Abstract:
Background: Exposure to organophosphate (OP) pesticides, a common class of insecticides used in the Lower Yakima Valley of Washington, has been linked to asthma outcomes and biomarkers in children, potentially through immunological pathways; however, mechanistic understanding of this relationship is limited. Measurement of a profile of cytokines in biological media is a powerful tool for gleaning pathophysiological insight about these respiratory responses to these agricultural exposures. Additionally, cytokines provide a perspective through which to assess temporal trends in both OP pesticide exposures and inflammatory responses, a consideration particularly important for agricultural communities with unique seasonal variability in exposure profiles. Methods: This study aims to 1) assess cytokine variability over time and across a population of children in an OP-intensive agricultural region of Washington and 2) explore relationships between low-level OP exposure and inflammatory responses related to respiratory health, notably asthma. To achieve these aims, dialkylphosphate metabolites were measured in urine and a profile of cytokines was measured in plasma throughout three agricultural seasons in 2011 for children in the University of Washington Center for Child Environmental Health Risks Research (CHC) cohort. Bayesian mixed effects models fit via Markov chain Monte Carlo Hamiltonian sampling methods were leveraged to assess seasonal and demographic variability while linear mixed effects regressions and logistic binomial regressions were used to explore relationships between OP exposure, inflammation, and asthma status. Results: Through these methods, significant seasonal variability was found for levels of IFN-? and IL-8 in child plasma for this agricultural cohort; however, no significant associations were discerned between OP exposure, inflammation, and asthma. Conclusion: This work illustrates how strategically defining systems-based cytokine profiles provides a perspective through which to gain mechanistic insight through epidemiological methods. These results highlight the importance of harnessing seasonal granularity for understanding environmental determinants of inflammation and respiratory health and that other methods of investigating these relationships may be underestimating some of the variability at play.