Analysis of the Microbiome in the Healthy Smokers and COPD Patients

This study is to build a microbiome cohort by collecting sputum and fecal samples every few months for three years from healthy smokers and chronic obstructive pulmonary disease (COPD) patients. The aim of this study is to analyze the composition of microbiome of various samples (e.g. sputum, feces) and describe the difference between healthy smokers and COPD patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Disease, Chronic Obstructive; Microbiota
• Intervention / Treatment: Diagnostic test: Obtain samples from sputum and feces

Detailed Description

After the introduction of the gut-lung axis theory, extensive studies revealed the diversity of microbiomes among healthy smokers and COPD patients form the respiratory samples or lung tissues. In the previous study, distinct difference in composition of microbiome in lung tissue between healthy smokers and COPD patients was reported. This study is to build a microbiome cohort by collecting sputum and fecal samples every few months for three years from healthy smokers and chronic obstructive pulmonary disease (COPD) patients who are being followed up by Asan Medical Center. The aim of this study is to analyze the composition of microbiome of various samples (e.g. sputum, feces) and describe the difference between healthy smokers and COPD patients. This study would help establishing gut-lung axis model in humans.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy smoker Healthy smokers with smoking history at least 10 pack-years and normal spirometry value

COPD patient Patients with smoking history at least 10 pack-years and persistent airflow limitation that was not fully reversible (e.g. post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.7)

Description

Inclusion Criteria:

• Patients with smoking history at least 10 pack-year
• Patients with persistent airflow limitation that was not fully reversible (e.g. post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.7)

Exclusion Criteria:

• Patients with co-existing illness that would interfere with study results (e.g., malignancy, congestive heart failure, cerebrovascular disorders, chronic renal failure, diabetes with severe complications, or uncontrolled hypertension)
• Patients with respiratory disease other than obstructive lung disease (e.g., previous pulmonary resection, tuberculosis-destroyed lung, and bronchiectasis)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy smoker; Healthy smokers with smoking history at least 10 pack-years and normal spirometry value	Diagnostic test: Obtain samples from sputum and feces; Samples are obtained from participants. No further intervention is required. Obtained samples will be further analyzed.
COPD patient; Patients with smoking history at least 10 pack-years and persistent airflow limitation that was not fully reversible (e.g. post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.7)	Diagnostic test: Obtain samples from sputum and feces; Samples are obtained from participants. No further intervention is required. Obtained samples will be further analyzed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alpha diversity measured by operational taxonomic unit (OTU) quantitative analysis	DNA is extracted from each sample from each patient by using a DNA Isolation Kit. The 16S universal primers are used for amplification of 16S ribosomal ribonucleic acid (rRNA) genes with polymerase chain reaction (PCR) system. After amplication, sequencing is performed using the GREENGENES database, after which a metagenomic analysis was performed by the MD Healthcare corporation using MDx-Pro software (Ver.1, Seoul, South Korea). Taxonomic assignment of these sequences is carried out with an operational taxonomic unit (OTU) cutoff of 3%.	An average of 3 months
Microbiome composition by metagenomic analysis	The composition of microbiome is presented as bar graph.	An average of 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biodiversity described by the Shannon diversity index and the Simpson index	The Shannon index and the Simpson index is calculated by using metagenomic data.	An average of 3 months
Biodiversity described by Principal Component Analysis (PCA)	PCA is performed for all 16S rRNA gene reads clustered at a 97% similarity.	An average of 3 months

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Sei Won Lee, M.D. Ph.D., University of Ulsan College of Medicine, Asan Medical Center

Publications and helpful links

General Publications

• Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, Young VB, Toews GB, Curtis JL, Sundaram B, Martinez FJ, Huffnagle GB. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One. 2011 Feb 22;6(2):e16384. doi: 10.1371/journal.pone.0016384.
• Kim HJ, Kim YS, Kim KH, Choi JP, Kim YK, Yun S, Sharma L, Dela Cruz CS, Lee JS, Oh YM, Lee SD, Lee SW. The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients. Exp Mol Med. 2017 Apr 14;49(4):e316. doi: 10.1038/emm.2017.7.
• Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, Flores SC, Fontenot AP, Ghedin E, Huang L, Jablonski K, Kleerup E, Lynch SV, Sodergren E, Twigg H, Young VB, Bassis CM, Venkataraman A, Schmidt TM, Weinstock GM; Lung HIV Microbiome Project. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013 May 15;187(10):1067-75. doi: 10.1164/rccm.201210-1913OC.
• Cabrera-Rubio R, Garcia-Nunez M, Seto L, Anto JM, Moya A, Monso E, Mira A. Microbiome diversity in the bronchial tracts of patients with chronic obstructive pulmonary disease. J Clin Microbiol. 2012 Nov;50(11):3562-8. doi: 10.1128/JCM.00767-12. Epub 2012 Aug 22.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 6, 2020
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: April 3, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (ACTUAL): April 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2020
• Last Update Submitted That Met QC Criteria: April 3, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Microbiome; Chronic obstructive pulmonary disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: Microbiome cohort

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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