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Mechanistic Indicators of Childhood Asthma (MICA): piloting an integrative design for evaluating environmental health
GALLAGHER, J., D. M. Reif, B. HEIDENFELDER, L. M. NEAS, E. E. HUDGENS, A. H. WILLIAMS, J. P. INMON, S. W. RHONEY, R. W. WILLIAMS, G. L. Andrews, M. M. Johnson, H. A. OZKAYNAK, S. W. Edwards, S. W. Cohen, AND E. A. Hubal. Mechanistic Indicators of Childhood Asthma (MICA): piloting an integrative design for evaluating environmental health. BMC PUBLIC HEALTH 11(1):344, (2011).
Based on integrative design, the MICA study provides an opportunity to evaluate complex relationships between environmental factors, physiological biomarkers, genetic susceptibility and health outcomes.
Background: Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma; however appropriately designed studies are critical for these methods to reach their full potential. Objective: We used a case-control study to investigate whether genomic data (blood gene expression), viewed together with a spectrum of exposure effects and susceptibility markers (blood, urine and nail), can provide a mechanistic explanation for the increased susceptibility of asthmatics to ambient air pollutants. Methods: We studied 205 non-asthmatic and asthmatic children, (9-12 years of age) who participated in a clinical study in Detroit, Michigan. The study combines a traditional epidemiological design with an integrative approach to investigate the environmental exposure of children to indoor-outdoor air. The study includes measurements of internal dose (metals, allergen specific IgE, PAH and VOC metabolites) and clinical measures of health outcome (immunological, cardiovascular and respiratory). Results: Expected immunological indications of asthma have been obtained. In addition, initial results from our analyses point to the complex nature of childhood health and risk factors linked to metabolic syndrome (obesity, blood pressure and dyslipidemia). For example, 31% and 34% of the asthmatic MICA subjects were either overweight (BMI > 25) or hypertensive, (age and gender adjusted blood pressure values> 90th percentile). Conclusion: This study represents a new paradigm for epidemiological studies in which traditional health endpoints and biomarkers are coupled with genetics and high content (Omics) data to expand the use of mechanistic models for human risk assessment.