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

NCT04803695 | Unknown

• 1 other identifier: v.11 27/02/18
• Study Type: observational
• Target: 96
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bronchiectasis; Microbial Colonization; Pseudomonas Aeruginosa; Biofilm

Outcome Measures

Primary Outcomes (1)

• Number of exacerbations per year

  Exacerbations during the follow up

  1 year

Secondary Outcomes (1)

• Levels of inflammatory biomarkers during the follow up and in exacerbations

  1 year

Interventions

Microbial biofilm diagnose DIAGNOSTIC_TEST

Usage of new microbiological methods for biofilm detection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

96 BE patients (48 with BE and 48 with BE-COPD), and with positive sputum culture for PA. Follow-up will be performed for 12 months after the first isolation of PA. All patients must sign informed consent before recruitment in the study.

You may qualify if:

• BE criteria (with and without COPD)
• Isolation of PA in sputum in the stable phase. \* A prospective screening of BQ patients in outpatient consultations will be conducted to prospectively detect those with isolation of PA in the sputum.

You may not qualify if:

• Immunosuppression (primary and secondary, with the exception of cases of IgG deficiency in stable substitution treatment)
• Sarcoidosis
• Tuberculosis, active infection by nontuberculous mycobacteria
• Diffuse interstitial lung disease
• Altered state of consciousness or disability to understand the study and perform the tests provided by it, involving the patient in another intervention study (clinical trials).
• Patients with CF are excluded because the role of PA biofilms in CF has been extensively studied, as argued in the background of the present proposal and the selected literature. It is also a totally different disease from the one we intend to study, with patients of much younger ages. Finally, this is a very vulnerable population in which it would be very difficult to obtain all the samples sequentially.

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• ISCIII: collaborator

Study Sites (1)

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Sputum Serum

MeSH Terms

Conditions

Bronchiectasis; Communicable Diseases; Pseudomonas Infections

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Fernández-Barat Laia

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fernández-Barat Laia, Biology

CONTACT

932275400; lfernan1@clinic.cat

Torres Marti Antonio, Medicine

CONTACT

932275400; atorres@clinic.cat

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 18, 2021
• Study Start: March 1, 2018
• Primary Completion: January 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 18, 2021

Record last verified: 2021-03

Locations

ES (1)