Characteristics of Intestinal Microbiome in the Progression of Early COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

Characteristics of Intestinal Microbiome in the Progression of Early Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04876833
• Other study ID #: MR-61-21-012951
• Status: Not yet recruiting
• Start date: May 2021
• Est. completion date: July 2022

Study information

• Verified date: May 2021
• Source: Second Affiliated Hospital of Xi'an Jiaotong University
• Contact: Yun Liu, MD
• Phone: 0086-13572887605
• Email: 27556828[@]qq.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This study is aiming at explore the characteristics of intestinal microbiome during the early progression of COPD, the correlation between the changes of intestinal microbiome and the severity and risk of acute exacerbation of COPD, the correlation between microbial metabolites SCFA and immune function of COPD. Then reveal the influence of intestinal microecology on the development of COPD and the possible mechanism of intestinal microecology in the pathogenesis of COPD.

Description:

1. Invite participants according to inclusion criteria and exclusion criteria and divide them into 4 groups, including healthy control (HC), high-risk COPD group (HG), early COPD group (EG), mild and moderate COPD group (MG). Research contents will be explained detailedly to the participants, and the healthy participants and COPD patients who volunteer to participate in this study will sign the informed consent form (ICF) under the premise of adequate understanding.

2. Collect clinical data of the participants and asses the severity of symptoms and the risk of acute exacerbation of COPD patients. Clinical data include general condition, history of past illness, history of present illness, personal history, family history and the examination results of blood routine, pulmonary function and compatible computed tomography. Breathlessness measurement adopt the modified British Medical Reseach Council (mMRC); symptoms measurement adopt COPD assessment test (CAT); quality of life measurement adopt St. George's Respiratory Questionnaire (SGRQ); risk of acute exacerbation measurement adopt dyspnea，degree of airflow obstruction，smoking status and the number of exacerbation (DOSE) scoring system.

3. Collect fecal specimens from the participants on the morning of the same day. During the first three days of collection, they should keep their daily dietary habits and avoid sudden changes in dietary habits. Considerations: first remove the urine, excrement into a clean dry container, do not mix with urine and other sundries; the part of the feces that do not contact the air and container is taken from the specimen; women who are menstruating cannot be sampled. Each participant collect 3 fecal samples with a sterile spoon in a sterile enzyme-free cryopreservation tube, label the sample name and date, quickly placed in a -20℃ refrigerator, and transported to the hospital within 2 hours, where they were stored at -80℃. Fecal microbiome are detected by 16S rRNA gene sequencing and metabolite short chain fatty acid (SCFA) are detected by Gaschromatography (GC).

4. Serum of participants are collected at the clinical laboratory and detect indicators related to immune function by enzyme-linked immunosorbent assay (ELISA).

5. Explore the characteristics of intestinal microbiome during the early progression of COPD, the correlation between the changes of intestinal microbiome and the severity and risk of acute exacerbation of COPD, the correlation between microbial metabolites SCFA and immune function of COPD.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: July 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. =10 pack-years smoking history;

2. Examination of pulmonary function and compatible computed tomography meeting group requirements (as shown in Groups and Interventions).

Exclusion Criteria:

1. Take antibiotics, probiotics, prebiotics, synbiotics and other drugs that obviously interfere with intestinal microbiome within 2 months;

2. Suffer from other chronic respiratory diseases other than COPD (such as bronchial asthma, allergic rhinitis, pulmonary interstitial fibrosis, bronchiectasis, lung cancer, etc.);

3. Suffer from severe intestinal diseases (such as inflammatory bowel disease, intestinal infections, colorectal cancer, etc.);

4. Suffer from serious hematopoietic system diseases, and the brain, heart, liver, kidney and other important organs are damaged;

5. Suffer from severe hypertension, coronary heart disease, diabetes and other chronic diseases and taking drugs for long-term maintenance;

6. Suffer from active infectious diseases (hepatitis B, tuberculosis, etc.);

7. Pregnant or lactating women;

8. Patients with obvious anxiety, depression and other psychiatric symptoms and patients with schizophrenia.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Locations

Country	Name	City	State
China	Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Xi'an Jiaotong University	Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Country where clinical trial is conducted

China, 

References & Publications (16)

Bowerman KL, Rehman SF, Vaughan A, Lachner N, Budden KF, Kim RY, Wood DLA, Gellatly SL, Shukla SD, Wood LG, Yang IA, Wark PA, Hugenholtz P, Hansbro PM. Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary — View Citation

Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M, Hugenholtz P, Hansbro PM. Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol. 2017 Jan;15(1):55-63. doi: 10.1038/nrmicro.2016.142. Epub 2016 Oct 3. Review. — View Citation

Çolak Y, Afzal S, Nordestgaard BG, Vestbo J, Lange P. Prevalence, Characteristics, and Prognosis of Early Chronic Obstructive Pulmonary Disease. The Copenhagen General Population Study. Am J Respir Crit Care Med. 2020 Mar 15;201(6):671-680. doi: 10.1164/r — View Citation

GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis f — View Citation

Jang YO, Lee SH, Choi JJ, Kim DH, Choi JM, Kang MJ, Oh YM, Park YJ, Shin Y, Lee SW. Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis. Exp Mol Med. 2020 Jul;52(7):1128-1139. do — View Citation

Keely S, Talley NJ, Hansbro PM. Pulmonary-intestinal cross-talk in mucosal inflammatory disease. Mucosal Immunol. 2012 Jan;5(1):7-18. doi: 10.1038/mi.2011.55. Epub 2011 Nov 16. Review. — View Citation

Lee SH, Yun Y, Kim SJ, Lee EJ, Chang Y, Ryu S, Shin H, Kim HL, Kim HN, Lee JH. Association between Cigarette Smoking Status and Composition of Gut Microbiota: Population-Based Cross-Sectional Study. J Clin Med. 2018 Sep 14;7(9). pii: E282. doi: 10.3390/jc — View Citation

Li N, Yang Z, Liao B, Pan T, Pu J, Hao B, Fu Z, Cao W, Zhou Y, He F, Li B, Ran P. Chronic exposure to ambient particulate matter induces gut microbial dysbiosis in a rat COPD model. Respir Res. 2020 Oct 19;21(1):271. doi: 10.1186/s12931-020-01529-3. — View Citation

Mortaz E, Adcock IM, Ricciardolo FL, Varahram M, Jamaati H, Velayati AA, Folkerts G, Garssen J. Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages. PLoS One. 2015 Aug 28;10(8):e013 — View Citation

Reale M, Boscolo P, Bellante V, Tarantelli C, Di Nicola M, Forcella L, Li Q, Morimoto K, Muraro R. Daily intake of Lactobacillus casei Shirota increases natural killer cell activity in smokers. Br J Nutr. 2012 Jul;108(2):308-14. doi: 10.1017/S000711451100 — View Citation

Sprooten RTM, Lenaerts K, Braeken DCW, Grimbergen I, Rutten EP, Wouters EFM, Rohde GGU. Increased Small Intestinal Permeability during Severe Acute Exacerbations of COPD. Respiration. 2018;95(5):334-342. doi: 10.1159/000485935. Epub 2018 Jan 25. — View Citation

Stockley RA, Halpin DMG, Celli BR, Singh D. Chronic Obstructive Pulmonary Disease Biomarkers and Their Interpretation. Am J Respir Crit Care Med. 2019 May 15;199(10):1195-1204. doi: 10.1164/rccm.201810-1860SO. Review. — View Citation

Tomoda K, Kubo K, Dairiki K, Yamaji T, Yamamoto Y, Nishii Y, Nakamura A, Yoshikawa M, Hamada K, Kimura H. Whey peptide-based enteral diet attenuated elastase-induced emphysema with increase in short chain fatty acids in mice. BMC Pulm Med. 2015 Jun 10;15: — View Citation

Tsay JJ, Segal LN. Could the Sputum Microbiota Be a Biomarker That Predicts Mortality after Acute Exacerbations of Chronic Obstructive Pulmonary Disease? Am J Respir Crit Care Med. 2019 May 15;199(10):1175-1176. doi: 10.1164/rccm.201811-2138ED. — View Citation

Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, Kang J, Ran P, Shen H, Wen F, Huang K, Yao W, Sun T, Shan G, Yang T, Lin Y, Wu S, Zhu J, Wang R, Shi Z, Zhao J, Ye X, Song Y, Wang Q, Zhou Y, Ding L, Yang T, Chen Y, Guo Y, Xiao F, Lu Y, Peng X, Zhang B, Xiao D, — View Citation

Wypych TP, Wickramasinghe LC, Marsland BJ. The influence of the microbiome on respiratory health. Nat Immunol. 2019 Oct;20(10):1279-1290. doi: 10.1038/s41590-019-0451-9. Epub 2019 Sep 9. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Breathlessness measurement	modified British Medical Reseach Council (mMRC):the score increases from 0 to 4,and higher scores mean a heavier symptom.	1 month
Primary	Symptoms measurement	COPD assessment test (CAT):the score increases from 0 to 40,and higher scores mean a heavier symptom.	1 month
Primary	Quality of life measurement	St. George's Respiratory Questionnaire (SGRQ): the score increases from 0 to 100,and higher scores mean a heavier symptom.	1 month
Primary	Risk of acute exacerbation of participants	dyspnea,degree of airflow obstruction,smoking status,the number of exacerbation (DOSE): the score increases from 0 to 9,and higher scores mean a higher risk of acute exacerbation.	1 month
Primary	Pulmonary function	Forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), FEV1%predicted, MMEF25-75%: range from 0%-100%, and higher percentages mean a heavier symptom.	1 month
Primary	Compatible computed tomography	mean lung density	1 month
Primary	Characteristics of intestinal microbiome	Alpha diversity,Beta diversity,Species differences between groups at different taxonomic levels.	1 month
Primary	Contents of short chain fatty acid in fecal samples	acetic acid, propionic acid, butyric acid	1 month
Primary	Blood routine	neutrophilic granulocyte percent, eosinophilic granulocyte percent: higher percentages mean a heavier symptom.	1 month
Primary	Concentration of protein in serum	fibrinogen, C-reactive protein, surfactant protein-D(SP-D)	1 month
Primary	Concentration of enzyme in serum	neutrophil elastase, alpha1-antitrypsin	1 month
Primary	Concentration of inflammatory factor in serum	TNF-a, IFN-?, IL-6, IL-8, IL-17	1 month
Primary	Concentration of chemokine in serum	CCL-16, CCL-18	1 month

External Links

•   Characteristics of intestinal flora in patients with chronic obstructive pulmonary disease and their correlation with inflammatory markers and pulmonary function status
•   Correlation index analysis of intestinal flora and inflammatory factors in patients with chronic obstructive pulmonary disease