Abstract
Introduction: Most children are diagnosed with cystic fibrosis (CF) at a young age, nowadays often through neonatal screening. CF is associated with frequent respiratory tract infections. These exacerbations are often viral induced at a young age. Frequent airway infections lead to early colonization of the airways with pathogenic bacteria. Moreover, infection leads to inflammation and dysregulation of the mucus production via mucin upregulation. The result is disease progression with destruction of the normal airway structure and lung tissue.
Objectives: To gain insights into the mechanisms by which viral infections leading to respiratory exacerbations induce a more pathogenic airway microbiome in young children with CF, from birth to preschool age, through airway inflammation and mucin regulation. This will help formulate informed treatment strategies both at the level of pathogenic as well as potentially beneficial microbiota members in the CF airways.
Methods: Young children with CF from birth to the age of 5 years will be included at CF clinic in UZA. Oropharyngeal swabs will be collected at set time points in a longitudinal way to study the dynamics of the airway microbiome and inflammatory markers and mucins. At the moment of exacerbations extra swabs will be collected to investigate the interactions of viruses and bacteria and their influence on increased inflammation and mucin production. These data will be linked to clinical outcome measures such as lung clearance index and questionnaires on quality of life. The final part of the project exists of an in vitro study investigating the effects of specific CF respiratory microbiota members as such or in combination with viruses on TLR induction, transcriptional factor activation, cytokine and interferon signalling stimulation, and ultimately on the virus-associated infection and cytopathic effects.
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