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Therapeutic effects of melatonin on the lungs of rats exposed to passive smoking. 褪黑素对被动吸烟大鼠肺部的治疗效果。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-19 DOI: 10.1186/s12931-024-03042-3
Juanjuan Xiong, Li Xie, YiRan Huang, JiaHui Zhu, ZhiYan Hong, HaoYun Qian, Jingjing Liu

Background: Passive smoke has a significant impact on lung function and constitutes a critical public health issue, as smoking generates free radicals that damage the lungs and other tissues. Currently, limited research exists on whether the antioxidant melatonin can mitigate lung damage caused by smoking. This study aims to investigate the mechanisms through which melatonin alleviates acute lung disease induced by passive smoking.

Methods: Rats were divided into five groups (n = 6): a control group and three groups exposed to low, medium, and high concentrations of smoke, and a melatonin treatment group.

Results: Data indicated that in the high concentration passive smoking group, the alveolar structure of the lung tissue was destroyed, and the total antioxidant capacity in lung tissue diminished as the concentration of smoke increased. The expressions of TNF-α, IL-6, and IL-1β exhibited similar results. The anti-apoptotic factors Bcl-2 and Bcl-xL mRNA level significantly decreased in the high concentration smoking group, while no significant changes were observed in the medium and low concentration groups. Conversely, the high concentration passive smoking increased the pro-apoptotic factors Bax and Caspase-3 mRNA levels. Additionally, endogenous melatonin levels in lung tissue gradually decreased following exposure to smoke, whereas the exogenous melatonin alleviated the changes in inflammatory factors and apoptosis-related factors in lung tissue. Furthermore, at high smoking concentrations, the mRNA levels of lung cancer-related genes vascular endothelial growth factor (VEGF), cytochromeP450 1A1 (CYP1A1), and cytochrome P450 1B1 (CYP1B1) were significantly increased, while exogenous melatonin reduced the expression of these genes in lung tissue.

Conclusions: These findings suggest that melatonin can diminish lung tissue damage, apoptosis, and inflammatory responses induced by passive smoking, as well as decrease the expression of lung cancer-related genes. Further experimental investigations involving exogenous melatonin treatments will be needed.

背景:被动吸烟会产生自由基,对肺部和其他组织造成损害,因此对肺功能有重大影响,是一个重要的公共卫生问题。目前,关于抗氧化剂褪黑素能否减轻吸烟对肺部造成的损伤的研究还很有限。本研究旨在探讨褪黑激素缓解被动吸烟引起的急性肺部疾病的机制:方法:将大鼠分为五组(n = 6):对照组和暴露于低、中、高浓度烟雾的三组,以及褪黑素治疗组:数据表明,高浓度被动吸烟组的肺组织肺泡结构遭到破坏,肺组织的总抗氧化能力随着烟雾浓度的增加而降低。TNF-α、IL-6和IL-1β的表达也表现出相似的结果。高浓度吸烟组的抗凋亡因子 Bcl-2 和 Bcl-xL mRNA 水平明显下降,而中低浓度组则无明显变化。相反,高浓度被动吸烟组促凋亡因子 Bax 和 Caspase-3 mRNA 水平升高。此外,暴露于烟雾后,肺组织中的内源性褪黑素水平逐渐下降,而外源性褪黑素则缓解了肺组织中炎症因子和细胞凋亡相关因子的变化。此外,在高浓度吸烟时,肺癌相关基因血管内皮细胞生长因子(VEGF)、细胞色素P450 1A1(CYP1A1)和细胞色素P450 1B1(CYP1B1)的mRNA水平显著升高,而外源性褪黑素可降低这些基因在肺组织中的表达:这些研究结果表明,褪黑素可减少被动吸烟引起的肺组织损伤、细胞凋亡和炎症反应,并降低肺癌相关基因的表达。还需要对外源性褪黑素治疗进行进一步的实验研究。
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引用次数: 0
Prognostic risk prediction model for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD): a systematic review and meta-analysis. 慢性阻塞性肺疾病(AECOPD)急性加重期患者的预后风险预测模型:系统综述与荟萃分析。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-14 DOI: 10.1186/s12931-024-03033-4
Zihan Xu, Fan Li, You Xin, Ye Wang, Yuping Wang

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use.

Method: PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024. Data extraction and evaluation were conducted using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). The Prediction model Risk Of Bias Assessment Tool (PROBAST) was employed to assess the risk of bias and applicability of the models.

Results: After deduplication and screening 5942 retrieved articles, 46 studies comprising 53 models were included. Of these, 17 (37.0%) studies developed from studies conducted in China. All models were based on cohort studies. Mortality was the predicted outcome in 27 (50.9%) models. Logistic regression was used in 41 (77.4%) models, while machine learning methods were employed in 9 (17.0%) models. The median (minimum, maximum) sample size for model development was 672 (106, 150,035). The median (minimum, maximum) number of predictors per model was 5 (2, 42). Frequently used predictors included age (n = 28), dyspnea severity scores (n = 12), and PaCO2 (n = 11). The pooled AUC was 0.80 for mortality prediction models and 0.84 for hospitalization-related outcomes. 52 models have a high overall risk of bias, and all models were judged to have low concern regarding applicability. Major sources of bias included insufficient sample sizes (83.0%), reliance on univariate analysis for predictor selection (73.6%), inappropriate internal and external validation methods (54.7%), inappropriate inclusion and exclusion criteria for study subjects (50.9%) and so on. The only model with low bias was the PEARL score.

Conclusion: Current prognostic risk prediction models for patients with AECOPD generally exhibit high bias. Future efforts should standardize model development and validation methods, and develop widely usable clinical models.

背景:慢性阻塞性肺疾病(COPD)是一种常见的呼吸系统疾病,也是导致死亡的主要原因之一,急性加重期(AECOPD)使其管理和预后大大复杂化。尽管针对 AECOPD 患者开发了各种预后预测模型,但其性能和临床适用性仍不明确,因此有必要对这些模型进行系统性回顾评估,并为其未来改进和临床应用提供指导:方法:检索了 PubMed、Web of Science、CINAHL、Scopus、EMBASE 和 Medline 上从开始到 2024 年 2 月 5 日发表的研究。数据提取和评估采用预测模型研究系统综述批判性评估和数据提取核对表(CHARMS)进行。预测模型偏倚风险评估工具(PROBAST)用于评估模型的偏倚风险和适用性:在对检索到的 5942 篇文章进行去重和筛选后,共纳入了 46 项研究,包括 53 个模型。其中,17 项研究(37.0%)源自在中国进行的研究。所有模型均基于队列研究。在 27 个(50.9%)模型中,死亡率是预测结果。41个(77.4%)模型采用了逻辑回归,9个(17.0%)模型采用了机器学习方法。模型开发样本量的中位数(最小,最大)为 672(106,150,035)。每个模型预测因子数量的中位数(最小,最大)为 5(2,42)。常用的预测因子包括年龄(n = 28)、呼吸困难严重程度评分(n = 12)和 PaCO2(n = 11)。死亡率预测模型的集合 AUC 为 0.80,住院相关结果的集合 AUC 为 0.84。52 个模型的总体偏倚风险较高,所有模型的适用性均被判定为较低。偏倚的主要来源包括样本量不足(83.0%)、依赖单变量分析选择预测因子(73.6%)、内部和外部验证方法不当(54.7%)、研究对象的纳入和排除标准不当(50.9%)等。唯一偏倚较低的模型是 PEARL 评分:结论:目前针对 AECOPD 患者的预后风险预测模型普遍存在较高的偏倚性。结论:目前针对 AECOPD 患者的预后风险预测模型普遍存在较高的偏倚性,今后的工作应规范模型的开发和验证方法,并开发出广泛可用的临床模型。
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引用次数: 0
Letter to the editor: Incidence rate of occult lymph node metastasis in clinical T1 - 2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study. 致编辑的信:基于对比增强 CT 成像的临床 T1 - 2N0M0 小细胞肺癌患者隐匿性淋巴结转移发生率和放射学预测:一项多中心研究。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-13 DOI: 10.1186/s12931-024-02940-w
Zhe Hu, Zhikang Tian, Xi Wei, Yueqin Chen
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引用次数: 0
Mortality after treatment of malignant pleural effusions with indwelling pleural catheters versus chemical pleurodesis: a population-based study. 使用留置胸膜导管与化学胸膜穿刺术治疗恶性胸腔积液后的死亡率:一项基于人群的研究。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-13 DOI: 10.1186/s12931-024-03023-6
Chanel Kwok, Kednapa Thavorn, Kayvan Amjadi, Shawn D Aaron, Tetyana Kendzerska

Background: Little is known about patient outcomes following treatment of malignant pleural effusions (MPE) in the real-world setting.

Research question: We aimed to compare post-procedure all-cause mortality between individuals who received indwelling pleural catheter (IPC) insertion versus chemical pleurodesis for managing MPEs.

Study design and methods: We performed a retrospective population-based study using provincial health administrative data (Ontario, Canada) of adults with a MPE who underwent IPC insertion or chemical pleurodesis between 2015 and 2019. Individuals were followed until death or March 31, 2021. Difference in post-procedure mortality was calculated using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis to balance potential confounders at baseline.

Results: We identified 4,790 (77.3%) individuals who received an IPC and 1,407 (22.7%) who had chemical pleurodesis for MPE. IPC insertions are increasing and chemical pleurodesis procedures are decreasing. The majority of IPCs were inserted in outpatients (61%), by pulmonologists (64.2%) and at sites with higher annual IPC volume, while chemical pleurodesis procedures were generally done by thoracic surgeons (74%) and at sites with higher annual pleurodesis volumes. In unadjusted comparison median time from initial cancer diagnosis to intervention was significantly longer in the IPC group (244 days, interquartile range [IQR]:33-903) compared to pleurodesis group (81 days, IQR:10-737; p < 0.0001). Unadjusted median time from index procedure to death was significantly longer in the pleurodesis group (165[IQR:48-457] days vs. 81[IQR:29-256] days, p < 0.0001), however the difference between groups became insignificant after the IPTW was applied (HR 1.27, 95%CI 0.95-1.69). 35% of IPCs were removed prior to death or end of follow-up.

Interpretation: After adjusting for differences in baseline characteristics there was no difference in post-procedure mortality between IPC and chemical pleurodesis groups. In the real world, there are significant differences in the characteristics of patients who receive these two procedures and notable regional practice variation between procedure use. Future research should evaluate these variations in care and their effect on patient outcomes.

背景:在现实世界中,人们对恶性胸腔积液(MPE)治疗后的患者预后知之甚少:研究设计与方法:我们旨在比较接受留置胸膜导管插入术(IPC)和化学胸膜穿刺术治疗 MPE 的患者术后全因死亡率:我们利用省级卫生行政数据(加拿大安大略省)对在 2015 年至 2019 年期间接受过留置胸膜导管插入术或化学胸膜穿刺术的 MPE 成人进行了一项基于人群的回顾性研究。研究人员对患者进行了随访,直至其死亡或 2021 年 3 月 31 日。采用逆概率治疗加权(IPTW)调整后的考克斯比例危险回归分析计算术后死亡率的差异,以平衡基线的潜在混杂因素:我们发现 4,790 人(77.3%)接受了 IPC,1,407 人(22.7%)接受了 MPE 化学胸膜穿刺术。插入 IPC 的人数在增加,而化学胸膜穿刺术在减少。大多数IPC是在门诊病人(61%)、肺科医生(64.2%)和年IPC手术量较高的医院进行的,而化学性胸膜穿刺术一般是由胸外科医生(74%)和年胸膜穿刺术量较高的医院进行的。在未经调整的比较中,IPC 组从癌症初步诊断到介入治疗的中位时间(244 天,四分位数间距[IQR]:33-903)明显长于胸膜腔穿刺组(81 天,IQR:10-737;P 解释:IPC 组从癌症初步诊断到介入治疗的中位时间(244 天,四分位数间距[IQR]:33-903):调整基线特征差异后,IPC 组和化学胸膜穿刺组的术后死亡率没有差异。在现实世界中,接受这两种手术的患者特征存在显著差异,而且不同地区在使用这两种手术时也存在明显差异。未来的研究应评估这些护理差异及其对患者预后的影响。
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引用次数: 0
Euphorbium compositum SN improves the innate defenses of the airway mucosal barrier network during rhinovirus infection. 在鼻病毒感染过程中,大戟科植物 SN 可提高气道粘膜屏障网络的先天防御能力。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-13 DOI: 10.1186/s12931-024-03030-7
Charu Rajput, Haleh Ganjian, Ganesh Muruganandam, Kathrin Weyer, Julia Dannenmaier, Bernd Seilheimer, Umadevi Sajjan

Background: Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection.

Methods: Mucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined.

Results: ECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance.

Conclusions: ECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections.

背景:鼻病毒(RV)是健康人患普通感冒的主要原因,也与慢性肺部疾病患者的急性加重有关。然而,目前还没有针对鼻病毒的疫苗或有效治疗方法。本研究调查了由天然成分制成的多成分、多靶点药物--Euphorbium compositum SN(ECSN6)对RV感染过程中粘膜屏障网络的影响:方法:用RV或假性RV感染粘膜分化气道上皮细胞培养物,并用20%的ECSN6或安慰剂治疗,每天两次。通过测量经上皮阻力(TER)、对菊粉的通透性以及细胞间连接蛋白(IJ)的表达和定位来评估屏障完整性。此外,还测量了纤毛搏动频率(CBF)、促炎细胞因子、抗病毒干扰素和粘蛋白的表达以及病毒载量。C57BL/6 小鼠经鼻感染 RV 或假性 RV,并接受 40% ECSN6 或安慰剂治疗,每天两次。测定鼻窦粘膜炎症、E-cadherin定位、病毒载量和粘蛋白基因表达:结果:ECSN6处理的未感染细胞培养物的TER比安慰剂处理的细胞培养物有小幅但显著的增加,这与E-cadherin和ZO-1在IJ上的定位增强有关。在 RV 感染的培养物中,使用 ECSN6(而非安慰剂)处理可防止 RV 引起的以下情况:(1)TER 降低;(2)E-cadherin 和 ZO-1 与 IJ 分离;(3)粘蛋白表达;以及(4)CBF 衰减。ECSN6 还能降低 RV 刺激的促炎细胞因子的表达和对菊粉的通透性。虽然 ECSN6 能明显增加一些抗病毒 I 型和 III 型干扰素的表达,但它并不能改变病毒载量。在体内,ECSN6减轻了RV-A1诱导的鼻粘膜中度炎症,有益地影响了RV-A1诱导的细胞因子反应和Muc5ac mRNA的表达,并防止了RV导致的E-cadherin与鼻粘膜IJ的解离,但对病毒清除没有影响:结论:ECSN6可预防RV引起的气道粘膜屏障功能障碍,并改善免疫和粘膜屏障功能。ECSN6 可通过促进紧密连接蛋白和粘附连接蛋白在 IJ 上的定位来维持屏障功能的完整性。这反过来又可能导致体外观察到的 RV 诱导的促炎反应减少。通过改善气道粘膜屏障网络的先天防御功能,ECSN6 可减轻 RV 感染引起的呼吸道症状。
{"title":"Euphorbium compositum SN improves the innate defenses of the airway mucosal barrier network during rhinovirus infection.","authors":"Charu Rajput, Haleh Ganjian, Ganesh Muruganandam, Kathrin Weyer, Julia Dannenmaier, Bernd Seilheimer, Umadevi Sajjan","doi":"10.1186/s12931-024-03030-7","DOIUrl":"10.1186/s12931-024-03030-7","url":null,"abstract":"<p><strong>Background: </strong>Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection.</p><p><strong>Methods: </strong>Mucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined.</p><p><strong>Results: </strong>ECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance.</p><p><strong>Conclusions: </strong>ECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"407"},"PeriodicalIF":5.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631156","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}
引用次数: 0
Serum soluble isoform of receptor for advanced glycation end product is a predictive biomarker for acute exacerbation of idiopathic pulmonary fibrosis: a German and Japanese cohort study. 血清高级糖化终产物受体可溶性同工酶是特发性肺纤维化急性加重的预测性生物标志物:一项德国和日本的队列研究。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-11 DOI: 10.1186/s12931-024-03014-7
Erika Kitadai, Kakuhiro Yamaguchi, Shinichiro Ohshimo, Hiroshi Iwamoto, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Taku Nakashima, Hironobu Hamada, Francesco Bonella, Josune Guzman, Ulrich Costabel, Noboru Hattori

Background: The receptor for advanced glycation end product (RAGE) is a transmembrane receptor accelerating a pro-inflammatory signal. RAGE signalling is promoted by decreased soluble isoform of RAGE (sRAGE), which is a decoy receptor for RAGE ligands, and RAGE SNP rs2070600 minor allele. In Caucasian and Japanese cohorts, low circulatory sRAGE levels and presence of the minor allele are associated with poor survival of idiopathic pulmonary fibrosis (IPF) and increased disease susceptibility to interstitial lung disease, respectively. However, whether sRAGE and RAGE SNP rs2070600 are associated with acute exacerbation of IPF (AE-IPF) is unclear.

Methods: This retrospective cohort study evaluated the association between the onset of AE-IPF and serum sRAGE levels in 69 German and 102 Japanese patients with IPF. The association of AE-IPF with RAGE SNP rs2070600 in 51 German and 84 Japanese patients, whose DNA samples were stored, was also investigated.

Results: In each cohort, the incidence of AE-IPF was significantly and reproducibly higher in the patients with sRAGE < 467.1 pg/mL. In a pooled exploratory analysis, the incidence of AE-IPF was lowest in the patients with higher sRAGE levels and rs2070600 minor allele, although no significant difference in the incidence was observed between the patients with and without the rs2070600 minor allele.

Conclusions: Low sRAGE levels were associated with increased incidence of AE-IPF in two independent cohorts of different ethnicities. The combination of rs2070600 and sRAGE levels may stratify patients with IPF for the risk of AE.

背景:高级糖化终产物受体(RAGE)是一种跨膜受体,可加速产生促炎信号。作为 RAGE 配体诱饵受体的 RAGE 可溶性异构体(sRAGE)的减少以及 RAGE SNP rs2070600 小等位基因会促进 RAGE 信号的传递。在白种人和日本人队列中,循环中 sRAGE 水平低和小等位基因的存在分别与特发性肺纤维化(IPF)存活率低和间质性肺病易感性增加有关。然而,sRAGE 和 RAGE SNP rs2070600 是否与 IPF 急性加重(AE-IPF)相关尚不清楚:这项回顾性队列研究评估了 69 名德国和 102 名日本 IPF 患者 AE-IPF 发病与血清 sRAGE 水平之间的关系。研究还调查了 51 名德国患者和 84 名日本患者的 AE-IPF 与 RAGE SNP rs2070600 的关系,这些患者的 DNA 样本已被保存:结果:在每个队列中,sRAGE 患者的 AE-IPF 发生率都明显较高,且具有可重复性:在两个不同种族的独立队列中,低 sRAGE 水平与 AE-IPF 发病率增加有关。结合 rs2070600 和 sRAGE 水平可对 IPF 患者进行 AE 风险分层。
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引用次数: 0
Beyond diagnosis: maximizing the role of medical thoracoscopy in pleural disease treatment. 超越诊断:最大限度地发挥内科胸腔镜在胸膜疾病治疗中的作用。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-11 DOI: 10.1186/s12931-024-03001-y
Kaige Wang, Ling Zuo, Panwen Tian, Fen Tan, Weimin Li

Medical thoracoscopy has been extensively utilized in the diagnosis of pleural disease, yet its potential therapeutic applications remain underutilized. This article presents a comprehensive overview of the various uses of medical thoracoscopy in managing pleural diseases. It has been employed to facilitate thoracic drainage and reduce hospitalization duration of patients with complicated parapneumonic effusions and empyema. Additionally, medical thoracoscopic occlusion therapy can be used for bronchoscopic closure and refractory pneumothorax. However, there is currently a lack of standardized protocols for utilizing medical thoracoscopy to reduce the volume of giant emphysematous bullae. Furthermore, medical thoracoscopy allows for pleurodesis or photodynamic therapy in patients with malignant pleural effusion. Nevertheless, further high-quality clinical research is needed to validate these findings.

医用胸腔镜已被广泛用于胸膜疾病的诊断,但其潜在的治疗应用仍未得到充分利用。本文全面概述了内科胸腔镜在治疗胸膜疾病方面的各种用途。它已被用于促进胸腔引流,缩短复杂性肺旁积液和肺水肿患者的住院时间。此外,医学胸腔镜闭塞疗法还可用于支气管镜闭塞和难治性气胸。然而,目前还缺乏利用医用胸腔镜缩小巨大气肿体积的标准化方案。此外,医用胸腔镜还可对恶性胸腔积液患者进行胸膜腔穿刺术或光动力疗法。不过,还需要进一步的高质量临床研究来验证这些发现。
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引用次数: 0
Computed tomography morphological assessments of central airways in interstitial lung abnormalities and idiopathic pulmonary fibrosis. 对肺间质异常和特发性肺纤维化的中央气道进行计算机断层扫描形态学评估。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-10 DOI: 10.1186/s12931-024-03032-5
Tomoki Maetani, Naoya Tanabe, Kiminobu Tanizawa, Ryo Sakamoto, Yusuke Shiraishi, Yusuke Hayashi, Michihiro Uyama, Atsushi Matsunashi, Susumu Sato, Katsuhiro Suzuki, Izuru Masuda, Motonari Fukui, Shizuo Kaji, Tomohiro Handa, Toyohiro Hirai

Background: Little is known about whether central airway morphological changes beyond traction bronchiectasis develop and affect clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to compare central airway structure comprehensively between patients with IPF, subjects with interstitial lung abnormality (ILA), and those without ILA (control) using computed tomography (CT). We further examined the prognostic impact of IPF-specific CT airway parameters in patients with IPF.

Methods: This retrospective study included male patients with IPF, and male health checkup subjects divided into those with ILA and control based on lung cancer screening CT. Using an artificial intelligence-based segmentation technique, the extent of fibrotic regions in the lung was quantified. After airway tree segmentation, CT parameters for central airway morphology, including the lumen area of the extrapulmonary airways (LAextra), wall and lumen area of the segmental/subsegmental intrapulmonary airways (WAintra and LAintra), tracheal distortion (tortuosity and curvature) and bifurcation angle of the main carina, were calculated.

Results: There were 106 patients with IPF, 53 subjects with ILA, and 1295 controls. Multivariable models adjusted for age, height and smoking history revealed that LAintra and WAintra were larger in both ILA and IPF, and that tracheal tortuosity and curvature were higher in IPF, but not in ILA, than in the control, whereas the bifurcation angle did not differ between the 3 groups. According to multivariable Cox proportional hazards models including only patients with IPF, increased WAintra was significantly associated with greater mortality (standardized hazard ratio [95% confidence interval] = 1.58 [1.17, 2.14]), independent of the volume of fibrotic regions, normal-appearing regions, or the whole airway tree in the lung.

Conclusion: Increased lumen area and wall thickening of the central airways may be involved in the pathogenesis of ILA and IPF, and wall thickening may affect the prognosis of patients with IPF.

背景:对于特发性肺纤维化(IPF)患者除牵引性支气管扩张外是否还会发生中心气道形态学改变并影响临床预后,目前所知甚少。本研究旨在使用计算机断层扫描(CT)全面比较 IPF 患者、肺间质异常(ILA)患者和无 ILA 患者(对照组)的中心气道结构。我们进一步研究了 IPF 特异性 CT 气道参数对 IPF 患者预后的影响:这项回顾性研究包括 IPF 男性患者,以及根据肺癌筛查 CT 将 ILA 患者和对照组分为两组的男性健康体检者。采用基于人工智能的分割技术,对肺部纤维化区域的范围进行量化。气道树分割后,计算中央气道形态的CT参数,包括肺外气道的管腔面积(LAextra)、肺内气道节段/亚节段的管壁和管腔面积(WAintra和LAintra)、气管变形(迂曲度和弯曲度)以及主心尖的分叉角:共有 106 名 IPF 患者、53 名 ILA 患者和 1295 名对照者。根据年龄、身高和吸烟史调整的多变量模型显示,ILA 和 IPF 患者的 LAintra 和 WAintra 均较大,IPF 患者的气管迂曲度和弯曲度高于对照组,但 ILA 患者的气管迂曲度和弯曲度不高于对照组,而 3 组患者的分叉角没有差异。根据仅包括IPF患者的多变量Cox比例危险模型,WAintra增加与死亡率升高显著相关(标准化危险比[95%置信区间] = 1.58 [1.17,2.14]),与纤维化区域、外观正常区域或肺部整个气道树的体积无关:结论:中心气道管腔面积增大和管壁增厚可能与 ILA 和 IPF 的发病机制有关,管壁增厚可能会影响 IPF 患者的预后。
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引用次数: 0
Atomized inhalation of indocyanine green in thoracoscopic surgery for intralobar pulmonary sequestration: a multicenter study. 在胸腔镜手术中雾化吸入吲哚菁绿治疗肺内封堵:一项多中心研究。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-10 DOI: 10.1186/s12931-024-03024-5
Ye Yin, Guofeng Zhang, Wei Li, Didi Zhuansun, Xiaofeng Xiong, Yanan Li, Yin He, Wenjing Wang, Tianqi Zhu, Jiexiong Feng

Background: Investigate the safety and efficacy of preoperative atomization inhalation of indocyanine green (ICG) solution in precise lesion resection of pediatric thoracoscopic intralobar pulmonary sequestration.

Methods: A multicenter 1:1 matched case-control study was adopted, to compare the safety and efficacy of the ICG group (preoperative atomization inhalation of 0.5 mg/kg ICG solution) with traditional group (no preoperative atomization inhalation of ICG solution). The baseline, intraoperative, and postoperative recovery conditions of the two groups were observed. Outpatient follow-up visits were conducted 3 to 6 months after surgery, including lung CT scans and pulmonary ventilation function tests.

Results: 134 patients were included in the study. The ICG group included 67 patients, and the traditional surgery group included 67 patients matched at a ratio of 1:1 according to age and lesion location. There were no reports of deaths or adverse reactions. The postoperative chest drainage tube indwelling time [(53.19 ± 8.15) hours vs. (73.25 ± 15.51) hours, P < 0.001] and postoperative hospital stay [(4.81 ± 1.84) days vs. (6.72 ± 1.31) days, P < 0.001] were shorter in the ICG group than in the traditional group. More importantly, the postoperative pulmonary function in the ICG group was better than that in the traditional group. No residual lesions were found in the postoperative CT examination of both groups.

Conclusions: The innovative application of atomization inhalation of ICG provides the possibility for precise localization and lesion resection of pediatric thoracoscopic intralobar pulmonary sequestration. This maximizes the preservation of normal lung parenchyma, better improves postoperative pulmonary function, and shortens postoperative recovery time.

背景:探讨术前雾化吸入吲哚菁绿(ICG)溶液在小儿胸腔镜下肺动脉内嵌塞精确病灶切除术中的安全性和有效性:采用多中心1:1匹配病例对照研究,比较ICG组(术前雾化吸入0.5 mg/kg ICG溶液)与传统组(术前不雾化吸入ICG溶液)的安全性和有效性。观察了两组的基线、术中和术后恢复情况。术后 3 至 6 个月进行门诊随访,包括肺 CT 扫描和肺通气功能测试:研究共纳入 134 名患者。ICG组包括67名患者,传统手术组包括67名患者,两组患者的年龄和病变位置比例为1:1。无死亡或不良反应报告。术后胸腔引流管留置时间[(53.19±8.15)小时 vs. (73.25±15.51)小时,P 结论:ICG 技术在传统手术中的创新性应用,为患者提供了更多的选择:雾化吸入 ICG 的创新应用为小儿胸腔镜下肺内嵌塞的精确定位和病灶切除提供了可能。这最大限度地保留了正常肺实质,更好地改善了术后肺功能,缩短了术后恢复时间。
{"title":"Atomized inhalation of indocyanine green in thoracoscopic surgery for intralobar pulmonary sequestration: a multicenter study.","authors":"Ye Yin, Guofeng Zhang, Wei Li, Didi Zhuansun, Xiaofeng Xiong, Yanan Li, Yin He, Wenjing Wang, Tianqi Zhu, Jiexiong Feng","doi":"10.1186/s12931-024-03024-5","DOIUrl":"10.1186/s12931-024-03024-5","url":null,"abstract":"<p><strong>Background: </strong>Investigate the safety and efficacy of preoperative atomization inhalation of indocyanine green (ICG) solution in precise lesion resection of pediatric thoracoscopic intralobar pulmonary sequestration.</p><p><strong>Methods: </strong>A multicenter 1:1 matched case-control study was adopted, to compare the safety and efficacy of the ICG group (preoperative atomization inhalation of 0.5 mg/kg ICG solution) with traditional group (no preoperative atomization inhalation of ICG solution). The baseline, intraoperative, and postoperative recovery conditions of the two groups were observed. Outpatient follow-up visits were conducted 3 to 6 months after surgery, including lung CT scans and pulmonary ventilation function tests.</p><p><strong>Results: </strong>134 patients were included in the study. The ICG group included 67 patients, and the traditional surgery group included 67 patients matched at a ratio of 1:1 according to age and lesion location. There were no reports of deaths or adverse reactions. The postoperative chest drainage tube indwelling time [(53.19 ± 8.15) hours vs. (73.25 ± 15.51) hours, P < 0.001] and postoperative hospital stay [(4.81 ± 1.84) days vs. (6.72 ± 1.31) days, P < 0.001] were shorter in the ICG group than in the traditional group. More importantly, the postoperative pulmonary function in the ICG group was better than that in the traditional group. No residual lesions were found in the postoperative CT examination of both groups.</p><p><strong>Conclusions: </strong>The innovative application of atomization inhalation of ICG provides the possibility for precise localization and lesion resection of pediatric thoracoscopic intralobar pulmonary sequestration. This maximizes the preservation of normal lung parenchyma, better improves postoperative pulmonary function, and shortens postoperative recovery time.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"403"},"PeriodicalIF":5.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631151","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}
引用次数: 0
Repeated inhalation of GM-CSF by nonhuman primates induces bronchus-associated lymphoid tissue along the lower respiratory tract. 非人灵长类动物反复吸入 GM-CSF 会诱导下呼吸道支气管相关淋巴组织。
IF 5.8 2区 医学 Q1 Medicine Pub Date : 2024-11-10 DOI: 10.1186/s12931-024-03003-w
Ryushi Tazawa, Riuko Ohashi, Nobutaka Kitamura, Takahiro Tanaka, Kazuhide Nakagaki, Sachiko Yuki, Atsushi Fujiwara, Koh Nakata

Background: Repeated inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently approved in Japan as a treatment for autoimmune pulmonary alveolar proteinosis. However, the detailed physiological and pathological effects of repeated inhalation in the long term, especially at increasing doses, remain unclear.

Methods: In this chronic safety study, we administered 24 cynomolgus monkeys (Macaca fascicularis) aged 2-3 years with aerosolized sargramostim (a yeast-derived recombinant human GM-CSF [rhGM-CSF]) biweekly for 26 weeks across four dosing groups (0, 5, 100, and 500 µg/kg/day). We measured the serum GM-CSF antibody (GM-Ab) concentration by an ELISA and assessed the neutralizing capacity of GM-Ab using the GM-CSF-dependent cell line TF-1. We subjected lung tissue samples taken from all monkeys at 27 weeks to histopathological assessment using a sargramostim-specific monoclonal antibody to detect localization of residual sargramostim.

Results: All the animals maintained good body condition and showed steady weight gain throughout the study. The pathological analyses of the lung revealed the formation of induced bronchus-associated lymphoid tissue (iBALT) in the lower respiratory tract, even at the clinical dose of 5 µg/kg/day. There was a relationship between the number or size of BALT and sargramostim dose or the serum GM-Ab levels. Immunohistochemical analyses revealed GM-Ab-producing cells in the follicular region of iBALT, with residual sargramostim in the follicles. Leucocyte counts were inversely correlated with GM-Ab levels in the high-dose groups. Additionally, serum GM-Ab from the treated animals significantly suppressed the alveolar macrophage proliferation activity of both Cynomolgus recombinant and rhGM-CSF in vitro.

Conclusion: Long-term repeated inhalation of sargramostim led to iBALT formation in the lower respiratory tract, even at the clinical dose of 5 µg/kg/day, with the extent of iBALT formation increasing in a dose-dependent manner. Inhaled sargramostim was localized to the follicular region of iBALT nodules, which may induce the production of GM-Ab.

背景:最近,日本批准重复吸入粒细胞-巨噬细胞集落刺激因子(GM-CSF)治疗自身免疫性肺泡蛋白沉着症。然而,长期反复吸入(尤其是增加剂量时)对生理和病理影响的详细情况仍不清楚:在这项慢性安全性研究中,我们给 24 只 2-3 岁的猕猴(Macaca fascicularis)注射了气雾化沙格列莫司汀(一种从酵母中提取的重组人 GM-CSF [rhGM-CSF]),每两周一次,持续 26 周,共分为四个剂量组(0、5、100 和 500 µg/kg/天)。我们用酶联免疫吸附法测定了血清中 GM-CSF 抗体(GM-Ab)的浓度,并用依赖 GM-CSF 的细胞株 TF-1 评估了 GM-Ab 的中和能力。我们对所有猴子在27周时采集的肺组织样本进行了组织病理学评估,使用沙格列莫司汀特异性单克隆抗体检测残留沙格列莫司汀的定位:在整个研究过程中,所有动物均保持良好的身体状况,体重稳步增长。肺部病理分析显示,即使临床剂量为5微克/千克/天,下呼吸道也会形成诱导支气管相关淋巴组织(iBALT)。BALT的数量或大小与沙格列莫司汀剂量或血清GM-Ab水平之间存在关系。免疫组化分析显示,iBALT的滤泡区有产生GM-Ab的细胞,滤泡内有残留的沙格氏剂。在高剂量组中,白细胞计数与 GM-Ab 水平成反比。此外,治疗动物的血清 GM-Ab 能显著抑制体外 Cynomolgus 重组和 rhGM-CSF 的肺泡巨噬细胞增殖活性:结论:长期反复吸入沙格列莫司汀会导致下呼吸道中iBALT的形成,即使临床剂量为5 µg/kg/天,iBALT形成的程度也呈剂量依赖性增加。吸入的沙格列莫司汀被定位在 iBALT 结节的滤泡区,这可能会诱导 GM-Ab 的产生。
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引用次数: 0
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Respiratory Research
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