The Effects of Immunotherapy in the Nose (Birch11)

Allergic rhinitis might be caused by decreased resistance of nasal barrier to allergens and other environmental insults. About 20 % of the European population suffers from pollen allergies. Birch pollen allergic rhinitis is the most common allergic disease in the Scandinavia and it exists widely also in the Central Europe. Suffering and high costs of pollen allergies may be reduced by understanding the molecular biology of the nasal barriers during allergic response. Our aim is to observe the effect of season and birch pollen immunotherapy on the molecular biology of nasal epithelium and the microbiome.

This is a controlled study with an intervention arm, and a control group of healthy volunteers. The population is composed of nonsmoking healthy adults and patients having birch or timothy pollen allergy with rhinoconjuctivitis symptoms and without other diseases. The diagnosis of pollen allergy is verified with positive history, skin prick test, and allergen specific IgE antibodies. Subjects undergo a spirometry with a bronchodilatator test and a histamine challenge. Quality of life and patient history data is collected by questionnaires. Four peripheral blood samples, as well as nasal cell swabs from nasal mucosa without local anesthesia are collected from each patient; in spring and winter before the group of the intervention arm starts with birch pollen subcutaneous immunotherapy; and during the first spring and winter when a subgroups has received the birch pollen immunotherapy. We plan to perform the following analyses for the nasal specimens: transcriptomics and their regulators, sequencing of 16SrRNA and RT-qPCR for assessing mucosal microbiome, mass spectrometry for analyses of proteins and protein-protein complexes, immunohistochemistry for tissue level localization and quantitation of proteins, in silico analyses for the data mining, integration and display. In addition we observe the alterations in inflammatory mediators after in vitro allergen activation of purified peripheral blood leukocytes by ELISA and real time qPCR.

Transcriptomics are evaluated By Next Generation Sequencing. The total number of differentially expressed transcripts are defined from nasal epithelial brushing samples taken at -6 months vs. at +6 months in the two subject groups. The subject groups are the Subcutaneous immunotherapy group and No immunotherapy group.

Visual analogue scale (VAS) was measured as 0-100 mm per each symptom question. VAS value 0 (mm) indicates no symptoms, and value 100 (mm) indicates the worst case. Total VAS score = sum of the VAS scores for the 41 symptoms The minimum value of the total VAS score is 0, and the maximum value is 4100. Relative change = [(measure at time +6 months - measure at time -6 months)]/measure at time -6 months * 100%. Measure = total VAS score

Inclusion Criteria: allergic rhinoconjunctivitis of birch pollen OR healthy controls Exclusion Criteria: smoking, asthma, any other disease than allergic rhinoconjunctivitis, requiring constant medication

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