Microbial Colonization Distribution and Adaptive Evolution of Lower Respiratory Tract in Bronchiectasis Patients.

Microbial Colonization Distribution and Adaptive Evolution of Lower Respiratory Tract in Bronchiectasia Patients.

Qualified sputum samples from bronchiectasis patients were collected regularly every month for three consecutive years to analyze the microbiome changes of lower respiratory tract of bronchiectasis patients by metagenomic sequencing. Pseudomonas aeruginosa was isolated and the whole genome was sequenced to analyze the adaptive evolution，including virulence, quorum sensing and drug resistance under host pressure. The aim of the study is to clarify the rule of microflora colonization distribution and adaptive evolution in the lower respiratory tract of patients with bronchiectasis, to predict the acute attack and prognosis of patients with microbiome changes, and to find more new prevention and treatment methods by adjusting the microbiome of the lower respiratory tract.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis

Detailed Description

Bronchiectasis is an abnormal, permanent dilatation of the bronchi, which presents as cough, expectoration and recurrent pulmonary infections. Epidemiological survey researchs have found that the number of bronchiectasis has increased rather than decreased in the last decades. Asia has the highest prevalence of bronchiectasis, with 1,200 cases in every 100,000 people over the age of 40 in China, and this rate can be seriously underestimated due to difficulties in identifying COPD. The mortality rate of bronchiectasis patients is more than twice that of the general population, placing an increasing burden on global health care systems. Chronic infection in bronchiectasis is common and had a big influence on prognosis. Pseudomonas aeruginosa is considered to be the most common colonization bacterium. At present, the mechanism of bronchiectasis and its relationship with lower respiratory tract infection have not been fully elucidated. Therefore, it is important to have an in-depth understanding of the colonization distribution and adaptive evolution of the microbiome in the lower respiratory tract, to predict the acute attack and prognosis with the application of microbiome changes, and to find more new and effective prevention and treatment methods by regulating the microbiome in the lower respiratory tract. Qualified sputum specimens from bronchiectasis patients were collected regularly every month for three consecutive years. Metagenomic sequencing was used to analyze the microbiome changes of lower respiratory tract in these patients. Pseudomonas aeruginosa was isolated and the whole genome was sequenced to analyze the adaptive evolution of its virulence, group sensitivity and drug resistance under host pressure.

• Study Type: Observational
• Enrollment (Estimated): 1850

Contacts and Locations

• Study Contact: Name: Feng Xu, Doctor; Phone Number: 13666697918; Email: xufeng99@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • 2ndAffiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Bronchiectasis patients aged 18 to 79.

Description

Inclusion Criteria:

• Bronchiectasis patients in clinically stable period;
• Two or more chest infections in the previous year;
• Chest CT confirmed bronchiectasis (bronchial to arterial ratio >1).
• Chronic colonization of pseudomonas aeruginosa and was clinically stable in 6 months prior to the study.

Exclusion Criteria:

• deterioration of illness (defined as at least 24 hours of three or more of the following symptoms: increased cough, increased sputum volume, purulent sputum, hemoptysis, increased dyspnea, increased wheezing, fever ((≥38°C) or discomfort, the attending physician agrees that antibiotic treatment is required);
• current smokers, or former smokers who have stopped smoking less than 1 year ago, have a history of more than 15 packets of age, or CT showed as emphysema;
• cystic fibrosis patients;
• active allergic bronchopulmonary aspergillosis;
• active tuberculosis patients;
• patients with poor asthma control;
• pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Bronchiectasis patients group; Bronchiectasis patients group: Sputum specimens from bronchiectasis patients aged 18 to 79 years old .
Healthy control group; Healthy control group: Sputum specimens from healthy people.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline SNP of PA population in sputum samples	To assess the SNP changes of PA population in sputum samples compared with PAO1 wildtype	once per 3 month for 3 years
Species richness and antibiotic suscepibility change from baseline in sputum samples	To assess the species richness and antibiotic suscepibility change from baseline in sputum samples	once per 3 month for 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pulmonary function	To assess the lung functon change	once per year for 3 years
chest CT	To assess the severity of lung lesions	once per year for 3 years
BSI scores	To assess the severity index of bronchiectasis.	once per year for 3 years
E-FACED scores	To assess the severity index of bronchiectasis.	once per year for 3 years
SGRQ questionnaire	To assess the impaired health and quality of life of patients with respiratory diseases	once per year for 3 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Tongji Hospital; The Affiliated Hospital of Qingdao University; Xuanwu Hospital, Beijing; Beijing Chao Yang Hospital; Zhejiang Provincial People's Hospital; Huadong Hospital; The First Medical Center of Chinese PLA General Hospital; Nanjing Jiangning Hospital; Shandong Public Health Clinical Center; Beijing Chest Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2020
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Bronchiectasis; Microbiology
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: 2020-066

Drug and device information, study documents

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