NCT06938022 - Respiratory Microbiota, Infection Characteristics and Imaging Manifestations in Patients With Chronic Airway Inflammation | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: (1) Age: 18 to 80 years old (inclusive), without restrictions on gender or ethnicity. (2) Disease Diagnosis: 1. COPD patients must meet the GOLD diagnostic criteria, with post-bronchodilator FEV1/FVC \< 70% and FEV1 \< 80% of the predicted value. 2. 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. 3. 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: 1. 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. 2. 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. 3. 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. 4. 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: 1. 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. 2. 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: 1. All participants must voluntarily participate in the study and sign the informed consent form. 2. 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: 1. 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. 2. In other studies, exclude patients who have used antibiotics, immunosuppressants, cytotoxic agents, or hormones systemically within the last 4 weeks. (2) Other Significant Diseases: 1. 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. 2. 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: 1. Female patients who are pregnant or breastfeeding. 2. Patients with poor compliance. 3. Patients who cannot complete sample collection due to physical or psychological factors, especially those who need to collect multiple samples. 4. 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.

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

Secondary Outcomes

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.

Time frame: Baseline, Week 4, Week 8 follow-up.

FEV1（Forced Expiratory Volume in 1 second）

Pulmonary function FEV1 index was evaluated in liters (L). It refers to the volume of air exhaled in the first second by the subject exhaling at the fastest rate after the maximum inspiration.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

PEF（Peak Expiratory Flow）

PEF is measured in liters per minute (L/min). It refers to the maximum flow rate that can be achieved when exhaling at the fastest speed after the maximum inspiration. This indicator can reflect how open the airway is.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

MMEF75/25（Maximal Mid-Expiratory Flow between 75% and 25% of FVC）

MMEF75/25 is measured in liters per minute (L/min). This is the average expiratory flow rate over the course of 75% to 25% of the forced expiratory volume. It is primarily used to assess the function of the small airways.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

FVC（Forced Vital Capacity）

FVC is measured in liters (L). It is the maximum volume of air that can be exhaled by exhaling forcefully as fast as possible after the maximum inhalation. This indicator reflects the ventilatory function of the lungs. FVC is generally around 3.5 - 5 L in normal adult males and slightly lower in females. FVC can be used to assess the elasticity of the lungs, the patency of the airways, etc.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

FEV1/FVC（Forced Expiratory Volume in 1 second to Forced Vital Capacity Ratio）

The unit of FEV1/FVC is %. It is mainly used to determine if there is an airflow obstruction. Normally, FEV1/FVC should be greater than 70%.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

Blood Routine Test

Including CRP, WBC, Neu, Mono, Eos, RBC, Hb, and PLT.

Time frame: Baseline, Week 4 , Week 8 follow-up.

Serum viral Antibody IgG

The serum viral antibody titer is measured by ELISA, which is a commonly used method for detecting and quantifying antibodies in patient samples. Then, these results will be used to analyze the relationship between viral infection and disease status, severity, or treatment response.

Time frame: Baseline, Week 4 , Week 8 follow-up.

Anxiety Levels

Anxiety symptoms will be assessed using the Hamilton Anxiety Rating Scale (HAMA), a validated scale with scores ranging from 0 to 56, where higher scores indicate greater anxiety severity.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

Depression Levels

Depressive symptoms will be observed using the Hamilton Depression Rating Scale (HAMD), which scores from 0 to 52, with higher scores indicating more severe depression.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

Incidence of Serious Adverse Events (SAEs)

The safety will be assessed by monitoring and recording the incidence of treatment-emergent serious adverse events (SAEs) using the Serious Adverse Event Report Form (SAE Report). The research team will document, analyze, and provide appropriate medical responses to any incidents.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Number of Emergency Visits and Hospitalizations

Record the number of emergency visits and hospitalizations to evaluate the clinical effectiveness of treatment.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Number of Acute Exacerbations

The unit of Number of Acute Exacerbations is number of events. Total count of acute exacerbations experienced by participants.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Exacerbation Events

Acute exacerbation events of the disease will be assessed using Asthma, COPD, Bronchiectasis exacerbation records, recording the timing, frequency, and severity of each exacerbation. and grade the severity as mild, moderate, or severe.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Frequency of Emergency Department Visits

The number of emergency department visits due to acute exacerbations of Asthma, Chronic Obstructive Pulmonary Disease (COPD), and Bronchiectasis will be tracked using patients' self-reports and verified through medical records. This measure helps to evaluate the severity of the diseases.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Frequency of Hospitalizations

The number of people hospitalized due to acute exacerbations of Asthma, COPD (Chronic Obstructive Pulmonary Disease), and Bronchiectasis will be recorded, including detailed information such as the length of hospital stay and the treatments administered.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Severity Grading of Acute Exacerbations

The unit of Severity Grading of Acute Exacerbations is units on a severity scale. Severity of each acute exacerbation categorized by a standardized scale (e.g., mild/moderate/severe or graded numerically, such as Grade 1-3).

Time frame: Baseline, Week 4, Week 8, 3-month, 6-month, 9-month, and 12-month follow-up.

Occurrence of Respiratory Failure

Documentation of respiratory failure events during hospital stays, including clinical criteria for diagnosis and management details.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Number of Moderate to Severe Acute Exacerbations

The unit of Number of Moderate to Severe Acute Exacerbations is number of events. Count of exacerbations classified as moderate or severe based on the severity grading scale.

Time frame: Baseline, Week 4, Week 8, 3-month, 6-month, 9-month, and 12-month follow-up.

Use of Non-Invasive Ventilation

Documentation of the use of non-invasive ventilation during hospitalization, including indications and duration of use.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

ICU Admission and Intubation

Records of ICU admissions and whether intubation was required during hospitalization, including associated clinical details.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Systemic Steroid Use

Documentation of systemic corticosteroid use during hospital stays, including dosage and duration.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

Length of Hospital Stay

Total duration of each hospital stay will be recorded to assess the impact of the intervention on hospitalization length.

Time frame: Baseline, Week 4, Week 8，3-month，6-month，9-month，and 12-month follow-up.

CAT（COPD Assessment Test） Score

It is used to evaluate the quality of life of COPD patients in groups other than the chronic airway inflammation ICS research group. It includes 8 items, involving dyspnea, exercise ability, cough, sputum, chest tightness, sleep quality, self - confidence and energy level. The scoring range is 0 - 10 points. Grade division: 0 - 2 points: Mild. 3 - 5 points: Moderate. 6 - 10 points: Severe.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

SGRQ（St. George's Respiratory Questionnaire）Score

The SGRQ is used to evaluate the quality of life of patients with chronic respiratory diseases. It consists of three parts: symptoms, activities, and impact on daily life. The scoring range is 0 - 100 points. The higher the total score, the poorer the patient's quality of life.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

mMRC（Modified Medical Research Council Dyspnea Scale）Score

The mMRC Score is used to assess the severity of dyspnoea and is divided into grades 0 - 4. The higher the score, the more severe the dyspnoea. Grade 0: Dyspnoea occurs only during strenuous exercise. Grade 1: Dyspnoea occurs when walking fast on flat ground or climbing a gentle slope. Grade 2: Dyspnoea causes the patient to stop and rest when walking on flat ground. Grade 3: Dyspnoea causes the patient to stop and rest after walking less than 100 metres or for a few minutes on flat ground. Grade 4: The patient is unable to leave home due to dyspnoea, or dyspnoea occurs when dressing or undressing.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

ACT（Asthma Control Test） Score

The ACT Score is used to evaluate the quality of life of asthma patients in groups other than the chronic airway inflammation ICS research group. The scoring range is 5 - 25 points. Grade division: 20 - 25 points: Asthma is well - controlled. 16 - 19 points: Asthma is partially - controlled. Less than 16 points: Asthma is uncontrolled.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

AQLQ（Asthma Quality of Life Questionnaire）Score

The Asthma Quality of Life Questionnaire is used to evaluate the quality of life of asthma patients. The scoring range is 1 - 7 points. The higher the score, the better the quality of life.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

FACED Score

FACED Score includes Forced Expiratory Volume in 1 second (FEV1)、Age、Chronic colonization by Pseudomonas aeruginosa (PA)、Extension (number of pulmonary lobes affected)、Dyspnea (mMRC score).It is used to assess the severity of bronchiectasis. The scoring range is from 0 to 10 points. Grade classification: 0 - 2 points: Mild. 3 - 5 points: Moderate. 6 - 10 points: Severe.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

BEST（Bronchiectasis Evaluation Score for Treatment)）Score

The BEST Score is used to assess the symptoms of dyspnea and cough. The scoring range is from 0 to 10 points. Grade classification: 0 - 2 points: Mild. 3 - 5 points: Moderate. 6 - 10 points: Severe.

Time frame: Baseline, Week 4 , Week 8 , and 3-month follow-up.

Respiratory Microbiota, Infection Characteristics and Imaging Manifestations in Patients With Chronic Airway Inflammation

Overview

Conditions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts