Screening for Cystic Fibrosis and Cystic Fibrosis Related Disorders in Chinese Adults With Bronchiectasis

The Clinical and Genetic Characteristics of Cystic Fibrosis and Cystic Fibrosis Disorders in Chinese Adults With Bronchiectasis

The study carries out Sweet Tests and CFTR-mutation screening to explore the prevalence, clinical characteristics, and prognosis of cystic fibrosis, as well as the CFTR-mutation spectrum in Chinese adults with bronchiectasis. The study is multi-centered, prospective, non-interventional, and observational.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis, Pulmonary
• Intervention / Treatment: Diagnostic test: Sweat Test

Detailed Description

The incidence of cystic fibrosis (CF) or CFTR dysfunction in China remains unclear due to the absence of a diagnosis and different genetic backgrounds. However, the CF case rate in western countries is relatively high, up to 1/2500. According to the limited statistics, the most common classic clinical symptom of Chinese CF patients is bronchiectasis. Other symptoms often seen in diseased western groups, such as pancreatic insufficiency, are rarely seen in Chinese patients. Thus, Chinese CF or CFTR dysfunction patients easily misdiagnose bronchiectasis, Chronic pneumonia, asthma, etc. Sweet test and CFTR-mutation screening are urgently needed for diagnosing and treating CF or CFTR dysfunction patients in Chinese adults with bronchiectasis. The study will focus on the change in CFTR function, genetic susceptibility factors, and disease progression to explore the incidence, clinical characteristics, and prognosis of cystic fibrosis, as well as the CFTR mutation spectrum in Chinese adults with bronchiectasis.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Jin-fu Xu, MD; Phone Number: +86 13321922898; Email: jfxucn@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
      • Contact: Jin-fu Xu, MD; Phone Number: +8613321922898; Email: jfxucn@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient recruitment relies on the China Bronchiectasis Registry and Research Collaboration. The final study population will be dynamically adjusted according to the incidence of CF in Chinese adults with bronchiectasis, which will be concluded by the primary study conducted on 200 bronchiectasis patients. 1000 bronchiectasis patients are temporarily decided to be enrolled.

Description

Inclusion Criteria:

• Age>18 years, the diagnosis of bronchiectasis needs a reference to the definition of "non-cystic fibrosis bronchiectasis guideline" published by the British Thoracic Society in 2017 or 2021 China bronchiectasis expert consensus, clinical symptoms of cough and expectoration, with or without intermittent hemoptysis, and chest CT showed bronchiectasis
• Patients who are willing to sign the consent form and participate in the study.

Exclusion Criteria:

• Patients with incomplete essential information, which is needed for the integrity of data analysis. Essential information includes CT images, respiratory sample cultures, spirometry, and exacerbation history for at least one year.
• Patients under 18 years old.

Sweat Test Exclusion Criteria:

• Patients with an implanted device, such as a defibrillator, neurostimulator, pacemaker, or ECG monitor.
• Patients with a history of epilepsy or seizures.
• Patients who are pregnant.
• Patients that have a known sensitivity or allergy to any ingredient.
• Over-damaged, denuded skin or other recent scar tissue.
• Patients with Cardiac Conditions or with suspected heart problems.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adult patients with bronchiectasis (unknown cause); Diagnosis of bronchiectasis was performed using chest HRCT scans in suspected patients with coughing and expectoration, or long durations of hemoptysis. High-resolution images were obtained during full inspiration at 1-mm collimation and 10-mm intervals from the apex to the base of the lungs. The presence of bronchiectasis was confirmed based on the following criteria: 1) lack of tapering in the bronchi; 2) dilation of the bronchi where the internal diameter was larger than that of the adjacent pulmonary artery; or 3) visualization of the peripheral bronchi within 1 cm of the costal pleural surface or the adjacent mediastinal pleural surface.

Diagnostic test: Sweat Test; In people with cystic fibrosis (CF), there is a problem in the transport of chloride across cell membranes. This results in higher concentrations of chloride (as salt) in sweat compared to those who do not have cystic fibrosis. So, if there is a family history or a possibility of CF, the sweat test is part of the special tests to help make, or exclude, a diagnosis of cystic fibrosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sweat chloride and conductivity	Sweat chloride and conductivity is the measured analyte most directly related to the abnormal function of the cystic fibrosis transmembrane regulator (CFTR), the chloride channel that is defective in cystic fibrosis patients	within 14 days after sweat collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CFTR-mutation screening	CFTR-mutation screening will be carried out in Patients with abnormal results of Sweat Test. Mutation detection analysis will be performed in Next Generation Sequencing method using the genomic DNA extracted from peripheral whole blood.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevelance of CF or CFTR dysfunction	The CF and CFTR dysfunction diagnosis is according to the results of sweat tests combined with CFTR sequencing results. CF is defined as a chloride concentration above 59 mmol/L combined with more than one CFTR mutation, while CFTR dysfunction is defined as a chloride concentration between 30-59mmol/L combined with one or two CFTR mutations.	1 year
Microbiology	Sputum or bronchoalveolar lavage fluid culture	through study completion, an average of 1 year
Bronchiectasis severity Score (BSI)	The scale is presented online. It consists of 9 items including Age, BMI(Body Mass Index), % FEV1 Predicted, Previous Hospital Admission in the past 2 years, number of exacerbations in previous year, MRC Breathlessness Score, Pseudomonas Colonisation, Colonisation with other organisms,affected lobes. 0-4 Mild Bronchiectasis. 5 - 8 Moderate Bronchiectasis. 9 + Severe Bronchiectasis.	At baseline and updated once a year for 3 years
Lung function (FEV1 %, FVC %, FEV1/FVC %)	Lung function would be tested by spirometry when patients visit the clinic.	1 year
E-FACED score	It consists of 6 items including exacerbation history in the past year, % FEV1 predicted, Age, Chronic colonization by Pseudomonas aeruginosa, n° of pulmonary lobes affected,and Dyspnea (measured by mMRC score) mild: 0-3 points, moderate: 4-6 points; and severe: 7-9 points	At baseline and updated once a year for 3 years
Comorbidity	Comorbidity would be recorded.	At baseline and updated every year for up to 3 years

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Investigators: Study Chair: Jin-fu Xu, MD, Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 21, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Lung Diseases, Interstitial; Fibrosis; Bronchiectasis; Pulmonary Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 20220922

Drug and device information, study documents

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