Open Respiratory Archives最新文献_第2页

DIAGNOSTIC TRANSCRIPTOMIC SIGNATURES FOR MYCOPLASMA PNEUMONIAE PNEUMONIA TO GUIDEPEDIATRIC PATIENT TREATMENT 肺炎支原体肺炎的诊断转录组特征指导儿科患者治疗

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100569

Sandra Viz-Lasheras , Alberto Gómez-Carballa , Irene Rivero-Calle , Federico Martinón-Torres , Antonio Salas

Introduction

Mycoplasma pneumoniae is a frequent cause of atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to β-lactam antibiotics, the first-line treatment for classical bacterial pneumonia. Current microbiological diagnostic tests for M. pneumoniae are often slow, insensitive or non-specific, which leads clinicians to prescribe empirical antibiotics. Therefore, there is an urgent need for accurate, rapid and host-based diagnostic tools to guide antimicrobial therapy more precisely.

Objectives

This study aims to delineate the host blood transcriptomic response associated with M. pneumoniae pneumonia and to derive minimal gene expression signatures that reliably distinguish M. pneumoniae pneumonia from other bacterial and viral pneumonias in pediatric patients.

Methods

Using blood microarray data from 107 children hospitalized with pneumonia — including 30 with confirmed M. pneumoniae infection — we performed differential expression analyses followed by a resampling-based penalized regression (LASSO) approach to identify optimal small-size transcriptomic signatures. These signatures (3 to 10 transcripts) were then validated in an independent RNA-seq cohort of pediatric pneumonia patients. In addition, we performed pathway-level analysis (GSVA) to characterize functional host-response differences between M. pneumoniae and viral pneumonias.

Results

We identified eight robust transcriptomic signatures (each comprising 3–10 genes) that discriminate M. pneumoniae pneumonia from other bacterial or viral pneumonias with high accuracy (AUC range: 0.84 – 0.95). Existing broadly used signatures to distinguish bacterial from viral infections/pneumonias performed poorly in identifying M. pneumoniae. Our new signatures retained strong performance in the independent RNA-seq validation cohort, demonstrating their robustness and reproducibility. Pathway analysis revealed that M. pneumoniae pneumonia triggers distinct host immune and inflammatory pathways compared to viral pneumonia, supporting the biological plausibility of the identified signatures.

Conclusions

Mycoplasma pneumoniae pneumonia produces a unique host transcriptomic response that can be captured by small, robust signatures. These diagnostic gene signatures have the potential to significantly improve the timely and accurate identification of M. pneumoniae in pediatric pneumonia patients, inform antimicrobial decision-making (e.g., macrolide vs β-lactam), and help reduce inappropriate antibiotic use. Adoption of such transcriptome-based diagnostics could enhance patient management and antimicrobial stewardship in clinical practice.

肺炎支原体是儿童和青年非典型肺炎的常见病因。由于缺乏细胞壁，它对β-内酰胺类抗生素具有耐药性，而β-内酰胺类抗生素是经典细菌性肺炎的一线治疗药物。目前肺炎支原体的微生物诊断检测通常是缓慢的、不敏感的或非特异性的，这导致临床医生开出经验性抗生素。因此，迫切需要准确、快速和基于宿主的诊断工具，以更精确地指导抗菌药物治疗。目的：本研究旨在描述与肺炎支原体肺炎相关的宿主血液转录组反应，并获得可靠区分儿科患者肺炎支原体肺炎与其他细菌性和病毒性肺炎的最小基因表达特征。方法使用107名肺炎住院儿童的血液微阵列数据，包括30名确诊肺炎支原体感染的儿童，我们进行了差异表达分析，然后采用基于重采样的惩罚回归（LASSO）方法来确定最佳的小尺寸转录组特征。这些特征（3到10个转录本）随后在独立的儿科肺炎患者RNA-seq队列中得到验证。此外，我们进行了途径水平分析（GSVA）来表征肺炎支原体和病毒性肺炎之间的功能性宿主反应差异。结果我们鉴定出8个稳健的转录组特征（每个特征包含3-10个基因），可以高精度地将肺炎支原体肺炎与其他细菌或病毒性肺炎区分开来（AUC范围：0.84 - 0.95）。现有广泛用于区分细菌感染和病毒感染/肺炎的特征在识别肺炎支原体方面表现不佳。我们的新签名在独立的RNA-seq验证队列中保持了强大的性能，证明了它们的稳健性和可重复性。途径分析显示，与病毒性肺炎相比，肺炎支原体肺炎触发不同的宿主免疫和炎症途径，支持所识别特征的生物学合理性。结论肺炎支原体肺炎产生独特的宿主转录组反应，可以通过小而强大的特征来捕获。这些诊断基因特征有可能显著提高儿科肺炎患者肺炎支原体的及时和准确鉴定，为抗菌决策提供信息（例如大环内酯与β-内酰胺），并有助于减少不适当的抗生素使用。采用这种基于转录组的诊断可以加强临床实践中的患者管理和抗菌药物管理。

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引用次数: 0

Comité de Dirección y Comisión de Formación CIBERES-CIBER-BBN CIBERES-CIBER-BBN指导委员会和培训委员会

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/S2659-6636(26)00058-5

引用次数: 0

TRACK RECORD AND CAPABILITIES OF THE BIOMEDICAL ENGINEERING GROUP AT THE UNIVERSITY OF VALLADOLID IN RESPIRATORY DISEASE RESEARCH 巴利亚多利德大学生物医学工程小组在呼吸道疾病研究方面的记录和能力

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100543

Fernando Vaquerizo-Villar , Verónica Barroso-García , Daniel Álvarez , Gonzalo C. Gutiérrez-Tobal , Javier Gómez-Pilar , Adrián Martín-Montero , Jorge Jiménez-García , Clara García-Vicente , Tomás Ruíz-Albi , Félix del Campo , Roberto Hornero

Introduction

The Biomedical Engineering Group (Grupo de Ingeniería Biomédica, GIB) at the University of Valladolid (UVa), member of CIBER-BBN (CB19/01/00012 group), has more than 20 years of research experience in the field of respiratory diseases. Working closely with national and international physicians specializing in areas such as pneumology, emergencies, and pediatrics, among others, we focus on applying different advanced processing techniques for biomedical data analysis, and artificial intelligence methods to develop predictive models for detection, prognosis, and personalized diagnosis of diverse respiratory pathologies.

Methods

we have expertise in analyzing a wide range of respiratory data—including biomedical signals and images, electronic health records, and blood biomarkers—across diverse conditions such as sleep apnea (in both adults and children), chronic obstructive pulmonary disease (COPD), asthma, and COVID-19. We have also experience in developing fully functional software applications that provide real-time analysis of biomedical data for the screening and management of respiratory diseases in healthcare systems.

Results

Our research has demonstrated significant clinical impact, supporting earlier interventions, simplified diagnostic systems, more accurate decision-making, and improved patient outcomes. Our track record is evidenced by near 80 Journal Citation Report (JCR) articles, five of them in collaboration with a researcher from the CIBERES (CB22/06/00035 group). We have also participated in more than 20 R&D regional, national, and European projects, and two patents in the USA.

Conclusions

We believe that this experience and these capabilities could be of great value in establishing collaborations with CIBERES groups.

巴利亚杜德大学（UVa）的生物医学工程小组（Grupo de Ingeniería biomdica， GIB）是CIBER-BBN （CB19/01/00012小组）的成员，在呼吸系统疾病领域有20多年的研究经验。我们与国内和国际上从事肺炎学、急诊和儿科等领域的医生密切合作，专注于应用不同的先进处理技术进行生物医学数据分析，并采用人工智能方法开发预测模型，用于检测、预后和个性化诊断各种呼吸系统疾病。方法我们在分析广泛的呼吸数据方面拥有专业知识，包括生物医学信号和图像、电子健康记录和血液生物标志物，涵盖不同的疾病，如睡眠呼吸暂停（成人和儿童）、慢性阻塞性肺疾病（COPD）、哮喘和COVID-19。我们在开发功能齐全的软件应用程序方面也有经验，这些应用程序为医疗系统中呼吸系统疾病的筛查和管理提供生物医学数据的实时分析。结果我们的研究显示了显著的临床影响，支持早期干预，简化诊断系统，更准确的决策，改善患者预后。近80篇期刊引用报告（JCR）证明了我们的业绩，其中5篇是与CIBERES （CB22/06/00035组）的一名研究员合作完成的。我们还参与了20多个地区、国家和欧洲的研发项目，并在美国获得了两项专利。我们相信这些经验和这些能力在与CIBERES小组建立合作方面具有很大的价值。

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引用次数: 0

CHARACTERIZATION OF EOSINOPHILS IN INDUCED SPUTUM AND LUNG BIOPSY USING SINGLE CELL RNA-SEQ WITHOUT SUBTYPE DISTINCTION 利用单细胞rna-seq检测诱导痰和肺活检中嗜酸性粒细胞的特征，不区分亚型

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100567

D. Rodríguez González , JA. Cañas , BG. Cosío , A. Iglesias , J. Bernaola , EJ. Pinillos-Robles , D. Betancor , J. Sastre , M.J. Rodríguez Nieto , V. del Pozo

Introduction

Recently, the existence of different eosinophil subtypes has been suggested based on the differential expression of several surface molecules. However, the existence of eosinophil subtypes remains controversial. So, the objective of this study is to investigate the existence of eosinophil subtypes in induced sputum and lung biopsy.

Methods

Induced sputum was collected from five patients with severe eosinophilic asthma. Additionally, six lung biopsy samples were taken from three severe asthmatic patients previous biological-treated and three patients after failure of biological drugs. The cell atlas were studied by Single Cell RNA-seq technique on the BD Rhapsody^TM scanner. Then, the bioinformatic analysis allowed grouping the different cell types according to their gene expression.

Results

Several clusters composed by different cell types such as eosinophils, macrophages, neutrophils, and epithelial cells were established in both induced sputum and in lung biopsies. Eosinophil-related genes were analyzed (EPX, CCR3, CD101, CLC, SELL, ANXA1, SIGLEC10, ADGRE1, ITGAX, ITGB2, ALOX15), resulting in an “eosinophil gene signature” that allowed to differentiate these cells from other cell types. However, it was not possible to differentiate eosinophil subtypes in either sputum or biopsies. Additionally, in lung biopsies, there were observed differences in the gene expression of ALOX15, POSTN, DPP10 or WFDC2 between both patient groups in eosinophils and, also, eosinophils from non-responder patients showed a different interactome respect to pre-treated asthmatic patients.

Conclusions

Single cell RNA-seq enabled the characterization of eosinophils and other cell populations in induced sputum and lung biopsies. However, it was not possible to unequivocally objectify the existence of eosinophil subtypes based on their gene expression. Furthermore, in lung biopsies, cellular interactions between patients before biological drug treatment and non-responder patients were different.

近年来，基于几种表面分子的差异表达，提出了不同嗜酸性粒细胞亚型的存在。然而，嗜酸性粒细胞亚型的存在仍然存在争议。因此，本研究的目的是探讨在诱导痰和肺活检中是否存在嗜酸性粒细胞亚型。方法收集5例重度嗜酸性哮喘患者的诱导痰。此外，还从3例既往生物药物治疗和3例生物药物治疗失败的重症哮喘患者中提取了6例肺活检样本。在BD RhapsodyTM扫描仪上采用单细胞RNA-seq技术对细胞图谱进行研究。然后，生物信息学分析允许根据基因表达对不同的细胞类型进行分组。结果在诱导痰和肺活检中均可建立由嗜酸性细胞、巨噬细胞、中性粒细胞和上皮细胞等不同类型细胞组成的细胞簇。对嗜酸性粒细胞相关基因（EPX、CCR3、CD101、CLC、SELL、ANXA1、SIGLEC10、ADGRE1、ITGAX、ITGB2、ALOX15）进行分析，得出“嗜酸性粒细胞基因标记”，从而将这些细胞与其他细胞类型区分开来。然而，在痰液或活检中无法区分嗜酸性粒细胞亚型。此外，在肺活检中，观察到两组患者嗜酸性粒细胞中ALOX15、POSTN、DPP10或WFDC2基因表达的差异，并且，无反应患者的嗜酸性粒细胞与治疗前的哮喘患者表现出不同的相互作用组。结论单细胞RNA-seq技术能够在诱导痰和肺活检中鉴定嗜酸性粒细胞和其他细胞群。然而，这是不可能明确客观存在的嗜酸性粒细胞亚型基于他们的基因表达。此外，在肺活检中，生物药物治疗前和无反应患者之间的细胞相互作用是不同的。

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引用次数: 0

CONSUMPTION PATTERNS AND WITHDRAWAL SYMPTOMS IN DUAL CANNABIS-TOBACCO USERS IN SPAIN: CROSS-SECTIONAL STUDY 西班牙大麻-烟草双重使用者的消费模式和戒断症状：横断面研究

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100568

Judith Saura , Ariadna Feliu , Marta Enríquez , Xavier Roca , Montse Ballbè , Marcela Fu , Lidia Segura , Esteve Fernández , Cristina Martínez

Background

Cannabis use has increased worldwide, with over 188 million users annually. In Spain, past-year prevalence among people aged 15–64 is 10.6%. Dual use of cannabis and tobacco is common, increasing health risks and complicating cessation. This study examines consumption patterns and cannabis withdrawal severity among dual users undergoing treatment for cannabis use disorder (CUD).

Methods

A cross-sectional study was conducted in substance use treatment programs in Catalonia, Spain. Participants were cannabis users initiating CUD treatment. A questionnaire collected sociodemographic data, cannabis and tobacco use characteristics (e.g., number of spliffs, tobacco amount), nicotine dependence, motivation to quit, and cannabis withdrawal symptoms. Descriptive and bivariate analyses were used to examine consumption differences. A hierarchical cluster analysis using Gower's distance identified behavioral patterns among participants.

Results

Data from 94 participants seeking CUD treatment were included. Daily tobacco use was reported by 91.5%, with a mean Fagerström score of 4.2/10. Most participants (88.1%) co-used cannabis with tobacco, and 75.8% experienced cannabis withdrawal symptoms, with women reporting greater severity. Cluster analysis revealed two profiles: Cluster 1 (71.0%) included mostly older males with higher motivation to quit and fewer withdrawal symptoms; Cluster 2 (29.0%) was younger, more gender-balanced, and showed higher nicotine dependence, and more severe withdrawal symptoms.

Conclusions

Co-use of cannabis and tobacco is highly prevalent among individuals entering CUD treatment. Higher nicotine dependence is associated with more severe withdrawal symptoms. Older males with higher motivation and fewer withdrawal symptoms may have better prognosis, highlighting motivation as cessation predictor. Findings are directly applicable to respiratory care, as identifying high-risk dual users can guide integrated cessation strategies and potentially reduce chronic respiratory disease.

Key words: Cannabis use disorder; tobacco use; co-use; nicotine dependence; cannabis withdrawal; motivation to quit; hierarchical clustering; substance use treatment

大麻的使用在世界范围内有所增加，每年有超过1.88亿人使用大麻。在西班牙，过去一年15-64岁人群的患病率为10.6%。大麻和烟草的双重使用很常见，增加了健康风险，并使戒烟复杂化。本研究调查了大麻使用障碍（CUD）治疗的双重使用者的消费模式和大麻戒断严重程度。方法对西班牙加泰罗尼亚地区药物使用治疗方案进行横断面研究。参与者是开始CUD治疗的大麻使用者。问卷收集了社会人口统计数据、大麻和烟草使用特征（如吸食次数、烟草量）、尼古丁依赖、戒烟动机和大麻戒断症状。使用描述性和双变量分析来检验消费差异。使用高尔距离的分层聚类分析确定了参与者之间的行为模式。结果纳入了94名寻求CUD治疗的参与者的数据。每天吸烟的比例为91.5%，平均Fagerström得分为4.2/10。大多数参与者（88.1%）同时使用大麻和烟草，75.8%的参与者出现过大麻戒断症状，其中女性报告的症状更严重。聚类分析显示两种情况：聚类1（71.0%）主要包括老年男性，戒烟动机较高，戒断症状较少；第2组（29.0%）更年轻，性别更平衡，尼古丁依赖程度更高，戒断症状更严重。结论大麻和烟草的双重使用在进入CUD治疗的个体中非常普遍。高度的尼古丁依赖与更严重的戒断症状相关。动机较高且戒断症状较少的老年男性可能预后较好，强调动机是戒烟的预测因素。研究结果直接适用于呼吸保健，因为识别高风险的双重使用者可以指导综合戒烟策略，并有可能减少慢性呼吸道疾病。关键词：大麻使用障碍；烟草使用;co-use;尼古丁依赖;大麻撤军;戒烟的动机；层次聚类;药物使用治疗

{"title":"CONSUMPTION PATTERNS AND WITHDRAWAL SYMPTOMS IN DUAL CANNABIS-TOBACCO USERS IN SPAIN: CROSS-SECTIONAL STUDY","authors":"Judith Saura , Ariadna Feliu , Marta Enríquez , Xavier Roca , Montse Ballbè , Marcela Fu , Lidia Segura , Esteve Fernández , Cristina Martínez","doi":"10.1016/j.opresp.2026.100568","DOIUrl":"10.1016/j.opresp.2026.100568","url":null,"abstract":"<div><h3>Background</h3><div>Cannabis use has increased worldwide, with over 188 million users annually. In Spain, past-year prevalence among people aged 15–64 is 10.6%. Dual use of cannabis and tobacco is common, increasing health risks and complicating cessation. This study examines consumption patterns and cannabis withdrawal severity among dual users undergoing treatment for cannabis use disorder (CUD).</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted in substance use treatment programs in Catalonia, Spain. Participants were cannabis users initiating CUD treatment. A questionnaire collected sociodemographic data, cannabis and tobacco use characteristics (e.g., number of spliffs, tobacco amount), nicotine dependence, motivation to quit, and cannabis withdrawal symptoms. Descriptive and bivariate analyses were used to examine consumption differences. A hierarchical cluster analysis using Gower's distance identified behavioral patterns among participants.</div></div><div><h3>Results</h3><div>Data from 94 participants seeking CUD treatment were included. Daily tobacco use was reported by 91.5%, with a mean Fagerström score of 4.2/10. Most participants (88.1%) co-used cannabis with tobacco, and 75.8% experienced cannabis withdrawal symptoms, with women reporting greater severity. Cluster analysis revealed two profiles: Cluster 1 (71.0%) included mostly older males with higher motivation to quit and fewer withdrawal symptoms; Cluster 2 (29.0%) was younger, more gender-balanced, and showed higher nicotine dependence, and more severe withdrawal symptoms.</div></div><div><h3>Conclusions</h3><div>Co-use of cannabis and tobacco is highly prevalent among individuals entering CUD treatment. Higher nicotine dependence is associated with more severe withdrawal symptoms. Older males with higher motivation and fewer withdrawal symptoms may have better prognosis, highlighting motivation as cessation predictor. Findings are directly applicable to respiratory care, as identifying high-risk dual users can guide integrated cessation strategies and potentially reduce chronic respiratory disease.</div><div><strong>Key words</strong>: Cannabis use disorder; tobacco use; co-use; nicotine dependence; cannabis withdrawal; motivation to quit; hierarchical clustering; substance use treatment</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100568"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PROTEOMIC SIGNATURES OF INFLAMMATION AND CARDIOVASCULAR RISK IN PEDIATRIC OBSTRUCTIVE SLEEP APNEA (OSA) 儿童阻塞性睡眠呼吸暂停（osa）的炎症和心血管风险的蛋白质组学特征

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100548

Belén García-Mediano , Esther Solano-Pérez , María Castillo-García , Adriana Rodríguez-Perojo , Sofía Romero-Peralta , Laura Silgado-Martínez , María Esther Viejo-Ayuso , Leticia Álvarez-Balado , Pilar Resano-Barrio , Manuel Sánchez-de-La-Torre , Olga Mediano

Introduction

Pediatric obstructive sleep apnea (OSA) is associated with inflammation and cardiovascular (CV) risk, although biomarkers for early risk stratification are scarce.

Objectives

To characterise children with OSA by exploring inflammatory and CV protein profiles.

Methods

Serum samples from 88 children in the Kids Trial cohort were analysed: 35 controls with an obstructive apnoea-hypopnoea index (OAHI) <3/h and 53 with moderate/severe OSA (OAHI ≥5/h). Proteomic analysis included volcano plots combining fold change with p-values and false discovery rate (FDR)-adjusted values. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was performed. ROC analysis was used to assess the classification performance of the proteins, along with the AUC, sensitivity, specificity, and optimal cut-off values.

Results

Of the 272 analysed proteins, 51 were found to be differentially expressed, with 3 remaining significant after correction for FDR (Fig. 1). sPLS-DA revealed partial separation between OSA group and controls. IL-1Ra contributed most to the separation between groups (Fig. 2). AUC analysis identified the top 5 proteins that best discriminated between the groups. Gal-9 showed good discriminatory ability between OSA and controls (AUC = 0.84, Fig. 3).

Conclusions

Children with OSA exhibit increased inflammatory and CV protein profiles compared to controls. Gal-9 may represent a valuable biomarker for identifying children with OSA, with implications for diagnosis and clinical management.

儿童阻塞性睡眠呼吸暂停（OSA）与炎症和心血管（CV）风险相关，尽管早期风险分层的生物标志物很少。目的通过研究炎症和CV蛋白谱来确定OSA患儿的特征。方法对88例儿童的血清样本进行分析：35例为阻塞性呼吸暂停-低通气指数(OAHI)≥3/h， 53例为中/重度OSA （OAHI≥5/h）。蛋白质组学分析包括火山图，结合折叠变化与p值和错误发现率（FDR）调整值。进行稀疏偏最小二乘判别分析（sPLS-DA）。ROC分析用于评估蛋白质的分类性能，以及AUC、敏感性、特异性和最佳截止值。结果在分析的272个蛋白中，发现51个蛋白存在差异表达，其中3个蛋白在FDR校正后仍具有显著性（图1）。sPLS-DA显示OSA组与对照组之间存在部分分离。IL-1Ra对组间分离的贡献最大（图2）。AUC分析确定了最能区分两组的前5个蛋白。Gal-9在OSA和对照组之间表现出良好的区分能力（AUC = 0.84，图3）。结论：与对照组相比，OSA患儿炎症和CV蛋白谱升高。Gal-9可能是鉴别OSA患儿的一种有价值的生物标志物，对诊断和临床管理具有重要意义。

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引用次数: 0

PERSISTENCE OF HAEMOPHILUS INFLUENZAE AND PSEUDOMONAS AERUGINOSA STRAINS IN BRONCHIECTASIS PATIENTS: A LONGITUDINAL STUDY 支气管扩张患者中流感嗜血杆菌和铜绿假单胞菌菌株的持续存在：一项纵向研究

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100549

I. Cadenas-Jiménez , P. Camps-Massa , Y. Benaali-Bakkar , F. Gonçalves-Carvalho , L. Rodríguez , A. Antuori , L. Saiz-Escobedo , S. Calvo-Silveria , A. Oliver , MA. Dominguez , S. Santos , F. Tubau , A. González-Díaz , C. Ardanuy , A. Marin , S. Martí , on behalf of the BRONCHIOMICS study group

Introduction

Bronchiectasis (BQ) is a chronic respiratory condition characterized by a widening of the bronchial airways, leading to inflammation and recurrent exacerbations. Inflammation is frequently associated with gram-negative microorganisms, particularly Haemophilus influenzae and Pseudomonas aeruginosa, which are the main pathogens causing chronic infections. This study aimed to describe long-term bacterial persistence and antimicrobial resistance levels in non-cystic fibrosis bronchiectasis (non-CF-BQ).

Methods

The study involved seven Spanish hospitals (2019-2020). Strains were isolated in routine visits (V0=initial; V1=6m; V2=12m) and exacerbations (Fig.1). Persistence was defined as the same clone found over three months apart. All strains were tested for antimicrobial susceptibility and hypermutability in P. aeruginosa. Finally, whole genome sequencing was performed using Illumina Miseq/NextSeq platforms, with mutations identified using Geneious software.

Results

A total of 62 patients were included in the study. Of these, 31 patients harboured H. influenzae, 28 had P. aeruginosa and three patients had both microorganisms. Eighteen exacerbation episodes were identified: H. influenzae was isolated in nine episodes (9/18; 50%), P. aeruginosa in two (2/18; 11.1%), Streptococcus pneumoniae in two (2/18; 11.1%) and commensal microbiota in the remaining episodes.

Persistent colonization was observed in 16 patients (Fig. 1): seven with H. influenzae (7/16; 43.8%) and nine with P. aeruginosa (9/16; 56.2%). Notably, six (6/7; 85.7%) patients with persistent H. influenzae had exacerbation episodes, compared to only two (2/9; 22.2%) with P. aeruginosa. Antimicrobial resistance rates showed no statistical significance between persistent and non-persistent strains (Figure 1). However, four patients acquired antimicrobial resistance during the longitudinal study, in two cases, after an exacerbation. Patient HUGTiP-P09 developed aminoglycoside resistance, this patient received nebulized antimicrobial treatment since visit 0 due to chronic P. aeruginosa infection. For patient HM-P09, moxifloxacin was successfully used to treat an exacerbation caused by an sporadic P. aeruginosa clone (ST4386), but led to fluoroquinolone resistance in the persistent P. aeruginosa clone (ST2555). Two patients with persistent P. aeruginosa harboured hypermutable strains (2/16; 12.5%).

Conclusions

Persistent colonization was more frequently observed in P. aeruginosa, while exacerbations were more commonly related to H. influenzae. Antimicrobial treatment for exacerbations led to the acquisition of antibiotic resistance in persistent strains.

支气管扩张（BQ）是一种以支气管气道扩张为特征的慢性呼吸系统疾病，可导致炎症和反复发作。炎症通常与革兰氏阴性微生物有关，特别是流感嗜血杆菌和铜绿假单胞菌，它们是引起慢性感染的主要病原体。本研究旨在描述非囊性纤维化支气管扩张（non-CF-BQ）的长期细菌持久性和抗微生物药物耐药性水平。方法研究对象为西班牙7家医院（2019-2020年）。在常规访视（V0=初始；V1=6m; V2=12m）和加重期（图1）中分离菌株。持久性定义为相隔三个月以上发现的同一个克隆。对所有菌株进行了铜绿假单胞菌的药敏和超易变性试验。最后，使用Illumina Miseq/NextSeq平台进行全基因组测序，使用genous软件进行突变鉴定。结果共纳入62例患者。其中，31名患者携带流感嗜血杆菌，28名患者携带铜绿假单胞菌，3名患者同时携带两种微生物。共发现18次急性发作：9次发作分离出流感嗜血杆菌（9/18,50%），2次分离出铜绿假单胞菌（2/18,11.1%），2次分离出肺炎链球菌（2/18,11.1%），其余发作分离出共生菌群。16例患者观察到持续定植（图1）：7例感染流感嗜血杆菌（7/16,43.8%），9例感染铜绿假单胞菌（9/16,56.2%）。值得注意的是，6例（6/7;85.7%）持续性流感嗜血杆菌患者有加重发作，而铜绿假单胞菌患者只有2例（2/9;22.2%）。持久菌株和非持久菌株的耐药率无统计学意义（图1）。然而，在纵向研究期间，有4例患者获得了抗菌素耐药性，其中2例是在病情加重后获得的。患者HUGTiP-P09出现氨基糖苷类耐药，该患者因慢性铜绿假单胞菌感染从第0次就诊开始接受雾化抗菌药物治疗。对于患者HM-P09，莫西沙星成功用于治疗散发的铜绿假单胞菌克隆（ST4386）引起的病情加重，但导致持续性铜绿假单胞菌克隆（ST2555）对氟喹诺酮类药物产生耐药性。2例持续性铜绿假单胞菌携带超变菌株（2/16;12.5%）。结论铜绿假单胞菌的持续定殖更为常见，而流感嗜血杆菌的加重更为常见。对病情加重的抗菌素治疗导致持续菌株获得抗生素耐药性。

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引用次数: 0

TIGIT: NEW IMMUNE CHECKPOINT IN OBSTRUCTIVE SLEEP APNOEA [Comunicación premiada] TIGIT：阻塞性睡眠呼吸暂停的新免疫检查点[Comunicación premiada]

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100555

Paula Pérez-Moreno , Elena Díaz-García , Cristina López-Fernández , Aldara García-Sánchez , Laura Pozuelo-Sánchez , María Torres-Varga , Elisabet Martínez Cerón , Raquel Casitas Mateo , Raúl Galera Martínez , Francisco García Río , Carolina Cubillos Zapata

Introduction

Obstructive sleep apnoea (OSA) is a syndrome characterized by the partial or complete obstruction of the upper airways during sleep, leading to intermittent hypoxia among others conditions. These physiological disturbances are associated with an increased risk of various diseases, such as cardiovascular disease and cancer. In fact, the prevalence of cancer in individuals with OSA is 1.53 times higher than in patients without OSA. This increase could be due to the disruption of immune surveillance caused by the effect of certain immune checkpoints (IC) on T cells. One of this IC is TIGIT, an inhibitory receptor expressed in lymphocytes that interacts with the ligands CD155 and CD112, which are present on antigen-presenting and tumor cells. The binding of this receptor to its ligands downregulated T cell functions.

Objectives

Thus, we aim to explore TIGIT and its ligands expression on lymphocytes and monocytes respectively of patients with OSA, assessing the role of intermittent hypoxia in this context.

Methods

This study includes a cohort of patients with and without OSA who underwent a sleep study. We explore TIGIT, CD155 and CD112 expression from OSA patients and control subjects and the role of intermittent hypoxia with in vitro models. We obtained these results through flow cytometry and qPCR.

Results

Our findings show that TIGIT expression in lymphocyte T membrane is upregulated in patients with severe OSA and correlates with parameters indicating OSA severity, suggesting an association between OSA and TIGIT expression. Finally, in vitro model data suggested intermittent hypoxia were associated with upregulation of TIGIT in patients with severe OSA.

Conclusions

In patients with obstructive sleep apnea (OSA), TIGIT overexpression on the T cell membrane is mediated by intermittent hypoxia via activation of hypoxia-inducible factor 1-alpha (HIF-1α).

梗阻性睡眠呼吸暂停（OSA）是一种以睡眠时上呼吸道部分或完全阻塞为特征的综合征，可导致间歇性缺氧等症状。这些生理障碍与各种疾病的风险增加有关，如心血管疾病和癌症。事实上，阻塞性睡眠呼吸暂停患者的癌症患病率是非阻塞性睡眠呼吸暂停患者的1.53倍。这种增加可能是由于某些免疫检查点（IC）对T细胞的影响导致免疫监视中断。其中一种IC是TIGIT，这是一种在淋巴细胞中表达的抑制性受体，可与存在于抗原呈递细胞和肿瘤细胞上的配体CD155和CD112相互作用。这种受体与其配体的结合下调了T细胞的功能。因此，我们旨在探讨TIGIT及其配体在OSA患者淋巴细胞和单核细胞上的表达，评估间歇性缺氧在这一背景下的作用。方法本研究纳入了一组接受睡眠研究的OSA患者和非OSA患者。我们通过体外模型研究OSA患者和对照组的TIGIT、CD155和CD112的表达以及间歇性缺氧的作用。我们通过流式细胞术和qPCR得到这些结果。结果我们的研究结果表明，严重OSA患者淋巴细胞T膜中TIGIT表达上调，并与OSA严重程度参数相关，提示OSA与TIGIT表达相关。最后，体外模型数据显示，间歇性缺氧与严重OSA患者的TIGIT上调有关。结论在阻塞性睡眠呼吸暂停（OSA）患者中，间歇性缺氧可通过激活缺氧诱导因子1- α (HIF-1α)介导TIGIT在T细胞膜上的过表达。

{"title":"TIGIT: NEW IMMUNE CHECKPOINT IN OBSTRUCTIVE SLEEP APNOEA [Comunicación premiada]","authors":"Paula Pérez-Moreno , Elena Díaz-García , Cristina López-Fernández , Aldara García-Sánchez , Laura Pozuelo-Sánchez , María Torres-Varga , Elisabet Martínez Cerón , Raquel Casitas Mateo , Raúl Galera Martínez , Francisco García Río , Carolina Cubillos Zapata","doi":"10.1016/j.opresp.2026.100555","DOIUrl":"10.1016/j.opresp.2026.100555","url":null,"abstract":"<div><h3>Introduction</h3><div>Obstructive sleep apnoea (OSA) is a syndrome characterized by the partial or complete obstruction of the upper airways during sleep, leading to intermittent hypoxia among others conditions. These physiological disturbances are associated with an increased risk of various diseases, such as cardiovascular disease and cancer. In fact, the prevalence of cancer in individuals with OSA is 1.53 times higher than in patients without OSA. This increase could be due to the disruption of immune surveillance caused by the effect of certain immune checkpoints (IC) on T cells. One of this IC is TIGIT, an inhibitory receptor expressed in lymphocytes that interacts with the ligands CD155 and CD112, which are present on antigen-presenting and tumor cells. The binding of this receptor to its ligands downregulated T cell functions.</div></div><div><h3>Objectives</h3><div>Thus, we aim to explore TIGIT and its ligands expression on lymphocytes and monocytes respectively of patients with OSA, assessing the role of intermittent hypoxia in this context.</div></div><div><h3>Methods</h3><div>This study includes a cohort of patients with and without OSA who underwent a sleep study. We explore TIGIT, CD155 and CD112 expression from OSA patients and control subjects and the role of intermittent hypoxia with in vitro models. We obtained these results through flow cytometry and qPCR.</div></div><div><h3>Results</h3><div>Our findings show that TIGIT expression in lymphocyte T membrane is upregulated in patients with severe OSA and correlates with parameters indicating OSA severity, suggesting an association between OSA and TIGIT expression. Finally, in vitro model data suggested intermittent hypoxia were associated with upregulation of TIGIT in patients with severe OSA.</div></div><div><h3>Conclusions</h3><div>In patients with obstructive sleep apnea (OSA), TIGIT overexpression on the T cell membrane is mediated by intermittent hypoxia via activation of hypoxia-inducible factor 1-alpha (HIF-1α).</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100555"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SLEEP APNEA ASSESSMENT IN STROKE PATIENTS USING A SMARTPHONE 使用智能手机对中风患者进行睡眠呼吸暂停评估

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100539

Yolanda Castillo-Escario , Sergiu Albu , Hatice Kumru , Raimon Jané

Introduction

Sleep apnea is common but often underdiagnosed after stroke, hindering rehabilitation and functional recovery. Access to sleep studies remains limited for stroke patients, partly due to the inconvenience of current diagnostic tools. The widespread availability and built-in sensors of smartphones make them powerful solutions for mobile health applications, including sleep monitoring.

Objectives

This study aims to detect and evaluate sleep apnea in post-stroke patients using a smartphone and extract multimodal digital biomarkers to characterize their sleep patterns.

Methods

Sleep tests were conducted on 20 patients with subacute ischemic stroke (11 men and 9 women, mean age 51±12 years) and 20 age- and sex-matched control subjects, using a smartphone-based system that recorded audio, accelerometer, and oximetry data. Signals were analyzed with custom-made automatic algorithms to compute respiratory, oxygenation, and sleep position indices.

Results

The apnea-hypopnea index (AHI) was significantly higher in the stroke than the control group (28±20 vs 15±10, p=0.01). Moderate-to-severe sleep apnea (AHI≥15) was present in 70% of stroke patients and 45% of control subjects. Stroke patients spent more time mouth breathing (23% vs 10%, p<0.001) and sleeping in supine position (67% vs 37%, p=0.004) than controls, contributing to upper airway obstruction.

Conclusions

These findings obtained through novel multimodal digital biomarkers advance the understanding of post-stroke sleep apnea patterns and show the potential of smartphones as portable screening and monitoring tools. This approach can facilitate early sleep apnea detection after stroke, thereby reducing its substantial burden and improving rehabilitation outcomes.

睡眠呼吸暂停是卒中后常见的疾病，但常被误诊，影响康复和功能恢复。中风患者获得睡眠研究的机会仍然有限，部分原因是目前的诊断工具不方便。智能手机的广泛可用性和内置传感器使其成为移动健康应用（包括睡眠监测）的强大解决方案。本研究旨在通过智能手机检测和评估卒中后患者的睡眠呼吸暂停，并提取多模态数字生物标志物来表征其睡眠模式。方法对20例亚急性缺血性脑卒中患者（男性11例，女性9例，平均年龄51±12岁）和20例年龄和性别匹配的对照组进行睡眠测试，使用基于智能手机的系统记录音频、加速度计和血氧仪数据。用定制的自动算法分析信号，计算呼吸、氧合和睡眠姿势指数。结果脑卒中患者呼吸暂停低通气指数（AHI）明显高于对照组（28±20 vs 15±10,p=0.01）。70%的脑卒中患者和45%的对照组存在中度至重度睡眠呼吸暂停（AHI≥15）。卒中患者的口呼吸时间（23%比10%，p= 0.001）和仰卧位睡眠时间（67%比37%，p=0.004）均高于对照组，导致上呼吸道阻塞。结论通过新型多模态数字生物标志物获得的这些发现促进了对中风后睡眠呼吸暂停模式的理解，并显示了智能手机作为便携式筛查和监测工具的潜力。这种方法可以促进中风后早期睡眠呼吸暂停的检测，从而减轻其沉重的负担，提高康复效果。

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引用次数: 0

THREE NOVEL MOLECULAR GATE BIOSENSORS FOR THE RAPID AND ACCURATE DETECTION OF RESPIRATORY PATHOGENS: INFLUENZA A, SARS-COV-2 AND PSEUDOMONAS AERUGINOSA 用于快速准确检测呼吸道病原体的三种新型分子门生物传感器：甲型流感、sars-cov-2和铜绿假单胞菌

Q4 Medicine

Open Respiratory Archives

Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100541

Andrea Torres-Mesado , Alba Lopez-Palacios , Estela Climent , Ramón Martínez-Mañez , Elena Aznar

Introduction

Each year, about 4.8 million people die from infectious respiratory diseases, mainly of bacterial origin but also viral. Current detection methods are hindered by slow diagnosis, low specificity, and costly equipment. Rapid, accurate identification of viruses and bacterial is vital, especially since acute respiratory infections present overlapping symptoms, such as those from influenza A virus (IVA) and SARS-CoV-2. Additionally, the bacterium Pseudomonas aeruginosa causes severe infections in immunocompromised patients, with high mortality rates. The current gold standard, PCR testing, is limited by long turnaround times, need for specialized staff, and high cost.

Methods

Three independent smart nanodevice-based biosensors with gated porous supports have been developed. Each one is designed to detect a specific pathogen. These biosensors combine molecular gates tailored to their target analytes with optical fluorescence transducers to amplify the signal. Specifically, the IVA-Biosensor detects IVA proteins, the SARS-Biosensor detects the Spike SARS-CoV-2 protein, and the Pae-Biosensor detects biomarkers of P. aeruginosa. The response of all three optical biosensors was monitored by the release of fluorescence cargo (Rodamine B) (λexc = 555 nm, λem = 585 nm). Additional high-resolution FESEM images and EDXS analysis of the materials' surface composition and absorption spectra were performed.

Results

All of the biosensors demonstrated high sensitivity even at low pathogen concentrations (0.7–1 nM for the IVA and SARS biosensors and 10–28 CFU/mL for the Pae-Biosensor), outperforming traditional molecular techniques. They also demonstrate high specificity and selectivity compared to other common nosocomial pathogens. Clinical tests showed promising accuracy. Nasopharyngeal samples differentiated infected patients from healthy ones for the viral biosensors, and urine samples confirmed the rapid (∼30 min) identification of P. aeruginosa. Finally, the Pae-Biosensor has been integrated into a lateral flow device with in situ fluorescent measurement, enabling one-minute sample discrimination.

Conclusions

Three smart nanodevice-based biosensors, which are sensitive and selective, have been developed to detect the pathogens IVA, SARS-CoV-2 and P. aeruginosa in complex clinical samples in less than 30 minutes, based on new nanomaterials capped with molecular gates. These biosensors do not require complex laboratory equipment, pretreatment or highly specialised personnel, making them suitable for use in hospitals.

每年约有480万人死于传染性呼吸道疾病，主要是细菌性疾病，但也有病毒性疾病。目前的检测方法受到诊断缓慢、特异性低和设备昂贵的阻碍。快速、准确地识别病毒和细菌至关重要，特别是因为急性呼吸道感染会出现重叠症状，例如甲型流感病毒和SARS-CoV-2。此外，铜绿假单胞菌在免疫功能低下的患者中引起严重感染，死亡率高。目前的黄金标准，PCR检测，受到周转时间长，需要专业人员和高成本的限制。方法研制了三种独立的智能纳米器件生物传感器。每一个都被设计用来检测一种特定的病原体。这些生物传感器结合了为目标分析物量身定制的分子门和光学荧光换能器来放大信号。其中，IVA- biosensor检测IVA蛋白，SARS-Biosensor检测Spike SARS-CoV-2蛋白，Pae-Biosensor检测铜绿假单胞菌的生物标志物。通过释放荧光货物（罗丹明B）（λexc = 555 nm, λem = 585 nm）来监测三种光学生物传感器的响应。对材料的表面成分和吸收光谱进行了额外的高分辨率FESEM图像和EDXS分析。结果所有生物传感器在低病原体浓度下（IVA和SARS生物传感器为0.7 ~ 1 nM， pae生物传感器为10 ~ 28 CFU/mL）均表现出较高的灵敏度，优于传统的分子技术。与其他常见的医院病原体相比，它们也表现出高特异性和选择性。临床试验显示了良好的准确性。鼻咽样本用于病毒生物传感器区分感染患者和健康患者，尿液样本证实了铜绿假单胞菌的快速识别（~ 30分钟）。最后，Pae-Biosensor已集成到一个横向流动装置与原位荧光测量，使一分钟的样品鉴别。结论基于分子门封盖的新型纳米材料，开发了3种灵敏、选择性高的智能纳米生物传感器，可在30分钟内检测复杂临床样品中的IVA、SARS-CoV-2和P. aeruginosa病原体。这些生物传感器不需要复杂的实验室设备、预处理或高度专业化的人员，因此适合在医院使用。

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引用次数: 0