Investigators
André Schultz, Timo Lassman, Anthony Kicic, Sarah Munns, Anne Chang, Mark Nicol, Kat Ramsey, Steven Mascaro, Lesley Versteegh, Peter Richmond, Chris Blyth, Sam Buckberry, Kim Isaacs, Maree Toombs, Alex Brown, Bep Uink, Thomas Iosifidis, Luke Garratt
Project description
Bronchiolitis is a serious lung infection caused by a virus. Bronchiolitis is the most common reason globally for children be hospitalised. In Australia, Indigenous children are ~6 times more likely than other children to be admitted in hospital for bronchiolitis. A study from Eastern Australia found that 1:5 Aboriginal and/or Torres Strait Islander children hospitalised for bronchiolitis were later found to have bronchiectasis. Bronchiectasis is a serious lung condition that reflects permanent lung damage. If we could find out why some Aboriginal children, and not others, develop bronchiectasis we can try to help prevent the disease.
As both bronchiolitis and bronchiectasis are diseases of the airway surface, we will comprehensively study the airway surface and factors affecting the airway surface in infants hospitalised with bronchiolitis. Study of the airway surface will include the mucosal lining (epithelial cells) with overlying mucus and local inflammatory cells, and the transcriptome (genes switched on during and after infection). We will compare the characteristics, processes and behaviour of cells that make up the airway surface in infants who recover post-hospitalisation to those who develop chronic disease. We’ll also measure factors that affect the airway surface like bacteria in the upper airways, exposures to smoking, overcrowding etc. If we find out how the airway surface is different between infants who develop chronic disease compared with those who don’t, we may find ways to prevent bronchiectasis in those who are vulnerable.
This project will carry out a cohort study to determine why such a high proportion of Indigenous children develop bronchiectasis after bronchiolitis.
Any vulnerability is likely related to the airway surface such as the mucin, cilia, epithelium, or inflammatory cells active at the airway surface.
The vulnerability could extend to factors that influence the airway surface, for example:
- the nasopharyngeal microbiome and biofilm that is micro-aspirated onto the lower airway surface
- background factors intrinsic to the individual e.g., premature birth, low birth weight, nutrition
- background factors related to the individual’s external environment e.g., overcrowding, tobacco smoke exposure
- maternal factors e.g., stress and
- the virus causing the bronchiolitis.
This cohort study involving >200 children will assess the factors above.
The information will be integrated into a Bayesian network (a probabilistic graphical model) to quantify the relative importance, and conditional dependencies, of all the variables affecting the airway surface, thereby allowing identification, and understanding of factor(s) leading to chronic lung disease post-bronchiolitis. This will provide feasible approaches to mitigate airway injury.
Funders of the project
WA Child Research Fund (WACRF)
External collaborators
- The University of Western Australia
- Child and Adolescent Health Service, WA Department of Health
- Menzies School of Health Research
- The University of Sydney
- Murdoch University, Western Australia