Clinical trial NCT04259736: Prospective Cohort Study of Molecular Mechanism of Lower Respiratory Tract Microbes in Patients With AECOPD
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Microbiome
Keywords: Lower Respiratory Tract
Microbes
COPD
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2020-02-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: FEV1
timeFrame: 12 months
Secondary outcomes:
measure: CAT scores
timeFrame: 12 months
measure: mMRC scores
timeFrame: 12 months
measure: other lung function parameters
timeFrame: 12 months
measure: Incidence of COPD exacerbation
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan hospital,Fudan university
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Shengqing Li, PhD
role: PRINCIPAL_INVESTIGATOR
References: