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Background <p>Childhood obesity-associated asthma represents a distinct phenotype with incompletely understood metabolic mechanisms. This hypothesis-generating study aimed to screen candidate biomarkers associated with small airway dysfunction in children with obese type 2 asthma and explore preliminary associations between obesity-related metabolic alterations and airway function.</p> Methods <p>Thirty age- and sex-matched children with asthma (6–14 years) were enrolled: 15 with obese type 2 asthma and 15 with non-obese asthma. Plasma samples underwent proteomic analysis using data-independent acquisition mass spectrometry and untargeted metabolomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analyses included multiple linear regression, mediation analysis, receiver operating characteristic (ROC) curve analysis, and nomogram construction.</p> Results <p>Proteomic analysis identified 176 differential proteins, with four enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Metabolomic analysis revealed 153 differential metabolites, predominantly lipids (28.3%), with L-acetylcarnitine notably elevated. Children with obese type 2 asthma exhibited significantly lower maximal mid-expiratory flow (MMEF) : 48.5% vs. 70.2% and elevated systemic inflammation. Fatty acid-binding protein 4 (FABP4) and waist-to-height ratio (WHtR) were independent predictors of MMEF. Exploratory mediation analysis identified statistical dependency patterns suggesting indirect associations of WHtR with MMEF through FABP4 (21.1%) and of FABP4 with MMEF through L-acetylcarnitine (13.9%), though cross-sectional design precludes causal inference. A three-biomarker model (FABP4 + L-acetylcarnitine + interleukin-6 [IL-6]) showed an apparent area under the curve (AUC) of 0.981; leave-one-out cross-validation (LOOCV) and bootstrap correction yielded AUCs of 0.904 and 0.952, respectively.</p> Conclusions <p>FABP4 and L-acetylcarnitine may be candidate biomarkers associated with small airway dysfunction in obese type 2 asthma. Over-representation of PPAR pathway members alongside lipid metabolic alterations provides a preliminary observational basis for future investigation. All findings require validation in independent, larger cohorts.</p>

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FABP4 and L-acetylcarnitine as candidate biomarkers for small airway dysfunction in children with obese type 2 asthma: a pilot cross-sectional multi-omics study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Zhiyuan Wang,
  • Junlin Zhao,
  • Yanan Wang,
  • Qianqian Dai,
  • Shengmeng Qu,
  • Zhenzhen Guo,
  • Liang Ru

摘要

Background

Childhood obesity-associated asthma represents a distinct phenotype with incompletely understood metabolic mechanisms. This hypothesis-generating study aimed to screen candidate biomarkers associated with small airway dysfunction in children with obese type 2 asthma and explore preliminary associations between obesity-related metabolic alterations and airway function.

Methods

Thirty age- and sex-matched children with asthma (6–14 years) were enrolled: 15 with obese type 2 asthma and 15 with non-obese asthma. Plasma samples underwent proteomic analysis using data-independent acquisition mass spectrometry and untargeted metabolomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analyses included multiple linear regression, mediation analysis, receiver operating characteristic (ROC) curve analysis, and nomogram construction.

Results

Proteomic analysis identified 176 differential proteins, with four enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Metabolomic analysis revealed 153 differential metabolites, predominantly lipids (28.3%), with L-acetylcarnitine notably elevated. Children with obese type 2 asthma exhibited significantly lower maximal mid-expiratory flow (MMEF) : 48.5% vs. 70.2% and elevated systemic inflammation. Fatty acid-binding protein 4 (FABP4) and waist-to-height ratio (WHtR) were independent predictors of MMEF. Exploratory mediation analysis identified statistical dependency patterns suggesting indirect associations of WHtR with MMEF through FABP4 (21.1%) and of FABP4 with MMEF through L-acetylcarnitine (13.9%), though cross-sectional design precludes causal inference. A three-biomarker model (FABP4 + L-acetylcarnitine + interleukin-6 [IL-6]) showed an apparent area under the curve (AUC) of 0.981; leave-one-out cross-validation (LOOCV) and bootstrap correction yielded AUCs of 0.904 and 0.952, respectively.

Conclusions

FABP4 and L-acetylcarnitine may be candidate biomarkers associated with small airway dysfunction in obese type 2 asthma. Over-representation of PPAR pathway members alongside lipid metabolic alterations provides a preliminary observational basis for future investigation. All findings require validation in independent, larger cohorts.