The C-BRIDGE Study: China Bronchiectasis Research Involving Databases, Genomics, and Endotyping

Bronchiectasis is a heterogeneous airway disease with diverse causes, making precise diagnosis, prognosis, and treatment response prediction challenging. Identifying patient subgroups (phenotypes) and molecular profiles (endotypes) can enhance individualized assessment and management. While prior studies, primarily in European populations, have identified key phenotypes and endotypes, their relevance to Chinese patients remains unclear due to geographic and clinical differences. Specific causes of bronchiectasis, such as allergic bronchopulmonary aspergillosis (ABPA) and primary ciliary dyskinesia (PCD), may also exhibit distinct pathophysiology requiring further exploration. The C-BRIDGE Study seeks to characterize phenotypes and endotypes in Chinese bronchiectasis patients during stable disease and exacerbations, evaluate differences in clinical outcomes across these subgroups, and develop personalized medicine strategies based on these findings, applicable in China and globally.

Primary Objective: To identify molecular endotypes of bronchiectasis that accurately predict prognosis and guide treatment responses.

Secondary Objectives:

To characterize molecular endotypes of stable bronchiectasis in Chinese patients.

To define molecular endotypes of bronchiectasis exacerbations in Chinese patients.

To investigate molecular endotypes specific to allergic bronchopulmonary aspergillosis (ABPA).

To explore genotypes and inflammatory endotypes of cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) in Chinese patients.

To validate candidate biomarkers for stable and exacerbation endotypes to support stratified medicine.

To conduct in vivo or in vitro proof-of-concept studies using phenotypic data to identify patient subgroups likely to benefit from specific pharmacological interventions.

Study Design: This observational cohort study will link identified patient subgroups with meaningful clinical outcomes to inform prognosis and optimize treatment strategies.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis Adult

Detailed Description

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:

1. Characterize molecular endotypes of stable bronchiectasis in Chinese patients.
2. Identify molecular endotypes of bronchiectasis exacerbations in Chinese patients.
3. Investigate molecular endotypes in patients with allergic bronchopulmonary aspergillosis (ABPA).
4. Develop a screening algorithm and elucidate genotypes and inflammatory endotypes of cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) in China.
5. Validate candidate biomarkers for stable and exacerbation endotypes to enable stratified medicine.
6. 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.

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Yong-hua Gao, Ph.D.; Phone Number: +86 17321278520; Email: gaoyonghuahust@163.com

Study Locations

• China
  • Guizhou
    • Guiyang, Guizhou, China
      • Recruiting
      • Lin Liu
      • Contact: Lin Liu, MD; Phone Number: +8618685109665; Email: liulin0956@163.com
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • Lei Song
      • Contact: Lei Song, PhD; Phone Number: +8615948025862; Email: lsong@jlu.edu.cn
  • Shangdong
    • Jinan, Shangdong, China
      • Recruiting
      • Qian Qi
      • Contact: Qian Qi, MD; Phone Number: +8613706380314; Email: qiqianqlh@163.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Recruiting
      • He-feng Chen
      • Contact: He-feng Chen, MD; Phone Number: +8613917472201; Email: 13917472201@163.com
    • Shanghai, Shanghai Municipality, China, 200433
      • Recruiting
      • Zhou-fang Mei
      • Contact: Zhou-fang Mei, MD; Phone Number: 13817546940; Email: meizhoufang8@163.com
    • Shanghai, Shanghai Municipality, China, 200437
      • Recruiting
      • Jun She
      • Contact: Jun She, PhD; Phone Number: +8613641093865; Email: she.jun@zs-hospital.sh.cn
    • Shanghai, Shanghai Municipality, China, 200437
      • Recruiting
      • Xue-ling Wu
      • Contact: Xue-ling Wu, MD; Phone Number: +8618321035326
    • Shanghai, Shanghai Municipality, China, 200437
      • Recruiting
      • Yong-hua Gao
      • Contact: Yong-hua Gao, PhD; Phone Number: +8617321278520; Email: gaoyonghuahust@163.com
  • Zhejiang
    • Jiaxing, Zhejiang, China
      • Recruiting
      • Xiao-long Ma
      • Contact: Xiao-long Ma, MD; Phone Number: +8618805839188; Email: maxiaolong801005@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with bronchiectasis

Description

Inclusion Criteria:

• A prior CT scan confirming bronchiectasis, accompanied by a compatible clinical syndrome including cough, sputum production, and/or recurrent respiratory tract infections.
• At the screening visit, participants must have been clinically stable for 4 weeks, defined as no antibiotic or corticosteroid treatment for a pulmonary exacerbation in the preceding 4 weeks.

Exclusion Criteria:

• Inability to provide informed consent
• Age under 18 years
• Patients with active tuberculosis
• Use of antibiotics or corticosteroids for a pulmonary exacerbation within the past 4 weeks

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with bronchiectasis; Adult patients diagnosed with bronchiectasis who meet the study's inclusion criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of bronchiectasis exacerbations	Worsening of respiratory symptoms, as defined by the EMBARC/BRR criteria (Eur Respir J. 2017;49(6):1700051), requiring adjustments to treatment strategies.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Survival during the study	3 years
Time to the first exacerbation	Worsening of respiratory symptoms, as defined by the EMBARC/BRR criteria (Eur Respir J. 2017;49(6):1700051), requiring adjustments to treatment strategies.	2 years
Forced expiratory volume in 1 second (FEV1)	Spirometry	2 years
Hospitalization for severe exacerbations	Admission to hospital for an exacerbation meeting the EMBARC/BRR exacerbation	2 years
The Quality of Life Bronchiectasis Respiratory Symptom Scales (QOL-B-RSS)	The Quality-of-Life-Bronchiectasis (QoL-B) questionnaire is a disease-specific survey designed for patients with bronchiectasis. The Respiratory Symptoms scale is a component of the QoL-B questionnaire, with a scale range from 0 to 100. Higher scores on this scale signify a better health status. In bronchiectasis, the established minimal clinically important difference (MCID) is 8 points.	2 years
The Bronchiectasis Health Questionnaire (BHQ)	The BHQ is a brief, self-administered tool consisting of 10 items that assess health status over the previous 14 days. It uses 7-point Likert scales, with scores ranging from 0 to 100, where higher scores reflect better health-related quality of life (HRQoL). In bronchiectasis, the established minimal clinically important difference (MCID) is 3 points.	2 years
The St Georges Respiratory Questionnaire (SGRQ)	St.George Respiratory Questionnaire (SGRQ): a validated questionnaire for use in bronchiectasis population. This questionnaire is structured into 3 main components: symptoms, activity and impacts. Scale range is 0-100, where lower scores correspond to the better health status. Each questionnaire response has a unique empirically derived "weight". Each component of the questionnaire is scored separately in three steps: i. The weights for all items with a positive responses are summed. ii. The weights for missed items are deducted from the maximum possible weight for each component. The weights for all missed items are deducted from the maximum possible weight for the Total score. iii. The score is calculated by dividing the summed weights by the adjusted maximum possible weight for that component and expressing the result as a percentage The Total score is calculated in similar way. In bronchiectasis, the established MCID is 4 points.	2 years
The bronchiectasis exacerbation and symptom tool (BEST)	The Bronchiectasis Exacerbation and Symptom Tool (BEST) is a validated questionnaire designed to evaluate daily symptoms in patients with bronchiectasis. It has a maximum score of 26, with higher scores reflecting a greater symptom burden. In bronchiectasis, the minimal clinically important difference (MCID) is 4 points.	2 years
The Bronchiectasis Impact Measure (BIM)	The Bronchiectasis Impact Measure (BIM) is a validated patient-reported outcome measure for patients with bronchiectasis. The BIM includes eight domains (cough, sputum, breathlessness, tiredness, activity, general health, control, exacerbations) and is numbered 0-10. Higher scores on this scale signify a greater impact of these domains on daily life. In bronchiectasis, the minimal clinically important difference (MCID) for each domain as 1.5 points on a 10-point scale.	2 years
Bronchiectasis Symptom VAS (BS-VAS)	The Bronchiectasis Symptom Visual Analogue Scale (BS-VAS) is a simple, patient-reported tool designed to quantify the severity of individual symptom burden in patients with bronchiectasis. It consists of 11 separate 100-mm horizontal visual analogue scales, each assessing a different core symptom: cough, sputum volume, sputum colour, sputum viscosity, dyspnoea, fatigue, wheezing, chest tightness, chest pain, exercise tolerance, and haemoptysis. Patients are instructed to mark a vertical line on each 10-mm scale to indicate symptom severity over the past 24 hours, with the left anchor (0 mm) defined as "No symptom at all" and the right anchor (10 mm) defined as "Worst imaginable". Each item is measured from 0 to 10 mm (scored 0-10 with one decimal place).	2 years

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Investigators: Principal Investigator: Yong-hua Gao, Ph.D., Shanghai Pulmonary Hospital, Shanghai, China

Publications and helpful links

General Publications

• Chalmers JD, Aliberti S, Filonenko A, Shteinberg M, Goeminne PC, Hill AT, Fardon TC, Obradovic D, Gerlinger C, Sotgiu G, Operschall E, Rutherford RM, Dimakou K, Polverino E, De Soyza A, McDonnell MJ. Characterization of the "Frequent Exacerbator Phenotype" in Bronchiectasis. Am J Respir Crit Care Med. 2018 Jun 1;197(11):1410-1420. doi: 10.1164/rccm.201711-2202OC.
• Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS, Feldman C, Flume P, Goeminne PC, Loebinger MR, Menendez R, Morgan L, Murris M, Polverino E, Quittner A, Ringshausen FC, Tino G, Torres A, Vendrell M, Welte T, Wilson R, Wong C, O'Donnell A, Aksamit T; EMBARC/BRR definitions working group. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J. 2017 Jun 8;49(6):1700051. doi: 10.1183/13993003.00051-2017. Print 2017 Jun.
• Gao Y, Richardson H, Dicker AJ, Barton A, Kuzmanova E, Shteinberg M, Perea L, Goeminne PC, Cant E, Hennayake C, Pollock J, Abo Leyah H, Choi H, Polverino E, Blasi F, Welte T, Aliberti S, Long M, Shoemark A, Sibila O, Huang JTJ, Chalmers JD. Endotypes of Exacerbation in Bronchiectasis: An Observational Cohort Study. Am J Respir Crit Care Med. 2024 Jul 1;210(1):77-86. doi: 10.1164/rccm.202310-1729OC.
• Choi H, Ryu S, Keir HR, Giam YH, Dicker AJ, Perea L, Richardson H, Huang JTJ, Cant E, Blasi F, Pollock J, Shteinberg M, Finch S, Aliberti S, Sibila O, Shoemark A, Chalmers JD. Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study. Am J Respir Crit Care Med. 2023 Dec 1;208(11):1166-1176. doi: 10.1164/rccm.202303-0499OC.
• Shoemark A, Shteinberg M, De Soyza A, Haworth CS, Richardson H, Gao Y, Perea L, Dicker AJ, Goeminne PC, Cant E, Polverino E, Altenburg J, Keir HR, Loebinger MR, Blasi F, Welte T, Sibila O, Aliberti S, Chalmers JD. Characterization of Eosinophilic Bronchiectasis: A European Multicohort Study. Am J Respir Crit Care Med. 2022 Apr 15;205(8):894-902. doi: 10.1164/rccm.202108-1889OC.
• Huang JT, Cant E, Keir HR, Barton AK, Kuzmanova E, Shuttleworth M, Pollock J, Finch S, Polverino E, Bottier M, Dicker AJ, Shoemark A, Chalmers JD. Endotyping Chronic Obstructive Pulmonary Disease, Bronchiectasis, and the "Chronic Obstructive Pulmonary Disease-Bronchiectasis Association". Am J Respir Crit Care Med. 2022 Aug 15;206(4):417-426. doi: 10.1164/rccm.202108-1943OC.
• Shoemark A, Griffin H, Wheway G, Hogg C, Lucas JS; Genomics England Research Consortium; Camps C, Taylor J, Carroll M, Loebinger MR, Chalmers JD, Morris-Rosendahl D, Mitchison HM, De Soyza A; Genomics England Research Consortium:; Brown D, Ambrose JC, Arumugam P, Bevers R, Bleda M, Boardman-Pretty F, Boustred CR, Brittain H, Caulfield MJ, Chan GC, Fowler T, Giess A, Hamblin A, Henderson S, Hubbard TJP, Jackson R, Jones LJ, Kasperaviciute D, Kayikci M, Kousathanas A, Lahnstein L, Leigh SEA, Leong IUS, Lopez FJ, Maleady-Crowe F, McEntagart M, Minneci F, Moutsianas L, Mueller M, Murugaesu N, Need AC, O'Donovan P, Odhams CA, Patch C, Perez-Gil D, Pereira MB, Pullinger J, Rahim T, Rendon A, Rogers T, Savage K, Sawant K, Scott RH, Siddiq A, Sieghart A, Smith SC, Sosinsky A, Stuckey A, Tanguy M, Taylor Tavares AL, Thomas ERA, Thompson SR, Tucci A, Welland MJ, Williams E, Witkowska K, Wood SM. Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis. Eur Respir J. 2022 Nov 17;60(5):2200176. doi: 10.1183/13993003.00176-2022. Print 2022 Nov.
• Aliberti S, Lonni S, Dore S, McDonnell MJ, Goeminne PC, Dimakou K, Fardon TC, Rutherford R, Pesci A, Restrepo MI, Sotgiu G, Chalmers JD. Clinical phenotypes in adult patients with bronchiectasis. Eur Respir J. 2016 Apr;47(4):1113-22. doi: 10.1183/13993003.01899-2015. Epub 2016 Feb 4.
• Chalmers JD, Aliberti S, Polverino E, Vendrell M, Crichton M, Loebinger M, Dimakou K, Clifton I, van der Eerden M, Rohde G, Murris-Espin M, Masefield S, Gerada E, Shteinberg M, Ringshausen F, Haworth C, Boersma W, Rademacher J, Hill AT, Aksamit T, O'Donnell A, Morgan L, Milenkovic B, Tramma L, Neves J, Menendez R, Paggiaro P, Botnaru V, Skrgat S, Wilson R, Goeminne P, De Soyza A, Welte T, Torres A, Elborn JS, Blasi F. The EMBARC European Bronchiectasis Registry: protocol for an international observational study. ERJ Open Res. 2016 Jan 20;2(1):00081-2015. doi: 10.1183/23120541.00081-2015. eCollection 2016 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: March 23, 2025
• First Submitted That Met QC Criteria: March 23, 2025
• First Posted (Actual): March 28, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: phenotype; bronchiectasis; precision medicine; multi-omics; endotype
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: 2024ZD0529700

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No