Respiratory Research最新文献

{"title":"Airway MMP-12 and DNA methylation in COPD: an integrative approach.","authors":"Jonas Eriksson Ström, Simon Kebede Merid, Robert Linder, Jamshid Pourazar, Anne Lindberg, Erik Melén, Annelie F Behndig","doi":"10.1186/s12931-024-03088-3","DOIUrl":"10.1186/s12931-024-03088-3","url":null,"abstract":"<p><strong>Background: </strong>In COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regulated, but to what extent this regulation occurs through epigenetic mechanisms remains unknown.</p><p><strong>Methods: </strong>To explore the interplay between MMPs, TIMPs, and DNA methylation (DNAm) we (1) analysed MMP-9, -12, and TIMP-1 concentrations in BAL fluid, and profiled DNAm in BAL cells from 18 COPD and 30 control subjects, (2) estimated protein-COPD relationships using multivariable regression, (3) identified protein quantitative trait methylation loci (pQTMs) with COPD as a potential modifier in a separate interaction model, and (4) integrated significant interactions with a previous COPD GWAS meta-analysis.</p><p><strong>Results: </strong>COPD was associated with higher levels of BAL MMP-12 (p = 0.016) but not with MMP-9 or TIMP-1. Further examination of MMP-12 identified association with DNAm at 34 loci (pQTMs), with TGFBR2 (p = 2.25 × 10^-10) and THBS4 (p = 1.11 × 10^-9) among the top ten pQTM genes. The interaction model identified 66 sites where the DNAm-MMP-12 association was significantly different in COPD compared to controls. Of these, one was colocalized with SNPs previously associated with COPD.</p><p><strong>Conclusions: </strong>Our findings indicate that airway MMP-12 may partially be regulated by epigenetic mechanisms and that this regulation is disrupted in COPD. Furthermore, integration with COPD GWAS data suggests that this dysregulation is influenced by a combination of environmental factors, disease processes, and genetics, with the latter potentially playing a lesser role.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"10"},"PeriodicalIF":5.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967246","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":"Airway pressures generated by high flow nasal cannula in patients with acute hypoxemic respiratory failure: a computational study.","authors":"Hossein Shamohammadi, Liam Weaver, Sina Saffaran, Roberto Tonelli, Marianna Laviola, John G Laffey, Luigi Camporota, Timothy E Scott, Jonathan G Hardman, Enrico Clini, Declan G Bates","doi":"10.1186/s12931-025-03096-x","DOIUrl":"10.1186/s12931-025-03096-x","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>High flow nasal cannula (HFNC) therapy is an increasingly popular mode of non-invasive respiratory support for the treatment of patients with acute hypoxemic respiratory failure (AHRF). Previous experimental studies in healthy subjects have established that HFNC generates flow-dependent positive airway pressures, but no data is available on the levels of mean airway pressure (mP_aw) or positive end-expiratory pressure (PEEP) generated by HFNC therapy in AHRF patients. We aimed to estimate the airway pressures generated by HFNC at different flow rates in patients with AHRF, whose functional lung volume may be significantly reduced compared to healthy subjects due to alveolar consolidation and/or collapse.</p><p><strong>Materials and methods: </strong>We developed a high-fidelity mechanistic computational model of the cardiopulmonary system during HFNC therapy using data from healthy subjects, and then measured the mP_aw and PEEP levels produced when different amounts of alveolar consolidation/collapse were incorporated into the model.</p><p><strong>Results: </strong>When calibrated to represent normal lung physiology in healthy subjects, our model recapitulates the airway pressures produced by HFNC at different flow rates in healthy volunteers who were breathing normally, with their mouths closed or open. When different amounts of alveolar consolidation/collapse are implemented in the model to reflect the pathophysiology of AHRF, the mP_aw and PEEP produced by HFNC at all flow rates increase as the functional lung volume decreases (up to a mP_aw of 11.53 and a PEEP of 11.41 cmH₂O at 60 L/min with the mouth closed when 50% of the model's alveolar compartments are non-aerated). When the model was matched to individual patient data from a cohort of 58 patients with AHRF receiving HFNC at 60 L/min, the mean (standard deviation) of the mP_aw / PEEP produced by HFNC in the models of these patients was 8.56 (1.50) / 8.92 (1.49) cmH₂O with mouths closed, and 1.73 (0.31) / 1.36 (0.36) cmH₂O with mouths open.</p><p><strong>Conclusions: </strong>Our results suggest that the airway pressures produced by HFNC in patients with AHRF could be higher than is currently assumed based on experimental data from healthy subjects, particularly in patients whose mouths remain closed. Higher levels of PEEP could be beneficial if they lead to alveolar recruitment and improved lung compliance, but could cause alveolar overdistension if they do not, motivating the close monitoring of the effects of HFNC on lung mechanics. Further clinical studies are warranted to directly measure the airway pressures produced by HFNC in patients with different severities of AHRF.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"9"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957596","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 different response of PM_2.5 stimulated nasal epithelial spheroids in control, asthma and COPD groups.","authors":"Paulina Misiukiewicz-Stępień, Elwira Zajusz-Zubek, Katarzyna Górska, Rafał Krenke, Magdalena Paplińska-Goryca","doi":"10.1186/s12931-025-03097-w","DOIUrl":"10.1186/s12931-025-03097-w","url":null,"abstract":"<p><strong>Background: </strong>Pathobiology of asthma and chronic obstructive pulmonary disease (COPD) is associated with changes among respiratory epithelium structure and function. Increased levels of PM_2.5 from urban particulate matter (UPM) are correlated with enlarged rate of asthma and COPD morbidity as well as acute disease exacerbation. It has been suggested that pre-existing pulmonary obstructive diseases predispose epithelium for different biological response than in healthy airways. The aim of this study was to assess the impact of PM_2.5 on the biological response of healthy as well as asthma and COPD respiratory epithelium using 3D/spheroid culture model.</p><p><strong>Methods: </strong>The spheroids from 5 healthy controls, 8 asthma patients, and 8 COPD patients were exposed to 100 µg/ml of PM_2.5 for 24 h.</p><p><strong>Results: </strong>The common pattern for healthy asthma and COPD epithelium inflammatory response to PM_2.5 stimulation include the increase in IL-1β, IL-6, IL-8 mRNA expression, and secretion of IL-6. Asthmatic spheroids produced higher amount of TNF-α and IL-8, whereas COPD spheroids expressed increased mRNA level of MUC5AC and decreased level of MMP7. PM_2.5 treatment induced changes in AHR and TLR4 expression on secretory epithelium in COPD.</p><p><strong>Conclusion: </strong>The response of airway epithelium to air pollution is different in healthy people than in obstructive lung disease patients. The impairment of airway epithelium in asthma and COPD changes their response to toxic environmental stimuli. This physiological dysfunction might be associated with diseases exacerbation of obstructive lung diseases.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"8"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957614","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":"Interaction study of the effects of environmental exposure and gene polymorphisms of inflammatory and immune-active factors on chronic obstructive pulmonary disease.","authors":"Rui Wang, Yuanyuan Li, Yuting Jiang, Xiaona Liu, Hongqi Feng, Zhe Jiao, Bingyun Li, Chang Liu, Yuncheng Shen, Fang Chu, Chenpeng Zhu, Dianjun Sun, Wei Zhang","doi":"10.1186/s12931-024-03079-4","DOIUrl":"10.1186/s12931-024-03079-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, influenced by both environmental and genetic factors. Single nucleotide polymorphism (SNP) in the human genome may influence the risk of developing COPD and the response to treatment. We assessed the effects of gene polymorphism of inflammatory and immune-active factors and gene-environment interaction on risk of COPD in middle-aged and older Chinese individuals.</p><p><strong>Methods: </strong>In this community-based case-control study, 471 patients with COPD and 485 controls aged 40-76 years in Heilongjiang Province, China were included. Face-to-face interviews, lung function tests, and multiplex polymerase chain reaction were used to obtain data. Logistic regression model, generalized multifactor dimensionality reduction and crossover analysis were used to analyse the effects of SNPs, gene-gene interactions, and gene-environment interactions on COPD.</p><p><strong>Results: </strong>CRP gene[rs1130864-A allele (OR, 1.77; 95% CI 1.11-2.81); G/A + A/A genotype (OR, 1.75; 95% CI 1.07-2.84)], FCAR gene[rs4806606-G (OR, 0.72; 95% CI 0.53-0.98); rs8112766-G (OR, 0.79; 95% CI 0.64-0.98)] and FCGR2A gene[rs4656308-C (OR, 0.74; 95% CI 0.55-1.00); rs4656309-T (OR, 0.81; 95% CI 0.66-0.99)] are independent influential factors for COPD. Rs1205 [RERI: 0.15 (0.07-1.00)] and rs1130864 [RERI: 2.45 (0.73-4.18)] of CRP gene, rs11084376 [OR: 0.54 (0.29-0.97)] of FCAR gene, rs844 of FCGR2B [SI: 0.30 (0.11-0.77); OR: 0.46 (0.24-0.90)] gene, rs4656308-rs4656309-rs2165088 haplotype [SI: 0.48 (0.26-0.89)] of FCGR2A gene and exposure to smoking index > 200, indoor coal/wood/straw use, and outdoor straw burning play synergistic or antagonistic roles in the development of COPD.</p><p><strong>Conclusions: </strong>Alleles and genotypes of the CRP/FCAR/FCGR2A gene can increase the susceptibility to COPD in the northern Chinese population. For the first time, environmental exposure to the CRP/FCAR/FCGR2A/FCGR2B genes has been shown to have synergistic or antagonistic effects on COPD susceptibility on genotypes or haplotypes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"5"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957609","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":"Sexual dimorphism in lung transcriptomic adaptations in fetal alcohol spectrum disorders.","authors":"Vishal D Naik, Dylan J Millikin, Daniel Moussa, Hong Jiang, Alexander L Carabulea, Joseph D Janeski, Jiahui Ding, Kang Chen, Marta Rodriguez-Garcia, Sunil Jaiman, Stephen A Krawetz, Gil Mor, Jayanth Ramadoss","doi":"10.1186/s12931-025-03094-z","DOIUrl":"10.1186/s12931-025-03094-z","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Current fetal alcohol spectrum disorders (FASD) studies primarily focus on alcohol's actions on the fetal brain although respiratory infections are a leading cause of morbidity/mortality in newborns. The limited studies examining the pulmonary adaptations in FASD demonstrate decreased surfactant protein A and alveolar macrophage phagocytosis, impaired differentiation, and increased risk of Group B streptococcal pneumonia with no study examining sexual dimorphism in adaptations. We hypothesized that developmental alcohol exposure in pregnancy will lead to sexually dimorphic fetal lung morphological and immune adaptations. Pregnant rats were orogastrically treated once daily with alcohol (4.5 g/kg, gestational day [GD] 4 to 10, peak BAC, 216 mg/dl; 6.0 g/kg, GD 11 to 20, peak BAC, 289 mg/dl) or 50% maltose dextrin (isocalorically matched pair-fed controls) to control for calories derived from ethanol. Male and female fetal lung RNA from a total of 20 dams were assessed using the TapeStation (Agilent) and Qubit RNA broad-range assay. Samples with RNA Integrity Numbers (RINs) &gt; 8 were prepared using the NEBNext Poly(A) mRNA Magnetic Isolation Module (NEB), xGen Broad-range RNA Library Prep (IDT), and xGen Normalase UDI Primer Plate 2 (IDT). Final libraries were checked for quality and quantity by Qubit hsDNA and LabChip. The samples were sequenced on the Illumina NovaSeq S4 Paired-end 150 bp. Fetal lung tissue were analyzed for histopathological assessments. Mean fetal weight, crown-rump length and placental efficiency of the alcohol-administered rats were significantly lower (P &lt; 0.05) than the pair-fed control pups. Differentially expressed genes indicated a sex-linked gene regulation dichotomy with a significantly higher number of genes altered in the female fetal lungs compared to the male. Network analysis plot of downregulated genes in the females exposed to alcohol in utero showed a negative impact on T cell activation and regulation, T cell differentiation, decrease in CD8&lt;sup&gt;+&lt;/sup&gt; T cell number etc. The most altered genes were Cd8b, Ccl25, Cd3e, Cd27, Cd247, Cd3d, Ccr9, Cd2, Cd8a and were decreased by a log2fold change of &gt; 2 (P &lt; 0.05) in the female fetal lungs. KEGG analyses showed that male and female fetal lungs had downregulated genes associated with development and mitosis, whereas the females alone showed dysregulation of T cell genes. Comparison of gross appearance and histopathologic morphology showed that the developing lungs of both male and female fetal pups, displayed stunted differentiation, were relatively hypoplastic, and displayed a diminution of alveolar size and air spaces. Similarly, in both sexes, decreased alveolar capillarization was also evident in the alcohol-exposed fetal lungs. These data provide novel information in a growing area focused on alcohol effects on the offspring lung and its influence on appropriate fetal/neonatal immune responses and highlights the importance of examining sexual dimorphism in","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"6"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957613","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":"Dynamic EIT technology for real-time non-invasive monitoring of acute pulmonary embolism: a porcine model experiment.","authors":"Junyao Li, Mingxu Zhu, Yitong Guo, Weichen Li, Qing He, Yu Wang, Yuxuan Liu, Benyuan Liu, Yang Liu, Weice Wang, Zhenyu Ji, Xuetao Shi","doi":"10.1186/s12931-024-03090-9","DOIUrl":"10.1186/s12931-024-03090-9","url":null,"abstract":"<p><strong>Background: </strong>Acute pulmonary embolism represents the third most prevalent cardiovascular pathology, following coronary heart disease and hypertension. Its untreated mortality rate is as high as 20-30%, which represents a significant threat to patient survival. In view of the current lack of real-time monitoring techniques for acute pulmonary embolism, this study primarily investigates the potential of the pulsatility electrical impedance tomography (EIT) technique for the detection and real-time monitoring of acute pulmonary embolism through the collection and imaging of the pulsatile signal of pulmonary blood flow.</p><p><strong>Methods: </strong>A before-and-after self-control experiment was conducted on anaesthetised domestic pigs (N = 12, 20.75 ± 2.56 kg). The changes in pulmonary perfusion caused by an acute pulmonary embolism (artificially induced) were monitored in real time using the pulsation method. This enabled the extraction of indicators such as Amplitude, Forward (Negative) Slope, and S_ARC, which were used to assess the local pulmonary blood flow perfusion state. Furthermore, the degree of ventilation/perfusion matching in the lungs was evaluated concurrently with the analysis of the pulmonary ventilation area. Subsequently, a control verification was conducted utilising the conventional invasive hypertonic saline (5 ml 10% NaCl) contrast technique.</p><p><strong>Results: </strong>The perfusion alterations subsequent to embolism in the pulsatility method are highly concordant with those observed in the hypertonic saline method, as evidenced by the imaging and indicator data. In particular, the perfusion area on the side of the embolism is markedly diminished, and the absolute values of all perfusion indicators are significantly reduced. Among these, Amplitude (P < 0.001) and S_ARC (P < 0.001) exhibit the most pronounced alterations. Furthermore, the extracted indicators from regional ventilation demonstrated notable discrepancies, the V/Q match% (P < 0.001) and Dead Space% (P < 0.001) exhibited the most pronounced sensitivity to alterations in acute pulmonary embolism. Subsequently, a control verification was conducted utilising the hypertonic saline method, which revealed a high degree of consistency between the two methods in the detection of acute pulmonary embolism (Kappa = 0.75, P < 0.05).</p><p><strong>Conclusions: </strong>The EIT imaging method, which is based on the analysis of blood flow pulsation, has the potential to reflect in real time the changes in pulmonary blood flow that occur before and after an embolism. This provides a new avenue for the non-invasive real-time monitoring of patients with acute pulmonary embolism in a clinical setting.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"7"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957607","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":"Outcome and safety 90 days after combined airway valve treatment of the right upper and middle lobes in patients with severe pulmonary emphysema.","authors":"A Susanne Dittrich, Cosimo Carlo De Pace, Judith Maria Brock, Franziska Trudzinski, Claus Peter Heussel, Ralf Eberhardt, Felix J F Herth, Konstantina Kontogianni","doi":"10.1186/s12931-024-03069-6","DOIUrl":"https://doi.org/10.1186/s12931-024-03069-6","url":null,"abstract":"<p><strong>Background: </strong>In COPD patients with severe right-sided emphysema, complete major and incomplete minor fissure, implantation of one-way valves in both the right upper (RUL) and middle lobes (ML) is a possible approach for endoscopic lung volume reduction. The aim of this retrospective analysis was to evaluate the response to therapy and the complication rate at 90 days (90d-FU) after combined RUL-ML valve implantation.</p><p><strong>Methods: </strong>This retrospective, monocentric study included all patients from the Thoraxklinik Heidelberg who underwent RUL-ML valve treatment between 2012 and 2023 with available follow-up data. Quantitative chest imaging, lung function, 6-minute walking distance (6-MWD), complications and indications for re-bronchoscopies until 90d-FU were analysed.</p><p><strong>Results: </strong>28 patients underwent combined RUL-ML valve treatment, predominantly sequentially (92.86%, n = 26/28). Neither lung function nor 6MWD improved significantly in the overall cohort. However, in the subgroup with heterogeneous emphysema (71.4%, n = 20/28), FEV1 (Δ = 116.00 mL ± 195.77 mL, p < 0.05) and 6-MWD (Δ = 50.23 ± 69.10 m, p < 0.05) increased significantly at 90d-FU. Consistent with this, the baseline difference in emphysema volume between the RUL + ML and the right lower lobe correlated significantly with the increase in FEV1 at 90d-FU (R = 0.74, p < 0.001). Pneumothorax occurred in 5 cases in 4 patients (14.3%) following ML treatment. Severe pneumonia and/or COPD exacerbations occurred in 32.1% (9/28) of patients.</p><p><strong>Conclusions: </strong>Although only studied in a small cohort, our data suggest that combined RUL and ML valve implantation appears to be a promising interventional treatment strategy in patients with severe heterogenous RUL and ML emphysema.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"4"},"PeriodicalIF":5.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957611","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":"Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13.","authors":"Cheng Tan, Hang Zhou, Qiangfei Xiong, Xian Xian, Qiyuan Liu, Zexin Zhang, Jingjing Xu, Hao Yao","doi":"10.1186/s12931-024-03045-0","DOIUrl":"https://doi.org/10.1186/s12931-024-03045-0","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a systemic inflammatory response caused by infection. When this inflammatory response spreads to the lungs, it can lead to acute lung injury (ALI) or more severe acute respiratory distress syndrome (ARDS). Pulmonary fibrosis is a potential complication of these conditions, and the early occurrence of pulmonary fibrosis is associated with a higher mortality rate. The underlying mechanism of ARDS-related pulmonary fibrosis remains unclear.</p><p><strong>Methods: </strong>To evaluate the role of mast cell in sepsis-induced pulmonary fibrosis and elucidate its molecular mechanism. We investigated the level of mast cell and epithelial-mesenchymal transition(EMT) in LPS-induced mouse model and cellular model. We also explored the influence of cromolyn sodium and mast cell knockout on pulmonary fibrosis. Additionally, we explored the effect of MC-derived IL-13 on the EMT and illustrated the relationship between mast cell and pulmonary fibrosis.</p><p><strong>Results: </strong>Mast cell was up-regulated in the lung tissues of the pulmonary fibrotic mouse model compared to control groups. Cromolyn sodium and mast cell knockout decreased the expression of EMT-related protein and IL-13, alleviated the symptoms of pulmonary fibrosis in vivo and in vitro. The PI3K/AKT/mTOR signaling was activated in fibrotic lung tissue, whereas Cromolyn sodium and mast cell knockout inhibited this pathway.</p><p><strong>Conclusion: </strong>The expression level of mast cell is increased in fibrotic lungs. Cromolyn sodium intervention and mast cell knockout alleviate the symptoms of pulmonary fibrosis probably via the PI3K/AKT/mTOR signaling pathway. Therefore, mast cell inhibition is a potential therapeutic target for sepsis-induced pulmonary fibrosis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"3"},"PeriodicalIF":5.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957606","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":"Global, regional, and national burden of chronic obstructive pulmonary disease and its attributable risk factors from 1990 to 2021: an analysis for the Global Burden of Disease Study 2021.","authors":"Zhufeng Wang, Junfeng Lin, Lina Liang, Feifei Huang, Xiaoyin Yao, Kang Peng, Yi Gao, Jinping Zheng","doi":"10.1186/s12931-024-03051-2","DOIUrl":"10.1186/s12931-024-03051-2","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) continues to be a significant issue, leading to premature death or reduced quality of life. It's important to assess the current burden of COPD and its risk factors on a geographical basis to guide health policy.</p><p><strong>Methods: </strong>Data on the prevalence, deaths, and disability-adjusted life years (DALYs) related to COPD, and risk-attributable burden were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. The relationship between COPD DALYs and the sociodemographic index (SDI) was estimated using Smoothing Splines models.</p><p><strong>Results: </strong>Between 1990 and 2021, the changes were -1.46% (95% uncertainty interval [UI] -3.36% to 0.39%) in age-standardized prevalence, -37.12% (-43.37% to -27.68%) in mortality, and -36.98% (-42.37% to -28.54%) in DALYs rate. In 2021, a total of 213.39 million prevalent cases of COPD were estimated. The age-standardized prevalence of COPD increased with age and was more common in males. The age-standardized COPD DALYs had a reversed U-shaped relationship with SDI at the regional level, with the highest burden at an SDI of about 0.45. At the global level, smoking had the highest influence on COPD DALYs, accounting for 34.8%, followed by ambient particulate matter pollution (22.2%), household air pollution from solid fuels (19.5%), and occupational particulate matter, gases, and fumes (15.8%).</p><p><strong>Conclusions: </strong>The overall burden of COPD has been increasing despite improvements in some rates since 1990. It's crucial to focus on interventions such as smoking cessation and addressing environmental and occupational exposures.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"2"},"PeriodicalIF":5.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923694","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 characterization of molecular mechanisms of paraquat-induced lung injury in a mouse model.","authors":"Yu Qing Zhou, Jin Jin Peng, Li Ping Shan, Wei Liu","doi":"10.1186/s12931-024-03072-x","DOIUrl":"10.1186/s12931-024-03072-x","url":null,"abstract":"<p><strong>Background: </strong>We sought to explore the molecular mechanisms underpinning acute lung injury (ALI) caused by poisoning with paraquat (PQ).</p><p><strong>Methods: </strong>Selection mice were intraperitoneally injected with PQ at 40 mg/kg, whereas controls were injected with sterile saline. On days 2, 7, and 14 after administration, mice were anesthetized and sacrificed, and lung tissue was removed. Lung pathological changes were observed with conventional staining techniques. Lung tissue components were assessed with tandem mass spectrometry tag technology, and differentially expressed proteins (DEPs) were bioinformatically analyzed and investigated with parallel reaction monitoring.</p><p><strong>Results: </strong>The expression of 91, 160, and 78 proteins was significantly altered at days 2, 7, and 14, respectively. Gene Ontology analyses revealed that the DEPs in the PQ-2d and PQ-7d groups were involved primarily in humoral immunity and coagulation-related reactions, whereas those in the PQ-14d group were implicated primarily in chemotactic and regulatory responses. Kyoto Encyclopedia of Genes and Genomes analyses indicated that complement and coagulation cascades were key pathways in the PQ-2d and PQ-7d groups, whereas xenobiotic metabolism by cytochrome P450 was a key pathway in the PQ-14d group. Nine proteins at PQ-2d and eight proteins at PQ-7d were validated through parallel reaction monitoring (PRM).</p><p><strong>Conclusions: </strong>PQ-induced ALI depends on over-activation of immune responses by damaged alveolar/endothelial cells, and the complement/coagulation cascade pathway plays a key role during this process. The proteins identified herein might provide new therapeutic targets or biomarkers for PQ poisoning.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"1"},"PeriodicalIF":5.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923755","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}