Sei Won Lee

Background Obesity is a chronic inflammatory and metabolic condition implicated in the pathogenesis of several fibrotic diseases. However, population-based evidence regarding the association between obesity and the risk of idiopathic pulmonary fibrosis (IPF) remains limited.Methods This is a nationwide population-based cohort study using the National Health Information Database of South Korea. Adults aged ≥20 years who participated in the National Health Screening Program in 2012 were included. Individuals with prevalent IPF or those diagnosed within 1 year after baseline were excluded. Obesity was assessed using body mass index (BMI ≥25 kg/m² by Asian criteria) and waist circumference (WC). Incident IPF was defined by insurance claims with the International Classification of Diseases, 10th Revision code J84.1 in conjunction with registration in the Rare Intractable Diseases programme.Results Among 4 788 202 participants followed for a mean of 10.15 years, 1 591 830 (33.2%) were classified as obese. Higher BMI was associated with an increased risk of IPF in a dose–response manner after multivariable adjustment. Compared with participants with BMI 18.5–22.9 kg/m², adjusted HRs for IPF were 1.25 (95% CI 1.16 to 1.35) for BMI 23–24.9 kg/m², 1.55 (95% CI 1.45 to 1.66) for BMI 25–29.9 kg/m² and 1.66 (95% CI 1.42 to 1.94) for BMI ≥30 kg/m². In contrast, underweight individuals (BMI <18.5 kg/m²) had a lower risk of IPF. WC demonstrated a similar trend, with higher values independently associated with increased IPF risk.Conclusions In this large nationwide cohort, both general and abdominal obesity were independently associated with an increased risk of incident IPF. These findings provide population-based evidence supporting a potential role of increased adiposity in IPF pathogenesis.

Background: Severe asthma is characterized by persistent airway inflammation and heterogeneous responses to biologic therapies. Growing evidence implicates the gut–lung axis in asthma pathophysiology; however, few studies have concurrently characterized gut and airway microbiomes in relation to treatment response in severe asthma. Methods: We profiled microbiomes of stool bacteria (STB), stool‐derived extracellular vesicles (STE), and exhaled breath condensate (EBC) from 48 patients with severe asthma receiving dupilumab. Microbial composition, alpha diversity, and predicted functional profiles were compared across sample types and longitudinally according to treatment response. Associations between microbial features and asthma‐related clinical markers were also evaluated. Results: Distinct taxonomic and predicted functional signatures were identified across biological compartments. EBC samples were enriched in Proteobacteria, including Pseudomonas , and exhibited a higher predicted abundance of pathways related to two‐component systems and bacterial secretion systems. EBC microbial diversity was positively associated with baseline sputum eosinophil levels ( p = 0.018), whereas stool microbial richness demonstrated a time‐dependent association with blood eosinophil counts after treatment ( p for interaction = 0.023). Treatment responders exhibited lower abundances of Lachnospira (STB q = 0.046; STE q = 0.042) and Escherichia–Shigella (STE q = 0.038), and a higher relative abundance of the Oscillospiraceae NK4A214 group (STB q = 5.5 × 10 ⁻⁷ , STE q = 1.4 × 10 ⁻⁸ ) in stool‐derived profiles. Conclusion: Gut and airway‐derived microbiomes appear to play complementary roles in severe asthma. Stool‐derived microbial features may reflect systemic inflammatory signals associated with treatment response, whereas airway‐derived microbial profiles reflect local airway inflammation. Integrating multi‐compartment microbiome data may improve the understanding of heterogeneity in biologic treatment response among patients with severe asthma.

Background: Endobronchial ultrasound (EBUS)–guided transbronchial needle aspiration (TBNA) is strongly recommended for mediastinal staging in resectable non–small cell lung cancer (NSCLC). However, the optimal sampling extent remains uncertain. This study aimed to evaluate whether the extent of nodal sampling during staging EBUS is associated with pathologic N2 upstaging in clinical N0–N1 NSCLC. Methods: This retrospective cohort included patients with cN0–N1 NSCLC who underwent preoperative EBUS‐TBNA between January 2022 and December 2023. Patients were stratified into three groups according to the number of sampled lymph node stations at the N2/N3 levels: Group 1, ≤ 1 mediastinal station at N2 or N3; Group 2, one N2 and one N3 station; Group 3, ≥ 3 stations, including at least one N2 and one N3. The primary outcome was pathologic N2 upstaging, defined as N2 disease confirmed on surgical pathology despite preoperative stage N0–N1. Results: A total of 418 patients were included (mean age, 68.6 years; 64.1% male). Most had adenocarcinoma (75.4%) and cN0 disease (94.7%). Group distribution was 140 (33.5%) in Group 1, 92 (22.0%) in Group 2, and 186 (44.5%) in Group 3. Pathologic N2 upstaging occurred in 21/140 (15.0%) in Group 1, 8/92 (8.7%) in Group 2, and 8/186 (4.3%) in Group 3. The rate decreased with increasing sampling, with Group 3 showing a lower rate than Group 1 ( p = 0.005). Conclusions: Comprehensive staging EBUS‐TBNA with ≥ 3 N2/N3 stations was associated with a lower rate of occult N2 upstaging in clinical N0–N1 NSCLC, underscoring the importance of comprehensive nodal evaluation for accurate staging.

Depression as a Risk of Lung Cancer in Women: a Nationwide Cohort Study

Background: Post-tuberculosis lung disease (PTLD) is common after pulmonary tuberculosis (TB) and contributes to long-term morbidity, but spirometry is not routinely performed in clinical practice. We aimed to develop and externally validate a deep learning model that estimates spirometry from chest radiographs (CXR) to enable scalable functional surveillance after TB.Methods: In this retrospective multicentre study, we collected paired CXR and spirometry data from two tertiary hospitals in Seoul, South Korea. We developed multi-task (regression, reconstruction, and segmentation) models, including a ratio-constrained variant incorporating forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) loss. The models’ performances in prediction of FVC and FEV1 were assessed via Lin’s concordance correlation coefficient (CCC), mean absolute error (MAE), mean squared error (MSE), and root mean squared error (RMSE). Discrimination for restrictive (FVC%<80%) and obstructive (FEV1/FVC<70%) patterns was assessed by area under the receiver operating characteristic curve (AUROC).Findings: We used 35,364 paired CXR–spirometry datasets (32,627 internal; 2,737 external). In the temporally independent test set (n=3,262), the ratio-constrained multi-task model (rMTM) achieved CCC 0·878 (95% CI 0·870–0·886) for FVC and 0·812 (0·800–0·826) for FEV1. In the external dataset, the rMTM achieved CCC 0·750 (0·731–0·769) for FVC and 0·737 (0·716–0·757) for FEV1. For classification, the rMTM achieved AUROC 0·874 (0·862–0·886) for restriction and 0·802 (0·787–0·816) for obstruction in the internal test set, and 0·781 (0·762–0·798) and 0·770 (0·753–0·787) in the external test set.Interpretation: CXR-based deep learning estimation of spirometry showed high agreement in temporally independent testing and maintained performance on external validation in a TB-relevant population. This approach could support opportunistic functional screening and longitudinal surveillance after TB by prioritising individuals for confirmatory spirometry and follow-up in resource-constrained settings.

Background: Cigarette smoking is the key risk factor for chronic obstructive pulmonary disease, but even similar levels of smoking can result in different disease severity. We hypothesize that differences in gut microbiota and metabolites contribute to differences in emphysema severity through the gut–lung axis. In this study, we compared the microbiome and metabolome among non-emphysema, non-severe emphysema and severe emphysema groups. Additionally, the impact of fecal microbiota transplantation from non-emphysema, non-severe emphysema and severe emphysema groups on emphysema were investigated. Methods: A total of 78 participants with a smoking history were included in this study and categorized into three groups: non-emphysema, non-severe emphysema, and severe emphysema. Gut microbiota and metabolites were analyzed, and germ-free mice underwent fecal microbiota transplantation with feces from donors representative of each group prior to smoking exposure. Results: Significant differences in gut microbiota and metabolites were observed among the groups, with lower acetic acid levels in patients with severe emphysema, and a greater abundance of Prevotellaceae and Megasphaera in patients without emphysema. Fecal microbiota transplantation from donors with severe emphysema worsened lung pathology in mice subjected to smoking exposure, whereas fecal microbiota transplantation from donors without emphysema attenuated emphysema development. Conclusions: Gut microbiota and metabolites in participants with a smoking history differ according to the presence of emphysema and its severity, and can affect emphysema development. This suggests a role for gut microbiota in lung disease and provides a foundation for exploring gut microbiota as a potential therapeutic target for chronic obstructive pulmonary disease.

Background: Tobacco smoking is a major risk factor for lung cancer; however, more than one-third of newly diagnosed lung cancer cases in Korea occur in never-smokers. Among heavy smokers, the specific characteristics contributing to increased lung cancer risk remain unclear. We investigated the risk factors for lung cancer in never-smokers and in heavy smokers with ≥30 pack-years. Methods: We screened individuals who underwent the national health examination in 2012. We identified two groups: (I) 2,650,867 never-smokers and (II) 269,320 heavy smokers (≥30 pack-years) and followed them until December 2022. Newly diagnosed lung cancer cases were identified as follows: (I) 16,540 among never-smokers and (II) 9,895 among heavy smokers. Multivariable Cox proportional hazards models were applied to determine factors associated with lung cancer in each population. Results: Compared with never-smokers, heavy smokers had approximately fivefold higher lung cancer incidence rates. Lung cancer risk increased with older age, male sex, lower income, alcohol intake, smoking status (current smoking) and cumulative exposure (increasing pack-years), diabetes, history of tuberculosis (TB), and chronic obstructive pulmonary disease (COPD). A history of TB and COPD was associated with nearly twofold higher lung cancer risk. In contrast, body mass index was inversely associated with lung cancer risk. Most risk factors were more pronounced in younger (Conclusions: Sociodemographic factors, lifestyle behaviors, and comorbidities significantly influence lung cancer risk in both never-smokers and heavy smokers. Current smokers with high cumulative exposure were at greatest risk. TB history and COPD should be incorporated into future lung cancer risk prediction strategies.

Chronic obstructive pulmonary disease (COPD) remains a major health burden with few effective therapies, particularly for emphysema. The gut–lung axis and microbial metabolites, such as short-chain fatty acids (SCFAs), have emerged as modulators of lung inflammation. We investigated the therapeutic effects of Lactobacillus fermentum HEM20792 (LF), identified through a colon mimetic personalized pharmaceutical meta-analytical screening (PMAS) platform using fecal samples from severe COPD patients. LF and Lactobacillus sakei HEM20224 (LS) were orally administered to smoke-exposed mice, followed by lung function testing, histopathology, RNA sequencing, single-cell transcriptomics, and fecal microbiome/SCFAs analyses. LF attenuated emphysematous changes, improved compliance, and reduced macrophage and IL-17+ lymphocyte infiltration. Single-cell analysis showed restoration of alveolar macrophages and reduction of pathogenic C1q ⁺ macrophages, while transcriptomics revealed normalization of NF-κB and arachidonic acid pathways and attenuation of IL-17– and SPP1-associated signaling. LF also increased fecal SCFAs levels. These findings provide preclinical evidence for LF as a promising microbiome-based therapeutic candidate for COPD.

Background: Bronchiectasis is a respiratory disease structurally characterised by irreversible airway dilatation. Functional impairments are also implicated in bronchiectasis, but the detailed changes in pulmonary function and the impact of clinical factors are yet to be examined. We analysed pulmonary function in patients with bronchiectasis based on their clinical features. Methods: Two study cohorts—a multicentre bronchiectasis registry and health check-up examinees—were analysed. Airflow limitation was defined as forced expiratory volume in 1 s (FEV ₁ )/forced vital capacity (FVC) 1 , FEV ₁ /FVC and FVC values, and the highest prevalence of airflow limitation. In the bronchiectasis registry (n=768), lung function parameters were worse in those with more involved lobes and Pseudomonas colonisation. Multivariable logistic regression analysis showed that bronchiectasis was independently associated with airflow limitation (OR 2.22 (95% CI 1.75 to 2.82)). Conclusions: Bronchiectasis is an independent risk factor for airflow limitation, and disease severity, smoking and Pseudomonas colonisation were each associated with worsening in pulmonary function.

Interferon regulatory factor 5 (IRF5) is a key regulator of inflammatory responses; however, its role in chronic obstructive pulmonary disease remains unknown. A previous study showed increased IRF5 expression in the lungs of cigarette smoke (CS)-induced emphysema. Here we investigated the function of IRF5 in emphysema using Irf5- knockout (KO) mice. Alveolar destruction, inflammatory cell infiltration, cytokine levels and pyroptosis-related gene expression were assessed in CS-induced emphysema. To investigate the role of immune cells, Ly6C ⁺⁺ (Ly6C ^high ) monocytes and Ly6C ^high T cells from Irf5- KO mice were introduced into emphysema mice. The correlation between IRF5 levels and emphysema in humans was also evaluated. Irf5 -KO mice showed decreased alveolar destruction after CS exposure. NLRP3 expression was suppressed, and gasdermin D cleavage was altered in Irf5- KO mice, suggesting a protective effect against pyroptotic cell death. Moreover, Ly6C ^high monocytes and Ly6C ^high T cells were more abundant in the lungs of Irf5- KO mice after CS exposure, and their transfer attenuated NLRP3 expression and alveolar damage. Furthermore, IRF5 expression was significantly elevated in lung tissues from patients. Our findings highlight IRF5 as a critical regulator of emphysema pathogenesis via NLRP3-mediated pyroptosis and Ly6C ^high -expressing immune cells. Targeting IRF5 may be a potential therapeutic strategy for chronic obstructive pulmonary disease.