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

Fractional exhaled nitric oxide (F-ENO50), 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 F-ENO50 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. F-ENO50 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 F-ENO50 trajectories were estimated using generalised additive mixed models, with participant-level random effects. We evaluated whether sexspecific trajectories were influenced by race/ethnicity, body mass index (BMI) percentile, allergic rhinitis or puberty. Different F-ENO50 patterns were observed by sex in later childhood and several factors were associated with either F-ENO50 level or change in F-ENO50 as participants aged. F-ENO50-age trajectories were similar by sex until age similar to 11.5 years, after which males had greater F-ENO50 change than females. This divergence in F-ENO50-age trajectories coincides with puberty. Males with higher starting BMI percentile had attenuated F-ENO50-age slopes. Among males, F-ENO50 levels were lower in non-Hispanic white subjects. Among both sexes, participants with rhinitis had higher F-ENO50. F-ENO50 levels within individuals tracked over time; however, there was considerable variation in F-ENO50 patterns across participants. F-ENO50 trajectories from longitudinal data provide evidence of sex differences coinciding with puberty, suggesting potential hormone link. Improved understanding of determinants of F-ENO50 trajectories is needed to realise the potential for using individualised predicted F-ENO50 trajectories.