Relationship between longitudinal changes in type-2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Abstract

Background: Asthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated. Objective: To study longitudinal changes in type-2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics. Methods: Asthmatics (age 10–35 years, n = 253) were examined at baseline and at a follow-up visit, 43 [23–65] (median [range]) months later. Subjects were analyzed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen-specific IgE antibody (sIgE) concentration: <0.10, 0.10–0.34, and ≥0.35 kUA/L. The relationship between changes (Δ values) in type-2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B-Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined. Results: At follow up, FEV1 and FEV1/FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kUA/L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B-Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B-Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV1 (p < 0.05) and ΔFEV1/FVC% (p < 0.01). Sex-specific analysis showed that the independent association between ΔFeNO%, and ΔFEV1 remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02). Conclusion: In young asthmatics, IgE levels declined over 43 months, whereas FeNO and B-Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type-2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV1 in females.