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According to the 2017 National Air Pollutant Emissions Inventory (NEI), air pollutant emissions in the Republic of Korea comprised 817,420 metric tons (hereafter tons) of CO, 1,189,800 tons of NOx, 315,530 tons of SOx, 592,582 tons of TSP, 218,476 tons of PM10, 91,731 tons of PM2.5, 15,555 tons of black carbon (BC), 1,047,585 tons of VOCs, and 308,298 tons of NH3. Emissions of the 13 first-level emission source categories, which constitute the NEI, were estimated and, based on their characteristics, the emission source categories were grouped into five sectors (energy, industry, road, non-road, and everyday activities and others). In addition, the contributions of primary PM2.5 and its four precursors (NOx, SOx, VOCs, and NH3) to the 2017 NEI were assessed in this study. The emission contributions of NOx to the NEI were 36.5% for the road sector, which was the highest of those of all the air pollutants for this sector; NOx emissions for this sector were 4.2% lower than those in the previous year. The emission contributions of SOx and PM2.5 to the NEI were higher than those of the other air pollutants for the industry sector; SOx and PM2.5 emissions for this sector decreased by 9.8% and 19.7%, respectively, compared with those in the previous year. The emission contributions of VOCs and NH3 to the NEI were 65.3% and 83.9% for the everyday activities and others sector, respectively, higher than those of the other air pollutants for this sector; VOCs and NH3 emissions for this sector increased by 0.8% and 2.9%, respectively, compared with those in the previous year. A three-dimensional (3D) chemical transport modeling system was used to validate the emission estimates. These data suggest that simulated SOx emissions were overestimated in areas with dense large-scale industrial complexes, such as Jeollanam-do, Gyeongsangbuk- do, and Ulsan, and that simulated NOx emissions were overestimated in Seoul, Incheon, and Jeollanam-do.

Background: Lung epithelial cells serve as first line of defense against various inhaled pollutant particles. This study focused on assessing the impact of organic extracts of PM2.5 collected in Seoul, South Korea on primary human lung epithelial cells and identifying the relevant components and sources which induced lung epithelial cell injury.Results: We used primary lung epithelial cells isolated directly from healthy donors and evaluated the effects of organic compounds of twelve selected, seasonal PM2.5 on inflammation, cellular aging, and macroautophagy in primary lung epithelial cells. Organic extracts of PM2.5 specifically induced neutrophilic chemokine, interleukin-8, via extracellular signal regulated kinase activation. Moreover, PM2.5 significantly increased the expression of aging markers (p16, p21, and p27) and activated macroautophagy. Average mass concentrations, OC and EC, had no significant correlations with PM2.5 effects. However, regression analysis showed that polycyclic aromatic hydrocarbons and n-alkanes were the most relevant components of PM2.5 correlated with neutrophilic inflammation. Vegetative detritus and residential bituminous coal combustion sources were strongly correlated with neutrophilic inflammation, aging and macroautophagy activation.Conclusions: These data suggest that the chemical composition of PM2.5 is crucially important to determine the adverse health effects of PM2.5. Our study provides encouraging evidence to regulate the harmful components of PM2.5 in Seoul.

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.

Pulmonary fibrosis is a progressive and lethal lung disease characterized by the proliferation and differentiation of lung fibroblasts and the accumulation of extracellular matrices. Since pulmonary fibrosis was reported to be associated with adenosine monophosphate-activated protein kinase (AMPK) activation, which is negatively regulated by cereblon (CRBN), we aimed to determine whether CRBN is involved in the development of pulmonary fibrosis. Therefore, we evaluated the role of CRBN in bleomycin (BLM)-induced pulmonary fibrosis in mice and in transforming growth factor-beta 1 (TGF-β1)-induced differentiation of human lung fibroblasts. BLM-induced fibrosis and the mRNA expression of collagen and fibronectin were increased in the lung tissues of wild-type (WT) mice; however, they were significantly suppressed in Crbn knockout (KO) mice. While the concentrations of TGF-β1/2 in bronchoalveolar lavage fluid were increased via BLM treatment, they were similar between BLM-treated WT and Crbn KO mice. Knockdown of CRBN suppressed TGF-β1-induced activation of small mothers against decapentaplegic 3 (SMAD3), and overexpression of CRBN increased it. TGF-β1-induced activation of SMAD3 increased α-smooth muscle actin (α-SMA) and collagen levels. CRBN was found to be colocalized with AMPKα1 in lung fibroblasts. CRBN overexpression inactivated AMPKα1. When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of α-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-β1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKα1 inactivation. Taken together, these data suggest that CRBN is a profibrotic regulator and maybe a potential target for treating lung fibrosis., Lung disease: Putting the brakes on fibrosis Interventions that target a regulatory protein called cereblon could help reduce the damage inflicted on the lungs by idiopathic pulmonary fibrosis (IPF). This incurable and generally fatal condition is associated with the accumulation of scar tissue in the lungs, which leads to the gradual loss of respiratory function. Researchers led by Kyoung-Hee Lee at Seoul National University Hospital in South Korea have now identified cereblon as a potentially important contributor to this scarring process. They found that cereblon regulates a complex metabolic pathway that ultimately contributes to production of fibrosis-related proteins in a mouse model of IPF. Genetically modified animals that lacked the gene encoding cereblon showed reduced accumulation of these proteins in their lungs. These results suggest that cereblon-inhibiting agents could potentially control the progression of IPF and help preserve lung function.

In 2016, air pollutant emissions in the Republic of Korea were 795,044 metric tons (hereafter tons) of CO, 1,248,309 tons of NOx, 358,951 tons of SOx , 611,539 tons of TSP, 233,085 tons of PM10, 100,247 tons of PM2.5, 16,401 tons of BC, 1,024,029 tons of VOCs, and 301,301 tons of NH3. Including energy production, thirteen emission sources, which comprise the national air pollutant emission inventory, were classified by their characteristics into five sectors (Energy, Industry, Road, Non-road, and Everyday Activities and Other Emission Sources) to analyze their relative contributions to the national emissions. Specifically, their contributions by pollutant were as follows: NOx (11.0%), SOx (21.9%), PM2.5 (3.2%), VOCs (0.8%), NH3 (0.5%) from the energy sector; NOx (20.2%), SOx (59.7%), PM2.5 (42.1%), VOCs (24.3%), and NH3 (14.4%) from the industry sector; NOx (36.3%), SOx (0.1%), PM2.5 (9.7%), VOCs (4.6%), and NH3 (1.7%) from the road sector; NOx (24.8%), SOx (11.5%), PM2.5 (14.3%), VOCs (4.0%), and NH3 (0.04%) from the non-road sector; and NOx (7.6%), SOx (6.7%), PM2.5 (30.6%), VOCs (66.3%), and NH3 (83.4%) from the everyday activities and other emission sources sector. The data we calculate are used as official national emissions data for the establishment, implementation, and assessment of national atmospheric environment policy to improve air quality. As critical and necessary materials, the data are also utilized on a wide range of studies on policies such as customized regional particulate matter reduction measures. Thus, it is crucial to estimate highly reliable national emissions by enhancing the emissions factors and inventory and to establish a scientific emissions testing system by using air quality modeling and satellite data.

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.

Yun-Jeong Jeong,1,&ast; Kyoung-Hee Lee,2,&ast; Jisu Woo,2 Ji Yeon Kim,2 Chang-Hoon Lee,2,3 Chul-Gyu Yoo2,3 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongguk University Ilsan Hospital, Ilsan Dong-gu, Goyang-si, Gyeonggi-do, Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Chul-Gyu Yoo, 101 Daehakno, Jongno-gu, Seoul, 03080, Korea, Tel +82-2-2072-3760, Fax +82-2-762-9662, Email cgyoo@snu.ac.krBackground: Macroautophagy plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the role of chaperone-mediated autophagy (CMA) has not been investigated. We investigated if and how CMA is involved in the pathogenesis of COPD.Methods: We measured the level of lysosome-associated membrane protein-2A (LAMP-2A), which is a critical component of CMA that functions as a receptor for cytosolic substrate proteins, in total lung tissues and primary human bronchial epithelial cells (HBECs) from healthy never smokers, smokers, and COPD patients. We assessed the effects of LAMP-2A knock-down on cigarette smoke extract (CSE)-induced aging, cell cycle arrest, and apoptosis in BEAS-2B cells and the expression levels of apoptosis hallmarks in primary HBECs and lung tissue sections.Results: We found that the protein levels of LAMP-2A in lung homogenates and primary HBECs from smokers and COPD patients were lower than those from never smokers. In addition, its level in primary HBECs was negatively correlated with years of smoking. CSE caused degradation of LAMP-2A protein via the lysosomal pathway by activating macroautophagy. Knock-down of LAMP-2A markedly enhanced CSE-induced expression of senescence markers such as p16, p21, p27, and p53. G2/M cell cycle arrest, up-regulation of cyclin B1, and apoptosis in BEAS-2B cells. Apoptosis was increased in CSE-treated primary HBECs and in lung tissues from smokers and COPD patients.Conclusion: Cigarette smoke-induced down-regulation of LAMP-2A is involved in acceleration of aging and apoptosis of lung epithelial cells, which might at least partially contribute to COPD pathogenesis.Keywords: COPD, LAMP-2A, lung epithelial cells, aging, apoptosis

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

In 2015, air pollutant emissions in the Republic of Korea were 792,776 metric tons of CO, 1,157,728 metric tons of NOx, 352,292 metric tons of SOx, 604,243 metric tons of TSP, 233,177 metric tons of PM10, 98,806 tons of PM2.5, 15,934 metric tons of BC, 1,010,771 metric tons of VOCs, and 297,167 metric tons of NH3. Among major emission source categories, the main emission sources and the contributions to emissions, by pollutant, were as follows: road transport (31.0%), biomass burning (29.3%), and non-road transport (17.1%) for CO; road transport (31.9%), non-road transport (26.3%), and manufacturing industry (14.6%) for NOx; industrial processes (29.9%), energy production (25.9%), and manufacturing industry (24.2%) for SOx; fugitive dust (67.6%) manufacturing industry (20.1%) for TSP; fugitive dust (47.0%) and manufacturing industry (30.4%) for PM10; manufacturing industry (36.8%), fugitive dust (17.5%), and non-road transport (14.3%) for PM2.5; road transport (42.0%) and non-road transport (39.6%) for BC; solvent use (54.9%) and industrial processes (18.1%) for VOCs; and agriculture (77.8%) and industrial processes (13.3%) for NH3. The data we calculate can be used as official national emissions data for the establishment, implementation, and assessment of air quality-related policy, such as measures to deal with particulate matter, as well as for related modeling and other research.

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 and objective: Few studies have investigated the differences in the incidence of anxiety and depression among the interstitial lung diseases (ILDs). We evaluated the differences in the incidence of anxiety and depression between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD, and the changes after a 1-year follow-up period. Methods The study participants were patients included in a prospective ILD cohort of Seoul National University Hospital between March 2013 and August 2018. Clinical variables were recorded at baseline and at 1 year. The Hospital Anxiety and Depression Scale was used to assess patient anxiety and depression at baseline and at 1-year follow-up. Results A total of 224 patients in the cohort participated in the study (154 [68.8%] with IPF and 70 [31.2%] with non-IPF ILD). Among them, 111 patients completed a follow-up Hospital Anxiety and Depression Scale questionnaire 1 year later (77 in the IPF group, 34 in the non-IPF group). In the IPF group, 20.8% and 27.3% of patients suffered from anxiety and 29.9% and 31.2% suffered from depression at baseline and 1-year follow-up, respectively. In the non-IPF group, 14.3% and 23.5% of patients suffered from anxiety and 24.3% and 17.6% suffered from depression at baseline and 1-year follow-up, respectively. Total score on the St. George’s Respiratory Questionnaire at baseline was associated with depression both at baseline (odds ratio 1.05; 95% confidence interval 1.02–1.08) and at 1-year follow-up (odds ratio 1.03; 95% confidence interval 1.00-1.05), even after adjusting other factors. The interaction of prevalence change of anxiety and depression at baseline and 1-year follow-up between the IPF group and the non-IPF ILD group were not statistically significant (p-value 0.878 for anxiety and 0.376 for depression, respectively). Conclusion The prevalence of anxiety and depression at baseline and at 1-year follow-up were not significantly different between patients with IPF and non-IPF ILD. St. George’s Respiratory Questionnaire total score at baseline was associated with depression at baseline and at 1-year follow-up.

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.

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to infection owing to the impaired immune function of alveolar macrophages. This is presumed to be caused, at least partially, by cigarette smoke (CS), which is a major risk factor for COPD. Although CS has been reported to inhibit Toll-like receptor (TLR) function and phagocytosis in macrophages, the molecular mechanism of CS-mediated impairment of macrophage immune function has not been completely elucidated. We investigated the effects of CS extracts (CSE) on macrophage immune function and its molecular mechanism. We assessed lipopolysaccharide (LPS, TLR4 ligand)-, Pam3CSK4 (TLR2 ligand)-, or CpG-oligodeoxynucleotide (TLR9 ligand)-induced IL-6, TNF-α, and IL-1β production in macrophages. Upregulation of IL-6, TNF-α, and IL-1β mRNA and protein by TLR ligands was suppressed on treatment with CSE. However, LPS-induced MAP kinase activation, IκBα degradation, and nuclear translocation of NF-κB were not impeded by CSE. In contrast, CSE significantly suppressed NF-κB transcriptional activity in the nucleus. We found that p300, which acetylates RelA/p65 at lysine 310, and acetyl-p65 (K310) were downregulated upon CSE treatment. Knock-down of p300 suppressed LPS-induced acetylation of NF-κB p65 and production of inflammatory cytokine. To summarize, these results suggest that CSE impair cytokine response by decreasing the expression levels of p300.