WGS of Korean Idiopathic Bronchiectasis (WGS_UNK_BE)

Whole Genome Sequencing of Korean Patients With Idiopathic Bronchiectasis for Identification of Disease-Causing Variants

Whole genome sequencing of Korean patients with idiopathic bronchiectasis and their family will perform to identify disease-causing variants.

Study Overview

• Status: Unknown
• Conditions: Cystic Fibrosis; Bronchiectasis Idiopathic; Primary Ciliary Dyskinesia
• Intervention / Treatment: Diagnostic test: Whole genome sequencing

Detailed Description

Idiopathic bronchiectasis may be a manifestation of genetic diseases such as cystic fibrosis, primary ciliary dyskinesia, etc. Diagnosis of these rare genetic diseases is crucial not only because some of the rare diseases developed already effective treatment options, but also the detection of syndrome enables us to detect other organ damages before the deterioration of them.

Several diagnostic tools have been developed; however, the genetic panel has limited screening efficacy due to the genetic heterogeneity of diseases. Even more, especially in Korea, the incidence of idiopathic bronchiectasis caused by the genetic disease is rare, most clinics have limited to assess specialized diagnostic tools such as the specialized genetic panels, sweat chloride test, and the electromagnetic detection tools for ciliary movement.

Whole genome sequencing may be an excellent solution to identify the neglected genetic diseases causing idiopathic bronchiectasis and explore the heterogeneity of disease-causing variants in Korean patients.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Recruiting
    • Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine
    • Contact: Jae-Joon Yim, MD; Phone Number: +82-2-2072-2059; Email: yimjj@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Among the patients visiting Seoul National Univerisity Hospital outpatient clinic, bronchiectasis patients who have no clear etiology of bronchiectasis and their family will be enrolled.

Description

Inclusion Criteria:

• If the patient has bronchiectasis proved by computed tomography (CT).
• The clinical features of the patient are suitable for ciliary dysfunction disease (primary ciliary dyskinesia, cystic fibrosis), alpha1-antitrypsin deficiency, and primary immune deficiency (hyper-immunoglobulin E syndrome, hypogammaglobulinemia, activated phosphoinositide 3-kinase (PI3K) delta syndrome, bare lymphocyte syndrome)
• The patient has no apparent medical events causing bronchiectasis.

Exclusion Criteria:

• If the patient does not agree or withdraw
• If the patient has any clear etiology causing bronchiectasis including AIDS, malignancy, receiving immunosuppressant or chemotherapy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bronchiectasis; The patient with bronchiectasis who has no apparent bronchiectasis-causing etiology will be enrolled. The patient's family who has no bronchiectasis will be also enrolled to identify the patient-specific variants.	Diagnostic test: Whole genome sequencing; Whole genome sequencing of patients and their family will be performed. Among the variants detected by WGS, disease-causing variants will be analyzed by using segregation analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of diagnosed patients by using whole genome sequencing	The primary objective of this study is to evaluate the effectiveness of whole-genome sequencing (WGS) for idiopathic bronchiectasis patients in Korea. The number of patients newly diagnosed with WGS who are previously not diagnosed will be the primary outcome.	3 years

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Jae-June Yim, MD, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine

Publications and helpful links

General Publications

• Hill AT, Sullivan AL, Chalmers JD, De Soyza A, Elborn SJ, Floto AR, Grillo L, Gruffydd-Jones K, Harvey A, Haworth CS, Hiscocks E, Hurst JR, Johnson C, Kelleher PW, Bedi P, Payne K, Saleh H, Screaton NJ, Smith M, Tunney M, Whitters D, Wilson R, Loebinger MR. British Thoracic Society Guideline for bronchiectasis in adults. Thorax. 2019 Jan;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463. No abstract available.
• Lonni S, Chalmers JD, Goeminne PC, McDonnell MJ, Dimakou K, De Soyza A, Polverino E, Van de Kerkhove C, Rutherford R, Davison J, Rosales E, Pesci A, Restrepo MI, Torres A, Aliberti S. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Ann Am Thorac Soc. 2015 Dec;12(12):1764-70. doi: 10.1513/AnnalsATS.201507-472OC.
• Chandrasekaran R, Mac Aogain M, Chalmers JD, Elborn SJ, Chotirmall SH. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm Med. 2018 May 22;18(1):83. doi: 10.1186/s12890-018-0638-0.
• Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA 3rd, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA; Undiagnosed Diseases Network. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131-2139. doi: 10.1056/NEJMoa1714458. Epub 2018 Oct 10.

Helpful Links

• Whole genome sequencing enables definitive diagnosis of Cystic Fibrosis and Primary Ciliary Dyskinesia, bioRxiv, 2018

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: January 16, 2019
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): January 25, 2019
• Last Update Submitted That Met QC Criteria: January 23, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Neurologic Manifestations; Congenital Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Movement Disorders; Pancreatic Diseases; Abnormalities, Multiple; Ciliopathies; Bronchiectasis; Cystic Fibrosis; Dyskinesias; Ciliary Motility Disorders
• Other Study ID Numbers: WGS_UNK_BE

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