Tuberculosis and Respiratory Diseases最新文献

{"title":"SERPINA3 as a Secreted-Protein Biomarker Associated with Poor Prognosis and T-Cell Dysfunction in Non-small Cell Lung Cancer.","authors":"Joon Kim, Geunin Lee, Seung-Hyun Yong, Eun Young Kim, Yunju Jo, Wooju Jeong, Dongryeol Ryu, Chang-Myung Oh, Sang Hoon Lee","doi":"10.4046/trd.2026.0014","DOIUrl":"10.4046/trd.2026.0014","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains the leading cause of cancer-related mortality, with poor outcomes driven by late presentation and therapy resistance. While genes encoding secreted proteins may reflect tumor biology and have biomarker potential, systematic multi-cohort studies that identify and validate prognostically relevant secreted protein candidates in non-small cell lung cancer (NSCLC) are limited.</p><p><strong>Methods: </strong>We conducted a multi-cohort transcriptomic screen of 1,896 genes encoding secreted proteins to nominate prognostic candidates in NSCLC. Candidates were prioritized based on differential expression between tumor and normal tissues and survival associations across public NSCLC cohorts. Serpin family A member 3 (SERPINA3) was selected for further validation in The Cancer Genome Atlas (TCGA) NSCLC dataset. Tumors were stratified by SERPINA3 expression for Kaplan-Meier survival analysis and gene set enrichment analysis (GSEA) using the Hallmark and Kyoto Encyclopedia of Genes and Genomes (KEGG) collections. Translational relevance was assessed in a retrospective bronchoalveolar lavage fluid (BALF) registry using multivariable Cox models.</p><p><strong>Results: </strong>In the TCGA NSCLC dataset, SERPINA3-high tumors had shorter overall survival (OS; log-rank p=0.016) and progression-free survival (PFS; log-rank p=0.018). GSEA showed enrichment in tumor necrosis factor-α/nuclear factor-κB, inflammatory response, interleukin 6 (IL-6)-Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3), and IL-17 signaling pathways. The SERPINA3-high state exhibited a T-cell-infiltrated, checkpoint-high phenotype consistent with T-cell dysfunction, characterized by increased levels of transforming growth factor-β, IL-10, and indoleamine 2,3-dioxygenase (IDO). In the BALF registry, higher BALF-but not plasma-SERPINA3 independently predicted shorter PFS, with a nonsignificant trend toward OS after adjustment.</p><p><strong>Conclusion: </strong>Across datasets, SERPINA3 indicates an immune-inflammatory tumor state associated with worse survival. BALF-based measurement captured tumor-proximal signals that may be less apparent in plasma, supporting its potential clinical utility for risk stratification and warranting prospective validation.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"403-415"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Precision Approaches to Chronic Obstructive Pulmonary Disease.","authors":"Craig P Hersh","doi":"10.4046/trd.2026.0037","DOIUrl":"10.4046/trd.2026.0037","url":null,"abstract":"<p><p>Precision medicine aims to define subtypes of a heterogeneous disease, which can lead to more specific diagnosis, prognosis, and/or treatment. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and therefore appropriate for a precision medicine approach. The idea of COPD heterogeneity has been proposed for decades, initially with subtypes of emphysema and chronic bronchitis. Modern approaches include the use of chest computed tomography (CT) scan imaging and omics biomarkers. One path forward is to start by identifying a clinical question, then try to understand the epidemiology, to describe clinical phenotypes and disease subtypes. One can then incorporate omics biomarkers to arrive at an endotype, a subtype with a shared biologic mechanism. Eosinophilic COPD and alpha-1 antitrypsin deficiency-related emphysema are endotypes that already have specific therapies. Subtypes such as patients with frequent exacerbations can be targeted with several treatments, but multiple biological processes are likely to be important. This review will highlight these approaches, using examples such as airway-predominant COPD, frequent exacerbations, and asthma-COPD overlap. These investigations have been conducted in large observational studies, including the multi-center US Genetic Epidemiology of COPD Study (COPDGene). The analyses have leveraged the wealth of data in COPDGene, including clinical information, pulmonary function tests, chest CT scans, and multi-omics such as genetics, RNA-sequencing, and proteomics. Despite these advances, there are many challenges for COPD precision medicine, such as the requirement for large studies with longitudinal outcomes and available biospecimens. Clinical trials of targeted therapies will be needed for the ultimate application of precision medicine in COPD.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"359-369"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linezolid-Induced Optic Neuritis in Tuberculosis: A Systematic Review of Case Reports, Case Series, and Cohort Studies.","authors":"Sanjay Singhal, Ranganath Ganga, Pulkit Gupta, Aneeket Rastogi, Shilpi Arya, Shikha Agarwal, Shubham Singh, Ravindra Kumar Garg","doi":"10.4046/trd.2025.0214","DOIUrl":"10.4046/trd.2025.0214","url":null,"abstract":"<p><strong>Background: </strong>With the increasing use of linezolid for the treatment of drug-resistant tuberculosis, concerns have emerged regarding serious adverse effects, including optic neuritis. To systematically review the available evidence on the incidence of optic neuritis reported in the cohort, its onset, linezolid doses and duration, spectrum, management approaches, and outcomes across case reports and series studies.</p><p><strong>Methods: </strong>A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines after registration in International Prospective Register of Systematic Reviews (PROSPERO; CRD420251108339). We searched PubMed, EMBASE, and Scopus. Eligible studies included case reports, case series, and cohort studies of patients with tuberculosis who developed optic neuritis while receiving linezolid. Data were extracted independently by two reviewers, and methodological quality was assessed using a validated tool for evaluating case reports and case series. Results were synthesized narratively with descriptive statistics.</p><p><strong>Results: </strong>Nineteen case reports and case series, 35 cohort studies, and safety data from five randomized controlled trials were included. Most reported cases originated from India (61.6%), with a mean age of 30.6±13.0 years; 65.4% were male. Linezolid was administered at 600 mg/day in nearly 90% of cases, with a median exposure of 7 months. Visual symptoms were typically painless and bilateral. After discontinuation of linezolid, more than half of the patients achieved complete visual recovery, while 34.6% experienced residual visual impairment. Across cohort studies, the incidence of optic neuritis ranged from 0.47% to 30%, with higher rates observed in smaller studies from a single country and among patients with a low body mass index.</p><p><strong>Conclusion: </strong>This infrequent but clinically significant complication requires early recognition, prompt drug withdrawal, and routine ophthalmological monitoring.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"416-425"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Prognostic Impact of Progressive Pulmonary Fibrosis.","authors":"Joo Hun Park","doi":"10.4046/trd.2025.0216","DOIUrl":"10.4046/trd.2025.0216","url":null,"abstract":"<p><p>Progressive pulmonary fibrosis (PPF) is a clinical phenotype observed in various interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis. It is characterized by worsening fibrosis on high-resolution computed tomography, a progressive decline in lung function, and deteriorating respiratory symptoms. Despite shared pathophysiological mechanisms, the rate of disease progression and clinical outcomes vary significantly among the different subtypes of PPF. Key predictors of poor prognosis include advanced age, male sex, rapid lung function decline, hypoxemia, pulmonary hypertension, and radiologic features such as a usual interstitial pneumonia pattern and traction bronchiectasis. Genetic factors, particularly telomere shortening and mutations in telomere-related genes, have emerged as important determinants of prognosis and therapeutic response. Acute exacerbations of PPF are associated with a poor shortterm prognosis and represent a major cause of morbidity and mortality in PPF. The introduction of antifibrotic therapies has significantly altered the management of PPF by slowing the decline in lung function. However, their impact on long-term survival remains under investigation.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"370-381"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of PROgnostic ModEl for Chronic Lung Disease (PRO-MEL) and ILD-GAP Models in Predicting Mortality in Singaporean Interstitial Lung Disease Patients.","authors":"Gin Tsen Chai, Sheryl Hui-Xian Ng, Zi Yan Chiam, Michelle Li Wei Kam, Andrew Yunkai Li, Valencia Lim, Su Ying Low, Ziqin Ng, Yi Hern Tan, Felicia Su Wei Teo, Allyn Hum","doi":"10.4046/trd.2025.0207","DOIUrl":"10.4046/trd.2025.0207","url":null,"abstract":"","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"426-429"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Harmonized Respiratory-Gut Microbiome Cohort Framework for Idiopathic Pulmonary Fibrosis.","authors":"Eun Chong Yoon, Jinwoo Seok, Yang-Ki Kim, Hee-Young Yoon","doi":"10.4046/trd.2026.0032","DOIUrl":"10.4046/trd.2026.0032","url":null,"abstract":"","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"430-433"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Updates on Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration and Its Clinical Implications.","authors":"Kyungjong Lee","doi":"10.4046/trd.2026.0067","DOIUrl":"10.4046/trd.2026.0067","url":null,"abstract":"<p><p>Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard minimally invasive method for mediastinal staging in non-small cell lung cancer. As the tumor, node, metastasis (TNM) classification evolves with more refined prognostic stratification of N2 substages, accurate mediastinal evaluation has become increasingly critical. Beyond conventional staging, recent advances have significantly expanded the clinical utility of EBUS-TBNA. This review explores six key areas of development: evidence supporting systematic over targeted mediastinal sampling and the potential to omit confirmatory mediastinoscopy after negative EBUS-TBNA; the role of endoscopic ultrasound in accessing paraesophageal and inferior mediastinal stations; expanded procedural capabilities with third-generation thin scope EBUS; novel tissue acquisition devices, including the 19-gauge needle, mini forceps, and mediastinal cryobiopsy; considerations for tissue adequacy in next-generation sequencing; and image-based adjunctive tools such as elastography and artificial intelligence-driven sonographic analysis. Collectively, these developments underscore the growing role of EBUS-TBNA as a comprehensive diagnostic platform in thoracic oncology, extending its utility from mediastinal staging to peripheral lesion access, molecular profiling, and image-guided decision support.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"382-390"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Targeted Therapies in Asthma: From Upstream Epithelial Biology to Novel Biologic and Small-Molecule Strategies.","authors":"Hyun Woo Lee","doi":"10.4046/trd.2026.0033","DOIUrl":"10.4046/trd.2026.0033","url":null,"abstract":"<p><p>Biologic and targeted small-molecule therapies have revolutionized the management of severe asthma by specifically targeting key inflammatory pathways. These advances have led to significant reductions in exacerbations, improved lung function, and decreased dependence on corticosteroids. However, a substantial number of patients still experience breakthrough exacerbations and inadequate disease control, indicating that there are residual inflammatory mechanisms beyond the classical type-2 pathways. Current biologics that target immunoglobulin E, interleukin-5, interleukin-4 receptor alpha, and thymic stromal lymphopoietin show efficacy in biomarker-defined populations. Yet, their clinical benefits are closely tied to baseline type-2 biomarkers, and they often fall short for patients with non-type-2 or mixed inflammatory phenotypes. Emerging evidence from transcriptomic and clinical studies suggests that factors such as epithelial dysfunction, innate immune activation, and tissue repair pathways contribute to ongoing disease instability, even with targeted cytokine blockade. These insights have spurred the development of new therapeutic strategies, including biologics aimed at upstream epithelial alarmins like interleukin-33, oral small-molecule inhibitors such as Bruton tyrosine kinase inhibitors, lineage-directed eosinophil-suppressing agents, inhaled biologics, and nanobody-based therapies. Additionally, long-acting and ultra- long-acting biologics are designed to enhance treatment durability and adherence, while bispecific antibodies integrate both upstream and downstream inflammatory inhibition into a single molecular construct. These advancements signify a shift towards broader and more sustained modulation of inflammatory pathways. Future progress in asthma treatment will hinge on integrating insights from epithelial biology, refining biomarker- guided patient selection, and developing multispecific and upstream-targeting therapies to address persistent disease heterogeneity and improve long-term clinical outcomes.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"347-358"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologics in Chronic Obstructive Pulmonary Disease: Current Status and Future Prospects.","authors":"Joon Young Choi","doi":"10.4046/trd.2025.0180","DOIUrl":"10.4046/trd.2025.0180","url":null,"abstract":"<p><p>Significant progress has been made in managing chronic obstructive pulmonary disease (COPD), yet substantial unmet needs persist due to the disease&apos;s heterogeneity and the diverse underlying inflammatory mechanisms. Recent advances have broadened our understanding of COPD beyond a single pathophysiologic model, leading to the development of biologic therapies that target specific immune pathways. This review summarizes current evidence from clinical trials involving biologics in COPD. Early efforts to inhibit non-type 2 inflammation yielded limited results, highlighting the necessity for more refined, endotype-based approaches. Subsequent phase 3 trials have shown considerable clinical benefits in specific patient subsets: dupilumab, which blocks interleukin (IL)-4 and IL-13 signaling, and mepolizumab, which targets IL-5, consistently reduced exacerbation frequency among patients with high blood eosinophil counts (≥300 cells/μL). In contrast, other biologics-such as benralizumab, tezepelumab, and IL-33/suppression of tumorigenicity 2 pathway inhibitors like itepekimab, tozorakimab, and astegolimab-have demonstrated variable efficacy, often influenced by biomarker profiles and patient characteristics. These findings emphasize the importance of precise patient stratification based on inflammatory endotypes. While biologics mark a significant advancement for select COPD populations, further research is needed to clarify long-term outcomes, refine biomarker thresholds, and broaden treatment options for non-eosinophilic COPD.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"121-132"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcome Prediction by High-Resolution Computed Tomography and Echocardiography Assessment of Pulmonary Hypertension in Patients with Bronchiectasis.","authors":"Inhan Lee, Joon-Sung Joh, Ji Yeon Lee, Joohae Kim, Sooim Sin, Hyeon-Kyoung Koo, Ina Jeong","doi":"10.4046/trd.2025.0067","DOIUrl":"10.4046/trd.2025.0067","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the association between pulmonary hypertension and hospital admission rates in patients with bronchiectasis.</p><p><strong>Methods: </strong>We retrospectively analyzed data from 130 bronchiectasis patients at the National Medical Center, Korea (November 2012 to October 2022). Pulmonary hypertension was evaluated using high-resolution computed tomography (CT) and echocardiography. Patients were categorized into two groups based on the diameter of the main pulmonary artery (mPA). Logistic regression analysis was performed to identify risk factors associated with hospitalization.</p><p><strong>Results: </strong>Forty patients had suspected pulmonary hypertension on echocardiography. A higher percentage of patients with mPA diameter &gt;29 mm (n=61) had a history of previous exacerbations, elevated echocardiographic parameters related to pulmonary hypertension, and reduced lung function, compared to those with mPA diameter ≤29 mm (n=69). In univariate analysis, the hospitalization group showed increased mPA diameter; pulmonary artery to aorta ratio; involvement of lung lobes, cavities, and nodules; and increased systolic pulmonary artery pressure and peak tricuspid regurgitation velocity. In multivariate analysis, mPA diameter &gt;29 mm (adjusted odds ratio [OR], 2.47; 95% confidence interval [CI], 1.14 to 5.32) and the involvement of more than two lobes (adjusted OR, 2.57; 95% CI, 1.14 to 5.77) were significant risk factors for hospitalization.</p><p><strong>Conclusion: </strong>The CT parameters demonstrated comparable accuracy to models that incorporated echocardiographic data to predict hospitalization in bronchiectasis patients.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"297-305"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145709626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}