Lung Microbiome and Inflammation in Early COPD

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstuctive Pulmonary Disease
• Intervention / Treatment: Procedure: Bronchoscopy

• Study Type: Observational
• Enrollment (Estimated): 230

Contacts and Locations

• Study Contact: Name: Rosemary Schluger; Email: Rosemary.Schluger@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University School of Medicine
      • Contact: Kathryn Norris; Email: Kathryn.Norris@nyumc.org
      • Contact: Adrienne Scott; Email: Adrienne.Scott@nyumc.org
      • Sub-Investigator: Doreen J Addrizzo-Harris, MD
      • Sub-Investigator: Rany Condos, MD
      • Sub-Investigator: Stephanie Lau, MD
      • Sub-Investigator: Ashwin Basavaraj, MD
      • Sub-Investigator: Michael D Weiden, MD
      • Sub-Investigator: Yonghua Li, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Utilizing cohorts built at NYU over the last several years, this project is uniquely positioned to investigate the microbiome signatures among subjects with COPD.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic Obstructive Pulmonary Disease (COPD); Case of early COPD (GOLD 1-2, FEV1/FVC<70 and FEV1>50%)	Procedure: Bronchoscopy; 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.
Control; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Leopoldo Segal, MD, New York University Medical School

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimated): May 19, 2016

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease (COPD)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Inflammation
• Other Study ID Numbers: 14-01546

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No