Description: Exposure to high levels of particulate matter from wildfire smoke during pregnancy may negatively affect birth outcomes including birth weight, preterm delivery, and intrauterine growth restriction or later health during infancy, regardless of subsequent exposure levels or background ambient air pollution levels. We will investigate the effect of wildfire generated PM 10 and PM 2.5 on these birth outcomes, using California vital statistics records for 2003-2004 and exposures estimates created at the zipcode level for the week of the wildfires in eight counties in southern California. These estimates will be derived in a GIS framework using a combination of existing data from an extensive monitoring network, light extinction data, meteorological conditions, and smoke information extracted from MODIS satellite images. Exact addresses from records will be converted to mapping coordinates and assigned an exposure estimate for wildfire PM and for background ambient PM throughout the pregnancy. Logistic regression will then be used to determine whether an association exists with wildfire PM exposure for each of the outcomes of interest. Given previous evidence linking ambient PM to birth outcomes, we expect that peak exposures to extremely high levels of PM during critical developmental stages in pregnancy may also negatively affect birth outcomes, even after taking into account background ambient air pollution exposure.

Award Amount: $31, 500

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Modification of the DTT assay to increase its throughput and its sensitivity

Description: The chemical assay method, known as the dithiothreitol (DTT) assay, has been used successfully to measure the ability of ambient particles and vapors to generate reactive oxygen species (ROS) by their ability to catalyze the reduction of oxygen to superoxide and hydrogen with DTT as the electron source. However, the assay is a rate based assay requiring multiple time dependent measurements. If the assay could be altered to monitor the reaction continuously and with greater sensitivity, higher throughput would be achieved with smaller samples. The use of selective fluorescent probes for the detection of superoxide and hydrogen peroxide may be the answer to these needs. The activity of these probes is based on the nucleophilic property of these reactive oxygen species to breakdown a non-fluorescent probe to its fluorescent derivative. Superoxide and hydrogen peroxide have different nucleophilic properties and will react selectively with different derivatives. If these fluorescent sensors can be applied to our standard DTT assay, we can substantially increase the sensitivity of the method and adapt it into a high throughput assay, and ultimately, develop an on-site monitoring device measuring real time redox capacity of ambient air.

Award Amount: $18,457

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Description: Asthma is the most common chronic disease in children affecting approximately 1 in 12 children in the United States. The burden of disease in children and their families and the economic cost on families and on healthcare are enormous. To reduce the socio-economic burden of asthma and to maintain optimum respiratory health among children with asthma, the 2007 National Asthma Education and Prevention Program (NAEPP) guidelines have strongly emphasized the importance of asthma control. Among the environmental factors that could affect asthma control, oxidant stress-mediated airway inflammation is one of the key underlying mechanisms that have been associated with increased asthma risk as well as asthma exacerbations. A growing body of evidence indicates that residential proximity to traffic and variants in genes in the oxidant stress pathway are associated with increased asthma risk. Whether these factors delay the attainment of asthma control and maintenance of asthma control in children remains largely unknown. We are particularly interested in evaluating the impact of residential traffic proximities (distances of a

major road and nearest freeway from homes) on the time to achieve first asthma control, aintenance of asthma control at subsequent visits once control has been achieved, number and dosage of rescue and controller medications required to achieve and to maintain asthma control. We hypothesize that exposure to heavy traffic near homes is associated with poor asthma control. We also hypothesize that the association of residential traffic with asthma control varies by clinical phenotypes and by underlying genetic susceptibility.

Award Amount: $29,387

Description: Parkinson's disease (PD), a debilitating neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra, is increasingly recognized as having a complex multi-factorial etiology. Vitamin D, which is produced in the body principally in response to sunlight exposure, influences numerous biological processes, and has been investigated for its potential role in diseases such as multiple sclerosis (as an immune modulator), and some cancers (as an anti-oxidant). Evidence from a number of laboratory studies demonstrates that vitamin D acts as a neuro-protective agent in toxin-induced and genetic models of PD, and studies in humans suggest geographic differences in PD rates exist with north-south gradients. Whether inadequate sunlight exposure leading to deficient production of vitamin D is associated with PD, however, has not been adequately investigated to date in human populations. The goal of the proposed research is to generate pilot data investigating a potential novel mechanism of pathogenesis for sporadic PD; specifically, we will examine the hypothesis that long-term low levels of vitamin D either through inadequate sunlight exposure or alterations in metabolic genes that influence physiological vitamin D levels increase the risk of PD. We will utilize the unique existing resource created by our group at UCLA over the past decade in the NIEHS-funded Parkinson Environment Gene (PEG) study (368 cases, 401 population controls). In the PEG study, we have 1) access to a sophisticated and validated GIS model of UV exposure which we will apply to residential history of PEG subjects to generate individual estimates of cumulative lifetime and average annual UV radiation exposure, and 2) stored DNA samples with which we will assess polymorphisms and haplotype patterns in vitamin D pathway genes. We will test associations between long-term UV exposure measures and PD using multivariable logistic regression models adjusted for potential confounding factors such as age, race, gender, education, smoking, dietary sources of vitamin D, skin pigmentation and pesticide exposure. Similarly, we will examine whether genetic variations presumed to result in different physiological vitamin D activity in genes critical to the vitamin D pathway ( VDR, GC, CYP27A1, CYP27B1 and CYP24A1 ) increase the risk of PD. We will also preliminarily investigate gene-gene and gene-environment interactions to assess whether the estimated effects of sunlight exposure and hence circulating vitamin D metabolite levels on PD are modified by variants in the above genes, as well as whether the selected genes interact with each other to increase or decrease PD risk. The proposed research will thus explore a novel mechanism in the etiology of PD and generate pilot data that we plan use in a future RO1 application to justify replicating in our larger PD study (4000 cases and controls) currently underway in Denmark.

Award Amount: $5,200

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Description: The apparent immunomodulatory effect of ultraviolet radiation (UVR) and vitamin D purported the hypothesis that these factors could be involved in the development of asthma. In the Children's Health Study, we have observed strong protective effect of UVR exposure based on home address without accounting for interpersonal variability due to personal activity. We believe a better assessment of personal UVR exposure will show stronger association. This can be achieved by utilizing new tools to measure time and place of UVR exposure. On the other aspect, due to requirement of blood sample for vitamin D assessment, till current there is no population based studies in children exploring the role of vitamin D in children. Furthermore, there is no vitamin D prediction models based on noninvasive data for children as has been developed for adults. In this study we plan to address these issues in a clinical setting involving 50 asthma cases and 50 healthy controls. We will measure vitamin D and immune markers of those children, measure true personal UVR exposure of the children and build a vitamin D estimation model. We will also conduct focus groups among 5th to 10th graders and their parents to develop a blood collection protocol in research settings. This proposal will support grant applications by providing preliminary data as proof of principle for our approach.

Award Amount: $16,000

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