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.
- 1Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan Road, Xinshi District, Urumqi, Xinjiang, 830054, China.
- 2Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan Road, Xinshi District, Urumqi, Xinjiang, 830054, China. [email protected].
Abstract
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.
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BibTeX
@article{wang2026fabp4,
title = {{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.}},
author = {Zhiyuan Wang and Junlin Zhao and Yanan Wang and Qianqian Dai and Shengmeng Qu and Zhenzhen Guo and Liang Ru},
journal = {BMC pulmonary medicine},
year = {2026},
month = aug,
doi = {10.1186/s12890-026-04541-3},
url = {https://europepmc.org/article/MED/42968047},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Zhiyuan Wang
AU - Junlin Zhao
AU - Yanan Wang
AU - Qianqian Dai
AU - Shengmeng Qu
AU - Zhenzhen Guo
AU - Liang Ru
PY - 2026
DA - 2026/08/05
JO - BMC pulmonary medicine
DO - 10.1186/s12890-026-04541-3
UR - https://europepmc.org/article/MED/42968047
AB - 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.
SN - 1471-2466
ER -