Tidal breathing nasal nitric oxide measurement as a test for primary ciliary dyskinesia in young children

Nasal nitric oxide (nNO) measurement during velum closure is a useful test for primary ciliary dyskinesia (PCD) but is not feasible in young children. Measurement during tidal breathing is an alternative approach. Our objectives were to define a protocol with age-specific cut-off nNO values during tidal breathing and evaluate this method as an adjunctive test for PCD.

A standardised method for nNO measurement during tidal breathing was developed and tested at the University of North Carolina in children aged <6 years with PCD, asthma, cystic fibrosis and healthy controls. Normative curves were generated as a function of age and generalised 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.

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 under each curve for nNO cut-offs, 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 aged <6 years with PCD confirmed by ultrastructural ciliary analysis or genetic testing, with high specificity.

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.