Nasal Nitric Oxide in Primary Immunodeficiency and Primary Ciliary Dyskinesia: Helping to Distinguish Between Clinically Similar Diseases

Abstract

Purpose: Primary Ciliary Dyskinesia (PCD) is a rare disorder of mucociliary clearance leading to recurrent upper and lower respiratory tract infections. PCD is difficult to clinically distinguish from other entities leading to recurrent oto-sino-pulmonary infections, including primary immunodeficiency (PID). Nasal nitric oxide (nNO) is a sensitive and specific diagnostic test for PCD, but it has not been thoroughly examined in PID. Past publications have suggested an overlap in nNO levels among subjects with PCD and PID. We sought to determine if nNO measurements among patients diagnosed with PID would fall significantly above the established PCD diagnostic cutoff value of 77 nL/min. Methods: Children >5 years old and adults with definitive PID or PCD diagnoses were recruited from outpatient subspecialty clinics. Participants underwent nNO testing by standardized protocol using a chemiluminiescence analyzer and completed a questionnaire concerning their chronic otosino-pulmonary symptoms, including key clinical criteria specific to diagnosed PCD (neonatal *

Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

“…A low nNO concentration warrants continued evaluation for PCD, provided cystic fibrosis has been excluded. It is also important to note that people with primary immunodeficiencies, conditions that have clinical features that overlap with PCD, can have reduced nNO levels and further testing may be needed [ 96 ].…”

Limitations of Nasal Nitric Oxide Testing in Primary Ciliary Dyskinesia

“…When using established, standardized protocols ( 5 ), meta-analysis shows that low nNO measurements are “comparable to that of TEM and/or genetic testing”; however, the guideline states that “patients should still progress to further corroborative PCD diagnostic studies” ( 2 ). This recommendation is underscored by recent observations that some patients with primary immunodeficiency, a heterogeneous group of disorders sharing clinical features with PCD, can also have reduced nNO levels ( 6 ). In these cases, misdiagnosis may have serious consequences.…”

Diagnosis of primary ciliary dyskinesia: discrepancy according to different algorithms

“…nNO has a sensitivity and specificity of >95% compared with TEM or genetic testing when performed in children >5 years old with cystic fibrosis excluded [ 7 , 18 , 30 ]. However, a considerable risk for false negative [ 5 , 10 , 17 ] and false positive results [ 10 , 17 , 30 , 31 ] remains. Besides the five cases diagnosed with PCD based on the ATS algorithm only (“false positive” compared with the ERS and PCD-UNIBE algorithms), we also found two patients with a “false negative” diagnosis based on the ATS algorithm (patients 4 and 14).…”