Leffler Ja, Laing Ib, Le Souef PNb, Holt PGa, Bosco Aa, Strickland DHa
aThe Kids Research Institute Australia, The University of Western Australia, Perth Australia
bSchool of Paediatrics and Child Health, Princess Margaret Hospital and The University of Western Australia
Allergic asthma is a chronic inflammatory disease affecting the airways of mainly young children. The disease unfortunately has a particularly high prevalence in WA. Asthma is a very heterogeneous disease with a range of severities and some children suffer from very severe and recurrent exacerbations leading to frequent hospitalisations. Although much is known about asthma pathogenesis, we only have a limited understanding of recurrent exacerbations. To address this, we will investigate the systemic immunological and genetic profiles of children in WA with frequent exacerbations using a combination of flow cytometry and RNA sequencing. The outcome will inform us of the molecular and immunological processes associated with frequent exacerbations, which in the short term may be used to guide clinicians in better treating these patients and in the long term to identify novel therapeutic targets for this hard-to-treat patient group.
We are employing state of the art technology to characterize the cellular and molecular signatures of peripheral blood mononuclear cells (PBMC) collected from healthy individuals, and from young patients presenting at hospital during acute asthma exacerbations. The patients are then followed through the open patient administration system in WA to identify the frequency of respiratory events in each patient. We are performing multi-parameter flow cytometry and transcriptome profiling (RNA-Sequencing) of PBMC samples to determine proportions of cellular subsets, activation status and corresponding gene expression. These studies will improve our current understanding of the inflammatory responses in this hard-to-treat patient group and may unveil novel therapeutic targets leading to improved treatment options for these children.
Lay Summary
Allergic asthma is a chronic disease affecting many young children. Some children suffer from more frequent severe asthma attacks that require hospitalization and do not respond well to treatment that is currently available. We do not know the reason for this. This study is designed to identify the specific unique immune cell response that occurs in these children with recurrent disease. This will enhance our understanding of potential alternate treatments for this subset of patients.