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

NCT04702243 | Completed DMC

• 2 other identifiers: 20-05085U54HL096458-17
• Study Type: observational
• Target: 436
• Locations: 2 countries
• Sites: 8

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).

Conditions

Primary Ciliary Dyskinesia; Primary Immune Deficiency; Kartagener Syndrome

Outcome Measures

Primary Outcomes (13)

• Number of Participants with a Confirmed Diagnosis of PCD or PID

  A commercial genetic panel will be used to test for disease causing mutation in PCD or PID. If the commercial panel does not yield positive results, WES research testing will be used to identify disease causing mutations in PCD and PID in order to confirm the diagnosis.

  Up to approximately 4 years

• Prevalence of Neonatal Respiratory Distress Seen in PCD and PID

  Medical records will be reviewed to denote presence or absence of neonatal respiratory distress (occurs at birth).

  During a single 6-hour visit

• Prevalence of the Onset of Chronic Nasal Congestion Before Six Months of Age Seen in PCD and PID

  Medical records will be reviewed to denote presence or absence of the onset of chronic nasal congestion before age 6 months.

  During a single 6-hour visit

• Prevalence of the Onset of Daily Wet Cough Before Six Months of Age Seen in PCD and PID

  Medical records will be reviewed to denote presence or absence of the onset of daily wet cough before age 6 months.

  During a single 6-hour visit

• Prevalence of Laterality Defects Seen in PCD and PID

  Medical records will be reviewed to denote presence or absence of laterality defects (situs inversus/heterotaxy).

  During a single 6-hour visit

• Prevalence of Chronic/Recurrent Sinus Disease Seen in PCD and PID

  Medical records will be reviewed to denote presence or absence of chronic/recurrent sinus disease.

  During a single 6-hour visit

• Prevalence of Chronic/Recurrent Middle Ear Disease Seen in PCD and PID

  Medical records will be reviewed to denote presence or absence of chronic/recurrent middle ear disease.

  During a single 6-hour visit

• Prevalence of Recurrent Pneumonia/Sepsis Seen in PCD and PID

  Medical records will be reviewed to denote to denote presence or absence of recurrent pneumonia/sepsis (that is not bronchiectasis).

  During a single 6-hour visit

• Prevalence of Skin Infections/Abscesses Seen in PCD and PID

  Medical records will be reviewed to denote to denote presence or absence of skin infections/abscesses.

  During a single 6-hour visit

• Prevalence of Abnormal Nasal Nitric Oxide Values Seen in PCD and PID

  Nasal nitric oxide will be measured to determine the number of subjects who have an abnormal value, utilizing a cut-off of 77 nl/min.

  During a single 6-hour visit

• Prevalence of Abnormal Immunoglobulin G Values Seen in PCD and PID

  Immunoglobulin G will be measured to determine the number of subjects who have an abnormal value, utilizing the local laboratory age-defined cut-off ranges (United States: mg/dL; Canada: g/L).

  During a single 6-hour visit

• Prevalence of Abnormal Lymphocyte Markers Seen in PCD and PID (Laboratory Tests)

  Lymphocyte Markers will be measured to determine the number of subjects who have an abnormal value, utilizing the local laboratory age-defined cut-off ranges (% of lymphocytes).

  During a single 6-hour visit

• Mean FEV1 Percent Predicted Values in PCD and PID

  Forced expired volume in 1 second (FEV1) will be assessed by percentage of the predicted value (0-100%).

  During a single 6-hour visit

Study Arms (2)

Affected Participants

Subjects who have suppurative lung disease without a known genetic diagnosis

Diagnostic Test: Genetic Testing for PCD or PID

Unaffected Family Members

Unaffected family members may be enrolled in the study for collection of DNA only

Other: Unaffected Family Member Genetic Testing

Interventions

Genetic Testing for PCD or PID DIAGNOSTIC_TEST

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.

Affected Participants

Unaffected Family Member Genetic Testing OTHER

Unaffected family members will undergo genetic testing if genetic findings are identified in their affected family member.

Unaffected Family Members

Eligibility Criteria

• Age: 5 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Subjects who have suppurative lung disease but without a defined genetic diagnosis.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Washington University School of Medicine: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Children's Hospital Colorado: collaborator
• Stanford University: collaborator
• Seattle Children's Hospital: collaborator
• The Hospital for Sick Children: collaborator
• McGill University: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (8)

Stanford University

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

National Heart, Lung and Blood Institute

Bethesda, Maryland, 20814, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 0A4, Canada

Location

McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood draw or buccal swab

MeSH Terms

Conditions

Ciliary Motility Disorders; Primary Immunodeficiency Diseases; Kartagener Syndrome

Interventions

Genetic Testing; Apoptosis

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Immune System Diseases; Bronchiectasis; Bronchial Diseases; Respiratory System Abnormalities; Dextrocardia; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Situs Inversus

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Regulated Cell Death; Cell Death; Cell Physiological Phenomena

Study Officials

• Kenneth Olivier, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: January 8, 2021
• Study Start: December 1, 2020
• Primary Completion: August 6, 2025
• Study Completion: August 6, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Locations

US (6); CA (2)