[Arachidonic acid metabolic characteristics of allergic bronchopulmonary aspergillosis and their value in differential diagnosis].

Abstract

Objective: To investigate the characteristics of 14 arachidonic acid (AA) metabolites in the serum of patients with allergic bronchopulmonary aspergillosis (ABPA), screen for differential metabolic biomarkers that can distinguish it from severe allergic asthma (SA), and construct a diagnostic model. Methods: A cross-sectional study was conducted. A total of 19 patients with ABPA, 19 patients with SA, and 19 healthy controls (HC) from the First Affiliated Hospital of Guangzhou Medical University between December 2024 and July 2025 were enrolled as the training set. Additionally, a validation set consisting of 12 SA patients and 12 ABPA patients was recruited from the same center between September to December 2025. Peripheral blood cell counts and immunological and biochemical parameters were measured in all participants. Absolute quantification of 14 AA metabolites in serum was performed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on 5-(diisopropylamino) pentylamine derivative. Differences among groups were compared to identify significantly altered metabolites. In the training set, a combined clinical and metabolic indicator model was constructed using binary logistic regression. The diagnostic performance, calibration and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis, respectively. The model was further validated in the validation set. Results: A total of 19 patients in the ABPA group were enrolled, aged 45 (33, 60) years, with 12 males; 19 patients in the SA group were aged 39 (29, 47) years, with 11 males; and 19 subjects in the HC group were aged 43 (34, 52) years, with 11 males. Compared with the SA group, patients with ABPA exhibited significantly higher levels of total IgE [1 578.00 (1 346.00, 2 538.00) U/ml vs 599.30 (382.20, 1 462.00) U/ml] and Aspergillus fumigatus-specific IgE (Af.sIgE) [4.93 (0.95, 8.41) kUA/L vs 0.27 (0.13, 2.17) kUA/L] (both P<0.05). Serum levels of arachidonic acid (AA), prostaglandin D₂ (PGD₂), leukotriene B₄ (LTB₄), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE were significantly higher in the ABPA group than in the HC group (all P<0.05). Moreover, PGD₂ [1.80 (0.82, 2.13) μg/L vs 0.63 (0.37, 1.15) μg/L] and 15-HETE levels [16.39 (11.15, 20.41) μg/L vs 9.31 (6.57, 10.86) μg/L] were significantly elevated in the ABPA group compared with the SA group. A four-indicator combined diagnostic model incorporating total IgE, Af.sIgE, PGD₂, and 15-HETE was constructed. In the training set, the area under the curve (AUC) of the four-indicator combined model was 0.96 (95%CI: 0.92-1.00), with a sensitivity of 0.93 and specificity of 0.95. In the validation set, the AUC was 0.91 (95%CI: 0.81-1.00), with a sensitivity of 0.92 and specificity of 0.83. Calibration curves showed good consistency for the four-indicator model across all datasets, and decision curve analysis indicated favorable clinical applicability. Conclusions: ABPA patients exhibit characteristic AA metabolic disorders, and their characteristically elevated serum PGD2 and 15-HETE are potential specific biomarkers for differentiating ABPA from SA. The constructed four-indicator combined model including total IgE, Af.sIgE, PGD₂, and 15-HETE has good diagnostic efficacy in differentiating ABPA from SA.