Slimmen Lisa Jm, Broos Jelle Y, Manaï Badies Han, Estevão Silvia C, Giera Martin, Kooij Gijs, Unger Wendy Wj, Janssens Hettie M
Division of Respiratory Medicine and Allergology, Department of Paediatrics Erasmus MC Sophia Children's Hospital, Erasmus University Medical Centre Rotterdam The Netherlands.
Laboratory of Paediatrics, Infection and Immunity Group, Department of Paediatrics Erasmus University Medical Centre Rotterdam The Netherlands.
Clin Transl Immunology. 2024 Sep 16;13(9):e70000. doi: 10.1002/cti2.70000. eCollection 2024 Sep.
In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease-associated parameters.
Levels of omega (ω)-3/6 PUFAs and their LM derivatives were determined in bronchoalveolar lavage fluid (BALF) of children with CF ages 1-5 using a targeted high-performance liquid chromatography-tandem mass spectrometry approach. Hierarchical clustering analysis was performed on relative LM levels. Individual relative LM levels were correlated with neutrophilic inflammation (BALF %Neu) and structural lung damage (PRAGMA-CF %Disease). Significant correlations were included in a backward multivariate linear regression model to identify the LMs that are best related to disease progression.
A total of 65 BALF samples were analysed for ω-3/6 lipid content. LM profiles clustered into an arachidonic acid (AA)-enriched and a linoleic acid (LA)-enriched sample cluster. AA derivatives like 17-OH-DH-HETE, 5-HETE, 5,15-diHETE, 15-HETE, 15-KETE, LTB and 6-trans-LTB positively correlated with BALF %Neu and/or PRAGMA %Dis. Contrastingly, 9-HoTrE and the LA derivatives 9-HoDE, 9(10)-EpOME, 9(10)-DiHOME, 13-HoDE, 13-oxoODE and 12(13)-EpOME negatively correlated with BALF %Neu and/or PRAGMA %Dis. 6-trans-LTB was the strongest predictor for BALF %Neu. 5-HETE and 15-KETE contributed most to PRAGMA %Dis prediction.
Our data provide more insight into the lung lipidome of infants with CF, and show that a shift from LA derivatives to AA derivatives in BALF associates with early CF lung disease progression.
在囊性纤维化（CF）中，脂质代谢失衡与肺部炎症相关。关于特定脂质介质（LMs）在CF肺部炎症中所起的作用，以及它们在疾病早期进展过程中水平是否发生变化，目前知之甚少。因此，我们测量了年轻CF患者的气道LM谱，并将其与疾病相关参数进行关联。
采用靶向高效液相色谱-串联质谱法，测定1至5岁CF儿童支气管肺泡灌洗液（BALF）中ω-3/6多不饱和脂肪酸（PUFAs）及其LM衍生物的水平。对相对LM水平进行层次聚类分析。个体相对LM水平与中性粒细胞炎症（BALF中中性粒细胞百分比）和肺部结构损伤（PRAGMA-CF疾病百分比）相关。显著相关性纳入反向多变量线性回归模型，以确定与疾病进展最相关的LMs。
共分析了65份BALF样本的ω-3/6脂质含量。LM谱聚类为富含花生四烯酸（AA）和富含亚油酸（LA）的样本簇。AA衍生物如17-OH-DH-HETE、5-HETE、5,15-二HETE、15-HETE、15-KETE、LTB和6-反式-LTB与BALF中中性粒细胞百分比和/或PRAGMA疾病百分比呈正相关。相反，9-HoTrE和LA衍生物9-HoDE、9(10)-EpOME、9(10)-DiHOME、13-HoDE、13-氧代ODE和12(13)-EpOME与BALF中中性粒细胞百分比和/或PRAGMA疾病百分比呈负相关。6-反式-LTB是BALF中中性粒细胞百分比的最强预测因子。5-HETE和15-KETE对PRAGMA疾病百分比预测贡献最大。
我们的数据为CF婴儿的肺脂质组提供了更多见解，并表明BALF中从LA衍生物向AA衍生物的转变与CF肺部疾病早期进展相关。
