LAUSR

RATIONALE Lung function and growth are adversely associated with nitrogen dioxide (NO2) exposure. Lower levels of circulating club cell secretory protein (CC16) in childhood are also associated with subsequent decreased lung function. NO2 exposure may induce epithelial damage in lungs and alter club cell proliferation and morphology. OBJECTIVES Our objective was to determine if increased ambient NO2 levels at participants' home addresses in early life were associated with decreased levels of CC16 from age 6-32 years. METHODS Participants were enrolled at birth in the Tucson Children's Respiratory Study and had circulating CC16 measured at least once between age 6-32. Linear mixed models were used to determine the association between estimated ambient NO2 exposure at participants' home address at birth or age 6 with CC16 levels from age 6-32. MEASUREMENTS AND MAIN RESULTS NO2 exposures at birth or age 6 were available for 777 children with ≥1 CC16 measurement. We found a negative association between NO2 exposure and CC16 levels, with a 4.7% (95% CI -8.6, -0.7) decrease in CC16 levels from age 6-32 per interquartile (IQR) increase in NO2 exposure (6.0 ppb) at the participants' birth address. We observed modification by race (p interaction = 0.04), with stronger associations among participants with at least one Black parent (-29.6% [95% CI -42.9%, -13.2%] per IQR). NO2 at participant's age 6 address was not significantly associated with CC16 levels (-1.9%, 95% CI -6.3, 2.6). CONCLUSIONS Higher exposure to NO2 at birth is associated with persistently low levels of CC16 from 6-32 years.