Biomarkers Could Reveal Small Airway Dysfunction in Childhood Asthma

Researchers have identified two potential biomarkers that could help detect small airway dysfunction in children with obesity-associated type 2 asthma, offering new insight into the metabolic mechanisms that may contribute to this distinct asthma phenotype.

The pilot study, published in BMC Pulmonary Medicine, combined proteomic and metabolomic analyses to investigate differences between children with obese type 2 asthma and those with asthma who did not have obesity. The findings highlighted fatty acid-binding protein 4 (FABP4) and L-acetylcarnitine as candidate markers associated with impaired small airway function.

Multi-Omics Analysis Reveals Metabolic Differences

The cross-sectional study included 30 children aged 6–14 years, comprising 15 with obese type 2 asthma and 15 age- and sex-matched children with non-obese asthma.

Researchers analysed plasma samples using mass spectrometry-based proteomics and untargeted metabolomics. The analysis identified 176 proteins and 153 metabolites that differed between the two groups.

Four of the differential proteins were enriched in the peroxisome proliferator-activated receptor (PPAR) signalling pathway, which plays an important role in lipid metabolism and inflammation. More than one-quarter of the differential metabolites were lipids, with L-acetylcarnitine notably elevated among children with obese type 2 asthma.

Obesity-Associated Asthma Linked to Poorer Airway Function

Children with obese type 2 asthma demonstrated substantially poorer small airway function. Their maximal mid-expiratory flow (MMEF) averaged 48.5%, compared with 70.2% among children with non-obese asthma.

The obesity-associated group also demonstrated greater systemic inflammation.

Further analysis identified FABP4 and waist-to-height ratio as independent predictors of MMEF. Exploratory analyses additionally suggested statistical links between waist-to-height ratio, FABP4, L-acetylcarnitine, and airway function, although the researchers cautioned that the cross-sectional design means causal relationships cannot be established.

Biomarker Combination Shows Strong Predictive Performance

Researchers subsequently developed a model combining FABP4, L-acetylcarnitine, and the inflammatory marker interleukin-6 (IL-6).

The three-biomarker model achieved an apparent area under the receiver operating characteristic curve of 0.981. Performance remained high following leave-one-out cross-validation and bootstrap correction, with AUC values of 0.904 and 0.952, respectively.

The findings suggest that combining metabolic and inflammatory biomarkers could eventually help identify children with obesity-associated asthma who are particularly vulnerable to small airway impairment.

Findings Could Inform More Personalised Asthma Care

The study adds to growing evidence that obesity-associated childhood asthma may involve metabolic abnormalities extending beyond conventional airway inflammation.

In particular, alterations involving FABP4, L-acetylcarnitine, lipid metabolism, and PPAR signalling could provide new avenues for investigating how obesity influences airway disease.

However, the researchers emphasised that the study was exploratory and included only 30 children. Larger, independent and prospective studies will therefore be needed to validate the biomarkers and determine whether they can reliably predict small airway dysfunction or inform clinical management.

If confirmed, the findings could ultimately contribute to more precise identification and monitoring of children with obesity-associated asthma and provide potential targets for future therapeutic research.

Reference

Wang Z  et al. 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. BMC Pulm Med. 2026;DOI: 10.1186/s12890-026-04541-3.