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Inflammation, oxidative stress, and protease–antiprotease imbalance have been suggested to be a pathogenic triad in chronic obstructive pulmonary disease (COPD). However, it is not clear how proteases interact with components of inflammatory pathways. Therefore, this study aimed to evaluate the effect of neutrophil elastase (NE) on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production and determine the molecular mechanism in human bronchial epithelial cells (HBECs). Immortalized bronchial epithelial cells and primary HBECs were used to investigate the impact of NE on LPS-induced IL-8 production. The molecular mechanism by which NE modulated LPS-induced IL-8 production was confirmed in elastase-treated C57BL/6 mice and primary HBECs obtained from COPD patients and healthy controls. The results showed that NE treatment synergistically augmented LPS-induced IL-8 production in both immortalized bronchial epithelial cells and primary HBECs. NE partially degraded peroxisome proliferator-activated receptor gamma (PPARγ), which is known to regulate IL-8 production in the nucleus. Treatment with a PPARγ agonist and overexpression of PPARγ reversed the NE-induced synergistic increase in LPS-induced IL-8 production. Moreover, PPARγ levels were lower in lung homogenates and lung epithelial cells from elastase-treated mice than in those from saline-treated mice. In accordance with the findings in mice, PPARγ levels were lower in primary HBECs from COPD patients than in those from healthy never-smokers or healthy smokers. In conclusion, a vicious cycle of mutual augmentation of protease activity and inflammation resulting from PPARγ degradation plays a role in the pathogenesis of COPD., Lung disease: getting to the root of inflammation Tracing how a protein-degrading enzyme called neutrophil elastase (NE) interacts with cytokines, molecules that trigger inflammation, has revealed a potential new treatment target for chronic obstructive pulmonary disease (COPD). COPD is a progressive disease in which chronic inflammation damages lung function. Although it was known that cytokines play key roles in COPD, the detailed molecular mechanism was not well understood. Chul-Gyu Yoo at Seoul National University College of Medicine in South Korea and co-workers investigated the role that NE plays in inflammation in COPD. They found that NE degraded peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor that keeps cytokine production in check. Patients with COPD showed low levels of PPARγ, and boosting PPARγ or suppressing NE in cultured cells showed potential for reducing inflammation. These results highlight PPARγ as a candidate for development of COPD treatments.

Background Desaturation is a common complication of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Dexmedetomidine (DEX), a commonly used sedative in intensive care, is associated with less respiratory depression compared with other sedatives. Objective We compared DEX with midazolam (MDZ) when used as a sedative during EBUS-TBNA. Design A randomised, parallel, double-blinded trial. Setting A university-affiliated teaching hospital between June 2014 and July 2015. Patients A total of 102 patients who underwent EBUS-TBNA were randomly allocated to two groups (48 DEX group, 54 MDZ group). Interventions DEX group received 0.25 to 0.75 μg kg-1 h-1 (start with 0.5 μg kg-1 h-1, modulated in three steps from 0.25 to 0.75 μg kg-1 h-1) of DEX after a loading dose of 0.25 μg kg-1 h-1 for 10 min to maintain a Ramsay Sedation Scale (RSS) of 3 to 5. If the patient was agitated, 1 mg of MDZ bolus was used as a rescue drug. Patients in the MDZ group initially received 0.05 mg kg-1 of MDZ as a bolus. For maintenance and rescue, 1 mg of MDZ bolus was used. Main outcome measures The primary outcome was the presence of oxygen desaturation. Secondary outcomes were level of sedation (Ramsay Sedation Scale score), cough score, sedation and procedure satisfaction score. Results The baseline characteristics of the patients, duration of EBUS-TBNA procedures and the use of rescue MDZ were not different between the groups. There was no significant difference in desaturation events between the DEX and MDZ groups (56.3 and 68.5%, respectively; P = 0.20). The level of sedation and the sedation satisfaction scores were similar between the two groups. However, cough score was significantly lower in the DEX group (41.9 vs. 53.4; P = 0.02). Conclusion The use of DEX during EBUS-TBNA was not superior to MDZ in terms of oxygen desaturation. Trial registration Clinicaltrials.gov identifier: NCT02157818.

No studies on idiopathic pulmonary fibrosis (IPF) have investigated the prognostic impact of extrapulmonary cancers in patients with IPF. We aimed to determine the prognostic impact of malignancies in patients with IPF. We retrospectively reviewed the medical records of patients diagnosed with IPF between 2001 and 2015. Patients were divided into three groups: IPF without cancer (n = 440), IPF with lung cancer (n = 69), and IPF with extrapulmonary cancer (n = 70). Of the 579 patients with IPF, 139 (24%) had cancer; the three most common types were lung (11.9%), gastric (2.4%), and colorectal (1.9%). Survival was significantly worse in patients with lung cancer than in those without cancer (hazard ratio [HR] = 1.83, 95% confidence interval [CI], 1.35–2.48) or those with extrapulmonary cancer (HR = 1.70, 95% CI, 1.14–2.54). The rate of hospitalisation for cancer-related complications was significantly higher in IPF patients with lung cancer than in those with extrapulmonary cancer. The annual rates of decline in percent predicted forced vital capacity and diffusion capacity for carbon monoxide did not differ among the groups. Physicians should pay attention to the development and progression of cancer and its prognostic impact in patients with IPF.

OBJECTIVES Prone position ventilation improves oxygenation and reduces the mortality of patients with severe acute respiratory distress syndrome. However, there is limited evidence about which patients would gain most survival benefit from prone positioning. Herein, we investigated whether the improvement in oxygenation after prone positioning is associated with survival and aimed to identify patients who will gain most survival benefit from prone positioning in patients with acute respiratory distress syndrome. DESIGN A retrospective cohort study. SETTING Medical ICU at a tertiary academic hospital between 2014 and 2020. PATIENTS Adult patients receiving prone positioning for moderate-to-severe acute respiratory distress syndrome. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The main outcomes were ICU and 28-day mortality. A total of 116 patients receiving prone positioning were included, of whom 45 (38.8%) were ICU survivors. Although there was no difference in PaO2:FIO2 ratio before the first prone session between ICU survivors and nonsurvivors, ICU survivors had a higher PaO2:FIO2 ratio after prone positioning than nonsurvivors, with significant between-group difference (p < 0.001). The area under the receiver operating characteristic curve of the percentage change in the PaO2:FIO2 ratio between the baseline and 8-12 hours after the first prone positioning to predict ICU mortality was 0.87 (95% CI, 0.80-0.94), with an optimal cutoff value of 53.5% (sensitivity, 91.5%; specificity, 73.3%). Prone responders were defined as an increase in PaO2:FIO2 ratio of greater than or equal to 53.5%. In the multivariate Cox regression analysis, prone responders (hazard ratio, 0.11; 95% CI, 0.05-0.25), immunocompromised condition (hazard ratio, 2.15; 95% CI, 1.15-4.03), and Sequential Organ Failure Assessment score (hazard ratio, 1.16; 95% CI, 1.06-1.27) were significantly associated with 28-day mortality. CONCLUSIONS The PaO2:FIO2 ratio after the first prone positioning differed significantly between ICU survivors and nonsurvivors. The improvement in oxygenation after the first prone positioning was a significant predictor of survival in patients with moderate-to-severe acute respiratory distress syndrome.

Aims Brain magnetic resonance imaging (MRI) is recommended during the initial work-up for nonsmall cell lung cancer (NSCLC). Although small enhancing brain nodules not radiologically confirmed as metastatic lesions have often been detected, their clinical course has not been well studied. Methods This nested case–control study included NSCLC patients who had small enhancing brain nodules detected by serial brain MRIs from January 2014 through December 2018 at a tertiary university hospital. Small enhancing brain nodules were defined as round enhancing nodules of ≤10 mm diameter without oedema in thin-section (1 mm) contrast MRIs. The incidence, natural course and risk factors of growing nodules were evaluated. Results A total of 171 small enhancing brain nodules in 123 patients were observed over an average of 22.1 months. The incidence of nodule growth was 49.1% with mean growth rate of 11 mm·year−1. We found that 25.0% of the growing nodules contributed to clinical upstaging compared to the initial stage. Cerebral events were more common in growing nodules; therefore, local therapy was performed more often. However, there was no difference in the cerebral event-related mortality. Nodule growth was more frequent in younger individuals, multiple nodules, advanced disease, poorly differentiated carcinoma, rim enhancement and larger initial size. In multivariable analysis, predictors of growth were N stage ≥1, existence of epidermal growth factor receptor mutation and larger initial size. Conclusion Considering the clinical course of small enhancing brain nodules, more intensive evaluation is required for early detection and pre-emptive intervention when accompanied by risk factors., Small enhancing brain nodules are found in 4.1% of NSCLC. Growth is found in the 49.1% with a rate of 11.0 mm per year. Lymph node metastasis, EGFR mutation and larger diameter are risk factors for growth. https://bit.ly/2ALqhhM

To evaluate the association of sleep duration with health-related quality of life (HRQOL) and examine the influence of age, sex, and common comorbidities on this association. Using appropriate survey design, we analyzed 50,181 adults who participated in the 2007–2015 Korea National Health and Nutrition Examination Survey. Participants were categorized into five groups according to self-reported sleep duration ≤ 5 (short sleeper), 6, 7, 8, and ≥ 9 h (long sleeper). HRQOL was measured with the European Quality of Life-5 Dimensions (EQ-5D) index and visual analogue scale (VAS). In multiple linear regression, short sleep duration was associated with lower EQ-5D index (β = − 0.024; 95% confidence interval [CI], − 0.027 to − 0.021) and lower EQ-VAS (β = − 3.0; 95% CI, − 3.7 to − 2.3), and long sleep duration was associated with lower EQ-5D index (β = − 0.016; 95% CI, − 0.021 to − 0.011) and lower EQ-VAS (β = − 2.2; 95% CI, − 3.1 to − 1.3) compared with 7-h sleepers. Old-age (≥ 65 years old) short and long sleepers had significantly lower EQ-5D index than those of

Background It has been suggested that a high-flow nasal cannula (HFNC) could help to remove carbon dioxide (CO2) from anatomical dead spaces, but evidence to support that is lacking. The objective of this study was to elucidate whether use of an HFNC could reduce the arterial partial pressure of CO2 (PaCO2) in patients with acute hypercapnic respiratory failure who are receiving conventional oxygen (O2) therapy. Methods A propensity score-matched observational study was conducted to evaluate patients treated with an HFNC for acute hypercapnic respiratory failure from 2015 to 2016. The hypercapnia group was defined as patients with a PaCO2 >50 mm Hg and arterial pH Results Eighteen patients in the hypercapnia group and 177 patients in the nonhypercapnia group were eligible for the present study. Eighteen patients in each group were matched by propensity score. Decreased PaCO2 and consequent pH normalization over time occurred in the hypercapnia group (P=0.002 and P=0.005, respectively). The initial PaCO2 level correlated linearly with PaCO2 removal after the use of an HFNC (R2=0.378, P=0.010). The fraction of inspired O2 used in the intensive care unit was consistently higher for 48 hours in the nonhypercapnia group. Physiological parameters such as respiratory rate and arterial partial pressure of O2 improved over time in both groups. Conclusions Physiological parameters can improve after the use of an HFNC in patients with acute hypercapnic respiratory failure given low-flow O2 therapy via a facial mask. Further studies are needed to identify which hypercapnic patients might benefit from an HFNC.

The association between GOLD categorizations and future exacerbations has not been fully investigated. This study elucidates whether the GOLD 2017 classification is associated with different future exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) compared with the previous GOLD categorization. Another objective was to investigate the impacts of the symptoms and FEV1 on the predicted future exacerbation independently of previous exacerbation history.We analyzed patients from three prospective COPD cohorts (SNUH, KOCOSS, and KOLD) and evaluated the risk of moderate to severe exacerbation among different models, including GOLD grade (FEV1), GOLD 2011, and GOLD 2017.In total, 611 COPD patients were included (36 from SNUH, 257 from KOCOSS, and 318 from KOLD). GOLD 2017 classification, excluding FEV1% for categorization criteria, showed no differences in future exacerbation risk compared with GOLD grade and GOLD 2011 based on c-statistics. Among those with no frequent exacerbation history and FEV1 ≥50%, the group with more symptoms was significantly associated with future exacerbations than the group with less symptoms. A lower FEV1 (FEV150%) was not associated with a higher future exacerbation risk than a higher FEV1 (FEV1 ≥50%), regardless of prior exacerbation history and symptom group.The GOLD 2017 classification was not different from GOLD grade and GOLD 2011 regarding the association with future exacerbation risk, and there were no significant differences in exacerbation risk according to FEV1%. This suggests that FEV1 might not be an important factor in future exacerbation risk. These results partly support the GOLD 2017 assessment tool.

Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9). Conclusion Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.

Background: Overlap syndrome of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is associated with increased mortality. We aimed to assess all-cause mortality in patients with COPD, OSA, and the overlap syndrome and evaluate which polysomnographic indices—apnea-hypopnea index (AHI) or hypoxemic load measurements—better predict mortality within 10 years.Methods: Adults who underwent polysomnography, spirometry, and bronchodilator response tests between 2000 and 2018 were included and divided into four groups according to the presence of COPD and moderate-to-severe OSA (AHI ³15/h). We estimated mortality using Cox model adjusted for demographic/anthropometric covariates and comorbidities; this was called the clinical model. To evaluate prognostic performance, we compared the concordance index (C-index) between the clinical model and extended models, which incorporated one of the polysomnographic indices—AHI, sleep time spent with SpO2 < 90% (TS90), and mean and lowest SpO2.Results: Among 355 participants, patients with overlap syndrome of COPD and moderate-to-severe OSA had the highest risk of death (adjusted hazard ratio, 3.19; 95% confidence interval, 1.02 to 9.96). The C-indices of the extended models with TS90 (%) and mean SpO2 were significantly higher than that of the clinical model (0.765 vs. 0.737 and 0.756 vs. 0.737, respectively; all P P=0.15).Conclusions: All-cause mortality was highest in patients with the overlap syndrome. The measurements of the hypoxemic load, not AHI, better predicted mortality in patients with COPD, OSA, and the overlap syndrome.

Lysine-specific demethylase 1 (LSD1) is an epigenetic regulator that modulates the chromatin status, contributing to gene activation or repression. The post-translational modification of LSD1 is critical for the regulation of many of its biological processes. Phosphorylation of serine 112 of LSD1 by protein kinase C alpha (PKCα) is crucial for regulating inflammation, but its physiological significance is not fully understood. This study aimed to investigate the role of Lsd1-S112A, a phosphorylation defective mutant, in the cigarette smoke extract/LPS-induced chronic obstructive pulmonary disease (COPD) model using Lsd1SA/SA mice and to explore the potential mechanism underpinning the development of COPD. We found that Lsd1SA/SA mice exhibited increased susceptibility to CSE/LPS-induced COPD, including high inflammatory cell influx into the bronchoalveolar lavage fluid and airspace enlargement. Additionally, the high gene expression associated with the inflammatory response and oxidative stress was observed in cells and mice containing Lsd1-S112A. Similar results were obtained from the mouse embryonic fibroblasts exposed to a PKCα inhibitor, Go6976. Thus, the lack of LSD1 phosphorylation exacerbates CSE/LPS-induced COPD by elevating inflammation and oxidative stress. [BMB Reports 2021; 54(10): 522-527].

Introduction: In the general population, short and long sleep durations have been associated with adverse health outcomes. However, this association remains unclear in patients with chronic kidney disease (CKD). We examined the relationship of sleep duration to mortality and health-related quality of life (HRQOL) in individuals with CKD. Methods: A total of 1,783 adults with CKD who participated in the 2007–2015 Korea National Health and Nutrition Examination Survey were analyzed. CKD was defined as an estimated glomerular filtration rate of 2. Participants were categorized into 3 groups according to self-reported sleep duration: 8 h (long sleepers). The outcome variables were all-cause mortality and HRQOL. HRQOL was assessed using the European Quality of Life-5 Dimensions (EQ-5D) index. Results: During a median of 6.4 years, 481 (27%) deaths occurred. In unadjusted Cox regression analysis, long sleepers with CKD had an increased risk of death (hazard ratio [HR], 1.62; 95% confidence interval [CI]: 1.26–2.09). This significant association remained after adjusting for age, sex, and BMI (HR, 1.36; 95% CI: 1.05–1.75); however, it was lost after adjusting for CKD stage, social and lifestyle factors, and presence of comorbidities (HR, 1.15; 95% CI: 0.89–1.49). Compared with 6- to 8-h sleepers with CKD, long sleepers with CKD had significantly worse HRQOL in multivariable linear regression models. The adjusted means of the EQ-5D index were 0.80 (95% CI: 0.77–0.82) for short sleepers, 0.81 (95% CI: 0.80–0.82) for 6- to 8-h sleepers, and 0.76 (95% CI: 0.73–0.79) for long sleepers (p = 0.01). Discussion/Conclusion: Long sleep duration is associated with poor HRQOL in Korean adults with CKD. The weak association between long sleep duration and mortality was attenuated after multivariable adjustment in this study.

The objective was to evaluate the prevalence of patients at a high risk of having OSA by using a screening questionnaire and to investigate whether the questionnaire can predict patients who are at risk of cardiopulmonary events occurring during a bronchoscopy under sedation. We prospectively enrolled consecutive adult patients who underwent flexible bronchoscopies under moderate sedation. The snoring, tiredness, observed apnea, high blood pressure-body mass index, age, neck circumference and gender (STOP-Bang) questionnaire was used to identify patients at a high (score ≥ 3 of 8) or low risk (score 2, and procedure time revealed that a STOP-Bang score of ≥ 3 was significantly associated with cardiopulmonary events in a subgroup of patients without a history of cerebrovascular disease (adjusted odds ratio, 1.94; 95% confidence interval, 1.06–3.54). The STOP-Bang questionnaire can predict cardiopulmonary events occurring during this procedure.Trial registration: NCT03325153.

Background: Respiratory failure requiring intubation is a risk factor for mortality in immunocompromised patients, therefore, noninvasive methods to avoid intubation are preferred in such patients. A high-flow nasal cannula (HFNC) is an alternative noninvasive technique for oxygen delivery but can be potentially harmful in cases of delayed intubation. We sought to identify the physiological predictors of outcome to assess the responsiveness to HFNC of immunocompromised patients with acute respiratory failure. Methods: We retrospectively analyzed the medical records of immunocompromised patients treated with HFNC in 2015 and 2016 in a tertiary hospital. Oxygenation was assessed by calculating the SpO 2 /FiO 2 (SF) ratio. Subjects were defined as “SF-improved” when HFNC resulted in an increase in the SF ratio compared with baseline. The values were collected at baseline, 12, 24, and 48 h. Results: Ninety-one patients with a median age of 64 years were analyzed; 68.1% were men. There was no significant difference between the SF 48 -improved and the SF 48 -nonimproved groups in clinical baseline characteristics or severity of illness as evaluated at the time of initiation of HFNC by APACHE II, SAPS II, and SOFA. The 28-day mortality was significantly lower in the SF 48 -improved compared with the SF 48 -nonimproved group. In univariate analysis, mortality was significantly associated with body mass index (BMI), poor functional status, do-not-intubate (DNI) status, the “SF 48 -improved” group, the reason for immunocompromise, and the severity of illness at the time of initiation of HFNC. In multivariate analysis, “SF 48 -improved” group was not significantly associated with increased mortality [odds ratio (OR) 0.462; 95% confidence interval (CI), 0.107–1.988; P=0.299]. Conclusions: In immunocompromised patients with acute respiratory failure, an improved SF ratio 48 h after HFNC treatment was associated with improved 28-day mortality.

Purpose: To assess the impact of rapid muscle loss before admission to intensive care unit (ICU) in critically ill patients with cirrhosis. Materials and Methods: Patients with cirrhosis who had undergone 2 or more recent computed tomography scans before admission to the medical ICU were included. Muscle cross-sectional area at the level of the third lumbar vertebra was quantified using OsiriX software. The rate of muscle mass change and skeletal muscle index (SMI) were also calculated. Multivariable Cox proportional hazards regression was used to evaluate the association between muscle loss and mortality. Results: Among 125 patients, 113 (90.4%) patients were classified as having sarcopenia. The mean body mass index was 22.6 (3.9) kg/m2. Thirty-nine (31.2%) patients were within the normal range for muscle mass change, while 86 (68.8%) patients demonstrated rapid decline in muscle mass before admission to the ICU. Patients with rapid muscle loss showed high ICU mortality (59.3%) and in-hospital mortality (77.9%). Multivariate Cox analysis showed that ICU mortality and in-hospital mortality were independently associated with malignancy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, SMI, and rapid muscle loss. Conclusion: Rapid muscle decline is correlated with increased ICU mortality and in-hospital mortality in critically ill patients with cirrhosis.

Background/aims Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. Methods We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. Results The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. Conclusions The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.

Background Acute respiratory distress syndrome (ARDS) is related to high mortality and morbidity. There are no proven therapeutic measures however, to improve the clinical course of ARDS, except using low tidal volume ventilation. Metformin is known to have pleiotropic effects including anti-inflammatory activity. We hypothesized that pre-admission metformin might alter the progress of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM). Methods We performed a retrospective cohort study from January 1, 2005, to April 30, 2005 of patients who were admitted to the medical ICU at Seoul National University Hospital because of ARDS, and reviewed ARDS patients with DM. Metformin use was defined as prescribed within 3-month pre-admission. Results Of 558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33 patients were treated with metformin monotherapy or in combination with other antidiabetic medications. Demographic characteristics, cause of ARDS, and comorbid conditions (except chronic kidney disease) were not different between metformin users and nonusers. Several severity indexes of ARDS were similar in both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in metformin nonusers. On multivariable regression analysis, use of metformin was not significantly related to a reduced 30-day mortality (adjusted β-coefficient, -0.19; 95% confidence interval, -1.76 to 1.39; p=0.816). Propensity score-matched analyses showed similar results. Conclusion Pre-admission metformin use was not associated with reduced 30-day mortality among ARDS patients with DM in our medical ICU.

Background It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients. Methods Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models. Results Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15–0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants. Conclusions Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0587-9) contains supplementary material, which is available to authorized users.

Background: Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effct of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS. Methods: We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching. Results: A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer du- ration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001). Conclusions: ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Background All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. Methods Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. Results Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5–1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1–143.8; P P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097–0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631–15.736). Conclusion Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.

Background and objective Alveolar macrophages of patients with COPD display impaired cytokine release and diminished phagocytosis. COPD exacerbations exhibit immune dysfunction towards the respiratory pathogens. CS and CSE were reported to aggravate bacterial infections in COPD patients. Methods MARCO is highly expressed in lungs and is involved in pathogen clearance. We investigated the effect of CSE on MARCO expression and its regulatory mechanisms. After relevant siRNA transfection and treatment with CSE and/or LPS, we measured the levels of MARCO by q-RT PCR, immunoblotting and flow cytometry. Immunofluorescence staining and immunoprecipitation were used to evaluate the mechanism. Results CSE decreased LPS-induced expression of MARCO mRNA and protein. Upregulation of MARCO by LPS was Nrf2-dependent. Nrf2 knockdown significantly suppressed LPS-induced increase in MARCO transcripts. CSE did not block nuclear translocation of Nrf2 in LPS-treated cells, but rather CSE itself strongly accumulated Nrf2 in the nucleus through the degradation of its cytoplasmic inhibitor, KEAP1. However, CSE markedly suppressed LPS-induced Nrf2 acetylation. Histone acetyltransferase p300/CBP directly acetylates Nrf2, which augments promoter-specific DNA binding of Nrf2. Our results reveal CSE-induced polyubiquitinylation and subsequent degradation of p300 via the proteasome. Pretreatment with proteasome inhibitors completely blocked CSE-induced degradation of p300 and suppression of MARCO expression. Conclusion These findings suggest that CSE decreases MARCO expression via the proteasomal degradation of p300 in macrophages, which may be in part responsible for impaired bacterial phagocytosis.

Background We aimed to evaluate whether serum activin-A levels are elevated and have any value in predicting severity and prognosis in acute respiratory distress syndrome (ARDS). Methods Retrospective cohort study was performed with patients who were admitted to MICU with diagnosis of ARDS and have serum samples stored within 48 h of Intensive care unit (ICU) admission between March 2013 and December 2016 at a single tertiary referral hospital. Serum activin-A levels were measured with ELISA kit, and were compared with those of normal healthy control and non-ARDS sepsis patients. Results Total 97 ARDS patients were included for the study. Levels of Activin-A were elevated in ARDS patients compared to those of healthy controls (Log-transformed activin-A levels 2.89 ± 0.36 vs. 2.34 ± 0.11, p

Background The proportion of never-smokers with non-small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never-smokers with NSCLC in a large single institution. Methods We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014. Results Of the 1860 NSCLC patients, 707 (38.0%) were never-smokers. The proportions of women (83.7% vs. 5.6%) and adenocarcinoma (89.8% vs. 44.9%) were higher among never-smokers than among ever-smokers. Significantly more never-smokers were diagnosed at a younger median age (65 vs. 68 years, P

Background Previous studies report that apoptosis and autophagy are involved in the pathogenesis of emphysema, and macroautophagy is one of the processes regulating the apoptosis pathway. However, few studies have evaluated whether chaperone-mediated autophagy (CMA) contributes to the regulation of apoptosis. In this study, we investigated the impact of autophagy, including both macroautophagy and CMA, on the apoptosis in bronchial epithelial cells. Methods Cigarette smoke extract (CSE) was injected intratracheally into C57BL/6 mice, and emphysema and apoptosis were evaluated in the lungs. After treatment with CSE, apoptosis, macroautophagy, and CMA were measured in BEAS2-B cells, and the impact of autophagy on the apoptosis was evaluated following knockdown of autophagy-related genes by short interfering RNAs (siRNAs). Results Intratracheal CSE injection resulted in the development of emphysema and an increase in apoptosis in mice. CSE increased the apoptosis in BEAS2-B cells, and also elevated the expression of proteins related to both macroautophagy and CMA in BEAS2-B cells. The knockdown experiment with siRNAs showed that macroautophagy increases apoptosis in BEAS2-B cells, while CMA suppresses apoptosis. Conclusion The intratracheal injection of CSE induces pulmonary emphysema and an increase in apoptosis in mice. CSE also induces apoptosis, macroautophagy, and CMA of bronchial epithelial cells. Macroautophagy and CMA regulate apoptosis in opposite directions.

Background: The number of elderly patients admitted to the intensive care unit is constantly growing. However, a decision regarding intensive care in these populations remains a challenge. Aim: To identify factors that influences the decision of elderly patients and their families about whether to initiate intensive care in case of an acute event. Design/participants: Medical records of patients (>80 years), who were admitted to general wards and referred for intensive care, were retrospectively reviewed. Patients who received intensive care were compared with those not agreeing to the initiation of intensive care. Results: Among the 125 patients, 45 agreed to receiving intensive care. Baseline characteristics at the time of intensive care unit referral were similar between the intensive care and non-intensive care groups. Only one patient had advance directives before the intensive care unit referral. Lower economic status (odds ratio = 0.27, 95% confidence interval = 0.08–0.94) and cognitive impairment (odds ratio = 0.20, 95% confidence interval = 0.07–0.56) were found associated with a lower likelihood of agreeing to intensive care, while a large number of participants involved in the decision-making process were associated with a higher likelihood of intensive care unit use (odds ratio = 1.82, 95% confidence interval = 1.08–3.09). Mean duration of hospital stay was longer for the intensive care group as compared with the non-intensive care group (28.8 days and 19.8 days, respectively, p = 0.03). However, there was no significant difference in the survival rate. Conclusion: The initiation of intensive care in elderly patients was influenced not only by medical conditions but also by the patient’s economic status and the number of family members involved in the decision-making process.

Background and objective There are limited data regarding serum activin-A as a biomarker for sepsis. We examined whether serum activin-A concentration could predict sepsis severity and prognosis in the management of critically ill patients with sepsis. Methods The subjects were adult patients suspected of having sepsis and admitted to intensive care unit (ICU) from January 2013 to March 2014. Serum activin-A concentration was measured in blood sampled within 48 h after ICU admission. The primary and secondary outcomes were the diagnostic value of serum activin-A concentration as a biomarker of sepsis and the prognostic value for predicting the clinical outcomes of sepsis, respectively. Results One hundred and thirty patients who had clinically suspected sepsis were included. Most (66.2%) were male; their median age was 65 years, and their Acute Physiology and Chronic Health Evaluation II score was 22.3. Serum activin-A concentration tended to increase with sepsis severity and differed significantly between those with non-sepsis and severe sepsis and between those with severe sepsis and septic shock. The risks of sepsis, severe sepsis and septic shock were significantly higher in patients with a serum activin-A concentration of 251, 319 and 432 pg/mL or greater, respectively. Serum activin-A concentration was significantly associated with the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, Charlson comorbidity index and ICU mortality. Conclusion Serum activin-A was a predictor of sepsis severity and a prognostic marker in critically ill patients with sepsis. Serum activin-A concentration in the early phase of sepsis was associated with prognostic indexes on ICU admission and with ICU mortality.

Background/aims Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). Methods All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. Results A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). Conclusions Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC.

SETTING A referral centre in South Korea. OBJECTIVE To investigate trends in drug resistance, treatment modalities and outcomes, and adverse events of multidrug-resistant tuberculosis (MDR-TB) over two decades. DESIGN MDR-TB patients treated at Seoul National Hospital University between 1996 and 2015 were divided into four 5-year cohorts according to the date of initial diagnosis. Changes in demographic characteristics, drug resistance, drugs used, treatment outcomes and adverse events over time were elucidated. RESULTS Between 1996 and 2015, 418 patients were treated for MDR-TB: 86 patients between 1996 and 2000, 125 between 2001 and 2005, 123 between 2006 and 2010, and 84 between 2011 and 2015. The proportion of patients with positive acid-fast bacilli sputum (60.5-29.7%, P < 0.001) or cavities on chest radiographs (86.0-40.5%, P < 0.001) decreased over time. Resistance to pyrazinamide, fluoroquinolones, cycloserine and p-aminosalicylic acid decreased. Later-generation fluoroquinolones (77.9-90.5%) and linezolid (0-26.2%) became more frequently prescribed. The treatment success rate increased (45.3-88.1%, P < 0.001); neurological adverse events, including peripheral neuropathy also increased (4.7-13.1%, P = 0.027). CONCLUSION MDR-TB patients presented with less severe disease and better resistance profiles over time in South Korea, with treatment outcomes improving continuously.

Background Severe viral pneumonia is associated with a high mortality rate. However, due to the vulnerability of critically ill patients, invasive diagnostic methods should be performed with caution in the intensive care unit (ICU). It would be helpful if the prevalence, risk factors, and clinical impact of virus detection are elucidated. Methods We evaluated patients with severe pneumonia between January 1st 2008 and December 31st 2015. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for 8 respiratory viruses when viral pathogen could not be excluded as the origin of severe pneumonia. The baseline characteristics, laboratory results, microbiological findings, and clinical outcomes of the patients were analyzed. Results Of the 2,347 patients admitted to the medical ICU, 515 underwent RT-PCR for respiratory viruses, 69 of whom had positive results. The detection rate was higher during the winter, with a community onset, in patients with history of recent chemotherapy, and low platelet count. Additional bronchoscopic sampling along with upper respiratory specimen increased the yield of viral detection. Respiratory syncytial virus was the most common pathogen detected, while influenza A was the most common virus with bacterial coinfection. Respiratory virus detection led to changes in clinical management in one-third of the patients. Conclusions The detection of viral pathogens in patients with severe pneumonia is not rare, and can be more common in certain group of patients. Invasive sampling for RT-PCR can be helpful, and such detection can lead to positive changes in clinical management.

Background: The number of elderly patients admitted to intensive care units (ICUs) is growing with the increasing proportion of elderly persons in the Korean general population. It is often difficult to make decisions about ICU care for elderly patients, especially when they are in their 90s. Data regarding the proportion of elderly patients in their 90s along with their clinical characteristics in ICU are scarce. Methods: The records of Korean patients ≥ 90 years old who were admitted to the medical ICU in a tertiary referral hospital between January 2005 and December 2014 were retrospectively reviewed. We compared the trend in ICU use and characteristics of these elderly patients between 2005-2009 and 2010-2014. Results: Among 6,186 referred patients, 55 aged ≥ 90 years were admitted to the medical ICU from 2005 to 2014. About 58.2% of these patients were male, and their mean age was 92.7 years. Their median Charlson comorbidity index score was 2 (IQR 1-3) and their mean APACHE II score was 25.0 (IQR 19.0-34.0). The most common reason for ICU care was acute respiratory failure. There were no differences in the survival rates between the earlier and more recent cohorts. However, after excluding patients who had specified “do not resuscitate” (DNR), the more recent group showed a significantly higher survival rate (53.8% mortality for the earlier group and 0% mortality for the recent group). Among the survivors, over half were discharged to their homes. More patients in the recent cohort (n=26 [78.8%]) specified DNR than in the earlier cohort (n=7 [35.0%], p=0.004). The number and proportion of patients ≥ 90 years old among patients using ICU during the 2005-2014 study period did not differ. Conclusions: The use of ICU care by elderly patients ≥ 90 years old was consistent from 2005-2014. The overall mortality rate tended to decrease, but this was not statistically significant. However, the proportion of patients specifying DNR was higher among more recent patients, and the recent group showed an even better survivorship after sensitivity analysis excluded patients specifying DNR.

Cryptococcosis is a systemic opportunistic infection mostly occurred in immunosuppressed patients. Pulmonary cryptococcosis in immunocompetent host is usually localized and self-limiting disease. Pulmonary nodule or mass is the most common radiologic finding, however involvement of mediastinal lymph nodes is rare. Here we report a case of pulmonary cryptococcosis with massive mediastinal lymph nodes involvement in immunocompetent host.

Background Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IκBα)/nuclear factor-kappa B (NF-κB) pathway in RAW 264.7 cells. Methods Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IκBα and nuclear translocation of NF-κB p65 were measured by Western blotting, and IκB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IκBα/NF-κB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. Results The increase of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IκBα degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-κB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IκBα degradation and NF-κB transcription by AVP was abolished by tolvaptan treatment. Conclusions Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IκBα/NF-κB cascade in mouse macrophages via V2 receptors.

SETTING After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. DESIGN Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. RESULTS Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. CONCLUSION Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.

History of treatment for tuberculosis (TB) is a risk factor for obstructive lung disease. However, it has been unclear whether the clinical characteristics of patients with destroyed lung by TB differ according to the presence or absence of airflow limitation. The objective of the study was to evaluate differences in acute exacerbations and forced expiratory volume in 1 second (FEV1) decline in patients with destroyed lung by TB according to the presence or absence of airflow limitation. We performed a retrospective cohort study and enrolled patients with destroyed lung by TB. The presence of airflow limitation was defined as FEV1/forced vital capacity (FVC) < 0.7. One hundred and fifty-nine patients were enrolled, and 128 (80.5%) had airflow limitation. The proportion of patients who experienced acute exacerbation was higher in patients with airflow limitation compared to those without (89.1 vs. 67.7%, respectively; P = 0.009). The rate of acute exacerbation was higher in patients with airflow limitation (IRR, 1.19; 95% CI, 1.11-1.27). Low body mass index (X vs. X + 1; HR, 0.944; 95% CI, 0.895-0.996) in addition to airflow limitation (HR, 1.634; 95% CI, 1.012-2.638), was an independent risk factor for acute exacerbation. The annual decline of FEV1 was 2 mL in patients with airflow limitation and 36 mL in those without (P < 0.001). In conclusion, the presence of airflow limitation is an independent risk factor for acute exacerbation in patients with the destroyed lung by TB.

Background An adequate threshold for the Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) defining more symptomatic COPD patients has not been determined. We aimed to determine the efficacy of the CCQ and the appropriate CCQ threshold for more symptomatic COPD patients. Methods COPD patients aged > 40 years who smoked/had smoked ≥10 packs/year were prospectively enrolled over 1 year from three South Korean hospitals (n = 126). Correlations between the CCQ and St. George’s Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), the modified Medical Round Council (mMRC) scale, lung function, and exercise capacity were evaluated. “More symptomatic patients” were those with an SGRQ score ≥ 25. Area under the receiver operating curve and classification and regression tree analyses were performed to determine the CCQ threshold equivalent to an SGRQ score ≥ 25. Results The CCQ significantly correlated with the SGRQ, CAT, and mMRC scale (r = 0.76, 0.69, and 0.53, respectively). A CCQ cutoff of 1.4 predicted an SGRQ score of 25 better than others. A CCQ score of 1.4 was a significant determinant of an SGRQ score ≥ 25 even after adjusting for potential confounders. Conclusions The CCQ was correlated with other symptom indicators, lung function, and exercise capacity. A CCQ cutoff of 1.4 agreed better than CCQ cutoff of 1.0, suggested by guideline, and this cutoff value may identify more symptomatic COPD patients well. Trial registration ClinicalTrials.gov Identifier: NCT02527486. Date of registration: December 19, 2014, retrospectively registered.

Yong Suk Jo,1 Ho Il Yoon,2 Deog Kyeom Kim,3 Chul-Gyu Yoo,1 Chang-Hoon Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea Background and objective: Guidelines recommend the use of simple but comprehensive tools such as COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ) to assess health status in COPD patients. We aimed to compare the ability of CAT and CCQ to predict exacerbation in COPD patients. Methods: We organized a multicenter prospective cohort study that included COPD patients. The relationships between CAT, CCQ, and other clinical measurements were analyzed by correlation analysis, and the impact of CAT and CCQ scores on exacerbation was analyzed by logistic regression analyses and receiver operating characteristic curve. Results: Among 121 COPD patients, CAT and CCQ score correlated with other symptom measures, lung function and exercise capacity as well. Compared with patients who did not experience exacerbation, those who experienced exacerbation (n=45; 38.2%) exhibited more severe airflow limitation, were more likely to have a history of exacerbation in the year prior to enrollment, and demonstrated higher CAT scores. CCQ scores were not significantly associated with exacerbations. A CAT score of ≥15 was an independent risk factor for exacerbation (adjusted odds ratio [aOR], 2.40; 95% CI, 1.03–6.50; P=0.04). Furthermore, CAT scores of ≥15 demonstrated an increased predictive ability for exacerbation compared with currently accepted guidelines for the use of CAT (≥10) and CCQ (≥1) in the assessment of COPD patients (area under the curve for CAT ≥15, CAT ≥10, and CCQ ≥1 was 0.61±0.04, 0.53±0.03, and 0.50±0.03, respectively; P=0.03). Conclusion: A CAT score of ≥15 indicates increased risk of exacerbation in COPD patients, whereas there is no evidence for increased risk based on CCQ score. Keywords: COPD, exacerbation, questionnaire

Background: All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated yet. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. Methods: Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. We compared the mortality risk and causes of death between the bronchiectasis and non-bronchiectasis groups. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. Findings: Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were eventually included. The all-cause mortality rate in the bronchiectasis group was 1608·8 per 100,000 person-years (95% CI 1531·5-1690·0), which was higher than that in the non-bronchiectasis group (133·5 per 100,000 person-years; 95% CI 124·1-143·8; P

No study has determined whether the risk of mortality predicted by the GAP (gender, age, and physiologic variables) model matches the observed mortality from idiopathic pulmonary fibrosis (IPF) in non-Western populations. We evaluated the clinical course of IPF and validated the GAP model in Korean patients with IPF.We included 268 patients who received a diagnosis of IPF at Seoul National University Hospital between 2005 and 2009. For each patient, demographics and clinical data, such as lung physiologic parameters at IPF diagnosis, were evaluated. We validated the GAP model using discrimination and calibration to predict the risk of death in Korean patients with IPF.The study population comprised 181 men and 87 women (mean age, 65.9 years). The mean baseline % predicted FVC was 77, and % predicted diffusing capacity of lung for carbon monoxide was 65.9. A total of 157 deaths (58.6%) occurred during follow-up, and the median time to death was 4.64 years. The observed cumulative mortality at 1, 2, and 3 years was 10.4%, 20.9%, and 31.0%, respectively. The GAP model produced estimates of 1-year mortality risk consistent with the observed data (C statistic: GAP calculator, 0.74; GAP index and staging system, 0.72; P.29). However, calibration of the GAP model at 3 years was not satisfactory.The GAP model showed similar discrimination power compared with the original cohort but did not predict the 3-year risk of death accurately. Further multinational validation studies are needed.

SummaryBackgroundMultiple comorbidities related to chronic obstructive pulmonary disease (COPD) make it a difficult disease to treat. The relationship between these comorbidities and COPD has not been fully investigated. We aimed to determine whether COPD was independently associated with various comorbidities.MethodsThis was a cross-sectional study, which used data from the Korean National Health and Nutrition Examination Survey (KNHANES) V conducted between 2010 and 2012. Survey design analysis was employed to determine the association between COPD and 15 comorbidities. A COPD patient was defined as a smoker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Inflammation and oxidative stress have been suggested as an important pathogenesis of chronic obstructive pulmonary disease (COPD). We investigated the effect of YPL-001, the drug substance of Pseudolysimachion rotundum var. subintegrum , on cigarette smoke extract (CSE)-induced inflammation and anti-oxidative pathway in human bronchial epithelial cells. CSE induced interleukin-8 (IL-8) which was significantly suppressed by YPL-001. YPL-001 also suppressed IL-17A-induced IL-8 release, which suggests that the inhibitory effect of YPL-001 on IL-8 production is not CSE stimulation-specific. NF-κB is a major transcription factor that regulates the expression of several genes including inflammatory cytokines. Although YPL-001 did not block nuclear translocation of NF-κB subunit p65, it suppressed transcriptional activity of NF-κB by blocking acetylation of p65 (Lys310) and suppressed CSE or IL-17A-induced transcription of IL-8 gene. Histone deacetylases (HDACs) prevent gene transcription by condensing DNA structure and affecting NF-κB nuclear binding. YPL-001 alone increased HDAC activity and enhanced CSE-induced activation of HDAC. YPL-001-induced suppression of NF-κB transcriptional activity might be caused by increase in HDAC activity. Moreover, we found that YPL-001 increased Nrf2 expression via both degradation of its inhibitory protein, Keap1 and de novo protein synthesis, resulting in nuclear translocation of Nrf2. YPL-001 increased DNA binding activity of Nrf2. Consequently, YPL-001 up-regulated the expression of Nrf2-targeted anti-oxidant genes such as NQO1 and HO-1. Altogether, these results suggest that YPL-001 could be a good therapeutic candidate for treatment of COPD.

Background: The clinical outcome of eosinophilic airway inflammation in patients with chronic airway diseases is still unclear. Objectives: This study aimed to evaluate the incidence and predictors of exacerbations in patients with nonasthmatic eosinophilic bronchitis (NAEB), and to investigate predictors of improvement in eosinophilic inflammation in chronic airway diseases. Methods: We retrospectively enrolled patients with confirmed sputum eosinophilia (≥ 3%) who had visited our tertiary hospital between 2012 and 2015. About half of the patients were followed up with induced sputum tests for at least 1 year. Results: In total, 398 patients with sputum eosinophilia were enrolled. Of these, 152 (38.2%) had NAEB. The incidence rate of exacerbations requiring treatment with antibiotics, systemic corticosteroids, or hospital admission was 0.13 per patient-year (95% CI, 0.06–0.19) in patients with NAEB. Inhaled corticosteroid (ICS) therapy did not affect the risk of exacerbations, even in an analysis of propensity score. One hundred seventy-six patients had chronic airway diseases; in 37 of these (21.0%), sputum eosinophilia had improved at the 1-year follow-up. Patients who had persistent airflow limitation were less likely to show an improvement in eosinophilic inflammation (aOR, 0.26; 95% CI, 0.09–0.77) when they were treated with ICSs for less than 75% of the follow-up days. Conclusions: Exacerbations requiring systemic corticosteroids, antibiotics, or hospitalization did occur in NAEB patients. Among patients with chronic airway diseases, those with persistent airflow limitation were less likely to show an improvement in eosinophilic airway inflammation.

Cheong-Ju Kim,1 Hyoung-Kyu Yoon,2 Myung-Jae Park,3 Kwang-Ha Yoo,4 Ki-Suck Jung,5 Jeong-Woong Park,6 Seong Yong Lim,7 Jae Jeong Shim,8 Yong Chul Lee,9 Young-Sam Kim,10 Yeon-Mok Oh,11 Song Kim,12 Chul-Gyu Yoo13 1Department of Internal Medicine, National Health Insurance System Ilsan Hospital, Koyang, 2Division of Pulmonology, Department of Internal Medicine, St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Respiratory and Critical Care Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, 4Department of Internal Medicine, Konkuk University School of Medicine, Gwangjin-gu, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang-si, 6Division of Pulmonary and Allergy Medicine, Gachon University Gil Medical Center, Incheon, 7Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 8Department of Internal Medicine, Korea University College of Medicine, Seoul, 9Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonbuk, 10Department of Internal Medicine, Yonsei University College of Medicine, 11Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 12Clinical Development and Medical Affairs, Novartis Korea Ltd., Seoul, 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Background and objective: Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation. Methods: This was a multicenter, double-blind, parallel-group study, in which eligible patients were randomized (1:1) to receive either once-daily indacaterol 150 µg or placebo for 8 weeks. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s at Week 8; the secondary endpoints included changes in transition dyspnea index score and St George’s Respiratory Questionnaire for COPD score at Week 8. Safety was evaluated over 8 weeks. Results: Of the 136 patients randomized, 119 (87.5%) completed the study treatment. At Week 8, indacaterol significantly improved trough forced expiratory volume in 1 s versus placebo (treatment difference [TD] 140 mL, P

Purpose:Uric acid acts as both a pathogenic inflammatory mediator and an antioxidative agent. Several studies have shown that uric acid level correlates with the incidence, severity, and prognosis of pulmonary diseases. However, the association between uric acid level and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how serum uric acid level is related with clinical prognosis of ARDS.Methods:A retrospective cohort study with propensity score matching was conducted at a medical intensive care unit of a tertiary teaching hospital. The medical records of patients diagnosed with ARDS admitted from 2005 through 2011 were reviewed.Results:Two hundred thirty-seven patients with ARDS met the inclusion criteria. Patients with a serum uric acid level Conclusion:In patients with ARDS, a low serum uric acid level may be a prognostic marker of a low risk of in-hospital mortality.

Background Inhaled corticosteroid (ICS) is recommended in the management of patients with asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS), but its effectiveness has not been clearly proved. Objective To evaluate whether ICS has effects on outcomes of ACOS. Methods In this observational 12-year retrospective cohort study involving 125 patients with ACOS from Seoul National University Hospital, the annual rate of decrease in forced expiration volume in 1 second, the incidence rate of severe exacerbation, and overall mortality in an ICS-treated group were compared with those in a non-ICS–treated group. Results Of 125 patients with ACOS, 90 and 35 were categorized to the ICS and non-ICS treatment groups, respectively. There were no significant differences between the 2 groups in the annual rate of decrease in forced expiration volume in 1 second (9.61 mL/year in ICS treatment group vs 15.68 mL/year in non-ICS treatment group, P = .598). Compared with the non-ICS treatment group, the ICS treatment group did not show a decrease in the risk of severe exacerbation (adjusted incidence rate ratio 1.24, 95% confidence interval 0.44–3.46). Time to death also did not differ between the 2 groups. Even when analyses with propensity score matching were performed, the results were similar. Conclusion In the management of ACOS, the use of ICS was not significantly associated with improvements in the annual rate of decrease in forced expiration volume in 1 second, the incidence of severe exacerbations, and overall mortality compared with the non-ICS treatment group.