Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators.
20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre-treatment with saline nasal spray (placebo), then NAC with 14 days pre-treatment with INCS (220 μg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early-phase allergy biomarkers (≤30 min) and IL-13 and eosinophil cell counts as late-phase allergy biomarkers (3-7 h) in serum and nasal samples. Period-period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS.
NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL-13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC-induced IL-13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS.
NAC-induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation.

BACKGROUND: Predominantly, 2 animal models are used for allergic rhinitis (AR), which are established by intraperitoneal (IP) injection plus local challenge and nasal-only delivery. The differences between these 2 models are not fully understood. Moreover, dose-response relationship to allergens remains unclear.
METHODS: In this study, mice were sensitized by nasal drops (without adjuvant, once daily for 9 weeks) to set up a nasal-only delivery AR model. Five different doses of ovalbumin (OVA) nasal drops were served to explore the dose-response to allergens. Allergic symptoms, serum antibodies (IgE, IgG2a, and IgG1), spleen supernatant and nasal lavage fluid (NALF) cytokines (IL-4, IL-5, and IFN-r), and infiltrated eosinophils of the nasal mucosa were observed.
RESULTS: The allergic symptoms, serum antibodies, cytokines, and infiltrated eosinophils were significantly higher in the high OVA concentration compared with those of the control group. Different OVA concentrations associated with the severity of allergy. Within a certain concentration range, OVA concentration positively related to the severity of symptoms, IgE antibody level, and Th2 bias. Meanwhile, serum antibodies (IgE and IgG1) and cytokines (IL-4, IL-5 in spleen and IL-4 in NALF) were significantly higher in the classical IP injection group than in the nasal drip groups.
CONCLUSIONS: The IP injection model and the nasal-only delivery model are 2 typical models for AR that causes a different immune response. A positive dose-response relationship in the nasal-only delivery model is observed from 25 mg/mL to 0.025 mg/mL.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.