Children’s Urinary Phthalate Metabolites and Fractional Exhaled Nitric Oxide in an Urban Cohort

Allan C. Just, Robin M. Whyatt, Rachel L. Miller, Andrew G. Rundle, Qixuan Chen, Antonia M. Calafat, Adnan Divjan, Maria J. Rosa, Hanjie Zhang, Frederica P. Perera, Inge F. Goldstein, Matthew S. Perzanowski

Rationale: Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examined. Objectives: We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with Fe(NO) and that these associations would be stronger among children with seroatopy or wheeze. Methods: In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as Fe(NO) measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations. Measurements and Main Results: Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval [CI] 0.5-13.1%) and 8.7% (95% CI, 1.9-16.0%) increase in Fe(NO), respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and Fe(NO). There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016). Conclusions: Independent associations between exposures to DEP and BBzP and Fe(NO) in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.