Chronic systemic inflammatory syndrome has been implicated in the pathobiology of extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). We aimed to investigate which cell types within lung tissue are responsible for expressing major acute-phase reactants in COPD patients and disease-free (“resistant”) smokers. An observational case–control study was performed to investigate three different cell types in surgical lung samples of COPD patients and resistant smokers via expression of the C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) genes. Epithelial cells, macrophages and fibroblasts from the lung parenchyma were separated by magnetic microbeads (CD326, CD14 and anti-fibroblast), and gene expression was evaluated by RT-PCR. The sample consisted of 74 subjects, including 40 COPD patients and 34 smokers without disease. All three cell types were capable of synthesizing these biomarkers to some extent. In fibroblasts, gene expression analysis of the studied biomarkers demonstrated increased SAA2 and decreased SAA1 in patients with COPD. In epithelial cells, there was a marked increase in CRP, which was not observed in fibroblasts or macrophages. In macrophages, however, gene expression of these markers was decreased in COPD patients compared to controls. These results provide novel information regarding the gene expression of CRP and SAA in different cell types in the lung parenchyma. This study revealed differences in the expression of these markers according to cell type and disease status and contributes to the identification of cell types that are responsible for the secretion of these molecules.

Background: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) involves a multifaceted interplay of factors, including incomplete thrombus resolution, endothelial dysfunction, and vascular remodeling. Recent studies have highlighted the role of extracellular vesicles (EVs) in vascular diseases, suggesting their potential involvement in CTEPH progression. This study aims to investigate the role of EVs from various cellular sources in the development of CTEPH. Methods: An experimental study was conducted using 11 male three-month-old Large-White pigs. The EVs of endothelial origin (EEVs; CD146+), leukocyte-derived EVs (LEVs; CD45+, CD44+), and consistent with mesenchymal-origin EVs (CD90+, CD105+) were quantified. Measurements were taken at baseline, after the first embolization, and prior to each subsequent weekly embolization. Embolizations were repeated until chronic pulmonary hypertension (PH) was generated. Based on these findings, a clinical case-control study was performed involving nine patients previously diagnosed with CTEPH and 18 patients with pulmonary embolism who did not develop CTEPH after two years of follow-up. Results: The experimental study, consistent with the mesenchymal-origin EVs, exhibited a progressive decrease below baseline levels; LEVs decreased after PH was established, while EEVs remained elevated throughout the study. Subsequently, in the clinical case-control study, CD45+ LEVs emerged as a significant association of CTEPH, with an odds ratio (OR) of 21.25 (95% CI: 1.91–236.00; p = 0.013). Conclusions: Inflammation involving LEVs and EEVs plays a crucial role in sustaining the vascular alterations leading to pulmonary vasculature remodeling in CTEPH.

Introduction: In a previous study we found dysregulation of microRNAs (miRNAs) 16-5p and 451a before and after exercise in patients with perfusion defects after pulmonary embolism (PE). We found and association between levels of these miRNAs and cardiopulmonary exercise testing (CPET) parameters [peak oxygen consumption per mL, Kg and minute (VO2max/ml_kg_min) and ventilatory equivalent of CO2 at the anaerobic threshold (VE/VCO2 at AT)] Aim: To identify if these observations are specific of PE patients. Methods: Patients with persistent perfusion defects after PE and healthy subjects carried out a CPET. Blood samples were drawn pre- and post- exercise and miRNAs were quantified. Mixed linear regression models have been adjusted [response variable: miRNA levels, predictor variables: CPET variables, time (pre- or post- exercise) and group (PE or healthy). We evaluated interactions between CPET variables and group, and between the time and group. Results: 15 patients and 20 healthy subjects were analyzed. A significant interaction is observed between the time (pre- post-) and the group. We also found a significant interaction between VO2 max/ml_kg_min and group in the case of miR 16-5p (p = 0.023, Figure 1). This interaction does not become significant for VO2 max/ml_kg_min and miR 451a (p = 0.105). Conclusion: our observations support PE development affects miR-16-5p expression. erj;64/suppl_68/PA535/F1 F1 F1