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循环奇数链脂肪酸生物标志物特征可区分儿童过敏性鼻炎伴哮喘与相关过敏性气道表型

A circulating odd-chain fatty acid biomarker signature discriminates pediatric allergic rhinitis with asthma from related allergic airway phenotypes.

临床研究鼻科IF 4.3Q1

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中文摘要

背景: 在儿科人群中,仍缺乏可靠生物标志物来区分过敏性鼻炎伴哮喘(ARA)与相关过敏性气道表型。我们旨在识别并验证ARA的循环代谢生物标志物。
方法: 对380名参与者的血清样本进行了非靶向羧基组学分析,使用SPCSDCarboxyl,参与者包括健康对照(HC)、过敏性鼻炎(AR)、哮喘(AS)和ARA。在 mouse 模型中评估候选生物标志物,并在独立队列(n = 125)中使用靶向羧基组学进行验证。使用多变量和机器学习方法评估生物标志物性能。
结果: ARA与循环奇数链脂肪酸(OCFAs)改变相关,其中戊酸、庚酸、壬酸、十一酸和异戊酸在各队列中一致升高。庚酸、壬酸和十一酸在区分ARA与HC方面表现出色,曲线下面积(AUC)分别为0.96、0.98和0.94。然而,这三种OCFAs在所有过敏性气道表型中普遍升高,缺乏ARA特异性。最小绝对收缩和选择算子(LASSO)回归确定戊酸和十一酸为区分ARA与AR及AS的互补判别特征。其中戊酸表现出最强的表型判别性能,ARA与AR的AUC为0.72,ARA与AS的AUC为0.64。OCFA水平与炎症指标和肺功能显著相关,并在 mouse 模型中证实了类似改变。
结论: 这些发现确定了儿童ARA特异性的OCFA特征,代表一种涉及丙酰辅酶A代谢和脂肪酸氧化的独特免疫代谢内型。戊酸独特地区分ARA与孤立性AR,支持其作为血清参考标志物的潜力;与十一酸或临床参数联合可能进一步提高诊断性能。

英文摘要

BACKGROUND: Reliable biomarkers for discriminating allergic rhinitis with asthma (ARA) from related allergic airway phenotypes remain lacking in pediatric populations. We aimed to identify and validate circulating metabolic biomarkers of ARA.
METHODS: Serum samples from 380 participants, including healthy controls (HC), allergic rhinitis (AR), asthma (AS), and ARA, underwent untargeted carboxylomics profiling using SPCSDCarboxyl. Candidate biomarkers were evaluated in mouse models and validated in an independent cohort (n = 125) using targeted carboxylomics. Biomarker performance was assessed using multivariate and machine-learning approaches.
RESULTS: ARA was associated with altered circulating odd-chain fatty acids (OCFAs), with valeric, heptanoic, nonanoic, undecanoic, and isovaleric acids showing consistent increased across cohorts. Heptanoic, nonanoic, and undecanoic acids demonstrated excellent discrimination of ARA from HC, with areas under curve (AUC) of 0.96, 0.98, and 0.94, respectively. However, these three OCFAs were broadly elevated across all allergic airway phenotypes and lacked ARA specificity. Least absolute shrinkage and selection operator (LASSO) regression identified valeric and undecanoic acids as complementary discriminatory features for ARA versus AR and AS. Among valeric acid showed the most phenotype-discriminatory performance, with an AUC of 0.72 for ARA versus AR and 0.64 for ARA versus AS. OCFA levels correlated significantly with inflammatory indices and pulmonary function, and comparable alterations were confirmed in mouse models.
CONCLUSIONS: These findings identify a pediatric ARA-specific OCFA signature of a distinct immunometabolic endotype involving propionyl-CoA metabolism and fatty acid oxidation. Valeric acid uniquely discriminated ARA from isolated AR, supporting its potential as a serum reference marker; combination with undecanoic acid or clinical parameters may further improve diagnostic performance.