Lung Microbiome and Inflammation in Early COPD

Study Overview
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Brief Summary
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This is a cross sectional case controlled study to assess lung microbiome and inflammation in smokers with and without Chronic Obstructive Pulmonary Disease (COPD). Investigators will look at active bacterial metabolic pathways in the lower airways using metagenomic and metabolomic approaches an assess relationships among microbiome, metagenome, metabolome and host immune responses in COPD and controls. Investigators believe COPD cases will have higher prevalence of pneumotype supraglottic predominant taxa (SPT) than matched controls.

Official Title
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Lung Microbiome and Inflammation in Early Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstuctive Pulmonary Disease

Intervention / Treatment
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* Procedure: Bronchoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Case definition: Smokers (>20 pack-year) with airflow obstruction (FEV1/FVC<70) and FEV1>50% predicted (early COPD GOLD 1 or 2) Control definition: Smokers with normal spirometry will serve as controls. Exclusion Criteria: FEV1 < 50% NOT 70 Significant cardiovascular disease defined as abnormal EKG, known or suspected coronary artery disease or congestive heart failure. Diabetes mellitus Significant liver or renal disease Severe coagulopathy (INR > 1.4, PTT > 40 seconds and platelet count < 150x103 cells). Pregnancy ETOH use of more than >6 beers or >4 mixed drinks daily Lack of capacity to provide informed consent. Antibiotic use within the prior 2months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic Obstructive Pulmonary Disease (COPD)<br>Case of early COPD (GOLD 1-2, FEV1/FVC<70 and FEV1>50%) | Procedure: Bronchoscopy<br>* Flexible bronchoscopy with bronchoalveolar lavage (BAL) and bronchial brushings will be done in a standardized manner. The bronchoscope tip is sequentially wedged in sub-segments where BAL will be performed on a total of two segments of the lung (120 ml in each segment for a total of 360 ml). Two brushes will be done under direct visualization in both segments. Selection of segments to sample will be based on where abnormalities are in imaging.<br>|
| Control<br>No obstruction (FEV1/FVC<70). Controls will be recruited after each case and will be matched by: age (±5 year), 2) gender, 3) smoking (±5 pack-year) and 4) BMI (±5). | Procedure: Bronchoscopy<br>* Flexible bronchoscopy with bronchoalveolar lavage (BAL) and bronchial brushings will be done in a standardized manner. The bronchoscope tip is sequentially wedged in sub-segments where BAL will be performed on a total of two segments of the lung (120 ml in each segment for a total of 360 ml). Two brushes will be done under direct visualization in both segments. Selection of segments to sample will be based on where abnormalities are in imaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Site specific microbiome (supraglotic area) constituents using background subtraction and source tracking approaches via a multivariable conditional logistic regression model. following broncho-alveolar lavage, BAL |  | 4 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial metabolic pathways in the lower airways using metagenomic and metabolomic approaches | Bioinformatic methods such as Procrustes will be used to integrate the analysis of the generated multi-omic datasets through this study to attain a more accurately defined COPD phenotype. By elucidating the interplay between bacterial composition, microbiome functional repertoire, metabolism, and immunological status in the human lung, we will obtain further insights for hypothesis generation into the pathophysiological mechanisms underlying COPD. | 4 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease (COPD)