Multi-omics in Severe Asthma From Olive Pollen Allergy

Patients with severe olive pollen allergy exhibit characteristic sensitization profiles, marked by strong recognition of minor allergens like Ole e 7, and, more importantly, show poor clinical responses to pharmacological treatments and immunotherapy. Previous studies have revealed that these patients experience a permanent immunological dysfunction (notably, dysregulated effector T-cell function) leading to a systemic inflammatory state that persists beyond the pollen season. The hypothesis is that short-term treatment (6 months) with Dupilumab can stabilize and reverse the inflammatory state in patients with severe olive pollen allergy (Project PI22/01737), enabling them to transition to conventional allergen immunotherapy. This study aims to deepen our understanding of the mechanisms underlying this immunological stabilization through multi-omics profiling (metabolomics, proteomics, transcriptomics) to explain the resolution of inflammation. Specifically, the goal is to restore an effective regulatory T-cell response, allowing for allergen-specific immunotherapy, which can be administered for three years in routine clinical practice as the only treatment capable of altering the disease's progression. Since immunotherapy relies on functional regulatory T-cell responses, this approach could validate a therapeutic strategy for these patients that modifies the disease long-term, breaking the cycle of chronic inflammation. This would reduce dependency on costly biologic treatments and significantly improve the quality of life.

Inclusion Criteria: * Patients ≥ 18 years old, residing in areas with high olive pollen exposure (exceeding 10,000 grains/m³ during the past five pollen seasons). * Proven allergy to olive pollen with predominant or isolated sensitization to Ole e 7. * Diagnosis of asthma that remains uncontrolled despite completing steps 5-6 of the GEMA guidelines during the olive pollen season. * Controlled asthma with a forced expiratory volume in 1 second (FEV1) \> 80% of the predicted normal value before starting subcutaneous immunotherapy (SCIT). Exclusion criteria 1. Having received allergen immunotherapy or biological treatment in the last 5 years. 2. Pregnant women. 3. Relevant comorbidity: cancer, myocardial infarction, severe immunological disorder . 4. Contraindications contained in the official technical data sheet for Dupixent® (dupilumab). 5. Contraindications of SCIT.