BACKGROUND Inflammation is integral to early disease progression in children with CF. The effect of modifiable environmental factors on infection and inflammation in persons with CF is poorly understood. Our prior studies determined that secondhand smoke exposure (SHSe) is highly prevalent in young children with CF. SHSe is associated with increased inflammation, heightened bacterial burden, and worsened clinical outcomes. However, the specific metabolite and signaling pathways that regulate responses to SHSe in CF are relatively unknown. METHODS High-resolution metabolomics was performed on plasma samples from infants (n = 25) and children (n = 40) with CF compared to non-CF controls (n = 15). CF groups were stratified according to infant or child age and SHSe status. RESULTS Global metabolomic profiles segregated by age and SHSe status. SHSe in CF was associated with changes in pathways related to steroid biosynthesis, fatty acid metabolism, cysteine metabolism, and oxidative stress. CF infants with SHSe demonstrated enrichment for altered metabolite localization to the small intestine, liver, and striatum. CF children with SHSe demonstrated metabolite enrichment for organs/tissues associated with oxidative stress including mitochondria, peroxisomes, and the endoplasmic reticulum. In a confirmatory analysis, SHSe was associated with changes in biomarkers of oxidative stress and cellular adhesion including MMP-9, MPO, and ICAM-1. CONCLUSIONS SHSe in young children and infants with CF is associated with altered global metabolomics profiles and specific biochemical pathways, including enhanced oxidative stress. SHSe remains an important but understudied modifiable variable in early CF disease.

中文翻译：

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囊性纤维化儿童烟草暴露的代谢组学分析


背景炎症是 CF 儿童早期疾病进展不可或缺的一部分。可改变的环境因素对 CF 患者感染和炎症的影响尚不清楚。我们之前的研究表明，二手烟暴露 (SHSe) 在患有 CF 的幼儿中非常普遍。 SHSe 与炎症增加、细菌负荷增加和临床结果恶化有关。然而，调节 CF 中 SHSe 反应的具体代谢物和信号通路相对未知。方法 对患有 CF 的婴儿 (n = 25) 和儿童 (n = 40) 与非 CF 对照 (n = 15) 的血浆样本进行高分辨率代谢组学分析。 CF 组根据婴儿或儿童年龄和 SHSe 状态进行分层。结果 按年龄和 SHSe 状态划分的整体代谢组图谱。 CF 中的 SHSe 与类固醇生物合成、脂肪酸代谢、半胱氨酸代谢和氧化应激相关途径的变化有关。患有 SHSe 的 CF 婴儿表现出小肠、肝脏和纹状体代谢物定位改变的富集。患有 SHSe 的 CF 儿童表现出与氧化应激相关的器官/组织的代谢物富集，包括线粒体、过氧化物酶体和内质网。在一项验证性分析中，SHSe 与氧化应激和细胞粘附生物标志物的变化相关，包括 MMP-9、MPO 和 ICAM-1。结论 患有 CF 的幼儿和婴儿中的 SHSe 与整体代谢组学特征和特定生化途径的改变有关，包括氧化应激的增强。 SHSe 仍然是早期 CF 疾病中一个重要但尚未得到充分研究的可修改变量。