Patterns and determinants of exhaled nitric oxide trajectories in schoolchildren over a 7-year period

Abstract

Fractional exhaled nitric oxide (FENO50), a marker of allergic airway inflammation, is used in respiratory research and asthma clinical care; however, its trajectory with increasing age during childhood has not been well characterised. We examined FENO50 longitudinally during a period of important somatic growth to describe trajectories across childhood and adolescence in healthy participants and evaluate clinical factors as potential determinants of trajectories.FENO50 was collected at six visits over 8 years in a population-based cohort of 1791 schoolchildren without asthma (median age at entry 8.4 years). Smooth sex-specific FENO50 trajectories were estimated using generalised additive mixed models, with participant-level random effects. We evaluated whether sex-specific trajectories were influenced by race/ethnicity, body mass index (BMI) percentile, allergic rhinitis or puberty.Different FENO50 patterns were observed by sex in later childhood and several factors were associated with either FENO50 level or change in FENO50 as participants aged. FENO50–age trajectories were similar by sex until age ∼11.5 years, after which males had greater FENO50 change than females. This divergence in FENO50–age trajectories coincides with puberty. Males with higher starting BMI percentile had attenuated FENO50–age slopes. Among males, FENO50 levels were lower in non-Hispanic white subjects. Among both sexes, participants with rhinitis had higher FENO50. FENO50 levels within individuals tracked over time; however, there was considerable variation in FENO50 patterns across participants.FENO50 trajectories from longitudinal data provide evidence of sex differences coinciding with puberty, suggesting potential hormone link. Improved understanding of determinants of FENO50 trajectories is needed to realise the potential for using individualised predicted FENO50 trajectories.