Introduction/Aim:
Prior studies have identified a ?vulnerable? epithelial endotype, characterised by impaired response to injury, in childhood wheeze. Ezrin may be a suitable biomarker of airway epithelial integrity, respiratory morbidity and allow for targeted treatment in early life.We hypothesised that systemic levels of ezrin associate with impaired epithelial repair and wheeze morbidity in young children.

Methods:
Nasal airway epithelial cell (AEC) cultures of children with (4.1±3.8yr, n=12) and without (3.3±1.9yr; n=7) wheeze were wounded to assess repair and response to celecoxib treatment. Ezrin protein was quantified by ELISA in culture supernatant, plasma and urine samples from children with and without wheeze (n=46). The relationship between nasal AEC, ezrin and clinical outcomes (wheeze recurrence/severity) was assessed using Pearson?s correlation.

Results:
Nasal AEC from 7 children (of 12) with wheeze showed a dysregulated response to wounding, compared to non-wheeze counterparts. Ezrin protein expression was reduced in cultures from children with wheeze, however celecoxib treatment restored its expression to similar levels as non-wheeze controls. Reduced plasma (18.6±3.8ng/ml) and urine (24.0±5.4ng/ml) ezrin levels were detected in children with wheeze, particularly those with impaired AEC repair (plasma:13.1±3.2ng/ml; urine:20.5±1.0ng/ml) compared to non-wheeze controls (plasma: 28.3±6.5ng/ml; urine: 31.6±4.1ng/ml). Both plasma and urine ezrin levels negatively associated with future recurrence and severity of respiratory exacerbations.

Conclusion:
Our study highlights ezrin as a potential biomarker of epithelial dysfunction, response to treatment, and respiratory morbidity in children.