Eosinophil-Driven vs. Eosinophil-Associated Severe Asthma: Practical Implications for Target Treatment

Abstract

Severe asthma (SA) is a chronic inflammatory condition affecting approximately 10% of asthmatic patients, and eosinophils are considered key pathogenetic actors in a significant number of patients. Biological therapies have been demonstrated to improve asthma control by decreasing exacerbation rates and reducing the use of oral corticosteroids. In this context, phenotyping and endotyping patients with SA is essential for selecting the most effective therapeutic approach. For this purpose, biomarkers such as IgE, absolute blood eosinophil count, and fractional exhaled nitric oxide (FeNO) are crucial in defining a patient's inflammatory profile. Their integration provides a framework for classifying asthma into T2-high, T2-mild, or T2-low categories, guiding personalized treatment strategies. By incorporating multiple biomarkers into a unified model, it is possible to better stratify patients and optimize biologic therapy selection, paving the way for improved outcomes in SA management. This review aims to evaluate the role of phenotyping and endotyping SA patients, with particular attention to the impact of eosinophilic inflammation and combinatory biomarkers on decision-making processes for the selection of biological therapies.

Keywords: atopy biomarkers; biological therapies; eosinophils; personalized medicine; severe asthma; type 2 inflammation.

Figure 1

Proposed grading of T2 biomarkers and comorbidities routinely used for endo-phenotyping severe asthma patients. CRSwNP, chronic rhinosinusitis with nasal polyposis; SPT, skin prick tests; FeNO, fractional exhaled nitric oxide. Color legend: red, allergic asthma; yellow, eosinophilic asthma; orange, comorbidities.

Figure 2

Proposed algorithm for stratifying and tailoring the treatment of patients with varying degrees of eosinophilic and allergic status. OCS, oral corticosteroids. * In these cases, the possibility of hypereosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA) should be ruled out.