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

Inclusion Criteria:

Overall inclusion criteria for PCD and PID:

• Ages ≥ 5-45 years.

• Informed consent, and assent from minors.

Inclusion Criteria for PCD:

• Clinical features consistent with PCD plus

• At least one diagnostic test consistent with PCD:

1. Biallelic pathogenic variants in PCD-associated genes identified by geneticpanel testing including deletion/duplication analysis.

2. Ciliary ultrastructural defect by transmission electron microscopy known to bedisease causing, including outer dynein arm defects, outer and inner dynein armdefects, or inner dynein arm defects with microtubular disorganization.

Inclusion Criteria for PID:

• A clinical diagnosis of PID known to be associated with an increased risk ofinfections, 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

c. AND at least one of the following:

i. Poor antibody response to vaccines (and/or absent isohemagglutinins)

ii. Low switched memory B cells (<70 percent of age-related normal value)

d. AND secondary causes of hypogammaglobulinemia have been excluded (e.g., infection, protein loss, medication, malignancy)

e. AND diagnosis established after the 4th year of life

f. AND no evidence of profound T cell deficiency

Exclusion Criteria:

• Inability to undergo study procedures

• Reported increased respiratory symptoms within 3 weeks before the scheduled visit

• Congenital craniofacial abnormalities (cleft lip and/or palate, hemifacialmicrosomia) that may result in otologic or sinus disease

• Congenital hearing loss

• Diagnosis of Trisomy 21, Kabuki syndrome, DiGeorge anomaly or syndrome, 22q11deletion syndrome, or CHARGE syndrome

• History of intranasal illicit drug use (i.e. cocaine) or intranasal abuse of overthe counter or prescription drugs (i.e. oxycodone, acetaminophen, etc.)

• Pregnancy

• Known selective IgA deficiency, specific antibody deficiency (SPAD), selective IgGsubclass deficiency, selective IgM deficiency, mannose-binding lectin deficiency, aswell as inborn errors of immunity (IEIs) which are not known to be associated withan increased risk of infections (e.g. autoinflammatory syndromes; unclassifieddisorders of immune dysregulation)

• Medical condition that is known to cause secondary immunodeficiency, including humanimmunodeficiency 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