Respiratory Research最新文献

{"title":"The MFGE8/integrin β3 axis mitigates experimental neutrophilic asthma by suppressing NLRP3-Caspase-1 pathway-mediated NETosis.","authors":"Shanshan Wang, Tang Kun, Zhen Tian, Mengqi Huang, Yan Fan, Boyu Li, Hongyan Zheng, Rongman Xu, Meijia Wang, Jianping Zhao, Jungang Xie","doi":"10.1186/s12931-025-03313-7","DOIUrl":"10.1186/s12931-025-03313-7","url":null,"abstract":"<p><strong>Background: </strong>Neutrophilic asthma, characterized by the relative accumulation of neutrophils in the airways, constitutes a distinct endotype of asthma resistant to corticosteroid and associated with severe and uncontrolled cases. Milk fat globule-EGF factor 8 (MFGE8) is a soluble glycoprotein functioning in phagocytosis, tissue repair, angiogenesis, and the regulation of neutrophil activity. However, the role of this glycoprotein in neutrophilic asthma has not been thoroughly investigated.</p><p><strong>Methods: </strong>MFGE8 concentrations were assessed in asthmatic patients with various endotypes. Utilizing an ovalbumin (OVA)/complete Freund's adjuvant (CFA)-induced mouse model of neutrophilic asthma, we investigated the critical roles of MFGE8 in neutrophilic asthma in MFGE8-knockout (Mfge8^-/-) mice by assessment of H&E/PAS staining, bronchoalveolar lavage (BAL) cell counting, and lung function tests. Bioinformatic analyses were conducted to determine downstream functions, and mechanistic experiments were performed on primary cultures of neutrophils isolated from the mouse's lungs. Recombinant MFGE8 was administered to the mice to evaluate its therapeutic effects.</p><p><strong>Results: </strong>Our results demonstrated that MFGE8 is expressed in neutrophils, and its protein levels are significantly reduced in the sputum supernatant of patients suffering from neutrophilic and paucigranulocytic asthma. Mfge8^-/- mice exacerbated airway neutrophil infiltration, mucus secretion, and hyperresponsiveness. Further mechanistic studies, involving gene sequencing of sputum cells and lung tissue biopsies of asthmatic patients from GEO databases, identified neutrophil extracellular traps (NETs) as the critical factor in the progression of neutrophilic asthma. MFGE8 was shown to inhibit the formation of NETs (NETosis) through interaction with integrin β3. The absence of MFGE8 or the application of integrin β3 inhibitor was found to enhance NETosis and promote the release of pro-inflammatory cytokines via NLRP3-Caspase-1 pathway. Upstream mechanism indicated that USP14 mediated the ubiquitination of MFGE8 and participated in the development of NETosis. Moreover, recombinant MFGE8 was observed to effectively mitigate neutrophilic airway inflammation.</p><p><strong>Conclusions: </strong>This study underscored the significance of the MFGE8/integrin β3 axis in ameliorating NETosis and neutrophilic airway inflammation, suggesting MFGE8 as a potential therapeutic target for neutrophilic asthma.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"229"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555447","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":"An orally bioavailable BRD4 inhibitor disrupts expansion of a pathogenic epithelial-mesenchymal niche in bleomycin-induced fibrosis.","authors":"Melissa Skibba, Zonghui Ma, Carole L Wilson, Zhiqing Liu, Haiying Chen, Bing Tian, Thomas J Harr, Lynn M Schnapp, Nathan Sandbo, Jia Zhou, Allan R Brasier","doi":"10.1186/s12931-025-03306-6","DOIUrl":"10.1186/s12931-025-03306-6","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal disease with few effective therapies available. Fibrosis is driven, in part, by cell-state transitions of epithelial progenitors within the airways that repopulate the injured alveoli. This alveolar atypia affects gas exchange and stimulates ECM production. We sought to examine the role of BRD4 signaling in progenitor expansion in bleomycin-induced lung injury.</p><p><strong>Methods: </strong>Activation of the Bromodomain-containing protein 4 (BRD4) epigenetic regulator in distinct stem cell populations was quantitated in a high-resolution scRNA-seq time course of bleomycin-induced injury, and confirmed in scRNA-seq studies in human IPF. A potent, selective, and orally bioavailable BRD4 inhibitor (BRD4i, ZL0969) was rationally designed and synthesized. The effect of BRD4i on myofibroblast transition, progenitor cell expansion and fibrosis was evaluated using a therapeutic experimental design in C57BL6/mice.</p><p><strong>Results: </strong>We find that the BRD4 pathway is rapidly induced in regenerating activated alveolar type (AT)2 cells and persists in a population of pro-fibrotic Krt8 + progenitors expressing markers of epithelial mesenchymal transition as well as senescence. To test the functional role of BRD4 activation, we administered a potent, selective, and orally bioavailable BRD4 inhibitor (BRD4i, ZL0969) with ~ 80 nM IC₅₀ to bleomycin-treated mice. BRD4i reduced myofibroblast formation and deposition of denatured ECM (collagen and laminin a1) in the alveolar space and improved disease scores. Importantly, BRD4i reduced a pathogenic population of alveolar progenitor cells expressing integrin (ITG)-A6/B4, tumor related protein 63 (Trp63) and keratin (Krt). In mice given an LD₅₀ dose of bleomycin, BRD4 inhibition significantly improved their survival and reduced markers of disease.</p><p><strong>Conclusions: </strong>These data demonstrate that inhibition of BRD4 signaling prevents expansion of myofibroblasts and expansion of a pathogenic epithelial progenitor population controlling alveolar atypia and fibrosis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"221"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555412","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":"Epidemiological characteristics of acute respiratory infectious diseases in the first year after COVID-19 pandemic in Guangdong Province, China.","authors":"Ting Hu, Yali Zhuang, Lirong Zou, Zhencui Li, Yihong Li, Yan Li, Min Kang, Aiping Deng","doi":"10.1186/s12931-025-03308-4","DOIUrl":"10.1186/s12931-025-03308-4","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"222"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555431","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":"Integrating CT radiomics and clinical features using machine learning to predict post-COVID pulmonary fibrosis.","authors":"Qianqian Zhao, Yijie Li, Chunliu Zhao, Ran Dong, Jiaxin Tian, Ze Zhang, Lin Huang, Jingwen Huang, Junhai Yan, Zhitao Yang, Jiangnan Ruan, Ping Wang, Li Yu, Jieming Qu, Min Zhou","doi":"10.1186/s12931-025-03305-7","DOIUrl":"10.1186/s12931-025-03305-7","url":null,"abstract":"<p><strong>Background: </strong>The lack of reliable biomarkers for the early detection and risk stratification of post-COVID-19 pulmonary fibrosis (PCPF) underscores the urgency advanced predictive tools. This study aimed to develop a machine learning-based predictive model integrating quantitative CT (qCT) radiomics and clinical features to assess the risk of lung fibrosis in COVID-19 patients.</p><p><strong>Methods: </strong>A total of 204 patients with confirmed COVID-19 pneumonia were included in the study. Of these, 93 patients were assigned to the development cohort (74 for training and 19 for internal validation), while 111 patients from three independent hospitals constituted the external validation cohort. Chest CT images were analyzed using qCT software. Clinical data and laboratory parameters were obtained from electronic health records. Least absolute shrinkage and selection operator (LASSO) regression with 5-fold cross-validation was used to select the most predictive features. Twelve machine learning algorithms were independently trained. Their performances were evaluated by receiver operating characteristic (ROC) curves, area under the curve (AUC) values, sensitivity, and specificity.</p><p><strong>Results: </strong>Seventy-eight features were extracted and reduced to ten features for model development. These included two qCT radiomics signatures: (1) whole lung_reticulation (%) interstitial lung disease (ILD) texture analysis, (2) interstitial lung abnormality (ILA)_Num of lung zones ≥ 5%_whole lung_ILA. Among 12 machine learning algorithms evaluated, the support vector machine (SVM) model demonstrated the best predictive performance, with AUCs of 0.836 (95% CI: 0.830-0.842) in the training cohort, 0.796 (95% CI: 0.777-0.816) in the internal validation cohort, and 0.797 (95% CI: 0.691-0.873) in the external validation cohort.</p><p><strong>Conclusions: </strong>The integration of CT radiomics, clinical and laboratory variables using machine learning provides a robust tool for predicting pulmonary fibrosis progression in COVID-19 patients, facilitating early risk assessment and intervention.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"227"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555432","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":"Role of antifibrotics in progressive pulmonary fibrosis associated to autoimmune diseases: multicenter study from NEREA registry.","authors":"Maria Asuncion Nieto, Cristina Vadillo, Olga Sanchez Pernaute, Fredeswinda Romero-Bueno, María Jesús Rodriguez-Nieto, Rosalia Laporta, Hilda Godoy, Jesús Loarce, Juan Rigual, Leticia Leon, Lydia Abasolo","doi":"10.1186/s12931-025-03311-9","DOIUrl":"10.1186/s12931-025-03311-9","url":null,"abstract":"<p><strong>Background: </strong>To assess the incidence of functional respiratory impairment in interstitial lung disease (ILD) of autoimmune origin, starting progressive pulmonary fibrosis (PPF), and to evaluate the effectiveness of antifibrotics and other variables.</p><p><strong>Methods: </strong>A longitudinal multicenter study was conducted in ILD of autoimmune origin (ILD with autoimmune rheumatic diseases, IPAF, and unclassifiable autoimmune ILD) from 2006 to 2023 and followed until September 2024 in Madrid. Patients were those enrolled in NEREA [pNEumology RhEumatology Autoinmune] registry who met PPF criteria.</p><p><strong>Main outcome: </strong>functional respiratory impairment (≥ 5% absolute decline in predicted forced vital capacity (FVC%) within a year). Pulmonary function was assessed at baseline and every 6-12 months.</p><p><strong>Independent variable: </strong>antifibrotics. Covariates: sociodemographics, clinical, other treatments. Survival techniques were used to estimate the incidence rate (IR) and [95%CI] of functional respiratory impairment, (per 100 patients-year). Cox multivariate regression models were run to examine the influence of antifibrotics and other covariates on, main outcome (results expressed as hazard ratio (HR) and [95%CI]).</p><p><strong>Results: </strong>Among 150 patients, 21 were on antifibrotics at baseline, increasing to 52 during follow-up. Functional respiratory impairment occurred in 118 patients with 292 events (IR 57.4 [51.2-64.4]). Regarding multivariate analysis: antifibrotics lowered functional respiratory impairment risk (nintedanib: HR 0.58 [0.39-0.85], pirfenidone: HR 0.68 [0.5-0.94]). Emphysema (HR 1.32 [1.04-1.68]), smoking (HR 1.40 [1.06-1.84]), and cardiovascular risk (HR 1.02 [1.02-1.63]) increased the risk.</p><p><strong>Conclusions: </strong>The rate of worsening in PPF-ILD of autoimmune origin was considerable. Both antifibrotics reduced functional respiratory impairment risk in these patients, supporting prior clinical trials. Additional risk factors were identified.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"234"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555435","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":"Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function.","authors":"Abdo Durra, Caroline Cherry, Coline Luo, Emily Hou, Andrew Frauenpreis, Arunima Purkayastha, Isabella Passamano, Sara Makanani, Kristen Castillo, Andrew Lund, Woosuk Choi, Chandani Sen, Rachana Chandran, Tammy Rickabaugh, Prashant Kaushal, Mehdi Bouhaddou, Eszter K Vladar, Brigitte N Gomperts","doi":"10.1186/s12931-025-03302-w","DOIUrl":"10.1186/s12931-025-03302-w","url":null,"abstract":"<p><p>Electronic cigarettes (e-cigs) have been introduced as a safer alternative to traditional combustible cigarettes and have been growing in popularity. E-cig e-liquids all contain the carrier compounds, vegetable glycerin (VG), propylene glycol (PG), and nicotine, together with different flavors, but the effects of inhalation of these compounds on the airway are not well understood. This study investigates the effects of e-cig exposure on primary human airway epithelial cells grown in air-liquid interface (ALI) cultures, specifically focusing on mucociliary clearance, the lung's primary host defense mechanism whereby pathogens and particles trapped by mucus are cleared by unidirectional beating by ciliated cells. We developed a microcontroller-based exposure system to reproducibly examine cellular and molecular changes in ALI cultures from e-cig exposure. Here we show heterogeneous, donor-dependent effects of different e-cig flavors on airway epithelial cells. Examining the effects of the unflavored carrier compounds common to all e-cigs, we found that ALI airway cultures exposed to PG:VG (30:70 ratio) with 5% nicotine unflavored e-cigs show a reduction in ciliary beat frequency. Moreover, using transmission electron microscopy, we identified defects in ciliary ultrastructure induced by unflavored e-cigs. Phosphoproteomic analysis uncovered changes in phosphorylation of proteins involved in cadherin and actin binding and the Rho GTPase signaling pathway, which are all involved in cytoskeletal remodeling that may influence ciliary structure and function. Altogether, our findings suggest that exposure to all e-cigs reduces mucociliary clearance.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"223"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555449","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 genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension.","authors":"Yuan He, Qiangqiang Li, Chen Zhang, Bradley B Keller, Yiping Shen, Hong Gu","doi":"10.1186/s12931-025-03249-y","DOIUrl":"10.1186/s12931-025-03249-y","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to analyze the genetic characteristics, genotype-phenotype correlation and long-term prognosis of children with idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) in a Chinese tertiary medical center.</p><p><strong>Methods: </strong>A retrospective review was conducted for all children with IPAH/HPAH treated at Beijing Anzhen Hospital over the past 15 years. All patients underwent genetic testing.</p><p><strong>Results: </strong>In total, 170 children with IPAH/HPAH were included in the study (females n = 95, 56%), with a median age of diagnosis 6.46 (3.80, 10.70) years. The study population presented with severe conditions at baseline, with 77 patients assessed as clinically high-risk. Genetic testing identified pathogenic variants in 110 patients (64%), with BMPR2, ACVRL1, and TBX4 accounted for the main causal genes. Compared to non-carriers, carriers of pathogenic variants had a higher clinical risk at baseline (54% vs. 30%, p = 0.04). After targeted therapy, carriers experienced greater clinical deterioration (p = 0.008). The overall follow-up duration was 2.68 (1.60, 4.98) years, with the survival rate at 1-, 3-, and 5-year was 93.4%, 86.7%, and 68.6%, respectively. The prognosis of carriers was significantly worse than that of non-carriers (Log-rank p < 0.001). Multivariate Cox regression analysis indicated that pathogenic variants and higher pulmonary vascular resistance index (PVRI) and were associated with a higher risk of death.</p><p><strong>Conclusion: </strong>We uncovered a higher rate of pathogenic variants in Chinese pediatric PAH, while targeted therapy improves the overall prognosis of children with PAH, patients with pathogenic variants presented with poorer response to therapy and poorer prognosis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"231"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555446","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":"Spatial transcriptomic and morpho-functional information derived from single mouse FFPE slides allows in-depth fingerprinting of lung fibrosis.","authors":"Erica Ferrini, Costanza Bonfini, Giovanna Marchese, Martina Buccardi, Matteo Zoboli, Primetta Faccioli, Nicola Sverzellati, Gino Villetti, Simone Ottonello, Maria Ravo, Franco F Stellari","doi":"10.1186/s12931-025-03300-y","DOIUrl":"10.1186/s12931-025-03300-y","url":null,"abstract":"<p><strong>Background: </strong>Transcriptome profiling by RNA sequencing (RNAseq) can provide insightful information on the molecular processes underlying disease development and progression. Although fresh tissue represents the preferred source material for RNAseq, here, we investigated the feasibility of applying RNAseq analysis to single 10 μm thick formalin-fixed and paraffin-embedded (FFPE) lung slides from the lungs of control and bleomycin (BLM)-treated mice. This approach aims at providing spatial-oriented transcriptomic data, that can be integrated with in vivo and ex vivo readouts obtained on the same sample, as a way to enhance the mechanistic information and biomarker/target discovery potential of preclinical models of fibrotic lung diseases.</p><p><strong>Methods: </strong>RNAseq analysis was conducted on individual FFPE slides from the lungs of both controls and BLM-treated mice. The results were initially validated by comparison with publicly available bulk data from fresh-frozen (FF) mouse tissues, both untreated and BLM-treated, as well as human idiopathic pulmonary fibrosis (IPF) biopsies. Unsupervised cluster analysis was performed on Differentially Expressed Genes (DEGs) distinguishing untreated and BLM-treated fibrotic lung samples. For each sample, Pearson correlation analysis was used to compare expression levels of individual gene clusters with Ashcroft Scores and aeration compartments quantitatively assessed on the matched 2D micro-CT coronal slice.</p><p><strong>Results: </strong>Over 90% of annotated genes within the FFPE dataset were shared with gene signatures retrieved from FF bulk datasets. Differentially modulated gene clusters were mainly found to be associated with extracellular matrix (ECM) organization, tissue remodeling, and inflammatory response pathways. For each sample, expression levels of individual gene clusters were highly correlated with 2D histology readouts and aeration compartments determined on matched 2D coronal slices by micro-CT imaging.</p><p><strong>Conclusions: </strong>FFPE lung tissue represents a valuable alternative to fresh tissue for RNAseq analysis, allowing to achieve a more precise, spatially oriented picture of pulmonary disease development. This approach is thus instrumental to a better characterization of the molecular changes associated to each sample. It can also contribute to a more informed interpretation of histology and micro-CT imaging data, paving the way to the identification of translationally relevant biomarkers as well as novel candidate targets for the development of more effective therapeutic interventions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"225"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555437","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 potential clinical implications of slow vital capacity in patients with idiopathic pulmonary fibrosis.","authors":"Ho Cheol Kim, Sydney Guthrie, Christopher S King, Shazia Khan, Christopher A Thomas, Vikramjit Khangoora, Steven D Nathan","doi":"10.1186/s12931-025-03304-8","DOIUrl":"10.1186/s12931-025-03304-8","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a highly variable clinical course. Forced vital capacity (FVC) is widely used as a marker of disease severity and progression, yet its variability and dependence on patient effort raise concerns regarding its reliability. Given these limitations, we investigated the clinical significance of slow vital capacity (SVC) as a potential alternative measure of lung function in IPF.In a retrospective cohort of 89 IPF patients who underwent pulmonary function testing with concomitant SVC measurements, we observed a strong correlation between FVC and SVC (r = 0.973 at baseline, r = 0.978 at follow-up). However, in 99% of cases, SVC values were equal to or exceeded FVC, and follow-up assessments revealed that FVC exhibited greater variability than SVC. Notably, patients with a decrease in SVC demonstrated worse survival outcomes, whereas FVC decline did not show the same prognostic significance. These findings suggest that SVC may provide a more stable and clinically meaningful measure of disease progression in IPF. Moreover, its less effort-dependent nature could improve reproducibility, particularly in patients with advanced diseases.Our study highlights the potential role of SVC as a valuable metric in clinical practice and as an endpoint in future IPF trials. Prospective validation of these findings could further establish SVC as a superior tool for disease monitoring and therapeutic assessment.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"228"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555448","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":"Spatial phenotyping of human bronchial airways in obstructive lung disease.","authors":"Latifa Khalfaoui, Raymond M Moore, Jose C Villasboas, Kaitlyn R Whitaker, Brenna C Novotny, Michael A Thompson, Christina M Pabelick, Y S Prakash","doi":"10.1186/s12931-025-03315-5","DOIUrl":"10.1186/s12931-025-03315-5","url":null,"abstract":"<p><p>Chronic respiratory diseases such as asthma and COPD involve interactions between multiple resident and immune cell types within bronchial airways, resulting in structural and functional changes. Thus cellular heterogeneity, arrangements and associated neighborhoods as well as interactions between cells and matrices represent intriguing yet challenging areas of study. Spatial phenotypic profiling facilitates exploration of these issues of the cellular microenvironment and identification of context-dependent cell-cell interactions. Utilizing spatial phenotyping, we interrogated the features and cellular landscape of lungs from non-asthmatics, asthmatics, and COPD in FFPE samples by developing a 10-plex antibody panel for the Akoya PhenoCycler^®-Fusion system, focused on immune cells (CD45, CD3, CD4, CD8), proliferative cells (Ki67, PCNA), angiogenesis (CD34), epithelium (E-cadherin), smooth muscle (SMA) and extracellular matrix (collagen). We performed cell segmentation on multiplex immunofluorescence images and quantified marker intensity in each cell. Phenotypes were manually identified after normalization, integration, and clustering cells across samples. The composition, cell profiling, and distribution varied significantly between asthmatics and COPD compared to non-asthmatics emphasizing disease heterogeneity. Spatially agnostic analysis revealed that the matrix cluster was more abundant in COPD compared to non-asthmatics and asthmatics, consistent with a greater role for fibrosis. However, asthmatic patients had a higher proportion of unclassified and CD8 + clusters highlighting immune responses. Co-localization analysis showed near random distribution in non-asthmatics. But strong spatial interaction between T cells and other immune or matrix cells in asthma, and a higher avoidance of smooth muscle and immune cells, and of proliferative markers in both asthmatic and COPD. Niche analysis demonstrated different recurrent cell-cell interactions in asthmatic and COPD cohorts. In COPD, the matrix cell-enriched niche was more abundant, while in asthmatics, the unclassified cell-enriched niche was more prevalent compared to non-asthmatics. These findings provide insights into differential spatial organization of cells and tissues in asthma and COPD, with immune and epithelial mechanisms suggesting active inflammation and remodeling in asthma, but fibrotic processes in COPD, and potential role for vascular processes in both conditions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"232"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555436","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}