Airway epithelium respiratory illnesses and allergy (AERIAL) birth cohort: study protocol

作者：Elizabeth Kicic‐Starcevich, David G. Hancock, Thomas Iosifidis, Patricia Agudelo‐Romero, Jose Antonio Caparros-Martin, Yuliya V. Karpievitch, Desiree T Silva, Lidija Turkovic, Peter Neils Le Souëf, Anthony Bosco, David Martino, Anthony Kicic, Susan L. Prescott, Stephen Michael Stick · 发表于：Frontiers in Allergy · 年份：2024 · DOI：10.3389/falgy.2024.1349741 · 被引用次数：10 · 研究领域：Neonatal Respiratory Health Research、Health, Environment, Cognitive Aging、Pregnancy and Medication Impact

Introduction Recurrent wheezing disorders including asthma are complex and heterogeneous diseases that affect up to 30% of all children, contributing to a major burden on children, their families, and global healthcare systems. It is now recognized that a dysfunctional airway epithelium plays a central role in the pathogenesis of recurrent wheeze, although the underlying mechanisms are still not fully understood. This prospective birth cohort aims to bridge this knowledge gap by investigating the influence of intrinsic epithelial dysfunction on the risk for developing respiratory disorders and the modulation of this risk by maternal morbidities, in utero exposures, and respiratory exposures in the first year of life. Methods The Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) study is nested within the ORIGINS Project and will monitor 400 infants from birth to 5 years. The primary outcome of the AERIAL study will be the identification of epithelial endotypes and exposure variables that influence the development of recurrent wheezing, asthma, and allergic sensitisation. Nasal respiratory epithelium at birth to 6 weeks, 1, 3, and 5 years will be analysed by bulk RNA-seq and DNA methylation sequencing. Maternal morbidities and in utero exposures will be identified on maternal history and their effects measured through transcriptomic and epigenetic analyses of the amnion and newborn epithelium. Exposures within the first year of life will be identified based on infan...