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Abstract Background Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC)

Abstract The role of nutritional status as a prognostic factor in patients with Sjögren’s syndrome-associated interstitial lung disease (SjS-ILD) is currently unclear. This study aimed to predict the prognosis of patients with SjS-ILD through their nutritional status assessment. In this retrospective observational study, nutritional status was evaluated at the time of diagnosis using body mass index (BMI) and nutritional markers such as controlling nutritional status (CONUT), the Glasgow prognostic score (GPS), and prognostic nutrition index (PNI) for all participants. Receiver operating characteristic (ROC) analyses were performed using BMI and each nutritional marker data to compare the area under the ROC curve (AUC) and find the cutoff value using the maximum Youden index. Kaplan–Meier analysis and Cox proportional hazards regression analysis were performed to predict the prognosis of SjS-ILD patients. A total of 112 SjS-ILD patients were enrolled in the study, and 8.9% died during the follow-up period. The median time from diagnosis to follow-up period was 4.2 years. The AUC for PNI was the highest among nutritional markers and BMI, and PNI cutoff value was used to distinguish between the PNI

Abstract In 2023, WHO ranked chronic obstructive pulmonary disease (COPD) as the third leading cause of death, with 3.23 million fatalities in 2019. The intricate nature of the disease, which is influenced by genetics, environment, and lifestyle, is evident. The effect of air pollution and changes in atmospheric substances because of global warming highlight the need for this research. These environmental shifts are associated with the emergence of various respiratory infections such as COVID-19. RNA sequencing is pivotal in airway diseases, including COPD, as it enables comprehensive transcriptome analysis, biomarker discovery, and uncovers novel pathways. It facilitates personalized medicine by tracking dynamic changes in gene expression in response to various triggers. However, the limited research on East Asian populations may overlook the unique nuances of COPD development and progression. Bridging this gap and using peripheral blood samples for systemic analysis are crucial for comprehensive and globally applicable COPD diagnosis and treatment.

Background The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. Purpose This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. Methods This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. Results A total 150 children (66 females) aged 7.7 years (6.4–9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%–75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P

Background Exercise capacity is associated with lung function decline in chronicobstructive pulmonary disease (COPD) patients, but a discrepancy between exercisecapacity and airflow limitation exists. This study aimed to explore factors contributingto this discrepancy in COPD patients. Methods Data for this prospective study were obtained from the Korean COPD SubgroupStudy. The exercise capacity and airflow limitation were assessed using the6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1).Participants were divided into four groups: FEV1 >50%+6-MWD >350, FEV1 >50%+6-MWD ≤350, FEV1 ≤50%+6-MWD >350, and FEV1 ≤50%+6-MWD ≤350 and their clinicalcharacteristics were compared. Results A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) wereenrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, andamong 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multipleregression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval[CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008)were significantly associated with discrepancies in exercise capacity and airflow limitationin patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusioncapacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantlyassociated with discrepancies between exercise capacity and airflow limitation. Conclusion The exercise capacity of COPD patients may be influenced by factors otherthan airflow limitation, so these aspects should be considered when assessing andtreating patients.

Abstract Background The clinical staging of non‐small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real‐world data. Methods Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. Results Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET‐CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32–0.76, p = 0.001) and a higher clinical stage (p

AbstractBackground Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by dysregulation of fibroblast function, which often involves the lungs. Interstitial lung disease (ILD) associated with SSc (SSc-ILD) is a major cause of death among patients with SSc. Our study aimed to identify risk factors for mortality and compare the clinical characteristics of patients with SSc-ILD.Patients and methods Patients were retrospectively enrolled between 2010 and 2018 in a tertiary hospital in Korea. Patients with SSc-ILD were classified depending on the first pulmonary function test or radiologic findings: extensive (n = 46, >20% disease extent on computed tomography (CT) or forced vital capacity [FVC]

Arrhythmias range from mild nuisances to potentially fatal conditions, detectable through electrocardiograms (ECGs). With advancements in wearable technology, ECGs can now be monitored on-the-go, although these devices often capture noisy data, complicating accurate arrhythmia detection. This study aims to create a new deep learning model that utilizes generative adversarial networks (GANs) for effective noise removal and ResNet for precise arrhythmia classification from wearable ECG data. We developed a deep learning model that cleans ECG measurements from wearable devices and detects arrhythmias using refined data. We pretrained our model using the MIT-BIH Arrhythmia and Noise databases. Least squares GANs were used for noise reduction, maintaining the integrity of the original ECG signal, while a residual network classified the type of arrhythmia. After initial training, we applied transfer learning with actual ECG data. Our noise removal model significantly enhanced data clarity, achieving over 30 dB in a signal-to-noise ratio. The arrhythmia detection model was highly accurate, with an F1-score of 99.10% for noise-free data. The developed model is capable of real-time, accurate arrhythmia detection using wearable ECG devices, allowing for immediate patient notification and facilitating timely medical response.

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. Methods A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. Results More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. Conclusion Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3–5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

Background: Fine particulate matter (PM2.5) is a well-known risk factor for worse outcomes of chronic obstructive pulmonary disease (COPD). However, evidence-based guidance on effective personal behavioural strategies to minimise the effects of PM2.5 is limited. This study aimed to assess the effectiveness of a behavioural intervention in reducing PM2.5 exposure and improving clinical outcomes in patients with COPD. Materials and Methods: Participants were 1:1 randomised, and the intervention group received a behavioural intervention consisting of five activities, while the control group received usual care. The participants were followed up for 9 months. The primary outcomes were differences in the score of St. George’s Respiratory Questionnaire for patients with COPD (SGRQ-C) and COPD assessment test (CAT) from baseline. Results: A total of 106 participants were enrolled and 102 completed the study. At the end of the study, the intervention group showed significant improvements in the primary outcomes compared to the control group, with a group difference of −5.9 in the reduction of total SGRQ-C (−3.4 vs. 2.5; p = 0.049) and −3.8 in the CAT score (−1.2 vs. 2.7; p = 0.001). Participants with good adherence to the intervention demonstrated a greater extent of improvement in CAT score and lower PM2.5 levels compared to those who had poor adherence or were in the control group. Regular checking of air quality forecasts was significantly associated with a reduction in CAT scores among all the intervention activities. Conclusion: Individual-level behavioural interventions can be an effective strategy for mitigating the health hazards associated with PM2.5.ClinicalTrials.gov Identifier: NCT04878367.

Abstract Background The longitudinal relationship between adiposity and lung function is controversial. We aimed to investigate the long-term association between adiposity changes and lung function in a middle-aged general Asian population. Methods In total, 5011 participants (average age, 54 years; 45% men) were enrolled from a community-based prospective cohort. During the follow-up period (median 8 years), both spirometry and bio-electrical impedance analysis were performed biannually. Individual slopes of the fat mass index (FMI; fat mass divided by the square of height in meters) and waist-to-hip ratio (WHR) were calculated using linear regression analysis. Multivariate linear mixed regression analysis was used to determine the long-term association between adiposity changes and lung function. Results The FMI was inversely associated with forced vital capacity (FVC) (estimated: − 31.8 mL in men, − 27.8 mL in women) and forced expiratory volume in 1 s (FEV1) (estimated: − 38.2 mL in men, − 17.8 mL in women) after adjusting for baseline age, height, residential area, smoking exposure (pack-years, men only), initial adiposity indices, and baseline lung function. The WHR was also inversely associated with FVC (estimated = − 1242.2 mL) and FEV1 (estimated = − 849.8 mL) in men. The WHR-increased group showed a more rapid decline in lung function than the WHR-decreased group in both the fat-gain and fat-loss groups. Conclusion Adiposity was associated with the long-term impairment of lung function. Central obesity was the main driver of lung function impairment in the middle-aged general Asian population, regardless of fat mass changes.

Abstract Background Sarcopenia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), but its relationship with chronic obstructive pulmonary disease (COPD) has not been fully determined. This study is aimed to investigate the association between sarcopenia and risk for ASCVD in patients with COPD, independent of central obesity and fat mass. Methods Data regarding 704 men with COPD (mean age: 63.4 years) were extracted from the 2008 to 2011 Korean National Health and Nutrition Examination Surveys. Sarcopenia index and fat mass were assessed using dual-energy X-ray absorptiometry. Sarcopenia was defined according to the presence of sarcopenia index values 20%. Results The quartile-stratified sarcopenia index was negatively associated with ASCVD risk (P

IntroductionRegarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC).MethodsA review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0).ResultsAmong 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth’s bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration.ConclusionsGiven the incidence and favorable outcome of BM in patients with suspected early-stage NSCLC, selective screening with brain MRI may be considered, especially in patients with high-risk features.

COPD is a heterogeneous disease, and its acute exacerbation is a major prognostic factor. We used cluster analysis to predict COPD exacerbation due to subtypes of mild–moderate airflow limitation. In all, 924 patients from the Korea COPD Subgroup Study cohort, with a forced expiratory volume (FEV1) ≥ 50% and documented age, body mass index (BMI), smoking status, smoking pack-years, COPD assessment test (CAT) score, predicted post-bronchodilator FEV1, were enrolled. Four groups, putative chronic bronchitis (n = 224), emphysema (n = 235), young smokers (n = 248), and near normal (n = 217), were identified. The chronic bronchitis group had the highest BMI, and the one with emphysema had the oldest age, lowest BMI, and highest smoking pack-years. The young smokers group had the youngest age and the highest proportion of current smokers. The near-normal group had the highest proportion of never-smokers and near-normal lung function. When compared with the near-normal group, the emphysema group had a higher risk of acute exacerbation (OR: 1.93, 95% CI: 1.29–2.88). However, multiple logistic regression showed that chronic bronchitis (OR: 2.887, 95% CI: 1.065–8.192), predicted functional residual capacity (OR: 1.023, 95% CI: 1.007–1.040), fibrinogen (OR: 1.004, 95% CI: 1.001–1.008), and gastroesophageal reflux disease were independent predictors of exacerbation (OR: 2.646, 95% CI: 1.142–6.181). The exacerbation-susceptible subtypes require more aggressive prevention strategies.

Abstract We aimed to describe the clinical features of lymphangioleiomyomatosis (LAM) in Korean patients and identify factors associated with progressive disease (PD). Clinical features of 54 patients with definite or probable LAM from 2005 to 2018 were retrospectively analysed. Common features were pneumothorax (66.7%) and abdominal lymphadenopathy (50.0%). Twenty-three (42.6%) patients were initially treated with mechanistic target of rapamycin (mTOR) inhibitors. Lung transplantation (LT) was performed in 13 (24.1%) patients. Grouped based on the annual decline in forced expiratory volume in 1 s (FEV1) from baseline and LT, 36 (66.7%) patients exhibited stable disease (SD). All six deaths (11.1%) occurred in PD. Proportion of SD was higher in those treated initially with mTOR inhibitors than in those under observation (p = 0.043). Univariate analysis revealed sirolimus use, and baseline forced vital capacity, FEV1, and diffusing capacity of the lungs for carbon monoxide are associated with PD. Multivariate analysis showed that only sirolimus use (odds ratio 0.141, 95% confidence interval 0.021–0.949, p = 0.044) reduced PD. Kaplan–Meier analysis estimates overall survival of 92.0% and 74.7% at 5 and 10 years, respectively. A considerable proportion of LAM patients remain clinically stable without treatment. LT is an increasingly viable option for patients with severe lung function decline.

Abstract Background Diagnostic cutoff points for sarcopenia in chest computed tomography (CT) have not been established although CT is widely used for investigating skeletal muscles. This study aimed to determine reference values for sarcopenia of thoracic skeletal muscles acquired from chest CT scans and to analyse variables related to sarcopenia using the cutoff values determined in a general Asian population. Methods We retrospectively reviewed chest CT scans of 4470 participants (mean age 54.8 ± 9.9 years, 65.8% male) performed at a check‐up centre in South Korea (January 2016–August 2017). To determine cutoffs, 335 participants aged 19–39 years (mean age 35.2 ± 3.6 years, 75.2% male) were selected as the healthy and younger reference group, and 4135 participants aged ≥40 years (mean age 56.4 ± 8.4 years, 65.1% male) were selected as the study group. We measured the following: cross‐sectional area (CSA) of the pectoralis, intercostalis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA); T4CSA divided by height2 (T4MI); pectoralis muscle area (PMCSA); and PMCSA divided by height2 (PMI) at the 4th vertebral region. Sarcopenia cutoff was defined as sex‐specific values of less than −2 SD below the mean from the reference group. Results In the reference group, T4CSA, T4MI, PMCSA, and PMI cutoffs for sarcopenia were 100.06cm2, 33.69cm2/m2, 29.00cm2, and 10.17cm2/m2 in male, and 66.93cm2, 26.01cm2/m2, 18.29cm2, and 7.31cm2/m2 in female, respectively. The prevalence of sarcopenia in the study group measured with T4CSA, T4MI, PMCSA and PMI cutoffs were 11.4%, 8.7%, 8.5%, and 10.1%, respectively. Correlations were observed between appendicular skeletal mass divided by height2 measured by bioelectrical impedance analysis (BIA) and T4CSA (r = 0.82; P

OBJECTIVES This study was conducted to elucidate the effects of an air quality warning system (AQWS) implemented in January 2015 in Korea by analyzing changes in the incidence and exacerbation rates of environmental diseases. METHODS Data from patients with environmental diseases were extracted from the National Health Insurance Service-National Sample Cohort database from 2010 to 2019, and data on environmental risk factors were acquired from the AirKorea database. Patient and meteorological data were linked based on residential area. An interrupted time series analysis with Poisson segmented regression was used to compare the rates before and after AQWS introduction. Adjustment variables included seasonality, air pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, particulate matter less than 10 μm in diameter, and ozone), temperature, and humidity. RESULTS After AQWS implementation, the incidence of asthma gradually decreased by 20.5%. Cardiovascular disease and stroke incidence also significantly decreased (by 34.3 and 43.0%, respectively). However, no immediate or gradual decrease was identified in the exacerbation rate of any environmental disease after AQWS implementation. Sensitivity analyses were performed according to age, disability, and health insurance coverage type. Overall, the AQWS effectively mitigated the occurrence of most environmental diseases in Korea. However, the relationships between alarm system implementation and reduced incidence differed among diseases based on the characteristics of vulnerable and sensitive individuals. CONCLUSIONS Our results suggest that by tailoring the AQWS to demographic and sociological characteristics and providing enhanced education about the warning system, interventions can become an efficient policy tool to decrease air pollution-related health risks.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. Methods We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. Results During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). Conclusions The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Background Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea. Methods A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement). Results The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers. Conclusion Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Background Although it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases. Methods Nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test. Results Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66–1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed. Conclusion Prior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.

Background Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. Results We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Abstract Background Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer. Methods 16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses. Results In total, 84 patients were prospectively analyzed, of which 59 showed low (

Background: Bronchiectasis is associated with an increased incidence of atherosclerotic cardiovascular disease (ASCaVD) and atherosclerotic cerebrovascular disease (ASCeVD). Its effect on associated mortality is unclear. Objectives: This study investigated the effects of bronchiectasis exacerbation prior to ASCaVD or ASCeVD events on mortality in patients with bronchiectasis using a large population–based database. Methods: A retrospective cohort of patients with bronchiectasis who experienced ASCaVD ( n = 1066) or ASCeVD ( n = 825) was studied for the first time using a nationwide population–based database (National Health Insurance Service-National Sample Cohort, Korea, 2002–2015). We classified each cohort according to the presence of moderate bronchiectasis exacerbation within 1 year before the ASCaVD or ASCeVD event. We evaluated 90-day, 1-year, and all-cause mortalities risk. Results: Within 1 year before the index ASCaVD or ASCeVD event, 149 (13.9%) and 112 (13.6%) patients with bronchiectasis experienced moderate exacerbation(s), respectively. Mild exacerbations did not different in frequency between the survivors and nonsurvivors. In both cohorts, more nonsurvivors experienced moderate exacerbations than survivors. The odds ratios of 90-day and 1-year mortalities and hazard ratios of all-cause mortalities on experiencing moderate exacerbations were 2.27 [95% confidence interval (CI) = 1.26–4.10], 3.30 (95% CI = 2.03–5.38), and 1.78 (95% CI = 1.35–2.34) in the bronchiectasis-ASCaVD cohort and 1.73 (95% CI = 0.94–3.19), 1.79 (95% CI = 1.07–3.00), and 1.47 (95% CI = 1.10–1.95), in the bronchiectasis-ASCeVD cohort. Conclusion: Hospitalization or emergency room visit for bronchiectasis exacerbation within 1 year before ASCaVD or ASCeVD is associated with an increased ASCaVD- or ASCeVD-associated mortality.

Background: Studies on the risk and protective factors for lung function decline and mortality in rheumatoid arthritis–related interstitial lung disease (RA-ILD) are limited. Objectives: We aimed to investigate clinical factors and medication uses associated with lung function decline and mortality in RA-ILD. Methods: This retrospective cohort study examined the medical records of patients with RA-ILD who visited Severance Hospital between January 2006 and December 2019. We selected 170 patients with RA-ILD who had undergone at least one spirometry test and chest computed tomography scan. An absolute decline of ⩾10% in the functional vital capacity (FVC) was defined as significant decline in pulmonary function. Data for analysis were retrieved from electronic medical records. Results: Ninety patients (52.9%) were female; the mean age was 64.0 ± 10.2 years. Multivariate logistic regression showed that a high erythrocyte sediment rate level at baseline [odds ratio (OR) = 3.056; 95% confidence interval (CI) = 1.183–7.890] and methotrexate (MTX) use (OR = 0.269; 95% CI = 0.094–0.769) were risk and protective factors for lung function decline, respectively. Multivariate Cox regression analysis indicated that age ⩾65 years (OR = 2.723; 95% CI = 1.142–6.491), radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (OR = 3.948; 95% CI = 1.522–10.242), baseline functional vital capacity (FVC) % predicted (OR = 0.971; 95% CI = 0.948–0.994), and MTX use (OR = 0.284; 95% CI = 0.091–0.880) were predictive of mortality. Conclusion: We identified risk and protective factors for lung function decline and mortality in patients with RA-ILD. MTX use was associated with favorable outcome in terms of both lung function and mortality in our cohort.

Abstract Background With the emergence of bronchiectasis as a common respiratory disease, epidemiological data have accumulated. However, the prevalence and impact of psychological comorbidities were not sufficiently evaluated. The present study examined the prevalence of depression and its associated factors in patients with bronchiectasis. Methods This study involved a multicenter cohort of bronchiectasis patients recruited from 33 pulmonary specialist hospitals. The baseline characteristics and bronchiectasis-related factors at enrollment were analyzed. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Results Of the 810 patients enrolled in the study, 168 (20.7%) patients had relevant depression (PHQ-9 score ≥ 10), and only 20 (11.9%) patients had a diagnosis of depression. Significant differences were noted in the depressive symptoms with disease severity, which was assessed using the Bronchiectasis Severity Index and E-FACED (all p

Abstract This study investigated the impact of bronchiectasis on patients admitted to the intensive care unit (ICU) at a hospital in Korea. Patients with bronchiectasis were diagnosed using results of chest computed tomography performed before ICU admission. The severity of bronchiectasis was based on the number of affected lobes, and patients with ≥ 3 bronchiectatic lobes were classified into the severe bronchiectasis group. Overall, 823 patients were enrolled. The mean age was 66.0 ± 13.9 years, and 63.4% were men. Bronchiectasis and severe bronchiectasis were present in 148 (18.0%) and 108 (13.1%) patients, respectively. The increase in the number of bronchiectatic lobes was related to the rise in ICU mortality (P for trend = 0.012) and in-hospital mortality (P for trend = 0.004). Patients with severe bronchiectasis had higher odds for 28-day mortality [odds ratio (OR) 1.122, 95% confidence interval (CI) 1.024–1.230], ICU mortality (OR 1.119, 95% CI 1.023–1.223), and in-hospital mortality (OR 1.208, 95% CI 1.092–1.337). The severe bronchiectasis group showed lower overall survival (log-rank P

Birt–Hogg–Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G>A, c.139G>T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p < 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (>40), and maximal diameter of lung cysts (>2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G>A, c.139G>T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.

Abstract Background Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear. Methods We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies. Results We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were − 34.4 and − 112.2 mL (p = 0.168) in forced vital capacity (FVC), and − 0.53 and − 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DLCO) in the autoantibody-negative and autoantibody-positive groups, respectively. Conclusions Reductions in FVC and DLCO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

Abstract Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102–0.408, P 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

Abstract There is no validated clinical biomarker for disease severity or treatment response for nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the correlation between elevated serum carbohydrate antigen (CA) 19-9 levels and NTM-PD disease activity, defined using an imaging severity score based on chest computed tomography (CT). We retrospectively examined 79 patients with NTM-PD who underwent serum CA19-9 level assessments and chest CT less than 1 month apart. NTM-PD severity was rated using a CT-based scoring system. The correlation between the CT score and serum CA19-9 levels was evaluated. Chest CT revealed nodular bronchiectasis without cavitation in most patients (78.5%). Serum CA19-9 levels were elevated in 19 (24%) patients. Serum CA19-9 levels were positively correlated with the total CT score and bronchiectasis, bronchiolitis, cavity, and consolidation subscores. Partial correlation analysis revealed a significant positive correlation between serum CA19-9 levels and CT scores for total score and bronchiectasis, bronchiolitis, cavitation, and consolidation subscores after controlling for age, sex, and BMI. Serum CA19-9 levels were positively correlated with the CT severity score for NTM-PD. Serum CA19-9 may be useful in evaluating disease activity or therapeutic response in patients with NTM-PD.

Abstract Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19). This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients. A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model. Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively. The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs. 45.2%, P

Abstract The severity of the coronavirus disease (COVID-19) is associated with various comorbidities. However, no studies have yet demonstrated the potential risk of respiratory failure and mortality in COVID-19 patients with pre-existing asthma. We selected 7272 adult COVID-19 patients from the Korean Health Insurance Review and Assessment COVID-19 database for this nationwide retrospective cohort study. Among these, 686 patients with asthma were assessed by their severities and evaluated by the clinical outcome of COVID-19 compared to patients without asthma. Of 7272 adult COVID-19 patients, 686 with asthma and 6586 without asthma were compared. Asthma was not a significant risk factor for respiratory failure or mortality among all COVID-19 patients (odds ratio [OR] = 0.99, P = 0.997 and OR = 1.06, P = 0.759) after adjusting for age, sex, and the Charlson comorbidity score. However, a history of acute exacerbation (OR = 2.63, P = 0.043) was significant risk factors for death among COVID-19 patients with asthma. Asthma is not a risk factor for poor prognosis of COVID-19. However, asthma patients who had any experience of acute exacerbation in the previous year before COVID-19 showed higher COVID-19-related mortality, especially in case of old age and male sex.

Background Flexible bronchoscopy is one of the essential procedures for the diagnosis and treatment of pulmonary diseases. The purpose of this study was to identify the risk factors associated with the occurrence of hypoxia in adults undergoing flexible bronchoscopy under sedation. Methods We retrospectively analyzed 2,520 patients who underwent flexible bronchoscopy under sedation at our tertiary care university hospital in South Korea January 1, 2013–December 31, 2014. Hypoxia was defined as more than 5%-point reduction in the baseline percutaneous oxygen saturation (SpO2) or SpO2 1 minute during the procedure. Results The mean age was 64.7±13.5, and 565 patients developed hypoxia during the procedure. The mean sedation duration and midazolam dose for sedation were 31.1 minutes and 3.9 mg, respectively. The bivariate analysis showed that older age, a low forced expiratory volume in one second (FEV1), use of endobronchial ultrasound, the duration of sedation, and the midazolam dose were associated with the occurrence of hypoxia during the procedure, while the multivariate analysis found that age >60 (odds ratio [OR], 1.32), a low FEV1 (OR, 0.99), and a longer duration of sedation (>40 minutes; OR, 1.33) were significant risk factors. Conclusion The findings suggest that patients older than age 60 and those with a low FEV1 tend to develop hypoxia during the bronchoscopy under sedation. Also, longer duration of sedation (>40 minutes) was a significant risk factor for hypoxia.

Background Sepsis-induced cardiomyopathy (SIC) occurs frequently in critically ill patients, but the clinical features and prognostic impact of SIC on sepsis outcome remain controversial. Here, we investigated the predictors and outcomes of SIC. Methods Patients admitted to a single medical intensive care unit from June 2016 to September 2017 were retrospectively reviewed. SIC was diagnosed by ejection fraction (EF)

Background: Hyperbilirubinemia and hypoalbuminemia are frequently appeared and associated with poor prognosis in critically ill patients. We aim to evaluate the association between the bilirubin to albumin ratio and prognosis in intensive care unit (ICU) patients. Methods: This was a retrospective study of 731 patients who were admitted to the medical intensive care unit (MICU) at a tertiary-care center from July 2015 to September 2017. We analyzed the bilirubin to albumin ratio on admission to the MICU, including clinical characteristics and other examinations. Results: The overall 28-day survival of MICU patients was 69.1%. On univariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score (P

Abstract Background Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort. Methods We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model. Results Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = − 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels. Conclusions Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.

Background: Tuberculosis (TB) causes undernutrition, and it has a long recovery time after treatment. It is accompanied by adverse health outcomes, such as sarcopenia. Objective: We aimed to evaluate the prevalence of sarcopenia and its association with protein and total energy intakes among Korean TB survivors. Methods: Data of the population-based Korea National Health and Nutrition Examination Survey (2008–2011) were analyzed, including 9,203 participants aged ⩾ 40 years. We used three definitions for sarcopenia-appendicular skeletal muscle mass (ASM, kg) divided by body mass index (BMI, kg/m 2 ), weight (kg), or height squared (m 2 ). Daily protein and total energy intakes were estimated with a 24-h recall method. Multiple logistic regression was used to evaluate the association between dietary protein/total energy intake and sarcopenia among TB survivors. Results: The prevalence of sarcopenia was 11.2%, 10.7%, and 24.3% among TB survivors with sarcopenia defined by ASM divided by BMI, weight, and height squared, respectively. The prevalence of sarcopenia among TB survivors was higher than among those without TB. After adjusting for age, weight, sex, education level, employment status, smoking status, and drinking status, sufficient protein and total energy intakes were associated with a lower risk of sarcopenia in TB survivors. Conclusion: The prevalence of sarcopenia was higher in TB survivors than in those without TB. We suggest consuming sufficient protein intake along with increasing total energy intake in TB survivors.

Abstract Background In many clinical disorders, there is a relationship between the ratio of the diameter of the main pulmonary artery (mPA) to that of the aorta (Ao) on chest computed tomography (CT). The aim of this study was to determine if the mPA/Ao ratio at diagnosis is associated with the clinical characteristics and outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed the diameters of the pulmonary artery and aorta on chest CT, clinical characteristics, and results of other examinations in 303 patients at the time of initial diagnosis of IPF at our tertiary care center between 2011 and 2015. The primary outcomes were death and lung transplantation. The patients were followed up until June 2017. Results One hundred and eight patients (35.6%) died and 58 (19.1%) underwent lung transplantation during follow-up. The mean mPA and Ao diameters were 28.3 mm and 34.0 mm, respectively, and the mean mPA/Ao ratio was 0.84. Thirty-one patients (10.2%) had an mPA/Ao ratio > 1.0 and 182 (60.1%) had an mPA/Ao ratio > 0.8. Patients with an mPA/Ao ratio > 0.8 had a lower DLco value than those with an mPA/Ao ratio ≤ 0.8. In Kaplan-Meier analysis, patients with an mPA/Ao ratio > 1.0 or > 0.8 had worse outcomes than those with an mPA/Ao ratio ≤ 1.0 and ≤ 0.8, respectively. Conclusions A higher mPA/Ao ratio based on 1.0 and 0.8 is associated with unfavorable prognosis in patients with IPF.

Abstract Background Sarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients. Methods We retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan–Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality. Results Male patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3 ± 1.3 vs 4.0 ± 1.6, P = 0.012; T12MI, 3.2 ± 1.3 vs 4.1 ± 1.6, P = 0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P = 0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913–0.998; P = 0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856–1.121; P = 0.766). Conclusions Low skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF. Trial registration The research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4–2018-0454).

Background Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1. Methods A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks. Results When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks. Conclusion RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.

Background/Aims Delayed diagnosis and treatment of smear-negative pulmonary tuberculosis (TB) are major concerns for TB control. We evaluated characteristics of patients with smear-negative pulmonary TB who received a delayed diagnosis and identified risk factors that may have contributed to this delay. Methods We reviewed medical records of patients with smear-negative culture-positive pulmonary TB treated at a tertiary care hospital in South Korea between January 2017 and December 2018. Patients who initiated anti-TB treatment after positive cultures were included in the missed TB group, and those who initiated empirical treatment before positive cultures were included in the control group. Results Of 220 patients included, 117 (53.2%) and 103 (46.8%) were in the missed TB and control groups, respectively. Patients in the missed TB group were older (p = 0.001) and had a higher mean body mass index (BMI) (p = 0.019). Comorbidities (66.9% vs. 46.6%, p = 0.003) and immunocompromised patients (33.1% vs. 20.4%, p = 0.035) were more common in the missed TB group than in the control group. Old age (odds ratio [OR], 1.030; 95% confidence interval [CI], 1.012 to 1.048; p = 0.001), high BMI (OR, 1.114; 95% CI, 1.004 to 1.237; p = 0.042), and negative polymerase chain reaction (PCR) results (OR, 9.551; 95% CI, 4.925 to 18.521; p < 0.001) were associated with delayed diagnosis. Conclusions In more than half of patients with smear-negative pulmonary TB, the diagnosis was delayed. Patients with delayed TB diagnosis were older, had higher BMI, and negative PCR results.

Onodera's prognostic nutritional index (PNI) is useful in predicting prognosis of various diseases. But the usefulness of PNI in non-surgical patients has not been sufficiently proven yet. In patients with mycobacterium avium complex pulmonary disease (MAC-PD), malnutrition is an important factor that affects the quality of life and morbidity. Here, we aimed to evaluate whether PNI is related with clinical outcomes in MAC-PD patients. We examined 663 patients diagnosed with MAC-PD between May 2005 and November 2017. PNI score was calculated at the time of diagnosis and treatment initiation, and patients were divided into malnutrition and non-malnutrition groups according to a cut-off PNI score of 45. As the recommended duration of treatment for MAC-PD is 12 months following sputum conversion, treatment duration less than 12 months was defined as treatment intolerance. Survivals were compared with the log-rank test. Multivariate logistic regression and multivariate Cox proportional hazards models were used to estimate the odds ratio (OR) and hazards ratio (HR) for treatment intolerance and mortality, respectively. Of the 306 patients that received treatment, 193 received treatment longer than 12 months. In the multivariable logistic regression model, malnutrition at the time of treatment initiation was related with treatment intolerance (OR: 2.559, 95% confidence interval [CI]: 1.414-4.634, P = 0.002). Patients in the malnutrition group at the time of diagnosis exhibited lower survival (P

Abstract Background Bilirubin has been reported to be associated with respiratory diseases due to its antioxidant action. We aimed to evaluate the relationship between serum bilirubin concentration and annual lung function decline in the Korean general population. Methods The study included 7986 subjects aged 40–69 years from the Ansung-Ansan cohort database I (2001–2002)–III (2005–2006). We analyzed the relationships between serum bilirubin level and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and mean forced expiratory flow between 25 and 75% of FVC (FEF25–75%) at baseline, as well as the annual average changes in these lung parameters. Results The FEV1, FVC, and FEF25–75% were significantly associated with serum bilirubin levels after adjustment for age, sex, body mass index (BMI), and smoking status (all P

In addition to smoking, dietary habits may contribute to the development of chronic obstructive pulmonary disease (COPD). This study aimed to examine the association between dietary patterns and lung function in a Korean community cohort. A total of 5436 participants were included from the Ansan–Ansung cohort study. To identify the dietary patterns, we performed principal component factor analysis using the results of a semi-quantitative food frequency questionnaire. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were measured by spirometry. Multiple logistic regression models were used to evaluate the association between dietary patterns and lung function after adjusting for confounders. We identified four major dietary patterns; ‘prudent’, ‘coffee, fat, and sweet’, ‘westernized’, and ‘white rice’. After adjusting for potential confounders, the ‘coffee, fat, and sweet’ dietary pattern was negatively associated with lung function, particularly the FEV1/FVC ratio. Participants with high scores for the ‘coffee, fat and sweet’ pattern had a higher risk of COPD among men but not women. Therefore, these results indicate that the ‘coffee, fat and sweet’ dietary pattern is inversely related to lung function in Korean adults. Our results indicate that dietary habits may be modifiable risk factors for COPD.

Acute respiratory distress syndrome is the primary cause of death in patients with coronavirus disease 2019 (COVID-19) pneumonia. Our study aims to determine the association between serum markers and mortality in COVID-19 patients with respiratory failure. This retrospective study was conducted in a tertiary care hospital in South Korea. Forty-nine patients with COVID-19, who required high flow nasal cannulation or mechanical ventilation from February 2020 to April 2021, were included. Demographic and laboratory data were analyzed at baseline and on Day 7 of admission. We found that serum creatinine, troponin, procalcitonin, and soluble interleukin-2 receptor (sIL-2R) at baseline were more elevated in the non-survivor group, but were not associated with mechanical ventilator use on Day 7. Older age, PaO2/FiO2 ratio, lymphocyte and platelet counts, lactate dehydrogenase, IL-6, C-reactive protein, and sIL-2R on Day 7 were significantly associated with mortality. Delta sIL-2R (Day 7–Day 0) per standard deviation was significantly higher in the non-survivor group (adjusted hazard ratio 3.225, 95% confidence interval (CI) 1.151–9.037, p = 0.026). Therefore, sIL-2R could predict mortality in COVID-19 patients with respiratory failure. Its sustained elevation suggests a hyper-inflammatory state, and mirrors the severity of COVID-19 in patients with respiratory failure, thereby warranting further attention.

Abstract Background Methionyl-tRNA synthetase (MRS) plays a critical role in initiating translation by transferring Met to the initiator tRNA (tRNAi Met) and protection against ROS-mediated damage, suggesting that its overexpression is related to cancer growth and drug resistance. In this study, the clinical implication of MRS expression in non-small cell lung cancer (NSCLC) was evaluated. Methods Immunoblot and immunohistochemical (IHC) analyses were performed using tissue lysates and formalin-fixed paraffin embedded (FFPE) tissue blocks from wild type C57BL/6, LSL-Kras G12D, and LSL-Kras G12D:p53fl/fl mice. For human studies, 12 paired adjacent normal appearing lung tissue lysates and cancer tissue lysates, in addition to 231 FFPE tissue samples, were used. Results MRS was weakly expressed in the spleen and intestinal epithelium and only marginally expressed in the kidney, liver, and lungs of wild type C57BL/6 mice. On the other hand, MRS was strongly expressed in the neoplastic region of lung tissue from LSL-Kras G12D and LSL-Kras G12D:p53fl/fl mice. Immunoblot analysis of the human normal appearing adjacent and lung cancer paired tissue lysates revealed cancer-specific MRS overexpression, which was related to mTORC1 activity. IHC analysis of the 231 FFPE lung cancer tissue samples showed that MRS expression was frequently detected in the cytoplasm of lung cancer cells (179 out of 231, 77.4%), with a small proportion (73 out of 231, 31.6%) also showing nuclear expression. The proportion of cases with positive MRS expression was higher in the advanced pStage subgroup (P = 0.018, χ2-test) and cases with MRS expression also had shorter DFS (161.6 vs 142.3, P = 0.014, log-rank test). Conclusions Taken together, MRS is frequently overexpressed in NSCLC. Moreover, MRS is related to mTORC1 activity and its overexpression is associated with poor clinical outcomes, indicating that it has potential as a putative therapeutic target.

A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models. The synergism of this combination was evaluated by the Chou-Talalay Combination Index method. In vivo activity was evaluated by micro-CT. In NSCLC cells, there was a time and dose-dependent phosphorylation of SRC-JAK2-STAT3 by cisplatin, followed by increased expression of anti-apoptotic molecules. When the expression of the BCL-2 protein family members was evaluated in clinical samples, BCL-xL was most frequently overexpressed. Dominant negative STAT3 suppressed their expression, suggesting that STAT3 mediates cisplatin mediated overexpression of the anti-apoptotic molecules. ABT-737 displaced BCL-xL from mitochondria and induced oligomerization of BAK. ABT-737 itself showed cytotoxic effects and a combination of ABT-737 with cisplatin showed strong synergistic cytotoxicity. In a murine lung cancer model, co-treatment with ABT-737 and cisplatin induced significant tumor regression. These findings reveal a synergistic cytotoxic and anti-tumor activity of ABT-737 and cisplatin co-treatment in preclinical models, and suggest that clinical trials using this strategy may be beneficial in advanced NSCLC.

Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.