Clinical trial NCT03809091: WGS of Korean Idiopathic Bronchiectasis
Official title: Whole Genome Sequencing of Korean Patients With Idiopathic Bronchiectasis for Identification of Disease-Causing Variants
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bronchiectasis Idiopathic
Cystic Fibrosis
Primary Ciliary Dyskinesia
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2019-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
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.

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of diagnosed patients by using whole genome sequencing
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine
Study officials:
affiliation: Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine
name: Jae-June Yim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.