Asthma Biomarkers

Abstract

Advances in the understanding of asthma pathophysiology have enabled the identification of distinct phenotypes and endotypes, the latter defined primarily by biomarkers that reflect specific inflammatory mechanisms. Asthma encompasses heterogeneous inflammatory processes that can be grouped into type 1 (T1) and type 2 (T2) inflammatory pathways. T1 inflammation is characterized by corticosteroid resistance, bronchial hyperreactivity, and predominance of cytokines such as IFN‑γ and TNF‑α, although no validated biomarkers are yet available for routine clinical use. In contrast, T2 inflammation involves the cytokines IL‑4, IL‑5, and IL‑13, triggered by epithelial alarmins (IL‑33, IL‑25, and TSLP), and is predominant in eosinophilic and allergic asthma, typically showing good response to corticosteroids and targeted biological therapies. Among T2 biomarkers, the most relevant are blood eosinophil counts, fractional exhaled nitric oxide (FeNO), total IgE, and aeroallergen‑specific IgEs. Eosinophils are essential for assessing inflammatory activity, exacerbation risk, and therapeutic decision‑making, particularly when indicating anti‑IL‑5 and anti‑IL‑5R biologics. Values ≥150 cells/µL suggest T2 inflammation, whereas levels ≥300 cells/µL are used to determine eligibility for biological therapies. FeNO reflects activation of the IL‑4/IL‑13 pathway and is useful for diagnosis, monitoring airway inflammation, and assessing treatment adherence. Values ≥20 ppb already indicate T2 inflammation according to GINA 2025. IgE plays a central role in the allergic response, promoting activation of mast cells and basophils; its measurement supports the identification of atopy and the indication of anti‑IgE therapy (omalizumab). Aeroallergen‑specific IgEs complement the diagnosis of allergic asthma and are associated with systemic and local inflammation, including higher FeNO and eosinophilia. Integrating these biomarkers enables accurate endotype stratification, optimization of therapeutic selection, and implementation of personalized medicine. Thus, biomarkers are indispensable tools in the updated management of asthma, allowing an individualized approach based on the predominant inflammatory pathway. Understanding the role of each biomarker in the disease’s inflammatory cascade, as well as their predictive value for disease activity and treatment response, is fundamental for the appropriate use of biologics and for improving clinical outcomes.