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PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap PPARγ 可减轻哮喘-慢性阻塞性肺疾病重叠期肺泡巨噬细胞的细胞衰老
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-20 DOI: 10.1186/s12931-024-02790-6
Rongjun Wan, Prakhyath Srikaram, Shaobing Xie, Qiong Chen, Chengping Hu, Mei Wan, Yuanyuan Li, Peisong Gao
{"title":"PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap","authors":"Rongjun Wan, Prakhyath Srikaram, Shaobing Xie, Qiong Chen, Chengping Hu, Mei Wan, Yuanyuan Li, Peisong Gao","doi":"10.1186/s12931-024-02790-6","DOIUrl":"https://doi.org/10.1186/s12931-024-02790-6","url":null,"abstract":"Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"50 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629107","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}
引用次数: 0
Positive effect of deep diaphragmatic breathing training on gastroesophageal reflux-induced chronic cough: a clinical randomized controlled study 深隔膜呼吸训练对胃食管反流引起的慢性咳嗽的积极影响:一项临床随机对照研究
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-18 DOI: 10.1186/s12931-024-02783-5
Shanshan Niu, Tongyangzi Zhang, Wanzhen Li, Siwan Wen, Lei Dong, Shengyuan Wang, Wenbo Shi, Cuiqin Shi, Yuqin Shen, Qianchun Huang, Yaling Tan, Xianghuai Xu, Li Yu
{"title":"Positive effect of deep diaphragmatic breathing training on gastroesophageal reflux-induced chronic cough: a clinical randomized controlled study","authors":"Shanshan Niu, Tongyangzi Zhang, Wanzhen Li, Siwan Wen, Lei Dong, Shengyuan Wang, Wenbo Shi, Cuiqin Shi, Yuqin Shen, Qianchun Huang, Yaling Tan, Xianghuai Xu, Li Yu","doi":"10.1186/s12931-024-02783-5","DOIUrl":"https://doi.org/10.1186/s12931-024-02783-5","url":null,"abstract":"To explore the efficacy of deep diaphragmatic breathing training (DEP) in patients with gastroesophageal reflux-induced chronic cough (GERC). A randomized controlled study was conducted involving 60 GERC patients who were divided into the intervention group and the control group (each with 30 patients). Both groups received routine medication treatment for GERC, while the intervention group received DEP training additionally. Both groups were evaluated by cough symptom scores, Hull airway reflux questionnaire (HARQ), gastroesophageal reflux diagnostic questionnaire (GerdQ), generalized anxiety disorder scale-7 (GAD-7), patient health questionnaire-9 (PHQ-9), Pittsburgh sleep quality index (PSQI), the Leicester cough questionnaire (LCQ), as well as capsaicin cough sensitivity testing, B-ultrasound and surface electromyography (sEMG) of the diaphragmatic muscles before and after treatment. The cough resolution rate and changes of the above indictors was compared between the two groups after eight weeks of treatment. After eight weeks of treatment, cough symptoms improved in both groups, but the cough resolution rate in the intervention group of 94% was significantly higher than that in the control group of 77% (χ2 = 6.402, P = 0.041). The intervention group showed significant improvements to the control group in GerdQ (6.13(0.35) VS 6.57(0.77)), GAD-7 (0(0;1) VS 1(0;3)), PSQI (2(1;3) VS 4(3;6)), LCQ (17.19(1.56) VS 15.88(1.92)) and PHQ-9 (0(0;0) VS 0(0;3)) after treatment. Compared to control group, sEMG activity of the diaphragmatic muscle was significantly increased in the intervention group after treatment, measured during DEP (79.00(2.49) VS 74.65 (1.93)) and quiet breathing (72.73 (1.96) VS 67.15 (2.48)). DEP training can improve cough symptoms as an adjunctive treatment in GERC patients. The protocol was registered in February 2, 2022 via the Chinese Clinical Trials Register ( http://www.chictr.org.cn/ ) [ChiCTR2200056246].","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"87 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624887","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}
引用次数: 0
Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis 间充质基质细胞作为一种新的治疗方法在急性呼吸窘迫综合征和肺纤维化中的潜在应用
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-18 DOI: 10.1186/s12931-024-02795-1
Giulia Gazzaniga, Marta Voltini, Alessandro Carletti, Elisa Lenta, Federica Meloni, Domenica Federica Briganti, Maria Antonietta Avanzini, Patrizia Comoli, Mirko Belliato
{"title":"Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis","authors":"Giulia Gazzaniga, Marta Voltini, Alessandro Carletti, Elisa Lenta, Federica Meloni, Domenica Federica Briganti, Maria Antonietta Avanzini, Patrizia Comoli, Mirko Belliato","doi":"10.1186/s12931-024-02795-1","DOIUrl":"https://doi.org/10.1186/s12931-024-02795-1","url":null,"abstract":"While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"38 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629141","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}
引用次数: 0
The endothelium: gatekeeper to lung ischemia-reperfusion injury 内皮:肺缺血再灌注损伤的守门员
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-18 DOI: 10.1186/s12931-024-02776-4
Huy Q. Ta, Maniselvan Kuppusamy, Swapnil K. Sonkusare, Mark E. Roeser, Victor E. Laubach
{"title":"The endothelium: gatekeeper to lung ischemia-reperfusion injury","authors":"Huy Q. Ta, Maniselvan Kuppusamy, Swapnil K. Sonkusare, Mark E. Roeser, Victor E. Laubach","doi":"10.1186/s12931-024-02776-4","DOIUrl":"https://doi.org/10.1186/s12931-024-02776-4","url":null,"abstract":"The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a robust inflammatory response, lung dysfunction, endothelial barrier disruption, oxidative stress, vascular permeability, edema, and neutrophil infiltration. These events are dependent on the health of the endothelium, which is a primary target of IRI that results in pulmonary endothelial barrier dysfunction. Over the past 10 years, research has focused more on the endothelium, which is beginning to unravel the multi-factorial pathogenesis and immunologic mechanisms underlying IRI. Many important proteins, receptors, and signaling pathways that are involved in the pathogenesis of endothelial dysfunction after IR are starting to be identified and targeted as prospective therapies for lung IRI. In this review, we highlight the more significant mediators of IRI-induced endothelial dysfunction discovered over the past decade including the extracellular glycocalyx, endothelial ion channels, purinergic receptors, kinases, and integrins. While there are no definitive clinical therapies currently available to prevent lung IRI, we will discuss potential clinical strategies for targeting the endothelium for the treatment or prevention of IRI. The accruing evidence on the essential role the endothelium plays in lung IRI suggests that promising endothelial-directed treatments may be approaching the clinic soon. The application of therapies targeting the pulmonary endothelium may help to halt this rapid and potentially fatal injury.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624879","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}
引用次数: 0
Development and application of a deep learning-based comprehensive early diagnostic model for chronic obstructive pulmonary disease 基于深度学习的慢性阻塞性肺病综合早期诊断模型的开发与应用
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-18 DOI: 10.1186/s12931-024-02793-3
Zecheng Zhu, Shunjin Zhao, Jiahui Li, Yuting Wang, Luopiao Xu, Yubing Jia, Zihan Li, Wenyuan Li, Gang Chen, Xifeng Wu
{"title":"Development and application of a deep learning-based comprehensive early diagnostic model for chronic obstructive pulmonary disease","authors":"Zecheng Zhu, Shunjin Zhao, Jiahui Li, Yuting Wang, Luopiao Xu, Yubing Jia, Zihan Li, Wenyuan Li, Gang Chen, Xifeng Wu","doi":"10.1186/s12931-024-02793-3","DOIUrl":"https://doi.org/10.1186/s12931-024-02793-3","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a frequently diagnosed yet treatable condition, provided it is identified early and managed effectively. This study aims to develop an advanced COPD diagnostic model by integrating deep learning and radiomics features. We utilized a dataset comprising CT images from 2,983 participants, of which 2,317 participants also provided epidemiological data through questionnaires. Deep learning features were extracted using a Variational Autoencoder, and radiomics features were obtained using the PyRadiomics package. Multi-Layer Perceptrons were used to construct models based on deep learning and radiomics features independently, as well as a fusion model integrating both. Subsequently, epidemiological questionnaire data were incorporated to establish a more comprehensive model. The diagnostic performance of standalone models, the fusion model and the comprehensive model was evaluated and compared using metrics including accuracy, precision, recall, F1-score, Brier score, receiver operating characteristic curves, and area under the curve (AUC). The fusion model exhibited outstanding performance with an AUC of 0.952, surpassing the standalone models based solely on deep learning features (AUC = 0.844) or radiomics features (AUC = 0.944). Notably, the comprehensive model, incorporating deep learning features, radiomics features, and questionnaire variables demonstrated the highest diagnostic performance among all models, yielding an AUC of 0.971. We developed and implemented a data fusion strategy to construct a state-of-the-art COPD diagnostic model integrating deep learning features, radiomics features, and questionnaire variables. Our data fusion strategy proved effective, and the model can be easily deployed in clinical settings. Not applicable. This study is NOT a clinical trial, it does not report the results of a health care intervention on human participants.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"1 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625010","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}
引用次数: 0
Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study COVID-19 和非 COVID-19 重症患者的耐多药病原体与呼吸机相关肺炎:一项前瞻性单中心观察比较研究
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-18 DOI: 10.1186/s12931-024-02779-1
Giorgia Montrucchio, Eleonora Balzani, Gabriele Sales, Anna Vaninetti, Francesca Grillo, Anna Chiara Trompeo, Marinella Zanierato, Vito Fanelli, Silvia Corcione, Francesco Giuseppe De Rosa, Antonio Curtoni, Cristina Costa, Luca Brazzi
{"title":"Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study","authors":"Giorgia Montrucchio, Eleonora Balzani, Gabriele Sales, Anna Vaninetti, Francesca Grillo, Anna Chiara Trompeo, Marinella Zanierato, Vito Fanelli, Silvia Corcione, Francesco Giuseppe De Rosa, Antonio Curtoni, Cristina Costa, Luca Brazzi","doi":"10.1186/s12931-024-02779-1","DOIUrl":"https://doi.org/10.1186/s12931-024-02779-1","url":null,"abstract":"The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the “Città della Salute e della Scienza” University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7–11 vs. 10, IQR: 8–13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"20 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625017","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}
引用次数: 0
Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions 慢性阻塞性肺病、哮喘和 ACO 患者体内的蝶呤:与内皮和肺功能的关系
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-18 DOI: 10.1186/s12931-024-02784-4
Yangli Liu, Fengjia Chen, Zhimin Zeng, Chengcheng Lei, Dubo Chen, Xiaoyu Zhang
{"title":"Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions","authors":"Yangli Liu, Fengjia Chen, Zhimin Zeng, Chengcheng Lei, Dubo Chen, Xiaoyu Zhang","doi":"10.1186/s12931-024-02784-4","DOIUrl":"https://doi.org/10.1186/s12931-024-02784-4","url":null,"abstract":"Endothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients. A total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro. Endothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05). NP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624998","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}
引用次数: 0
Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis 细胞外囊泡中血清素 C1 的减少可预测肺肉样瘤病患者对甲氨蝶呤治疗的反应
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-16 DOI: 10.1186/s12931-024-02809-y
Raisa Kraaijvanger, Montse Janssen Bonás, Jan C. Grutters, Ioanna Paspali, Marcel Veltkamp, Dominique P. V. de Kleijn, Coline H. M. van Moorsel
{"title":"Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis","authors":"Raisa Kraaijvanger, Montse Janssen Bonás, Jan C. Grutters, Ioanna Paspali, Marcel Veltkamp, Dominique P. V. de Kleijn, Coline H. M. van Moorsel","doi":"10.1186/s12931-024-02809-y","DOIUrl":"https://doi.org/10.1186/s12931-024-02809-y","url":null,"abstract":"Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking. In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy. Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment). Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032). This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"11 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576248","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}
引用次数: 0
Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease 慢性阻塞性肺病气道微生物组的人类基因关联
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-16 DOI: 10.1186/s12931-024-02805-2
Jingyuan Gao, Yuqiong Yang, Xiaopeng Xiang, Huimin Zheng, Xinzhu Yi, Fengyan Wang, Zhenyu Liang, Dandan Chen, Weijuan Shi, Lingwei Wang, Di Wu, Shengchuan Feng, Qiaoyun Huang, Xueping Li, Wensheng Shu, Rongchang Chen, Nanshan Zhong, Zhang Wang
{"title":"Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease","authors":"Jingyuan Gao, Yuqiong Yang, Xiaopeng Xiang, Huimin Zheng, Xinzhu Yi, Fengyan Wang, Zhenyu Liang, Dandan Chen, Weijuan Shi, Lingwei Wang, Di Wu, Shengchuan Feng, Qiaoyun Huang, Xueping Li, Wensheng Shu, Rongchang Chen, Nanshan Zhong, Zhang Wang","doi":"10.1186/s12931-024-02805-2","DOIUrl":"https://doi.org/10.1186/s12931-024-02805-2","url":null,"abstract":"Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10−5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10−8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575989","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}
引用次数: 0
Systemic IL-26 correlates with improved asthma control in children sensitized to dog allergen 全身 IL-26 与对狗过敏原过敏的儿童哮喘控制率改善有关
IF 5.8 2区 医学
Respiratory Research Pub Date : 2024-04-15 DOI: 10.1186/s12931-024-02773-7
Melissa A. Kovach, Ulrika Käck, Karlhans F Che, Bettina Brundin, Jon R. Konradsen, Anders Lindén
{"title":"Systemic IL-26 correlates with improved asthma control in children sensitized to dog allergen","authors":"Melissa A. Kovach, Ulrika Käck, Karlhans F Che, Bettina Brundin, Jon R. Konradsen, Anders Lindén","doi":"10.1186/s12931-024-02773-7","DOIUrl":"https://doi.org/10.1186/s12931-024-02773-7","url":null,"abstract":"Interleukin (IL)-26 is produced by T helper type 17 (Type 17) cells and exerts immunomodulatory plus antimicrobial effects. Previous studies show that local IL-26 concentrations in the airways are higher in patients with uncontrolled than in those with controlled asthma, and that this intriguing cytokine bears biomarker potential. Here, we determined how systemic IL-26 relates to allergen sensitization, asthma severity, and to IL-17 A in children. Serum samples were obtained from children with (n = 60) and without (n = 17) sensitization to dog allergen, and IL-26 and IL-17 A protein concentrations were measured using ELISA. Self-reported history, including medication use and validated symptom-based questionnaire scores, was recorded. The serum concentrations of IL-26 were enhanced in allergen-sensitized subjects and correlated with those of IL-17 A in a positive manner. However, the IL-26 concentrations did not markedly differ between allergen-sensitized subjects with and without asthma, eczema, allergic rhinitis, or a history of food allergy. Notably, IL-26 concentrations correlated with increasing Asthma Control Test (ACT) scores in a positive manner and with inhaled corticosteroid in a negative manner, amongst sensitized subjects with asthma. Moreover, subjects with asthma requiring ≥ 1 course of oral corticosteroids in the preceding 12 months had decreased IL-26 concentrations. This study forwards evidence that systemic IL-26, just like IL-17 A, is involved in allergen sensitization among children. The association of systemic IL-26 with improved asthma control is compatible with the cellular sources being recruited into the airways in severe asthma, which supports that this kinocidin bears potential as a biomarker and therapeutic target.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"222 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589601","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}
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