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Abstract This post-hoc analysis of the SABINA III study evaluated the association of short-acting β2-agonist (SABA) prescriptions and self-reported over-the-counter (OTC) SABA purchase in the previous 12 months with asthma-related outcomes using multivariable regression models in 4556 patients (mean age, 48.9 years). Of the 2810 patients prescribed ≥3 SABA canisters, 776 (27.6%) also purchased ≥1 SABA OTC. This subset of 776 patients reported the highest disease burden; 73.2% had ≥1 severe exacerbation and 55.7% had uncontrolled asthma. Asthma-related outcomes worsened with any SABA OTC purchase, regardless of SABA prescriptions; disease burden was the highest in patients with ≥3 SABA prescriptions and ≥1 SABA OTC purchase vs 1–2 SABA prescriptions only (86% lower odds of having at least partly controlled asthma and 124% increased incidence of severe asthma (both P

Abstract Background Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Background: Tuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. Methods: We conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan–Meier analysis, and Cox proportional hazards models. Results: A total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan–Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose–response relationship against the DILI. Conclusion: Statin treatment had a protective effect against the risk of anti-TB DILI with a positive dose–response relationship.

Abstract Background Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). Methods This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. Results Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p

Background: This study investigates the impact of nontuberculous mycobacterial lung disease (NTM-LD) on mortality and mechanical ventilation use in critically ill patients. Methods: We enrolled patients with NTM-LD or tuberculosis (TB) in intensive care units (ICU) and analysed their association with 30-day mortality and with mechanical ventilator-free survival (VFS) at 30 days after ICU admission. Results: A total of 5996 ICU-admitted patients were included, of which 541 (9.0 %) had TB and 173 (2.9 %) had NTM-LD. The overall 30-day mortality was 22.2 %. The patients with NTM-LD had an adjusted hazard ratio (aHR) of 1.49 (95 % CI, 1.06–2.05), and TB patients had an aHR of 2.33 (95 % CI, 1.68–3.24), compared to ICU patients with negative sputum mycobacterial culture by multivariable Cox proportional hazard (PH) regression. The aHR of age

Introduction The EXAcerbations of Chronic obstructive lung disease (COPD) and their OutcomeS (EXACOS) International Study aimed to quantify the rate of severe exacerbations and examine healthcare resource utilisation (HCRU) and clinical outcomes in patients with COPD from low-income and middle-income countries.Methods EXACOS International was an observational, cross-sectional study with retrospective data collection from medical records for a period of up to 5 years. Data were collected from 12 countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Guatemala, Hong Kong, Mexico, Panama, Russia and Taiwan. The study population comprised patients ≥40 years of age with COPD. Outcomes/variables included the prevalence of severe exacerbations, the annual rate of severe exacerbations and time between severe exacerbations; change in lung function over time (measured by the forced expiratory volume in 1 s (FEV1)); peripheral blood eosinophil counts (BECs) and the prevalence of comorbidities; treatment patterns; and HCRU.Results In total, 1702 patients were included in the study. The study population had a mean age of 69.7 years, with 69.4% males, and a mean body mass index of 26.4 kg/m2. The mean annual prevalence of severe exacerbations was 20.1%, and 48.4% of patients experienced ≥1 severe exacerbation during the 5-year study period. As the number of severe exacerbations increased, the interval between successive exacerbations decreased. A statistically significant decrease in mean (SD) FEV1 from baseline to post-baseline was observed in patients with ≥1 severe exacerbation (1.23 (0.51) to 1.13 (0.52) L; p=0.0000). Mean BEC was 0.198 x109 cells/L, with 64.7% of patients having a BEC ≥0.1 x109 cells/L and 21.3% having a BEC ≥0.3 x109 cells/L. The most common comorbidity was hypertension (58.3%). An increasing number of severe exacerbations per year was associated with greater HCRU.Discussion The findings presented here indicate that effective treatment strategies to prevent severe exacerbations in patients with COPD remain a significant unmet need in low-income and middle-income countries.

Objectives: Persistent growth of Mycobacterium abscessus complex (MABC) in the respiratory system is not uncommon and may indicate continuous infection of MABC lung disease (MABC-LD), but its prevalence, risk factors, and clinical impact have not been investigated. Methods: The present study was conducted in two medical centers in northern Taiwan. We enrolled patients with MABC-LD and investigated the prevalence and predictors of persistent culture positivity (MABC-PP). Furthermore, we analyzed the association between MABC-PP and radiographic or clinical progression. Results: Among 189 patients with MABC-LD, 58 were in the MABC-PP group. Independent predictors for MABC-PP included an increasing radiographic score and highest acid-fast stain (AFS) of strong positivity (3-4+) at initial diagnosis (compared with negative AFS). MABC-PP and highest AFS were independently associated with MABC-LD progression by the multivariable analysis model. The adjusted hazard ratio increased to 3.56 when the two independent factors existed. Conclusions: MABC-PP accounted for 30.7% and was predicted by initial AFS grade and radiographic score. Patients with MABC-PP, and highest AFS grade might have disease progression.

Abstract Background Patients with influenza-related acute respiratory distress syndrome (ARDS) are critically ill and require mechanical ventilation (MV) support. Prolonged mechanical ventilation (PMV) is often seen in these cases and the optimal management strategy is not established. This study aimed to investigate risk factors for PMV and factors related to weaning failure in these patients. Methods This retrospective cohort study was conducted by eight medical centers in Taiwan. All patients in the intensive care unit with virology-proven influenza-related ARDS requiring invasive MV from January 1 to March 31, 2016, were included. Demographic data, critical illness data and clinical outcomes were collected and analyzed. PMV is defined as mechanical ventilation use for more than 21 days. Results There were 263 patients with influenza-related ARDS requiring invasive MV enrolled during the study period. Seventy-eight patients had PMV. The final weaning rate was 68.8% during 60 days of observation. The mortality rate in PMV group was 39.7%. Risk factors for PMV were body mass index (BMI) > 25 (kg/m2) [odds ratio (OR) 2.087; 95% confidence interval (CI) 1.006–4.329], extracorporeal membrane oxygenation (ECMO) use (OR 6.181; 95% CI 2.338–16.336), combined bacterial pneumonia (OR 4.115; 95% CI 2.002–8.456) and neuromuscular blockade use over 48 h (OR 2.8; 95% CI 1.334–5.879). In addition, risk factors for weaning failure in PMV patients were ECMO (OR 5.05; 95% CI 1.75–14.58) use and bacteremia (OR 3.91; 95% CI 1.20–12.69). Conclusions Patients with influenza-related ARDS and PMV have a high mortality rate. Risk factors for PMV include BMI > 25, ECMO use, combined bacterial pneumonia and neuromuscular blockade use over 48 h. In addition, ECMO use and bacteremia predict unsuccessful weaning in PMV patients.

Background: Type 2 diabetes mellitus (DM) is a risk factor for mycobacterial pulmonary infections (MPI), including tuberculosis (TB) and nontuberculous mycobacterial lung disease (NTM-LD). Dipeptidyl peptidase IV inhibitor (DPP4i), a common DM medication, has an immune-modulation effect that raises concerns about developing MPI. However, there is scarce research on the topic. Methods: This retrospective study was conducted in a tertiary-referral center in Taiwan from 2009 to 2016. Patients with type 2 DM who were receiving any DM medication were enrolled. TB and NTM-LD were defined by microbiological criteria. We analyzed the risk of MPI in DPP4i users using Cox proportional hazard regression with adjusted inverse probability of treatment weighting. Results: A total of 9963 patients were included. Among them, 3931 were classified as DPP4i users, and 6032 patients were DPP4i nonusers. DPP4i users had no increase in incidences of MPI (604 vs. 768 per 100,000 person-years, p = 0.776), NTM-LD (174 vs. 255 per 100,000 person-years, p = 0.228), and TB (542 vs. 449 per 100,000 person-years, p = 0.663) relative to those of DPP4i nonusers. After adjustment, the adjusted hazard ratios for MPI (aHR: 1.07, 95% CI: 0.79–1.45), TB (aHR: 1.15, 95% CI: 0.81–1.64) and NTM-LD (aHR: 0.85, 95% CI: 0.49–1.47) were not significantly increased relative to those of nonusers. The subgroup analysis also showed that DPP4i use did not increase the risk of MPI in different DM severities and comorbidities. Conclusions: According to our large cohort study, DPP4i use is safe for patients with type 2 DM and might not increase the risk of MPI.

Abstract Background To investigate the clinical outcomes and risk factors associated with progressive fibrosing interstitial lung disease (PF-ILD) in patients with primary Sjögren’s syndrome-associated interstitial lung disease (pSjS-ILD). Methods During 2015–2021, pSjS patients with ILD were retrospectively identified. Patients were grouped into non-PF-ILD and PF-ILD. Demographics, laboratory data, pulmonary function tests (PFTs), images, survival outcomes were compared between groups. Results 153 patients with SjS-ILD were reviewed, of whom 68 having primary SjS-ILD (pSjS-ILD) were classified into non-PF-ILD (n = 34) and PF-ILD groups (n = 34). PF-ILD group had persistently lower albumin levels and a smaller decline in immunoglobulin G (IgG) levels at the 3rd month of follow-up. The multivariate logistic regression analysis revealed that persistently low albumin levels were associated with PF-ILD. At the 12th month, the PF-ILD group experienced a smaller increase in FVC and a greater decline in the diffusion capacity of carbon monoxide (DLCO) than at baseline. The 3-year overall survival rate was 91.2%, and PF-ILD group had significantly poorer 3-year overall survival rate than non-PF-ILD group (82.4% vs. 100%, p = 0.011). Poor survival was also observed among female patients with PF-ILD. Conclusions Among patients with pSjS-ILD, the PF-ILD group had poorer 3-year survival outcomes. Persistent lower albumin level might be the risk factor of PF-ILD. Early lung function tests could be helpful for the early detection of PF-ILD.

Abstract Background Timely differentiating between pulmonary tuberculosis (TB) and nontuberculous mycobacterial lung disease (NTM-LD), which are radiographically similar, is important because infectiousness and treatment differ. This study aimed to evaluate whether artificial intelligence could distinguish between TB or NTM-LD patients by chest X-rays (CXRs) from suspects of mycobacterial lung disease. Methods A total of 1500 CXRs, including 500 each from patients with pulmonary TB, NTM-LD, and patients with clinical suspicion but negative mycobacterial culture (Imitator) from two hospitals, were retrospectively collected and evaluated in this study. We developed a deep neural network (DNN) and evaluated model performance using the area under the receiver operating characteristic curves (AUC) in both internal and external test sets. Furthermore, we conducted a reader study and tested our model under three scenarios of different mycobacteria prevalence. Results Among the internal and external test sets, the AUCs of our DNN model were 0.83 ± 0.005 and 0.76 ± 0.006 for pulmonary TB, 0.86 ± 0.006 and 0.64 ± 0.017 for NTM-LD, and 0.77 ± 0.007 and 0.74 ± 0.005 for Imitator. The DNN model showed higher performance on the internal test set in classification accuracy (66.5 ± 2.5%) than senior (50.8 ± 3.0%, p

Background: The extent of short-acting Beta-2-agonist (β2-agonist) (SABA) use across Asian countries is not well documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients with asthma from Asia. Methods: This cross-sectional study recruited patients (aged ≥12 years) with asthma from 8 Asian countries. Data on disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by practice type (primary or specialist care) and investigator-defined asthma severity (per Global Initiative for Asthma [GINA] 2017 recommendations). The association of SABA prescriptions with clinical outcomes was analyzed using multivariable regression models. Results: Overall, 3066 patients were analyzed, with a mean (standard deviation) age of 51.8 (16.7) years; of these patients, 2116 (69%) were female, 2517 (82.1%) had moderate-to-severe asthma and 2498 (81.5%) and 559 (18.2%) were treated in specialist and primary care, respectively. In total, 1423 (46.4%) patients had partly controlled/uncontrolled asthma, with 1149 (37.5%) patients experiencing ≥1 severe asthma exacerbation in the previous year. Overall, 800 (26.7%) patients were prescribed ≥3 SABA canisters in the previous year, which is regarded as overprescription and was associated with a significantly decreased odds of at least partly controlled asthma and increased incidence rates of severe exacerbations (P

Purpose: Limited data exist on asthma medication patterns in Taiwan. The objectives of the SABINA III cross-sectional study in Taiwan were thus, to describe patient demographics and clinical features and estimate short-acting β2-agonist (SABA) and inhaled corticosteroids (ICS) prescriptions per patient. Methods: Patients (≥18 years) with asthma were classified by investigator-defined asthma severity per the 2017 Global Initiative for Asthma (GINA) recommendations. Data on asthma symptom control (per GINA 2017 recommendations), severe exacerbation history, and prescribed treatments in the 12 months before study visit were collected using electronic case-report forms. Analyses were descriptive. Results: Overall, all 294 analyzed patients (mean [SD] age, 57.9 [15.6] years; female, 69%) were enrolled by specialists and had fully reimbursed healthcare. Most patients were classified with moderate-to-severe asthma (93.2%; GINA steps 3–5), were obese (53.4%) and nonsmokers (79.6%), reported high school or university and/or postgraduate education (61.9%), and had ≤2 comorbidities (89.1%). Mean (SD) asthma duration was 8.3 (10.0) years, with 37.8% of patients experiencing ≥1 severe exacerbation 12 months before the study visit. Overall, 62.2%, 26.2%, and 11.6% of patients had well-controlled, partly controlled, and uncontrolled asthma, respectively. Crucially, 19.3% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (overprescription). ICS, ICS + long-acting β2-agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 6.5%, 97.3%, and 31.6% of patients, respectively. Conclusion: Despite treatment by specialists and fully reimbursed healthcare, findings indicate room for improvement in asthma control and SABA prescription practices in Taiwan, emphasizing the need to adhere to latest evidence-based guidelines.

Background: Paradoxical upgrading reaction (PUR) indicates the unanticipated deterioration during therapy in patients with tuberculous lymphadenitis. We investigated the diagnostic performance of the ultrasonography and shear wave elastography (SWE) in predicting the therapeutic response of peripheral tuberculous lymphadenitis. Methods: A prospective observational study was conducted from December 2017 to August 2020. Participants diagnosed with peripheral tuberculous lymphadenitis were included for a longitudinal follow-up utilizing ultrasonography with two-dimensional SWE to record sonographic features and the maximum elasticity value (Emax). We defined PUR as the development of any worsening symptoms of the pre-existing lymphadenitis within one month after the previous ultrasonography. Results: A total of 108 sonographic and SWE examinations were performed in 20 enrollees (75% woman), and their mean ( ± standard deviation) age was 49.6 ( ± 22.7) years. The area under the receiver operating characteristic curve of Emax to predict the next-month PUR was 0.906 at the cut-point of 85 kPa, with an accuracy of 87.0%, a sensitivity of 81.1% and a specificity of 87.9%. Multivariate analysis indicated that Emax > 85 kPa (OR: 24.85, 95% CI: 4.01–154.08, p 2 kPa/month (OR: 15.14, 95% CI: 4.24–54.06, p

Abstract Background Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed. Methods Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded. Results From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than − 20 cmH2O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2–569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1–4 days vs 3–7 days], p

Background/Purpose: Both prone positioning and extracorporeal membrane oxygenation (ECMO) are used as rescue therapies for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS). This study compared outcomes between patients with severe influenza pneumonia-related ARDS who received prone positioning and those who received ECMO. Methods: This retrospective cohort study included eight tertiary referral centers in Taiwan. All patients who were diagnosed as having influenza pneumonia-related severe ARDS were enrolled between January and March 2016. We collected their demographic data and prone positioning and ECMO outcomes from medical records. Results: In total, 263 patients diagnosed as having ARDS were included, and 65 and 53 of them received prone positioning and ECMO, respectively. The baseline PaO2/FiO2 ratio, Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score did not significantly differ between the two groups. The 60-day mortality rate was significantly higher in the ECMO group than in the prone positioning group (60% vs. 28%, p = 0.001). A significantly higher mortality rate was still observed in the ECMO group after propensity score matching (59% vs. 36%, p = 0.033). In the multivariate Cox regression analysis, usage of prone positioning or ECMO was the single independent predictor for 60-day mortality (hazard ratio: 2.177, p = 0.034). Conclusion: While the patients receiving prone positioning had better outcome, the causality between prone positioning and the prognosis is unknown. However, the current data suggested that patients with influenza-related ARDS may receive prone positioning before ECMO support.

Background/Purpose: The application of the checkbox for identifying patients with traits of both chronic obstructive pulmonary disease (COPD) and asthma proposed by the 2015 Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations has not been well studied although such identification is important in clinical practice. Thus, we aimed to investigate the prevalence and features of COPD coexistent with asthma traits diagnosed based on the 2015 GINA/GOLD strategies, and explore the gap between guidelines and routine practice in the diagnosis and pharmacological management of such condition in a COPD cohort. Methods: COPD subjects were enrolled retrospectively throughout Taiwan. A patient record form was completed for each participant and the data were analyzed. Results: Of 340 participants, the prevalence of COPD coexistent with traits of asthma was 39.4% and 30.3% based on guidelines and physician's judgment, respectively. Coexistent patients were characterized by blood eosinophilia, higher total immunoglobulin E (IgE) levels, preserved lung function, and the presence of gastro-esophageal reflux disease and atopic disease while total IgE level > 100 kU/L and the presence of atopic disease were predictors for coexistent patients. Gaps existed in the diagnosis (a weak agreement with kappa = 0.53) and treatment (non-adherence to the preferred therapy in 18.4% of physician-judged coexistent patients) in COPD patients with asthma traits. The exacerbation history was similar between coexistent and non-coexistent patients. Conclusion: We found that measuring circulatory eosinophil and total IgE levels may raise clinicians’ awareness of the presence of traits of asthma in the management of COPD.

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

Abstract 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.

Abstract This study aims to investigate the prevalence of short-acting β2-agonist (SABA) overuse in asthma and the associated risk of acute exacerbation and mortality in Taiwan. We used the Taiwanese pay-for-performance asthma program database, which included patients aged between 12 and 100 years who were enrolled in the program between 2001 and 2015. Among a total of 218,039 patients, 34,641 (15.9%) patients are classified as SABA over-users. Compared with patients who did not receive inhaled corticosteroids (ICS) and collected ≤2 canisters, SABA over-users had a higher risk of severe exacerbations. SABA over-users had a higher risk of all-cause mortality compared with patients who did not receive ICS and collected ≤2 canisters. The overall prevalence of SABA overuse in Taiwan is 15.9%, and this is even higher in concomitant ICS users. In addition, the overuse of SABA is associated with an increased risk of severe exacerbation and death.

Abstract Objectives To investigate the incidence of active tuberculosis (TB) among COPD patients using fluticasone/salmeterol or budesonide/formoterol, and to identify any differences between these two groups of patients. Methods The study enrolled COPD patients from Taiwan NHIRD who received treatment with fluticasone/salmeterol or budesonide/formoterol for > 90 days between 2004 and 2011. The incidence of active TB was the primary outcome. Results Among the intention-to-treat population prior to matching, the incidence rates of active TB were 0.94 and 0.61% in the fluticasone/salmeterol and budesonide/formoterol groups, respectively. After matching, the fluticasone/salmeterol group had significantly higher rates of active TB (adjusted HR, 1.41, 95% CI, 1.17–1.70) compared with the budesonide/formoterol group. The significant difference between these two groups remained after a competing risk analysis (HR, 1.45, 95% CI, 1.21–1.74). Following propensity score matching, the fluticasone/salmeterol group had significantly higher rates of active TB compared with the budesonide/formoterol group (adjusted HR, 1.45, 95% CI, 1.14–1.85). A similar trend was observed after a competing risk analysis (HR, 1.44, 95% CI, 1.19–1.75). A higher risk of active TB was observed in the fluticasone/salmeterol group compared with the budesonide/formoterol group across all subgroups, but some differences did not reach statistical significance. Conclusion Fluticasone/salmeterol carried a higher risk of active TB compared with budesonide/formoterol among COPD patients.

Abstract Background Corticosteroid treatment has been widely used in the treatment of septic shock, influenza, and ARDS, although some previous studies discourage its use in severe influenza patients. This multicenter retrospective cohort study conducted in the intensive care units (ICUs) of eight medical centers across Taiwan aims to determine the real-world status of corticosteroid treatment in patients with influenza-associated acute respiratory distress syndrome (ARDS) and its impact on clinical outcomes. Between October 2015 and March 2016, consecutive ICU patients with virology-proven influenza infections who fulfilled ARDS and received invasive mechanical ventilation were enrolled. The impact of early corticosteroid treatment (≥ 200 mg hydrocortisone equivalent dose within 3 days after ICU admission, determined by a sensitivity analysis) on hospital mortality (the primary outcome) was assessed by multivariable logistic regression analysis, and further confirmed in a propensity score-matched cohort. Results Among the 241 patients with influenza-associated ARDS, 85 (35.3%) patients receiving early corticosteroid treatment had similar baseline characteristics, but a significantly higher hospital mortality rate than those without early corticosteroid treatment [43.5% (37/85) vs. 19.2% (30/156), p

Background: We hypothesized urine albumin concentration may detect the early increasing cardiac load during the spontaneous breathing trial (SBT). The purpose of our study is to determine whether the changes in urine albumin concentration before and after the SBT correlate with SBT outcome. Methods: This prospective observational study was conducted from January 2013 to September 2013. Patients receiving endotracheal tube intubation due to acute respiratory failure were included. Urine albumin concentration was measured upon admission to the intensive care unit, before and after the SBT. Results: A total of 211 patients with respiratory failure were screened. Finally, 69 patients were included for analysis. Among the 69 patients received the SBT, 61 patients passed the SBT while 8 patients didn't. Urine albumin concentration upon admission was 251.00 ± 108.21 mg/g in the SBT success group and 260.87 ± 77.95 mg/g in the SBT failure group (p = 0.97). The mean percent change in urine albumin concentration during the SBT was significantly higher in the SBT failure group (+58.44%) than in the SBT success group (+13.11%) (p = 0.02). Univariable and multivariable logistic regression model showed that the difference of urine albumin concentration before and after the SBT correlated significantly with SBT failure (adjusted OR:1.04, p = 0.01). Conclusion: This open label pilot study demonstrates the significant association of the changes in urine albumin concentration with SBT outcome. Further study is warranted to investigate the predictive value of urine albumin concentration. Keywords: Albuminuria, Spontaneous breathing trial, Weaning from mechanical ventilation

Idiopathic pulmonary fibrosis (IPF) causes progressive lung fibrosis with subsequent fatality and has limited treatment options. NICEFIT is the first Taiwan-based prospective, observational, and non-interventional registry for IPF progression under routine clinical practice in Taiwan. Data on 101 patients (aged 74.6 ± 9.1 years and 83.2% men) with IPF were collected over 2 years (2018−2020) from medical centers in Taiwan at baseline, 1 month, and subsequent 3-month intervals. Treated patients (n = 88) received the antifibrotics nintedanib or pirfenidone, compared with the untreated group (n = 13). The 2-year assessment revealed overall preserved lung functionality in the treated patients, with insignificant changes from baseline for percent predicted forced vital capacity or FVC (±1.7%). The presence of respiratory comorbidities significantly increased the risk of both AE and death (with or without AE) over the full study duration. Furthermore, the decline of predicted FVC significantly increased with the risk of acute exacerbations (AE) in the second year. Overall, antifibrotic medication was beneficial in stalling IPF progression, reducing AEs, and delaying mortality in the treated cohort, despite their lower baseline lung functions. Further, no new safety concerns over antifibrotic treatments were observed for the Taiwanese population.

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

Backgrounds: Severe influenza infection causes substantial morbidity and mortality worldwide and remains an important threat to global health. This study addressed factors related to treatment outcomes in subjects of complicated influenza infection with acute respiratory distress syndrome (ARDS) during the Taiwan epidemic in the Spring of 2016. Methods: This is a retrospective study conducted by Taiwan Severe Influenza Research Consortium (TSIRC), including eight tertiary referral medical centers. Patients with virology-proven influenza infection admitted to intensive care unit (ICU) between January and March 2016 were included for analysis. Results: We identified 263 patients with complicated influenza infection who fulfilled ARDS criteria; the mean age was 59.8 ± 14.6 (years), and 66.1% (166/263) were male. Type A influenza (77.9%, 205/263) virus was the main pathogen during this epidemic. The 30-day mortality rate was 23.2% (61/263). The mean tidal volume (VT) in the first three days after intubation was greater than 8 mL/kg of predicted body weight (PBW). Patients whose first measured VT was >8 mL/kg PBW had an increased 30-day mortality (p = 0.04, log-rank test). In a multivariate Cox proportional hazard regression model, an increase of 1 mL/kg PBW of first VT was associated with 26.1% increase in 30-day mortality (adjusted hazard ratio 1.261, 95% confidence interval [CI] 1.072–1.484, p

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: Patients with severe influenza-related acute respiratory distress syndrome (ARDS) have high morbidity and mortality. Moreover, nosocomial lower respiratory tract infection (NLRTI) complicates their clinical management and possibly worsens their outcomes. This study aimed to explore the clinical features and impact of NLRTI in patients with severe influenza-related ARDS. Methods: This was an institutional review board approved, retrospective, observational study conducted in eight medical centers in Taiwan. From January 1 to March 31 in 2016, subjects were enrolled from intensive care units (ICUs) with virology-proven influenza pneumonia, while all of those patients with ARDS requiring invasive mechanical ventilation and without bacterial community-acquired pneumonia (CAP) were analyzed. Baseline characteristics, critical-illness data and clinical outcomes were recorded. Results: Among the 316 screened patients with severe influenza pneumonia, 250 with acute respiratory failure requiring intubation met the criteria of ARDS, without having bacterial CAP. Among them, 72 patients developed NLRTI. The independent risk factors for NLRTI included immunosuppressant use before influenza infection [odds ratio (OR), 5.669; 95% confidence interval (CI), 1.770–18.154], extracorporeal membrane oxygenation (ECMO) use after ARDS (OR, 2.440; 95% CI, 1.214–4.904) and larger corticosteroid dosage after ARDS (OR, 1.209; 95% CI, 1.038–1.407). Patients with NLRTI had higher in-hospital mortality and longer ICU stay, hospitalization and duration on mechanical ventilation. Conclusion: We found that immunosuppressant use before influenza infection, ECMO use, and larger steroid dosage after ARDS independently predict NLRTI in influenza-related ARDS. Moreover, NLRTI results in poorer outcomes in patients with severe influenza. The reviews of this paper are available via the supplemental material section.

Nontuberculous mycobacteria (NTM) are critical emerging global infectious pathogens. Though NTM can be mere colonizers when isolated from human specimens, NTM are also responsible for diverse human infections. NTM–lung disease (NTM-LD) is the most common human disease entity. The present review aims to provide general insight into NTM-LD epidemiology in Taiwan.In reviewing NTM epidemiology in Taiwan, we discovered three distinguishing features. First, NTM disease incidence has increased in Taiwan over the past decade. Second, the distribution of NTM varies geographically in Taiwan. Mycobacterium avium-intracellulare complex (MAC) is the dominant species in northern Taiwan, whereas Mycobacterium abscessus complex and MAC may be equally dominant in southern Taiwan. Third, researchers in Taiwan have published valuable research investigating NTM among special patient populations, including patients in intensive care units, with ventilator dependency, with pulmonary tuberculosis, and who are infected with specific NTM species. The largest obstacle to clarifying NTM epidemiology in Taiwan may be the lack of routine NTM species identification in laboratories. Increased awareness of NTM diseases and acknowledgment that NTM species identification is crucial and guides clinical management are essential steps for facilitating the identification of NTM species in laboratories.

ObjectivesCurrent mortality prediction models used in the intensive care unit (ICU) have a limited role for specific diseases such as influenza, and we aimed to establish an explainable machine learning (ML) model for predicting mortality in critically ill influenza patients using a real-world severe influenza data set.Study designA cross-sectional retrospective multicentre study in TaiwanSettingEight medical centres in Taiwan.ParticipantsA total of 336 patients requiring ICU-admission for virology-proven influenza at eight hospitals during an influenza epidemic between October 2015 and March 2016.Primary and secondary outcome measuresWe employed extreme gradient boosting (XGBoost) to establish the prediction model, compared the performance with logistic regression (LR) and random forest (RF), demonstrated the feature importance categorised by clinical domains, and used SHapley Additive exPlanations (SHAP) for visualised interpretation.ResultsThe data set contained 76 features of the 336 patients with severe influenza. The severity was apparently high, as shown by the high Acute Physiology and Chronic Health Evaluation II score (22, 17 to 29) and pneumonia severity index score (118, 88 to 151). XGBoost model (area under the curve (AUC): 0.842; 95% CI 0.749 to 0.928) outperformed RF (AUC: 0.809; 95% CI 0.629 to 0.891) and LR (AUC: 0.701; 95% CI 0.573 to 0.825) for predicting 30-day mortality. To give clinicians an intuitive understanding of feature exploitation, we stratified features by the clinical domain. The cumulative feature importance in the fluid balance domain, ventilation domain, laboratory data domain, demographic and symptom domain, management domain and severity score domain was 0.253, 0.113, 0.177, 0.140, 0.152 and 0.165, respectively. We further used SHAP plots to illustrate associations between features and 30-day mortality in critically ill influenza patients.ConclusionsWe used a real-world data set and applied an ML approach, mainly XGBoost, to establish a practical and explainable mortality prediction model in critically ill influenza patients.

There are more single inhaler device triple therapy available for COPD patients now. However, the effect of long-term triple therapy fixed dose combination (FDC) on mortality remains unclear. This study aimed to evaluate the impact of one-year single inhaler device triple therapy, including long-acting β2-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), and inhaled corticosteroids (ICSs), with dual therapies, comprised of either LABA/LAMA or ICS/LABA, on the mortality of patients with COPD. We searched the PubMed, Cochrane library, Web of Science, Embase databases, and clinical trial registry of clinicaltrials.gov and WHO ICTRP. Randomized controlled trials (RCTs) compared single inhaler device triple and dual therapies for 52 weeks were selected for the meta-analysis. The primary endpoint was all-cause mortality. A total of 6 RCTs were selected for the meta-analysis, including 10,274 patients who received single inhaler device triple therapy (ICS/LABA/LAMA FDC) and 12,395 patients who received ICS/LABA or LABA/LAMA dual therapy. Risk of death was significantly lower in the ICS/LABA/LAMA FDC group compared to the LABA/LAMA group (RR = 0.69, 95% CI = 0.53–0.90, p = 0.007). There was no significant difference in mortality between the ICS/LABA/LAMA FDC and ICS/LABA therapy groups (RR = 0.94, 95% CI = 0.72–1.24, p = 0.66). In addition, patients receiving ICS/LABA/LAMA FDC therapy had less moderate or severe exacerbations compared with the dual therapy groups (RR = 0.76, 95% CI = 0.73–0.80, p < 0.001 for LABA/LAMA; RR = 0.84, 95% CI = 0.78–0.90, p < 0.001 for ICS/LABA). By contrast, the risk of pneumonia in the ICS/LABA/LAMA FDC group was higher than in the LABA/LAMA group (RR = 1.43, 95% CI = 1.21–1.68, p < 0.001). In conclusion, ICS/LABA/LAMA FDC therapy could help improve the clinical outcomes of patients with COPD. However, triple therapy could increase the risk of pneumonia in comparison with LABA/LAMA dual therapy.

Abstract Background Patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS). Prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ARDS. The aim of this study is to investigate the survival predictors of prone positioning in patients with ARDS caused by influenza pneumonia. Methods This retrospective study was conducted by eight tertiary referral centers in Taiwan. From January 1 to March 31 in 2016, all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ARDS and receiving prone positioning were enrolled. Demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis. Results During the study period, 336 patients with severe influenza pneumonia were screened and 263 patients met the diagnosis of ARDS. Totally, 65 patients receiving prone positioning were included for analysis. The 60-day survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score, pneumonia severity index (PSI), creatinine level and lower rate of receiving renal replacement therapy than non-survivors (22.4 ± 8.5 vs. 29.2 ± 7.4, p = 0.003; 106.6 ± 40.9 vs. 135.3 ± 48.6, p = 0.019; 1.2 ± 0.9 mg/dL vs. 3.1 ± 3.6 mg/dL, p = 0.040; and 4% vs. 42%, p

Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26–2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05–4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47–3.18; p = < 0.0001). Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.

Abstract Studies about prognostic assessment in cancer patients requiring prolonged mechanical ventilation (PMV) for post-intensive care are scarce. We retrospectively enrolled 112 cancer patients requiring PMV support who were admitted to the respiratory care center (RCC), a specialized post-intensive care weaning facility, from November 2009 through September 2013. The weaning success rate was 44.6%, and mortality rates at hospital discharge and after 1 year were 43.8% and 76.9%, respectively. Multivariate logistic regression showed that weaning failure, in addition to underlying cancer status, was significantly associated with an increased 1-year mortality (odds ratio, 6.269; 95% confidence interval, 1.800–21.834; P = 0.004). Patients who had controlled non-hematologic cancers and successful weaning had the longest median survival, while those with other cancers who failed weaning had the worst. Patients with low maximal inspiratory pressure, anemia, and poor oxygenation at RCC admission had an increased risk of weaning failure. In conclusion, cancer status and weaning outcome were the most important determinants associated with long-term mortality in cancer patients requiring PMV. We suggest palliative care for those patients with clinical features associated with worse outcomes. It is unknown whether survival in this specific patient population could be improved by modifying the risk of weaning failure.

Chronic obstructive pulmonary disease (COPD) is preventable and treatable. However, many patients remain undiagnosed and untreated due to the underutilization or unavailability of spirometers. Accordingly, we used Spirobank Smart, an app-based spirometer, for facilitating the early detection of COPD in outpatient clinics. This prospective study recruited individuals who were at risk of COPD (i.e., with age of ≥40 years, ≥10 pack-years of smoking, and at least one respiratory symptoms) but had no previous COPD diagnosis. Eligible participants were examined with Spirobank Smart and then underwent confirmatory spirometry (performed using a diagnostic spirometer), regardless of their Spirobank Smart test results. COPD was defined and confirmed using the postbronchodilator forced expiratory volume in 1 s/forced vital capacity values of 1/FVC ratio of

The pneumonia severity index (PSI) both contains some risk factors of drug-resistant pathogens (DRPs) and represents the severity of health care-associated pneumonia. The aim of this study was to investigate whether the PSI could be used to predict DRPs and whether there were risk factors beyond the PSI. Methods: A retrospective observational study enrolled 530 patients with health care-associated pneumonia who were admitted from January 2005 to December 2010 in a tertiary care hospital. Results: A total of 206 patients (38.9%) had DRPs, of which the most common was Pseudomonas aeruginosa (24.3%). The incidence of DRPs increased with increasing PSI classes (6.7%, 25.5%, 36.9%, and 44.6% in PSI II, III, IV, and V, respectively). An analysis of the risk factors for DRPs by PSI classes revealed that wound care was associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in PSI V (p = 0.045). Nasogastric tube feeding (odds ratio, 3.88; 95% confidence interval, 1.75–8.60; p = 0.006), and bronchiectasis (odds ratio, 3.12; 95% confidence interval, 0.66–14.69; p = 0.007) were risk factors for DRPs in PSI III and IV. The area under the receiver operating characteristic curve progressed from 0.578 to 0.651 while integrating these risk factors with PSI classes. Conclusion: The findings suggested that PSI plus risk factors predicted the risk of DRPs. PSI II had a low risk of DRPs and could be treated as community-acquired pneumonia. Antibiotics of PSI III and IV with risk factors could be targeted DRPs. PSI V with wound care had a higher risk of MRSA, and empirical anti-MRSA antibiotics could be added.

Fluid balance is a fundamental management of patients with sepsis, and this study aimed to investigate the impact of cumulative fluid balance on critically ill patients with influenza admitted to an intensive care unit (ICU).This multicenter retrospective cohort study was conducted by the Taiwan Severe Influenza Research Consortium (TSIRC) which includes eight medical centers. Patients with virology-proven influenza infection admitted to ICUs between October 2015 and March 2016 were included for analysis.A total of 296 patients were enrolled (mean age: 61.4±15.6 years; 62.8% men), and 92.2% (273/296) of them required mechanical ventilation. In the survivors, the daily fluid balance was positive from day 1 to day 3, and then gradually became negative from day 4 to day 7, whereas daily fluid balance was continuously positive in the non-survivors. Using the cumulative fluid balance from day 1-4 as a cut-off point, we found that a negative cumulative day 1-4 fluid balance was associated with a lower 30-day mortality rate (log-rank test, P = 0.003). To evaluate the impact of shock on this association, we divided the patients into shock and non-shock groups. The positive correlation between negative day 1-4 fluid balance and mortality was significant in the non-shock group (log-rank test, P = 0.008), but not in the shock group (log-rank test, P = 0.396). In a multivariate Cox proportional hazard regression model adjusted for age, sex, cerebrovascular disease, and PaO2/FiO2, day 1-4 fluid balance was independently associated with a higher 30-day mortality rate (aHR 1.088, 95% CI: 1.007-1.174).A negative day 1-4 cumulative fluid balance was associated with a lower mortality rate in critically ill patients with influenza. Our findings indicate the critical role of conservative fluid strategy in the management of patients with complicated influenza.

Higher mesothelial cell counts (HM) greater than 5% of total cell counts in tuberculous pleural effusions (TBPE) have been described in human immunodeficiency virus (HIV)-infected patients, however the nature and risk factors in HIV-negative patients with TBPE are unknown. The purpose of the study was to characterize the clinical manifestation of HM in HIV-negative patients with TBPE and evaluate the risk factors of developing HM-TBPE. Methods: This retrospective study was undertaken in HIV-negative patients with TBPE from the Far Eastern Memorial Hospital Tuberculosis database. The cytologist and examining specialist differentiated and quantified the cell counts. HM-TBPE was defined when more than 5% of total cell counts in the pleural fluid were mesothelial cells. Multivariate analysis was calculated with stepwise logistic regression for HM-TBPE risk factors. Results: Nineteen patients were diagnosed as HM-TBPE, while 30 were diagnosed with lower mesothelial cell counts TBPE (LM-TBPE). Compared with LM-TBPE patients, those with HM-TBPE had significantly decreased hemoglobin and serum albumin levels (p

Pneumothorax as a complication of adult cavitary pulmonary tuberculosis is well known and not at all rare, but its occurrence as a complication of miliary tuberculosis is extremely rare. We report a 22-year-old woman who had nonproductive cough and fever for 3 days. Chest radiography showed diffuse, symmetrical miliary nodulation throughout both lung fields. The patient was treated for a presumed diagnosis of miliary tuberculosis with standard antituberculous regimen. Bilateral pneumothorax occurred simultaneously during hospitalization and chest tube thoracostomy was performed. Three days later, recurrent right pneumothorax developed. Video-assisted thoracoscopic surgery (VATS) lung biopsy of the right lung was performed and pathology showed granulomatous interstitial pneumonia with acid-fast positive bacilli. Lung tissue culture was positive for Mycobacterium tuberculosis. In the following 2 months, bilateral pneumothorax recurred twice and chemical pleurodesis with minocycline was performed on both sides, but air leakage persisted. VATS pleurodesis was performed on both sides successfully without recurrence of pneumothorax on either side. Our experience highlights the fact that pneumothorax should be suspected in an adult with miliary tuberculosis who suddenly develops acute respiratory distress. Recurrent pneumothorax can be managed, apart from medical therapy of miliary tuberculosis, with surgical intervention.

Tuberculous prosthetic joint infection is rare. While early diagnosis is critical for treatment, it is usually delayed. Here, we present the case of a 72-year-old patient who underwent total knee arthroplasty for his right knee due to degenerative arthritis 4 years ago. Three years after arthroplasty, pulmonary tuberculosis was found and he hesitated on starting antituberculosis chemotherapy. He suffered from progressive pain and swelling of the right prosthetic knee for 2 months before this admission. The pathologic report of the debridement of the right prosthetic knee was caseous granulomatous inflammation with positive acid-fast staining bacilli. The culture of the debridement also yielded Mycobacterium tuberculosis. He died due to aspiration pneumonia with multiorgan dysfunction. This case is a reminder of the possibility of tuberculosis while dealing with prosthetic joint infection. [J Formos Med Assoc 2007;106(1):82-85]

Hemoperitoneum caused by ruptured hepatocellular carcinoma (HCC) is not uncommon in patients with HCC. Hemothorax due to rupture of metastatic HCC, however, is a very rare complication with high mortality because of uncontrollable hemorrhage. We describe a 42-year-old male HCC patient with chest wall metastasis complicated by hemothorax with an unusual presentation of massive hemoptysis. He received tube thoracotomy immediately and emergency surgery because of persistent bleeding. Hemostasis was achieved transiently. Despite intensive care, he died of multiple organ failure on the 6th postoperative day. We conclude that hemothorax due to a ruptured HCC, as in this case, indicates a very poor prognosis despite intensive treatment.

This study aimed to explore the association between obstructive sleep apnea (OSA) severity and pharyngeal parameters using sub-mental ultrasonography (US), and investigate the accuracy of US for identifying severe OSA patients.One hundred and five consecutive referrals for suspected OSA were enrolled. The diameters of the retro-glossal (RG) and retro-palatal (RP) regions were measured via sub-mental US upon expiration during tidal breathing, forced inspiration, and Müller maneuver (MM). Independent factors associated with severe OSA identified from two-thirds of randomly-selected patients (model-development group) were used to construct a model for predicting severe OSA. The accuracy of the model was validated in the remaining one-third of patients (validation group).Fifty severe OSA patients, 30 with mild-moderate OSA, and 25 without OSA were enrolled. Compared to non-OSA and mild-moderate OSA patients, those with severe OSA had narrower RP diameter in all three maneuvers. Using the prediction model constructed with changes of RP diameters at MM and neck circumference, the independent predictors of severe OSA in the model-development group had 100% sensitivity and 65% specificity.Sub-mental US can accurately discriminate the severity of OSA and be used to identify patients with severe OSA.ClinicalTrials.gov NCT00674076.

Leptospirosis and scrub typhus coinfections have been reported in up to 41% of agricultural workers with acute leptospirosis in Thailand, but only sporadically in Taiwan. Because of the nonspecific clinical presentations, it is difficult to differentiate patients with coinfections from leptospirosis alone. However, failure to identify coinfection may lead to mortality if inappropriate antibiotics are used. We report a 31-year-old man coinfected with leptospirosis and scrub typhus, which manifested as diffuse alveolar hemorrhage and acute renal failure mimicking pulmonary-renal syndrome. The patient was treated by early plasma exchange and a 7-day course of moxifloxacin therapy. Both pulmonary hemorrhage and hypoxemia resolved substantially on the 4th day of hospitalization. He had a complete recovery from the disease after 6 weeks of hospitalization. [J Formos Med Assoc 2007;106(2 Suppl):S1-S6]