Clinical trial NCT04702243: Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults
Official title: Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Ciliary Dyskinesia
Primary Immune Deficiency
Kartagener Syndrome
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Children's Hospital Colorado
name: Stanford University
name: Seattle Children's Hospital
name: The Hospital for Sick Children
name: McGill University
name: Children's Hospital Medical Center, Cincinnati
First posted: 2021-01-08
Enrollment: 1500
Sex: ALL
Minimum age (years): 5
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects who have suppurative lung disease but without a defined genetic diagnosis.

Brief summary: 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).

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants with a Confirmed Diagnosis of PCD or PID
timeFrame: Up to approximately 4 years
measure: Prevalence of Neonatal Respiratory Distress Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of the Onset of Chronic Nasal Congestion Before Six Months of Age Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of the Onset of Daily Wet Cough Before Six Months of Age Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Laterality Defects Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Chronic/Recurrent Sinus Disease Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Chronic/Recurrent Middle Ear Disease Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Recurrent Pneumonia/Sepsis Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Skin Infections/Abscesses Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Abnormal Nasal Nitric Oxide Values Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Abnormal Immunoglobulin G Values Seen in PCD and PID
timeFrame: During a single 6-hour visit
measure: Prevalence of Abnormal Lymphocyte Markers Seen in PCD and PID (Laboratory Tests)
timeFrame: During a single 6-hour visit
measure: Mean FEV1 Percent Predicted Values in PCD and PID
timeFrame: During a single 6-hour visit
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Bethesda
country: United States
facility: National Heart, Lung and Blood Institute
state: Maryland
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montréal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kenneth Olivier, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: