Rationale Nasal nitric oxide (nNO) measurement during velum closure is a useful test for primary ciliary dyskinesia (PCD) but not feasible in young children. Measurement during tidal breathing is an alternative approach. Objectives To define a protocol with age-specific cut-off values for nNO measurements during tidal breathing and evaluate as an adjunctive test for PCD. Methods A standardized method for nNO measurement during tidal breathing was developed and tested at University of North Carolina in children under 6-years with PCD, asthma, cystic fibrosis, and healty controls. Normative curves were generated as a function of age and generalized estimating equations were used to define age-specific cut-off values. The protocol was subsequently validated in 107 children undergoing evaluation for PCD at eight additional sites. Results In healthy controls, tidal breathing nNO values increased from birth to age 6-years, but remained low for children with PCD. With sensitivity set at 0.98, cut-off values of nNO increased from 13.9 nL·min −1 at 2-months to 47.7 nL·min −1 at 5-years of age. Receiver operating characteristic curves had high areas for nNO cut-offs under each curve, ranging from 0.98 to 0.99 across the ages represented in the study. Validation testing at participating sites showed tidal breathing nNO accurately identified 93% of the 60 children under 6 years with PCD confirmed by ultrastructural ciliary analysis or genetic testing, with high specificity. Conclusion Tidal breathing nNO measurement is a useful adjunctive test to distinguish young children with PCD from healthy controls as young as 2-months using age-specific cut-off nNO values.
Leigh et al. (2026) studied this question.