A Translational Study for Phenotyping and Endotyping Chinese Patients With NCFBE

AstraZeneca

Status: Enrolling

Conditions: Non-cystic Fibrosis Bronchiectasis

Treatments: Other: Participant Follow-up

Study type: Observational

Funder types: Industry

Identifiers

NCT07245407

D9186R00001

Details and patient eligibility

About

Background/Rationale:

Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic respiratory disease characterized by a clinical syndrome of chronic productive cough and recurrent respiratory infections in the presence of abnormal and permanent dilation of the bronchi. Recent epidemiological studies have clearly shown that the prevalence and incidence of NCFBE are quickly rising both in high- and low-income countries. With the increase of prevalence, bronchiectasis brings huge medical and economic burden to the society.

Recently published Chinese Bronchiectasis Registry study (BE-China) data showed that Chinese bronchiectasis patients exhibit unique clinical characteristics when compared to western countries. The proportion of post-infective causes and tuberculosis in China was twice that of the European Multicenter Bronchiectasis Audit and Research Collaboration (EMBARC) cohort. Moreover, Chinese patients had a lower FEV1% of predicted value, and a higher proportion of obstruction compared to the EMBARC cohort. Pseudomonas aeruginosa (PsA) was the most common pathogen in both cohorts. Chinese patients exhibited a higher frequency of hospitalization compared to the EMBARC cohort (57.2% vs 26.4%); however, unlike the frequency of hospitalization, Chinese patients had fewer exacerbations in the year before enrollment compared to the EMBARC cohort, with most having only one exacerbation. The proportion of patients with three or more exacerbations was much higher in the EMBARC cohort than in China (12.3% vs 38.8%). Except for Aspergillus fumigatus, the positive culture rates of other pathogens were much higher in the EMBARC cohort than in China.

Significant difference in aetiology and clinical phenotypes of NCFBE has been demonstrated by many registry studies conducted in different geographical regions including EMBARC and BE-China. However, the biological processes and mechanisms driving the disease development, so-called "endotypes", have not been fully investigated within the patient populations in these studies. It is remaining unknown that if these differences reported in clinical phenotypes were truly caused by or linked to different endotypes in NCFBE.

In this study, the investigator will perform biomarker assessments and multi-omics analysis on NCFBE patients and healthy participants in China to validate the link of disease pathways to pathophysiological features and uncover the molecular endotypes behind clinical phenotypesof Chinese patients with NCFBE.

Enrollment: 320 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Healthy control cohort:

· Age ≥30 years

Bronchiectasis cohort:

• Capable of giving signed informed consent.
• Participant must be ≥18 years of age, at the time of signing the ICF.
• Able to perform acceptable lung function testing according to ATS/ERS 2019 acceptability criteria.
• Able and willing to comply with the requirements of the protocol including ability to read, write, be fluent in the translated language of all participants facing questionnaires used at center, and use electronic devices (e.g. FENO and spirometry).
• Documented physician-diagnosed bronchiectasis: with a clinical history consistent with bronchiectasis (chronic cough and daily sputum production etc.) and having performed chest HRCT indicating bronchiectasis.
• Remaining clinically stable upon recruitment. Patients with exacerbations are allowed to be enrolled into the registry at least 4 weeks after antibiotic discontinuation.

Exclusion criteria

Healthy control cohort:

• Any respiratory diagnosis (asthma, COPD, bronchiectasis, pulmonary fibrosis or any other chronic respiratory condition requiring regular treatment).
• Inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease, any other connective tissue disease.
• Active malignancy excluding non-melanoma skin cancer.
• Antibiotic treatment for an acute respiratory tract infection in the previous 4 weeks or current sinusitis.
• Any contraindication to study procedures including bronchoscopy.
• Current smoking or smoking in the preceding 3 months.
• Treatment with anti-coagulants.

Bronchiectasis cohort:

• Traction bronchiectasis associated with interstitial lung disease or other pulmonary disorders (e.g., pulmonary fibrosis and cystic fibrosis).
• Primary diagnosis of another pulmonary condition, including COPD, asthma. Patients with a secondary diagnosis of these pulmonary diseases will be allowed to participate as long as bronchiectasis is considered by the investigator to be the primary diagnosis.
• Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:
• Affect the safety of the participant throughout the study
• Influence the findings of the study or the interpretation
• Impede the participant's ability to complete the entire duration of study
• The participant has a history of alcohol or drug abuse within the past year, which, in the opinion of the responsible physician, contra-indicates their participation.
• Active malignancy excluding non-melanoma skin cancer.
• Participants is female who is pregnant or lactating or up to 6 weeks post-partum or 6 weeks cessation of breastfeeding.
• The participant has an altered mental status at the time of informed consent.
• History or current evidence of an upper or lower respiratory infection or symptoms(including common cold) within 2 weeks of baseline assessments
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study center).
• Terminal disease and/or organ failure or participants otherwise considered not appropriate for the study participation.

Trial design

320 participants in 2 patient groups

Healthy control cohort

Description:

Healthy controls will include at least 20 healthy participants aged 30 years or older, with no clinically significant lung disease or chronic lung disease.

Treatment:

Other: Participant Follow-up

Bronchiectasis cohort

Description:

A total of up to 300 NCFBE patients (males and females aged 18 years or older) will be recruited and enrolled into the study. Patient numbers are mainly based on feasible situation. Approximately 30% of NCFBE patients in the study will be required to have had at least 2 exacerbations in the past 12 months.

Treatment:

Other: Participant Follow-up