Respiratory Research最新文献

{"title":"Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids.","authors":"Janesh Pillay, Antine W Flikweert, Matijs van Meurs, Marco J Grootenboers, Simone van der Sar-van der Brugge, Peter H J van der Voort, Morten A Karsdal, Jannie M B Sand, Diana J Leeming, Janette K Burgess, Jill Moser","doi":"10.1186/s12931-025-03098-9","DOIUrl":"10.1186/s12931-025-03098-9","url":null,"abstract":"<p><strong>Background: </strong>Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers.</p><p><strong>Methods: </strong>We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers.</p><p><strong>Results: </strong>Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX.</p><p><strong>Conclusion: </strong>Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"32"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025255","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":"Incident Cheyne-Stokes respiration occurring in CPAP-treated patients and cardiovascular risk: a 2-years prospective follow-up (The Alertapnee study).","authors":"Arnaud Prigent, Joëlle Texereau, Sébastien Bailly, Renaud Gervais, Anne-Laure Serandour, Régis Luraine, Jean Louis Pépin","doi":"10.1186/s12931-025-03109-9","DOIUrl":"10.1186/s12931-025-03109-9","url":null,"abstract":"<p><p>The Alertapnée study followed 555 adults with obstructive sleep apnea treated with CPAP and found that the occurrence of Cheyne-Stokes respiration (CSR) was linked to a 14-fold increase in the risk of significant cardiac events (SCE) after one year. However, the progression and clinical significance of CSR episodes over time remain unclear. This ancillary study aimed to assess CSR progression and clinical outcomes during a second year of follow-up in 66 patients who had experienced at least one CSR episode in the first year. The study focused on the number of nights with CSR, percentage of CSR, SCEs. Results showed that 62 of 66 patients with CSR in the first year also experienced CSR in the second year, with a significant increase in the median number of CSR nights, particularly when CSR was related to cardiovascular conditions (37 vs. 19 nights, p = 0.006). Patients who experienced a SCE in year 2 had significantly more nights with CSR (median 48/90nights; IQR = 35) and a significantly greater mean percentage of CSR (median 13.8%; interquartile range (IQR) = 13.7) as compared with patients free of SCE (median 9.5/90 nights IQR = 27.8 (p = 0.012); 6.1% IQR = 4.5 (p = 0.008), respectively). In conclusion, CSR occurrence and severity depend on the underlying condition. CSR related to cardiovascular aetiology increases over time and is associated with SCEs, whereas CSR linked to non-cardiovascular conditions does not indicate a poor prognosis. Identifying CSR patterns related to cardiovascular aetiologies could enable early detection of SCEs through telemonitoring in CPAP-treated patients.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"31"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025257","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 effect of immunosuppression on outcomes in elderly patients with community-acquired pneumonia.","authors":"Lixue Huang, Bingxuan Weng, Yuanqi Wang, Mengyuan Wang, Yin Mei, Wei Chen, Meng Ma, Jingnan Li, Jianzhen Weng, Yang Ju, Xuefeng Zhong, Xunliang Tong, Yanming Li","doi":"10.1186/s12931-024-03080-x","DOIUrl":"10.1186/s12931-024-03080-x","url":null,"abstract":"<p><strong>Background: </strong>The effect of immunosuppression on clinical manifestations and outcomes was unclear in elderly patients with CAP.</p><p><strong>Methods: </strong>Elderly hospitalised patients with CAP were consecutively enrolled and were divided into immunocompromised hosts (ICHs) or non-ICHs groups. Clinical manifestations, severity, and outcomes were compared. The logistic regression model was used to determine the association between immunosuppression and outcomes. The primary outcome was 30-day mortality.</p><p><strong>Results: </strong>A total of 822 patients were enrolled, of whom 133 (16.2%) were immunocompromised. There were no differences between the two groups in vital signs, oxygenation, admission laboratory tests, need for mechanical ventilation and intensive care unit admission, except for a lower lymphocyte count in the ICH group (0.9*10^9/L, IQR 0.6-1.3*10^9/L [ICH group] vs. 1.2*10^9/L, IQR 0.8-1.7*10^9/L [non-ICH group]; p < 0.001). The 30-day mortality in ICHs was 15.8%, significantly higher than the 5.1% in non-ICHs (p < 0.001). The risk distribution of severity was similar between the two groups when assessed by CURB-65 on admission; however, the significant difference was found when assessed by PSI. Notably, in the CURB-65 low-risk group, the 30-day mortality was significantly higher in ICHs than in non-ICHs (9.7% vs. 1.1%, p < 0.001); but there was no difference between ICHs and non-ICHs in PSI low-risk group (3.7% vs. 0.6%; p > 0.05). After adjusting for age, sex, and comorbidities, immunosuppression was significantly associated with a higher risk of 30-day mortality (odds ratio 5.004, 95% CI [2.618-9.530]).</p><p><strong>Conclusions: </strong>Immunosuppression was independently associated with an increased risk of 30-day mortality. CURB-65 may underestimate the mortality risk of ICHs.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"30"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025346","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":"Dysfunction in mitochondrial electron transport chain drives the pathogenesis of pulmonary arterial hypertension: insights from a multi-omics investigation.","authors":"Xin Zhang, Jieling Li, Minyi Fu, Xijie Geng, Junjie Hu, Ke-Jing Tang, Pan Chen, Jianyong Zou, Xiaoman Liu, Bo Zeng","doi":"10.1186/s12931-025-03099-8","DOIUrl":"10.1186/s12931-025-03099-8","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a progressive disorder that can lead to right ventricular failure and severe consequences. Despite extensive efforts, limited progress has been made in preventing the progression of PAH. Mitochondrial dysfunction is implicated in the development of PAH, but the key mitochondrial functional alterations in the pathogenesis have yet to be elucidated.</p><p><strong>Methods: </strong>We integrated three microarray datasets from the Gene Expression Omnibus (GEO), including 222 lung samples (164 PAH, 58 controls), for differential expression and functional enrichment analyses. Machine learning identified key mitochondria-related signaling pathways. PAH and control lung tissue samples were collected, and transcriptomic and metabolomic profiling were performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis investigated shared pathways, and canonical correlation analysis assessed gene-metabolite relationships.</p><p><strong>Results: </strong>In the GEO datasets, mitochondria-related signaling pathways were significantly enriched in PAH samples, in particular the electron transport chain (ETC) in mitochondrial oxidative phosphorylation system. Notably, the electron transport from cytochrome c to oxygen in ETC was identified as the most crucial mitochondria-related pathway, which was down-regulated in PAH samples. Transcriptomic profiling of the clinical lung tissue analysis identified 14 differentially expressed genes (DEGs) related to mitochondrial function. Metabolomic analysis revealed three differential metabolites in PAH samples: increased 3-phenyllactic acid and ADP, and decreased citric acid. Mitochondria-related genes highly correlated with these metabolites included KIT, OTC, CAMK2A, and CHRNA1.</p><p><strong>Conclusions: </strong>Down-regulation of electron transport from cytochrome c to oxygen in mitochondrial ETC and disruption of the citric acid cycle homeostasis may contribute to PAH pathogenesis. 3-phenyllactic acid emerges as a potential novel diagnostic biomarker for PAH. These findings offer insights for developing novel PAH therapies and diagnostics.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"29"},"PeriodicalIF":5.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014718","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":"Neutrophil elastase inhibitor (Sivelestat) in the treatment of acute respiratory distress syndrome induced by COVID-19: a multicenter retrospective cohort study.","authors":"Yuting Li, Jianjun Zhao, Jiahui Wei, Yanhong Zhang, Haitao Zhang, Ying Li, Ting Liao, Yang Hu, Bo Yuan, Xinmei Zhang, Wanyan Liu, Changgang Liu, Qingsong Cui, Shunzi Wu, Hongmei Jiang, Wenge Liu, Weiheng Liu, Hongguang Xu, Gang Li, Yuyan Cai, Liting Chen, Bingwei Chen, Dong Zhang","doi":"10.1186/s12931-025-03100-4","DOIUrl":"10.1186/s12931-025-03100-4","url":null,"abstract":"<p><strong>Background: </strong>Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat and improvement in oxygenation among patients with acute respiratory distress syndrome (ARDS) induced by COVID-19.</p><p><strong>Methods: </strong>A large multicentre cohort study of patients with ARDS induced by COVID-19 who had been admitted to intensive care units (ICUs). We used propensity score matching to compare the outcomes of patients treated with sivelestat to those who were not. The differences in continuous outcomes were assessed with the Wilcoxon signed-rank test. Kaplan-Meier method was used to show the 28-day survival curves in the matched cohorts. A log-rank P-test stratified on the matched pairs was used to test the equality of the estimated survival curves. A Cox proportional hazards model that incorporated a robust sandwich-type variance estimator to account for the matched nature of the data was used to estimate hazard ratios (HR). All statistical analyses were performed with SPSS 26.0 and R 4.2.3. A two-sided p-value of < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>A total of 387 patients met inclusion criteria, including 259 patients (66.9%) who were treated with sivelestat. In 158 patients matched on the propensity for treatment, receipt of sivelestat was associated with improved oxygenation, decreased Murray lung injury score, increased non-mechanical ventilation time within 28 days, increased alive and ICU-free days within 28 days (HR, 1.85; 95% CI 1.29 to 2.64; log-rank p < 0.001), shortened ICU stay and ultimately improved survival (HR, 2.78; 95% CI 1.32 to 5.88; log-rank p = 0.0074).</p><p><strong>Conclusions: </strong>Among patients with ARDS induce by COVID-19, sivelestat administration is associated with improved clinical outcomes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"28"},"PeriodicalIF":5.8,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014686","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":"Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation.","authors":"Alexandra Bouyssi, Alexis Trecourt, Tanguy Déméautis, Florence Persat, Olivier Glehen, Martine Wallon, Gilles Devouassoux, Abderrazzak Bentaher, Jean Menotti","doi":"10.1186/s12931-024-03092-7","DOIUrl":"10.1186/s12931-024-03092-7","url":null,"abstract":"<p><strong>Background: </strong>In patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate whether cell inflammation could worsen after exposure to A. fumigatus spores in vitro and then, in mice, following chronic exposure to cigarette smoke mimicking COPD.</p><p><strong>Methods: </strong>The inflammatory response to cigarette smoke alone or with A. fumigatus was investigated in cell culture models of murine macrophages and alveolar epithelial cells. In an animal model, mice were exposed daily to two cigarettes smoke over 14 weeks, and two intranasal instillations of 10⁵ spores at weeks 7 and 14. Then, their lungs were recovered to perform inflammatory and histopathological analyses.</p><p><strong>Results: </strong>In co-cultures of macrophages and epithelial cells treated with both cigarette smoke extracts (CSE) and A. fumigatus compared to CSE alone there were significant inductions in TNF-α (6.2-fold) and CXCL-2 (21.5-fold) gene expression, confirmed by significant increases in the corresponding protein secretion. In the murine model, histological analyses of the lung after chronic smoke exposure showed an increase in airspace enlargement. Moreover, a Bio-Plex approach on bronchoalveolar lavage of cigarette smoke and A. fumigatus-treated mice showed significant increases in multiple inflammatory proteins secreted in the lung.</p><p><strong>Conclusions: </strong>There was a stronger inflammatory response after cigarette smoke exposure with A. fumigatus compared to cigarette smoke alone. These findings were correlated with histopathological changes in the mouse lung in vivo.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"25"},"PeriodicalIF":5.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014708","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":"Relevance of superoxide dismutase type 1 to lipoid pneumonia: the first retrospective case-control study.","authors":"Yinan Hu, Yanhong Ren, Yinzhen Han, Zhen Li, Weiqing Meng, Yuhui Qiang, Mengyuan Liu, Huaping Dai","doi":"10.1186/s12931-025-03101-3","DOIUrl":"10.1186/s12931-025-03101-3","url":null,"abstract":"<p><strong>Background: </strong>Lipoid pneumonia (LP) is a rare disease caused by the accumulation of lipids and lipid-laden macrophages in the alveoli inducing damage. LP is difficult to differentiate from other similar diseases without pathological evidence, such as upper respiratory tract infection (URTI), pneumonia, cryptogenic organizing pneumonia (COP), pulmonary alveolar proteinosis (PAP), lung mucinous adenocarcinoma and pulmonary edema. Given the high misdiagnosis rate and limited statistical clinical and treatment data, there is an urgent need for novel indicators of LP. Superoxide dismutase type1 (SOD1) plays an essential role in macrophage polarization, promoting inflammation and oxidative stress, but its association with LP remains unknown.</p><p><strong>Methods: </strong>The clinical data of 22 patients with proven LP from January 2008 to June 2024 and their prognostic information up to June 2024 were retrospectively gathered (ClinicalTrials.gov, NCT06430008). Additionally, information on patients with URTI, bacterial and fungal pneumonia, COP, PAP, lung mucinous adenocarcinoma and pulmonary edema, was collected totaling 140 patients as control subjects. Receiver operating characteristic curve, machine learning (ML), regression and survival analyses were performed to analyze the data.</p><p><strong>Results: </strong>In multivariate regression analysis, the sole independent risk factor of LP was the level of SOD1 (OR 0.922, 95% CI: 0.878 ~ 0.967, P < 0.001), while smoking status (β= -0.177, 95% CI -18.645~-2.836, P = 0.008), diabetes mellitus (β= -0.191, 95% CI: -20.442~-3.592, P = 0.005), and total sialic acid (TSA) (β= -0.426, 95% CI: -0.915~ -0.433, P < 0.001) independently influenced the level of SOD1. SOD1 had the highest importance score in ML-based LP predictive models. Additionally, advanced age may be associated with higher mortality in LP.</p><p><strong>Conclusion: </strong>SOD1 is a potential biomarker for LP, but the smoking status, diabetes comorbidities, and TSA level need to be considered.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"24"},"PeriodicalIF":5.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014770","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":"Medical thoracoscopy combined with intrapleural injection of urokinase for treatment of pleural infection-a multicenter, prospective, randomized controlled study: study protocol.","authors":"Kaige Wang, Linhui Yang, Panwen Tian, Fen Tan, Dan Liu, Weimin Li","doi":"10.1186/s12931-025-03106-y","DOIUrl":"10.1186/s12931-025-03106-y","url":null,"abstract":"<p><strong>Background: </strong>Pleural diseases is a common respiratory disorder, mainly characterized as pleural effusion and patients with pleural effusion caused by pneumonia and empyema constituted 29% of the cohort, which suggests pleural infection as the predominant etiology of pleural effusion in China. Medical thoracoscopy (MT) combined with intrapleural injection of Urokinase holds significant therapeutic value for patients with early to moderate-stage empyema. However, there remains a lack of high-quality evidence regarding the efficacy and safety of combining MT with intrapleural injection of Urokinase administration in patients with pleural infections.</p><p><strong>Methods: </strong>This study is a prospective, multicenter, randomized controlled clinical trial involving patients with pleural infections. The intervention involves medical thoracoscopy. The control group receives conventional treatment involving intrapleural urokinase injection followed by chest tube placement for drainage. The study outcomes include efficacy and health economic benefits. The estimated minimum sample size for each group is 64 cases, totaling 128 cases. The study groups are delineated as follows: patients in group A receives intrapleural urokinase injection followed by chest tube placement for drainage, while patients in group B undergoes MT to remove multiple septa and necrotic tissue followed by chest tube placement for drainage, and then intrapleural urokinase injection the day after MT. It is recommended that the diameter of the chest tube be 12-14 F, with three daily flushes of 30 ml normal saline to ensure optimal drainage. Subsequently, comprehensive statistical analyses will be conducted to compare treatment effects and complications across all groups, ultimately leading to conclusive findings.</p><p><strong>Discussion: </strong>The study is the first prospective, multicenter clinical trial on the efficacy and safety of medical thoracoscopy combined with intrapleural urokinase injection for the treatment of pleural infection. This study aims to offer clinical guidance for the management of pleural infection.</p><p><strong>Registration number: </strong>ChiCTR2300078352 (Registration Date: 2023/12/06).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"21"},"PeriodicalIF":5.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014724","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":"Shorter telomere length in COPD cases secondary to biomass-burning smoke exposure.","authors":"Angélica Domínguez-de-Barros, Gloria Pérez-Rubio, Ingrid Fricke-Galindo, Alejandra Ramírez-Venegas, Malena Gajate-Arenas, Rafael Hernández-Zenteno, Salvador García-Carmona, Robinson Robles-Hernández, María E Ramírez-Díaz, Filiberto Cruz-Vicente, María L Martínez-Gómez, Jacob Lorenzo-Morales, Ramcés Falfán-Valencia, Elizabeth Córdoba-Lanús","doi":"10.1186/s12931-024-03074-9","DOIUrl":"10.1186/s12931-024-03074-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and destruction of lung tissue, primarily attributed to tobacco smoking. However, other factors like biomass-burning smoke (BS) exposure are also implicated. COPD has been described as an accelerated aging disease, and telomere length is a biomarker of aging.</p><p><strong>Methods: </strong>This study examined telomere length in 189 Mexican individuals, from which 93 developed COPD secondary to BS exposure (BE-COPD); the rest of the participants were exposed to BS but did not develop the disease. Lung function parameters were measured by spirometry, and relative telomere length (rTL) from peripheral blood DNA was determined using multiplex qPCR.</p><p><strong>Results: </strong>Results showed rTL to inversely correlate with age (R²=-0.207, p = 0.006) and with the hours-a-day of BS exposure (R²=-0.297, p < 0.001). Within BE-COPD cases, rTL was associated with daily BS exposure, and BE-COPD individuals exhibited a reduced rTL compared to controls (1.39 ± 0.45 vs. 0.89 ± 0.50; p < 0.001). When compared by rTL length in BE-COPD cases, longer telomeres were associated with decreased COPD risk (β = 0.134, 95% CI = 0.053-0.339; p < 0.001). However, no significant relationship was found between rTL and clinical or lung function parameters in the BE-COPD group.</p><p><strong>Conclusions: </strong>This is the first study to document that individuals with COPD secondary to biomass smoke exposure present shorter telomeres than BS-exposed subjects who did not develop the disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"23"},"PeriodicalIF":5.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014771","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":"Radiation decreases bronchial epithelial progenitor function as assessed by organoid formation.","authors":"Merian E Kuipers, Dennis K Ninaber, Krista C J van Doorn-Wink, Annelies M Slats, Pieter S Hiemstra","doi":"10.1186/s12931-025-03105-z","DOIUrl":"10.1186/s12931-025-03105-z","url":null,"abstract":"<p><strong>Objective: </strong>Radiation-induced lung injury (RILI) is a serious side-effect of radiotherapy for lung cancer, in which effects on the normal lung epithelium may play a key role. Since these effects are incompletely understood, the aim of the present study was to evaluate the effect of ionizing radiation (IR) on cultured well-differentiated primary bronchial epithelial cells (PBEC) with a focus on cytotoxicity, barrier formation, inflammation and epithelial progenitor function.</p><p><strong>Materials and methods: </strong>PBEC were cultured at the Air-Liquid Interface (ALI-PBEC) to allow mucociliary differentiation. Effect of IR (1, 2, 4, 8 Gy [Gy]) on ALI-PBEC cultures was investigated by lactate dehydrogenase (LDH) release, Trans Epithelial Electrical Resistance (TEER; as a measure of barrier function), qPCR (P21/CDKNA1, MKI67, AEN, E2F1, ATF3) and immunofluorescence staining (γH2Ax-foci). The impact on epithelial progenitor function was assessed by studying organoid formation capacity of irradiated ALI-PBEC at 24 h and 7 days after IR.</p><p><strong>Results and discussion: </strong>IR increased the number of γH2Ax-foci (marker of double stranded DNA breaks) in ALI-PBEC, but did not affect markers of toxicity (LDH-release or TEER). IR did also not affect mRNA markers for inflammation or epithelial-mesenchymal transition (EMT), but did increase mRNA levels of the cell cycle inhibitor P21/CDKN1A and resulted in downregulation of the proliferation markers MKI67 and E2F1. Finally, IR of ALI-PBEC had a marked effect on organoid formation capacity, which was markedly impaired following IR in a dose-dependent manner.</p><p><strong>Conclusion: </strong>In conclusion, epithelial progenitor cell function as assessed by organoid formation capacity is strongly reduced by IR and persists for at least 7 days. Despite an effect on organoid formation capacity, DNA breaks, P21/CDKN1A expression and reduced expression of MKI67 and E2F1, this effect was not accompanied by IR-induced cytotoxicity, or an increase in markers of inflammation or EMT. This study indicates that studying the effects of IR on organoid formation is a valid and sensitive tool to study adverse effects of IR on normal lung epithelial cells and could be used as a tool to study RILI.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"20"},"PeriodicalIF":5.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014700","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}