Respiratory Microbiome and COPD Exacerbations (RESMECOPD) (RESMECOPD)

Respiratory Microbiome and COPD Exacerbations

The global objective of this coordinated project is to test the following hypotheses: 1) the lung microbiome in chronic obstructive pulmonary disease (COPD) is different in patients suffering from frequent exacerbations (FE) compared those who do not (NE ); 2) The microbial profile of patients with FE is associated with a different local and systemic inflammatory pattern; and 3) the inflammatory and immune characteristics of COPD are modulated by the intestinal microbiome.

The project is based on bronchoalveolar lavage (BAL) for sampling lung microbiome, and includes analysis of regional variability (intrapulmonary) and temporal variability. The project will also assess the correlation between BAL samples obtained from the proximal airway (oral cavity, oropharynx and sputum), and the representation of lung microbiome in them. A cohort of COPD patients (n = 50 FE; n = 50 NE) and healthy subjects (n= 30), matched by age, sex and tobacco consumption. Respiratory secretion samples will be collected in clinical stability samples, with resampling in a quarter of the participants at 6-9 months. Coordinator Project: Bacterial and fungal microbiota will be determined by 16S rRNA and ITS amplification and sequencing. Virome and functional metagenomics will be analyzed in a quarter of the participants. Subprojects: Regional variability in the lung, local and systemic inflammatory response, and the relationship between the intestinal microbiome and inflammatory and clinical characteristics of the disease will be determined. The integration of the results will be performed using network medicine methodologies. 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.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Disease, Chronic Obstructive; Exacerbation COPD
• Intervention / Treatment: Other: Biomarkers

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• Spain
  • Badalona, Spain
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital Del Mar
  • Barcelona, Spain
    • Hospital Clinic
  • Barcelona, Spain
    • Hospital de Bellitge
  • Barcelona, Spain
    • Hosptial de Sant Pau
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Eligible subjects were COPD patients GOLD II/III in stable situation.

Description

Inclusion Criteria:

• Spirometry: FEV1/FVC < 70%; FEV1 between 50 and 80% predicted (GOLD II/III)
• Clinical Stability (no therapeutic change and/or use of antibiotics) during 8 weeks. - The treatment received will be registered for post-hoc studies stratified by this condition.

Exclusion Criteria:

• Drug addiction, alcohol abuse,
• Use of long-term oral or nebulised antibiotic therapy.
• History of allergies, asthma or other chronic respiratory disease, sanitary worker, working exposure to dust or fumes.
• Other diseases: Severe cardiovascular, neurological, psychiatric, renal, hepatic or gastrointestinal , that might interfere with the daily life activities.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COPD and frequent exacerbation; Patient with COPD diagnosis and at least two exacerbations by year (FE)	Other: Biomarkers; This is an observational study, there is no intervention
COPD no frequent exacerbation; Patient with COPD diagnosis with no frequent exacerbation, less than 2 by year (NE).	Other: Biomarkers; This is an observational study, there is no intervention
Healthy (control); Healthy volunteers patients (H)	Other: Biomarkers; This is an observational study, there is no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Microbiome in COPD patients with FE and NE.	Respiratory Microbiome composition will be determined by using metagenomic aproaches.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteria related to pulmonary and systemic inflamatory factors (FE vs NE)	Determination of pulmonary and systemic markers with ELISA kit. Microbiome will be determined by metagenomic techniques.	7 days
Longitudinal variability of respiratory microbiome in COPD patients (FE vs NE).	Change of respiratory Microbiome (diversity and abundance)	12 months
Inmunological response of lung epithelial cells COPD patients after an infectious and inflammatory stimuli	The in vitro response of epithelial cells will be determined with ELISA kits.	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spatial variability of respiratory microbiome in COPD patients (FE vs NE).	Respiratory Microbiome Composition of different types of samples.	1 day

Collaborators and Investigators

• Sponsor: Corporacion Parc Tauli
• Collaborators: Hospital Clinic of Barcelona; Germans Trias i Pujol Hospital; Hospital Arnau de Vilanova; Hospital del Mar; Hospital Universitari de Bellvitge; Hospital de Sant Pau; Centre for Genomic Regulation
• Investigators: Principal Investigator: Oriol Sibila, Hospital de Sant Pau; Principal Investigator: Rosa Faner, Hospital Clinic; Study Director: Eduard Monso, Hospital Parc Tauli

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 7, 2016
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (ACTUAL): February 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Microbiome; COPD; Exacerbation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: PI15/0157 (2015607)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Sequencing data will be available in public databases.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No