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 16S rRNA 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 IFITM3 and ISG15 for bacterial exacerbations, DEFA3 for viral, and CD47 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.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Background: The recently proposed Staging of Airflow Obstruction by Ratio (STAR) system classifies severity based on the FEV₁/FVC ratio, potentially offering improved prognostic performance. This study aimed to evaluate the prognostic performance of STAR in patients hospitalized for COPD exacerbation. Methods: A retrospective observational single-center study was conducted including COPD patients who were discharged after hospitalization for a severe exacerbation at a university hospital. The clinical and spirometric data in a stable condition, GOLD classification, STAR system, and mortality outcomes were recorded. Results: A total of 197 patients (23% female) were included. The follow-up was performed for a minimum of 38 months or until death if it occurred earlier. During the study period, 91 patients died (46%). Patients were distributed according to the STAR classification as follows: 21% in STAR 1, 32% in STAR 2, 28% in STAR 3, and 19% in STAR 4. The agreement between STAR and GOLD was fair (Cohen’s kappa = 0.28), with a moderate correlation (Tau-b = 0.49, p < 0.001). STAR grades 2 to 4 demonstrated progressively increasing mortality, while STAR grade 1 showed a mortality similar to grade 2. STAR showed a trend toward a superior discrimination for mortality than GOLD (AUC 0.63 [95%CI 0.55–0.71] vs. 0.55 [0.47–0.63]; p = 0.055), although BODEx remained the most accurate predictor (AUC = 0.70 [0.63–0.77]). Conclusions: The STAR system effectively stratified the mortality risk among hospitalized COPD patients across grades 2 to 4. However, STAR grade 1 failed to differentiate patients with a lower risk. Although STAR may underestimate severity in individual patients with relatively preserved ratios, its integration into clinical evaluation could enhance prognostic assessments.