Birch pollen allergy in Europe.

Birch and other related trees of the families Betulaceae and Fagaceae (alder, hazel, oak, hornbeam, chestnut, and beech) constitute the birch homologous group. This grouping is primarily based on the extensive IgE cross-reactivity of allergen homologs to the major birch allergen Bet v 1. Birch pollen is the most dominant tree pollen in Northern and Central Europe and is a major cause of allergic rhinitis and, possibly, asthma symptoms. Over the last few decades, levels of birch pollen have risen and the period of exposure has increased due to climate changes. Subsequently, the prevalence of birch pollen sensitization has also increased. The cross-reactivity and sequential pollen seasons within the birch homologous group create a prolonged symptomatic allergy period beyond birch pollen alone. Furthermore, many plant food allergens contain homologs to Bet v 1, meaning that the majority of patients with birch pollen allergy suffer from secondary pollen food syndrome (PFS). As a result, the negative impact on health-related quality of life (HRQoL) in patients allergic to birch pollen is significant. The purpose of this manuscript was to narratively review topics of interest such as taxonomy, cross-reactivity, prevalence, clinical relevance, PFS, and HRQoL with regard to birch pollen allergy from a European perspective.

Side-effects of allergen-specific immunotherapy: a prospective multi-centre study.

BACKGROUND AND OBJECTIVE: The safety of allergen-specific immunotherapy (SIT) is a parameter of great interest in the overall assessment of the treatment. A clinical database was developed in order to obtain early warnings of changes in the frequency and severity of side-effects and sufficient data for the evaluation of possible risk factors. METHODS: During a 3-year period, four allergy centres in Copenhagen, Denmark, included data from all patients initiating SIT to a common database. Information on initial allergic symptoms, allergens used for treatment, treatment regimens and systemic side-effects (SSEs) during the build-up phase was collected. RESULTS: A total of 1,038 patients received treatment with 1,709 allergens (timothy, birch, mugwort, house dust mite (HDM), cat, and wasp and bee venom), 23,047 injections in total. Most SIT patients completed the updosing phase without side-effects, but there was a significant difference between allergens: wasp (89%), birch (82%), HDM (81%), cat (74%) and grass (70%) (P=0.004). A total of 582 SSEs were registered in 341 patients. Most side-effects were mild grade 2 reactions (78%). A difference in severity between allergens was observed (P=0.02), with grass giving most problems. The type of allergen but not patient- or centre-related parameters seemed predictive of side-effects. CONCLUSIONS: Allergen extracts differ in their tendency to produce side-effects. Multi-centre studies like the present one allow more patients to be evaluated, and thereby provide a more efficient surveillance of side-effects. Online Internet-based registration to a central national database of every allergen injection would be an even more powerful tool for evaluation of risk factors and surveillance of side-effects.

Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. II. Side-effects.

BACKGROUND: Allergen-specific immunotherapy (IT) involves the risk of side-effects. Different side-effect profiles have been reported for different allergens, and it would be of great benefit to be able more precisely to predict patient- and allergen-related risk factors. METHODS: Fifty-two patients with rhinoconjunctivitis and allergy to birch as well as grass pollen participated in a 3-year IT study, with a baseline year followed by 2 years of treatment. During the first treatment year, the patients received double-blinded IT with either birch (Betula verrucosa) or grass (Phleum pratense) pollen extracts adsorbed to aluminum hydroxide. The following year, the other allergen extract was added. Assessment of systemic reactions (SRs) was performed, and related to patient pretreatment parameters such as seasonal symptoms and medication requirement, skin prick test (SPT), conjunctival provocation test (CPT), nasal provocation test (NPT), total and specific IgE, basophil histamine release (HR), eosinophil count (EOS), eosinophil cationic protein (ECP), and eosinophil protein X (EPX). RESULTS: In total, 44 and 47 patients started IT with birch- and grass-pollen extracts, respectively. All SRs occurred during the dose-increase phase. No life-threatening SRs were observed. There were a higher number of patients with SRs during IT with grass pollen than IT with birch pollen, 21 vs five patients (P<0.001), with SRs to 3.3% of grass-pollen injections compared to 0.7% of birch-pollen injections (P<0.0001). The SRs of birch-pollen IT were mild, consisting of rhinoconjunctivitis and oral-pharyngeal itching, whereas asthma and urticaria episodes were observed in the grass-pollen IT. No difference was found in sensitivity to birch and grass, when measured by SPT, CPT, NPT, specific IgE, or HR, and no difference was found in age, duration of allergic symptoms, prevalence of asthma, mean seasonal birch/grass symptom score, eye-drop use, or antihistamine or prednisolone intake between the group with and without subsequent SRs to IT. No difference was found in EOS, serum ECP, or EPX, between the group with and without subsequent SRs to IT. CONCLUSIONS: IT with grass-pollen extract seems to be associated with a higher number and more severe SRs than birch-pollen IT. Neither demographic data nor diagnostic tests of allergy such as specific IgE, HR, SPT, CPT, and NPT could identify the patients with subsequent SRs.

Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. I. Efficacy estimated by a model reducing the bias of annual differences in pollen counts.

BACKGROUND: Evaluation of the efficacy of allergen-specific immunotherapy (IT) with pollen extracts is complicated by annual variation in pollen intensity. Our study aimed to evaluate the efficacy of birch and grass IT, taking into consideration these variations. METHODS: After 1 year of observation, 52 patients with rhinoconjunctivitis and allergy to birch as well as grass pollen were allocated to double-blinded clustered IT with aluminum-adsorbed extract produced from either birch (Betula verrucosa) pollen or grass (PIleum pratense) pollen. After 1 year of treatment, the patients continued IT with their original extract and also received the other extract. During the three consecutive pollen seasons, the rhinoconjunctivitis symptom score and the use of antihistamines, eye-drops, and oral prednisolone were recorded. Longitudinal data analysis was used to investigate the relation between different pollen counts and the magnitude of clinical efficacy. RESULTS: An effect of IT was found on symptom score, antihistamine intake, and eye-drop use for both birch and grass (P values <0.05). The mean reduction in symptom score/medication by IT ranged from 24% to 95%, depending on mean seasonal pollen counts. A minimum mean seasonal grass-pollen count of 20-30 pollen grains m3 was required for the efficacy of grass IT to emerge. CONCLUSIONS: A model was developed for evaluation of efficacy in longitudinal IT studies, taking the differences in annual pollen counts into consideration. The model showed a significant beneficial role of pollen IT in rhinoconjunctivitis patients allergic to birch and grass pollen.

Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis.

BACKGROUND: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen. METHODS: The above tests were performed on blood samples obtained from 49 allergic rhinitis patients during the birch-pollen season, during the grass-pollen season, and after the seasons. Symptom-medication diaries were filled in during both pollen seasons. We used partial least square (PLS) analysis to establish an optimal statistical link between the symptom score and medication and the laboratory tests, in an investigator-independent way. RESULTS: Increases in specific IgE, basophil histamine release, eosinophil counts, serum ECP and EPX, and plasma EPX were observed from the birch-pollen season to the grass-pollen season, followed by a decrease from the grass-pollen season to after the pollen seasons, except for the specific IgE. No seasonal changes in plasma ECP and total IgE were seen. The PLS analysis found a relationship between symptom score and medication and the aggregate laboratory tests (F-test value 40.2, correlation 0.34 for the cumulative relation). However, the variation in laboratory tests could explain only half of the total variation in symptoms and less than a quarter of the total variation in medication. The symptom score and, to a minor degree, medication were especially correlated with the basophil histamine-release results, with a decreasing relevance of specific IgE, eosinophil counts, total IgE, serum and plasma EPX, and serum ECP. Plasma ECP was not related to the symptom score and medication. CONCLUSIONS: A significant relationship between the severity of allergic rhinitis and various allergic inflammatory markers was found but could account for only a minor part of the variation in the patients' evaluation of their disease.