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Long-term Exposures to Air Pollutants Affect FeNO in Children: A Longitudinal Study

Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation shown to be responsive to short-term air pollution exposures; however, effects of long-term exposures are uncertain. Using longitudinal assessments of FeNO and air pollutant exposures, we aimed to determine whether FeNO is a marker for chronic effects of air pollution exposures after accounting for short-term exposures effects. FeNO was assessed up to six times 2004-2012 in 3607 schoolchildren from 12 communities in the Southern California Children's Health Study. Within-community long-term ambient air pollution exposures (PM2.5, PM10, NO2, O3) were represented by differences between community-specific annual averages and the eight-year average spanning the study period. Linear mixed-effect models estimated within-participant associations of annual average air pollution with current FeNO, controlling for previous FeNO, prior seven-day average pollution, potential confounders, and community-level random intercepts. We considered effect modification by sex, ethnicity, asthma, and allergy at baseline. We found FeNO was positively associated with annual average air pollution, after accounting for short-term exposures. One standard deviation higher annual PM2.5 and NO2 exposures (PM2.5:2.0 g/m3; NO2:2.7 ppb) were associated, respectively, with 4.6% (95%CI:2.3%-6.8%) and 6.5% (95%CI:4.1%-8.9%) higher FeNO. These associations were larger among females. We found little evidence supporting association with PM10 or O3. Annual average PM2.5 and NO2 levels were associated with FeNO in schoolchildren, adding new evidence that long-term exposure affects FeNO beyond the well-documented short-term effects. Longitudinal FeNO measurements may be useful as an early marker of chronic respiratory effects of long-term PM2.5 and NO2 exposures in children.