Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) birth cohort: study protocol

Abstract

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 and Analysis: The Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) study is nested within the ORIGINS Project and will monitor 400 infants from birth to five 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 six weeks, one, three, and five 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 infant medical history as well as on background and symptomatic nasal sampling for viral PCR and microbiome analysis. Daily temperatures and symptoms recorded in a study-specific Smartphone App will be used to identify symptomatic respiratory illnesses. Ethics and Dissemination: Ethical approval has been obtained from Ramsey Health Care HREC WA-SA (#1908). Results will be disseminated through open-access peer-reviewed manuscripts, conference presentations, and through different media channels to consumers, ORIGINS families, and the wider community.

Profiling epithelial viral receptor expression in amniotic membrane and nasal epithelial cells at birth

“…Future research to assess in utero exposures, viral receptor expression levels in fetal tissues at birth and tracking of postnatal respiratory health outcomes to understand how these exposures modify the airway epithelium and future respiratory outcomes in infants should be undertaken. Both the AERIAL Study and ORIGINS Project with bio banked samples [37,38] and data would be able to facilitate such research.…”

“…The Airway Epithelium Respiratory Illnesses and ALlergy (AERIAL) [37] and the NewbOrn nasal Sampling Evaluation (NOSE) studies are being conducted in accordance with the Helsinki Declaration and was approved by the Ramsey Health Care HREC WA-SA (# 1746 and 1908 respectively). Written informed consent was obtained from each participant's legal guardian after being fully informed about the nature and purpose of the study prior to collection of samples.…”

“…The remaining amniotic membrane strip was xed in 10% (v/v) neutral buffered formalin (NBF) at 4°C and para n embedded for histological assessments. Newborn nasal samples were collected within 72 hours (36.0 ± 16.5 hours) post birth, as previously described [30,37] and cryopreserved in DNA/RNA Shield™ at -80°C until extracted for RNA.…”