Characteristics of Intestinal Microbiome in the Progression of Early COPD

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Chronic Obstructive Pulmonary Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥10 pack-years smoking history; Examination of pulmonary function and compatible computed tomography meeting group requirements (as shown in Groups and Interventions). Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HC，healthy control<br>18-65 years old，no smoking history，normal pulmonary function，normal compatible computed tomography. | |
| HG，high-risk COPD group<br>18-60 years old，≥10 pack-years smoking history，normal pulmonary function，normal compatible computed tomography. | |
| EG，early COPD group<br>18-60 years old，≥10 pack-years smoking history，and with any of the following abnormalities： Forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than 80%; Compatible computed tomography abnormalities：airway abnormality and/or emphysema，air trapping, or bronchial thickening； FEV1 decline (≥60 mL per year). | |
| MG，mild and moderate COPD group<br>18-65 years old，FEV1/FVC<70%，FEV1%predicted ≥50%. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, Intestinal Microbiome, Metabolite, Immune Function