Role of Pseudomonas Aeruginosa Biofilms in Exacerbations in Patients With Bronchiectasis With and Without Chronic Obstructive Pulmonary Disease

Plain-language summary

Exacerbations, in particular during chronic Pseudomonas aeruginosa (PA) infection, are very important in the prognosis of patients with non-cystic fibrosis bronchiectasis (BE). In Cystic Fibrosis patients, PA biofilms are associated with chronic respiratory infections and are the primary cause of their increased morbidity and mortality. However, the presence and role in exacerbations of PA biofilms, microbiome dysbiosis and inflammatory biomarkers has not been studied in depth in BE patients. Our aim is to determine the association between PA chronic infection and its biofilms with the number of exacerbations in the next year (primary outcome), time until next exacerbation, quality of life, FEV1 and inflammatory biomarkers (secondary outcomes) in BE patients with or without chronic obstructive pulmonary disease (COPD). The investigators will include and follow up during 12 months post study inclusion, 48 patients with BE and 48 with BE-COPD, with a positive sputum culture of PA. During stability and follow up (and in each exacerbation) The investigators will collect 4 sputum, 4 serum samples, perform spirometry, and quality of life tests every three months. For the biomarkers subproject, 4 additional serum samples will be collected at: exacerbation, 3-5 days after treatment, at 30 days and three months post-exacerbation. Biomarkers will be measured by commercial kits and Luminex. The investigators will quantify PA colony forming units (CFU)/mL, their resistance pattern, their mutation frequency and isolate mucoid and non-mucoid colonies. In each sputum, the investigators will analyze by Confocal Laser Scanning Microscopy (CLSM) and Fluorescent in situ Hybridizatrion (FISH) PA biofilms, their size, bacterial density and their in situ growth rate. Specific serum antibodies against PA will be determined through Crossed Immunoelectrophoresis. In addition, the investigators will indentify potential respiratory microbiome and gene expression patterns predictive for exacerbations, or with a protective role against chronic PA infection, as well as their association with biofilms. Microbiome analysis will be performed through the Illumina Miseq platform. Finally, the investigators will explore the antimicrobial activity of novel combinations of antibiotics against PA, both in in vitro planktonic cultures and in a biofilm model, and will include testing of antibiotic-containing alginate nanoparticles.

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