Pulmonary desmosome protein expression increases following inhaler therapy in preterm-born children with bronchopulmonary dysplasia

<bold>Background:</bold> Lung function impairments in childhood are a known consequence of preterm birth, especially for those with bronchopulmonary dysplasia in infancy, yet the underlying mechanisms remain poorly characterised. <bold>Aims and Objectives:</bold> We characterised the exhaled breath condensate (EBC) proteome in preterm-born children, with and without BPD, and before and after inhaler treatment. <bold>Methods:</bold> EBC from children aged 7 to 12 years, from the Respiratory Health Outcomes in Neonates study, were analysed by Nano-LC Mass Spectrometry with Tandem Mass Tag labelling. Children with percent predicted FEV1 ≤85% were enrolled to a 12-week blinded randomised trial of inhaled corticosteroids alone (ICS) or with long-acting β2-agonist (ICS/LABA) or placebo. <bold>Results:</bold> EBC was analysed from 218 children at baseline, and 46 children received randomised inhaled therapy. 210 proteins were detected in total. 19 proteins were detected in every sample, including three desmosome proteins; desmoglein-1, desmocollin-1 and plakoglobin, which were significantly decreased, and cytokeratin-6A which was increased in preterm-born children with BPD when compared to controls. ICS/LABA significantly increased abundance of desmoglein-1, desmocollin-1 and plakoglobin in the BPD group with low lung function, and significantly increased plakoglobin in those without BPD, to quantities comparable with term-born children at baseline. No differences in desmosome proteins were noted after ICS or placebo. <bold>Conclusions:</bold> The airway proteome of preterm-born children with low lung function and BPD shows evidence of ongoing pulmonary structural changes, which were reversed with 12-weeks ICS/LABA therapy.