Clinical Impacts and Biological Mechanisms of Prenatal and Early-Life Environmental Exposures and Telomere Length on Childhood Allergic Diseases

Background and Significance: There has been large increases in prevalence of childhood allergic diseases around the world including Taiwan over the past few decades, which occurred too rapidly to be accounted by genomic changes alone and is more likely to be the results of changes in prenatal or early-life environmental exposures in susceptible subjects. Prior studies provide supportive evidence regarding the potential effects of ambient air pollution exposure on allergic diseases in children and adults. Air pollution triggers oxidative stress and inflammation, consequently, may influence telomere length. Previous studies have barely investigated the association of telomere length with allergic diseases. Although some studies have reported the associations of exposure to single air pollutant with the risk of childhood allergic diseases, to our knowledge, no study has simultaneously accounted for interplay of prenatal and early-life exposure to ambient air pollution and telomere length, and examined their impacts on childhood allergic diseases.Study Design: This project provides an unique opportunity to address several current research gaps in childhood allergic diseases, by utilizing comprehensive clinical and epidemiological data collected from the study cohorts (Prediction of Allergies in Taiwanese CHildren [PATCH] and Longitudinal Investigation of Global Health in Taiwanese Schoolchildren [LIGHTS] cohorts) along with environmental data obtained from the National Aeronautics and Space Administration (NASA) in the U.S. and the Environmental Protection Administration (EPA) in Taiwan. We will also apply state-of-the-art approaches to measure telomere length and scrutinize biological mechanisms induced by air pollution, such as oxidative stress, inflammatory response, aryl hydrocarbon receptor and telomerase activity in human airway epithelial cells. The PATCH and LIGHTS cohorts are population-based cohorts of more than 2,800 subjects with well-documented clinical and laboratory data and biological specimens. We have published several first/corresponding author papers on well-known SCI journals (J Asthma 2011; Clin Exp Allergy 2011; Eur Respir J 2012; PLoS One 2013; Allergy 2014; J Allergy Clin Immunol 2014; PLoS One 2014; J Pediatr 2014; Allergy 2016; Sci Rep 2017; PLoS One 2017; WAO J 2018; Allergy 2019; WAO J 2019). In this study, we will investigate the following proposed specific aims:Aim 1: To investigate impacts of ambient air pollution during prenatal and early-life periods on the development of childhood allergic diseases.Aim 2: To examine impacts of exposure to ambient air pollution during prenatal and early-life periods on telomere length.Aim 3: To determine whether telomere length is associated with the development of childhood allergic diseases.Aim 4: To evaluate interplay of telomere length, ambient air pollution during prenatal and early-life periods, and childhood allergic diseases.Aim 5: To elucidate whether particulate matter extracts induce telomere shortening in human airway epithelial cells through the roles of oxidative stress and inflammation.Aim 6 (Exploratory analysis): To explore the relationship between surrounding greenness exposure, telomere length and development of childhood allergic diseases.Expected Contributions: By optimizing our available resources and closely working with a highly experienced multidisciplinary team, this project will be well-positioned to uncover the clinical impacts and biological mechanisms of prenatal and early-life environmental exposures and telomere length on the development childhood allergic diseases.

Project ID:PC10907-1231
External Project ID:MOST109-2314-B182-042-MY3