Acute viral bronchiolitis in infants and young children

Jones A^a, Bosco A^a , Strickland DH^a, Holt PG^a in collaboration with Sly PD^b
Division of Cell Biology^a, Telethon Kids Institute, University of Western Australia, Perth, Australia
^bQueensland Children’s Medical Research Institute, Brisbane, Australia.

This is a shared project with the Human Immunology team and the Systems Immunology team. 

Severe lower respiratory viral infections (sLRI) cause acute viral bronchiolitis (AVB) in infancy and are a major risk factor for the development of asthma. Current treatments for this age group are suboptimal and new advances in effective treatment options are necessary. To enable the development of new therapies we need to identify and characterise the molecular mechanisms that underpin the pathogenesis of AVB during infancy, which are currently unknown. We will employ cutting-edge systems biology approach to dissect the inflammatory gene networks in local and systemic responses underlying AVB. Further, we aim to investigate the contribution of different cell populations to the inflammatory response in AVB and will identify age-related changes in AVB-associated inflammatory responses. Molecular profiling (RNA-Seq) is being carried out on airway epithelial cells (AECs) and PBMC derived inflammatory cells acquired from hospitalised infants (<18 months of age) and pre-schoolers (>18 months – 5 years of age) with moderate to severe AVB, and at 6-8 weeks convalescence, at Royal Children’s Hospital Brisbane. The gene expression profiling data will be analysed with network analysis and bioinformatics to elucidate the underlying disease mechanisms. Drug compounds will then be screened in silico, to identify drugs that perturb AVB-associated gene networks. Finally, the identified drug candidates will be validated with in vitro cell culture. The project will be the first study to look at AECs from the upper airway mucosa and their likely contribution to the local inflammation in the airways. It will allow for a direct comparison between local versus systemic signals in AVB.

Plain language summary: The drugs currently available for treatment of severe AVB in infants have all been developed based on studies on older children and adults.  However it is known that immune and inflammatory functions are immature in infants and it is unclear whether the currently available anti-inflammatory drugs are therefore appropriate for this age group.  This project aims to plug this knowledge gap, and to open up new opportunities for development of better treatments targeted specifically at infants.

Funder: National Health and Medical Research Council of Australia.