Measuring exhaled nitric oxide in infants during tidal breathing: Methodological issues

Abstract

Exhaled nitric oxide (FENO) may provide a tool for identifying infants at risk of developing allergic disease in childhood. In infants there is no standardized collection technique; however, the easiest method is to measure FENO during tidal breathing. In this study we investigated various methodological issues for tidal breathing (TB) FENO in infants. These included the effect of ambient NO, oral or nasal breathing, sedation, and tidal expiratory flow. Furthermore, we compared TB FENO in 88 infants with and without wheeze. Ambient NO greater than 5 ppb significantly affected FENO. There was no significant difference between NO levels measured during either oral or nasal breathing; however, there was a significant difference between levels collected from infants before and after sedation (P < 0.001). Tidal breathing FENO decreased with increasing tidal flows (P < 0.001) and increased with age (P = 0.002). There was no significant difference in mixed expired NO between healthy and wheezy children, but children with doctor-diagnosed eczema had significantly raised levels (P = 0.014). There seem to be important methodological limitations for measuring FENO in infants during TB.

Exhaled Nitric Oxide Differentiates Airway Diseases in the First Two Years of Life

“…This would also imply that our study underestimates any differences between groups. However, it has been shown that both nasal and oral NO levels reflect mixed exhaled NO in infants (28) and techniques to avoid nasal contamination of exhaled air in infants require complicated and demanding equipment, unlikely to become useful in practice (30,31). Also, standardization for expiratory flow in infants is technically possible, but difficult (20), and may be unnecessary.…”

Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children

“…Here, measurements based on quiet tidal breathing usually result in higher proportions of children being able to perform the maneuver satisfactorily than spirometry as a forced expiratory maneuver, as illustrated in a review on lung function tests in preschool children with cystic fibrosis (16). Until now, multiple-breath eNO (eNOmb) measurements have mostly been performed in infants and toddlers (17)(18)(19)(20)(21). Despite requiring less cooperation beyond infancy, criteria for standardization of eNOmb measurements are not yet included in the current ERS/ATS guidelines due to methodological issues (9).…”

Exhaled Nitric Oxide Predicts Persistence Of Wheezing, Exacerbations, And Decline In Lung Function In Wheezy Infants And Toddlers

“…Variable expiratory flow is problematic due the highly flow dependent nature of FE NO . [27,28] Although the prevalence of recurrent wheezing among infants/toddlers is high, this group of children is heterogeneous. The majority of wheezy infants/toddlers do not have asthma, but rather wheeze for a variety of anatomic and/or pathophysiologic reasons, including but not limited to post-viral airway inflammation and injury, small airway caliber, central airway malacia, or dysphagia.…”

“…could not perform acceptable tidal breathing FE NO measurements, indicating that unsedated tidalbreathing FE NO may be technically challenging to measure in infants/toddlers. [26] Additional limitations of tidal breathing-FE NO in infants include: potential nasal NO contamination as nasal NO production far exceeds lower airway production, and variable expiratory flow which is problematic due the highly flow dependent nature of FE NO [27,28].…”