Non-cystic Fibrosis Bronchiectasis
Conditions
Keywords
NCFBE
Brief summary
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. 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.
Detailed description
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.
Interventions
This is a longitudinal multi-center, observational, translational study which includes patients with a physician diagnosis of NCFBE by chest HRCT and healthy controls (at baseline only). This study will consist of a baseline visit, a 6-month (site visit or telephone visit) and a 12-month visit as well as planned unscheduled visits for exacerbation events and one optional visit for bronchoscopy.Healthy participants will be only enrolled in the baseline visit and bronchoscopy visit.
Sponsors
AstraZeneca
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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 study at least 4 weeks after the end of exacerbations. If a patient experiencing exacerbation and directly enters the exacerbation visit, the patient is required to come to the study site for baseline visit (after confirming that all inclusion/
Exclusion criteria
are met) within 4 weeks /+ 3 days after the end of exacerbation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1/FVC% | 12 month | Evaluation of lung function |
| FEF25-75 L/s | 12 month | Evaluation of small airway function |
| FENO ppb | 12 month | Evaluation of airway inflammation: FENO. |
| HRCT | 12 month | Evaluation of lung structure profile and change through radiological parameters. |
| cell percentage (%) | 12 month | Measurement of immune cell (including but not limited to neutrophils and eosinophils) percentages in blood |
| Gene expression read counts by RNAseq | 12 month | Functional and transcriptional characterization of airway immune cells, bronchial epithelial cells andsmooth muscle cells (optional). |
| Molecular deliverables | 12 month | MUC5AC/5B in sputum |
| on-set age(years-old) | 12 month | Risk factor assessment: on-set age(years-old) |
| Sex(M/F) | 12 month | Risk factor assessment: Sex(M/F) |
| body mass index(kg/m^2) | 12 month | Risk factor assessment: body mass index(kg/m\^2) |
| comorbidities | 12 month | Risk factor assessment: comorbidities |
| medical history | 12 month | Risk factor assessment: medical history, especially TB history |
| smoking status(never/current/former) | 12 month | Risk factor assessment: smoking status(never/current/former) |
| smoking pack years(pack/year) | 12 month | Risk factor assessment: smoking pack years(pack/year) |
| Sputum microbiology (CFU) | 12 month | Bronchiectasis aetiology evaluation |
| Historical Exacerbation | 12 month | Risk factor assessment: exacerbation number in the previous year |
| BSI score | 12 month | Evaluation of ronchiectasis disease severity: BSI score(0-4 mild,5-8 moderate, ≥9 severe) |
| QoL-B-RSS | 12 month | Evaluation of quality of life: Patient reported outcome: QoL-B-RSS (0-100, higher score stands for lower symptom burden and higher quality of life) |
| BHQ | 12 month | Evaluation of quality of life: Patient reported outcome: BHQ(10-70,higher score stands for higher symptom burden and pooer quality of life ) |
| BEST | 12 month | eDiary: BEST(MCID 4 points may standfor an exacerbation.) |
| Treatment pattern | 12 month | Evaluation of treatment pattern: inhaled antibiotic, macrolide, and mucoactive drugs,etc. |
| Exacerbation assessment | 12 month | Exacerbation assessment: number of exacerbations per patient per year |
| Cell counts (10^9/L) | 12 month | Measurement of immune cell (including but not limited to neutrophils and eosinophils) counts in blood |
| Exacerbation assessment about hospitalization | 12 month | Exacerbation assessment: number of exacerbations lead to hospitalization per patient per year |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJinfu Xu, Doctor
Shanghai Tongji Hospital, Tongji University School of Medicine
Outcome results
None listed