Respiratory Research最新文献

{"title":"Atypical mesenchyme in congenital pulmonary airways malformation: a promising new focus.","authors":"Pascal Azar, Yannick Avila, Anita Hiltbrunner, Christophe Delacourt, Anne-Laure Rougemont, Isabelle Vidal, Marie-Luce Bochaton-Piallat, Isabelle Ruchonnet-Metrailler","doi":"10.1186/s12931-025-03332-4","DOIUrl":"https://doi.org/10.1186/s12931-025-03332-4","url":null,"abstract":"<p><strong>Background: </strong>Congenital pulmonary airways malformations (CPAM) belong to a group of rare congenital lung anomalies whose pathological origin is still mostly unknown. The current research project aims to study the possible role of the underlying mesenchyme in CPAM pathophysiology by comparing data from fetal tissue and healthy lung with CPAM.</p><p><strong>Methods: </strong>Tissue samples from CPAM patients and healthy adjacent parts were collected during planned surgical resections. Fetal lung tissue obtained from abortions was also used. The mesenchymal parts of pathological, healthy and fetal lung tissues were analyzed using quantitative proteomic, bulk RNA sequencing and multiplex immunohistochemistry to identify the difference in genes and proteins expressed in CPAM.</p><p><strong>Results: </strong>When compared to healthy adjacent lung tissue, transcriptomic data of CPAM tissue highlighted downregulation of genes implicated in the transforming-growth factor-β and immune-related signaling pathways. Conversely, epithelial-mesenchymal transition genes were upregulated in CPAM, suggesting an abnormal branching associated with abnormal mesenchyme. Quantitative proteomic results showed that the expression of various proteins implicated in muscle differentiation, such as desmin, calponin1 and α-smooth muscle actin, were decreased in CPAM compared to healthy adjacent lung. Multiplex immunostaining confirmed these results with a more significant difference for CPAM type 1 compared to healthy adjacent tissue or to fetal lung. Several pathways known to be crucial in epithelial proliferation, differentiation or branching such as PI3K-AKT-mTOR pathway were dampened.</p><p><strong>Conclusion: </strong>Our study reveals the presence of abnormal mesenchyme and muscle in and surrounding cystic tissue. Despite normal lung function during pediatric follow-up, the atypical mesenchyme with possible impaired epithelial-mesenchymal transition could potentially contribute to the development of late adult pathologies such as chronic obstructive pulmonary disease or lung tumors and should be assessed accordingly.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"262"},"PeriodicalIF":5.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975855","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":"Pulmonary and neurobehavioral efficacies of AVR-48, a TLR4 modulator, in a preterm lamb model of bronchopulmonary dysplasia.","authors":"Suchismita Acharya, David Riley, Adam Dayoub, Eesha Acharya, Andrew Rebentisch, Maggie Simmons, Sydney Bowen, Joanna Beachy, Elaine Dawson, Emily Major, Michael Borton, Jakob Van Boerum, Mar Janna Dahl, Vineet Bhandari, Suhas G Kallapur, Dale J Christensen, Kurt H Albertine","doi":"10.1186/s12931-025-03337-z","DOIUrl":"https://doi.org/10.1186/s12931-025-03337-z","url":null,"abstract":"<p><strong>Background: </strong>AVR-48 is a small molecule that modulates toll-like receptor 4 (TLR4) activity, changing macrophage phenotype from pro- to anti-inflammatory and increasing the anti-inflammatory cytokine IL-10. Treatment with AVR-48 via intraperitoneal injection effectively prevented hyperoxia-induced pathology in a newborn mouse model of bronchopulmonary dysplasia (BPD).</p><p><strong>Objective: </strong>To evaluate the early and late-stage efficacy of AVR-48 in preventing BPD and associated complications in a mechanically ventilated preterm lamb model that mimics human BPD.</p><p><strong>Design and methods: </strong>Preterm lambs were delivered at 128 days (d; about 85% gestation) following the administration of maternal antenatal steroids, intubated, given surfactant, and managed with invasive mechanical ventilation for seven days, followed by three days of noninvasive respiratory support. Either vehicle or AVR-48 was administered to the preterm lambs via intravenous bolus infusion six hours after birth and continued for seven days (every 12 h). Equivalent early (10 d) and late-stage (90 d) endpoints were selected to model human clinical outcomes at 36 weeks and 12-18 months post-natal age, respectively. Survival, growth, pulmonary pathology, respiratory system function, cardiovascular function, and neurobehavioral parameters were evaluated at both early and late stages. The forced oscillation technique was used to assess the resistance and reactance of the respiratory system. Blood samples were collected to determine the pharmacokinetics of AVR-48 and to measure levels of inflammatory and anti-inflammatory cytokines. Lung homogenates were analyzed for TLR4, cleaved caspase-3, p53, PCNA, VEGF, VEGF-R2, and other biomarkers using immunoblot and RT-PCR.</p><p><strong>Results: </strong>Compared to the vehicle, AVR-48 at 3.0 mg/kg significantly reduced respiratory severity scores, increased lung compliance, decreased lung resistance, and preserved alveolar formation without inflammation or fibrosis at 10d. In the 90d study, AVR-48 improved respiratory system mechanics, alveolar formation, and neurodevelopmental outcomes compared to vehicle controls. A decrease in the pro-inflammatory cytokines (IL-1β, IL-6) and an increase in the anti-inflammatory cytokine IL-10 in lamb plasma collected between days 1 and 10 were noted. Lung tissue showed decreased TLR4 protein and inflammatory cytokines at 90d.</p><p><strong>Conclusion: </strong>AVR-48 is a promising novel candidate drug for further development in preventing BPD and has the potential to reduce the associated adverse neurodevelopmental sequelae in preterm neonates.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"261"},"PeriodicalIF":5.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976021","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":"Pleural fluid biomarkers to predict response to pleurodesis or indwelling pleural catheter for malignant pleural effusion: still a long way to go.","authors":"Katrine Fjaellegaard, Sina Ahmadzai, José M Porcel, Federico Mei, Jane A Shaw, Uffe Bodtger","doi":"10.1186/s12931-025-03288-5","DOIUrl":"https://doi.org/10.1186/s12931-025-03288-5","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"259"},"PeriodicalIF":5.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976039","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":"Correction: Trends in initial pharmacological COPD treatment in primary care (2010-2021): a population-based study using the PHARMO Data Network.","authors":"Guilherme Rodrigues, Joana Antão, Qichen Deng, Brenda N Baak, Alda Marques, Frits M E Franssen, Martijn A Spruit","doi":"10.1186/s12931-025-03341-3","DOIUrl":"https://doi.org/10.1186/s12931-025-03341-3","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"260"},"PeriodicalIF":5.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975930","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":"Correction: Effect of different CPAP levels on ultrasound-assessed lung aeration and gas exchange in neonates.","authors":"Victor Sartorius, Barbara Loi, Laura Vivalda, Giulia Regiroli, Sofia De La Rubia-Ortega, Lucilla Pezza, Manon Midavaine, Shivani Shankar-Aguilera, Rafik Ben-Ammar, Daniele De Luca","doi":"10.1186/s12931-025-03333-3","DOIUrl":"10.1186/s12931-025-03333-3","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"258"},"PeriodicalIF":5.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795964","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":"Reply to \"matters arising: \"local and systemic effects in e-cigarette users compared to cigarette smokers, dual users, and non-smokers\".","authors":"Shanzina Sompa, Lena Palmberg","doi":"10.1186/s12931-025-03329-z","DOIUrl":"10.1186/s12931-025-03329-z","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"257"},"PeriodicalIF":5.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790460","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":"Caution required in interpreting inflammatory effects of e-cigarette use: correcting methodological and conceptual weaknesses.","authors":"Lucia Spicuzza, Francesco Pennisi, Davide Campagna","doi":"10.1186/s12931-025-03328-0","DOIUrl":"10.1186/s12931-025-03328-0","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"256"},"PeriodicalIF":5.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785773","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":"The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease.","authors":"Ming Dong, Gaolei Hu, Xi Chen, Lingling Zhang, Yuxiao Zhang, Yanting Fang, Shuilin Liao, Yukai Wang, Qian Li, Peiyan Zheng, Bingpeng Guo, Tinpou Lai, Qun Luo, Huimin Huang, Qian Han, Baoqing Sun","doi":"10.1186/s12931-025-03326-2","DOIUrl":"10.1186/s12931-025-03326-2","url":null,"abstract":"<p><strong>Background: </strong>Exosome liquid biopsies might be a good supplement for early diagnosis of interstitial lung disease (ILD), especially those challenging cases such as connective tissue disease-ILD (CTD-ILD).</p><p><strong>Methods: </strong>We developed a circulating exosomal proteomic signature to identify novel biomarkers of ILDs combined with high-resolution CT (HRCT) examination and a new method that makes exosome testing clinically feasible. Blood-derived exosomes were extracted and characterized using a centrifugal microfluidic disc system (Exo-CMDS)-based chemiluminescence immunoassay before being subjected to proteomic analysis by mass spectrometry. Significantly differentially expressed proteins (DEPs) were identified and validated in > 600 clinical samples (collected at three hospitals) by comparing the ILD and disease/healthy control groups. Multivariable logistic regression (LR) analysis was implemented to test the diagnostic performance of the selected biomarkers either alone or in combination.</p><p><strong>Results: </strong>Candidate biomarkers KL-6, CAPN2, SP-B were selected from the top DEPs. An LR model that combined exosomal KL-6/CAPN2/SP-B levels performed well in both the discovery (AUC = 0.987, 95%CI = 0.975-0.998) and validation (AUC = 0.936, 95%CI = 0.911-0.960) sets. The LR model based on the three biomarkers exhibited markedly better diagnostic performance (AUC = 0.880, 95%CI = 0.834-0.925) in serum-KL-6-negative ILD, than the conventional serum-KL-6-based method and could also accurately diagnose connective tissue disease associated-ILD (CTD-ILD) in the context of CTD.</p><p><strong>Conclusion: </strong>The circulating exosomal protein detection system used in this study represents a valuable tool for identifying promising exosomal biomarkers for ILD and holds promise for improving the diagnosis and prognosis of patients with ILD in the future.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"255"},"PeriodicalIF":5.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765709","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":"Extracellular vesicles from bronchoalveolar lavage fluid provide insights into the inhaled corticosteroids treatment response in COPD.","authors":"Jiahua Fang, Justina C Wolters, Karim Rafie, Changshuo Wang, Sabine Bartel, Maarten van den Berge, Machteld N Hylkema","doi":"10.1186/s12931-025-03330-6","DOIUrl":"10.1186/s12931-025-03330-6","url":null,"abstract":"<p><strong>Background: </strong>Inhaled corticosteroids (ICS) are widely used to treat chronic obstructive pulmonary disease (COPD), but treatment responses vary among individuals. Identifying biomarkers that can improve our understanding of disease mechanisms and help predict ICS responsiveness is urgently needed. Extracellular vesicles (EVs), key mediators of intercellular communication, may offer novel insights and serve as a potential biomarker source.</p><p><strong>Methods: </strong>34 COPD patients participated were treated for 6 months with either placebo or ICS (500 µg fluticasone ± 50 µg salmeterol). Lung function (FEV1% predicted, FEV1/FVC%, and RV/TLC% predicted) was assessed at baseline and 6 months. Proteins from BALF-derived EVs were analyzed at both time points using label-free quantitative proteomics. Weighted gene co-expression network analysis was applied to identify EV protein modules associated with lung function (n = 24) at baseline. Baseline EV protein levels were further correlated with changes in lung function after ICS treatment. Statistical analyses were performed in R (v4.3.2), using Mann-Whitney U (two groups) or Kruskal-Wallis with Dunn's post hoc (multiple groups), Student's t-test for paired data, and Pearson correlation. Statistical significance was set at p < 0.05.</p><p><strong>Results: </strong>Thirteen EV protein co-expression modules were identified. Each module was assigned a color-based label. The red and salmon modules showed significant associations with baseline lung function: FEV1% predicted (r = - 0.46, p = 0.02) and FEV1/FVC% (r = 0.43, p = 0.04), respectively. Furthermore, 25 proteins from the red and 11 from the salmon module were significantly correlated with lung function improvements post-ICS treatment. Members of the cystatin (CST) superfamily, particularly CST1, showed strong correlations with ΔFEV1% predicted (r = 0.61, p = 0.003) and ΔFEV1/FVC% (r = 0.46, p = 0.035). These proteins also exhibited contrasting expression patterns between ICS responders and non-responders, suggesting a potential role in treatment sensitivity and links to type 2 inflammation.</p><p><strong>Conclusions: </strong>Our findings highlight the potential of BALF-derived EVs as a biomarker source for predicting ICS responsiveness in COPD. The CST family, especially CST1, potentially serves as a valuable indicator for identifying patients who are more likely to benefit from ICS treatment.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT00158847, pre-registered April 2000.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"254"},"PeriodicalIF":5.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754948","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":"Respiratory microphysiological system in respiratory research: recent advances and future prospects.","authors":"Jiaxiang Yin, Zirong Bi, Tiankai Dai, Xiaoyue Zhu, Tao Xu, Huisheng Liu","doi":"10.1186/s12931-025-03327-1","DOIUrl":"10.1186/s12931-025-03327-1","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"253"},"PeriodicalIF":5.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718921","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}