Prospective Cohort Study of Molecular Mechanism of Lower Respiratory Tract Microbes in Patients With AECOPD (REASON)

A Prospective Cohort Study of Molecular Mechanism of Lower Respiratory Tract Microbes in Patients With Acute Obstructive Pulmonary Disease (AECOPD) by Regulating the Transcriptional Balance of NF-κB and PPARγ in Alveolar Macrophages

How to reduce the rapid decline of lung function in patients with AECOPD is a clinically urgent problem to be solved. Studies have suggested that there is a bacterial flora imbalance in the lower respiratory tract of COPD patients. To explore the relationship between microbiology and host immunity is a hot topic in the field of COPD. The investigators use NGS (next generation sequencing) technology to fully explore the specific molecular mechanism of the lower respiratory tract microbiome in patients with COPD by regulating the transcriptional activities of NF-κB and PPARγ in alveolar macrophages, resulting in pulmonary parenchymal remodeling and decreased lung function. In this study, a prospective cohort study will be used to evaluate the effect of the lower respiratory tract microbiome on lung tissue (alveolar space and pulmonary vascular) remodeling and pulmonary function decline in patients with AECOPD.

Study Overview

• Status: Unknown
• Conditions: Microbiome; Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Detailed Description

This study will be based on a prospective cohort design in patients with COPD who are eligible for the study. Fifty patients who met the criteria for inclusion and exclusion of COPD exacerbations and signed informed consent will participate in the study. The purpose of this study is to evaluate the effect of the lower respiratory tract microbiome on lung tissue remodeling, decreased lung function, and clinical symptoms in patients with AECOPD.

Baseline screening includes demographic data, medical history, combined medication records, symptoms, signs, symptom scores, number of acute exacerbations, blood cells and inflammatory factors, electrocardiogram, lung function, alveolar lavage fluid microbe NGS, and safety observation indicators.

Patients will be followed up every 3 months for a period of 1 year. The primary and secondary endpoints are as follows.

Primary endpoint： Changes in FEV1 (forced expiratory volume in the first second) within 1 year of follow-up

Secondary endpoint： Changes in CAT, CCQ, mMRC scores during 1 year of follow-up Changes in lung function during 1 year of follow-up: FEV1 / FVC Changes in blood routine, IgE, and eosinophil count within 1 year of follow-up Number of hospital admissions due to acute exacerbation during 1 year of follow-up

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Shengqing Li, PhD; Phone Number: +8602152887072; Email: shengqingli9655@163.com
• Study Contact Backup: Name: Jingwen Xia, MD; Phone Number: +8602152887072; Email: xjw2006@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital，Fudan University
      • Contact: Shengqing Li, PhD; Phone Number: 02152887072; Email: shengqingli9655@163.com
      • Contact: Jingwen Xia, MD; Phone Number: +8602152887072; Email: xjw2006@126.com
      • Sub-Investigator: Jingwen Xia, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Fifty patients who met the criteria for inclusion and exclusion of COPD exacerbations and signed informed consent will participate in the study. Patients will be followed up every 3 months for a period of 1 year.

Description

Inclusion Criteria:

1. Patients with a diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) according to the GOLD2018 guidelines (patients with FEV1pred> 30% and no concurrent respiratory failure);
2. Age ≥18, ≤80 years, regardless of gender;
3. No antibiotics have been used after this acute exacerbation;
4. Treatment according to GOLD guidelines;

5. Those with the following bronchoscopy indications:

   1. Collect lower respiratory tract secretions for bacteriological examination;
   2. Chest radiographs have invasive lesions of unknown origin;
   3. bronchoalveolar lavage, bronchial administration and suction treatment;
   4. unexplained hemoptysis or chronic irritating cough;
   5. Bronchial obstructions such as localized wheezing, localized emphysema, obstructive pneumonia, or any atelectasis;
   6. Suspected of trachea and bronchial tumors;
   7. paralysis of the recurrent laryngeal or phrenic nerve of unknown cause;
   8. Cancer cells or Mycobacterium tuberculosis are found in sputum and no lesions are found on chest radiograph;
   9. Suspected of bronchial foreign bodies or stones;
   10. diffuse lesions of the lungs or masses around the lungs that require lung biopsy, brushing, or lavage for cytology or bacteriological examination to confirm the diagnosis;
   11. Patients who have a long-term indwelling cannula after tracheotomy and know whether the trachea is damaged or necrotic;
   12. hilar swollen, unexplained lung mass;
   13. Select lipiodol or iodine radiography of a lung lobe or segment.
6. Voluntary signed informed consent.

Exclusion Criteria:

1. active phase of tuberculosis;
2. Patients with malignant tumor disease;
3. patients with rheumatic diseases;
4. Patients with contraindications to bronchoscopy;
5. patients with mental illness;
6. Exclude those with severe medical diseases: such as heart, liver, and kidney dysfunction or coagulation dysfunction; uncontrolled hypertension, hyperglycemia or arrhythmia;
7. pregnancy and lactation;
8. Patients who participated in other clinical trials in the past 3 months;
9. Staff members and their families in this research institution.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1	Forced expiratory volume in the first second	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAT scores	COPD Assessment Test score; Score: 0-10, Low impact; Score: 10-20, Moderate impact; Score 20-30, High impact; Score 30-40, Very high impact.	12 months
mMRC scores	The modified British Medical ResearchCouncil (mMRC) questionnaire total score ranges from 0 to 4, with higher grades indicating more severe breathlessness.	12 months
other lung function parameters	FEV1/ FVC	12 months
Incidence of COPD exacerbation	Number of Incidence of COPD exacerbation	12 months

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Principal Investigator: Shengqing Li, PhD, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: COPD; Microbes; Lower Respiratory Tract
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: KY2018-362

Drug and device information, study documents

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