Bello-Perez Melissa, García-Pachón Eduardo, Gonzalo-Jimenez Nieves, Ruiz-García Montserrat, Zamora-Molina Lucía, Baeza-Martinez Carlos, Galiana Antonio
Hospital General Universitario de Elche-FISABIO, 03203 Elche, Spain.
Infectious Diseases Unit, Hospital General Universitario de Elche, 03203 Elche, Spain.
Int J Mol Sci. 2025 Jan 13;26(2):627. doi: 10.3390/ijms26020627.
Chronic obstructive pulmonary disease (COPD) exacerbations are major contributors to morbidity and mortality, highlighting the need to better understand their molecular mechanisms to improve prevention, diagnosis, and treatment. This study investigated differential gene expression profiles and key biological processes in COPD exacerbations categorized based on sputum microbiome profiling. An observational study was performed on a cohort of 16 COPD patients, who provided blood and sputum samples during exacerbations, along with five stable-state samples as controls. Exacerbations were classified using sequencing to analyze the sputum microbiota and multiplex PCR to detect respiratory viruses. Blood transcriptomic profiling was conducted using Oxford Nanopore technology, followed by differential gene expression and pathway enrichment analyses. A total of 768 regulated genes were identified across the exacerbation groups, with 35 shared genes associated with neutrophil activation. Bacterial exacerbations activated pathways related to phagocytosis and toll-like receptor signaling, while viral exacerbations were linked to pro-inflammatory responses and mitochondrial damage. Exacerbations of unknown origin showed activation of pathways involved in protozoan defense and neutrophilic asthma. Biomarkers such as and for bacterial exacerbations, for viral, and for unknown-origin exacerbations were identified. These findings highlight distinct transcriptomic profiles and biological pathways in COPD exacerbations, emphasizing the central role of neutrophil-driven inflammation and identifying potential biomarkers for improved differential diagnosis and personalized management.
慢性阻塞性肺疾病（COPD）急性加重是发病和死亡的主要原因，这凸显了更好地了解其分子机制以改善预防、诊断和治疗的必要性。本研究调查了基于痰液微生物组分析分类的COPD急性加重中的差异基因表达谱和关键生物学过程。对16例COPD患者进行了一项观察性研究，这些患者在急性加重期提供了血液和痰液样本，以及5份稳定期样本作为对照。使用测序分析痰液微生物群，并使用多重PCR检测呼吸道病毒，对急性加重进行分类。使用牛津纳米孔技术进行血液转录组分析，随后进行差异基因表达和通路富集分析。在各个急性加重组中总共鉴定出768个受调控基因，其中35个共享基因与中性粒细胞活化相关。细菌感染导致的急性加重激活了与吞噬作用和Toll样受体信号传导相关的通路，而病毒感染导致的急性加重则与促炎反应和线粒体损伤有关。不明原因的急性加重显示参与原生动物防御和嗜中性哮喘的通路被激活。确定了细菌感染导致的急性加重的生物标志物如 和 、病毒感染导致的急性加重的生物标志物 以及不明原因急性加重的生物标志物 。这些发现突出了COPD急性加重中不同的转录组谱和生物学通路，强调了中性粒细胞驱动的炎症的核心作用，并确定了潜在的生物标志物，以改善鉴别诊断和个性化管理。
