CC16 levels into adult life are associated with nitrogen dioxide exposure at birth

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: To determine if increased ambient NO₂ levels at participants' home addresses in early life were associated with decreased levels of CC16 from age 6 to 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 and 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 to 32. Measurements and Main Results: NO₂ exposures at birth or age 6 were available for 777 children with one or more CC16 measurement. We found a negative association between NO₂ exposure and CC16 levels, with a 4.7% (95% confidence interval, -8.6 to -0.7) decrease in CC16 levels from age 6 to 32 per interquartile range 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% confidence interval, -42.9% to -13.2%] per interquartile range). NO₂ at participant's age 6 address was not significantly associated with CC16 levels (-1.9%; 95% confidence interval, -6.3 to 2.6). Conclusions: Higher exposure to NO₂ at birth is associated with persistently low levels of CC16 from 6 to 32 years.