Urinary CC16, a potential indicator of lung integrity and inflammation, increases in children after short-term exposure to PM2.5/PM10 and is driven by the CC16 38GG genotype

Abstract

Particular matter (PM) exposure is a big hazard for public health, especially for children. Serum CC16 is a wellknown biomarker of respiratory health. Urinary CC16 (U-CC16) can be a noninvasive alternative, albeit requiring adequate adjustment for renal handling. Moreover, the SNP CC16 G38A influences CC16 levels. This study aimed to monitor the effect of short-term PM exposure on CC16 levels, measured noninvasively in schoolchildren, using an integrative approach. We used a selection of urine and buccal DNA samples from 86 children stored in an existing biobank. Using a multiple reaction monitoring method, we measured U-CC16, as well as RBP4 (retinol binding protein 4) and beta 2M (beta-2-microglobulin), required for adjustment. Buccal DNA samples were used for CC16 G38A genotyping. Linear mixed-effects models were used to find relevant associations between U-CC16 and previously obtained data from recent daily PM = 2.5 or 10 mu m exposure (PM2.5, PM10) modeled at the child's residence. Our study showed that exposure to low PM at the child's residence (median levels 18.9 mu g/m(3) (PM2.5) and 23.6 mu g/m(3) (PM10)) one day before sampling had an effect on the covariates-adjusted U-CC16 levels. This effect was dependent on the CC16 G38A genotype, due to its strong interaction with the association between PM levels and covariates-adjusted U-CC16 (P = 0.024 (PM2.5); P = 0.061 (PM10)). Only children carrying the 38GG genotype showed an increase of covariates-adjusted U-CC16, measured 24h after exposure, with increasing PM2.5 and PM10 (beta = 0.332; 95% CI: 0.110 to 0.554 and beta = 0.372; 95% CI: 0.101 to 0.643, respectively). To the best of our knowledge, this is the first study using an integrative approach to investigate short-term PM exposure of children, using urine to detect early signs of pulmonary damage, and taking into account important determinants such as the genetic background and adequate adjustment of the measured biomarker in urine.