The Microbiome of Sputum, Urine and Feces in Healthy Persons and Chronic Obstructive Pulmonary Disease (COPD) Patients (COPD)

Extensive studies suggest composition of microbiome of respiratory samples or lung tissues in COPD patients is different from the composition of healthy smokers. Aim of this study is to analyze composition of microbiome of various samples (e.g. feces, sputum, and urine) and to describe difference of composition between COPD patients and healthy smokers.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Disease, Chronic Obstructive; Microbiota; Emphysema or COPD
• Intervention / Treatment: Diagnostic test: obtain samples from sputum, feces and urine

Detailed Description

After the introduction of the Gut-Lung axis theory, extensive studies revealed 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 is a cross sectional study to analyze composition of microbiome of various samples (e.g. feces, sputum, and urine) and to compare difference of composition between COPD patients and healthy smokers. 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
  • Songpa
    • Seoul, Songpa, Korea, Republic of, 05505
      • Recruiting
      • Asan Medical Center, University of Ulsan College of Medicine
      • Contact: Sei Won Lee, MD PhD; Phone Number: +82-2-3010-3990; Email: iseiwon@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

COPD group

- Same as above

Healthy smokers

• Participants with smoking history
• Participants with normal spirometry results

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)
• Patients with recent (8 weeks prior to screening) exacerbation or other respiratory illness

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Smoker; Healthy smoker with normal spirometry value	Diagnostic test: obtain samples from sputum, feces and urine; Samples are obtained from participants. No further intervention is required. Obtained samples will be further analyzed.
COPD; 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)	Diagnostic test: obtain samples from sputum, feces and urine; 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 1 month
Microbiome composition by metagenomic analysis	The composition of microbiome is presented as bar graph.	An average of 1 month

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 1 month
Biodiversity described by Principal Component Analysis (PCA)	PCA is performed for all 16S rRNA gene reads clustered at a 97% similarity.	An average of 1 month

Collaborators and Investigators

• Sponsor: Asan Medical Center

Publications and helpful links

General Publications

• 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.
• Marsland BJ, Trompette A, Gollwitzer ES. The Gut-Lung Axis in Respiratory Disease. Ann Am Thorac Soc. 2015 Nov;12 Suppl 2:S150-6. doi: 10.1513/AnnalsATS.201503-133AW.
• Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 2012;7(10):e47305. doi: 10.1371/journal.pone.0047305. Epub 2012 Oct 11.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): March 31, 2019
• Study Completion (Anticipated): September 30, 2019

Study Registration Dates

• First Submitted: November 20, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): November 28, 2018
• Last Update Submitted That Met QC Criteria: November 26, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Microbiome; Emphysema
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: 2018-0980 (Other Identifier: M D Anderson Cancer Center)

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