FeNO Measured at Fixed Exhalation Flow Rate during Controlled Tidal Breathing in Children from the Age of 2 Yr

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Abstract
We have outlined a new method to measure exhaled nitric oxide on-line at fixed flow rate during controlled tidal breathing (FeNO [controlled]) in young children aged 2 yr and older. FeNO(controlled) measures NO on-line during operator-controlled tidal breathing. The operator targets the exhaled flow of the child within preset limits of 0.4-0.6 L/s by continuously adjusting an expiratory resistance. FeNO(controlled) is estimated during end exhalation. We have validated this method against the reference method of the single breath on-line (SBOL) maneuvre (FeNO[SBOL]) and compared it with NO in mixed exhaled air collected in a bag (FeNO [mixed]). Sixty-seven children were studied: 16 school children and 51 children aged 2-5 yr; 14 of the young children were healthy, 22 had asthma treated with regular inhaled budesonide, and 15 had mild episodic wheeze treated with inhaled terbutaline as necessary. FeNO (controlled) showed good agreement with FeNO(SBOL) (factor difference 0.7-1.4), whereas FeNO(mixed) showed poor agreement with FeNO(SBOL) (factor difference 0.51-5.37). FeNO(controlled) (mean [95% confidence interval]) was 6 ppb (4-8 ppb) in young children with asthma, 5 ppb (3-7 ppb) in young children with mild episodic wheeze, and 3 ppb (2-4 ppb) in healthy control subjects (asthma versus control subjects: p = 0.006; episodic wheeze versus control subjects: p = 0.057). FeNO(controlled) increased from 4 ppb (2-7 ppb) to 13 ppb (10-18 ppb) (p < 0.0001) when the mean daily maintenance dose of budesonide was tapered in nine young children with asthma. FeNO(controlled) is feasible in young children from age 2 and shows better agreement with FeNO(SBOL) than FeNO(mixed). FeNO(controlled) covaries with asthma disease severity and steroid dose. FeNO(controlled) is therefore suggested as a noninvasive diagnostic tool for monitoring asthma disease activity in young children with asthma from the age of 2 yr.