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| ID | Type | Description | Link |
|---|---|---|---|
| 5U54HL096458-17 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Washington University School of Medicine | OTHER |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Children's Hospital Colorado | OTHER |
| Stanford University |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Affected Participants | Subjects who have suppurative lung disease without a known genetic diagnosis |
| |
| Unaffected Family Members | Unaffected family members may be enrolled in the study for collection of DNA only |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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
Major Clinical Criteria
- Bronchiectasis in > 1 lobe
Minor Clinical Criteria, Lung
Minor Clinical Criteria, Other
Exclusion Criteria:
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Subjects who have suppurative lung disease but without a defined genetic diagnosis.
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| Name | Affiliation | Role |
|---|---|---|
| Kenneth Olivier, MD, MPH | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Palo Alto | California | 94304 | United States | ||
| Children's Hospital Colorado |
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| OTHER |
| Seattle Children's Hospital | OTHER |
| The Hospital for Sick Children | OTHER |
| McGill University | OTHER |
| Children's Hospital Medical Center, Cincinnati | OTHER |
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blood draw or buccal swab
| Unaffected Family Member Genetic Testing | Other | Unaffected family members will undergo genetic testing if genetic findings are identified in their affected family member. |
|
| 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 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| National Heart, Lung and Blood Institute | Bethesda | Maryland | 20814 | United States |
| Washington University in St. Louis | St Louis | Missouri | 63130 | United States |
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| The Hospital for Sick Children | Toronto | Ontario | M5G 0A4 | Canada |
| McGill University | Montreal | Quebec | H4A 3J1 | Canada |
| ID | Term |
|---|---|
| D002925 | Ciliary Motility Disorders |
| D000081207 | Primary Immunodeficiency Diseases |
| D007619 | Kartagener Syndrome |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D000072661 | Ciliopathies |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D001987 | Bronchiectasis |
| D001982 | Bronchial Diseases |
| D015619 | Respiratory System Abnormalities |
| D003914 | Dextrocardia |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D012857 | Situs Inversus |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| D017209 | Apoptosis |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
| D000079404 | Regulated Cell Death |
| D016923 | Cell Death |
| D002468 | Cell Physiological Phenomena |
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