Open Respiratory Archives最新文献

{"title":"RAPID, FLEXIBLE, AND SCALABLE ALTERNATIVES TO CONVENTIONAL HIGH-THROUGHPUT WHOLE GENOMA SEQUENCING TO ENHANCE SURVEILLANCE OF TUBERCULOSIS TRANSMISSION","authors":"Sheri M. Saleeb ,&nbsp;Teresa Cabezas Fernández ,&nbsp;Silvia Vallejo-Godoy ,&nbsp;Miguel Martínez-Lirola ,&nbsp;Pilar Barroso-García ,&nbsp;Francisca Escabias-Machuca ,&nbsp;Marta Herranz ,&nbsp;Marta López-LLaría ,&nbsp;Guadalupe Bernal ,&nbsp;Sergio Buenestado-Serrano ,&nbsp;Linfeng Wang ,&nbsp;Patricia Muñoz ,&nbsp;Mercedes Guida Piqueras ,&nbsp;Andrea López Suárez ,&nbsp;Begoña Santiago ,&nbsp;Laura Pérez-Lago ,&nbsp;Darío García de Viedma","doi":"10.1016/j.opresp.2026.100551","DOIUrl":"10.1016/j.opresp.2026.100551","url":null,"abstract":"<div><h3>Introduction</h3><div>Whole genome sequencing (WGS) is essential for monitoring tuberculosis (TB) transmission, enabling precise clustering of cases. Illumina sequencing, while accurate, depends on batch processing and often introduces delays that limit timely interventions. Nanopore sequencing offers a flexible, case-by-case alternative that can accelerate genomic data availability.</div></div><div><h3>Methods</h3><div>We prospectively applied nanopore sequencing to 33 primary cultures and 51 clinical sputa during active contact tracing. All cultures achieved optimal WGS performance (≥90% genome coverage at ≥20X), allowing integration of 27 new cases into genomic networks within the 21-day tracing window.</div></div><div><h3>Results</h3><div>Beyond SNP clustering, evolutionary network analysis improved interpretation of transmission dynamics, revealing ongoing chains, reactivations, and diagnostic delays. Among sputa, 31.3% achieved optimal coverage and 15.7% suboptimal results, but these were still usable through a rescue pipeline that exploited circulating marker SNPs, enabling assignment of suboptimal sequences to ongoing clusters. To accelerate responses during high-risk events, we designed a targeted amplicon-based nanopore approach focusing on cluster-defining SNPs. Using 8 marker SNPs, we tracked potential cases linked to an interterritorial cluster associated with a super-spreader, highlighting further cluster expansion without requiring full WGS.</div></div><div><h3>Conclusions</h3><div>By integrating real-time nanopore sequencing, rescue pipelines, and targeted SNP-based amplicon sequencing, we demonstrate rapid, flexible, and scalable alternatives to Illumina-based high-throughput WGS. These strategies strengthen genomic epidemiology and enable more effective, timely TB control interventions.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100551"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161735","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}

{"title":"SUBSTRATE STIFFNESS DRIVES A TRANSCRIPTIONAL PROGRAM LINKED TO POOR PROGNOSIS IN LUNG ADENOCARCINOMA","authors":"Manuel Chacón ,&nbsp;Natalia Campo-Ortiz de Zárate ,&nbsp;Sara María Exojo-Ramírez ,&nbsp;Loreto Pérez-Riesgo ,&nbsp;Guillermo Muñíz Albaiceta","doi":"10.1016/j.opresp.2026.100563","DOIUrl":"10.1016/j.opresp.2026.100563","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify stiffness-associated transcriptional changes in lung cancer cells and evaluate their prognostic relevance in adenocarcinoma cohorts.</div></div><div><h3>Methods</h3><div>A549 cell were cultured on soft (2kPa) and stiff (32kPa) substrates. Proliferation was measured by MTT at days 3, 5 and 7, and RNA-seq was performed in parallel. Differentially expressed genes at 7 days (padj &lt; 0.05, |log2FC| &gt; 1) were tested for survival association in the GSE68465 (n=439) using multivariate Cox regression. Genes both stiffness-regulated and survival-associated defined a 78-gene rigidity signature. Prognostic value was evaluated with in Cox models and validated in an independent cohort (GSE72094, n=393). Functional enrichment analysis identified related biological processes.</div></div><div><h3>Results</h3><div>Proliferation increased significantly at 7 days on stiff matrices. Transcriptomic analysis identified 2585 differentially expressed genes, 235 associated with survival and 78 forming the rigidity signature In the discovery cohort, this signature predicted worse survival (HR per SD = 1.7 CI 1.45-1.9, concordance = 0.74, p&lt;0.001). Validation in an independent cohort confirmed its prognostic power (HR per SD = 1.7 CI 1.4-2.0, concordance = 0.71, p&lt;0.001). Enrichment analysis revealed pathways related to positive regulation of locomotion and cell migration.</div></div><div><h3>Conclusions</h3><div>Substrate stiffness modulates cancer cell behaviour, inducing a transcriptional phenotype associated with increased mortality in lung adenocarcinoma.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100563"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161942","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}

{"title":"EVOLUTION OF INVASIVE PNEUMOCOCCAL DISEASE IN ADULTS IN SPAIN (2009-2024): IMPACT OF CONJUGATE VACCINES PCV20 Y PCV21","authors":"Elsa García ,&nbsp;Mirella Llamosí ,&nbsp;Covadonga Pérez ,&nbsp;Aída Úbeda ,&nbsp;Erick Joan Vidal ,&nbsp;Juan Carlos Sanz ,&nbsp;Mirian Domenech ,&nbsp;Julio Sempere ,&nbsp;José Enrique Yuste","doi":"10.1016/j.opresp.2026.100571","DOIUrl":"10.1016/j.opresp.2026.100571","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Streptococcus pneumoniae&lt;/em&gt; has a critical relevance in public health due to its ability to cause severe invasive diseases. Conjugate vaccines have been essential to control its impact. The recently implemented PCV-20 and PCV-21 protect against 20 and 21 serotypes, respectively. Besides, the PCV-21 contains serotypes never before included, being also a vaccine mainly directed to adults. However, serotype replacement has emerged with many non-vaccine serotypes showing antibiotic resistance, specially to β-lactams, macrolides and tetracyclines.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This study is part of the microbiological surveillance work carried out by the National Microbiology Centre (CNM), where the Pneumococcus Unit acts as the National Reference Laboratory (LNR). Pneumococcus isolates were analysed between 2009 and 2024. Given that these represent approximately 80% of the actual total number of cases, a correction factor was applied to estimate the incidence.&lt;/div&gt;&lt;div&gt;The isolates were identified using optochin discs and bile salt solubility tests. Subsequently, antimicrobial sensitivity was evaluated using the disc-plate method, and the minimum inhibitory concentration (MIC) was determined in those isolates that showed resistance. Serotyping was performed by dot-blot. In inconclusive cases, PCR and sequencing of the capsular wzy gene were used.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Since the introduction of PCV13 in 2010, PCV20-non-21 serotypes have markedly declined, while PCV21-non-20 serotypes have increased, especially among adults over 65 and 80 years old. During the COVID-19 pandemic, cases sharply declined at all ages due to non-pharmacological measures like masking, isolation, and social distancing. From 2021 onwards, coinciding with the lifting of these measures, is observed a gradual increase and recovery in incidence, reaching pre-pandemic levels in the period 2023-2024.&lt;/div&gt;&lt;div&gt;The PCV20-non-21 serotypes showed a heterogeneous distribution, with a few of them causing the most cases. After PCV13 introduction, some, like 1 and 5, declined strongly. Serotype 4 has notably increased, becoming one of the most prevalent after the COVID-19 pandemic, while 9V and 19F remain frequent and with a high antimicrobial resistance.&lt;/div&gt;&lt;div&gt;In contrast, serotypes PCV21-non-20 showed a more uniform distribution, although with an increasing incidence in recent years in all age groups.&lt;/div&gt;&lt;div&gt;In addition, were analysed the MIC and MIC of serotypes with increasing circulation associated with high antibiotic resistance. Serotypes 9V, 14, and 19F, belonging to PCV20-non-21, showed much higher MIC values and against more antibiotic families, which can be explained by the fact that they have been exposed to a selective pressure by the vaccine. Serotypes 15A, 23B, and 35B, belonging to PCV21-non-20, showed lower MICs and were also susceptible to more antibiotic families, which can be explained by the lack of sel","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100571"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161958","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}

{"title":"IDENTIFYING LEUKOCYTE POPULATIONS AS BIOMARKERS FOR CHRONIC LUNG ALLOGRAFT DYSFUNCTION","authors":"Iván Martínez-Ballestero ,&nbsp;Meritxell Boada Pérez ,&nbsp;Victoria Ruiz de Miguel ,&nbsp;Oriol Grau-Bosch ,&nbsp;Eva Revilla-López ,&nbsp;Carles Bravo Masgoret ,&nbsp;Berta Saez Gimenez ,&nbsp;Marta Zapata-Ortega ,&nbsp;Manuel López Meseguer ,&nbsp;Roser Escobar ,&nbsp;Victor Monforte Torres ,&nbsp;Cristina Berastegui García ,&nbsp;Susana Gómez-Ollés","doi":"10.1016/j.opresp.2026.100557","DOIUrl":"10.1016/j.opresp.2026.100557","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung transplantation (LT) is a life-saving therapy for end-stage respiratory diseases, but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Early detection is essential to prevent irreversible damage.</div></div><div><h3>Objectives</h3><div>To determine which leukocyte populations in peripheral blood are altered in CLAD after bilateral LT, in order to identify potential biomarkers for improved diagnosis.</div></div><div><h3>Methods</h3><div>A case-control study included 68 bilateral LT recipients (LTR): Stable LTR (n=29), Established CLAD (n=28), and De novo CLAD (n=11). Leukocyte subpopulations were analyzed by flow cytometry using five DuraClone panels (basic phenotyping, TCRs, Treg, granulocytes and dendritic cells (DC)). Absolute counts were quantified with Flow-Count fluorospheres.</div></div><div><h3>Results</h3><div>Five leukocyte subpopulations differed significantly between groups. De novo CLAD patients showed reduced plasmacytoid DCs (HLA-DR+ Lin- CD123+ CD11c-), conventional DCs type 1 (HLA-DR+ Lin- CD123- CD11c+ CD16- Clec9A+), and regulatory NK cells (CD56high CD16-) compared with stable LTR (<strong>Fig. 1</strong>). Additional differences were found in TCRγδ+Vδ2+ T cells and Helios+CD39- Tregs.</div></div><div><h3>Conclusions</h3><div>Reduced levels of plasmacytoid DCs, cDC1, and NKreg cells suggest a role for impaired regulatory immune subsets in CLAD onset and highlight their potential as biomarkers for early detection.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100557"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162086","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}

{"title":"PNEUMOCOCCAL MENINGITIS IN ADULTS: ANALYSIS OF SEROTYPE DISTRIBUTION AND ANTIMICROBIAL RESISTANCE","authors":"Sara Calvo-Silveria ,&nbsp;Aida González-Díaz ,&nbsp;Lluïsa Guillem ,&nbsp;Dàmaris Berbel ,&nbsp;Fe Tubau ,&nbsp;Josefina Liñares ,&nbsp;Pedro F. Viladrich ,&nbsp;Rocío España-Bonilla ,&nbsp;Sara Martí ,&nbsp;Jordi Càmara ,&nbsp;Carmen Cabellos ,&nbsp;Carmen Ardanuy","doi":"10.1016/j.opresp.2026.100573","DOIUrl":"10.1016/j.opresp.2026.100573","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Streptococcus pneumoniae</em> can cause a wide range of diseases. Among them, meningitis is associated with the highest mortality rates. This study analysed trends in pneumococcal meningitis from 1990 to 2022.</div></div><div><h3>Methods</h3><div>A laboratory-based retrospective study including all adult (≥18 years) with pneumococcal meningitis. Pneumococci were serotyped (Quellung or sequenced) and tested for antimicrobial susceptibility (microdilution, EUCAST). For analysis, three periods were defined regarding on the subsequent introduction of pneumococcal conjugate vaccines (PCV) in the paediatric schedule: Pre-PCV7 (1990-2000), Pre-PCV13 (2001-2011) and Post-PCV13 (2012-2022).</div></div><div><h3>Results</h3><div>There were 199 pneumococcal meningitis over the study period (51, 81 and 67, in each respective period). Cerebrospinal fluid (CSF) leak (35.3%) was the main focus in the Pre-PCV7 period, whereas acute otitis media (AOM) was it in the subsequent periods (45.7% and 53.7%, respectively). The overall mortality rates were 27.5%, 11.1% and 13.4%, respectively. Based on the meningitis focus, serotypes 16F, 23F, and 24F were the most frequent among patients with a CSF fistula; serotypes 3, 19A, and 19F in AOM; and serotypes 8, 10A, and 22F in the haematogenous focus (Figure1). After PCVs introduction, the proportion of meningitis cases caused by PCV13 or PCV20 serotypes decreased progressively from 56.9% and 72.5% to 25.4% and 49.3%, respectively (Figure2). Over the study period, rates of penicillin- (PEN) and cefotaxime-susceptibility (CTX) increased from 60.8% and 74.5% to 74.6% and 94.0%, respectively. Serotypes 9V, 14 and 19A were associated with non-susceptibility over the whole period (Figure3). Additionally, the antibiotic-resistant serotype 6C has garnered interest in recent years.</div></div><div><h3>Conclusions</h3><div>The PCVs introduction for children changed the epidemiology of pneumococcal meningitis in adults. Despite the overall decrease in PCV13 serotypes, serotype 3 persisted across all periods associated with AOM focus. Besides the resilience of serotype 19A, susceptibility to penicillin and cefotaxime increased over the study period. These findings underscore the need for continued surveillance of serotype distribution and antimicrobial resistance trends.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100573"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162087","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}

{"title":"GENOME-WIDE AND PATHWAY-SPECIFIC POLYGENIC EFFECTS ON CORTICOSTEROID RESPONSE IN PATIENTS WITH SEVERE INFECTIONS","authors":"Melody Ramirez-Falcon ,&nbsp;Eva Suarez-Pajes ,&nbsp;Luis A. Rubio-Rodríguez ,&nbsp;Silvia Diz-de Almeida ,&nbsp;Silvia Gonzalez-Barbuzano ,&nbsp;Eva Tosco-Herrera ,&nbsp;Almudena Corrales ,&nbsp;José M. Lorenzo-Salazar ,&nbsp;Raquel Cruz ,&nbsp;José A. Riancho ,&nbsp;Augusto Rojas-Martinez ,&nbsp;Pablo Lapunzina ,&nbsp;Angel Carracedo ,&nbsp;Tamara Hernandez-Beeftink ,&nbsp;Louise V. Wain ,&nbsp;Beatriz Guillen-Guio ,&nbsp;Carlos Flores","doi":"10.1016/j.opresp.2026.100556","DOIUrl":"10.1016/j.opresp.2026.100556","url":null,"abstract":"<div><h3>Introduction</h3><div>Corticosteroids (CS) improve survival in severe infections, but variable responses have been reported. We aimed to identify genetic variants that could be associated with the differential CS response.</div></div><div><h3>Methods</h3><div>We performed a genome-wide association study (GWAS) of 90day mortality in a cohort of hospitalized COVID-19 patients treated with CS from the SCOURGE consortium (Ncases=375, Ncontrols=1,850). Logistic regression models were conducted in ∼9.5M TOPMed-imputed variants (significance set at <em>p</em>=5x10^-8). Then, we tested the polygenic overlap of the CS response between COVID-19 and all-cause sepsis using PRSice-2 to perform polygenic risk scores (PRS). The PRS were tested on the independent CS-treated all-cause sepsis patients (Ncases=21, Ncontrols=69) from the GEN-SEP cohort. The best PRS model was subject to pathway-specific PRS studies using PRSet to evaluate which pathways were related to the differential CS response.</div></div><div><h3>Results</h3><div>Three <em>PLCG2</em> variants, two intronic and one in the 3’-UTR region, were associated with CS response in COVID-19 (<em>p</em>_lowest=2.79x10⁻⁸). A PRS model including 31,374 variants reaching a <em>p_threshold</em>=0.0298 in the GWAS was nominally associated with CS response among all-cause sepsis patients (<em>p</em>=0.044). Pathway-specific PRS analyses revealed the regulation of the cholesterol biosynthesis pathway as the most significantly associated with CS response in all-cause sepsis (<em>p</em>=0.001).</div></div><div><h3>Conclusions</h3><div>Overlapping polygenic effects of the CS response between COVID-19 and all-cause sepsis were observed. Genetic variants affecting the regulation of cholesterol biosynthesis pathway could underlie the CS response differences during critical illness.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100556"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161787","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}

{"title":"INTEGRATED CLINICAL-MOLECULAR APPROACH WITH PLASMA MIRNOME PROFILING PREDICTS SUBPHENOTYPE-SPECIFIC MORTALITY IN ELDERLY COVID-19","authors":"Manel Perez-Pons ,&nbsp;Iván D. Benítez ,&nbsp;Marina Rogel Vilanova ,&nbsp;Pilar Nogales Moreno ,&nbsp;Mariona Puente Moreno ,&nbsp;Elena Balaña Prim ,&nbsp;Thais Comella ,&nbsp;Anna Pérez-Sainz ,&nbsp;Irene Cuadrat ,&nbsp;Laia Utrillo-Montagut ,&nbsp;Francisco Nicolas-Sánchez ,&nbsp;Thalía Belmonte ,&nbsp;Marta Molinero ,&nbsp;María C. García-Hidalgo ,&nbsp;Carlos Rodríguez-Muñoz ,&nbsp;Anna Moncusí-Moix ,&nbsp;Clara Gort-Paniello ,&nbsp;Tamara Postigo ,&nbsp;Alicia Ortega ,&nbsp;Jessica González ,&nbsp;David de Gonzalo-Calvo","doi":"10.1016/j.opresp.2026.100552","DOIUrl":"10.1016/j.opresp.2026.100552","url":null,"abstract":"<div><h3>Background</h3><div>Elderly patients with viral respiratory infections, who exhibit considerable clinical heterogeneity, present a high mortality risk. Circulating microRNAs (miRNAs) are promising biomarkers for predicting outcomes, but their prognostic value in this complex population remains unclear. The main objective of this study is to assess whether miRNA profiling provides prognostic information in elderly COVID-19 patients.</div></div><div><h3>Methods</h3><div>Multicenter study including hospitalized COVID-19 patients aged ≥ 65 years [n=763, COVID-Ponent (NCT04824677), participation of several CIBERES groups]. Subphenotypes were identified using sociodemographic, baseline, infection-timing and admission-registered clinical data via elbow criteria-based cluster analysis. Plasma miRNome was profiled using qPCR. VSURF was applied to develop clinical-molecular models for 90-day mortality. Functional analyses based on an external RNA-seq dataset were performed using GO, Reactome, and KEGG databases.</div></div><div><h3>Results</h3><div>Results: The mean age was 79 years, with 44.0% women. The 90-day mortality rate was 26.7%. Thirteen candidate miRNAs were identified during the screening phase (n=39), but no association with 90-day mortality was found in the derivation cohort (n=340). Three subphenotypes (eCOVID-1, -2 and -3) with distinct clinical features and mortality risks (22.0%-34.2%) were identified. Differential miRNA expression patterns and molecular mechanisms were found across subphenotypes. In eCOVID-2 (eldest and most comorbid subphenotype) miR-106b-3p was the strongest predictor, selected in a VSURF model with PaO₂/FiO₂, age, and CRP. Metabolic and immune processes were linked to the fatal outcome in eCOVID-2.</div></div><div><h3>Conclusions</h3><div>Plasma miRNAs lack biomarker value in the overall population but provide complementary prognostic information when combined with clinical variables in specific elderly COVID-19 subphenotypes. These results offer a novel framework for stratifying elderly patients in the context of viral respiratory infections.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100552"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161736","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}

{"title":"THE FOOTPRINT OF HYPERCAPNIA ON INFLAMMATORY PATHWAYS DURING BACTERIAL INFECTION","authors":"E. Campaña-Duel ,&nbsp;A. Ceccato ,&nbsp;A. Areny-Balagueró ,&nbsp;V. Monforte ,&nbsp;L. Blanch ,&nbsp;L. Fernandez ,&nbsp;A. Artigas ,&nbsp;M. Camprubí-Rimblas","doi":"10.1016/j.opresp.2026.100550","DOIUrl":"10.1016/j.opresp.2026.100550","url":null,"abstract":"<div><h3>Introduction</h3><div>Pneumonia frequently occurs under hypercapnic conditions. Previous studies in hypercapnic models have reported that elevated CO₂ levels inhibit the NF-κB pathway, resulting in reduced inflammation. Notably, our prior work demonstrated that hypercapnia combined with bacterial infection increased IL-1β secretion.</div></div><div><h3>Objectives</h3><div>To study how hypercapnia affects the expression of key inflammation-related genes in in vitro models of macrophages (THP-1) and co-cultures with alveolar epithelium (HPAEpiC) following infection with Pseudomonas aeruginosa (PA) or Streptococcus pneumoniae (SP).</div></div><div><h3>Methods</h3><div>Macrophage-like THP-1 cell monocultures and co-cultures of HPAEpiC and THP-1 cells were infected with PA or SPNE for 1 h and maintained for 24 h under normocapnia, hypercapnia, or reverted hypercapnia. Expression of inflammatory markers was analysed by RT-qPCR.</div></div><div><h3>Results</h3><div>Hypercapnia enhanced IL-1β expression in infected cultures, with NLRP3 upregulated in PA infection. IRAK1 expression was inhibited under hypercapnia, particularly in co-cultures. RIPK1 was stable in monocultures but increased in co-cultures under hypercapnia. Reversion to normocapnia restored inflammatory levels in monocultures but only partially in co-cultures.</div></div><div><h3>Conclusions</h3><div>Hypercapnia amplifies pro-inflammatory responses to bacterial infection, partly through alternative pathways beyond canonical NF-κB signalling. In co-culture, these effects are further modulated by interactions with alveolar epithelial cells.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100550"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161734","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}

{"title":"EXTRACELLULAR VESICLE PROFILING IN SEVERE COVID-19 RELATED ARDS: THE IMPACT OF CHRONIC LIVER DISEASE","authors":"José Luis Román ,&nbsp;Mireya Montero ,&nbsp;Antonio Ferruelo ,&nbsp;Raquel Murillo ,&nbsp;Christian Ruiz ,&nbsp;Marta Puerto ,&nbsp;Ainoa Martín ,&nbsp;Javier Vaquero ,&nbsp;Óscar Peñuelas ,&nbsp;José Ángel Lorente ,&nbsp;Raquel Herrero","doi":"10.1016/j.opresp.2026.100553","DOIUrl":"10.1016/j.opresp.2026.100553","url":null,"abstract":"<div><h3>Rationale</h3><div>Chronic liver disease (CLD) increases the risk of acute respiratory distress syndrome (ARDS). Extracellular vesicles (EVs) and their microRNA (EV-miRNA) cargo mediate liver–lung interaction, but their role in ARDS remains unclear.</div></div><div><h3>Objectives</h3><div>1) To characterize EV-miRNA profiles in critically ill patients with COVID-19 pneumonia with and without CLD, and 2) to identify molecular pathways through which CLD influences lung injury.</div></div><div><h3>Methods</h3><div>In a case-control study, serum was collected on ICU day 1 from patients with SARS-CoV-2 pneumonia, with CLD and non-CLD groups matched for sex, age, pneumonia severity, respiratory support, and ICU length of stay. EVs were isolated with the Norgen system, size exclusion chromatography (Izon), or both, and characterized by NTA, flow cytometry, and western blot. EV-miRNAs were extracted, and 21 lung and liver-related candidates were quantified by RT-qPCR. Differential expression was assessed with REST/NormFinder, and dysregulated miRNAs were explored by Reactome, miRNet 2.0, and PANTHER for pathway and network enrichment.</div></div><div><h3>Results</h3><div>Thirty-one patients were included (14 with CLD). Norgen was the most effective EV isolation method. Five EV-miRNAs were significantly dysregulated in patients with CLD (adjusted P &lt;0.05): miR-26a-5p, miR-142-5p, and miR-223-3p (downregulated) and miR-197-3p, miR-144-5p (upregulated). Network analysis identified FOXO3, PTEN, and SOD2 as key target genes. Enrichment revealed pathways in host–virus interactions, immune signaling, inflammation, growth factor/neurotrophic signaling, and cell migration, intersecting with RHO GTPase, VEGF, and TGF-β signaling relevant to pulmonary homeostasis.</div></div><div><h3>Conclusions</h3><div>In critically ill COVID-19 patients, CLD is associated with differential EV-miRNA expression that influences immune, viral, and lung injury pathways, suggesting that CLD may worsen ARDS via EV-mediated signaling. This study also highlights the most effective EV isolation method for future biomarker use.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100553"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161784","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}

{"title":"DIAGNOSTIC TRANSCRIPTOMIC SIGNATURES FOR MYCOPLASMA PNEUMONIAE PNEUMONIA TO GUIDEPEDIATRIC PATIENT TREATMENT","authors":"Sandra Viz-Lasheras ,&nbsp;Alberto Gómez-Carballa ,&nbsp;Irene Rivero-Calle ,&nbsp;Federico Martinón-Torres ,&nbsp;Antonio Salas","doi":"10.1016/j.opresp.2026.100569","DOIUrl":"10.1016/j.opresp.2026.100569","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Mycoplasma pneumoniae</em> 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 <em>M. pneumoniae</em> 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.</div></div><div><h3>Objectives</h3><div>This study aims to delineate the host blood transcriptomic response associated with <em>M. pneumoniae</em> pneumonia and to derive minimal gene expression signatures that reliably distinguish <em>M. pneumoniae</em> pneumonia from other bacterial and viral pneumonias in pediatric patients.</div></div><div><h3>Methods</h3><div>Using blood microarray data from 107 children hospitalized with pneumonia — including 30 with confirmed <em>M. pneumoniae</em> 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 <em>M. pneumoniae</em> and viral pneumonias.</div></div><div><h3>Results</h3><div>We identified eight robust transcriptomic signatures (each comprising 3–10 genes) that discriminate <em>M. pneumoniae</em> 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 <em>M. pneumoniae</em>. Our new signatures retained strong performance in the independent RNA-seq validation cohort, demonstrating their robustness and reproducibility. Pathway analysis revealed that <em>M. pneumoniae</em> pneumonia triggers distinct host immune and inflammatory pathways compared to viral pneumonia, supporting the biological plausibility of the identified signatures.</div></div><div><h3>Conclusions</h3><div><em>Mycoplasma pneumoniae</em> 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 <em>M. pneumoniae</em> 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.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100569"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161956","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}