Predicting the start, peak and end of the Betula pollen season in Bavaria, Germany.

Betula pollen is frequently found in the atmosphere of central and northern Europe. Betula pollen are health relevant as they cause severe allergic reactions in the population. We developed models of thermal requirements to predict start, peak and end dates of the Betula main pollen season for Bavaria (Germany). Betula pollen data of one season from 19 locations were used to train the models. Estimated dates were compared with observed dates, and the errors were spatially represented. External validation was carried out with time series datasets of 3 different locations (36years in total). RESULTS: The temperature requirements to detonate the main pollen season proved non-linear. For the start date model (error of 8,75days during external validation), daily mean temperatures above a threshold of 10°C from 28th of February onwards were the most relevant. The peak model (error of 3.58days) takes into account mean daily temperatures accumulated since the first date of the main pollen season in which the daily average temperature exceeded 11°C. The end model (error of 3.75days) takes into account all temperatures accumulated since the start of the main pollen season. CONCLUSION: These models perform predictions that enable the allergic population to better manage their disease. With the established relationship between temperatures and pollen season dates, changes in the phenological behaviour of Betula species due to climate change can be also estimated in future studies by taking into account the different climate scenarios proposed by previous climate change studies.

New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.

Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis - an EAACI position paper.

BACKGROUND: Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. METHODS: A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. RESULTS: The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for 'pollen season', 'high pollen season' (or 'peak pollen period') and 'high pollen days'. CONCLUSION: This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.

Personalized symptoms forecasting for pollen-induced allergic rhinitis sufferers.

Hay fever is a pollen-induced allergic reaction that strongly affects the overall quality of life of many individuals. The disorder may vary in severity and symptoms depending on patient-specific factors such as genetic disposition, individual threshold of pollen concentration levels, medication, former immunotherapy, and others. Thus, information services that improve the quality of life of hay fever sufferers must address the needs of each individual separately. In this paper, we demonstrate the development of information services that offer personalized pollen-induced symptoms forecasts. The backbone of these services consists of data of allergic symptoms reported by the users of the Personal Hay Fever Diary system and pollen concentration levels (European Aeroallergen Network) in several sampling sites. Data were analyzed using computational intelligence methods, resulting in highly customizable forecasting models that offer personalized warnings to users of the Patient Hay Fever Diary system. The overall system performance for the pilot area (Vienna and Lower Austria) reached a correlation coefficient of r = 0.71 ± 0.17 (average ± standard deviation) in a sample of 219 users with major contribution to the Pollen Hay Fever Diary system and an overall performance of r = 0.66 ± 0.18 in a second sample of 393 users, with minor contribution to the system. These findings provide an example of combining data from different sources using advanced data engineering in order to develop innovative e-health services with the capacity to provide more direct and personalized information to allergic rhinitis sufferers.

Geographic and temporal variations in pollen exposure across Europe.

BACKGROUND: The EC-funded EuroPrevall project examined the prevalence of food allergy across Europe. A well-established factor in the occurrence of food allergy is primary sensitization to pollen. OBJECTIVE: To analyse geographic and temporal variations in pollen exposure, allowing the investigation of how these variations influence the prevalence and incidence of food allergies across Europe. METHODS: Airborne pollen data for two decades (1990-2009) were obtained from 13 monitoring sites located as close as possible to the EuroPrevall survey centres. Start dates, intensity and duration of Betulaceae, Oleaceae, Poaceae and Asteraceae pollen seasons were examined. Mean, slope of the regression, probability level (P) and dominant taxa (%) were calculated. Trends were considered significant at P < 0.05. RESULTS: On a European scale, Betulaceae, in particular Betula, is the most dominant pollen exposure, two folds higher than to Poaceae, and greater than five folds higher than to Oleaceae and Asteraceae. Only in Reykjavik, Madrid and Derby was Poaceae the dominant pollen, as was Oleaceae in Thessaloniki. Weed pollen (Asteraceae) was never dominant, exposure accounted for >10% of total pollen exposure only in Siauliai (Artemisia) and Legnano (Ambrosia). Consistent trends towards changing intensity or duration of exposure were not observed, possibly with the exception of (not significant) decreased exposure to Artemisia and increased exposure to Ambrosia. CONCLUSIONS: This is the first comprehensive study quantifying exposure to the major allergenic pollen families Betulaceae, Oleaceae, Poaceae and Asteraceae across Europe. These data can now be used for studies into patterns of sensitization and allergy to pollen and foods.

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma.

BACKGROUND: The treatment of allergic asthma by specific immunotherapy (SIT) is hampered by potential side-effects. OBJECTIVE: The aim of this study was to study the effect of omalizumab, a monoclonal anti-IgE antibody, in combination with SIT in patients with seasonal allergic rhinoconjunctivitis (SAR) and co-morbid seasonal allergic asthma (SAA) incompletely controlled by conventional pharmacotherapy. METHODS: A randomized, double-blind, placebo-controlled, multi-centre trial was performed to assess the efficacy and safety of omalizumab (Xolair) vs. placebo in combination with depigmented SIT (Depigoid) during the grass pollen season. Omalizumab or placebo was started 2 weeks before SIT; the whole treatment lasted 18 weeks. Primary endpoint was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use. RESULTS: A total of 140 patients (age 11-46 years) were randomized; and a total of 130 finished the study. Combination therapy reduced the symptom load by 39% (P=0.0464, Wilcoxon test) over SIT monotherapy. This difference was mainly due to reduced symptom severity (P=0.0044), while rescue medication use did not change significantly. Combination therapy also improved asthma control (Asthma Control Questionnaire, P=0.0295) and quality of life in the case of asthma (Asthma Quality of Life Questionnaire, P=0.0293) and rhinoconjunctivitis (Rhinoconjunctivitis Quality of Life Questionnaire, P=0.0537). Numbers of patients with 'excellent or good' treatment efficacy according to ratings of investigators (75.0% vs. 36.9%) or patients (78.5% vs. 46.1%) were markedly higher in the combination group than under SIT alone. CONCLUSION: Combination of omalizumab with SIT for treatment of patients with SAR and co-morbid SAA was safe and reduced the symptom load in a statistically significant and clinically meaningful manner.

A case-control study of the relation between plasma selenium and asthma in European populations: a GAL2EN project.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

[Allergy and lectins: action between IgE-mediated histamine release and glycoproteins from Viscum album L. (mistletoe)]. / Allergie und Lektine: Wechselwirkung zwischen IgE-vermittelter Histaminfreisetzung und Glykoproteinen aus Viscum album L. (Mistel).

Low-molecular constituents from Viscum album (toxic) release, in irritatively toxic manner, histamine from human leukocytes without destroying the cells (cytotox test). This histamine release is prevented by preincubation with viscum lectins. The viscum lectin blocks the Fc-portion of allergen-specific IgE against anti-IgE [125I]. Lectin also inhibits the allergen-specific histamine release from human leukocytes occurring through IgE; this can be demonstrated on leukocytes from patients with atopic extrinsic asthma. The inhibitory effect of lectin could also be due to a primary membrane effect, in addition to blockage of IgE.

[Isolation and characterization of mistletoe extracts (Viscum album L.). II. Effect of agglutinating and cytotoxic fractions on mouse ascites tumor cells]. / Isolierung und Charakterisierung von Inhaltsstoffen der Mistel (Viscum album L.). II. Wirkung von agglutinierenden und zytotoxischen Fraktionen auf Mäuse-Aszites-Tumorzellen

Lectin from mistletoe (Viscum album L.) was studied for its relations with the toxins from Viscum album, ascites tumor cells of mouse, and human immunoglobulins. Using affinity chromatography on glutaraldehyde-crosslinked IgG (human) from viscum crude extract, a fraction was isolated which exhibited full agglutination capacity and high toxicity. The supernatant showed no agglutination capacity but a strong toxic effect on mouse ascites tumor cells. This toxic effect could not be influenced by further additions of insolubilized IgG. Chromatography on DEAE cellulose also gave agglutinating fractions with toxic effects and a non-agglutinating toxic portion. Column chromatography on Sephadex G 75 allowed separation of toxic from agglutinating components. The molecular weight of the toxin remaining after lectin removal was above 10,000. Lectin was found to bind more readily to mouse ascites tumor cells than to erythrocytes.