Experimental data suggest that endotoxin may interact with organic components of particulate matter (PM) air pollution to induce acute inflammatory response in the airways, but there are no repeated measures data to assess whether this occurs in children with asthma. We previously found associations between 10 repeated measures of daily personal air pollutant exposures and daily acute asthma outcomes in a panel cohort study of 58 school children with asthma ages 9-18 years who were followed in southern California. Using these existing data we will assess for the first time whether repeated personal exposure to endotoxin is an effect modifier of the relation between repeated exposure to air pollution and acute asthma outcomes in subjects with diagnosed asthma (Aim 1). Health outcomes will include airway inflammation (exhaled nitric oxide) and expiratory lung function. Air pollutants will include personal exposure to NO2 and to PM2.5 mass, elemental carbon, and organic carbon. Furthermore, experimental data also show that components of PM derived from the combustion of fossil fuels from traffic sources may have the potential to induce oxidative stress initiated by reactive oxygen species. However, the concentrations of these redox active components can be independent of total regulated PM mass (PM2.5). It is possible that associations previously observed between worsening asthma and PM2.5 were related to the ability of particle mixtures to induce oxidative stress and inflammatory responses, which are hallmarks of the underlying pathology of asthma. To address this issue, we will analyze the relation of asthma outcomes to the oxidant potential of ambient PM2.5 using in vitro bioassays of archived daily particle samples (Aim 2). We hypothesize that asthma outcomes will be related to the oxidant potential of the collected particle samples. We further hypothesize that the magnitude of associations of asthma outcomes with PM2.5 oxidant potential will be greater than that for PM2.5 mass. Finally, to tie the previous two aims together, we will evaluate effect modification of associations between asthma outcomes and the oxidant potential of ambient PM2.5 by exposure to endotoxin (Aim 3). The oxidant potential of ambient particle mixtures may interact more strongly with endotoxin than interactions of endotoxin with surrogate tracers of pro-oxidant organic particle components such as elemental carbon (Aim 1). In the proposed study, we will produce new findings from a panel cohort study to address gaps in knowledge and to demonstrate the potential usefulness of new methods of exposure assessment. This includes new data on the importance to asthma health from joint exposures to endotoxin and air pollution, and from exposure to PM that varies according to a key air pollutant property, its oxidant potential. Our long-term goal is to advance epidemiologic methods of researching air pollution and health by establishing greater coherence with experimental toxicology.
The knowledge that will emerge from the proposed study of these subjects will be of benefit to public health by identifying whether the joint exposure to endotoxin and air pollution affects respiratory health outcomes among children with asthma. We will address major gaps in scientific knowledge by advancing understanding on the components of particulate air pollution that are responsible for associations of acute changes in asthma outcomes with total mass concentrations of regulated fine particulate matter. Our proposed use of repeated measurements of personal exposure to particles with different oxidant potential may influence the way future studies of air pollution and asthma are conducted.
|Delfino, Ralph J; Staimer, Norbert; Tjoa, Thomas et al. (2015) Relations of exhaled nitric oxide and FEV1 to personal endotoxin exposure in schoolchildren with asthma. Occup Environ Med 72:830-6|
|Delfino, Ralph J; Staimer, Norbert; Tjoa, Thomas et al. (2013) Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel. J Expo Sci Environ Epidemiol 23:466-73|
|Delfino, Ralph J; Staimer, Norbert; Tjoa, Thomas (2011) Personal endotoxin exposure in a panel study of school children with asthma. Environ Health 10:69|