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

Abstract

BackgroundAsthma 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/Design205 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.DiscussionBased 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 approvalIRB 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.

Data-Driven Asthma Endotypes Defined from Blood Biomarker and Gene Expression Data

“…Details of the Mechanistic Indicators of Childhood Asthma (MICA) study have been previously published [ 20 ]. MICA was a cross-sectional study of a cohort of 205 children comprising two strata: children with asthma and children without asthma selected in an approximately 1:1 ratio.…”

“…Total RNA from blood collected during observational clinic visits [ 20 ] was used for Affymetrix gene expression analysis as previously described [ 23 ]. Briefly, blood collected in PAXgene tubes was used for total RNA isolation using DNAase treatment.…”

“…The Mechanistic Indicators of Childhood Asthma (MICA) study collected clinical and blood gene expression biomarkers on a cohort of 192 predominantly African American children from Detroit, MI with and without asthma [ 20 ]. Despite a higher prevalence of asthma in low-income and minority children in the U.S., African Americans represent one of the least studied races with regards to asthma [ 21 , 22 ].…”

La influencia del exposoma en los primeros 1,000 días de vida y la salud gastrointestinal

“…[15][16][17][18] El entendimiento de la correlación entre el exposoma, el genotipo y la epigenética de un individuo podría contribuir a una mejor comprensión de la etiopatogenia de ciertas enfermedades, como algunos trastornos del neurodesarrollo, el asma o la obesidad. [19][20][21][22][23] En este contexto, actualmente se están llevando a cabo seis estudios de cohorte en Europa relacionados con este tema. (Cuadro 2) Al igual que en el Proyecto del Genoma Humano, se concentraron estancias internacionales para coordinar un intercambio continuo de datos y evitar la dispersión de esfuerzos por los equipos que actualmente trabajan en este tema.…”

The Human Early Life Exposome (HELIX): Project Rationale and Design

“…Environmental exposures during fetal or early life have been associated with adverse fetal growth and with developmental neurotoxic, immunotoxic, and obesogenic effects in children; but for many of these associations, evidence has been classified as limited or inadequate (e.g., Bellinger 2013; Gascon et al 2013a;La Merrill and Birnbaum 2011;Wigle et al 2008). Neurodevelopmental disabilities, obesity, and asthma are common and highly complex chronic pathologies, and it is hypothesized that improved understanding of how simultaneous environmental risk factors interact among themselves, with individual characteristics (e.g., genetics), and with epigenetics, can help elucidate their causes (Bousquet et al 2011;Gallagher et al 2011;Trasande et al 2009; Van den Bergh 2011). Up to now, the field of environment and child health has almost uniquely focused on single exposure-health effect relationships; there is no global view of how various types of exposures co-exist and jointly affect health.…”