Impaired responses to oxidative stress in the airways of preterm-born school-aged children with a history of bronchopulmonary dysplasia

<bold>Background:</bold> Whilst lung function impairments in later life are a recognised consequence of preterm birth, especially for those with bronchopulmonary dysplasia (BPD) in infancy, the mechanisms remain incompletely understood. We characterised the exhaled breath condensate (EBC) metabolome from preterm-born children, both with and without BPD. <bold>Methods:</bold> EBC from children aged 7-12 years, from the Respiratory Health Outcomes in Neonates study, were analysed using Time-of-Flight Mass Spectrometry. Metabolite Set Enrichment Analysis (MSEA) linked significantly altered metabolites to biological processes. Linear regression models examined relationships between metabolites and participant characteristics, including spirometry parameters. <bold>Results:</bold> EBC was analysed from 214 children; 144 were born preterm, including 34 with BPD. 235 metabolites were detected, with 38 above the limit of detection in every sample. Alanine and pyroglutamic acid were significantly reduced in BPD when compared to preterm- and term-controls, with reduced quantities of glutamic acid and glycine seen when compared to the term group. MSEA demonstrated reduced glutathione metabolism. Reduced quantities of alanine, ornithine and urea in the BPD group were linked with an alteration of the urea cycle. Multivariable linear regression revealed significant associations between these metabolites and BPD when other participant characteristics were considered, but not with lung function measures. <bold>Conclusions:</bold> The airway metabolome of school-aged children with BPD shows changes consistent with a reduced quantity of glutathione, suggesting an active disease process characterised by oxidative stress