Accurately measuring personal exposure to air pollutants remains the greatest obstacle to determining their impact on human health. The need for more precise exposure assessment is particularly evident for children and adolescents whose exposure can vary widely based on their time-activity patterns including time spent outdoors, at home, school, and in vehicles. In order to meet the need of epidemiologists to characterize personal exposure, we have developed and validated in laboratory settings a novel personal sensor capable of measuring, with high spatiotemporal resolution, exposure to ultrafine particles (UFP). Results of an initial field test found the sensor to be mobile, rugged, and able to provide accurate spatiotemporal measurements of personal UFP exposure. Feedback from children participating in the initial field test indicated that barriers to its use included its voume, weight, and noise. Therefore, we now propose a two-phase project to: 1) evaluate the usability of the sensor after reducing its size, weight, and noise while maintaining its previous measurement capabilities (R21 Phase) and 2) deploy the modified sensor to characterize personal UFP exposure for adolescents enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) and assess the impact of short-term and peak UFP exposure on respiratory health (R33 Phase). The proposed study represents a continued collaboration between tool-developers and environmental epidemiologists and will allow for the iterative refinement of a personal sensor for UFP exposure. In addition, the application of the sensor in a large-scale epidemiologic study during the R33 phase will address a significant research question regarding the association between short-term and peak UFP exposure and respiratory health. Successful completion of the proposed project will result in a new tool for measuring personal UFP exposure in real world settings and demonstrate the value of the sensor to address novel hypotheses through improved exposure assessment.

Accurately measuring personal exposure to air pollutants remains the greatest obstacle to determining their impact on human health. The need for more precise exposure assessment is particularly evident for children and adolescents whose exposure can vary widely based on their time-activity patterns including time spent outdoors, at home, school, and in vehicles. In order to meet the need of epidemiologists to characterize personal exposure, we have developed and validated in laboratory settings a novel personal sensor capable of measuring, with high spatiotemporal resolution, exposure to ultrafine particles (UFP). Results of an initial field test found the sensor to be mobile, rugged, and able to provide accurate spatiotemporal measurements of personal UFP exposure. Feedback from children participating in the initial field test indicated that barriers to its use included its volume, weight, and noise. Therefore, we now propose a two-phase project to: 1) evaluate the usability of the sensor after reducing its size, weight, and noise while maintaining its previous measurement capabilities (R21 Phase) and 2) deploy the modified sensor to characterize personal UFP exposure for adolescents enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) and assess the impact of short-term and peak UFP exposure on respiratory health (R33 Phase). The proposed study represents a continued collaboration between tool-developers and environmental epidemiologists and will allow for the iterative refinement of a personal sensor for UFP exposure. In addition, the application of the sensor in a large-scale epidemiologic study during the R33 phase will address a significant research question regarding the association between short-term and peak UFP exposure and respiratory health. Successful completion of the proposed project will result in a new tool for measuring personal UFP exposure in real world settings and demonstrate the value of the sensor to address novel hypotheses through improved exposure assessment.

The interplay between environmental exposures, respiratory tract microbiome, and immune responses related to asthma and other respiratory diseases is not well understood. High levels of traffic-related air pollutants (TRAP) have been associated with children's asthma. TRAP can increase adherence of microorganisms to the epithelial cells of the respiratory tract and damage the epithelial layers resulting in increased susceptibility to microbial growth. Many studies suggest a role for altered human microbiota in the etiology of asthma. Furthermore, circumstantial evidence indicates that bacterial infections in the respiratory tract may play a role in asthma development. The airway microbiota may interact with the innate and adaptive arms of the children's developing mucosal immune system in the respiratory tract, which can be critically important in maintaining tolerance against allergc immune responses. Our recent data show that increased exposure to traffic-related particles at birth is associated with longitudinal childhood wheezing. We hypothesize that exposure to TRAP early in life significantly alters the diversity of microorganisms in the respiratory tract in chilren and this effect persists to early adolescence. In Specific Aim 1, we will characterize the respiratory tract microbiome of adolescent children exposed to high and low levels of traffic related air pollution during childhood. Children from the existing cohort of the NIEHS-funded Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) will be recruited for this purpose. This cohort is well characterized regarding childhood exposure to TRAP and indoor aeroallergens as well respiratory health of children from birth to age 12. TRAP exposure at ages 12-15 will be estimated by a land use regression (LUR) model of exposure to truck and bus traffic. Bacterial composition, operational taxonomic units (OTUs), and diversity indices in the respiratory tract of children will be characterized by collecting induced sputum samples, extracting DNA, amplifying bacteria-specific PCR products (using 16S rRNA primers), analyzing DNA sequences by deep sequencing, clustering and assignment of Illumina MiSeq reads into Operational Taxonomic Units (OTUs), analysis of OTUs, and determination of bacterial diversity by RDP database and pipeline, as well as MG-RAST and Qiime software packages. In Specific Aim 2, we will assess associations between bacterial OTUs, diversity indices, and TRAP. To our knowledge, there are no previous reports on the effects of air pollutants on the human respiratory tract microbiome, particularly among children. This information is critically important to understand the interaction between air pollution, human microbiome, and respiratory health among children.

The proposed study will address the hypothesis that exposure to traffic-related air pollution (TRAP) during critical periods of brain development is significantly associated with altered neurobehavior including deficits in cognition, attention, memory, executive function, global intelligence, neuromotor function, behavioral regulation, and altered brain anatomy and physiology. Exposure to environmental neurotoxicants prenatally and during early childhood has been associated with neurobehavioral deficits and altered brain structure. Recent toxicological evidence suggests that TRAP, a complex mixture of metals, elemental and organic carbon, polycyclic aromatic hydrocarbons, and fine and ultrafine particulate matter, is capable of inducing neuroinflammation and translocation across the blood-brain barrier resulting in direct exposure to the brain. The aims of this study are to determine if children exposed to increased levels of TRAP during early stages of brain development have neurobehavioral deficits in childhood and to assess the physiologic impact of TRAP exposure on brain structure, organization, and function. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective cohort study, provides an extraordinary opportunity to accomplish these aims. The CCAAPS cohort was recruited to examine the association between traffic exhaust and the development of allergic disease and asthma. Children enrolled in CCAAPS must have resided either less than 400 m or greater than 1500 m from a major highway at the time of their birth. TRAP exposure during early childhood has been characterized using ambient air monitoring and spatial models. Clinical health assessments, biomarkers, health questionnaires, and addresses of all home, daycare, and school locations have been collected at ages 1-4 and 7. The proposed study is innovative as it exploits all of the collected health, air monitoring, and modeling data and extends the focus of the CCAAPS cohort to examine the impact of early childhood TRAP exposure on neurobehavior and neuroimaging outcomes. A carefully selected battery of valid and reliable tests will be administered at age 11-12 to assess neurobehavioral development. Another unique aspect is the proposed nested study of children with high and low exposure to TRAP during early childhood to assess the physiologic impact of TRAP on the developing brain using quantitative magnetic resonance imaging (MRI). The anticipated results will address a significant gap in scientific knowledge of the potential neurotoxicity of a ubiquitous environmental exposure with far-reaching consequences for future studies and public health.

This collaborative community-driven study is motivated by the concern of the Cincinnati school community including administrators, teachers, public health officials and nurses, parents, and others childhood exposure to traffic-related particles at schools. Traffic-related particles have been shown to exacerbate existing asthma in school-age children. It is unknown, however, the concentrations of these pollutants at schools compared to community background levels. Furthermore, anti-idling campaigns have been conducted with limited success and without measures of environmental or health impact. In order to address the community's concerns and the lack of quantitative data, a new partnership has been formed between environmental health researchers at the University of Cincinnati and community-based organizations including the Cincinnati Public Schools and the Cincinnati Health Department. This partnership will build upon the strengths of each organization to collaboratively accomplish three specific aims: 1) determine if children are exposed to increased levels of traffic-related PM at school compared to ambient levels in the communities where the children reside, 2) develop and implement a community-driven anti-idling campaign aimed at reducing children's exposure to traffic-related air pollution during school hours, and 3) evaluate the effectiveness of the research partnership and anti-idling campaign by assessing the reduction of exposure in schools and the impact on the health of children with asthma who attend these schools. The results of this reciprocal research relationship will guide future public health actions in the Cincinnati community and elsewhere, provide training and education for public health nurses, provide children with asthma and their families with objective health data, engage bus drivers in order to reduce idling, and provide a foundation for future collaborative efforts between University of Cincinnati researchers and community partners. PUBLIC HEALTH RELEVANCE: This collaborative community-driven study is motivated by the concern of the Cincinnati school community including administrators, teachers, public health officials, school nurses, and parents regarding childhood exposure to traffic-related particles at school. This partnership between the University of Cincinnati, Cincinnati Health Department, and the Cincinnati Public Schools will build upon the strengths of each organization to collaboratively determine if children are exposed to increased levels of traffic-related PM at school compared to ambient levels in the communities where the children reside. In addition, a community-driven anti-idling campaign will be developed and implemented with the goal of reducing children's exposure to traffic-related air pollution during school hours. Finally, the effectiveness of the research partnership and anti-idling campaign will be evaluated by assessing the reduction of exposure at schools and the impact on the health of children with asthma.