The recent 2011 State of the Air report from the American Lung Association found that 50.3% of the US population lives in counties that have unhealthy levels of ozone air pollution and as a result the identification of strategies that reducs the risk of developing pulmonary function decrements in individuals exposed to ambient levels of ozone is of critical importance. We have recently developed and validated a two-compartment model of individual subject ozone exposure-response. The first compartment represents the delay to or cumulative dose of ozone at the onset of physiologic response. The second compartment is a fixed volume with a constant rate of elimination of a bioactive substance that activates the deep lung neural receptors that induce rapid shallow breathing and reductions in inspiratory capacity (ie decreased FEV1). The output of these two serially linked compartments is then multiplied by a proportionality coefficient A. Our central hypothesis is that vitamin C and uric acid contained within the respiratory tract lining fluid contributes to the antioxidant capaciy of the airway and the delay in onset of ozone-induced reflex decrements in pulmonary function and subjective symptoms. Our goal is a better understanding of the role of soluble antioxidants in determining ozone exposure response kinetics. These findings will provide further insight into how vitamin C and uric acid dietary modulation reduces the risk of developing pulmonary function decrements in individuals exposed to ambient levels of ozone. We will focus on individual subject ozone exposure-response kinetics and how they are altered by dietary modulation of vitamin C and uric acid. The systems biology approach of combining modeling of individual subject ozone exposure-response kinetics with vitamin C and uric acid dietary modulation will improve the integrated understanding of ozone-induced responses in humans. The proposed experiments will measure the system and its key responses while the computational model will be used to integrate the information to test our hypothesis. We expect that vitamin C and uric acid dietary modulation while attenuating ozone-induced decrements in FEV1 will also increase the number of subjects with a dose of onset in excess of the total cumulative dose of exposure and as a result have no pulmonary function or subjective symptom response with ozone exposure.
Ozone-induced physiologic and symptomatic responses can be viewed as being the result of a complex cascade of events. This cascade is composed of multiple interrelated stages. The goal of this application is to use a systems biology approach to examine the role of soluble antioxidants in determining ozone exposure response kinetics. These findings will provide further insight into how vitamin C and uric acid dietary modulation reduces the risk of developing pulmonary function decrements in individuals exposed to ambient levels of ozone.
