Mechanistic Indicators of Childhood Asthma (MICA) Study: piloting an integrative design for evaluating environmental health

BACKGROUND: Asthma is a common complex disease responsible for considerable morbidity and mortality, particularly in urban minority populations. The Mechanistic Indicators of Childhood Asthma study was designed to pilot an integrative approach in children's health research. The study incorporates exposure metrics, internal dose measures, and clinical indicators to decipher the biological complexity inherent in diseases such as asthma and cardiovascular disease with etiology related to gene-environment interactions. METHODS/DESIGN: 205 non-asthmatic and asthmatic children, (9-12 years of age) from Detroit, Michigan were recruited. The study includes environmental measures (indoor and outdoor air, vacuum dust), biomarkers of exposure (cotinine, metals, total and allergen specific Immunoglobulin E, polycyclic aromatic hydrocarbons, volatile organic carbon metabolites) and clinical indicators of health outcome (immunological, cardiovascular and respiratory). In addition, blood gene expression and candidate SNP analyses were conducted. DISCUSSION: Based on an integrative design, the MICA study provides an opportunity to evaluate complex relationships between environmental factors, physiological biomarkers, genetic susceptibility and health outcomes. PROJECT APPROVAL: IRB Number 05-EPA-2637: The human subjects' research protocol was reviewed by the Institutional Review Board (IRB) of the University of North Carolina; the IRB of Westat, Inc., the IRB of the Henry Ford Health System; and EPA's Human Subjects' Research Review Official

Advancing Methodologies Used in Trace Element-Based Mass Balance Studies to Separately Estimate Soil and Dust Ingestion Rates for Children

Historically, soil ingestion rate estimates were based on trace element-based mass balance (MB) study results. These were used in assessing exposures and health risks for children residing in Superfund or chemically contaminated communities. However, soil and dust can have considerable differences with respect to their sources, chemical, physical, and toxicological characteristics. Unfortunately, the MB approach is incapable of disentangling dust ingestion rates from soil ingestion rates. Alternative methods, such as activity pattern and biokinetic modeling techniques, have also been used to predict soil and dust ingestion rates. The results from these studies differed from those obtained from the MB studies. This research evaluated the MB methodology and formulated a physical model which characterized the environmental and behavioral determinants of soil and dust ingestion exposures by children. This new approach explicitly separates outdoor soil exposures from the indoor tracked-in soil portion of the dust and total dust exposures by utilizing information from five key MB studies along with new information derived from the SHEDS-Soil/Dust time-activity pattern-based modeling runs. Application of this new hybrid methodology showed that the predicted mean soil ingestion rates are 30%-70% less than the “total soil” ingestion rates obtained from the selected MB studies. In contrast, most of the predicted dust ingestion rate estimates were typically greater than the predicted soil ingestion rates. Moreover, the predicted total soil plus dust ingestion rates were found to be mostly higher (by ≤ 60%) than the MB-based “total soil” ingestion rates. Except for one study these results were higher than the results produced by the stand-alone SHEDS-Soil/Dust model runs. Across the MB studies analyzed, predicted outdoor soil ingestion rate contributions to “total soil” ingestion rates varied between 29% and 70% while the tracked-in soil portion of the indoor dust ingestion rates varied between 30% and 71%

Mechanistic Indicators of Childhood Asthma (MICA) Study: piloting an integrative design for evaluating environmental health

Abstract Background Asthma is a common complex disease responsible for considerable morbidity and mortality, particularly in urban minority populations. The Mechanistic Indicators of Childhood Asthma study was designed to pilot an integrative approach in children's health research. The study incorporates exposure metrics, internal dose measures, and clinical indicators to decipher the biological complexity inherent in diseases such as asthma and cardiovascular disease with etiology related to gene-environment interactions. Methods/Design 205 non-asthmatic and asthmatic children, (9-12 years of age) from Detroit, Michigan were recruited. The study includes environmental measures (indoor and outdoor air, vacuum dust), biomarkers of exposure (cotinine, metals, total and allergen specific Immunoglobulin E, polycyclic aromatic hydrocarbons, volatile organic carbon metabolites) and clinical indicators of health outcome (immunological, cardiovascular and respiratory). In addition, blood gene expression and candidate SNP analyses were conducted. Discussion Based on an integrative design, the MICA study provides an opportunity to evaluate complex relationships between environmental factors, physiological biomarkers, genetic susceptibility and health outcomes. Project approval IRB Number 05-EPA-2637: The human subjects' research protocol was reviewed by the Institutional Review Board (IRB) of the University of North Carolina; the IRB of Westat, Inc., the IRB of the Henry Ford Health System; and EPA's Human Subjects' Research Review Official.</p