Treatment Impact on Inflammatory Markers in Patients with Asthma and Allergic Bronchopulmonary Aspergillosis

Abstract

Abstract Allergic bronchopulmonary aspergillosis (ABPA) is a type 2 inflammatory disorder resulting from an exaggerated immune response to Aspergillus species, most frequently A. fumigatus, and occurring most commonly in patients with asthma. Systemic corticosteroids, antifungal agents, and increasingly biologic therapies modify the underlying inflammatory response; however, no single biomarker reliably reflects disease activity across all treatment classes. This review summarizes current evidence on treatment-associated changes in inflammatory biomarkers in patients with asthma and ABPA. Serum total IgE remains the most widely used biomarker for monitoring treatment response. A decline of ≥20% from baseline supports treatment response, whereas a ≥50% increase from the post-treatment baseline, accompanied by compatible clinical or radiological worsening, indicates an ABPA exacerbation. Accordingly, current guidelines incorporate total IgE into a multidimensional assessment rather than interpreting it in isolation. Nevertheless, changes in total IgE may be discordant with clinical and radiological improvement and can be difficult to interpret during anti-IgE therapy or biologics targeting interleukin (IL)-4/IL-13 or thymic stromal lymphopoietin pathways. A. fumigatus-specific IgE and IgG show inconsistent treatment-related trajectories. Peripheral blood eosinophil counts and fractional exhaled nitric oxide are strongly dependent on treatment mechanisms and may reflect pharmacodynamic target engagement rather than overall ABPA activity. Emerging biomarkers, including recombinant A. fumigatus allergens, thymus and activation-regulated chemokine, periostin, eotaxin, carcinoembryonic antigen, and eosinophil-derived neurotoxin, provide additional mechanistic insights. However, none have demonstrated sufficient longitudinal validation for routine monitoring. Overall, biomarker trajectories in ABPA are strongly influenced by treatment mechanisms and may be dissociated from clinical benefit. Although several inflammatory markers decline with treatment, no individual marker is sufficiently sensitive and specific to serve as a universal marker of immune response. Treatment response should be assessed by integrating clinical and radiological improvement with appropriately interpreted immunological biomarkers rather than relying on a single laboratory measurement. Future studies should develop and validate treatment-specific biomarker signatures that distinguish pharmacodynamic target engagement from genuine control of ABPA activity.