Metabolomics identify serum biomarkers for predicting acute exacerbation and severity of bronchiectasis

Abstract

Background

Bronchiectasis (BE) is a chronic respiratory disease. Acute BE exacerbation caused by recurrent infections can lead to hemoptysis and even asphyxia, with high mortality and long hospitalization. This study aimed to identify novel diagnostic metabolic biomarkers for predicting acute exacerbation and severity of BE.

Methods

A liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomic analysis was performed for serum samples from 45 patients with acute BE exacerbation and 15 healthy controls. The diagnostic value of the candidate metabolites was evaluated using receiver operating characteristic (ROC) curves.

Results

Based on bronchiectasis severity index (BSI) scores, patients with acute BE exacerbation were classified into mild, moderate, and severe BE groups. Compared to healthy controls, the abundance of 4-acetamidobutyric acid was elevated in the mild, moderate, and severe groups (p < 0.05), with no significant difference among the three groups. In the severe BE group, the abundances of taurochenodecoxycholic acid, oleamide, hexadecanamide, and glycodeoxycholic acid were significantly elevated from those in mild and moderate BE groups (p < 0.05), with Youden index (YI) ≥ 0.8 for all metabolites; the combination of these 4 metabolites had an area under the ROC curve (AUROC) of 0.99, a sensitivity of 100 % and a specificity of 93.3 % for identifying severe BE. Pathway analysis reveals that abnormally enriched metabolites in BE patients are associated with PI3K-Akt signaling pathway, mTOR signaling pathway, FoxO signaling pathway, renin-angiotensin system signaling pathway, asthma signaling pathway, and FcεRI signaling pathway, where prostaglandin D2 exerts direct or indirect impacts on these pathways.

Conclusion

4-Acetamidobutyric acid can serve as a biomarker for predicting acute BE exacerbation, while taurochenodecoxycholic acid, oleamide, hexadecanamide, and glycodeoxycholic acid are robust biomarkers for predicting severe BE. Prostaglandin D2 plays a crucial role in promoting the pathogenesis of pulmonary inflammatory cell recruitment, cell autophagy, and pulmonary fibrosis during acute BE exacerbation. Overall, this study identifies biomarkers for predicting acute BE exacerbation and provides new targets for drug development.