Association Between Trimethylamine N-oxide and Adverse Kidney Outcomes and Overall Mortality in Type 2 Diabetes Mellitus.

CONTEXT: Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. OBJECTIVE: To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. METHODS: Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. RESULTS: Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 µM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. CONCLUSION: Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D.

Toward Evaluating Critical Factors of Extubation Outcome with XCSR-Generated Rules.

Predicting the correct timing for extubation is pivotal for critically ill patients with mechanical ventilation support. Evidence suggests that extubation failure occurs in approximately 15-20% of patients, despite their passing of the extubation evaluation, necessitating reintubation. For critically ill patients, reintubation invariably increases mortality risk and medical costs. The numerous parameters that have been proposed for extubation decision-making, which constitute the key predictors of successful extubation, remains unclear. In this study, an extended classifier system capable of processing real-value inputs was proposed to select features of successful extubation. In total, 40 features linked to clinical information and variables acquired during spontaneous breathing trial (SBT) were used as the environmental inputs. According to the number of "don't care" rules in a population set, Probusage, the probability of the feature not being classified as above rules, can be calculated. A total of 228 subjects' results showed that Probusage was higher than 90% for minute ventilation at the 1st, 30th, 60th, and 90th minutes; respiratory rate at the 90th minute; and body weight, indicating that the variance in respiratory parameters during an SBT are critical predictors of successful extubation. The present XCSR model is useful to evaluate critical factors of extubation outcomes. Additionally, the current findings suggest that SBT duration should exceed 90 min, and that clinicians should consider the variance in respiratory variables during an SBT before making extubation decisions.

Association of depression and parasympathetic activation with glycemic control in type 2 diabetes mellitus.

AIM: Patients with type 2 diabetes mellitus exhibited autonomic nervous system (ANS) dysfunction and comorbidities with depressive or anxiety symptoms were related to poor glycemic control. Heart rate variability (HRV) converted from electrocardiogram (ECG) has been used as the ANS index. The study aimed to explore the associations between depression, anxiety, HRV, and glycemic control in patients with type 2 diabetes mellitus. METHODS: The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires were used to assess depressive and anxiety symptoms in 647 patients with type 2 diabetes mellitus (mean age was 63 ± 10 years, 56 % males). The ECG raw signals were collected from a 5-min sitting and resting baseline and then transformed to HRV indices referring ANS activation. Blood glucose and lipid profiles including glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride were obtained from the electronic medical records. RESULTS: Ninety-nine (15 %) participants had depressive symptoms and 59 (9 %) had anxiety symptoms. Depression and HbA1c were negatively correlated with parasympathetic activation. Depression and anxiety were positively correlated with sympathetic activation. After controlling for demographic data and lipid profiles, depression was a significant positive predictor for HbA1c levels; and HRV indices (lnLF and lnHF) were the significant negative predictors for HbA1c levels. Mediation effect analysis showed that depression was a mediator between parasympathetic activation and glycemic control. CONCLUSIONS: Lower parasympathetic activation and higher depressive symptoms may affect glycemic control in patients with type 2 diabetes mellitus. Intervention programs targeting to increase parasympathetic activities and reducing depression could be further tested for their effects on glycemic outcomes for potential clinical use.

Establishing Quality of Life in Southern Taiwan COPD Patients Using Long-Acting Bronchodilator.

Background: To assess the health-related quality of life (HRQoL) of Taiwan patients with different stages of chronic obstructive pulmonary disease (COPD) and using different combination therapies and to explore the factors affecting HRQoL in these patients. Methods: This cross-sectional study included outpatient participants aged 35 years old and older who were receiving long-acting bronchodilator treatment in one of two hospitals in Southern Taiwan. Participants were categorized according to their Global Initiative for Obstructive Lung Disease (GOLD) classification as either their COPD group, based on symptoms and exacerbation risk, or their COPD stage, based on spirometry results. Patients' HRQoL was assessed using the St. George's Respiratory Questionnaire score (SGRQ), World Health Organization Quality of Life Quality of Life-BREF (WHOQOL-BREF), and EQ-5D-5L. The total scores of the SGRQ, WHOQOL-BREF, EQ-5D utility index, and EQ-VAS were presented as mean ± standard deviation (SD) among different combination treatments. Univariate and multivariate analyses were used to explore the association of patients' baseline characteristics and environmental factors with HRQoL. Results: A total of 218 patients were enrolled in the study. The distribution of patients using GOLD group classification were as follows: 73.39% in group A, 20.19% group B, 1.83% group C and 4.59% group D. Triple therapy patients mostly showed a lower quality of life than other combination therapies, regardless of the GOLD classification system. However, only the SGRQ scores of GOLD groups A and B were significantly different when using different drug combinations (p-value = 0.0072 and 0.0430, respectively). The COPD assessment test (CAT) score, a questionnaire to assess impact of COPD on health status, was found to be associated with all the questionnaires. Conclusion: The HRQoL is impaired in patients with COPD, and it deteriorates with an increase of severity. The CAT was the strongest predictor of HRQoL.

Adequacy of prescribed caloric and protein intake and reduction of mortality in critically ill patients with body mass indices <30 kg/m2.

OBJECTIVE: Although the provision of nutrition helps minimize adverse outcomes in most patients in intensive care units (ICUs), little is known about the relative effect of energy and protein delivered on mortality in ICU patients with different ranges of body mass index (BMI). The aim of this study was to examine the relationships between adequacy of dietary energy and protein intakes separately and simultaneously, and short-term mortality in medical ICU patients across four BMI categories. METHODS: We enrolled 1693 patients admitted to a medical center ICU in Taiwan during the period of 2005 to 2011, subcategorizing them by BMI levels: <18.5(n = 418), 18.5-24.9 (n = 889), 25-29.9 (n = 289), and ≥30 kg/m2 (n = 97). Dietary energy and protein intake (DEI and DPI) were defined by the percent of prescribed dosages that each patient actually received: highly adequate (>80%), moderately adequate (60-80%), and inadequate (<60%), during the first 10 d in the ICU. RESULTS: Mean DEI was 1237 kcal/d and DPI 47 g protein/d. Analyzed separately in our multiple regression models, moderately and highly adequate DEI (Ptrends = 0.003-0.026) and DPI (Ptrends = 0.001-0.004) were both significantly correlated with reduced mortality in patients with BMI <18.5, 18.5-24.9, and 25-29.9 kg/m2 but not in those with BMI levels ≥30 kg/m2. With DEI and DPI analyzed simultaneously, only APACHE II scores and DPI levels remained significantly related to reduced mortality in patients with BMI <30 kg/m2. CONCLUSION: Although the adequacy of delivery of prescribed DEI or DPI dosages appeared to be important for reduced risks for mortality in ICU patients with BMI <30 kg/m2 when analyzed separately, DPI had a stronger effect on decreases in ICU mortality when the two were analyzed simultaneously. Further investigation may be needed to study the role of increased protein in improving clinical outcomes.

Performance and Clinical Utility of Various Chronic Obstructive Pulmonary Disease Case-Finding Tools.

BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) is frequently underdiagnosed because of the unavailability of spirometers, especially in resource-limited outpatient settings. This study provides real-world evidence to identify optimal approaches for COPD case finding in outpatient settings. METHODS: This retrospective study enrolled individuals who were at risk of COPD (age ≥40 years, ≥10 pack-years, and ≥1 respiratory symptom). Eligible participants were examined using various COPD case-finding tools, namely the COPD Population Screener (COPD-PS) questionnaire, a COPD prediction (PCOPD) model, and a microspirometer, Spirobank Smart; subsequently, the participants underwent confirmatory spirometry. The definition and confirmation of COPD were based on conventional spirometry. Receiver operating characteristic curve (ROC), area under the curve (AUC), and decision curve analyses were conducted, and a clinical impact curve was constructed. RESULTS: In total, 385 participants took part in the study [284 without COPD (73.77%) and 101 with COPD (26.23%)]. The microspirometer exhibited a higher AUC value than did the COPD-PS questionnaire and the PCOPD model. The AUC for microspirometry was 0.908 (95% confidence interval [CI] = 0.87-0.95), that for the PCOPD model was 0.788 (95% CI = 0.74-0.84), and that for the COPD-PS questionnaire was 0.726 (95% CI = 0.67-0.78). Decision and clinical impact curve analyses revealed that a microspirometry-derived FEV1/FVC ratio of <74% had superior clinical utility to the other measurement tools. CONCLUSION: The PCOPD model and COPD-PS questionnaire were useful for identifying symptomatic patients likely to have COPD, but microspirometry was more accurate and had higher clinical utility. This study provides real-world evidence to identify optimal practices for COPD case finding; such practices ensure that physicians have convenient access to up-to-date evidence when they encounter a symptomatic patient likely to have COPD.

Is the asynchronous phase of thoracoabdominal movement a novel feature of successful extubation? A preliminary result.

Mechanical ventilation is necessary to maintain patients' life in intensive care units. However, too early or too late extubation may injure the muscles or lead to respiratory failure. Therefore, the spontaneous breathing trial (SBT) is applied for testing whether the patients can spontaneously breathe or not. However, previous evidence still reported 15%~20% of the rate of extubation fail. The monitor only considers the ventilation variables during SBT. Therefore, this study measures the asynchronization between thoracic and abdomen wall movement (TWM and AWM) by using instantaneous phase difference method (IPD) during SBT for 120 minutes. The respiratory inductive plethysmography were used for TWM and AWM measurement. The preliminary result recruited 31 signals for further analysis. The result showed that in successful extubation group can be classified into two groups, IPD increase group, and IPD decrease group; but in extubation fail group, the IPD value only increase. Therefore, the IPD decrease group can almost perfectly be discriminated with extubation fail group, especially after 70 minutes (Area under curve of operating characteristic curve was 1). These results showed IPD is an important key factor to find whether the patient is suitable for extubation or not. These finding suggest that the asynchronization between TWM and AWM should be considered as a predictor of extubation outcome. In future work, we plan to recruit 150 subjects to validate the result of this preliminary result. In addition, advanced machine learning method is considered to apply for building effective models to discriminate the IPD increase group and extubation fail group.Clinical Relevance- The finding of this study is that the patients whose average IPD of 95 to 100 minutes was smaller than average IPD of first 5 minutes of SBT could be 100% successful extubation. In addition, ability of discrimination of average IPD after 70 minutes presents AUC 1.

Novel App-Based Portable Spirometer for the Early Detection of COPD.

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 <0.70 as measured by confirmatory spirometry. A total of 767 participants were enrolled and examined using Spirobank Smart; 370 participants (94.3% men, mean age of 60.9 years and mean 42.6 pack-years of smoking) underwent confirmatory spirometry. Confirmatory spirometry identified COPD in 103 participants (27.8%). At the optimal cutoff point of 0.74 that was determined using Spirobank Smart for COPD diagnosis, the area under the receiver operating characteristic was 0.903 (95% confidence interval (CI) = 0.860-0.947). Multivariate logistic regression revealed that participants who have an FEV1/FVC ratio of <74% that was determined using Spirobank Smart (odds ratio (OR) = 58.58, 95% CI = 27.29-125.75) and old age (OR = 3.23, 95% CI = 1.04-10.07 for 60 ≤ age < 65; OR = 5.82, 95% CI = 2.22-15.27 for age ≥ 65) had a higher risk of COPD. The Spirobank Smart is a simple and adequate tool for early COPD detection in outpatient clinics. Early diagnosis and appropriate therapy based on GOLD guidelines can positively influence respiratory symptoms and quality of life.

Novel mechanical ventilator weaning predictive model.

Mechanical ventilation (MV) is a common life support system in intensive care units. Accurate identification of patients who are capable of being extubated can shorten the MV duration and potentially reduce MV-related complications. Therefore, prediction of patients who can successfully be weaned from the mechanical ventilator is an important issue. The electronic medical record system (EMRs) has been applied and developed in respiratory therapy in recent years. It can increase the quality of critical care. However, there is no perfect index available that can be used to determine successful MV weaning. Our purpose was to establish a novel model that can predict successful weaning from MV. Patients' information was collected from the Kaohsiung Medical University Hospital respiratory therapy EMRs. In this retrospective study, we collected basic information, classic weaning index, and respiratory parameters during spontaneous breathing trials of patients eligible for extubation. According to the results of extubation, patients were divided into successful extubation and extubation failure groups. This retrospective cohort study included 169 patients. Statistical analysis revealed successful extubation predictors, including sex; height; oxygen saturation; Glasgow Coma Scale; Acute Physiology and Chronic Health Evaluation II score; pulmonary disease history; and the first, 30th, 60th, and 90th minute respiratory parameters. We built a predictive model based on these predictors. The area under the curve of this model was 0.889. We established a model for predicting the successful extubation. This model was novel to combine with serial weaning parameters and thus can help intensivists to make extubation decisions easily.

Impact of corticosteroid treatment on clinical outcomes of influenza-associated ARDS: a nationwide multicenter study.

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 < 0.001]. Early corticosteroid treatment was independently associated with increased hospital mortality in overall patients [adjusted odds ratio (95% CI) = 5.02 (2.39-10.54), p < 0.001] and in all subgroups. Earlier treatment and higher dosing were associated with higher hospital mortality. Early corticosteroid treatment was associated with a significantly increased odds of subsequent bacteremia [adjusted odds ratio (95% CI) = 2.37 (1.01-5.56)]. The analyses using a propensity score-matched cohort showed consistent results. CONCLUSIONS: Early corticosteroid treatment was associated with a significantly increased hospital mortality in adult patients with influenza-associated ARDS. Earlier treatment and higher dosing were associated with higher hospital mortality. Clinicians should be cautious while using corticosteroid treatment in this patient group.

Mortality and vertebral fracture risk associated with long-term oral steroid use in patients with chronic obstructive pulmonary disease: A systemic review and meta-analysis.

Short-term oral steroid use may improve lung function and respiratory symptoms in patients with stable chronic obstructive pulmonary disease (COPD). However, long-term oral steroid (LTOS) use is not recommended owing to its potential adverse effects. Our study aimed to investigate whether chronic use of oral steroids for more than 4 months would increase mortality and vertebral fracture risk in patients with stable COPD. A systemic search of the PubMed database was conducted, and meta-analysis was performed using Review Manager 5.3. Five studies with a total of 1795 patients showed there was an increased risk of mortality in patients using LTOS (relative risk, 1.63; 95% confidence interval (CI), 1.19-2.23; p < 0.0001; I2 = 86%). In addition, four studies with a total of 17,764 patients showed there was an increased risk of vertebral fracture in patients using LTOS (odds ratio, 2.31; 95% CI, 1.52-3.50; p = 0.03; I2 = 65%). Our meta-analysis showed LTOS was associated with increased mortality and vertebral fracture risk in patients with COPD, and this risk may be due to the adverse effects of LTOS and progression COPD.

The epidemiology, antibiograms and predictors of mortality among critically-ill patients with central line-associated bloodstream infections.

BACKGROUND/PURPOSE: For high risk of central line-associated bloodstream infections (CLABSIs) in patients of intensive care units (ICUs) and scarcely epidemiology and therapeutic recommendations in Asia, we aimed to evaluate the annual change in epidemiology, antibiogram, and risk factors for 14-day mortality. METHODS: A retrospective study of ICUs patients with CLABSIs at a medical center in Taiwan (2010-2016), where central line care bundle implemented since 2014, by reviewing clinical data, pathogens, and the antibiogram. RESULTS: Gram-negative bacteria (59.3%) were main microorganisms of CLABSIs, and 9.0% of all GNB were MDROs. Acinetobacter spp., Enterobacter spp., and Stenotrophomonas maltophilia were the most frequently isolated. In multivariate analysis, malignancy, inadequate empirical antimicrobial therapy, inadequate definite antimicrobial therapy, and infection by fungi or multidrug-resistant organisms (MDROs) were associated with 14-day mortality (all p < 0.05). The CLABSI incidence rate decreased from 5.54 to 2.18 per 1000 catheter-day (from 2014 to 2015) with improved compliance to care bundle. Carbapenem and aminoglycoside were suitable empirical drugs in the hospital setting when GNB is predominant for CLABSI. Significant decreasing susceptibility of ampicillin/sulbactam in Enterobacter spp. (36.7%-0.0%), and ampicillin/sulbactam (12.5%-0.0%), ceftazidime (100.0%-52.9%), and tigecycline (87.5%-35.3%) in Serratia marcescens. CONCLUSION: We identified Gram-negative bacteria as leading pathogens of CLABSIs in a Taiwan medical center, and good compliance to care bundle is associated with reduced CLABSI incidence rate. Malignancy, infection by MDROs or fungi, inadequate empirical or definite antimicrobial therapy are significant factors for 14-day mortality.

Long-acting beta2-agonists versus long-acting muscarinic antagonists in patients with stable COPD: A systematic review and meta-analysis of randomized controlled trials.

Several long-acting bronchodilators have been developed and are widely used as first-line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers' websites to identify relevant randomized clinical trials for meta-analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV1 ), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74-0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86-0.97, P = 0.005). There were no significant differences in trough FEV1 , TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.

Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway.

Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244-amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan-Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future.

Anti-inflammatory Effects of Resveratrol on Hypoxia/Reoxygenation-Induced Alveolar Epithelial Cell Dysfunction.

Reducing oxidative stress is crucial to prevent hypoxia-reoxygenation (H/R)-induced lung injury. Resveratrol has excellent antioxidant and anti-inflammatory effects, and this study investigated its role in H/R-induced type II pneumocyte dysfunction. H/R conditions increased expression of inflammatory cytokines including interleukin (IL)-1ß (142.3 ± 21.2%, P < 0.05) and IL-6 (301.9 ± 35.1%, P < 0.01) in a type II alveolar epithelial cell line (A549), while the anti-inflammatory cytokine IL-10 (64.6 ± 9.8%, P < 0.05) and surfactant proteins (SPs) decreased. However, resveratrol treatment effectively inhibited these effects. H/R significantly activated an inflammatory transcription factor, nuclear factor (NF)-κB, while resveratrol significantly inhibited H/R-induced NF-κB transcription activities. To the best of our knowledge, this is the first study showing resveratrol-mediated reversal of H/R-induced inflammatory responses and dysfunction of type II pneumocyte cells in vitro. The effects of resveratrol were partially mediated by promoting SP expression and inhibiting inflammation with NF-κB pathway involvement. Therefore, our study provides new insights into mechanisms underlying the action of resveratrol in type II pneumocyte dysfunction.

Risk factors for microbiologic failure among Taiwanese adults with Mycobacterium abscessus complex pulmonary disease.

BACKGROUND: The Mycobacterium abscessus complex is a common cause of pulmonary nontuberculous mycobacteria infections in Taiwan. We examined the risk factors associated with treatment outcome in Taiwanese adults with pulmonary disease caused by the M. abscessus complex. METHODS: We retrospectively reviewed the records of all patients from a southern Taiwan medical center from 2006 to 2012 who had respiratory specimens identified as M. abscessus complex and met the American Thoracic Society criteria for pulmonary disease. RESULTS: Of the 106 included patients, females (58.5%) and nonsmokers (79.2%) predominated. The mean age of patients was 64.8 years. Sixty-three patients (59.4%) had pre-existing lung disease. Previous mycobacterial pulmonary disease (34.9%) was the most common underlying disorder. Chest radiography indicated that bronchiectasis was common (47.2%) and that cavitations were less common (14.2%). Fifty-six patients received antibiotic treatment. Clinicians were more likely to prescribe antibiotics if the initial sputum acid-fast staining was positive (p < 0.001). Treatment outcome was analyzed in 26 patients who were treated for more than 3 months; three of these patients (11.5%) had clinical failure and 18 (69.2%) experienced sputum conversion. Patients with cavitary lesions were more likely to experience microbiologic failure (p = 0.02). Nine patients had positive cultures after antibiotic treatment for > 1 year. Previous mycobacterial pulmonary disease (p = 0.011) and cavitary lesion (p = 0.034) are risk factors for persistence of M. abscessus complex. CONCLUSION: With antimicrobial therapy, previous mycobacterial disease, and cavitary lesion are associated with microbiologic failure in Taiwanese adults with M. abscessus complex pulmonary disease.

Krüppel-like factor 5 mediates proinflammatory cytokine expression in lipopolysaccharide-induced acute lung injury through upregulation of nuclear factor-κB phosphorylation in vitro and in vivo.

Acute lung injury (ALI) is associated with an inflammation-mediated process, and the transcription factor, Krüppel-like factor 5 (KLF5), might play a crucial role in inflammatory lung disease. In this study, we evaluated KLF5, reactive oxygen species (ROS), and inflammatory responses in a lipopolysaccharide- (LPS-) induced ALI model to elucidate the role of KLF5 in ALI. Our data indicated that LPS upregulates proinflammatory cytokine expression in human bronchial epithelial cells in a dose-dependent manner. We observed upregulated KLF5 protein expression in human bronchial epithelial cells exposed to LPS, with peak expression 1 h after LPS treatment, and subsequent upregulation of p65 protein expression and p65 phosphorylation at Ser276. These results indicate that KLF5 mediates proinflammatory cytokine expression by upregulating nuclear factor-kappaB (NF-κB) phosphorylation at p65 in response to LPS. LPS treatment also increased ROS production and simultaneously upregulated KLF5 expression and NF-κB translocation. N-acetylcysteine significantly reduced ROS levels and KLF5 and NF-κB translocation in nuclear extracts. Therefore, N-acetylcysteine pretreatment before LPS exposure reduces ROS, downregulates KLF5 expression, and subsequently reduces inflammatory responses by scavenging ROS. Overall, our study results indicate that KLF5 mediates proinflammatory cytokine expression through upregulation of NF-κB phosphorylation at p65 in LPS-induced ALI.