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Completed

NCT Number: NCT04702243

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

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).

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Key information

Conditions

Primary Ciliary Dyskinesia Abnormalities, Multiple Bronchial Diseases Bronchiectasis Cardiovascular Abnormalities Cardiovascular Diseases Ciliary Motility Disorders Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dextrocardia Genetic Diseases, Inborn Heart Defects, Congenital Heart Diseases Immune System Diseases Immunologic Deficiency Syndromes Kartagener Syndrome Otorhinolaryngologic Diseases Primary Immune Deficiency Primary Immunodeficiency Diseases Respiratory System Abnormalities Respiratory Tract Diseases Situs Inversus

Age range

5 year–45 year

Sex eligibility

All sexes

Study type

Observational

Primary location

The Hospital for Sick Children, Toronto, Ontario, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Unaffected Family Member Genetic Testing

Other

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

Primary outcomes

  1. Number of Participants with a Confirmed Diagnosis of PCD or PID

    Time frame: Up to approximately 4 years

    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.

  2. Prevalence of Neonatal Respiratory Distress Seen in PCD and PID

    Time frame: During a single 6-hour visit

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

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

    Time frame: During a single 6-hour visit

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

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

    Time frame: During a single 6-hour visit

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

  5. Prevalence of Laterality Defects Seen in PCD and PID

    Time frame: During a single 6-hour visit

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

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

    Time frame: During a single 6-hour visit

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

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

    Time frame: During a single 6-hour visit

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

  8. Prevalence of Recurrent Pneumonia/Sepsis Seen in PCD and PID

    Time frame: During a single 6-hour visit

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

  9. Prevalence of Skin Infections/Abscesses Seen in PCD and PID

    Time frame: During a single 6-hour visit

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

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

    Time frame: During a single 6-hour visit

    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.

  11. Prevalence of Abnormal Immunoglobulin G Values Seen in PCD and PID

    Time frame: During a single 6-hour visit

    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).

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

    Time frame: During a single 6-hour visit

    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).

  13. Mean FEV1 Percent Predicted Values in PCD and PID

    Time frame: During a single 6-hour visit

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

Sponsors and collaborators

Lead sponsor

University of North Carolina, Chapel Hill

Other

Collaborators

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

Registry information

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Jan 8, 2021
Registry last updated
Aug 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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