Dataset Information

Denver Asthma Panel Study-CHEAR Ancillary Study (part II)

ABSTRACT: Urban environments remain a poorly understood toxic environment for children with asthma, where improved exposure characterization and estimation of exposurehealth outcome relationships are clearly needed. The goal of this project is to investigate the interactions between relevant environmental exposures and asthma severity in a year-long longitudinal study of urban children with asthma. Environmental and clinical samples are being collected at 3 seasonal visits. Using these samples, we will measure the effects of multiple relevant exposures (environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), phthalates, and volatile organic compounds (VOCs)) on biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids) and asthma outcomes. Our overall hypothesis is that relevant environmental exposures and their interactions drive disease severity in urban children with asthma. We will test this hypothesis by investigating the following aims: Aim 1: To investigate how environmental exposures (ETS, PAHs, phthalates, and VOCs) and their interactions contribute to asthma severity in urban children. Aim 2: To determine if environmental exposures in children with asthma are associated with changes in in biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids). Aim 3: To determine which biological responses mediate the relationships between environmental exposures and asthma severity. Aim 4: To compare environmental exposures and biological responses in asthmatic and non-asthmatic children

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Urine

DISEASE(S): Asthma

SUBMITTER: Karan Uppal

PROVIDER: ST001039 | MetabolomicsWorkbench | Thu Jul 12 00:00:00 BST 2018

REPOSITORIES: MetabolomicsWorkbench

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Project description:SICAS 1 and SICAS 2 have extraordinary opportunity to evaluate the role of diet, environmental exposures and asthma in the context of school and home specific exposures and capitalize on all the data we are already collecting. Asthma affects 25 million Americans, particularly urban minority children. Children spend nearly all day in school, yet little is known about the role of a child’s exposure to widely disseminated industrial chemicals on asthma morbidity. Early animal models and population studies have begun to identify an association between phenolic chemical exposure and asthma development through proposed increased regulation of an individual’s allergic immune response. This study, nested within a school-based environmental intervention trial, (School Inner-City Asthma Intervention Study, SICAS2) , will enable urinary biomarker analyses during a school-based academic year-long environmental intervention trial to analyze the source and impact of exposures on urinary environmental exposure biomarker levels as well as the relationship between these biomarkers levels and asthma morbidity. We are poised to leverage the clinical and exposure data being collected in the clinical trial and generate cross-sectional urinary phenol biomarker data (at baseline) within the resources of CHEAR. If successful, our study will assess the impact of exposures on these biomarker levels and the impact that these exposures have on asthma morbidity, controlling comprehensively for other personal, home, and school environmental factors associated with asthma outcomes. We hypothesize that exposure to environmental exposures (e.g. phenols, phthalates, environmental tobacco smoke) in urban school children and higher urinary biomarkers will preliminarily be associated with higher asthma morbidity. Specific aims are: Aim 1. To determine the source of exposure to environmental exposures (e.g. phenols, phthalates, environmental tobacco smoke) in inner-city school children as assessed by questionnaire, product use assessment and comprehensive school and home environmental assessment of children with physician-diagnosed asthma. Aim 2. To determine whether urinary phenol/phathalate/cotinine biomarkers are associated with asthma control (e.g. asthma symptoms, such as asthma-related symptom days (primary outcome), and other phenotypes of asthma/allergic symptoms and inflammation such as allergic sensitization, health care utilization and pulmonary lung function

Project description:Background: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored. Aim: To analyze dysfunctions of epithelium in dust mite allergic respiratory disease (rhinitis ¬± asthma) in children. Methods: Expression profilings of nasal epithelial cells collected by brushing were performed on Affymetrix Hugene 1.0 ST arrays. All allergic patients were sensitized to dust mite. 19 patients had an isolated allergic rhinitis (AR). 14 patients had AR associated with asthma. Patients were compared to 12 controls, their severity and control being assessed according to NAEPP and ARIA criteria. Infections by respiratory viruses were excluded by real-time PCR measurements. Results: 61 probes were able to distinguish allergic rhinitis children from healthy controls. A majority of these probes was under the control of Th2 cytokines, as evidenced by parallel experiments performed on primary cultures of nasal epithelial cells. In uncontrolled asthmatic patients, we observed not only an enhanced expression of these Th2-responsive transcripts, but also a down-regulation of interferon-responsive genes. Conclusion: Our study identifies a Th2 driven epithelial phenotype common to all dust mite allergic children. Besides, it suggests that epithelium is involved in the severity of the disease. Expression profiles observed in uncontrolled asthmatic patients suggest that severity of asthma is linked at the same time to atopy and to impaired viral response. Nasal epithelium gene expression profiling of dust mite allergic children with isolated rhinitis, rhinitis associated with asthma and controls. 38 samples classified in 4 categories : 14 isolated rhinitis (R), 6 rhinitis with uncontrolled asthma (UA), 7 rhinitis with controlled asthma (CA) and 11 healthy subjects (C )

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Denver Asthma Panel Study-CHEAR Ancillary Study (part II)

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