Lung最新文献

{"title":"NOP2 Exacerbates Pulmonary Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease by Inducing Neutrophil Extracellular Traps Mediating M1 Macrophage Polarization.","authors":"Chunyan Guo, Sai Chen, Zhuxiang Shao, Shengping Zhai","doi":"10.1007/s00408-026-00943-6","DOIUrl":"https://doi.org/10.1007/s00408-026-00943-6","url":null,"abstract":"<p><strong>Background: </strong>This study aims to explore the molecular mechanism of NOP2 in inducing neutrophil extracellular traps (NETs) and M1 macrophage polarization in a murine model of COPD.</p><p><strong>Methods: </strong>A murine model of COPD was established using cigarette smoke exposure combined with LPS stimulation. Lung pathological changes and fibrosis were evaluated by H&E and Masson staining. The inflammatory cytokines in bronchoalveolar lavage fluid and NETs-related biomarkers in serum were detected by ELISA. Immunofluorescence was applied to observe the colocalization of Cit-H3 with CD86/CD206 in lung tissues. In vitro, RAW264.7 macrophages were treated with cigarette smoke extract. NETs were induced by PMA and co-cultured with RAW264.7 cells. Cell viability, macrophage polarization, and the expression of NOP2, TUG1, TRIM27, EZH2, iNOS and Arg-1 were determined by CCK-8, flow cytometry, qRT-PCR or Western blot. MeRIP, actinomycin D assay, RNA pull-down, RIP and Co-IP were performed to detect m5C modification, TUG1 stability, molecular binding and EZH2 ubiquitination.</p><p><strong>Results: </strong>NOP2, TUG1 and TRIM27 were highly expressed in our murine model of COPD. NOP2 inhibition alleviated lung injury, suppressed NETs, M1 polarization and pulmonary inflammation. Mechanistically, NOP2 stabilized and elevated TUG1 expression via m5C modification. TUG1 acted as a molecular scaffold to recruit TRIM27 and EZH2, facilitating TRIM27-mediated EZH2 ubiquitination. TUG1 overexpression or EZH2 inhibition partially reversed the protective effects of NOP2 silencing.</p><p><strong>Conclusions: </strong>NOP2 aggravates pulmonary inflammation in a murine model of COPD by promoting NETs and M1 polarization via the TUG1/TRIM27/EZH2 axis.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Vulnerability and Pulmonary Nodule Malignancy: Race, Mediation, and a Nodule-Level Mismatch Deserve Closer Scrutiny.","authors":"Fajar Farid, Haider Imran, Abdul Basit Munir","doi":"10.1007/s00408-026-00941-8","DOIUrl":"10.1007/s00408-026-00941-8","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author's Response to: Nebulised Heparin for Lung Disease: Three Overlooked Risks that Merit Study Before Chronic Clinical Use.","authors":"Margarid Miranda, Marc Brown, Frank Mp van Haren, Bethany Brown, Clive Page","doi":"10.1007/s00408-026-00938-3","DOIUrl":"10.1007/s00408-026-00938-3","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menthol for the Relief of Dyspnea: A Systematic Review of Randomized Controlled Trials.","authors":"Kuheli Das Gupta, Kay Choong See","doi":"10.1007/s00408-026-00926-7","DOIUrl":"10.1007/s00408-026-00926-7","url":null,"abstract":"<p><strong>Background: </strong>Dyspnea is a symptom that can cause significant burden on activities of daily living. Overall, dyspnea has associations with increasing age, high body mass index (BMI), female sex and cardiorespiratory diseases. Aside from pharmacological treatments for underlying cardiorespiratory conditions that cause dyspnea, menthol has been discussed as a potential non-pharmacological intervention. However, its role remains contentious with uncertainty regarding efficacy and potential harm. Thus, this systematic review aims to explore the impact of menthol on dyspnea.</p><p><strong>Methods: </strong>A comprehensive search of databases (MEDLINE, Embase, Cochrane Library) was performed from inception of each database to June 2026. Appropriate randomized controlled trials (RCTs) investigating the effects of menthol on dyspnea outcomes were identified based on strict inclusion criteria. The RCTs included patients with dyspnea from underlying respiratory conditions and lab-based studies that simulated dyspnea in people with no underlying lung pathology through exercise. Studies with patients with respiratory conditions also induced dyspnea through exercise and inspiratory loaded breathing. The primary outcome was dyspnea which was measured through scores like Borg and Multidimensional Dyspnea Profile (MDP). Secondary outcomes included adverse events identified and impact on physiological parameters. Subsequently a descriptive analysis of data was carried out.</p><p><strong>Results: </strong>All eight studies selected showed improvement in dyspnea scores. Four studies positively impacted the immediate perception and sensory qualities domains of the MDP, while one study using a visual analogue scale score decreased dyspnea scores by 42% in one subgroup (flow-resistive loading) and 19% in another (elastic loading). Four studies used the modified Borg score to report dyspnea. Amongst these, Kanezaki et al [12] demonstrated a reduction in score by - 2 at maximal time and - 1 with maximal inspiratory resistive load showing a minimal clinical important difference in dyspnea (MCID). Prieur et al. [16]; Schaeffer et al. [14] and Vanden Bossche et al. [21] reduced Borg scores by 0.3, 0.7, 0.67 respectively but did not reach the MCID. However, all three studies did have participants that showed MCID. One study used the 11-point feeling scale to measure breathing comfort and showcased 1.5-point increase in bre̲athing comfort with menthol ingestion and 1 point increase in comfort with menthol rinse. There were no significant documented negative implications of menthol. Menthol had no impact on forced expiratory volume in one second and airway resistance measures.</p><p><strong>Conclusion: </strong>Menthol is an effective and safe treatment option for the short-term and symptomatic relief of dyspnea both at rest and during exercise.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nebulised Heparin for Lung Disease: Three Overlooked Risks that Merit Study Before Chronic Clinical Use.","authors":"Fajar Farid, Haider Imran","doi":"10.1007/s00408-026-00937-4","DOIUrl":"10.1007/s00408-026-00937-4","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult-Onset Interstitial Lung Disease Due to Homozygous SFTPB Variant.","authors":"Claudio Tirelli, Niamh Logan, Krunal Mahida, Felix Chua, Sujal R Desai, Deborah J Morris-Rosendahl, Elisabetta Renzoni","doi":"10.1007/s00408-026-00940-9","DOIUrl":"10.1007/s00408-026-00940-9","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling BRAF Mutations in Non-small Cell Lung Cancer: State of the Art and Future Perspectives.","authors":"Maria Colombino, Panagiotis Paliogiannis, Grazia Palomba, Marina Pisano, Milena Casula, Alessandro Giuseppe Fois, Angelo Zinellu, Giuseppe Palmieri","doi":"10.1007/s00408-026-00932-9","DOIUrl":"10.1007/s00408-026-00932-9","url":null,"abstract":"<p><strong>Background and purpose: </strong>Lung cancer is the most frequently diagnosed malignancy worldwide in recent decades, representing the leading cause of cancer-related mortality globally. Lung cancer is mainly divided into two types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC being the most common, representing about 85% of cases. NSCLC is increasingly recognized to harbor various druggable genetic alterations; among them, activating BRAF mutations are found in approximately 3-4% of NSCLC patients. The objective of this review is to provide a comprehensive overview of the key biological and pathophysiological characteristics of BRAF molecular alterations, their impact on clinical practice, and emerging insights from translational research.</p><p><strong>Methods: </strong>We performed a search of the PubMed database on April 22, 2026. A review of retrieved literature related to BRAF mutations and their clinical implications in NSCLC was completed. The Catalogue of Somatic Mutation in Cancer (COSMIC) database and the NCCN-NSCLC Guidelines were evaluated.</p><p><strong>Results: </strong>Functional classification of BRAF genetic alterations, molecular assays for detection of BRAF gene mutation, advancements of targeted therapies and immunotherapy for BRAF‑mutant NSCLC, and treatment resistance mechanisms were described. Several ongoing studies currently evaluating novel agents with broader biological activity and various drug combinations were reported. Emerging strategies-including next-generation MAPK inhibitors, ADCs, and engineered cellular therapies-were discussed, offering promising avenues to enhance efficacy, overcome resistance, and expand therapeutic options for these patients.</p><p><strong>Conclusion: </strong>Despite limited clinical data, particularly in first line and neoadjuvant settings, remain major challenges, addressing critical questions will be useful to optimize the management of BRAF-mutant NSCLC.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 Receptor Agonists in Pulmonary Hypertension: Mechanistic Rationale, Preclinical Evidence, and Clinical Knowledge Gaps.","authors":"Laith Allaham, Baylee King, Fahiye Ali, Ishita Gupta, Rajesh Metuku, Isabella Nieto, Andrew Lurie, Farah N Amer, Raju Reddy, Bashar Alzghoul","doi":"10.1007/s00408-026-00939-2","DOIUrl":"10.1007/s00408-026-00939-2","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) frequently coexists with type 2 diabetes mellitus, obesity, and heart failure with preserved ejection fraction (HFpEF), particularly in World Symposium on Pulmonary Hypertension (WSPH) Group 2 disease. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists improve several cardiometabolic conditions and have anti-inflammatory and vascular effects. Whether these agents directly modify pulmonary haemodynamics or clinical outcomes in PH remains unknown.</p><p><strong>Methods: </strong>A structured narrative review was conducted using PubMed/MEDLINE and Google Scholar from database inception through March 2026, with additional studies identified by reference-list screening. Search terms encompassed GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonists, pulmonary hypertension, pulmonary vascular remodelling, endothelial dysfunction, inflammation, and HFpEF. The structured search yielded 491 unique PubMed/MEDLINE records. Of these, 189 were assessed at full-text level alongside 40 additional articles identified through reference-list screening; 67 publications were included in the final synthesis. Evidence was organized by mechanism, experimental model, WSPH group, and whether PH evidence was direct or indirect.</p><p><strong>Results: </strong>GLP-1 receptor expression has been demonstrated in pulmonary arterial smooth muscle in human and non-human primate tissue and in selected alveolar cell populations in rodent studies; however, available studies do not establish greater expression in pulmonary than systemic vascular smooth muscle. GLP-1 receptor signalling modulates inflammatory, endothelial nitric oxide, endothelin-1, and mitochondrial pathways relevant to PH. In monocrotaline- and hypoxia-induced models that primarily resemble Group 1 pre-capillary pulmonary arterial hypertension (PAH), liraglutide reduced right ventricular pressures or hypertrophy and pulmonary vascular remodelling, while semaglutide improved right ventricular mitochondrial and functional measures in an experimental pressure-overload model. By contrast, available human evidence is observational or derived indirectly from HFpEF studies, involves populations likely enriched for Group 2 or unclassified PH, and lacks prespecified, catheterization-confirmed PH endpoints. Consequently, these studies do not establish that GLP-1-based therapy prevents or treats PH.</p><p><strong>Conclusions: </strong>Current evidence supports a mechanistic hypothesis and a preclinical signal, not clinical efficacy in PH. Future cardiometabolic and HFpEF trials should incorporate standardized PH and right ventricular measures, and dedicated prospective studies with haemodynamic classification are required before GLP-1-based therapies can be considered for PH.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining Early Recurrence in Resectable Non-small Cell Lung Cancer Using Post-Recurrence Survival.","authors":"Wara Naeem, Arsalan A Khan, Erik E Rabin, Sierra Broad, Keri L Denson, Thalia Casanova, Sanjib Basu, Gillian Alex, Nicole Geissen, Michael J Liptay, Christopher W Seder","doi":"10.1007/s00408-026-00934-7","DOIUrl":"10.1007/s00408-026-00934-7","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to define a data-driven threshold in NSCLC using post-recurrence survival.</p><p><strong>Methods: </strong>Patients who underwent lung resection for stage I-IIIA NSCLC and experienced recurrence at a single institution from 2010 to 2021 were identified. Exclusion criteria included indeterminate N stage, M1 status, neoadjuvant therapy, and positive surgical margins. Time to recurrence was measured from surgery to recurrence, and post-recurrence survival from recurrence to death or last follow-up. Grid search and Kaplan-Meier analysis identified the time cut-point with the greatest survival difference, which was validated using multivariable Cox regression adjusted for age, race, tumor size, smoking history (pack-years), comorbodities, pathological N stage, histology, surgical procedure, and receipt of adjuvant therapy.</p><p><strong>Results: </strong>A total of 227 patients met inclusion criteria, with 50% (114/227) female and 78% (177/227) white patients. The median age was 70 years (IQR 63-76), the tumor size was 2.6 cm (IQR 1.8-4.1), and time to recurrence was 17 months (IQR 9-30). Cut-point analysis identified 12 months as the threshold most strongly associated with survival after recurrence. Median post-recurrence survival was 14 months (IQR 4-32) versus 22 months (IQR 10-40) for patients that recurred within and after 12 months, respectively (log-rank p = 0.002). On multivariable analysis, the 12-month cut-point remained associated with survival after recurrence (HR 1.49, 95% CI 1.03-2.15, p = 0.03).</p><p><strong>Conclusion: </strong>Recurrence within 12 months after resection of early-stage NSCLC is associated with worse post-recurrence survival, making this cutoff a useful indicator of early recurrence.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab Alleviates Pulmonary Fibrosis by Interrupting Profibrotic Macrophage-Fibroblast Crosstalk and IL4R/JAK/STAT Signaling.","authors":"Qi Chen, Yupei Zhang, Shiyang Wang, Ruxuan Chen, Yujie Shi, Zhiyi Li, Chi Shao, Shaoyan Gao, Honggang Zhou, Hui Huang","doi":"10.1007/s00408-026-00936-5","DOIUrl":"10.1007/s00408-026-00936-5","url":null,"abstract":"<p><strong>Purpose: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) of unclear etiology. Dupilumab, a humanized monoclonal antibody binding to interleukin-4 receptor alpha (IL-4Rα), suppresses both IL-4 and IL-13 signaling pathways. However, the therapeutic potential in IPF is unclear. This research aimed to evaluate the antifibrotic efficacy of dupilumab and illustrate the underlying mechanisms.</p><p><strong>Methods: </strong>The antifibrotic efficacy of dupilumab was assessed both in vitro and in vivo. In vitro, a fibroblast activation model and a macrophage-fibroblast co-culture model were established. In vivo, pulmonary fibrosis was induced in C57BL/6 mice by intratracheal bleomycin injection. Lung function, micro-computed tomography (micro-CT), histopathology, inflammatory responses, and fibrosis-related signaling pathways were assessed.</p><p><strong>Results: </strong>Dupilumab significantly suppressed TGF-β1-induced fibroblast activation. In the macrophage-fibroblast coculture system, dupilumab inhibited the profibrotic phenotype of IL-4/IL-13-stimulated macrophages, as well as macrophage-induced myofibroblast activation. In bleomycin-challenged mice, dupilumab improved pulmonary function, alleviated radiographic and histopathological fibrosis, reduced inflammatory cell counts and inflammatory cytokine levels in bronchoalveolar lavage fluid. Mechanistically, dupilumab suppressed activation of both the TGF-β1/Smad and JAK/STAT pathways in fibrotic lung tissues.</p><p><strong>Conclusions: </strong>Dupilumab attenuates pulmonary fibrosis by disrupting profibrotic macrophage-fibroblast crosstalk and suppressing fibroblast activation. In preclinical models, dupilumab mitigated BLM-induced pulmonary inflammation and early-stage fibrosis in mice and inhibited the TGF-β1-Smad and JAK-STAT signal transduction cascades. These findings identify IL-4Rα-mediated signaling as a promising intervention point in pulmonary fibrosis and support further investigation of dupilumab as a candidate therapy for fibrotic lung diseases.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"204 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}