough, ICS can be prescribed if the FeNO is 33.9 ppb or more.

Background/PurposeThe collection of exhaled breath condensate (EBC) is a noninvasive method that can be used to monitor the inflammatory status of patients with chronic airway diseases. We aimed to study differences in cytokine expression between patients with exacerbations of chronic obstructive pulmonary disease (COPD) and patients with asthma attacks.MethodsUsing a custom-made device and methods based on American Thoracic Society (ATS)/European Respiratory Society (ERS) recommendations, EBC samples were collected from nine COPD patients, 12 asthma patients and 10 healthy individuals. Cytokine concentrations in serum and EBC were measured via commercial ELISA kits.ResultsOf four cytokines measured in EBC [interleukin-8 (IL-8), IL-17, IL-4 and tumor necrosis factor-α (TNF-α)], only IL-8 was significantly higher in COPD than in asthma patients (5.27 ± 0.18 vs. 4.36 ± 0.34 pg/mL, p = 0.001). Moreover, COPD patients had higher serum IL-8 than asthma patients (10.57 ± 0.55 vs. 5.15 ± 0.24 pg/mL, p

Background/PurposeSevere sepsis and septic shock are life-threatening disorders. Integrating treatments into a bundle strategy has been proposed to facilitate timely resuscitation, but is difficult to implement. We implemented protocol-driven therapy for severe sepsis, and analyzed retrospectively the key process indicators of mortality in managing sepsis.MethodsContinuous quality improvement was begun to implement a tailored protocol-driven therapy for sepsis in a 24-bed respiratory intensive care unit (RICU) of Taichung Veterans General Hospital from January 2007 to February 2008. Patients, who were admitted to the RICU directly, or within 24 hours, were enrolled if they met the criteria for severe sepsis and septic shock. Disease severity [Acute Physiology and Chronic Health Evaluation (APACHE) II and lactate level], causes of sepsis, comorbidity and site of sepsis onset were recorded. Process-of-care indicators included resuscitation time (Tr-s), RICU bed availability (Ti-s) and the ratio of completing the elements of the protocol at 1, 2, 4 and 6 hours. The structure and process-of-care indicators related to mortality at 7 days after RICU admission and at RICU discharge were identified retrospectively.ResultsEighty-six patients (mean age, 71 ± 14 years; 72 men, 14 women; APACHE II, 25.0 ± 7.0) were enrolled. APACHE II scores and lactate levels were higher for mortality than survival at 7 days after RICU admission (p < 0.01). For the process-of-care indicators, Ti-s (562.2 ± 483.3 vs.1017.3 ± 557.8 minutes, p = 0.03) and Tr-s (60.7 ± 207.8 vs. 248.5 ± 453.1 minutes, p = 0.07) were shorter for survival than mortality at 7 days after RICU admission. The logistic regression study showed that Tr-s was an important indicator. The ratio of completing the elements of protocols at 1, 2, 4 and 6 hours ranged from 70% to 90% and was not related to mortality.ConclusionProtocol-driven therapy for sepsis was put into clinical practice. Early resuscitation and ICU bed availability were key process indicators in managing sepsis, to reduce mortality.