Team members:

Principal Investigator:

Dr Takao Fujisawa (Japan)

Co-Investigators:

Dr Norihiro Harada, Assembly Head (Japan)
Dr Chang-Keun Kim, Assembly Head-Elect (Republic of Korea)

Project term:

1 September 2025 – 31 August 2027

Project summary:

Allergen immunotherapy (AIT) is an evidence-based therapy for both allergic rhinitis (AR) and asthma [1, 2] and involves administering gradually increasing doses of offending allergens to a person with allergic disease. The eventual goal of AIT is reducing or eliminating adverse clinical responses to future allergen exposures [3]. AIT has been shown to reduce symptoms and medication use in patients with AR; however, the mechanisms of action are unclear. One possible mechanism is through its effect on Th2 responses, T cells closely related with eosinophils. Though some studies show inhibition of eosinophil increases during seasonal AR, others have produced contradictory results.

Subcutaneous SIT (SCIT) presents the risk of inducing local and systemic side effects as a result of allergen injection. Consequently, several recommendations have been made to minimize the risk of side effects [4]. There is a paucity of studies on efficacy of SCIT for allergic disease. Furthermore, there is a need for studies on the efficacy of SCIT for house dust mite (HDM) sensitivity, in particular, because in practice the benefits are not as easily perceived by patients and caregivers as SCIT for seasonal allergens like cedar. There is also a lack of objective markers for determining SCIT efficacy.

Eosinophils are multifunctional leukocytes and major effector cells of the allergic process. Measuring eosinophils has been the gold standard for treating and monitoring eosinophil-related diseases like asthma, atopic dermatitis, and allergic rhinitis. However, eosinophil numbers/percentages yield little information about eosinophil activity. Eosinophil activation leads to extracellular release of four granule proteins, with the most promising biomarker of the four being eosinophil-derived neurotoxin (EDN). EDN is more easily recovered from measuring instruments and cell surfaces than other eosinophil

biomarkers because of its weaker electrical charge [5]. EDN is known to be released from eosinophils at a greater efficiency [6], adding to its recoverability. EDN can be measured in several bodily fluids, including blood, urine, sputum, nasal secretions, and bronchoalveolar lavage. EDN is also stable for more than 1 year when frozen [7], adding to its utility as a biomarker. For these reasons, EDN has been identified as a good biomarker for many eosinophil-associated diseases like AR and asthma.

We aim to assess SCIT’s efficacy in reducing eosinophil activity, as measured by the eosinophil biomarker EDN, in Korean and Japanese pediatric patients with allergic asthma and rhinitis. Symptom and rescue medication use reduction and effect on lung function will also be investigated.