CC16 Levels into Adult Life Are Associated with Nitrogen Dioxide Exposure at Birth.

Lung function and growth are adversely associated with nitrogen dioxide (NO) exposure. Lower levels of circulating club cell secretory protein (CC16) in childhood are also associated with subsequent decreased lung function. NO exposure may induce epithelial damage in lungs and alter club cell proliferation and morphology. To determine if increased ambient NO levels at participants' home addresses in early life were associated with decreased levels of CC16 from age 6 to 32 years. 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 NO exposure at participants' home address at birth or age 6 with CC16 levels from age 6 to 32. NO exposures at birth or age 6 were available for 777 children with one or more CC16 measurement. We found a negative association between NO 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 NO 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). NO at participant's age 6 address was not significantly associated with CC16 levels (-1.9%; 95% confidence interval, -6.3 to 2.6). Higher exposure to NO at birth is associated with persistently low levels of CC16 from 6 to 32 years.