Background: Mepolizumab improves asthma control in severe eosinophilic asthma (SEA). However, its multidimensional effects on airway and systemic biomarkers are still incompletely understood. Methods: In this prospective study, 15 SEA patients were evaluated at baseline (T-0), 6 (T-6), and 12 months (T-12) after starting mepolizumab. Lung function, FeNO values, asthma control, blood eosinophil count (BEC), cytokines, and metabolomic profiles (H-1-NMR) were evaluated in serum, nasal secretions, and exhaled breath condensate (EBC). Univariate and multivariate (PCA, OPLS-DA) analyses were performed. Results: Mepolizumab reduced exacerbations, from a median of 2 at T-0 to 0 at both T-6 (p = 0.001) and T-12 (p = 0.003). ACT improved from 18.7 +/- 4.7 at baseline to 23.0 +/- 2.8 at T-6 (p = 0.026) and 23.4 +/- 3.3 at T-12 (p = 0.032), while FEV1 increased by 270 mL at T-6 (p = 0.032) and remained stable at T-12. Median BEC decreased from 450.0 (350.0-560.0) to 65.0 (50.0-87.5) cells/mu L at T-6 and to 50.0 (35.0-160.0) at T-12 (p < 0.001), while FeNO showed a non-significant downward trend. IL-13 significantly decreased in serum and nasal secretions at T-6 and T-12, while IL-5 increased in nasal secretions at both timepoints and remained unchanged in serum. IL-2 showed opposite trends in serum and nasal samples, whereas GM-CSF and IFN-gamma increased in nasal secretions at T-12. Metabolomic profiling suggested compartment-specific changes, with decreased short-chain alcohols in EBC, increased amino acids in nasal secretions and serum at T-6, and elevated pyruvate in serum at T-12, although none reached statistical significance in univariate analysis. Conclusions: Mepolizumab induced consistent clinical, immunologic, and metabolic changes across compartments, supporting the use of integrated cytokine and H-1-NMR metabolomic profiling as a complementary approach for response assessment in SEA.
Cytokine and Metabolomic Signatures of Mepolizumab Response Across Upper and Lower Airway Compartments in Severe Eosinophilic Asthma: An Exploratory Analysis
Dina Visca;
2025-01-01
Abstract
Background: Mepolizumab improves asthma control in severe eosinophilic asthma (SEA). However, its multidimensional effects on airway and systemic biomarkers are still incompletely understood. Methods: In this prospective study, 15 SEA patients were evaluated at baseline (T-0), 6 (T-6), and 12 months (T-12) after starting mepolizumab. Lung function, FeNO values, asthma control, blood eosinophil count (BEC), cytokines, and metabolomic profiles (H-1-NMR) were evaluated in serum, nasal secretions, and exhaled breath condensate (EBC). Univariate and multivariate (PCA, OPLS-DA) analyses were performed. Results: Mepolizumab reduced exacerbations, from a median of 2 at T-0 to 0 at both T-6 (p = 0.001) and T-12 (p = 0.003). ACT improved from 18.7 +/- 4.7 at baseline to 23.0 +/- 2.8 at T-6 (p = 0.026) and 23.4 +/- 3.3 at T-12 (p = 0.032), while FEV1 increased by 270 mL at T-6 (p = 0.032) and remained stable at T-12. Median BEC decreased from 450.0 (350.0-560.0) to 65.0 (50.0-87.5) cells/mu L at T-6 and to 50.0 (35.0-160.0) at T-12 (p < 0.001), while FeNO showed a non-significant downward trend. IL-13 significantly decreased in serum and nasal secretions at T-6 and T-12, while IL-5 increased in nasal secretions at both timepoints and remained unchanged in serum. IL-2 showed opposite trends in serum and nasal samples, whereas GM-CSF and IFN-gamma increased in nasal secretions at T-12. Metabolomic profiling suggested compartment-specific changes, with decreased short-chain alcohols in EBC, increased amino acids in nasal secretions and serum at T-6, and elevated pyruvate in serum at T-12, although none reached statistical significance in univariate analysis. Conclusions: Mepolizumab induced consistent clinical, immunologic, and metabolic changes across compartments, supporting the use of integrated cytokine and H-1-NMR metabolomic profiling as a complementary approach for response assessment in SEA.
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