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.
Birch pollen sensitized subjects
Moderate to severe allergic rhinitis to birch pollen allergen for at least two seasons according to their medical history
Sensitization to Bet v 1 (Bet v 1 specific IgE: 3.5 kU/L or higher as specified by UniCAP-FEIA)
CD203c or CD63 upregulation upon challenge with Bet v 1 in flow cytometric basophil activation tests (≥20% upregulation of CD63 or CD203c upon Bet v 1 stimulation in comparison with unstimulated controls as measured by flow cytometry)
Evidence of acute, chronic, malignant or general diseases- assessed by asking the patient (e.g. Did you suffer or are you currently suffering from any malignant or generalised disease? Did you suffer or are you currently suffering from any chronic disease? Did you have any acute disease in the past two weeks?).
A History of anaphylaxis.
Utilization of leukotriene modifiers.
Utilization of long-acting antihistamines.
Parallel
Blood sampling
Procedure/SurgeryBlood samples will be taken by puncture of the antecubital vein for peripheral blood mononuclear cells (PBMCs) isolation, cytokines measurement, and flow cytometry analysis
Nasal biopsies
Procedure/SurgeryNasal 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
Nasal specimen collection
Biological/VaccineNasal specimen collection will be conducted. Nasosorption FXi/PU (containing a synthetic absorptive matrix (SAM)) will be obtained.
Mucosal RNA sampling
Procedure/SurgeryA 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
Intranasal challenge
Procedure/SurgeryThe 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.
Skin prick test
Procedure/SurgeryIn 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.
Peak Nasal Inspiratory Flow (PNIF)
Procedure/SurgeryThe 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
Pregnancy test
Biological/VaccineIn 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.
Quantification of IgE producing cells
Quantification of the number of IgE producing cells in blood and nasal biopsies (Number of IgE producing cells of total cells) by flow cytometry and microscopy
Click on the lead sponsor to view all of their trials.
