Respiratory Research最新文献

{"title":"PPP2R2C promotes aerobic glycolysis and mediates pemetrexed resistance in lung adenocarcinomas by upregulating TCP1-dependent protein folding of glycolytic enzymes.","authors":"Jia Chen, Xiaoshan Wang, Zhengyang Wang, Gang Li, Fei Han","doi":"10.1186/s12931-026-03681-8","DOIUrl":"https://doi.org/10.1186/s12931-026-03681-8","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) remains lethal primarily due to its tendency for early metastasis and the universal development of chemotherapy resistance. The results of this study delineate a coherent signaling axis, originating from the upregulation of PPP2R2C expression to metabolic reprogramming, which ultimately influences the malignant progression and chemotherapy resistance of LUAD.</p><p><strong>Methods: </strong>GEPIA analysis was used to evaluate PPP2R2C expression in NSCLC. Following shRNA-mediated knockdown, cell proliferation, migration, apoptosis, and glycolytic activity were assessed in NCI-H1299 and A549 cells. Subcutaneous tumor formation was evaluated four weeks after injection of LV-shPPP2R2C or control vector, followed by H&E staining and immunohistochemical analysis of PPP2R2C and Ki67.</p><p><strong>Results: </strong>Clinical analysis shows that PPP2R2C is highly expressed in LUAD and is associated with poor prognosis, lymph node metastasis, and advanced disease stage. In vitro knockdown of PPP2R2C suppresses proliferation and migration and promotes apoptosis. Mechanistically, PPP2R2C drives the Warburg effect by upregulating the molecular chaperone TCP1 to ensure proper folding of glycolytic enzymes. Blocking TCP1 or glycolysis (with 2-DG) reverses PPP2R2C-mediated survival advantage and pemetrexed resistance. In vivo experiments confirm that knocking down PPP2R2C or TCP1 similarly inhibits tumor growth and restores chemotherapy sensitivity.</p><p><strong>Conclusions: </strong>In summary, the results elucidate a novel mechanism whereby PPP2R2C enhances glycolysis by regulating TCP1-dependent protein refolding, thereby driving LUAD progression and chemoresistance. Thus, this study establishes a strong rationale for targeting this pathway as a potential therapeutic approach.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473922","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":"A USP15/KRT17-associated 13-gene prognostic cluster and functional validation in EGFR-mutant lung adenocarcinoma.","authors":"Jiamin Huang, Yi Huang, Qi Yuan, Aiwei Tang, Minzhe Su, Yuanyuan Li, Zhen Gan, Xiuxiu Yang, Junyi Song, Yaokai Ye, Qing Xie, Liyun Huo, Runmin Li, Miaoling Tang, Rong Lian, Junchao Cai, Tianyu Tao","doi":"10.1186/s12931-026-03819-8","DOIUrl":"https://doi.org/10.1186/s12931-026-03819-8","url":null,"abstract":"<p><strong>Background: </strong>EGFR-mutant lung adenocarcinoma (LUAD) exhibits significant prognostic heterogeneity despite the efficacy of tyrosine kinase inhibitors. To uncover the transcriptomic markers of rapid disease progression, we integrated clinical and transcriptomic data to develop robust prognostic biomarkers for risk stratification.</p><p><strong>Methods: </strong>We utilized ensemble machine learning algorithms, including Random Survival Forest and XGBoost, to analyze transcriptomic data from 293 patients with EGFR-mutant LUAD. Single-cell transcriptomic analysis combined with copy number variation (CNV) profiling was employed to assess the cellular distribution and tumor epithelial contribution of the identified prognostic signature. The functional effects of the candidate biomarkers, USP15 and KRT17, and their dynamic regulation by oncogenic EGFR signaling were experimentally validated in EGFR-mutant cell lines using siRNA knockdown, pharmacological blockade (osimertinib), and gain-of-function assays.</p><p><strong>Results: </strong>The optimized XGBoost model identified a 13-gene cluster with strong predictive performance (C-index = 0.863), which was independently validated in an external cohort (log-rank P = 0.0117; 1-year AUC = 0.698). Single-cell transcriptomic analysis demonstrated that the detectable 11-gene subset exhibited a mixed tumor-microenvironment distribution, including expression within CNV-defined malignant epithelial cells. Functional experiments further demonstrated that USP15 and KRT17 promote tumor cell proliferation, clonogenic growth, and migration. Moreover, the expression of both genes was responsive to downstream EGFR signaling. Collectively, these findings establish a robust 13-gene prognostic gene cluster with a mixed cellular origin and identify USP15- and KRT17-associated biology as a promising direction for future mechanistic investigation in EGFR-mutant LUAD.</p><p><strong>Conclusions: </strong>We identify a 13-gene prognostic cluster associated with poor survival in EGFR-mutant LUAD. These findings position the EGFR-regulated USP15/KRT17 axis as a novel framework for patient risk stratification, with potential implications for guiding targeted therapeutic strategies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457431","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":"Glycosylation-related gene risk model and functional validation of OSTC and TUBA1C in lung adenocarcinoma.","authors":"Xinyu Zhang, Zhengjie Zhou, Xiaofu Lian, Shuo Ma, Huili Chen, Feiyue Zhang, Qi Zhang, Xiangyi Zhang, Shengping Min, Chaoqun Lian","doi":"10.1186/s12931-026-03817-w","DOIUrl":"https://doi.org/10.1186/s12931-026-03817-w","url":null,"abstract":"<p><strong>Introduction: </strong>OSTC and TUBA1C drive the malignant progression of lung adenocarcinoma (LUAD) through the modulation of N-glycosylation and the PI3K/AKT signaling pathway; Silencing these two genes markedly suppresses the malignant phenotypes of tumor cells, thereby identifying them as promising novel candidate targets for LUAD diagnosis and therapeutic intervention.</p><p><strong>Methods: </strong>This study integrated multi-omics data from TCGA and GEO, constructed a risk model (GPRS) for LUAD using 10 machine learning algorithms based on a glycosylation gene set (GRGs). Prognosis was evaluated using Cox regression and survival plots, and analyses of gene function, the microenvironment, and drug sensitivity were conducted. Gene distribution was characterized using single-cell and spatial transcriptomics, and in vitro experiments validated the effects of OSTC and TUBA1C on the function of LUAD cells.</p><p><strong>Results: </strong>This study screened 134 GRGs to construct an 18-gene risk model, which showed high predictive precision in the TCGA-LUAD dataset (1-, 3-, and 5-year AUCs ranging from 0.966 to 0.982). The high-risk group displayed significant enrichment of the PI3K/AKT pathway, had a low immune score, and was sensitive to EGFR inhibitors; Bcl-2 inhibitors showed significant efficacy in the low-risk group. Single-cell profiling revealed high expression of OSTC and TUBA1C in the course of tumor progression. In vitro experiments confirmed that the knockdown of these two genes impairs LUAD cell proliferation and migration and triggers apoptosis, a mechanism correlated with decreased PI3K/AKT phosphorylation levels.</p><p><strong>Conclusion: </strong>This study identifies OSTC and TUBA1C as glycosylation-related oncogenes that drive LUAD progression via the PI3K/AKT pathway. The GPRS, derived from a multi-omics machine learning pipeline, serves as a discovery tool that captures the prognostic significance of these genes and reflects LUAD metabolic features, immune status, and drug responsiveness. Together, these findings provide mechanistic insights and candidate targets for precision therapy in LUAD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473761","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":"Association of PM_2.5 chemical components with metabolome and peak expiratory flow in patients with stable COPD: a panel study.","authors":"Jiachen Li, Lirong Liang, Yutong Samuel Cai, Di Zhang, Yong Luo, Zhaohui Tong","doi":"10.1186/s12931-026-03812-1","DOIUrl":"https://doi.org/10.1186/s12931-026-03812-1","url":null,"abstract":"<p><strong>Objective: </strong>The component‑specific toxicity of fine particulate matter (PM_2.5) and the underlying metabolic pathways driving airflow impairment in chronic obstructive pulmonary disease (COPD) remain unclear. We evaluated how specific PM_2.5 constituents alter circulating metabolites and mediate short‑term changes in peak expiratory flow (PEF) among COPD patients.</p><p><strong>Methods: </strong>A panel study was conducted in 32 patients with stable COPD in Beijing (2018-2019). Participants were followed-up across four seasons, yielding 3363 daily PEF measurements and 208 serum samples for untargeted metabolomics. PM_2.5 components concentrations were obtained from a high-resolution (1 km) dataset integrating ground observations, satellite retrievals, and model simulations. Linear mixed-effects models were used to estimate the associations between PM_2.5 components and PEF, and a meet-in-the-middle strategy was adopted to identify mediating metabolites and pathways.</p><p><strong>Results: </strong>PEF declines were associated with interquartile range increase in several PM_2.5 components (lag0-7 days moving average), most notably for black carbon [-5.88 (-8.76 ~ -3.01) L/min] and sulfate [-4.78 (-8.82 ~ -0.73) L/min]. Metabolomic analysis identified 12 metabolites significantly linked to PEF (q < 0.05). Pathway enrichment highlighted urea cycle/amino group metabolism (P = 0.041) and bile acid biosynthesis (P = 0.012) as key biological response routes. Five metabolites were identified as mediators of the associations between PM_2.5 components and PEF, notably Nb-arachidoyltryptamine and 6-nitrochrysene.</p><p><strong>Conclusion: </strong>These findings highlight black carbon and sulfate as primary drivers of PM_2.5-related lung function impairment in COPD patients, likely acting through systemic metabolic perturbations. Our study supports targeted emission controls and suggests metabolic profiling as a potential approach for targeted prevention in vulnerable populations.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457511","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":"Systems-level insights into bronchopulmonary dysplasia from meta-analysis of genome-scale studies.","authors":"Chris Happs, Prerna Khanna, Charlotte Scoynes, Nelly Muriungi, Akira J T Alexander, Josh A Rogers, Elizabeth Lake, Maximilian Pickup, Nicholas Parkinson, Jonathan E Millar, J Kenneth Baillie, Sara Clohisey Hendry","doi":"10.1186/s12931-026-03787-z","DOIUrl":"https://doi.org/10.1186/s12931-026-03787-z","url":null,"abstract":"<p><strong>Background: </strong>Despite marked improvements in survival following preterm birth, the incidence of bronchopulmonary dysplasia (BPD) remains the most prevalent complication of prematurity and carries the risk of long-term morbidity. Characterising the cellular and molecular mechanisms driving disease progression is critical for informing clinical management and improving outcomes. To this end, we conducted a meta-analysis of genome-scale studies to identify molecular pathways implicated in BPD progression in both human cohorts and animal models.</p><p><strong>Methods: </strong>Gene lists associated with BPD in humans, and in rodent models, were extracted from systematically identified genome-scale studies. These gene lists were subsequently analysed using the meta-analysis by information content (MAIC) algorithm, which integrates multiple datasets to generate a single aggregated, ranked gene list based on the cumulative strength of evidence for each gene. Comparative analyses were then performed between the human and rodent BPD datasets, as well as between the human BPD dataset and our previously generated Acute Respiratory Distress Syndrome MAIC dataset.</p><p><strong>Results: </strong>Across all analyses, a consistent enrichment of genes involved in leukocyte-mediated antigen presentation and lymphocyte development and activation was observed, suggesting a shift from acute innate immune injury toward a more sustained lymphoid-driven inflammatory process during BPD progression. Comparative analyses revealed limited overlap between BPD and ARDS gene sets, suggesting divergent disease mechanisms, while still highlighting shared immune activation pathways. Human-rodent comparisons showed divergence in tissue remodelling signatures, likely reflecting differences in sample sources, yet converged on key conserved signals such as CD3E and IL1R2, implicating common inflammatory regulatory mechanisms.</p><p><strong>Conclusions: </strong>MAIC effectively identifies conserved molecular signatures in BPD highlighting lymphoid lineage signatures that are not readily apparent in the primary data. These signatures offer insights relevant to immune-modulatory therapeutic strategies, highlighting key processes involved in antigen presentation and modulation of T-cell activation and development during the progression of Bronchopulmonary Dysplasia.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457466","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":"Biomarker profiles in idiopathic and progressive pulmonary fibrosis after LPA₁ antagonism: exploratory analysis from a phase 2 trial of admilparant.","authors":"Toby M Maher, Naftali Kaminski, Fang Wang, Manuela Funke-Chambour, Chun Wu, Yanhua Hu, Supriya Sharma, Peter Schafer, Matthew Schaller, Gerald Horan","doi":"10.1186/s12931-026-03809-w","DOIUrl":"https://doi.org/10.1186/s12931-026-03809-w","url":null,"abstract":"<p><strong>Background: </strong>In a phase 2 trial (NCT04308681), treatment with admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 (LPA₁) antagonist, reduced lung function decline in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). In this exploratory analysis, we evaluated post-treatment changes in circulating biomarkers of lung fibrosis to elucidate mechanisms of admilparant action.</p><p><strong>Methods: </strong>Patients with IPF or PPF were randomized 1:1:1 to receive twice-daily admilparant (30 or 60 mg) or placebo for 26 weeks; background antifibrotics were allowed. The IPF and PPF cohorts were analyzed separately. Changes from baseline (CfB) in serum proteins associated with epithelial injury, inflammation, and fibrosis were measured by quantitative immunoassays at 4, 12, and 26 weeks, and compared between patients who received admilparant versus placebo. Pharmacodynamic biomarker changes were evaluated by clinical response status at week 26. Plasma samples from patients with IPF were assessed post hoc by SomaScan v4.1 proteomics assay. Statistical evaluations used linear mixed-effects models.</p><p><strong>Results: </strong>In the IPF cohort (n=276), nine serum proteins showed significant CfB (p<0.05) at week 26 in patients treated with 60-mg admilparant versus placebo, including increased adiponectin, MMIF, CD163, CEA, and ENRAGE, and decreased markers of epithelial injury and fibrosis (CA-125/MUC16, MMP-7, TN-C, PRO-FIB). In the PPF cohort (n=116), significant differences at week 26 (p<0.05) were observed for 11 serum proteins, including increased CEA and decreased periostin, IL6Rβ, CD163, KIM-1, multiple inflammatory markers (YKL-40, VCAM-1, PECAM-1, ferritin), and collagen degradation markers (C3M and C4M). Two serum proteins, CA-125 and TN-C, showed significantly greater CfB (p<0.05) in responders compared with non-responders in the IPF cohort. Plasma proteomic analysis identified differential expression (adjusted p<0.1) of adiponectin, CKMT1A, ANGPTL3, PDCD1LG2, and IGFBP6 at week 26 in patients with IPF treated with 60-mg admilparant versus placebo.</p><p><strong>Conclusions: </strong>Treatment with 60-mg admilparant improved circulating biomarkers associated with epithelial injury and fibrosis in IPF, and with inflammation, fibrosis, and collagen degradation in PPF. Proteomic analysis identified additional biomarkers associated with mitochondrial and metabolic pathways in IPF. These findings expand our understanding of potential mechanisms of LPA₁ antagonism with admilparant and identify biomarkers that may help evaluate treatment response and disease activity.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457463","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":"Impact of benralizumab on airway structure/function in severe eosinophilic asthma.","authors":"Donna D Carstens, Wilfried De Backer, Kirsty Rhodes, Patrick Muchmore, Benjamin R Lavon, Sze Yan Ernestine Chung, Robert Fogel, Frank Trudo, Reynold Panettieri","doi":"10.1186/s12931-026-03742-y","DOIUrl":"https://doi.org/10.1186/s12931-026-03742-y","url":null,"abstract":"<p><strong>Background: </strong>The BURAN study (ClinicalTrials.gov: NCT05552508) was a multicenter open-label study evaluating airway structure/function changes in adults with severe eosinophilic asthma (SEA) following eosinophil depletion by benralizumab. We assessed the changes in airway structure/function following treatment with benralizumab in adults with SEA.</p><p><strong>Methods: </strong>We recruited adults (18-70 years) with SEA inadequately controlled with inhaled corticosteroids plus long-acting β2-agonists. Patients received subcutaneous benralizumab 30 mg every 4 weeks (three doses total). Computed tomography scans of the lungs were analyzed using Functional Respiratory Imaging (FRI). The primary endpoint was change from baseline to Week 13 in total mucus volume at total lung capacity. Secondary endpoints included change from baseline to Week 13 in mucus plug score and airway structure/function, and correlations between change in FRI endpoints and spirometry assessments (forced expiratory volume in 1 s [FEV₁] and forced vital capacity [FVC]).</p><p><strong>Results: </strong>The primary analysis set included 39 patients (mean [standard deviation] age, 54.5 [11.4] years; 59.0% female, 92.3% White). Total mucus volume from baseline to Week 13 was significantly reduced (Δ - 0.13 mL; P = .033), with more pronounced reduction in those with ≥ 4 mucus plugs at baseline (∆ -0.18; P = .036). Similarly, mucus plug scores were significantly reduced (Δ - 11.0; P = .042). Mucus burden reduction was accompanied by lung function improvement. No significant changes from baseline were observed in air trapping, airway wall volume, specific airway volume, and lung volume. At Week 13, changes in total mucus volume (r = - .501; P < .001) and total mucus plug scores (r = - .600; P < .001) were correlated with improvements in pre-bronchodilator FEV₁ and FVC.</p><p><strong>Conclusion: </strong>Mucus burden was significantly reduced following treatment with benralizumab in patients with SEA.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID: NCT05552508 (registration date: 23 September 2022).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457476","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":"Exploring the mechanism of interleukin-24 in regulating eosinophil differentiation in chronic obstructive pulmonary disease.","authors":"Xueting Cao, Rui Li, Chenyu Lin, Bingyu Li, Zongwei Guo, Xiangrui Kong, Lina Jiang, Li Xiao","doi":"10.1186/s12931-026-03687-2","DOIUrl":"https://doi.org/10.1186/s12931-026-03687-2","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) exacerbation is a common respiratory condition, particularly when accompanied by eosinophilia, which mediates inflammatory responses that significantly impair the integrity of the airway mucosal barrier. This study aims to elucidate the roles of interleukin-24 (IL-24) and eosinophils (EOS) in COPD-associated tissue remodeling, focusing on their effects on the expression of pro-inflammatory mediators and extracellular matrix (ECM) components in pulmonary fibroblasts, as well as the underlying molecular mechanisms. Based on the differential expression of IL-24 between healthy individuals and COPD patients and its correlation with EOS, we differentiated EOL-1 cells into EOS using butyrate and established a co-culture system with pulmonary fibroblasts. Concurrently, groups of fibroblasts were stimulated with varying concentrations of IL-24 alone. The regulatory effects on pro-inflammatory mediators and ECM expression were systematically analyzed using flow cytometry, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting. Under the present experimental conditions, IL-24 treatment was associated with enhanced fibrotic responses in pulmonary fibroblasts. Furthermore, compared with butyrate treatment alone, the combination of IL-24 and butyrate further increased the differentiation rate of EOL-1 cells into EOS cells. Differentiated EOS further stimulated pulmonary fibroblasts to secrete pro-inflammatory factors IL-6 and IL-8, as well as the tissue remodeling-related factor vascular endothelial growth factor (VEGF), thereby exacerbating the fibrotic process. This study confirms that IL-24 promotes the maturation and differentiation of EOL-1 cells and can induce a fibrotic phenotypic transformation in pulmonary fibroblasts. This interaction participates in regulating inflammatory responses and tissue remodeling during COPD progression, highlighting the critical role of eosinophil-fibroblast crosstalk in the pathological mechanisms of the disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457480","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":"High prevalence of malnutrition and sarcopenia in patients with NTM pulmonary disease: results from an Italian prospective multicentre study.","authors":"Paola Faverio, Alessia Fumagalli, Giulia Tarantino, Filippo Gozzi, Stefania Cerri, Filippo Valoriani, Renata Menozzi, Valentina Conio, Francesco Rocco Bertuccio, Lucrezia Pisanu, Francesca De Simeis, Sasha Trevisan, Samuele Gaggioli, Marta Tristan Asensi, Ilaria Giangrandi, Giacomo Barzaghi, Giacomo Castiglioni, Giovanni Franco, Erica Tugnoli, Andrea Gramegna, Anna Bulfamante, Rosa Di Matteo, Carmela Corso, Alice Repossi, Maurizio Ferrarese, Letizia Marinaro, Andrea Calcagno, Sara Conti, Lorenzo Giovanni Mantovani, Fabrizio Luppi, Luigi Codecasa, Francesco Blasi, Giovanni Sotgiu, Andrea Gori, Maura Spotti, Stefano Aliberti","doi":"10.1186/s12931-026-03815-y","DOIUrl":"https://doi.org/10.1186/s12931-026-03815-y","url":null,"abstract":"<p><strong>Background: </strong>NTM pulmonary disease (NTM-PD) is frequently associated with low body mass index and weight loss, yet comprehensive nutritional evaluation at diagnosis remains limited.</p><p><strong>Methods: </strong>We conducted a multicenter observational study across eight Italian referral centers to assess nutritional status and physical performance in newly diagnosed NTM-PD patients. Assessments included anthropometry, nutritional and physical activity questionnaires, bioelectrical impedance analysis, handgrip strength, gait speed, and pulmonary function tests in order to identify nutritional phenotypes and sarcopenia according to EWGSOP2 definition.</p><p><strong>Results: </strong>69 patients (77% female, mean age 69 years) were enrolled. The majority had Mycobacterium avium complex infection (74%), and 29% had a cavitary disease. Lung function impairment was generally mild. However, physical performance was frequently reduced: 36% showed impaired gait speed and 45% reduced handgrip strength. Nutritional evaluation revealed a high burden of undernutrition: over 20% of participants were underweight, up to 40% were at risk of malnutrition or overtly malnourished according to screening tools and more than 20% already exhibited a malnourished phenotype. Sarcopenia was identified in 29% of subjects. Cavitary disease was associated with worse nutritional status and higher prevalence of severe sarcopenia. Overall, more than half of participants required nutritional intervention.</p><p><strong>Conclusion: </strong>Patients with NTM-PD at diagnosis show a high prevalence of impaired nutritional status (40% at risk of malnutrition or malnourished and requiring a nutritional intervention) and physical performance. Sarcopenia is also highly prevalent (29%) highlighting the need for dietary and physical interventions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450222","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":"Extracellular matrix remodeling modifies structural responses to ventilator-induced lung injury: a multiscale correlative imaging study.","authors":"Md Motiur Rahman Sagar, Lorenzo D'Amico, Richard T Deyhle, Ruth Meyer, Luca Fardin, Irma Mahmutovic Persson, Jose Luis Cercos-Pita, Gaetano Perchiazzi, Sarah Köster, Claudia V Benke, Frauke Alves, Giuliana Tromba, Lars E Olsson, Sam Bayat, Christian Dullin","doi":"10.1186/s12931-026-03807-y","DOIUrl":"10.1186/s12931-026-03807-y","url":null,"abstract":"<p><strong>Background: </strong>Mechanical ventilation (MV) can induce or exacerbate ventilator-induced lung injury (VILI), particularly in mechanically heterogeneous lungs with pre-existing injury.</p><p><strong>Methods: </strong>We investigated VILI in a rat model of bleomycin-induced lung injury and compared it with healthy controls using a combined in-vivo and ex-vivo imaging approach. Previously acquired in-vivo data from four-dimensional (4D) phase-contrast synchrotron micro-computed tomography (micro-CT) and forced oscillation measurements showed increased lung elastance and reduced local acinar deformation in bleomycin-induced injured lungs at baseline and after injurious MV. To identify structural and mechanical correlates, we performed automated three-dimensional (3D) pore analysis and atomic force microscopy (AFM) on formalin-fixed, paraffin-embedded lung tissue, complemented by histology and spatial co-registration.</p><p><strong>Results: </strong>Ex-vivo analysis revealed pronounced airspace enlargement after both injurious MV of healthy lungs, and in bleomycin-injured lungs with inflammation and early fibrotic changes, with the strongest cumulative effect in combined bleomycin and VILI. AFM demonstrated region-specific mechanical responses, and correlation analyses linked pore geometry and nanoscale stiffness to in-vivo lung mechanics. Spatial analysis further showed co-localization of VILI-associated airspace damage with injured regions.</p><p><strong>Conclusions: </strong>Extracellular matrix remodelling modifies the lung's response to injurious mechanical ventilation, with VILI-associated airspace damage preferentially co-localising with regions of pre-existing matrix injury. This multiscale correlative approach provides mechanistic insight into the interplay between lung injury and VILI and informs ventilation strategies in structurally altered lungs.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438666","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}