Characterizing the Upper Airway Manifestations in Primary Ciliary Dyskinesia and Primary Immunodeficiencies

NCT04919018 | Completed DMC

• 2 other identifiers: 20-11705U54HL096458-17
• Study Type: observational
• Target: 159
• Locations: 2 countries
• Sites: 4

Brief Summary

Though common, morbidities related to upper airway disease in primary ciliary dyskinesia (PCD) and primary immunodeficiencies (PID) have not been fully characterized. These conditions can be difficult to distinguish due to their overlapping phenotypes. The sinonasal and middle ear features are often identified as most problematic by patients and their families, and optimal, highly effective treatment regimens have not been established. The main objective of this project is to characterize and compare the upper airway phenotypes in individuals with confirmed diagnosis of PCD and PID, and to collect critical data to inform the design of future clinical trials of treatment of the upper airway diseases. The investigators anticipate that these investigations will discern the clinical, anatomical, and pathophysiological phenotypes of paranasal sinus disease in PCD and PID, identifying disease endpoints and biomarkers that differentiate these two overlapping disorders. Findings from these studies will also enhance our understanding of middle ear disease and associated hearing loss in a cross-sectional cohort of patients with PCD and PID. Ultimately, the long-term goal of our Consortium is to elucidate underlying phenotypes and genotypes of these diseases, potentially leading to novel therapeutics that will improve the lives of affected individuals. Given the COVID pandemic, certain procedures will have the option to be converted to telehealth visits to ensure compliance with local guidelines and participant safety.

Conditions

Primary Ciliary Dyskinesia; Kartagener Syndrome; Primary Immune Deficiency

Outcome Measures

Primary Outcomes (9)

• Mean Sinonasal Quality of Life SNOT-22 Score in PCD and PID

  SNOT-22 is a subject-completed questionnaire that consists of 22 questions. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be. The total score can range from 0-110, 0 being the best and 110 being the worst.

  During a single 6-hour visit

• Mean Quality of Life SN-5 Score in PCD and PID

  The Sinus and nasal quality of life survey questionnaire (SN-5) is a quality of life assessment completed by a subject/parent consisting of 5 specific symptoms-related questions (answered on a 7-point Likert scale on the frequency of symptoms, 1=none of the time, 7=all of the time), and 1 general overall quality of life question (answered on a visual analog scale from 0 to 10, worst to best).

  During a single 6-hour visit

• Mean Score of Burghart Sniffin' Sticks Threshold Test in PCD and PID

  Olfactory function will be evaluated through the Burghart Sniffin' Sticks test which is a validated psychophysical testing method. Sniffin' Sticks test is based on pen-like odor dispensing devices that will be presented to participants. In the the threshold test, subjects will identify an odor at varying concentrations (Continuous Variable Range: 1-16, 1 being the lowest score and 16 being the highest score).

  During a single 6-hour visit

• Mean Score of Burghart Sniffin' Sticks Discrimination Test in PCD and PID

  Olfactory function will be evaluated through the Burghart Sniffin' Sticks test which is a validated psychophysical testing method. Sniffin' Sticks test is based on pen-like odor dispensing devices that will be presented to participants. In the discrimination test, subjects will select which odor smells different from several options (Continuous Variable Range: 0-16, 0 being the lowest score and 16 being the highest score).

  During a single 6-hour visit

• Mean Score of Burghart Sniffin' Sticks Identification Test in PCD and PID

  Olfactory function will be evaluated through the Burghart Sniffin' Sticks test which is a validated psychophysical testing method. Sniffin' Sticks test is based on pen-like odor dispensing devices that will be presented to participants. In the identification test, subjects ages 12-45 will identify an odor from four choices (Continuous Variable Range: 0-16, 0 being the lowest score and 16 being the highest score).

  During a single 6-hour visit

• Mean Score of Burghart Sniffin' Kids Identification Test in PCD and PID

  Olfactory function will be evaluated through the Burghart Sniffin' Sticks test which is a validated psychophysical testing method. Sniffin' Sticks test is based on pen-like odor dispensing devices that will be presented to participants. In the identification test, subjects ages 5-11 will identify an odor from four choices (Continuous Variable Range: 0-14, 0 being the lowest score and 14 being the highest score).

  During a single 6-hour visit

• Mean Pure Tone Average Air Conduction in PCD and PID

  Audiometry completed by the research team to determine pure tone average in decibels (dB) (Continuous Variable Range: 0-110 dB)

  During a single 6-hour visit

• Mean Pure Tone Average Bone Conduction in PCD and PID

  Audiometry completed by the research team to determine pure tone average in decibels (dB) (Continuous Variable Range: 0-110 dB)

  During a single 6-hour visit

• Characterization of Tympanograms in PCD and PID

  Research team will conduct tympanometry and assign one of four types (Type A, Type B, Typc C or large volume) to the completed tympanogram

  During a single 6-hour visit

Study Arms (2)

Primary Ciliary Dyskinesia (PCD)

Subjects with a confirmed diagnosis of PCD

Primary Immune Deficiency (PID)

Subjects with a confirmed diagnosis of PID

Eligibility Criteria

• Age: 5 Years - 45 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with definite primary ciliary dyskinesia and primary immune deficiencies

You may qualify if:

• Ages ≥ 5-45 years.
• Informed consent, and assent from minors.
• Clinical features consistent with PCD plus
• At least one diagnostic test consistent with PCD:
• Biallelic pathogenic variants in PCD-associated genes identified by genetic panel testing including deletion/duplication analysis.
• Ciliary ultrastructural defect by transmission electron microscopy known to be disease causing, including outer dynein arm defects, outer and inner dynein arm defects, or inner dynein arm defects with microtubular disorganization.
• \- A clinical diagnosis of PID known to be associated with an increased risk of infections, as defined by the European Society of Immunodeficiencies (ESID) registry, AND a genetic confirmation with a known or likely pathogenic variant.
• OR a diagnosis of a common variable immunodeficiency (CVID) as defined by the ESID registry:
• a. At least one of the following:
• i. Increased susceptibility to infection
• ii. Autoimmune manifestations
• iii. Granulomatous disease
• iv. Unexplained polyclonal lymphoproliferation
• v. Affected family member with antibody deficiency
• b. AND marked decrease of IgG and IgA with or without low IgM levels

You may not qualify if:

• Inability to undergo study procedures
• Reported increased respiratory symptoms within 3 weeks before the scheduled visit
• Congenital craniofacial abnormalities (cleft lip and/or palate, hemifacial microsomia) that may result in otologic or sinus disease
• Congenital hearing loss
• Diagnosis of Trisomy 21, Kabuki syndrome, DiGeorge anomaly or syndrome, 22q11 deletion syndrome, or CHARGE syndrome
• History of intranasal illicit drug use (i.e. cocaine) or intranasal abuse of over the counter or prescription drugs (i.e. oxycodone, acetaminophen, etc.)
• Pregnancy
• Known selective IgA deficiency, specific antibody deficiency (SPAD), selective IgG subclass deficiency, selective IgM deficiency, mannose-binding lectin deficiency, as well as inborn errors of immunity (IEIs) which are not known to be associated with an increased risk of infections (e.g. autoinflammatory syndromes; unclassified disorders of immune dysregulation)
• Medical condition that is known to cause secondary immunodeficiency, including human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), and/or active malignancy
• Patients ever having received gene therapy, hematopoietic stem cell transplant, solid organ transplant, or thymus transplant
• Treatment with targeted immune modulators or immune modifiers
• Treatment with chronic systemic steroids

Sponsors & Collaborators

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

Study Sites (4)

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

The Hospital for Sick Children

Toronto, Ontario, M5G 0A4, Canada

Location

McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood draw for biobanking and future analysis

MeSH Terms

Conditions

Ciliary Motility Disorders; Kartagener Syndrome; Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Stephanie Davis, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 9, 2021
• Study Start: June 9, 2021
• Primary Completion: July 23, 2025
• Study Completion: July 23, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Locations

US (2); CA (2)