Respiratory Research最新文献

{"title":"YAP as a potential therapeutic target for myofibroblast formation in asthma.","authors":"Yanrong Guo, Yuran Zhou, Rui Wang, Yujing Lin, Huimin Lan, Yang Li, De-Yun Wang, Jinrui Dong, Kefeng Li, Yan Yan, Yongkang Qiao","doi":"10.1186/s12931-025-03115-x","DOIUrl":"10.1186/s12931-025-03115-x","url":null,"abstract":"<p><p>Myofibroblasts accumulation contributes to airway remodeling, with the mechanisms being poorly understood. It is steroid-insensitive and has not been therapeutically targeted in asthma. In this study, we explored the potential of yes-associated protein (YAP) as a therapeutic target for myofibroblasts formation in asthma, by revealing the novel role and mechanisms by which YAP activation in type II alveolar epithelial (ATII) cells promotes the fibroblast-to-myofibroblast transition in vitro and in vivo. By performing immunofluorescence staining, we showed that myofibroblasts were increased in the bronchial walls and alveolar parenchyma in clinical asthmatic and house dust mite (HDM)-induced mouse lung samples. This was accompanied by YAP overexpression and nuclear translocation in ATII cells, and connective tissue growth factor (CTGF) upregulation. In vitro, HDM or combination of rhIL-1β with rhTNF-α upregulated and activated YAP in human primary ATII cells and A549 cells, but not in the bronchial epithelial cells, BEAS-2B. This effect was mediated by F-actin polymerization and could be suppressed by pretreatment with latrunculin A but not budesonide. Inhibition of YAP/transcriptional coactivator with PDZ-binding motif (TAZ) in A549 cells by pretreatment with YAP/TAZ siRNA or verteporfin, but not budesonide, impaired the fibroblast-to-myofibroblast transition in vitro. In vivo, verteporfin partly or completely prevented HDM-induced bronchial or alveolar myofibroblast accumulation, and significantly suppressed CTGF expression and collagen deposition in mouse lungs, without profoundly affecting airway inflammation. Our results provide novel mechanistic insights into airway remodeling, and holds promise for the development of novel therapeutic strategies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"51"},"PeriodicalIF":5.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410891","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":"Neuropeptide S and its receptor aggravated asthma via TFEB dependent autophagy in bronchial epithelial cells.","authors":"Zhixu Wang, Peng Zhao, Gen Yan, Aijuan Sun, Li Xu, Jiao Li, Xiaorun Zhai, Xiangcen Liu, Tingting Mei, Yinghua Xuan, Yunjuan Nie","doi":"10.1186/s12931-025-03125-9","DOIUrl":"10.1186/s12931-025-03125-9","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a prevalent respiratory disorder with limited treatment strategy. Neuropeptide S (NPS) is a highly conserved peptide via binding to its receptor NPSR, a susceptibility gene for asthma from genomics studies. However, little is known about the role of NPS-NPSR in the pathogenesis of asthma. This study was performed to determine the effect and underlying mechanism of NPS-NPSR on asthma.</p><p><strong>Methods: </strong>NPSR knockdown was verified to affect asthma through autophagy by transcriptome sequencing and molecular biology experiments in animal models. Silencing of transcription factor EB in a bronchial epithelial cell line and validation of NPS-NPSR activation of autophagy dependent on transcription factor EB.</p><p><strong>Results: </strong>Our results showed that NPSR expression was markedly increased in asthmatic humans and mice, mainly localized in bronchial epithelial cells. Using ovalbumin (OVA) and papain-induced asthma mouse models, NPSR-deficient mice exhibited significantly alleviated asthma, with reduced small airway lesions and inflammatory infiltration compared with wild-type mice. OVA and papain promoted TFEB-mediated autophagy with increased ATG5 and LC3 II expression, and NPS effectively regulated the activation of TFEB and autophagy. In turn, specific TFEB knockdown could restore the effect of exogenous NPS and its receptor antagonist on the autophagy and cytokines secretion in bronchial epithelial cells. Furthermore, Prkcg may be the key upstream targeting of the TFEB-autophagy pathway involved in asthma.</p><p><strong>Conclusions: </strong>NPS-NPSR exacerbated asthma by regulating the TFEB-autophagy axis in airway epithelial injury, which may be a potential target for asthma therapy.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"50"},"PeriodicalIF":5.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392291","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":"Association of e-cigarette and cigarette use with self-reported chronic obstructive pulmonary disease (COPD): a multivariable analysis of a large United States data set.","authors":"Alicia J Burns, Alexander W Steinberg, James D Sargent, Jenny E Ozga, Zhiqun Tang, Cassandra A Stanton, Laura M Paulin","doi":"10.1186/s12931-024-03087-4","DOIUrl":"10.1186/s12931-024-03087-4","url":null,"abstract":"<p><strong>Background: </strong>Prior research has linked e-cigarette use with chronic obstructive pulmonary disease (COPD). We examined the relationship between e-cigarette use and COPD prevalence in older adults with varying cigarette use status.</p><p><strong>Methods: </strong>Data from the 2020 National Health Interview Survey were used to estimate the association between each of 9 exposure categories based on cigarette use (never, former, current) and e-cigarette use (never, former, current), with respondent-reported physician-diagnosed COPD prevalence in individuals 40 years and older (N = 22,997). Weighted multivariable analysis accounted for cigarette pack years, age of cigarette smoking onset, race, income-to-poverty ratio, rurality, gender, age, and medical comorbidities. Sensitivity of results was tested in 3 separate models with addition of years since quit cigarettes, smoking intensity and duration.</p><p><strong>Results: </strong>39.7% of individuals reported ever smoking cigarettes and 10.2% reported ever using e-cigarettes. Among individuals with ever e-cigarette use, 88.5% also reported current or former cigarette smoking. The weighted prevalence of COPD was 7.2%; Among those who reported former cigarette smoking, the highest risk of COPD prevalence compared to never cigarette/never e-cigarette use was in those currently using e-cigarettes (adjusted risk ratio (ARR) 2.82, 95% confidence interval (CI) [1.5, 5.3]). The ARR for former cigarette/current e-cigarette use was significantly larger than the ARR for former cigarette/never e-cigarette use (p < 0.002) in 3 out of 4 models; however, one model had the ARR attenuated to 1.35 (0.67, 2.76) when years since quitting smoking was added to the model. Other cigarette/e-cigarette combinations were also sensitive to how cigarette smoking history was modeled. For example, ARR for former cigarette/former e-cigarette (1.68 [1.00, 2.80] and current cigarette/former e-cigarette (2.50 [1.56,4.02]) were reduced to 1.05 (0.62, 1.77) and 1.04 (0.62, 1.75) respectively, when cigarette smoking duration was substituted for pack-years.</p><p><strong>Conclusions: </strong>Current e-cigarette use among former cigarette smokers was associated with significantly higher COPD prevalence compared to never e-cigarette use. However, COPD risk for most cigarette/e-cigarette combinations could be greatly attenuated by how cigarette smoking history was modeled, raising questions about the robustness of these associations in prior research and the possibility of reverse causality in prior cross-sectional research.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"49"},"PeriodicalIF":5.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371454","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":"One-step diagnosis of infection and lung cancer using metagenomic sequencing.","authors":"Shaoqiang Li, Yangqing Zhan, Yan Wang, Weilong Li, Xidong Wang, Haoru Wang, Wenjun Sun, Xuefang Cao, Zhengtu Li, Feng Ye","doi":"10.1186/s12931-025-03127-7","DOIUrl":"10.1186/s12931-025-03127-7","url":null,"abstract":"<p><strong>Background: </strong>Traditional detection methods face challenges in meeting the diverse clinical needs for diagnosing both lung cancer and infections within a single test. Onco-mNGS has emerged as a promising solution capable of accurately identifying infectious pathogens and tumors simultaneously. However, critical evidence is still lacking regarding its diagnostic performance in distinguishing between pulmonary infections, tumors, and non-infectious, non-tumor conditions in real clinical settings.</p><p><strong>Methods: </strong>In this study, data were gathered from 223 participants presenting symptoms of lung infection or tumor who underwent Onco-mNGS testing. Patients were categorized into four groups based on clinical diagnoses: infection, tumor, tumor with infection, and non-infection-non-tumor. Comparisons were made across different groups, subtypes, and stages of lung cancer regarding copy number variation (CNV) patterns, microbiome compositions, and clinical detection indices.</p><p><strong>Results: </strong>Compared to conventional infection testing methods, Onco-mNGS demonstrates superior infection detection performance, boasting a sensitivity of 81.82%, specificity of 72.55%, and an overall accuracy of 77.58%. In lung cancer diagnosis, Onco-mNGS showcases excellent diagnostic capabilities with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value reaching 88.46%, 100%, 91.41%, 100%, and 90.98%, respectively. In bronchoalveolar lavage fluid (BALF) samples, these values stand at 87.5%, 100%, 94.74%, 100%, and 91.67%, respectively. Notably, more abundant CNV mutation types and higher mutation rates were observed in adenocarcinoma (ADC) compared to squamous cell carcinoma (SCC). Concurrently, onco-mNGS data revealed specific enrichment of Capnocytophaga sputigeria in the ADC group and Candida parapsilosis in the SCC group. These species exhibited significant correlations with C reaction protein (CRP) and CA153 values. Furthermore, Haemophilus influenzae was enriched in the early-stage SCC group and significantly associated with CRP values.</p><p><strong>Conclusions: </strong>Onco-mNGS has exhibited exceptional efficiencies in the detection and differentiation of infection and lung cancer. This study provides a novel technological option for achieving single-step precise and swift detection of lung cancer.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"48"},"PeriodicalIF":5.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191089","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":"REDD1 mediates HDM-induced nuclear-cytoplasmic translocation and release of IL-33 in airway epithelial cells by downregulating Nrf2.","authors":"Tian Luo, Wentao Ji, Yuxin Gong, Lichang Chen, Chao Liu, Dandan Zhang, Xi Li, Yanhua Lv","doi":"10.1186/s12931-025-03119-7","DOIUrl":"10.1186/s12931-025-03119-7","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate whether REDD1 (Regulated in Development and DNA Damage Responses 1) mediates the nuclear-to-cytoplasmic translocation and release of IL-33 in airway epithelial cells induced by house dust mites (HDM).</p><p><strong>Methods: </strong>REDD1 expression levels in bronchial asthma patients were validated using public databases, followed by immunohistochemical analysis of REDD1 protein in airway epithelial cells from these patients. An asthma model was then established using HDM-induced 16HBE cell lines, with REDD1 gene knockout performed. The relationship between varying levels of REDD1 expression, Nrf2, and related inflammatory factors was assessed using Western blot and qPCR. To further investigate the role of the REDD1-Nrf2-IL-33 axis in the development of asthma, we employed Nrf2 activators and inhibitors to reassess the impact of REDD1 on IL-33.</p><p><strong>Results: </strong>At both mRNA and protein levels, we found that REDD1 was significantly overexpressed in samples from asthma patients (P < 0.05). In vitro, 24-hour exposure to HDM induced a notable nuclear-to-cytoplasmic translocation of IL-33 and increased its levels in the culture medium of 16HBE cells. In addition, HDM treatment significantly upregulated the expression of both REDD1 and Nrf2. Knockdown of REDD1 markedly suppressed HDM-induced IL-33 release and the expression of TNF-α, IL-6, and IL-1β, while enhancing Nrf2 expression. Moreover, treatment with the Nrf2 agonist curcumin inhibited HDM-induced nuclear-to-cytoplasmic translocation and extracellular secretion of IL-33, whereas the opposite effect was observed when using the Nrf2 antagonist ML385.</p><p><strong>Conclusion: </strong>This study reveals the crucial regulatory role of the REDD1-Nrf2-IL-33 axis in the pathological process of bronchial asthma. REDD1 modulates the expression of IL-33 and other inflammatory factors through the Nrf2 signaling pathway, thereby influencing the onset and progression of asthma.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"47"},"PeriodicalIF":5.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076056","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":"Targeting BRD4 ameliorates experimental emphysema by disrupting super-enhancer in polarized alveolar macrophage.","authors":"Difei Li, Xing Shi, Yuqiong Yang, Yao Deng, Dandan Chen, Shuyu Chen, Jinyong Wang, Guanxi Wen, Zhenyu Liang, Fengyan Wang, Jiaqi Gao, Yuanyuan Liu, Danna Wang, Ruifang Liang, Haizhao Xu, Rongchang Chen, Shanze Chen, Lingwei Wang","doi":"10.1186/s12931-025-03120-0","DOIUrl":"10.1186/s12931-025-03120-0","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a progressive chronic lung disease characterized by chronic airway inflammation and emphysema. Macrophage polarization plays an important role in COPD pathogenesis by secreting inflammatory mediators. Bromodomain-containing protein 4 (BRD4), an epigenetic reader that specifically binds to histones, plays a crucial role in inflammatory diseases by regulating macrophage polarization. Herein, we attempted to examine the hypothesis that modulating alveolar macrophage polarization via BRD4 inhibitors might has a potential for COPD treatment.</p><p><strong>Methods: </strong>We firstly analyzed BRD4 expression and its correlation with clinical parameters and macrophage polarization markers in sputum transcriptomes from 94 COPD patients and 36 healthy individuals. In vivo, BRD4 inhibitor JQ1 and degrader ARV-825 were intraperitoneally administrated into emphysema mice to assess their effects on lung emphysema and inflammation. In vitro, RNA-seq and CUT&Tag assay of BRD4 and H3K27ac were applied for elucidating how BRD4 regulates macrophage polarization.</p><p><strong>Results: </strong>We found an increased expression of BRD4 in the induced sputum from patients with COPD and unveiled a strong correlation between BRD4 expression and clinical parameters as well as macrophage polarization. Subsequently, BRD4 inhibitor JQ1 and degrader ARV-825 significantly mitigated emphysema and airway inflammation along with better protection of lung function in mice. BRD4 inhibition also suppressed both M1 and M2 alveolar macrophage polarization. The CUT&Tag assay of BRD4 and H3K27ac, revealed that BRD4 inhibition disrupted the super-enhancers (SEs) of IRF4 (a crucial transcription factor for M2 macrophage), and subsequently affected the expression of matrix metalloproteinase 12 (MMP12) which is vital for emphysema development.</p><p><strong>Conclusion: </strong>This study suggested that downregulation of BRD4 might suppress airway inflammation and emphysema through disrupting the SEs of IRF4 and alveolar macrophages polarization, which might be a potential target of therapeutic intervention in COPD. A diagram of the mechanism by which BRD4 mediated super-enhancer of IRF4 in M2 AMs. Graphic illustration showed targeting BRD4 in M2 polarized AMs lead to the downregulation of MMP12 expression, resulting in the amelioration of experimental emphysema by disrupting the super-enhancer of IRF4.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"46"},"PeriodicalIF":5.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076058","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":"NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome.","authors":"Vancheswaran Gopalakrishnan, Ben Sparklin, Jung Hwan Kim, Jerome Bouquet, Margaret Kehl, Tara Kenny, Christopher Morehouse, Carolina Caceres, Paul Warrener, Ventzislava A Hristova, Susan Wilson, Harini Shandilya, Arnita Barnes, Alexey Ruzin, Junmin Wang, Lisa Oberg, Bastian Angermann, Christopher McCrae, Adam Platt, Daniel Muthas, Sonja Hess, Christine Tkaczyk, Bret R Sellman, Kristoffer Ostridge, Maria G Belvisi, Tom M A Wilkinson, Karl J Staples, Antonio DiGiandomenico","doi":"10.1186/s12931-025-03113-z","DOIUrl":"10.1186/s12931-025-03113-z","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by airway obstruction and inflammation. Non-typeable Haemophilus influenzae (NTHi) lung infections are common in COPD, promoting frequent exacerbations and accelerated lung function decline. The relationship with immune responses and NTHi are poorly understood. Herein, we comprehensively characterized the respiratory microbiome and mycobiome of patients while investigating microbial dynamics and host immune changes attributable to NTHi killing activity. Mild-to-moderate COPD patients encompassing frequent and infrequent exacerbators and healthy volunteers (HV) were enrolled. Microbial composition, proteomics and NTHi killing activity was analyzed using bronchoalveolar lavage fluid (BALF). In addition, antigen-antibody titers in sera to COPD pathogens were determined using a multiplex assay. Differential abundance analysis revealed an enrichment of Actinobacteria and Bacteroidetes in the BALF of COPD and HV subjects respectively. Significant differences in the IgA titer response were observed against NTHi antigens in COPD vs. HV. Notably, there was also significantly greater killing activity against NTHi in BALF from COPD vs. HV subjects (OR = 5.64; 95% CI = 1.75-20.20; p = 0.001). Stratification of COPD patients by NTHi killing activity identified unique microbial and protein signatures wherein Firmicutes, Actinobacteria and haptoglobin were enriched in patients with killing activity. We report that differences in host immune responses and NTHi-killing activity are associated with microbiome changes in mild-to-moderate COPD. This is suggestive of a potential link between the respiratory microbiome and immune activity against NTHi in the context of COPD pathogenesis even at this disease stage.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"45"},"PeriodicalIF":5.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069118","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":"Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution.","authors":"Joyceline De Volder, Annelies Bontinck, Valerie Haelterman, Louis Boon, Guy F Joos, Guy G Brusselle, Tania Maes","doi":"10.1186/s12931-024-03082-9","DOIUrl":"10.1186/s12931-024-03082-9","url":null,"abstract":"<p><strong>Introduction: </strong>Diesel exhaust particles (DEP) have been proven to aggravate asthma pathogenesis. We previously demonstrated that concurrent exposure to house dust mite (HDM) and DEP in mice increases both eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) and also results in higher levels of neutrophil-recruiting chemokines and neutrophil extracellular trap (NET) formation compared to sole HDM, sole DEP or saline exposure. We aimed to evaluate whether treatment with anti-IL-5 can alleviate the asthmatic features in this mixed granulocytic asthma model. Moreover, we aimed to unravel whether neutrophils modulate the DEP-aggravated eosinophilic airway inflammation.</p><p><strong>Material and methods: </strong>Female C57BL6/J mice were intranasally exposed to saline or HDM and DEP for 3 weeks (subacute model). Interference with eosinophils was performed by intraperitoneal administration of anti-IL-5 (TRFK5), which neutralizes IL-5. Interference with neutrophils and neutrophil elastase was performed by intraperitoneal anti-Ly6G and sivelestat administration, respectively. Outcome parameters included eosinophils subsets (homeostatic EOS and inflammatory EOS), proinflammatory cytokines, goblet cell hyperplasia and airway hyperresponsiveness.</p><p><strong>Results: </strong>The administration of anti-IL-5 significantly decreased eosinophilic responses, affecting both inflammatory and homeostatic eosinophil subsets, upon subacute HDM + DEP exposure while BAL neutrophils, NET formation and other asthma features remained present. Neutrophils were significantly reduced after anti-Ly6G administration in BALF, lung and blood without affecting the eosinophilic inflammation upon HDM + DEP exposure. Sivelestat treatment tended to decrease BALF inflammation, including eosinophils, upon HDM + DEP exposure, but did not affect lung inflammation.</p><p><strong>Conclusion: </strong>Inhibition of IL-5 signalling, but not neutrophil interventions, significantly attenuates eosinophilic inflammation in a mouse model of mixed granulocytic asthma, elicited by air pollution exposure.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"43"},"PeriodicalIF":5.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061269","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":"Fibrosis in PCLS: comparing TGF-β and fibrotic cocktail.","authors":"Carlos Machahua, Thomas M Marti, Patrick Dorn, Manuela Funke-Chambour","doi":"10.1186/s12931-025-03110-2","DOIUrl":"10.1186/s12931-025-03110-2","url":null,"abstract":"<p><strong>Introduction: </strong>Fibrotic cocktail (FC) is a combination of pro-fibrotic and pro-inflammatory mediators that induces early fibrotic changes in organotypic lung models. We hypothesised that transforming growth factor beta 1 (TGF-β1) alone induces a pro-fibrotic effect similar to FC. Our aim was to compare the pro-fibrotic effects of TGF-β1 with FC in human precision-cut lung slices (PCLS).</p><p><strong>Methods: </strong>PCLS from \"healthy\" lung tissue of cancer patients undergoing surgery (n = 7) were incubated with TGF-β1, FC or control for 72 h. Gene expression markers for myofibroblasts differentiation, extracellular matrix (ECM), as well as TGF-β receptors were assessed (RT-qPCR). ECM proteins expression in lysates and supernatant was assessed by ELISA and immunofluorescence.</p><p><strong>Results: </strong>We found that TGF-β1 significantly increased gene expression of ACTA2, COL1A1, CCN2, and VIM compared to control but also compared to FC. FC showed a significant increase of matrix metalloproteinase (MMP) 7 and 1 compared to control, while TGF-β receptor 2 was lower after FC compared to TGF-β1 or control. FC or TGF-β1 showed similar fibronectin protein expression in lysates and supernatants, while type I collagen protein expression in lysates was significantly greater with TGF-β1 compared to control.</p><p><strong>Conclusions: </strong>Our findings show that TGF-β1 induces consistent pro-fibrotic changes in PCLS after 72 h. Compared to TGF-β1, FC treatment resulted in reduced gene expression of TGF-β receptor 2 and increased MMPs expression, potentially mitigating the early pro-fibrotic effects. Selecting specific pro-fibrotic stimuli may be preferable depending on the research question and time point of interest in lung fibrosis studies using PCLS.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"44"},"PeriodicalIF":5.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061270","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":"Comparative analysis of ambient, in-home, and personal exposures reveals associations between breathing zone pollutant levels and asthma exacerbations in high-risk children.","authors":"Camille M Moore, Jonathan Thornburg, Elizabeth A Secor, Katharine L Hamlington, Allison M Schiltz, Kristy L Freeman, Jamie L Everman, Tasha E Fingerlin, Andrew H Liu, Max A Seibold","doi":"10.1186/s12931-025-03114-y","DOIUrl":"10.1186/s12931-025-03114-y","url":null,"abstract":"<p><strong>Background: </strong>Air pollution is associated with poor asthma outcomes in children. However, most studies focus on ambient or indoor monitor pollution levels. Few studies evaluate breathing zone exposures, which may be more consequential for asthma outcomes.</p><p><strong>Methods: </strong>We measured personal exposures to NO₂, O₃, PM₁₀ and PM₁₀ constituents, including black carbon (BC), brown carbon (BrC), environmental tobacco smoke (ETS), endotoxins, and 𝛽-glucan, in a cohort of children with exacerbation-prone asthma for 72 h using wearable monitors. Personal exposures were compared to concentrations from in-home monitors in the child's bedroom and ambient EPA air quality monitoring using correlation analyses. Personal exposures were tested for association with lung function and compared between participants with and without well-controlled asthma and signs of exacerbation in the prior 60 days using censored regression with robust standard errors.</p><p><strong>Results: </strong>81 children completed 219 monitoring sessions. Personal NO₂, O₃, and PM₁₀ exposures ranged from < 2 to 99.1 parts per billion (ppb), < 1.5 to 23.3 ppb, and < 1 to 141.9 𝜇g/m³, respectively. Personal endotoxin ranged from 0.04 to 101.3 EU/m³, 𝛽-glucan from 18.5 to 1,162 pg/m³, BC from < 0.3 to 46.9 𝜇g/m³, BrC from < 0.3 to 6.1 𝜇g/m³, and ETS from < 0.3 to 56.6 𝜇g/m³. Correlations between personal and ambient PM₁₀, NO₂, and O₃ concentrations were poor, whereas personal PM₁₀ and NO₂ correlated with in-home concentrations. In-home monitoring less frequently detected BrC (Personal:79% > lower limit of detection, Home:36.8%) and ETS (Personal:83.7%, Home:4.1%) than personal exposures, and detected BC in participants without personal exposure (Personal: 26.5%, Home: 96%). Personal exposures were not significantly associated with lung function or daily asthma control. Children requiring corticosteroid treatment for asthma exacerbation within 60 days of exposure monitoring had 1.98, 2.21 and 2.04 times higher personal exposures to BrC (p < 0.001; 95% CI: 1.43-2.37), ETS (p = 0.007; 95% CI: 1.25-3.91), and endotoxin (p = 0.012; 95% CI: 1.14-3.68), respectively.</p><p><strong>Conclusions: </strong>Although in-home monitoring was correlated with personal exposure to PM₁₀ and NO₂, in-home detection of ETS and BrC was not associated with personal exposures. Personal PM₁₀ exposures in general, as well as BrC, ETS, and endotoxin levels were associated with recent childhood asthma exacerbations.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"40"},"PeriodicalIF":5.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053940","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}