Exposure to Traffic-related Particles and Endotoxin during Infancy Is Associated with Wheezing at Age 3 Years

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Rationale</jats:title> <jats:p>Murine models demonstrate a synergistic production of reactive oxygen species on coexposure to diesel exhaust particles and endotoxin.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>It was hypothesized that coexposure to traffic-related particles and endotoxin would have an additive effect on persistent wheezing during early childhood.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Persistent wheezing at age 36 months was assessed in the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk birth cohort. A time-weighted average exposure to traffic-related particles was determined by applying a land-use regression model to the homes, day cares, and other locations where children spent time from birth through age 36 months. Indoor levels of endotoxin were measured from dust samples collected before age 12 months. The relationship between dichotomized (&lt;/≥75th percentile) traffic-related particle and endotoxin exposure and persistent wheezing, controlling for potential covariates, was examined.</jats:p> </jats:sec> <jats:sec> <jats:title>Measurements and Main Results</jats:title> <jats:p>Persistent wheezing at age 36 months was significantly associated with exposure to increased levels of traffic-related particles before age 12 months (OR = 1.75; 95% confidence interval, 1.07–2.87). Coexposure to endotoxin had a synergistic effect with traffic exposure on persistent wheeze (OR = 5.85; 95% confidence interval, 1.89–18.13) after adjustment for significant covariates.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The association between traffic-related particle exposure and persistent wheezing at age 36 months is modified by exposure to endotoxin. This finding supports prior toxicological studies demonstrating a synergistic production of reactive oxygen species after coexposure to diesel exhaust particles and endotoxin. The effect of early versus later exposure to traffic-related particles, however, remains to be studied because of the high correlation between exposure throughout the first 3 years of life.</jats:p> </jats:sec>