The association between cumulative exposure to PM2.5 and DNA methylation measured using methyl-capture sequencing among COPD patients.

BACKGROUND: Particulate matter with a diameter of < 2.5 µm (PM2.5) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM2.5 exposure and DNA methylation in CpG islands as well as explore the associated gene pathways. METHODS: A total of 95 male patients with chronic obstructive pulmonary disease (COPD) were enrolled in this study. PM2.5 concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM2.5 exposure levels were calculated for short-term (7 days), mid-term (35 days), and long-term (90 days). DNA methylation analysis was performed on the blood samples, which, after PCR amplification and hybridization, were finally sequenced using an Illumina NovaSeq 6000 system. Correlation between PM2.5 exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM2.5 exposure to identify the relevant biological functions or pathways. RESULTS: The number of CpG sites showing differential methylation was 36, 381, and 182 for the short-, mid-, and long-term indoor models, respectively, and 3, 98, and 28 for the short-, mid-, and long-term estimated exposure models, respectively. The representative genes were TMTC2 (p = 1.63 × 10-3, R2 = 0.656), GLRX3 (p = 1.46 × 10-3, R2 = 0.623), DCAF15 (p = 2.43 × 10-4, R2 = 0.623), CNOT6L (p = 1.46 × 10-4, R2 = 0.609), BSN (p = 2.21 × 10-5, R2 = 0.606), and SENP6 (p = 1.59 × 10-4, R2 = 0.604). Functional enrichment analysis demonstrated that the related genes were mostly associated with pathways related to synaptic transmission in neurodegenerative diseases and cancer. CONCLUSION: A significant association was observed between PM2.5 exposure and DNA methylation upon short-term exposure, and the extent of DNA methylation was the highest upon mid-term exposure. Additionally, various pathways related to neurodegenerative diseases and cancer were associated with patients with COPD. GOV IDENTIFIER: NCT04878367.

The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.

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) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

Development and Validation of a Real-Time Service Model for Noise Removal and Arrhythmia Classification Using Electrocardiogram Signals.

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.

Malnutrition is associated with mortality in Sjögren's syndrome-associated interstitial lung disease.

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 < 47.7 and PNI ≥ 47.7 groups. A statistical difference was observed in the Kaplan-Meier analysis and log-rank test (p = 0.005). In multivariable analyses, PNI < 47.7 (hazard ratio 9.40, 95% confidence interval 1.54-57.21) is associated with increased mortality, suggesting the importance of early nutritional intervention for malnutrition in SjS-ILD patients.

Association between exposure to specific PM2.5 constituents and environment, lifestyle, and clinical parameters in patients with COPD.

This study investigated the correlation between the individual chemical constituents of particulate matter 2.5 µm (PM2.5) and respiratory parameters as well as the living environment and daily behaviors in patients with chronic obstructive pulmonary disease (COPD). Data were obtained from prospective COPD panel conducted in South Korea. Following collection via a microPEM, 18 metallic elements were determined using energy-dispersive X-ray fluorescence spectroscopy. All participants completed detailed questionnaires on living environments and lifestyle practices. Eighty-nine stable COPD patients (mean age 68.1 years; 94.4% male) were analyzed. Several constituents (titanium, aluminum, bromine, and silicone) were significantly associated with respiratory outcomes. Copper and manganese concentrations were significantly associated with the living environment. Increased ventilation time and air purifier operation were associated with lower concentrations of copper, silicone, barium, and titanium. These findings suggest varying relationships between PM2.5 constituents and clinical parameters in COPD patients, providing a basis for personalized interventions and future research.

Multi-center Korean cohort study based on RNA-sequencing data targeting COPD patients.

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.

Clinical Characteristics and Treatment Outcomes of Pulmonary Diseases Caused by Coinfections With Multiple Nontuberculous Mycobacterial Species.

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

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<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Factors affecting accuracy of clinical staging in resectable non-small cell lung cancer in a real-world study.

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 < 0.001) contributed to the clinical staging inaccuracy. Additionally, the presence of a bronchoscopy specialist was significantly associated with clinical staging accuracy (OR 1.53; 95% CI: 1.10-2.13, p = 0.011). CONCLUSION: Clinical staging accuracy in NSCLC improved compared to before the widespread use of PET-CT and EBUS in clinical staging work-up. Smoking history and absence of expert bronchoscopy specialists showed a meaningful correlation with the inaccuracy of clinical staging. Thus, training more bronchoscopy experts would improve the staging accuracy of NSCLC, which could positively affect the prognosis of NSCLC.

Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Factors Associated with the Discrepancy between Exercise Capacity and Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Exercise capacity is associated with lung function decline in chronic obstructive pulmonary disease (COPD) patients, but a discrepancy between exercise capacity and airflow limitation exists. This study aimed to explore factors contributing to this discrepancy in COPD patients. METHODS: Data for this prospective study were obtained from the Korean COPD Subgroup Study. The exercise capacity and airflow limitation were assessed using the 6-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 clinical characteristics were compared. RESULTS: A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) were enrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, and among 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multiple regression 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, 0.178 to 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 limitation in patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusion capacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantly associated with discrepancies between exercise capacity and airflow limitation. CONCLUSION: The exercise capacity of COPD patients may be influenced by factors other than airflow limitation, so these aspects should be considered when assessing and treating patients.

Randomised controlled trial of a behavioural intervention to reduce exposure to PM2.5 in patients with COPD.

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.

Subtypes of Patients with Mild to Moderate Airflow Limitation as Predictors of Chronic Obstructive Pulmonary Disease Exacerbation.

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.

Within-Host Evolution of SARS-CoV-2 in a B-Cell Depleted Patient With Successful Treatment.

Prolonged viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an immunocompromised host is a challenge as the treatment and infection control for chronic coronavirus disease 2019 infection is not well established and there is a potential risk of new variants emerging. A 48-year-old woman who underwent chemotherapy, including rituximab and steroid, had reactivation of SARS-CoV-2 68 days after the virus was first detected. She successfully recovered after receiving convalescent plasma and intravenous immunoglobulin. Genomic analysis demonstrated that viruses collected from the nasopharyngeal specimens at day 0 and day 68 had 18 different nucleotide mutations, implying within-host evolution after in-depth epidemiologic investigation.

Outstanding Characteristics of Birt-Hogg-Dube Syndrome in Korea.

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.

Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer.

Introduction: Regarding 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). Methods: A 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). Results: Among 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. Conclusions: Given 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.

Definitions of Chronic Obstructive Pulmonary Disease and Chronic Obstructive Pulmonary Disease Exacerbation: A Modified Delphi Survey.

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.

Summary of Korean Asthma Guideline.

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 ß2-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.

Characteristics and risk factors of mortality in patients with systemic sclerosis-associated interstitial lung disease.

BACKGROUND: 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] < 70% in indeterminate cases) and limited (n = 60, <20% disease extent on CT or FVC ≥70% in indeterminate cases). RESULTS: Patients in the extensive group were younger (mean age ± SD 49.3 ± 11.5) than those in the limited group (53.9 ± 12.5, p = .067) at diagnosis. The extensive group showed frequent pulmonary hypertension (43.5% vs. 16.7%, p = .009) and higher erythrocyte sedimentation rate (61.3 ± 33.7 vs. 42.1 ± 26.0, p = .003) and mortality (32.6%, mean duration of follow-up, 100.0 ± 44.7 months vs. 10.0%, 86.0 ± 53.4 months, p = .011). ILD was detected within five years from the first visit (median years 3.5 (1.0, 6.0) vs. 4.5 (0.6, 9.0), survivors vs. non-survivors), and mortality occurred in 19.8% of all patients during a 15-year follow-up. Older age, lower FVC, and initial disease stage (limited or extensive) were associated with mortality, but FVC decline was similar in the limited and extensive groups, such as 15-20% in the first year and 8-10% in the next year, regardless of the initial extent of the disease. CONCLUSIONS: Approximately 10% of patients with SSc-ILD in the limited and extensive group showed progression. ILD was detected at a median of less than five years from the first visit; therefore, it is necessary to carefully monitor patients' symptoms and signs from an early stage. Long-term surveillance is also required.Key messagesPatients with systemic sclerosis-interstitial lung disease manifested a heterogeneous disease course.Approximately 10% of the patients in the limited group showed progression, which was similar to the proportion of patients in the extensive group.Interstitial lung disease was detected at a median of less than five years from the first visit.

Longitudinal association between adiposity changes and lung function deterioration.

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.