Characteristics of Intestinal Microbiome in the Progression of Early COPD

NCT04876833 | Unknown

• 1 other identifier: MR-61-21-012951
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease; Intestinal Microbiome; Metabolite; Immune Function

Outcome Measures

Primary Outcomes (13)

• Breathlessness measurement

  modified British Medical Reseach Council (mMRC)：the score increases from 0 to 4，and higher scores mean a heavier symptom.

  1 month

• Symptoms measurement

  COPD assessment test (CAT)：the score increases from 0 to 40，and higher scores mean a heavier symptom.

  1 month

• 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

• 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

• 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

• Compatible computed tomography

  mean lung density

  1 month

• Characteristics of intestinal microbiome

  Alpha diversity，Beta diversity，Species differences between groups at different taxonomic levels.

  1 month

• Contents of short chain fatty acid in fecal samples

  acetic acid, propionic acid, butyric acid

  1 month

• Blood routine

  neutrophilic granulocyte percent, eosinophilic granulocyte percent: higher percentages mean a heavier symptom.

  1 month

• Concentration of protein in serum

  fibrinogen, C-reactive protein, surfactant protein-D(SP-D)

  1 month

• Concentration of enzyme in serum

  neutrophil elastase, alpha1-antitrypsin

  1 month

• Concentration of inflammatory factor in serum

  TNF-α, IFN-γ, IL-6, IL-8, IL-17

  1 month

• Concentration of chemokine in serum

  CCL-16, CCL-18

  1 month

Study Arms (4)

HC，healthy control

18-65 years old，no smoking history，normal pulmonary function，normal compatible computed tomography.

HG，high-risk COPD group

18-60 years old，≥10 pack-years smoking history，normal pulmonary function，normal compatible computed tomography.

EG，early COPD group

18-60 years old，≥10 pack-years smoking history，and with any of the following abnormalities： 1. Forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than 80%; 2. Compatible computed tomography abnormalities：airway abnormality and/or emphysema，air trapping, or bronchial thickening； 3. FEV1 decline (≥60 mL per year).

MG，mild and moderate COPD group

18-65 years old，FEV1/FVC\<70%，FEV1%predicted ≥50%.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants are from Physical Examination Department and Respiratory and Critical Care Medicine Department of the Second Affiliated Hospital of Xi 'an Jiaotong University.

You may qualify if:

• ≥10 pack-years smoking history;
• Examination of pulmonary function and compatible computed tomography meeting group requirements (as shown in Groups and Interventions).

You may not qualify if:

• Take antibiotics, probiotics, prebiotics, synbiotics and other drugs that obviously interfere with intestinal microbiome within 2 months;
• Suffer from other chronic respiratory diseases other than COPD (such as bronchial asthma, allergic rhinitis, pulmonary interstitial fibrosis, bronchiectasis, lung cancer, etc.);
• Suffer from severe intestinal diseases (such as inflammatory bowel disease, intestinal infections, colorectal cancer, etc.);
• Suffer from serious hematopoietic system diseases, and the brain, heart, liver, kidney and other important organs are damaged;
• Suffer from severe hypertension, coronary heart disease, diabetes and other chronic diseases and taking drugs for long-term maintenance;
• Suffer from active infectious diseases (hepatitis B, tuberculosis, etc.);
• Pregnant or lactating women;
• Patients with obvious anxiety, depression and other psychiatric symptoms and patients with schizophrenia.

Sponsors & Collaborators

• Second Affiliated Hospital of Xi'an Jiaotong University: lead
• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: collaborator

Study Sites (1)

Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

Location

Related Publications (16)

• 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. No abstract available.

  PMID: 30485116 BACKGROUND

• 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.

  PMID: 30592902 BACKGROUND

• 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.

  PMID: 27694885 BACKGROUND

• 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 for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017 Sep;5(9):691-706. doi: 10.1016/S2213-2600(17)30293-X. Epub 2017 Aug 16.

  PMID: 28822787 RESULT

• 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, Chen CS, Wang Z, Zhang H, Bu X, Zhang X, An L, Zhang S, Cao Z, Zhan Q, Yang Y, Cao B, Dai H, Liang L, He J; China Pulmonary Health Study Group. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet. 2018 Apr 28;391(10131):1706-1717. doi: 10.1016/S0140-6736(18)30841-9. Epub 2018 Apr 9.

  PMID: 29650248 RESULT

• Colak 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/rccm.201908-1644OC.

  PMID: 31770495 RESULT

• 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 disease. Nat Commun. 2020 Nov 18;11(1):5886. doi: 10.1038/s41467-020-19701-0.

  PMID: 33208745 RESULT

• 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. doi: 10.1038/s12276-020-0469-y. Epub 2020 Jul 17.

  PMID: 32681029 RESULT

• 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.

  PMID: 29393240 RESULT

• 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.

  PMID: 22089028 RESULT

• 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.

  PMID: 31501577 RESULT

• 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):e0136455. doi: 10.1371/journal.pone.0136455. eCollection 2015.

  PMID: 26317628 RESULT

• 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/S0007114511005630. Epub 2011 Dec 6.

  PMID: 22142891 RESULT

• 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;15:64. doi: 10.1186/s12890-015-0059-2.

  PMID: 26059026 RESULT

• 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):282. doi: 10.3390/jcm7090282.

  PMID: 30223529 RESULT

• 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.

  PMID: 33076910 RESULT

Related Links

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

Biospecimen

Retention: SAMPLES WITHOUT DNA

Fecal Specimen,Serum Specimen

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yun Liu, MD

  Second Affiliated Hospital of Xi'an Jiaotong University

  STUDY CHAIR

Central Study Contacts

Yun Liu, MD

CONTACT

0086-13572887605; 27556828@qq.com

Yangfan Hou

CONTACT

0086-18534899825; 1016429390@qq.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2021
• First Posted: May 7, 2021
• Study Start: May 1, 2021
• Primary Completion: April 1, 2022
• Study Completion: July 1, 2022
• Last Updated: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediately following publication; no end date
• Access Criteria: We plan to share with anyone who wishes to access the data for any purpose of analyses and data are available indefinitely.

Locations

CN (1)