Department of Child Health, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
Faculty of Life Sciences, University of Bristol, Bristol, UK.
Sci Rep. 2023 Nov 9;13(1):19465. doi: 10.1038/s41598-023-46499-w.
Preterm-born children are at risk of long-term pulmonary deficits, including those who developed bronchopulmonary dysplasia (BPD) in infancy, however the underlying mechanisms remain poorly understood. We characterised the exhaled breath condensate (EBC) metabolome from preterm-born children, both with and without BPD. Following spirometry, 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 of interest and participant demographics. EBC was analysed from 214 children, 144 were born preterm, including 34 with BPD. 235 metabolites were detected, with 38 above the detection limit in every sample. Alanine and pyroglutamic acid were significantly reduced in the BPD group when compared to preterm controls. MSEA demonstrated a reduction in glutathione metabolism. Reduced quantities of alanine, ornithine and urea in the BPD group were linked with alteration of the urea cycle. Linear regression revealed significant associations with BPD when other characteristics were considered, but not with current lung function parameters. In this exploratory study of the airway metabolome, preterm-born children with a history of BPD had changes consistent with reduced antioxidant mechanisms suggesting oxidative stress.
早产儿有发生长期肺部缺陷的风险，包括那些在婴儿期患有支气管肺发育不良（BPD）的早产儿，但潜在的机制仍不清楚。我们对早产儿的呼出气冷凝物（EBC）代谢组进行了特征分析，包括患有和不患有 BPD 的早产儿。在进行肺量测定后，使用飞行时间质谱法对来自新生儿呼吸系统健康研究的年龄在 7-12 岁的儿童的 EBC 进行了分析。代谢物集富集分析（MSEA）将显著改变的代谢物与生物过程联系起来。线性回归模型检查了感兴趣的代谢物与参与者人口统计学特征之间的关系。从 214 名儿童中分析了 EBC，其中 144 名是早产儿，包括 34 名患有 BPD。检测到 235 种代谢物，每种样本中有 38 种代谢物超过检测限。与早产儿对照组相比，BPD 组的丙氨酸和焦谷氨酸显著减少。MSEA 显示谷胱甘肽代谢减少。BPD 组中丙氨酸、鸟氨酸和尿素的数量减少与尿素循环的改变有关。当考虑其他特征时，线性回归显示与 BPD 有显著相关性，但与当前的肺功能参数无关。在这项对气道代谢组的探索性研究中，患有 BPD 的早产儿有变化与抗氧化机制减少一致，表明存在氧化应激。
