Respiratory Research最新文献

{"title":"Transcriptome reveals the landscape of alveolar macrophages exposed to combined hypoxia with cigarette smoke extract.","authors":"Qing Liu, Yushi Zhang, Ruirui Duan, Wanheng Li, Xuan Hou, Yiling Chen, Baicun Li, Ting Yang","doi":"10.1186/s12931-025-03303-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03303-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous chronic inflammatory disease that is one of the leading causes of age-standardised deaths globally. While studies have investigated altitude's effects on COPD, none have explored alveolar macrophage homeostatic alterations during its pathogenesis at high altitudes.</p><p><strong>Methods: </strong>We constructed a high-altitude COPD model through exposure of mouse alveolar macrophages (MH-S) to hypoxia and cigarette smoke extract (CSE). Hypoxia-inducible factor (HIF) expression was quantified in MH-S cells exposed to hypoxia combined with CSE and in the control group. HIF-1α short hairpin RNA (shRNA) was added to the MH-S cells. Transcriptome was used to characterise downstream signalling pathways of HIF-1α in MH-S cells treated with hypoxia and CSE exposure. Standard molecular techniques were used to validate the RNA sequencing results.</p><p><strong>Results: </strong>HIF-1α but not HIF-2α was significantly up-regulated in MH-S cells after exposure to hypoxia and CSE. RNA-sequencing analysis of MH-S cells showed the relevant pathways downstream of HIF-1α are mainly inflammation, glycolysis, M1 polarization, extracellular matrix remodelling and angiogenesis. Validation of RNA-sequencing analysis confirmed that the above signalling pathways were abnormally up-regulated after CSE exposure, and that combined hypoxic exposure further exacerbated the induced aberrant up-regulation, which was inhibited after treatment with HIF-1α shRNA.</p><p><strong>Conclusion: </strong>Downstream HIF-1α signalling pathways drive inflammation, M1 macrophage polarization, glycolysis, extracellular matrix remodelling, and angiogenesis, potentially disrupting alveolar macrophages homeostasis during high-altitude COPD pathogenesis. This disruption may be one reason underlying the high prevalence of COPD in high-altitude regions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"241"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610137","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":"Serum γ-glutamyl transferase as a novel risk indicator for lung cancer: insights from four million Koreans.","authors":"Chiwook Chung, Kyu Na Lee, Dong Wook Shin, Sei Won Lee, Kyungdo Han","doi":"10.1186/s12931-025-03317-3","DOIUrl":"https://doi.org/10.1186/s12931-025-03317-3","url":null,"abstract":"<p><strong>Background: </strong>γ-glutamyl transferase (GGT) is associated with carcinogenesis, cancer progression, and metastasis. We investigated associations between serum GGT levels and lung cancer in the Korean general population.</p><p><strong>Methods: </strong>Individuals participating in the national health examination in 2012 were screened in the Korean National Health Information Database. Overall, 2,414,755 males and 2,032,241 females aged ≥ 20 years were followed up until December 2022. Of these individuals, 25,728 males and 11,706 females were diagnosed with lung cancer based on health-insurance claims. Serum GGT levels were categorized into quartiles Q1 (low)-Q4 (high) or deciles D1 (low)-D10 (high). Multivariate Cox proportional hazard models were used to estimate the adjusted hazard ratio (aHR) of risk factors for lung cancer.</p><p><strong>Results: </strong>In quartile categories, the highest quartile of serum GGT levels (Q4, males: ≥54 IU/L; females: ≥24 IU/L) had the highest incidence (males: 1.24/1,000 person-years; females: 0.79/1,000 person-years) and risk (males: aHR 1.37, 95% confidence interval [CI] 1.32-1.42; females: aHR 1.13, 95% CI 1.06-1.19) of lung cancer. In the decile categories, the incidence and risk of lung cancer increased with increasing serum GGT levels, resulting in the highest risk of lung cancer in the D10 category (males: ≥93 IU/L, aHR 1.57, 95% CI 1.48-1.67; females: ≥37 IU/L, aHR 1.20, 95% CI 1.10-1.31). Stratified analyses identified age (middle-aged/older adults), smoking status (never/former smokers), or alcohol consumption (non/mild alcohol drinkers [< 10 g/day]) to be prominently associated with higher lung cancer risks.</p><p><strong>Conclusions: </strong>Increased serum levels of GGT correlated with higher risk of lung cancer, even after adjusting for smoking status, alcohol consumption, and chronic liver disease. These effects were more prominent in never/former smokers and in non/mild alcohol drinkers.</p><p><strong>Clinical trial number: </strong>not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"242"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610136","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":"Early development and dynamics of nasopharyngeal microbiota in infants during the COVID-19 pandemic: a 2-year prospective birth cohort study.","authors":"Aleix Lluansí, Pedro Brotons, Marta Díaz, Ariadna Rigalos, Cristina Garcia-Beltran, Amaresh Pérez-Argüello, Maria Cisneros, Miguel Blanco-Fuertes, Desirée Henares, Lourdes Ibáñez, Carmen Muñoz-Almagro","doi":"10.1186/s12931-025-03307-5","DOIUrl":"https://doi.org/10.1186/s12931-025-03307-5","url":null,"abstract":"<p><strong>Background: </strong>The nasopharyngeal microbiota, which plays a crucial role in respiratory health and disease during infancy, was significantly affected by the COVID-19 pandemic lockdown in children and adults. This study aimed to prospectively explore the dynamics of the nasopharyngeal microbiota in infants during the COVID-19 pandemic.</p><p><strong>Methods: </strong>We conducted a prospective birth cohort study at Hospital Sant Joan de Déu (Barcelona, Spain) involving 32 neonates born between December 2019 and December 2020. Epidemiological, clinical and microbiological variables as well as nasopharyngeal aspirates were collected during the firsts two years of life. Nasopharyngeal aspirates were used to characterize the nasopharyngeal microbiota through 16 S rRNA gene sequencing.</p><p><strong>Results: </strong>Our findings highlight the stabilization of the nasopharyngeal microbiota composition by 12 months of age. Key factors influencing nasopharyngeal microbiota patterns in the first two years of life included a history of upper respiratory tract infection episodes, a pattern of rapid post-natal weight gain, pneumococcal carriage detection, recent receipt of systematic vaccination, and the use of antibiotics and corticosteroids. Notably, rapid post-natal weight gain was associated with differences in the microbiota composition, with overrepresentation of potential beneficial bacteria such as Dolosigranulum pigrum and Corynebacterium spp., underrepresentation of Haemophilus influenzae and Moraxella catarrhalis, and functional pathways with enhanced metabolic activity.</p><p><strong>Conclusions: </strong>These findings demonstrate early stabilization of the nasopharyngeal microbiota composition by 12 months of age during the COVID-19 period and highlight the interplay between nasopharyngeal microbiota dynamics and early post-natal weight gain, with potential long-term impacts on metabolic outcomes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"240"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610133","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":"MTMR14 depletion aggravates intrapulmonary inflammation and emphysema in experimental COPD through activating macrophage M1 polarization.","authors":"Jiaheng Zhang, Yuan Zhan, Zhesong Deng, Shanshan Chen, Ruonan Yang, Yating Zhang, Hao Fu, Qian Huang, Jixing Wu, Yiya Gu, Jungang Xie","doi":"10.1186/s12931-025-03293-8","DOIUrl":"https://doi.org/10.1186/s12931-025-03293-8","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is typically characterized by chronic airway inflammation and emphysema. Macrophage polarization plays an important role in COPD, while the precise molecules and mechanisms underpinning it have yet to be fully elucidated. Pulmonary decrease of myotubularin-related protein 14 (MTMR14) expression conduces to the progression of COPD in our prior publication, while the further analysis reveals the differential expression of MTMR14 in alveolar macrophages, whose function and related mechanisms are worth further research. Our study aims to investigate the role and mechanism of MTMR14 in macrophages of COPD.</p><p><strong>Methods: </strong>The expression and potential role of MTMR14 in COPD macrophages was explored via bioinformatic analysis and clinical detection, as well as in vivo and vitro experiments. By constructing animal model with Mtmr14 knockout and cell model with the knockdown or over-expression of MTMR14, the effect of MTMR14 on polarization direction of macrophages and the related signaling pathways were elaborated. Indirect co-culture was performed to probe the influence of MTMR14 in the crosstalk between macrophages and alveolar epithelium. The regulation of ubiquitin-proteasome system on MTMR14 expression was investigated via (co-)immunoprecipitation and cycloheximide chase assay.</p><p><strong>Results: </strong>Based on analysis from open-access single-cell sequencing data, MTMR14 was down-regulated in macrophages of COPD patients, which was confirmed in clinical specimens, animal and cell models. Meanwhile, MTMR14 was functionally enriched in inflammatory response and macrophage activation. Correspondingly, the knockout of MTMR14 aggravated the pulmonary function decline, emphysema, inflammation and pro-inflammatory macrophage polarization in mice exposed by cigarette smoke (CS). Mechanically, MTMR14 negatively regulated the M1 polarization of macrophages under CS extract (CSE)-stimulation through PI3K/Akt and NF-κB pathways. In addition, damage from macrophages on alveolar epithelium was intensified by the down-regulation of MTMR14 in the formation of emphysema. Finally, TRIM21 was found to down-regulate MTMR14 through ubiquitin-proteasome system in CSE-stimulated macrophages.</p><p><strong>Conclusions: </strong>Our findings underscore the mitigative role of MTMR14 on macrophage polarization towards pro-inflammatory phenotype, offering a promising target for prevention and intervention for COPD in clinical settings.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"238"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610134","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":"Nocturnal hypoxemia is associated with poor pulmonary hemodynamics in patients with chronic thromboembolic pulmonary disease.","authors":"Teng Han, Qiang Huang, Zhenguo Zhai, Xiaolei Zhang","doi":"10.1186/s12931-025-03318-2","DOIUrl":"https://doi.org/10.1186/s12931-025-03318-2","url":null,"abstract":"<p><strong>Background: </strong>Although a general association between nocturnal hypoxemia or sleep-disordered breathing (SDB) and pulmonary arterial hypertension has been established, little is known about the unique pathophysiologic contributions of SDB and nocturnal hypoxemia to chronic thromboembolic pulmonary disease (CTEPD). We therefore chose to examine the associations of SDB and nocturnal hypoxemia with hemodynamic indices obtained via right heart catheterization (RHC) in hospitalized patients with CTEPD. We hypothesized that the severity of CTEPD would be associated with SDB and nocturnal hypoxemia severity.</p><p><strong>Methods: </strong>Patients with CTEPD with or without pulmonary hypertension (PH) who had undergone polysomnography (PSG) between July 2022 and March 2024 were enrolled. A nocturnal mean oxygen saturation by pulse oximetry (MeanSpO₂) < 90% was defined as nocturnal hypoxemia, and a percentage of total sleep time with oxygen saturation < 90% (T90) exceeding 20% indicated severe nocturnal hypoxemia. The relationships between right heart catheterization measurements and T90 or MeanSpO₂ were calculated using multiple linear regression and logistic regression analyses.</p><p><strong>Results: </strong>The prevalence of severe nocturnal hypoxemia in the entire cohort was 42.86%, and SDB (AHI ≥ 15/h) affected 55.84% of patients and was predominantly manifested as hypopnea. Nocturnal hypoxemia remained significantly associated with mean pulmonary artery pressure (mPAP) (T90: β = 0.296, P = 0.019; MeanSpO₂: β= -0.333, P = 0.009) and pulmonary vascular resistance (PVR) (T90: β = 0.294, P = 0.021; MeanSpO₂: β=-0.310, P = 0.015) after adjusting for age, sex, body mass index, apnea hypopnea index and diurnal arterial partial pressure of oxygen. Receiver operating characteristic (ROC) curves for the detection of a mPAP ≥ 25 mmHg, PVR > 3 WU and WHO FC III-IV indicated that nocturnal hypoxemia parameters had moderate predictive value. (T90: AUC_mPAP=0.698, AUC_PVR=0.733, AUC_WHO-FC=0.729, respectively; MeanSpO₂: AUC_mPAP=0.691, AUC_PVR=0.731, AUC_WHO-FC=0.707, respectively).</p><p><strong>Conclusions: </strong>SDB is highly prevalent in patients with CTEPD, which is predominantly manifested as hypopnea rather than apnea, and overweight is not a commonly reported characteristic. Independent of the severity of SDB, nocturnal hypoxemia is significantly correlated with hemodynamics in patients with CTEPD, which indicated the clinical necessity of promoting nocturnal oximetry monitoring among patients with CTEPD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"239"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610135","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 human PCLS model of lung injury and repair for discovery and pharmaceutical research.","authors":"Esther Bankole, Chun Wai Wong, Sally Kim, Matthew Hind, Charlotte H Dean","doi":"10.1186/s12931-025-03314-6","DOIUrl":"10.1186/s12931-025-03314-6","url":null,"abstract":"<p><strong>Background: </strong>The Acid Injury and Repair (AIR) model is an ex-vivo model of lung injury and repair, that was previously established using mouse precision-cut lung slices (PCLS). The AIR model provides a bridge between the current in -vitro and in-vivo models to study the effects of lung injury in 3D lung tissue slices. Here, we show that the AIR model can be adapted for use in human tissue as a translational model for discovery research and drug screening.</p><p><strong>Methods: </strong>To generate PCLS, resected human lung tissue was coated with alginate hydrogel to form an artificial pleura. Lung tissue was inflated by point injecting 3% agarose, followed by generation of 450-500 µM thick slices of tissue. An isolated area of each slice was injured by brief application of 0.1 M hydrochloric acid. AIR-PCLS were then washed and cultured for 48 h before immunostaining to assess proliferating cells (Ki67) alveolar type II/progenitor cell markers (HTII, proSP-C), lipofibroblasts (ADRP) and endothelial cells (ERG). Viability of PCLS was assessed by both MTT assay and Live/Dead staining.</p><p><strong>Results: </strong>We show that levels of proliferation do not change in response to acid injury. However, there is a significant increase in the percentage of proSP-C and HTII positive cells in the injured regions of AIR-PCLS. We also identify non-epithelial cell populations; lipofibroblasts and endothelial cells in human AIR-PCLS, to demonstrate that other repair relevant cell types can be identified and tracked in the human AIR (hAIR model).</p><p><strong>Conclusions: </strong>The hAIR model is an effective ex-vivo tool to study early mechanisms of lung repair following injury. By establishing an area of injured tissue adjacent to uninjured tissue, this model mimics the heterogenous pattern of lung injury frequently present in lung diseases. The hAIR model will facilitate mechanistic studies of human lung repair and provides a valuable pre-clinical model for drug testing.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"237"},"PeriodicalIF":5.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568030","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":"Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study.","authors":"Daniel E Guzman, Lisa Ruvuna, Claire J Guo, Yifei Sun, Katherine A Pratte, Ani W Manichaikul, John S Kim, Wendy S Post, Alain G Bertoni, Norrina B Allen, Karol E Watson, James S Pankow, Eric A Hoffman, Ruth F Dubin, Rajat Deo, Igor Z Barjaktarevic, Eugene R Bleecker, Christopher B Cooper, Victor E Ortega, Annette T Hastie, Robert Paine, James Michael Wells, Jeffrey L Curtis, Edwin K Silverman, Prescott G Woodruff, Christine Kim Garcia, Jerome I Rotter, Russell P Bowler, Peter Ganz, R Graham Barr","doi":"10.1186/s12931-025-03312-8","DOIUrl":"10.1186/s12931-025-03312-8","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets.</p><p><strong>Objective: </strong>We performed a proteomic discovery analysis of percent emphysema on computed tomography (CT) in a population-based, multiethnic sample from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Replication was performed in two chronic obstructive pulmonary disease (COPD)-based studies, the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) and the Genetic Epidemiology of COPD (COPDGene) Study.</p><p><strong>Methods: </strong>MESA recruited participants from the general population in 2000-02. The MESA Lung Study performed full-lung CT scans in 2010-12. Percent emphysema was defined as the percentage of lung voxels < -950 Hounsfield units. Over 7,200 plasma aptamers were measured via SomaScan. Cross-sectional linear and least absolute shrinkage and selection operator (LASSO) regression models were adjusted for demographics, anthropometrics, smoking, renal function, and scanner parameters. Statistical significance was defined as a false discovery rate p-value < 0.05. Gene Ontology (GO)/Reactome enrichment analyses were performed. LASSO-selected proteins' predictive performance was evaluated.</p><p><strong>Results: </strong>Among 2,504 participants in the MESA Lung Study, mean age was 69.4 years, 1,291 had ever smoked, and median percent emphysema-like lung was 1.4%. In total, 1,234 aptamers were significantly associated with percent emphysema in the MESA Lung Study, and 35 replicated in the SPIROMICS and COPDGene Studies. Novel associations included protein family with sequence similarity (FAM) 177A1, syntenin-2, ubiquitin carboxyl-terminal hydrolase 25, and uncharacterized protein C20orf173. Previously identified emphysema-associated proteins included soluble advanced glycosylation end product-specific receptor (sRAGE), protein S100-A12, high mobility group protein B1, and roundabout homolog 2. Enrichment analyses identified 40 GO biological processes, including chemokine production and regulation and cell-cell adhesion and regulation, and two Reactome pathways, including RAGE signaling. In tenfold cross-validation, novel proteins were largely retained by LASSO (R² = 5.4%), improved overall model performance (R² = 24.8%), and uniquely explained greater variance in percent emphysema.</p><p><strong>Conclusions: </strong>This analysis in a general population sample identified novel and previously characterized proteins whose functional roles were validated by GO/Reactome enriched pathways, offering new insights into emphysema pathophysiology and therapeutics.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"236"},"PeriodicalIF":5.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565433","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":"X-ray velocimetry provides temporally and spatially-resolved biomarkers of lung ventilation in small airways disease.","authors":"Bradley W Richmond, Michael G Lester, Vincent Lui, Jonathan Dusting, Sarath Raju, Gregory I Snell, Jessica B Blackburn, Katrina Douglas, Robert F Miller, Trishul Siddharthan, Andreas Fouras","doi":"10.1186/s12931-025-03295-6","DOIUrl":"10.1186/s12931-025-03295-6","url":null,"abstract":"<p><strong>Background: </strong>Small airways disease is a feature of many respiratory conditions. Currently available methods of diagnosing small airways lack sensitivity and/or cannot evaluate spatial heterogeneity. New diagnostic strategies for diagnosing small airways disease are needed.</p><p><strong>Methods: </strong>We determined the regional displacement of lung tissue calculated from fluoroscopic lung images acquired at multiple angles over sequential time points as a surrogate of ventilation. We applied this technique, which we call X-ray velocimetry (XV), to patients with chronic obstructive pulmonary disease (COPD) and impaired spirometry and veterans with deployment-related constrictive bronchiolitis (DR-CB) but preserved spirometry to determine XV-derived biomarkers specific for each condition.</p><p><strong>Results: </strong>We identified disease- and stage-specific XV biomarkers for COPD patients that correlated with airflow obstruction on spirometry. Further, we identified a set of XV-derived biomarkers that could distinguish veterans with DR-CB from controls despite normal spirometry in most patients from both groups.</p><p><strong>Conclusions: </strong>XV may provide a safe and widely-available strategy for diagnosing small airways disease while preserving spatial information. Future studies are required to validate the biomarkers described here in larger patient cohorts.</p><p><strong>Trial registration: </strong>Not required for this study. However, participants enrolled at VUMC were enrolled under ClinicalTrials.gov study NCT04489758 (submitted 07/23/2020).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"226"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555512","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":"ARTEMISIA: a mechanistic study of a novel Janus kinase 1 inhibitor to advance molecular understanding and precision medicine in asthma.","authors":"Davinder Paul Singh Dosanjh, Erika Darrah, Tina Jellesmark Jensen, Zala Jevnikar, Alese Halvorson, Mathias Cardner, Rod Hughes, Sarah S Grant, Adam Platt, Chris E Brightling","doi":"10.1186/s12931-025-03309-3","DOIUrl":"10.1186/s12931-025-03309-3","url":null,"abstract":"<p><strong>Background: </strong>Patients with uncontrolled asthma despite the use of inhaled corticosteroids (ICS), may have a variety of biological pathways driving their airway inflammation. Londamocitinib (AZD4604), a selective, inhaled, Janus kinase 1 inhibitor, has been designed to target a broad inflammatory cytokine profile including those classically unresponsive to ICS. The ARTEMISIA mechanistic study aims to provide a clear understanding of the pathways impacted by londamocitinib in the lung, determine how this impact is reflected in the nose and periphery, and identify candidate biomarkers of londamocitinib-treatment response in asthma. This article reports the design and objectives of the ARTEMISIA study.</p><p><strong>Methods: </strong>ARTEMISIA is a placebo-controlled, double-blind study of adults with moderate-to-severe asthma aiming to assess the effects of inhaled londamocitinib on Type 2 (T2) and non-T2 driven inflammatory pathways. Extensive parallel bio-sampling of the lung target tissue, nasal mucosa, blood and urine will be performed prior to the first dose and after 4-weeks of treatment with either londamocitinib or placebo. The main objectives of the study are to evaluate the effect of londamocitinib on gene expression in endobronchial brushings and signal transducer and activator of transcription (STAT) phosphorylation in endobronchial biopsies. Key exploratory objectives include investigating the correlation between inflammatory phenotype-specific bronchial epithelial gene signatures and other biomarkers in the lung and peripheral samples; as well as analysis of transcriptomic, proteomic, and metabolomic biomarkers in the nose, blood, and urine.</p><p><strong>Discussion: </strong>ARTEMISIA commenced recruitment in 2024 and is poised to deliver a deep understanding of the mechanism of action of londamocitinib and its potential to impact on a population of asthmatics with high unmet need. The multiomic analysis of paired central and peripheral samples may reveal novel insights into the connection and translation between these compartments, deepen understanding of airways disease, and identify novel candidate biomarkers for asthma and JAK activity. In addition to sampling the airway directly, with parallel nasal and peripheral bio-sampling mirrored by the Phase 2a AJAX study (NCT06020014), the ARTEMISIA study may provide a unique link between bronchial assessed mechanisms of action and clinical outcomes.</p><p><strong>Trial registration: </strong>NCT06435273 (ClinicalTrials.gov). Registered 24th May 2024.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"233"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555429","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":"Reference equations for pulmonary function testing in healthy Chinese children aged 4-18 years.","authors":"Jinhong Wu, Hao Zhang, Yufen Wu, Qiaoling Zhang, Ming Li, Fuli Dai, Changfu Xu, Yongsheng Shi, Ning Wang, ChunMei Jia, Sha Liu, Yuehua Zhang, Zhongping Zhang, Aihong Liu, Fei Wang, Li Liu, Qiang Chen, Jinrong Wang, Yuling Han, Yuxin Song, Yong Feng, Yun Sun, Huaping Rao, Lili Zhong, Quanhua Liu, Liya Wan, Zhen Long, Xiaoyan Dong, Yanli Zhang, Wenhui Jiang, Minghong Ji, Jianfeng Huang, Zhiwei Pan, Dongjun Ma, Suping Tang","doi":"10.1186/s12931-025-03298-3","DOIUrl":"10.1186/s12931-025-03298-3","url":null,"abstract":"<p><strong>Background: </strong>Accurate spirometry reference equations are essential for diagnosing and managing respiratory conditions in children. Although the GLI Global Equations have been proposed for general use, there were few Asian populations available for inclusion. This study aims to develop and validate spirometric reference equations for healthy Chinese children.</p><p><strong>Methods: </strong>From May 2018 to May 2021, a cross-sectional study involving healthy Chinese Han children aged 4 to 18 years was conducted by 33 research centers across 24 regions in China. Participants were recruited directly from schools, and physical growth indices (height, weight) were measured. Spirometry tests were performed and demographic and medical history data were collected through questionnaires. New prediction equations were developed using multiple linear regression models with age, height, and weight as predictors. And comparisons were made with existing Caucasian and Chinese pediatric reference equations.</p><p><strong>Results: </strong>Lung function was assessed in 8929 healthy Chinese Han children. Age, weight, and height emerged as strong predictors of lung function (p < 0.001), and sex-specific reference equations incorporating these factors demonstrated high accuracy in internal validation, yielding mean z-scores within a narrow range of -0.004 to -0.069. In comparison, the Zapletal equations overestimated FEV₁ and FEV₁/FVC while underestimating other lung function parameters. Additionally, the GLI equations underestimated lung function parameters, including FEV₁, FVC, and FEV₁/FVC, for both boys and girls. Compared to previous Chinese studies, the z-scores in this study ranged from - 0.97 to 0.93, with some cases showing significant deviations, highlighting the limitations of existing equations.</p><p><strong>Conclusion: </strong>This study developed new spirometry reference equations tailored for healthy Chinese children, with differences noted compared to existing equations. These equations reflect contemporary growth patterns and regional diversity in China, providing an additional option for clinical use.</p><p><strong>Trial registration: </strong>NO.: ChiCTR: 1,800,019,029. Registered 22 October 2018.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"224"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555434","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}