Clinically meaningful medium-term variability of fractional exhaled nitric oxide in a UK paediatric cohort

Abstract

Background: Fractional exhaled nitric oxide (FeNO) is a common biomarker used in the diagnosis and monitoring of asthma in children. Little is known about the variability of FeNO beyond one week in healthy or asthmatic children. We investigated the medium-term variability of FeNO in children with and without asthma.

Methods: Children from the Manchester Asthma and Allergy Study attended follow-up at the age of 11 years on two occasions. Skin prick testing was completed. FeNO and spirometry were measured on each visit. Clinically significant FeNO variability (∆FeNO) was defined according to ATS 2011 recommendations.

Results: Of the 425 children who had FeNO measured on two occasions [median (IQR) 20 (9-47) days apart], 11% had current asthma and 33% were atopic. Mean (SD) FeNO in children with current asthma [37.5 (31.6) ppb] or atopy [34.6 (32.2) ppb] was higher than those without [16.7 (21.0) ppb and 10.9 (9.4) ppb, respectively, p<0.001]. The change in FeNO was larger in those with current wheeze [6.7 (2.2-15.3) ppb] or atopy [5.7 (2.2-12.8) ppb] than those without [2.4 (0.9-4.5) ppb and 2.0 (0.8-3.8) ppb, respectively, p<0.001]. ∆FeNO was independently associated with history of hayfever [OR: 2.2 (95%CI: 1.0-4.4), p=0.04], atopy [4.2 (1.9-9.0), p<0.001] and use of asthma medication [3.5 (1.9-9.3), p=0.001]. Changes in FeNO were greater with increased mean FeNO (r=0.7, p<0.001) but not with FEV1.

Conclusion: Increased medium-term variability of FeNO were observed in children with current wheeze and atopy compared to those without. History of hayfever, asthma medication use and atopy were independent confounding factors for clinically significant variability in FeNO.