Wisconsin Infant Study Cohort (WISC) ECHO Pediatric Follow-Up

University Of Wisconsin-Madison, Madison WI

Investigators

Linked publications & trials

Abstract

Asthma affects approximately 10% of US children and is a leading cause of respiratory morbidity and hospitalization. The large population of the Environmental Influences on Child Health Outcomes (ECHO) study that includes children from all over the USA is ideal for identifying early-life causes for childhood asthma. The Wisconsin Infant Study Cohort (WISC) is a birth cohort of rural families and children, including those living in small towns and on farms. This population would bring unique data to ECHO related to home and neighborhood exposures (e.g., animals, microbiome, green space), and health outcomes (e.g., reduced rates of respiratory diseases). Our scientific goals focus on how environmental factors and hormonal influences in adolescence regulate molecular responses of nasal airway cells (NAC). We will analyze DNA methylation (DNAm) and gene expression from NAC samples in mid-childhood and early adolescence and combine these data to identify “molecular phenotypes.” We hypothesize that these phenotypes relate to specific environmental exposures in early life and asthma-related outcomes at ages 6-10 and during a three-year follow-up period. We therefore propose the following specific aims: Aim 1. To leverage ECHO Protocol 3.0 core data, we will analyze nasal cell gene expression and DNAm in children ages 6-10 years to identify airway cell molecular phenotypes and then test for associations with prenatal and early postnatal environmental exposures, personal factors, and clinical outcomes (asthma, rhinitis, lung function). Aim 2. We will reassess asthma outcomes and NAC three years later (ages 9-13 years) to determine how asthma disease activity and changes in severity relate to: a) the molecular phenotypes at 6-10 years, b) potential asthma modifying factors such as puberty, insulin resistance, and allergy, and c) changes in DNAm and gene expression. Aim 3. We propose updating and adapting existing WISC protocols, adopting new ECHO systems, and implementing the ECHO Cohort Protocol with high fidelity to maximize retention of existing participants, contribute to rural and farming exposures and lifestyles, and enhance the ECHO Cohort Protocol. These proposed studies will link modifiable environmental exposures to molecular regulation of airway cells and allergy and asthma clinical outcomes. The results will yield a treasure trove of information that could inform new strategies to prevent asthma and, in affected children, enable innovative approaches to promote disease control and remission.