Bronchiectasis is a common, heterogeneous chronic airway disease that remains
understudied in clinical and translational research. Although several phenotypes and
endotypes have been identified-primarily in European populations-data from Chinese
patients are limited. Racial and geographic differences suggest that bronchiectasis
phenotypes and endotypes in China may differ from those in Western cohorts. Recent
controlled trials have failed to meet primary endpoints, likely due to insufficient
identification of patient subgroups that optimally respond to antibiotics, mucoactive
agents, or anti-inflammatory therapies. The C-BRIDGE Study seeks to address this gap by
exploring the clinical, genomic, microbiological, inflammatory, and functional
heterogeneity of bronchiectasis in Chinese patients to define molecular endotypes for
stratified assessment and management.
Study Aims and Objectives:
Characterize molecular endotypes of stable bronchiectasis in Chinese patients.
Identify molecular endotypes of bronchiectasis exacerbations in Chinese patients.
Investigate molecular endotypes in patients with allergic bronchopulmonary
aspergillosis (ABPA).
Develop a screening algorithm and elucidate genotypes and inflammatory endotypes of
cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) in China.
Validate candidate biomarkers for stable and exacerbation endotypes to enable
stratified medicine.
Perform in vivo and in vitro proof-of-concept studies using phenotypic data to
pinpoint patient subgroups likely to benefit from specific pharmacological
treatments.
Study Design:
Observational cohort study.
Study Methods:
A target of 1,500 patients with bronchiectasis will be recruited across participating
centers for an observational study with the following aims:
Aim 1: Stable Disease Endotyping Up to 1,500 patients will be studied to define and
validate endotypes of stable bronchiectasis. Data collection will include clinical
assessments, sputum and nasal microbiome analysis, sputum proteomics, nasal and airway
transcriptomics, single-cell sequencing of bronchoalveolar lavage fluid (BALF), and
measurement of inflammatory markers in systemic, nasal, sputum, and BALF samples. A
sub-study (n=100) will use air-liquid interface cultures of primary airway epithelial
cells to assess responses to various stimuli and pharmacological interventions.
Aim 2: Exacerbation Endotyping A subset of 200 patients will be evaluated during
exacerbations to replicate the phenotyping approach. This will involve analyzing changes
from baseline in microbiome, proteomics, metabolomics, and other markers to identify
clusters linked to exacerbation onset, progression, and outcomes.
Aim 3: Allergic Bronchopulmonary Aspergillosis (ABPA) Subgroup Analysis A subset of 150
patients with ABPA will be studied to investigate molecular endotypes by integrating
single-cell sequencing, microbiome, mycobiome, proteomics, metabolomics, and other
markers to identify clusters associated with exacerbation, recurrence, and treatment
responses.
Aim 4: Idiopathic Bronchiectasis and Genetic Screening Patients with idiopathic
bronchiectasis will be screened for cystic fibrosis, CFTR-related disorders, and primary
ciliary dyskinesia (PCD) to identify genotypes and inflammatory endotypes. This will
integrate genomics, microbiome, proteomics, and metabolomics to explore associations
among phenotypes, genotypes, endotypes, and prognosis.
Aim 5: Biomarker Validation and Prediction Model Development Candidate phenotypes and
endotypes will be externally validated using registered, ethically approved biobanks.
Validated biomarkers will be correlated with clinically meaningful outcomes, such as
treatment responses, to enable their use in stratified medicine. Clinical data and
validated biomarkers will be integrated to construct and validate prediction models for
exacerbation frequency, time to first exacerbation, and lung function decline.
Participants will visit the Clinical Research Centre at least once for sampling and
clinical data collection, with consent obtained to link their samples to the C-BRIDGE
database.
Ethics Approval:
Approved by the Ethics Committee of Shanghai Pulmonary Hospital and other participating
centers.
Expected Outcomes:
The C-BRIDGE Study will establish detailed molecular endotypes of bronchiectasis in
Chinese patients, facilitating precise prognosis prediction and tailored treatment
strategies. By identifying and validating patient subgroups and biomarkers, it will
provide a foundation for personalized medicine in bronchiectasis management, with
potential relevance in China and worldwide.