Incidence of systemic vasculitides after Mycobacterium tuberculosis infection: A population-based cohort study in Korea.

BACKGROUND: Tuberculosis (TB) is a highly prevalent disease associated with significant morbidity and mortality globally, and is reported to be associated with the onset of autoimmunity. This study investigated the association between TB and the incidence of systemic vasculitides (SV). METHODS: Data were obtained from the South Korean National Claims database to identify patients with TB and controls (who had undergone appendectomy). The overall occurrence of SV and disease subtypes during the observation period was compared between the two groups. Adjusted Cox proportional hazards regression and Kaplan-Meier analysis were performed to identify the relationship between TB and SV and to compare SV incidence. RESULTS: We identified 418 677 patients with TB and 160 289 controls. The overall SV incidence rate was 192/1,000 000 person-years during a mean follow-up of 7.5 years and was higher in patients with TB than controls. Cox regression revealed that the risk of SV was elevated in the TB group independently (adjusted hazard ratio [aHR]: 1.72, 95% confidence interval [CI]: 1.45-2.05). Furthermore, the risk of SV was significantly higher in extrapulmonary TB (aHR: 4.28, 95% CI: 3.52-5.21) when the TB group was categorized into pulmonary and extrapulmonary TB. The findings remained identical even after applying a stabilized inverse probability of treatment weighting analysis. CONCLUSIONS: Patients with TB have increased risk of SV, which is prominent in extrapulmonary TB. As well as confirming TB is associated with increased incidence of immune-related vasculitis, our findings highlight the need for clinical vigilance for early diagnosis and initiation of treatment.

Association between Mycobacterium tuberculosis infection and the risk of inflammatory arthritides.

OBJECTIVES: Tuberculosis is a highly contagious disease that has a significant impact on global health. Emerging evidence suggests that tuberculosis can lead to an altered immune response. We investigated the association between tuberculosis and the onset of inflammatory arthritides (IA). METHODS: Patients with incident tuberculosis in the South Korean National Claims database from 2010 to 2021 were included, and those who had undergone appendectomy during 2010-2011 served as controls. The onset of IA (including seropositive rheumatoid arthritis [SPRA], ankylosing spondylitis [AS], and psoriatic arthritis [PsA]) after tuberculosis was compared between patients with tuberculosis and the control group. Sensitivity analysis was performed using stabilised inverse probability of treatment weighting (sIPTW). RESULTS: A total of 408,685 patients with tuberculosis and 159,675 controls were included. During the mean follow-up of 7.5 years, a total of 1,957 (0.3%) were diagnosed with IA (SPRA, 1,397; AS, 481; and PsA, 79). Multivariable Cox hazard analysis indicated that the overall risk of IA was elevated in the tuberculosis group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.51-1.93) compared with controls. This increased incidence in patients with tuberculosis was identical among IA subgroups even after adjustment (SPRA [HR, 1.72; 95% CI, 1.49-2.00], AS [HR, 1.64; 95% CI, 1.30-2.06], and PsA [HR, 2.59; 95% CI, 1.32-5.07]) and was replicated in the sIPTW. CONCLUSIONS: The increased overall risk of developing IA after tuberculosis corroborates the hypothesis that tuberculosis can trigger dysregulated immunity. This necessitates an increased awareness of autoimmunity in this patient group.

Particulate matter10-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

BACKGROUND: Particulate matter10 (PM10) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM10-treated murine mice models. METHODS: In female BALB/c mice, PM10 was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered. Chitinase-1 inhibitor (CPX) 6 times over 3 weeks or dexamethasone 3 times in the last week were intraperitoneally administered. Two days after the last challenges, mice were euthanized. Messenger RNA sequencing using lung homogenates was conducted to evaluate signaling pathways. RESULTS: PM10 and/or OVA-induced airway inflammation and fibrosis murine models were established. CPX and dexamethasone ameliorated PM10 or PM10/OVA-induced airway hyper-responsiveness, airway inflammation, and fibrosis. CPX and dexamethasone also reduced levels of various inflammatory markers in lung homogenates. PM10 and OVA also induced changes in mRNA expression across an extreme range of genes. CPX and dexamethasone decreased levels of mRNA expression especially associated with inflammation and immune regulation. They also significantly regulated asthma and asthma-related pathways, including the JACK-STAT signaling pathway. CONCLUSIONS: Chitinase-1 suppression by CPX can regulate PM10- and OVA-induced and aggravated airway inflammation and fibrosis via an asthma-related signaling pathway.

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients.

BACKGROUND: Previous studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea. METHODS: A single-center retrospective study was conducted. The study included 76 patients who received a lung transplant at a tertiary hospital in South Korea between January 2010 and March 2015. RESULTS: Nine patients (11.8%) had class I and/or class II panel-reactive antibodies greater than 50%. Twelve patients (15.8%) had anti-HLA antibodies with a low mean fluorescence intensity (MFI, 1000-3000), 7 (9.2%) with a moderate MFI (3000-5000), and 12 (15.8%) with a high MFI (> 5000). Ten patients (13.2%) had suspected donor-specific antibodies (DSA), and 60% (6/10) of these patients had antibodies with a high MFI. In an analysis of outcomes, high-grade (≥2) primary graft dysfunction (PGD) was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI values than in patients with low MFI values (39.4% vs. 14.0%, p = 0.011). Of 20 patients who survived longer than 2 years and evaluated for pBOS after transplant, potential bronchiolitis obliterans syndrome (pBOS) or BOS was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI than in patients with low MFI, although this difference was not statistically significant (50.0% vs. 14.3%, p = 0.131). CONCLUSIONS: The prevalence of anti-HLA antibodies with high MFI was not high in Korea. However, the MFI was relatively high in patients with DSA. Anti-HLA antibodies with moderate-to-high MFI values were related to high-grade PGD. Therefore, recipients with high MFI before lung transplantation should be considered for desensitization and close monitoring.

Factors associated with increased diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration: an observational single center study.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an innovative tool for diagnosing mediastinal diseases. We investigated the factors affecting the diagnostic yield of EBUS-TBNA and evaluated whether the effects of these factors (number of biopsies, core tissue acquisition rate, and diameter and volume of tissue) vary depending on computed tomography (CT) and/or positron emission tomography (PET)/CT results. Methods: We retrospectively analyzed lung cancer patients who underwent EBUS-TBNA at Korea University Ansan Hospital (January 2019-December 2022). Patients in whom EBUS-TBNA failed and those with missing diameter or volume data and no imaging data interpretation were excluded. Subgroup analysis was performed by dividing the patients into None (no cancer detected on CT or PET/CT), Either (cancer detected on either CT or PET/CT), and Both (cancer detected on both CT and PET/CT) groups. Results: In all, 228 patients were enrolled; 351 lymph node stations were analyzed. The median age of the patients was 69 years (male, 76.8%). Adenocarcinoma (28.5%) was the most common diagnosis. EBUS-TBNA was predominantly performed at station #4R (30.5%). Each examination involved two stations with a total procedure time of 30 minutes. An increased number of passes led to a higher diagnostic yield for EBUS-TBNA (P<0.001). Additionally, successful tissue sampling was associated with a large diameter (P=0.016) and volume (P=0.002) of the tissue. The effect of these factors was modified by imaging results. In the None and Either groups, an increase in the pass number was correlated with an increased diagnostic yield (adjusted P=0.003 and 0.007, respectively). However, in the Both group, it was not significant and remained at a suggestive level (P=0.304). The diameter and volume did not differ significantly across subgroups (adjusted P>0.05). Conclusions: Increasing the number of passes during EBUS-TBNA can maximize the diagnostic yield, especially when CT and/or PET/CT results are inconclusive.

Association Between Decreased Renal Function and Pulmonary Function Decline in Community-dwelling Adults.

BACKGROUND/AIM: Emerging evidence suggests that there is a close relationship between the human lung and kidney. This study evaluated whether decreased renal function was associated with accelerated pulmonary function decline in a large-scale community-based cohort. PATIENTS AND METHODS: A total of 10,028 subjects of the prospective Ansung-Ansan cohort were eligible for the longitudinal analysis of changes in pulmonary function associated with decreased renal function (glomerular filtration rate <60 ml/min/1.73 m2). Logistic regression analysis was performed to evaluate factors associated with decreased baseline renal function, and a linear mixed model compared changes in pulmonary function in participants with and without decreased renal function after propensity score matching (PSM). RESULTS: At baseline, subjects with and without decreased renal function showed distinct characteristics, and the factors associated with decreased renal function were age, baseline forced vital capacity, hypertension, and white blood cell (WBC) count. A 1:4 PSM of age, sex, body mass index, and smoking status showed that the proportion of those with hypertension and the WBC count differed between the patients with decreased and normal renal function. In the PSM population, those with decreased renal function had a greater decline in forced expiratory volume in the first second (FEV1) than those without (p=0.0402); however, these differences were not found to be evident when hypertension and WBC count were further matched (p=0.0807). CONCLUSION: The results of our study demonstrated that decreased renal function was not directly associated with the rapid decline in pulmonary function in a community-based general population setting.

Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer.

Purpose: In cases where rebiopsy fails to find the epidermal growth factor receptor (EGFR) T790M mutation, the criteria for selecting patients for repeated rebiopsy remains unclear. This study aimed to assess the impact of repeated rebiopsy on T790M mutation detection in non-small cell lung cancer (NSCLC) patients. Methods: Patients with advanced EGFR-mutated NSCLC between January 2018 and December 2021 at three-referral hospitals in South Korea underwent retrospective review. Of 682 patients who had rebiopsy after disease progression, T790M mutation status was assessed in plasma circulating tumor DNA (ctDNA) and/or tumor tissues. Results: The overall T790M positivity rate increased from 40.8% after the first rebiopsy to 52.9% following multiple rebiopsies in the entire study population. Longer duration of initial EGFR TKI use (OR 1.792, ≥8 months vs. <8 months, p=0.004), better EGFR TKI responses (OR 1.611, complete or partial response vs. stable disease, p=0.006), presence of bone metastasis (OR 2.286, p<0.001) were correlated with higher T790M positivity. Longer EGFR TKI use and better responses increased T790M positivity in repeated tissue rebiopsy, while bone metastasis favored liquid rebiopsy. Additionally, T790M status has been shown to be positive over time through repeated rebiopsies ranging from several months to years, suggesting its dynamic nature. Conclusion: In this study, among patients who initially tested negative for T790M in rebiopsy, repeated rebiopsies uncovered an additional 23.5% T790M positivity. Particularly, it is suggested that repeated rebiopsies may be valuable for patients with prolonged EGFR TKI usage, better responses to treatment, and bone metastasis.

UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer.

BACKGROUND: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. METHODS: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. RESULTS: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. CONCLUSION: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

Clinical and financial impact of immune checkpoint inhibitors following platinum chemotherapy in patients with advanced or metastatic non-small cell lung cancer: a nationwide population-based study.

Background: Although various studies have demonstrated that the clinical efficacy of immune checkpoint inhibitors (ICIs) improves the prognosis of patients with non-small cell lung cancer (NSCLC), studies on the financial aspects based on large population-based data are needed. This study aimed to analyze the differences in medical expenses and the effect of ICIs on the prognosis of patients with advanced or metastatic NSCLC. Methods: Patients newly diagnosed with stage IIIB or IV NSCLC who received palliative chemotherapy between 2013 and 2020 were selected from the nationwide database of the population covered by the Korean National Health Insurance Service. Interrupted time-series analysis was performed to evaluate the effects of subsequent ICI use after platinum-based cytotoxic chemotherapy (CC) on overall mortality. Progression-free survival and medical expenditure were also assessed. Results: In the final study population, 2,485 and 4,812 patients were included in the ICI and non-ICI groups, respectively. ICI treatment significantly lowered the risk of death [adjusted hazard ratio, 0.79; 95% confidence interval (CI): 0.75-0.84]. And the ICI-treated patients were less likely to experience disease progression (adjusted odds ratios, 0.92; 95% CI: 0.85-0.99). Furthermore, after the introduction of ICIs, both total and cancer-related medical expenses per capita showed an increasing trend [ß: $4.56K, standard error (SE): $0.27K, P<0.0001 and ß: $4.54K, SE: $0.27K, P<0.0001, respectively]. Conclusions: Subsequent ICI use after platinum-based CC improved the overall survival rate of patients with advanced NSCLC. With the increasing burden of individual medical expenses, further research is required to identify patients for whom ICI treatment may be effective.

Accumulation of plasmacytoid dendritic cell is associated with a treatment response to DNA-damaging treatment and favorable prognosis in lung adenocarcinoma.

Introduction: Favorable responses to the treatment including immune checkpoint inhibitors (ICIs) have been consistently reported in lung cancer with smoking history. As the tumor microenvironment (TME) may be involved in the treatment response to ICIs, we aimed to investigate the TME of lung cancer with different smoking status. Methods: Lung adenocarcinoma (LUAD) tissue (Tu) and adjacent normal-appearing lung tissue (NL) from current and never smokers were investigated by single-cell RNA sequencing and immunofluorescence and immunohistochemical staining. The clinical implications of identified biomarkers were validated using open-source datasets. Results: The lungs of smokers had an increased proportion of innate immune cells in NL tissues, whereas Tu tissues had a lower proportion of these cells than those of non-smokers. Monocyte-derived macrophages (mono-Mc), CD163-LGMN macrophages, monocyte-derived dendritic cells (DCs), and plasmacytoid DCs (pDCs) were significantly enriched in smokers' Tu. Among these clusters, pDCs, specifically enriched in the Tu of smokers. The expression of representative pDC markers, leukocyte immunoglobulin-like receptor A4 (LILRA4) and Toll-like receptor 9 (TLR9), was increased in the stromal cells of LUAD in patients with a smoking history. In an animal model of lung cancer, ionizing radiation induced robust TLR9 expressing immune cells in peritumoral area. Survival analysis using a TCGA-LUAD dataset indicated that patients overexpressing pDC markers exhibited superior clinical outcomes to age-, sex-, and smoking-matched control groups. Top 25% patients with high TLR9 expression exhibited significantly higher tumor mutational burden than that of low TLR9 expression group (bottom 25% patients) (5.81 mutations/Mb vs 4.36 mutations/Mb; P = 0.0059, Welch's two-sample t-test). Conclusion: There is an increased pDC in the TME of smokers' lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer.

Airflow obstruction and chronic obstructive pulmonary disease are common in pulmonary tuberculosis even without sequelae findings on chest X-ray.

PURPOSE: Pulmonary tuberculosis (TB) is a well-known risk factor for airflow obstruction and chronic obstructive pulmonary disease (COPD). The prognosis of TB without sequelae on chest X-ray (CXR) remains uncertain. METHODS: We used the 2008-2009 Korea National Health and Nutrition Examination Survey (KNHANES) data and 2007-2012 KNHANES-matched Health Insurance Review and Assessment Service cohort data. Airflow obstruction was assessed using a pulmonary function test. COPD was defined using diagnostic codes and the use of COPD medication for 3-year. We classified subjects into three groups based on TB history and sequelae on CXR. RESULTS: In 4911 subjects, the CXR(-) (no TB sequelae on CXR) post-TB group (n = 134) showed similar characteristics and normal lung function compared to that of the control group (n = 4,405), while the CXR(+) (TB sequelae on CXR) post-TB group (n = 372) showed different characteristics and reduced lung function. The prevalence of airflow obstruction was 9.3%, 13.4%, and 26.6% in control, CXR(-) post-TB, and CXR(+) post-TB groups, respectively. COPD was more common in the post-TB with CXR(+) (6.5%) or without CXR (-) (4.5%) groups, than in the control group (1.8%). Compared to the CXR(-) post-TB group, the control group showed a lower risk for airflow obstruction (OR, 0.774; p = .008). The CXR(+) post-TB group showed a higher risk for airflow obstruction (OR, 1.456; p = .011). The Control group also showed a lower risk for the development of COPD than the CXR(-) post-TB group (OR, 0.496; p = .011). CONCLUSIONS: We need to educate TB patients that airway obstruction and COPD can easily develop, even if TB sequelae are not observed on CXR.

Usefulness of bronchial washing fluid for detection of EGFR mutations in non-small cell lung cancer.

INTRODUCTION: The implementation of bronchial washing fluid (BWF) as a diagnostic specimen may complement the low diagnostic yields of plasma in detecting EGFR mutation (mEGFR) in non-small cell lung cancer. However, the diagnostic value of BWF in detecting mEGFR has yet to be clarified. MATERIALS AND METHODS: From March 2021 to August 2022, patients with histologically confirmed NSCLC with matched tumor tissue, BWF, and/or plasma samples were enrolled. Patients were classified into either initial diagnosis or rebiopsy groups. Diagnostic yields of mEGFR in BWF and plasma were evaluated using droplet digital polymerase chain reaction and compared to mEGFR in tumor tissue as standard. RESULTS: The study included 123 patients (74.1 %) in the initial diagnosis and 43 patients (25.9 %) in the rebiopsy group. BWF showed higher sensitivity, specificity, and concordance rates than plasma in both the initial diagnosis (57.4 %, 96.4 %, and 74.0 % vs. 16.4 %, 96.2 %, and 53.1 %) and the rebiopsy group (87.9 %, 60.0 %, and 81.4 % vs. 25.0 %, 75.0 %, and 41.7 %). In the initial diagnosis group, mEGFR was detected in the BWF of 13 out of 16 patients, even in the absence of tumor cells in the tissue biopsy. In these cases, EGFR test results obtained from BWF showed concordance with EGFR test results from the tumor tissue obtained through repeated biopsy or surgery later. In the rebiopsy group, T790M was detected in 16 patients (37.2 %) by tissue biopsy. The combined use of tissue biopsy and BWF increased detection, confirming T790M in 22 patients (51.2 %). DISCUSSION: The detection of mEGFR using BWF shows higher diagnostic yields than plasma for both initial diagnosis and rebiopsy. T790M was detected earlier in BWF than in tissue rebiopsy in some cases, providing patients with an early opportunity to access third-generation EGFR-TKIs. The complementary use of BWF with tumor tissue may improve precision in EGFR-mutated NSCLC treatment strategies.

Effects of chitinase-1 inhibitor in obesity-induced and -aggravated asthma in a murine model.

AIMS: Despite recent investigations on the role of chitinase in asthma, its role in obesity-induced asthma has not been evaluated. Therefore, we investigated the roles of chitin, chitinase-1, and a chitinase-1 inhibitor (compound X, CPX) in a murine model. MAIN METHODS: We assigned C57BL/6 mice to the ovalbumin (OVA) model or obesity model group. In the OVA model, mice received intraperitoneal OVA twice within a 2-week interval and intranasal OVA for 3 consecutive days. Additionally, chitin was intranasally administered for 3 consecutive days, and CPX was intraperitoneally injected three times over 5 days. In the obesity model, a high-fat diet (HFD) was maintained for 13 weeks, and CPX was intraperitoneally injected eight times over 4 weeks. KEY FINDINGS: In the OVA model, chitin aggravated OVA-induced airway hyper-responsiveness (AHR), increased bronchoalveolar lavage fluid (BALF) cell proliferation, increased fibrosis, and increased the levels of various inflammatory cytokines (including chitinase-1, TGF-ß, TNF-α, IL-1 ß, IL-6, IL-4, and IL-13). CPX treatment significantly ameliorated these effects. In the obesity model, HFD significantly increased AHR, BALF cell proliferation, fibrosis, and the levels of various inflammatory cytokines. Particularly, compared to the control group, the mRNA expression of chitinase, chitinase-like molecules, and other molecules associated with inflammation and the immune system was significantly upregulated in the HFD and HFD/OVA groups. Immunofluorescence analysis also showed increased chitinase-1 expression in these groups. CPX significantly ameliorated all these effects in this model. SIGNIFICANCE: This study showed that CPX can be an effective therapeutic agent in asthma, especially, obesity-induced and -aggravated asthma to protect against the progression to airway remodeling and fibrosis.

Associations between Phosphate Concentrations and Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation.

Phosphate concentrations change continuously throughout hospitalization; however, it is unclear which available phosphate measures are most clinically important for predicting hospital mortality. Therefore, we investigated phosphate concentrations in association with hospital mortality following admission to the intensive care unit. We retrospectively enrolled all adult patients receiving mechanical ventilation. Phosphate concentrations were divided into three categories: initially measured phosphate (iP); maximum−minimum phosphate values (ΔP); and phosphate arithmetic average (Pmean). In total, 175 patients were enrolled. The hospital mortality rate was 32.6%, and the most common primary diagnosis was respiratory failure. In multivariable logistic regression analyses, the odds ratios for hospital mortality in association with ΔP and Pmean values were 1.56 and 2.13, respectively (p < 0.0001). According to the obtained receiver operating characteristic curve, ΔP (0.75) and Pmean (0.72) each showed a fair predictive power for hospital mortality. In evaluating relative risks, we found that higher concentrations of Pmean and ΔP were each associated with a higher hospital mortality. ΔP and Pmean values were significantly associated with hospital mortality in critically ill patients, compared to iP. These findings showed that throughout hospitalization, it is important to reduce phosphate level fluctuations and maintain appropriate phosphate concentrations through consistent monitoring and corrections.

Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea.

PURPOSE: Early recognition and therapeutic intervention are important in patients at high risk of acute respiratory distress syndrome (ARDS). The lung injury prediction score (LIPS) has been used to predict ARDS development; however, it was developed based on the previous definition of ARDS. We investigated the predictive role of LIPS in ARDS development according to its Berlin definition in the Korean population. MATERIALS AND METHODS: This was a retrospective study that enrolled adult patients admitted to the intensive care unit (ICU) at a single university-affiliated hospital in Korea from September 1, 2018, to August 31, 2019. LIPS at the time of ICU admission and the development of ARDS were evaluated. RESULTS: Of the 548 enrolled patients, 33 (6.0%) fulfilled the Berlin ARDS definition. The LIPS for non-ARDS and ARDS groups were 4.96±3.05 and 8.53±2.45, respectively (p<0.001); it was significantly associated with ARDS development (odds ratio 1.48, 95% confidence interval, 1.29-1.69; p<0.001). LIPS >6 predicted the development of ARDS with a sensitivity of 84.8% and a specificity of 67.2% [area under the curve (AUC)=0.82]. A modified LIPS model adjusted for age and severity at ICU admission predicted ICU mortality in patients with ARDS (AUC=0.80), but not in those without ARDS (AUC=0.54). CONCLUSION: LIPS predicted the development of ARDS as diagnosed by the Berlin definition in the Korean population. LIPS provides useful information for managing patients with ARDS.

Risk factors and mortality of acute kidney injury within 1 month after lung transplantation.

After lung transplantation (LT), some patients are at risk of acute kidney injury (AKI), which is associated with worse outcomes and increased mortality. Previous studies focused on AKI development from 72 h to 1 week within LT, and reported main risk factors for AKI such as intraoperative hypotension, need of ECMO support, ischemia time or longer time on waiting list. However, this period interval rarely reflects medical risk factors probably happen in longer post-operative period. So, in this study we aimed to describe the incidence and risk factor of AKI within post-operative 1 month, which is longer follow up duration. Among 161 patients who underwent LT at Severance hospital in Seoul, Korea from October 2012 to September 2017, 148 patients were retrospectively enrolled. Multivariable logistic regression and Cox proportional hazard models were utilized. Among 148 patients, 59 (39.8%) developed AKI within 1-month after LT. Stage I or II, and stage III AKI were recorded in 26 (17.5%) and 33 (22.2%), respectively. We also classified AKI according to occurrence time, within 1 week as early AKI, from 1 week within 1 month was defined as late AKI. AKI III usually occurred within 7 days after transplantation (early vs. late AKI III, 72.5% vs 21.1%). Risk factor for AKI development was pre-operative anemia, higher units of red blood cells transfused during surgery, colistin intravenous infusion for treating multi drug resistant pathogens were independent risk factors for AKI development. Post-operative bleeding, grade 3 PGD within 72 h, and sepsis were more common complication in the AKI group. Patients with AKI III ([24/33] 72.7%) had significantly higher 1-year mortality than the no-AKI ([18/89] 20.2%), and AKI I or II group ([9/26] 34.6%), log-rank test, P < 0.001). AKI was associated with worse post-operative outcome, 3-month, and 1-year mortality after LT. Severity of AKI was usually determined in early post op period (ex. within 7 days) after LT, so optimal post-operative management as well as recipients selection should be considered.

Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements.

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient's quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Longitudinal Evaluation of the Relationship Between Low Socioeconomic Status and Incidence of Chronic Obstructive Pulmonary Disease: Korean Genome and Epidemiology Study (KoGES).

Background: Socioeconomic status (SES) is a strong determinant in the development of various diseases. We evaluated the relationship between SES and the incidence of chronic obstructive pulmonary disease (COPD) by using a community-based cohort data. Patients and Methods: Four-year follow-up data of 6341 adults (aged ≥ 40 years), who underwent serial pulmonary function test were analyzed. Incidence of COPD in the participants was defined as the absence of airflow obstruction compatible with COPD (pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio of <0.7) at baseline but documentation of airflow obstruction in serial testing. SES of patients was divided into quartiles according to household income and educational level. Multivariate logistic regression analyses were performed to estimate the association between SES and COPD incidence. Results: A total of 280 (4.4%) patients developed COPD during the follow-up. The proportion of subjects with lowest education (elementary school) and lowest household income levels (1st quartile) was significantly higher in the COPD group than in the non-COPD group (37.9% vs 29.5%, p<0.011 and 48.4% vs 30.8%, p<0.001, respectively). Logistic regression analysis revealed that education level of elementary school was independently associated with COPD incidence after adjustment for sex, age, body mass index, white blood cell count, residence area, and occupation (odds ratio 1.879, 95% confidence interval 1.124-3.141, p=0.016). Conclusion: In the general population, educational level of elementary school was an independent risk factor for COPD among the components comprising SES. Our results indicate that the implementation of preventive strategies for COPD in those with low educational status could be beneficial.

Abnormal Overcharging during Lithium-Ether Co-Intercalation in a Graphite System: Formation of Shuttling Species by the Reduction of the TFSI Anion.

Materializing an ultrafast charging system is one of the crucial technologies for next-generation Li-ion batteries (LIBs). Among many studies aimed at achieving fast charging systems, Li-ether solvent cointercalation into the graphite electrodes in LIB has been identified as a novel concept for achieving high power performance because this system does not consist of the sluggish desolvation step and a resistive solid-electrolyte interface (SEI) layer. Interestingly, while studying the Li-ether solvent cointercalation into graphite electrodes, employing lithium bis-trifluoromethane sulfonimide (LiTFSI) as the Li salt, we observed an abnormal overcharging phenomenon. Here, we screened the specific conditions, under which the abnormal overcharging occurred, and revealed that this abnormal overcharging was attributable to the shuttling mechanism. The formation of shuttling species could have been derived by the reduction of TFSI- anion. With this understanding of the underlying mechanism, we efficiently suppressed the abnormal overcharging by adding LiNO3 to the electrolyte. The shuttling and resulting overcharging could be prevented by the synergistic contributions of LiNO3 and SxOy, dissolved in the electrolyte, to the formation of a dense solid LiSxOy SEI layer on Li-metal. We expect that this work could be a great reference in analyzing many unsolved phenomena in systems utilizing TFSI-.

Age- and sex-related characteristics of the increasing trend of nontuberculous mycobacteria pulmonary disease in a tertiary hospital in South Korea from 2006 to 2016.

BACKGROUND/AIMS: The incidence rate of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. However, data regarding the age- and sex-specific epidemiology of NTM-PD are limited. This study aimed to investigate the long-term epidemiologic trends of NTM-PD within the recent 11- year period in a tertiary referral hospital in Korea. METHODS: We retrospectively reviewed the medical records of the patients diagnosed with NTM-PD between January 2006 and December 2016 at Severance Hospital, South Korea. RESULTS: There were 1,017 incident cases with NTM-PD during the study period. The mean age was 62.7 years, and 41.2% were men. Women were younger than men (59.9 years vs. 66.7 years, p < 0.001) and a higher proportion of women had bronchiectasis (88.6% vs. 77.1%, p < 0.001). The incidence rates of NTM-PD annually increased by 14% (95% confidence interval, 10% to 19%) from 1.2 in 2006 to 4.8 in 2016 (per 100,000 patients-year). The peak incidence rate was in the 50s for women and in the 70s for men, except for those aged ≥ 80 years. Mycobacterium avium complex was the most common causative species of NTM-PD (63.6%). CONCLUSION: The incidence rate of NTM-PD in a tertiary referral hospital in South Korea continued to increase from 2006 to 2016. Furthermore, there were age- and sex-related differences in the clinical characteristics, which might contribute to understanding the nature of the disease and inherited and acquired host factors.