Description: Exposure to air pollutants is associated with a wide spectrum of acute adverse health effects. Although some progress has been made in identifying the genes and pollutants involved in chronic respiratory health effects of air pollution, a better understanding of the effects of specific pollutants and relevant genetic variation is needed to improve prevention and regulatory approaches. We hypothesize that airway inflammation and oxidative stress mediate adverse respiratory effects from air pollution and that susceptibility depends upon genetic variation in inflammatory and antioxidant pathways. Direct measurement of pro-oxidant species in the airways from air pollution exposure and assessment of oxidative damage from airway inflammation and excess levels of oxidative stress may provide useful insights into relationship between exposure and level of airway oxidative damage. The levels of exposure to pro-oxidants in the respiratory lining fluid and the role of inflammation and oxidative stress has been difficult to study directly in the setting of clinical and large population-based studies. Until recently, measurement of airway oxidative damage has required tests that are infeasible for use in large studies. However, recently, markers of airway oxidative damage in exhaled breath condensates have been developed and tested. Among the most promising markers is 8-isoprostane, a marker of airway oxidative damage. Because collection of exhaled breath condensates is relatively simple to perform, they offer an exciting new opportunity to study the relationship between air pollution, inflammation, oxidative stress, oxidative damage, genetics and adverse health events. In this application, we propose to develop and test methods for collecting and analyzing species in exhaled breath condensates that reflect pro-oxidant exposures (such as PAHs) and oxidant damage.

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Description: The Southern California “Children's Health Study” (CHS) is concerned, in part, with the effect of air pollution on lung function. These pollutants are broadly distributed over space, so the assessment of the effects of these pollutants should take into account the different kinds of spatial dependency that may exist. We would like to analyze the effect of air pollution on respiratory function using multilevel Bayesian Spatial Models to properly account for spatial dependency. One aspect that we would like to incorporate into our multilevel models is the explicit modeling of exposure measurement error, especially in relation to the measurement of NO2 and 03 exposure. We will do this by considering observed NO2 and O3 measurements to be flawed indicators of the unobserved true exposure levels. Models will be employed to examine the spatial dependency between the various NO2 and O3 levels, and to detect and examine spatial interaction between these two pollutants. One advantage of using Bayesian methods to perform spatial modeling is that Bayesian models are amenable to modern Markov Chain Monte Carlo (MCMC) estimation methods that allow one to estimate complex multilevel models in a unified and statistically coherent way. In this application we propose to develop these models and fit them to CHS exposure and health outcome data. This will allow us to build and test a modeling framework that can be used to analyze new outcomes and intra-community variation exposure data as it arrives. This modeling framework will include the models themselves along with computer programs to estimate model parameters and display the results. The results obtained will serve as preliminary results for a future statistical methodology grant application.

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Description: Although childhood asthma prevalence is increasing, the etiology and the explanation for the increase have yet to be explained. However, there is growing evidence that community characteristics associated with socioeconomic status and stress and violence in community, and other factors not captured by personal level information, may partially account for asthma prevalence and morbidity. The purpose of this study is to examine the hypothesis that neighborhood, school and community characteristics indicative of the social environment and community stressors are associated with wheeze and asthma prevalence among 6000 school children enrolled in the Children's Health Study (CHS). The CHS is a population-based study of air pollution and respiratory disease in 12 communities in Southern California . Community characteristics will be obtained from various state and federal sources and will include neighborhood population density, unemployment rates, crime rates, and school free lunch statistics. These data will be linked with Children's Health Study participants by the USC GIS laboratory and examined in relation to lifetime history of wheeze and asthma at study entry. This pilot study will provide a new approach both to evaluating risk factors for asthma and to refining the assessment of effects of air pollution in the CHS.

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Description: The long-term goal of this proposal is to elucidate the effects of ultrafine particulate matter (UFP, concentrated from ambient air) on alveolar epithelial barrier function and delineate as to how UFP enters pneumocytes and subsequently crosses the biological barrier. In order to provide important basic information regarding how UFP affects alveolar epithelial barrier function and the mode of transport of UFP, we propose to investigate the following three Specific Aims: I) delineate mechanisms of UFP-induced derangement of alveolar epithelial barrier properties and elucidate effects of exogenously instilled antioxidant molecules (e.g., GSH) on UFP-induced derangement of alveolar epithelial barrier properties; ii) investigate the transport mechanisms of UFP uptake into pneumocytes and eventual crossing the alveolar epithelial barrier by studying the time course of UFP uptake into and translocation across type I and type II pneumocytes; and iii) determine the transport mechanisms of particle uptake into and translocation across alveolar epithelial barrier utilizing defined particles (e.g., submicrometer polystyrene particles).

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Description: A main research hypothesis in both the Children's Health Study and the SC PM Centre considers oxidative stress as an underlying pathway of effects of ambient air pollution. Given the relevance of the respiratory tract lining fluid as a first defense mechanism, measuring the antioxidant depletion activity could be a promising complementary approach to the PM Centre's and CHS' activities. In addition, to optimize the epidemiological model in the exposure assignment domain, one would ideally call for a ‘unifying exposure term' that describes the oxidative activity of the air in the CHS children breath. The applicability of such oxidative activity measures to CHS needs to be clarified as major questions relevant to the design of a large-scale application remain to be answered. These include the PM sampling requirements (e.g. direct impinging PM's in water versus filter sampling), spatial and temporal variability of these measures. This pilot project will make optimal use of a SC PM Centre project which samples weekly PM suspensions, for eight weeks (Feb/March 03 and Aug/Sept 03), at two distances from a highway. The aim of this piggy-backed project will be to describe the antioxidant depletion rate and the OH-formation potential of impinged fine and ultrafine particulate matter as well as of PM's sampled on filters. These results can be compared not only across the two locations and seasons but with the various measures of oxidative properties assessed in the SCPSC main study. The pilot will provide crucial results needed in the planning of a large-scale application of oxidative activity measures in the future CHS framework.

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