Respiratory Microbiota, Infection Characteristics and Ima... | NCT06938022

Status Module

Description Module

Brief Summary

This study，Respiratory microbiota, infection characteristics and imaging manifestations in patients with chronic airway inflammation， adopted a prospective, observational, multi-omics study design to comprehensively evaluate the effects of respiratory microbiota, infection characteristics and imaging manifestations on disease outcomes and quality of life in patients with chronic airway inflammation. Involving six parallel sub-studies, These include: (1) the differences and mechanisms of lung microecology in ICS treatment sensitivity and resistance in patients with chronic airway inflammation, (2) the study of respiratory viral infection and inflammatory markers in patients with acute exacerbation of chronic obstructive pulmonary disease, (3) the effect of respiratory viral infection on the airway inflammation and disease severity of asthma in acute exacerbation, (4) the clinical significance of fungal infection in acute exacerbation of bronchiectasis, (5) the role of pulmonary function test and chest CT in predicting acute exacerbation of chronic obstructive pulmonary disease, and (6) the predictive value of baseline pulmonary function and radiomics in acute exacerbation of bronchiectasis， Each sub-study targeted a different study purpose and a specific patient population. All sub-studies followed uniform research principles, including scientificity, ethics, and consistency. All subjects were required to sign an informed consent form before enrollment to ensure that they understood the purpose, process, possible risks and privacy protection measures of the study. The study plans to enroll about 1,000 eligible patients covering chronic airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis.

In this study, multi-omics techniques, including microbiome, metabolomics, radiomics, and transcriptomics, were used to comprehensively evaluate the effects of respiratory microbiota, infection characteristics, and imaging manifestations on disease outcomes and quality of life in patients with chronic airway inflammation.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
ICS treatment sensitivity and resistance in Chronic Airway Inflammation		Using a prospective, single-center, observational study design, 240 patients were planned to be enrolled, divided into ICS-sensitive and resistant. Through multi-omics technologies such as 16S rRNA gene sequencing, metagenomic sequencing, and metabolomics analysis, the composition, structure and functional gene differences of airway and intestinal microbiota were analyzed, and the microbiota-metabolite-host network was constructed by combining inflammatory factor detection and transcriptomic analysis, and the complex mechanism of ICS treatment response was analyzed.
The study of respiratory viral infection and inflammatory markers in patients with acute exacerbatio		A prospective, open-label, self-controlled trial design was adopted, and 150 patients were expected to be included. RT-PCR was used to detect respiratory viruses, and ELISA was used to detect inflammatory markers, and the dynamic changes of viral infection and inflammatory markers and their association with clinical phenotypes were analyzed.
The effect of respiratory viral infection on the airway inflammation and disease severity of asthma		Patients aged 18-80 years with a clinical diagnosis of asthma exacerbation were included, nasopharyngeal swabs and sputum samples were collected for viral analysis, and ELISA was used to detect airway inflammation markers, and the number and severity of acute exacerbations, hospitalization and questionnaire scores were evaluated.
The clinical significance of fungal infection in acute exacerbation of bronchiectasis		A prospective, observational study design was used and 150 patients were expected to be included. The diversity and abundance of fungi in sputum were detected by 18S rRNA technology, and the inflammatory markers were detected by ELISA, and the relationship between fungal infection and clinical manifestations, questionnaire scores and inflammatory markers was analyzed.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Respiratory microorganisms	Multiplex RT-qPCR analysis was performed to analyze the microbial species and abundance of respiratory tract microorganisms in sputum samples, nasopharyngeal swabs or exhaled air condensate of patients with chronic airway inflammation	Baseline, Week 4 (mid-intervention), and Week 8 (end of intervention) follow-up.
ACT（Asthma Control Test） Score	In the research group of ICS treatment sensitivity and resistance in Chronic Airway Inflammation, Asthma symptom control will be assessed using the Asthma Control Test (ACT), a validated questionnaire with scores ranging from 5 to 25. Higher scores indicate better asthma control.	Baseline, Week 4 , Week 8 , and 3-month follow-up.
CAT（COPD Assessment Test） Score	In the research group of ICS treatment sensitivity and resistance in Chronic Airway Inflammation, Chronic Obstructive Pulmonary Disease Assessment Test（CAT) is a tool used to assess the severity of chronic obstructive pulmonary disease (COPD) and the quality of life of patients. The scoring range is 0 - 10 points. Grade division: 0 - 2 points: Mild. 3 - 5 points: Moderate. 6 - 10 points: Severe.	Baseline, Week 4 , Week 8 , and 3-month follow-up.

Secondary Outcomes

Measure	Description	Time Frame
Changes in Airway Inflammation Markers	Detection of airway inflammatory factors by ELISA, such as IL-4, IL-5, IL-6, IL-8, IL-13, IL-33, TNF-α, IL-1β, etc.The concentration of Airway Inflammation Markers is measured in pg/mL.	Baseline, Week 4, Week 8 follow-up.
FEV1（Forced Expiratory Volume in 1 second）

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

(1) Age: 18 to 80 years old (inclusive), without restrictions on gender or ethnicity.

(2) Disease Diagnosis:

COPD patients must meet the GOLD diagnostic criteria, with post-bronchodilator FEV1/FVC < 70% and FEV1 < 80% of the predicted value.
Asthma patients must meet clinical diagnostic criteria, including recurrent wheezing, shortness of breath symptoms, frequently occurring at night; during attacks, wheezing sounds can be heard in both lungs; effective treatment with bronchodilators or corticosteroids, or symptoms can be relieved spontaneously, and at least one of the following tests must be positive: positive bronchial provocation test; positive bronchodilator test with FEV1 increase ≥12%, and FEV1 increase absolute value ≥200ml; daily peak expiratory flow (PEF) variability ≥10% within one week.
Bronchiectasis patients must meet the diagnostic criteria based on CT imaging, including: bronchial diameter/accompanying pulmonary artery diameter ratio >1; high-resolution CT (HRCT) showing dilated cystic, columnar, or cystic bronchial shadows.

(3) Disease Status:

Patients with chronic airway inflammation must be in a stable phase, defined as no acute exacerbations, hospitalizations, or use of other treatments for at least 4 weeks.
COPD patients with acute exacerbations must meet the definition of acute exacerbation: at least two major symptoms (dyspnea, increased sputum, and purulent sputum) worsen, or at least one major symptom and one minor symptom (wheezing, sore throat, cough without other causes, and fever) worsen.
Asthma patients in the acute attack phase must meet the definition of acute attack: sudden worsening of symptoms (including wheezing, shortness of breath, chest tightness, cough, etc.), decreased lung function, poor response to routine treatment, other clinically diagnosed acute attacks.
Bronchiectasis patients with acute exacerbations must meet the definition of acute exacerbation: increased cough, increased sputum or sputum viscosity, purulent sputum, dyspnea or decreased exercise tolerance, fatigue or discomfort, hemoptysis, at least three of the above six symptoms occur newly or significantly worsen, lasting ≥48 hours.

(4) Treatment Status:

In the chronic airway inflammation patient ICS treatment study, patients must require ICS treatment under routine care, i.e., have been recommended to use ICS and are currently using ICS treatment.
In other studies, patients must maintain unchanged long-term medication during the follow-up period, but may be appropriately adjusted according to the attending physician's clinical decision.

(5) Others:

All participants must voluntarily participate in the study and sign the informed consent form.
Patients must be able to communicate in language or writing, understand and sign the content of the informed consent form, and be able to complete the required pulmonary function and other auxiliary examinations for the trial.

Exclusion Criteria:

(1) Recent Medication Use:

In the chronic airway inflammation patient ICS study, exclude patients who have used corticosteroid-related treatment within the last 3 months, exclude patients who have received antibiotic treatment within the last 3 months.
In other studies, exclude patients who have used antibiotics, immunosuppressants, cytotoxic agents, or hormones systemically within the last 4 weeks.

(2) Other Significant Diseases:

Clinically significant pulmonary diseases other than the study disease, such as active tuberculosis, pulmonary embolism, pneumothorax, pneumothorax, pulmonary hypertension, interstitial lung disease, lung cancer, pulmonary fibrosis, tuberculosis, etc.
Severe other systemic diseases, such as myocardial infarction, severe arrhythmia, liver dysfunction, renal insufficiency, rheumatic immune system diseases, hematological diseases, active malignant tumors, etc.

(3) Disease Status:

[1] Patients who have experienced any degree of acute exacerbation within the last 4 weeks before screening for the stable phase study.

(4) Special Populations:

Female patients who are pregnant or breastfeeding.
Patients with poor compliance.
Patients who cannot complete sample collection due to physical or psychological factors, especially those who need to collect multiple samples.
Patients who are participating in other clinical trials. (5) Related Contraindications:

[1] Patients with contraindications to pulmonary function tests and chest CT, such as chest metal, history of myocardial infarction, stroke, aortic aneurysm, or ocular surgery or retinal detachment within the last 3 months.

Name	Role	Phone	Extension	Email
Chao Cao	Contact	+86-0574-87089878		caocdoctor@163.com
Shiyi He	Contact	+86-0574-87089878		shiyihii@163.com

ID	Term
D001249	Asthma
D029424	Pulmonary Disease, Chronic Obstructive
D001987	Bronchiectasis

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms