Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults

University of North Carolina (UNC)

Status

Enrolling

Conditions

Kartagener Syndrome

Primary Ciliary Dyskinesia

Primary Immune Deficiency

Treatments

Diagnostic Test: Genetic Testing for PCD or PID

Other: Unaffected Family Member Genetic Testing

Study type

Observational

Funder types

Other

NIH

Identifiers

NCT04702243

5U54HL096458-17 (U.S. NIH Grant/Contract)

20-0508

Details and patient eligibility

About

The investigators will utilize a systematic approach for the diagnostic evaluation of patients to identify characteristics which may distinguish between Primary Immunodeficiency (PID) disorders versus Primary Ciliary Dyskinesia (PCD).

Full description

This protocol utilizes a cross-sectional study design. Over a 5-year period, the investigators will enroll patients who have clinical and lab features characteristic of a PID disorder or PCD, but do not have a confirmed genetic diagnosis. Innovative, standardized methods (SOPs) will be utilized, including ciliary ultrastructural analyses by transmission electron microscopy (TEM), as pertinent. Measures of nasal nitric oxide (nNO) will be performed in all subjects to allow comparisons of nNO values in PID vs. PCD. Patients with high likelihood of a PID disorder or a high likelihood of PCD will initially undergo research genetic testing on a commercial approved panel for PID disorders or a panel of at least 37 PCD genes. All subjects who do not have a genetic diagnosis from the test panels will undergo whole exome sequencing (WES) to search for novel genetic etiologies for PID or PCD.

Enrollment

1,500 estimated patients

Sex

All

Ages

5 to 45 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Pediatric subjects (aged 5-17 years): Inclusion criteria include the major criterion (bronchiectasis in > 1 lobe on current or chest CT in previous 24 months, if available for review), plus one minor criterion, or two minor criteria, if bronchiectasis is not present, (including at least 1 "lung" minor criteria).

Adult subjects (aged 18-45 years): Inclusion criteria include the major criteria (bronchiectasis in > 1 lobe on current or chest CT in previous 36 months, if available for review), plus one minor criterion, or three minor criteria, if bronchiectasis is not present, (including at least 1 "lung" minor criteria).

Inclusion Criteria:

General Criteria

Age 5-45 years
Male and Female Subjects
All races and ethnicities

Major Clinical Criteria

Bronchiectasis in > 1 lobe

Minor Clinical Criteria, Lung

Neonatal respiratory distress (in term neonates with O2 requirement)
Chronic wet cough (year-round for at least 12 months)
Recurrent episodes of bacterial bronchitis
Recurrent pneumonia (confirmed on chest x-ray)
Respiratory non-tuberculous mycobacteria (NTM) (documented respiratory NTM culture)

Minor Clinical Criteria, Other

Chronic nasal congestion
Recurrent/chronic paranasal sinusitis
Ongoing middle-ear disease and/or tympanostomy tube placement at age ≥ 4 years
Organ laterality defect
Low nasal nitric oxide (< 77 nL/min) (by plateau measurement)
Confirmed family history of PID or PCD

Exclusion Criteria:

Anyone who has a confirmed genetic diagnosis of PCD or PID
Cystic Fibrosis
Alpha-antitrypsin deficiency in adults (18 years and older)
Congenital upper or lower airway anomalies
Post-lung or heart transplant, or other conditions requiring immunosuppression therapy
Other confounding features, such as lung disease due to prematurity (born < 28 weeks gestation) or HIV
Neurological compromise and evidence of recurrent aspiration
Conditions known to be commonly associated with bronchiectasis, such as prior mycobacterium tuberculosis
Have not had standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease, particularly cystic fibrosis, aspiration or airway anatomic abnormalities.