Respiratory Microbiome and COPD exacerbations
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Dr. Oriol Sibila (PRINCIPAL INVESTIGATOR)
Institut d’Investigació Biomèdica Sant Pau
Dra. Rosa Faner (PRINCIPAL INVESTIGATOR)
Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS)
Dra. Marian Garcia-Nuñez
Institut Universitari Parc Taulí
Dr. Jordi Dorca
Institut d’Investigació Biomèdica de Bellvitge
Dra. Judit Villar
Instituto del Hospital del Mar de Investigaciones Médicas (IMIM)
Dra. Alicia Marin
Fundació Institut d’Investigació en Ciéncies de la Salut Germans Trias i Pujol
Dr. Luis Fernando Casas
Instituto Institut d’Investigació Biomèdica de Lleida
Dr. Toni Gabaldón
Centre de Regulació Genòmica (CRG)
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The objective of this coordinated, multicenter and translational project is to test the hypothesis that the pulmonary microbiome is different in patients with Chronic Obstructive Pulmonary Disease (COPD) with frequent exacerbations (FE) compared with those COPD patients with no exacerbations (NE). Microbiome differences will be assessed in different pulmonary and extra-pulmonary (gut) compartments, and their relationship with the local and systemic immune response will be investigated. Likewise, the spatial reproducibility of the pulmonary microbiome and the potential translation of these findings to sputum as a clinically useful tool will be assessed.
Methodology: 150 individuals will be recruited (50 COPD patients with FE, 50 COPD patients with NE and 50 healthy non-smokers). Bronchoalveolar lavage (BAL) in different lung regions, Tracheal Aspirate (TA), sputum, nasal and oral swabs, peripherals blood and fecal samples will be collected. The microbiome sequencing and analysis will be performed using next-generation sequencing of 16S rRNA. The integration of the results will be performed using network medicine methodologies. In the supernatant of sputum and BAL, levels of mucins, antimicrobial peptides and inflammatory cytokines will be determined using ELISA techniques. Expression of TLR in lung leukocytes will be determined using sputum flow cytometry. Systemic immune response will be assessed by a number of inflammatory markers, bacterial translocation products and mRNA expression patterns in blood. The results of this project will help to understand the pathogenesis of COPD and its exacerbations with the final aim to identify new therapeutic targets.
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