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Volume 26
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Gene Expression Profiles Reveal Distinct Mechanisms Driving Chronic Obstructive Pulmonary Disease Exacerbations

by
Melissa Bello-Perez
1,2,*,
Eduardo García-Pachón
1,
Nieves Gonzalo-Jimenez
1,3,
Montserrat Ruiz-García
1,
Lucía Zamora-Molina
1,
Carlos Baeza-Martinez
1 and
Antonio Galiana
1
1
Hospital General Universitario de Elche-FISABIO, 03203 Elche, Spain
2
Infectious Diseases Unit, Hospital General Universitario de Elche, 03203 Elche, Spain
3
Biomedical Research Networking Center for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(2), 627; https://doi.org/10.3390/ijms26020627
Submission received: 18 December 2024 / Revised: 10 January 2025 / Accepted: 12 January 2025 / Published: 13 January 2025
(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease (COPD): From Pathogenesis to Therapy)
Versions Notes

Abstract

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.
Keywords: COPD; exacerbation; transcriptomics; microbiome; gene expression profiles; biomarkers; inflammatory responses; personalized management COPD; exacerbation; transcriptomics; microbiome; gene expression profiles; biomarkers; inflammatory responses; personalized management

Share and Cite

MDPI and ACS Style

Bello-Perez, M.; García-Pachón, E.; Gonzalo-Jimenez, N.; Ruiz-García, M.; Zamora-Molina, L.; Baeza-Martinez, C.; Galiana, A. Gene Expression Profiles Reveal Distinct Mechanisms Driving Chronic Obstructive Pulmonary Disease Exacerbations. Int. J. Mol. Sci. 2025, 26, 627. https://doi.org/10.3390/ijms26020627

AMA Style

Bello-Perez M, García-Pachón E, Gonzalo-Jimenez N, Ruiz-García M, Zamora-Molina L, Baeza-Martinez C, Galiana A. Gene Expression Profiles Reveal Distinct Mechanisms Driving Chronic Obstructive Pulmonary Disease Exacerbations. International Journal of Molecular Sciences. 2025; 26(2):627. https://doi.org/10.3390/ijms26020627

Chicago/Turabian Style

Bello-Perez, Melissa, Eduardo García-Pachón, Nieves Gonzalo-Jimenez, Montserrat Ruiz-García, Lucía Zamora-Molina, Carlos Baeza-Martinez, and Antonio Galiana. 2025. "Gene Expression Profiles Reveal Distinct Mechanisms Driving Chronic Obstructive Pulmonary Disease Exacerbations" International Journal of Molecular Sciences 26, no. 2: 627. https://doi.org/10.3390/ijms26020627

APA Style

Bello-Perez, M., García-Pachón, E., Gonzalo-Jimenez, N., Ruiz-García, M., Zamora-Molina, L., Baeza-Martinez, C., & Galiana, A. (2025). Gene Expression Profiles Reveal Distinct Mechanisms Driving Chronic Obstructive Pulmonary Disease Exacerbations. International Journal of Molecular Sciences, 26(2), 627. https://doi.org/10.3390/ijms26020627

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