Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects

Abstract

Introduction: Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20-30 s.

Methods: We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNO_vac; negative pressure was applied by pinching the sampling tube) for < 2 s resulted in enhanced suction of nasal air during measurement. Feasibility, success rate, discriminatory capacity, repeatability and agreement were assessed for all four sampling modalities.

Results: We included 13 patients with PCD, median (IQR) age of 21.8 (12.2-27.7) years and 17 HC, 25.3 (14.5-33.4) years. Measurements were highly feasible (96.7% success rate). Measured NO values with vrTB-nNO modalities differed significantly from TB-nNO measurements (HC: p < 0.001, PCD: p < 0.05). All modalities showed excellent discrimination. The vacuum method gave remarkably high values of nNO in both groups (1865 vs. 86 ppb), but retained excellent discrimination. vrTB-nNO_4sec, vrTB-nNO_6sec and vrTB-nNO_vac showed identical specificity to cTB-nNO (all: 1.0, 95% CI 0.77-1.0).

Conclusion: vrTB-nNO sampling requires only a few seconds of probe-in-nose time, is feasible, and provides excellent discrimination between PCD and HC. Rapid TB-nNO sampling needs standardisation and further investigations in infants, young children and patients referred for PCD workup.

Keywords: Nasal nitric oxide; Primary ciliary dyskinesia; Rare lung diseases.