Contribution of Nasal IgE Production to the Boost of Systemic Allergen-specific IgE Upon Nasal Allergen Contact

Summary

IgE-associated allergies are consistently on the rise forming an enormous wellbeing concern and affecting about 25% of the population around the world, with main prevalence in developed nations. Birch pollen is one important allergen driving allergic conjunctivitis and rhinitis. The characteristics and location IgE producing cells in the nose and their contribution to the subsequent increase in allergen-specific IgE levels in the serum have so far poorly been investigated. Understanding these mechanisms is critical for the development of new therapeutic approaches and is thus the aim of the proposed study. Thus, the investigators plan to conduct a two-armed study of a randomized placebo-controlled double-blind nasal allergen provocation where 30 patients will be provoked with birch pollen extract (n=20) or placebo (n=10) out of the birch pollen season (October) and follow them closely for up to 4 months. Therefore, the objective of this study is to investigate the localization and characteristics of IgE producing cells in the nasal mucosa contributing to the allergen-induced boosts of specific serum IgE upon natural and controlled nasal allergen exposure.

Conditions

• Allergy

Interventions

PROCEDURE

Blood sampling

Blood samples will be taken by puncture of the antecubital vein for peripheral blood mononuclear cells (PBMCs) isolation, cytokines measurement, and flow cytometry analysis

PROCEDURE

Nasal biopsies

Nasal biopsies will be taken from the lower fringe of the inferior turbinate, approximately 1-2cm from the anterior curved edge for RNA sequencing and confocal microscopy staining

BIOLOGICAL

Nasal specimen collection

Nasal specimen collection will be conducted. Nasosorption FXi/PU (containing a synthetic absorptive matrix (SAM)) will be obtained.

PROCEDURE

Mucosal RNA sampling

A 10 cm nasal curette will be used (Rhino-Probe, Arlington Scientific, USA). The curette is brought to lie against the mid-inferior portion of the inferior turbinate under direct visualisation. The curette is rubbed against the mucosal surface, going outwards. To ensure successful sample acquisition, this motion will be repeated 2-3 times

PROCEDURE

Intranasal challenge

The extract of birch pollen (Allergopharma, Vienna, Austria) will be freshly diluted in a 0.9 percent sterile sodium chloride solution and administered by means of a metered pump. The allergen will be administered supplying 15 μl per puff to both nostrils. Azelastine nasal spray or desloratadine 5mg will be given if the patient suffers from nasal or eye symptoms after the challenge. Equivalent amount of saline without allergens will be given to the control group.

PROCEDURE

Skin prick test

In order to evaluate the patient's sensitization profile at the screening visit, a regular skin prick test will be conducted with commercial birch pollen extract and a panel of allergens used in routine diagnosis in the allergy clinic of the ear, nose, and throat (ENT) department. Titrated skin prick test: Titrated skin prick test (SPT) to birch pollen extract is conducted by using increasing dilutions up to 1:100 000. As a result, it is possible to determine the lowest concentration that leads in a skin reaction.

PROCEDURE

Peak Nasal Inspiratory Flow (PNIF)

The functionality and convenience of the PNIF presents a rare opportunity to rapidly obtain objective measurements of nasal peak inspiratory flow. It was also validated during other nasal allergen challenge as a study tool

BIOLOGICAL

Pregnancy test

In female patients, a regular urine pregnancy test will rule out pregnancy. The test will be conducted at the screening visit before the first skin prick test and then once a month afterwards.

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Sven Schneider, MD · Medical University of Vienna

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-11-11

Primary Completion

2026-01-31

Completion

2026-09-30

Countries

• Austria

Study Locations