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The airway epithelium in children with acute wheeze: Just how different is it?

Looi, K., Harrison, L., Stick, S., Le Souef, P., Laing, I. and Kicic, A. (2020) The airway epithelium in children with acute wheeze: Just how different is it? Respirology, 25 (S1). p. 91.

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Introduction/Aim. Early childhood wheeze is a major risk factor for asthma. However, not all children who wheeze will develop the disease. The airway epithelium (including altered epithelial barrier function) has been shown to be involved in asthma pathogenesis (Looi et al, CEA 2018, 48:513). Despite this, the airway epithelium of children with acute wheeze remains poorly characterized. This study aimed to characterize the airway epithelium in children with acute wheeze.

Methods. Nasal epithelial cells (NECs) from children with acute wheeze (n = 11; 6 males; mean age 3.7 _ 1.3 years old) and community controls (n = 8; 4 males; mean age 2.7 _ 0.3 years old), were expanded (Martinovich et al, Sci Rep 2017, 7:17971) andalso differentiated into airliquid interface (ALI) cultures. Markers of epithelial lineage (Cytokeratin (Ck)-5, -19) and vimentin was assessed via qPCR and immunocytochemistry. Inflammatory cytokines (Interleukin (IL)-6, -8 and -1β) were measured using ELISA. Barrier integrity was determined via In-Cell Western assay for tight junction (TJ) expression and transepithelial electrical resistance (RT) measurement and permeability assay for epithelial function.

Results. NECs from children with acute wheeze had significantly higher Ck-19 and lower vimentin gene expression compared to community controls (P < 0.05) but Ck-5 was not significantly different. Similar staining intensities of Ck-5 and -19 proteins were observed in both acute wheeze and controls. IL-6 and -8 levels were not significantly different, but IL-1β was increased in NEC cultures of acute wheeze when compared to controls. TJ protein expression of claudin-1, occludin and ZO-1 were significantly lower in acute wheeze cohorts and was concomitant with decreased epithelial RT and increased permeability.

Conclusion. Airway epithelium of children experiencing acute wheeze appears abnormal primarily with compromised epithelial barrier integrity and function. Collectively, these data infer potentially exaggerated epithelial responses following pathogen exposure. The mechanisms underlying this compromised epithelial remains unknown and warrants further assessment.

Item Type: Journal Article
Murdoch Affiliation(s): School of Biological Sciences and Biotechnology
Publisher: Wiley
Copyright: © 2020 Asian Pacific Society of Respirology.
Other Information: Abstract given @ TSANZSRS 2020 The Australia & New Zealand Society of Respiratory Science and The Thoracic Society of Australia and New Zealand (ANZSRS/TSANZ) Annual Scientific Meeting for Leaders in Lung Health & Respiratory Science, 27–31 March 2020, Melbourne Convention and Exhibition Centre, VIC, Australia
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