Cardiorespiratory Effects of Indoor Ozone Exposure Associated with Changes in Metabolic Profiles among Children: A Repeated-Measure Panel Study

Ozone is one of the major gaseous pollutants associated with short-term adverse cardiopulmonary effects, even at concentrations below the current indoor air quality limits. However, the underlying biological mechanisms of cardiorespiratory changes with exposure to ozone remain unclear. To further explore molecular linkages between indoor ozone exposure and relevant cardiorespiratory effects, a repeated-measure panel study including 46 schoolchildren was conducted and real-time exposure measurements including ozone were performed inside classrooms every weekday during the study period. Repeated health measurements and urine sample collection were conducted in each participant. Ultra-high-performance liquid chromatography/tandem mass spectrometry and meet-in-metabolite approach were used in metabolomics analysis. Methods including mixed-effect models were adopted to identify metabolites associated with ozone exposure or health indices. Nine metabolites were found to be associated with ozone after mixed-effect model analysis, which are mainly involved in amino acid and bile acid metabolism. Boys may have a greater decrease in bile acid and RNA related metabolites. Four of the nine ozone-related metabolites were also associated with cardiorespiratory function indices. Furthermore, 26.67% of the positive association between ozone and heart rate was mediated by cholestane-3,7,12,25-tetrol-3-glucuronide. Exposure to ozone below the current indoor standards was associated with the deteriorated cardiovascular function by disturbing bile acid and endogenous nitric oxide-related oxidation and inflammation, and associated with the exacerbated airway inflammation by reducing GPx-related anti-oxidation. The results provide metabolic evidence of the cardiorespiratory effects of indoor ozone exposure. Indoor ozone pollution should be controlled further, and more attention should be paid to preventing its adverse health effects, especially in children.