Characterizing the symptomatology and pathophysiology of allergic rhinitis using a nasal allergen challenge model – a subset of the allergic rhinitis microbiome study

Linton, S., Hossenbaccus, L., Davis, A. et al.  Allergy Asthma Clin Immunol 21, 36 (2025). https://doi.org/10.1186/s13223-025-00980-5

Abstract

Background

Since 2015, our nasal allergen challenge (NAC) protocol has been used to investigate the pathophysiology of allergic rhinitis (AR) with various allergens. However, we have yet to publish a comprehensive examination of the pathophysiology associated with AR to ragweed pollen.

Methods

Nineteen ragweed pollen allergic and 12 healthy (nonallergic) control participants from Kingston, Ontario, Canada, completed the NAC to ragweed pollen extract out-of-season. Total nasal symptom score (TNSS) and percent fall in peak nasal inspiratory flow (PNIF) were collected up to 48 h post-exposure. Nasal fluid and serum samples were collected post-exposure, and white blood cell differential counts, serum ragweed-specific and total immunoglobulin-E (IgE), and nasal cytokine concentrations were analyzed. Statistical tests were performed using GraphPad Prism 10.4.0.

Results

Clinical symptoms induced by nasal allergen challenge (NAC)
with Ragweed pollen

The mean TNSS and percent PNIF fall from baseline were significantly higher in participants with ragweed pollen allergy compared to nonallergic controls up to 24 h (P ≤ 0.05) and 12 h (P ≤ 0.05) post-NAC, respectively.

Nasal eosinophils significantly increased in allergic participants at 6 h (P = 0.0010) and 24 h (P = 0.0049), while peripheral blood eosinophil percentages decreased significantly at 6 h compared to baseline (P = 0.0499). The specific to total IgE ratio for allergic participants significantly increased 1 h and 24 h (P = 0.0022 and P = 0.0034, respectively) post-NAC, with a decrease at 6 h compared to both 1 h and 24 h (P = 0.0224 and P = 0.0316, respectively). Allergic and nonallergic participants had significantly different cytokine profiles, particularly IL-4, IL-5, IL-6, IL-13, MIP-1β, and TNF-α.

Conclusions

This study confirms the effectiveness of our NAC protocol in eliciting clinical and biological responses in ragweed-allergic participants, particularly highlighting eosinophil activity, IgE, and cytokine dynamics. Future research should investigate the roles of specific IgE, IL-4, and eosinophil activation in allergic inflammation. Additionally, this NAC study population provides a strong foundation for examining the nasal microbiome in AR. Longitudinal studies exploring the relationship between allergic responses and microbiome shifts could offer deeper insights into the underlying mechanisms of disease.

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