Modelling of airborne birch pollen over Central Europe - model evaluation and sensitivity analysis.

Introduction and Aim of the Study: During the birch pollen season, cross-reactions between the allergen Bet v 1 and the Mal d 1 allergen from apples can induce pollen-related food allergy (prFA), particularly after apple consumption. The aim of this study is to investigate the molecular mechanisms of this allergy and present effective treatment and prevention methods, which could significantly improve the quality of life for allergy sufferers. Review Methods: The PubMed database was used for the literature review. English search terms included: “allergy,” “apple varieties,” “birch pollinosis,” “allergen-specific immunotherapy,” “birch pollen-associated food allergy syndrome,” and “Mal d 1.” Overview of Current Knowledge: Birch pollen allergy is one of the most common pollen allergies, with the Bet v 1 protein responsible for cross-reactive allergic responses following apple consumption. In apples, the Mal d 1 allergen triggers these reactions, which is particularly significant in Central and Northern Europe. Apples with red flesh are considered hypoallergenic due to their low Mal d 1 content and are a beneficial choice for allergic individuals. Various immunotherapy approaches, including sublingual immunotherapy, are utilized effectively to alleviate symptoms and support allergen tolerance. Conclusion: Pollen-related food allergy associated with birch pollen significantly affects the daily lives of allergy sufferers, especially during the birch pollen season. Advances in molecular mechanism research have allowed the identification of apple varieties with lower allergenic potential, enabling their use in immunotherapy and offering hope for improving patients' quality of life.

Background: Pollen-Food Allergy Syndrome (PFAS) typically presents as mild oral symptoms but can rarely progress to systemic reactions. Pathogenesis-related proteins group 10 (PR-10) are proteins usually associated with oral allergy syndrome due to their thermolabile and gastrolabile properties. Case Presentation: We report a 12-year-old boy with birch pollen allergy who developed anaphylaxis after raw carrot consumption without identified cofactors. Previously, he experienced only oral allergy syndrome with raw carrot and fennel. Molecular diagnostics confirmed isolated PR-10 sensitization. The reaction occurred during birch pollen season, and the patient tolerated cooked carrot, consistent with PR-10's thermal instability. Conclusions: This case highlights how PFAS, typically characterized by mild and localized symptoms, can occasionally manifest with systemic reactions. High levels of specific IgE for Bet v 1 and pollen season may represent risk factors for systemic reactions in PFAS patients. Clinicians must be aware that allergies due to pollen cross-reactive allergens can be associated with systemic reactions.

How does geographic location affect birch and grass pollen seasons? A comparative study of Iceland (Akureyri) and Poland (Kraków)

BackgroundSubcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis.MethodsIn this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed.ResultsDuring the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% (p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% (p < 0.001) and 56.3% (p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% (p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group (p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, p < 0.0001).No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II).ConclusionsTreatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.

BackgroundAllergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT‐tablet in a paediatric population (5–17 years) with moderate‐to‐severe AR/C induced by pollen from birch and trees in the birch homologous group.MethodsNine hundred and fifty‐two subjects were randomized (1:1) to daily treatment with SQ tree SLIT‐tablet or placebo for up to 52 weeks and had free access to AR/C symptom‐relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS).ResultsSQ tree SLIT‐tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment‐related adverse events were mild or moderate local administration site reactions.ConclusionThis is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT‐tablet in tree pollen‐induced AR/C in a paediatric population (5–17 years).

Birch pollen-induced signatures in dendritic cells are maintained upon additional cytomegalovirus exposure

Mast cells (MCs) develop from a rare population of peripheral blood circulating MC progenitors (MCps). Here, we investigated whether the frequency of circulating MCps is altered in asthma patients sensitized to birch pollen during pollen season, compared to out of season. Asthma patients were examined during birch pollen season in late April to early June (May), and out of season in November-January. Spirometry measurements, asthma and allergy-related symptoms, asthma control questionnaire (ACQ), and asthma control test (ACT) scores were assessed at both time points. The MCp frequency was determined by flow cytometry in ficoll-separated blood samples from patients with positive birch pollen-specific IgE, and analyzed in relation to basic and disease parameters. The frequency of MCps per liter of blood was higher in May than in November (p = .004), particularly in women (p = .009). Patients that reported moderate to severe asthma symptoms (<.0001), nose or eye symptoms (p = .02; p = .01), or reduced asthma control (higher ACQ, p = .01) had higher MCp frequency in May than those that did not report this. These associations remained significant after adjusting for sex and BMI. The change in asthma control to a lower ACT score in May correlated with an increase in MCp frequency in May (p = .006, rho = 0.46). The data suggest that the frequency of MCps increases in symptomatic patients with allergic asthma. Our results unravel a link between asthma symptoms and circulating MCps, and bring new insight into the impact of natural allergen exposure on the expansion of MCs.

The intensity of birch pollen season is expressed by seasonal pollen integral (SPIn, the sum of the mean daily pollen concentration during the birch pollination period) and the amount of Bet v 1 allergen released per birch pollen grain expressed by pollen allergen potency (PAP). Betula pollen and Bet v 1 allergen were simultaneously measured in the air of Bratislava from 2019 to 2022 by using two Burkard traps (Hirst-type and cyclone) in order to evaluate the causes of the seasonal variation in the SPIn and PAP levels. The highest SPIn (19,975 pollen/m3) was observed in 2022 and the lowest one (1484 pollen/m3) in 2021. The average daily PAP level (4.0 pg Bet v 1/pollen) was highest in 2019 and lowest (2.5 pg Bet v 1/pollen) in 2020. We found that seasonal variation in SPIn was associated mainly with the changes in environmental conditions during the pre-season period, whereas the year-to-year variation in PAP levels was attributed to environmental conditions during both pre- and in-season periods. Our results indicate that rainy weather in June 2020 and cold overcast weather in January‒February 2021 resulted in low SPIn in 2021. On the other hand, dry weather in June 2021 and warm weather in January‒February 2022 resulted in high SPIn in 2022. The low average daily PAP level in 2020 was associated with (1) low levels of gaseous air pollutants in March, when the ripening of pollen takes place; (2) an earlier start of the birch main pollen season (MPS); and (3) dry weather during the MPS. On the other hand, high PAP level in 2019 was associated with higher levels of air pollutants in March and during the MPS.

The experimental seasonal forecasts of the INM-CM5 climate model were used as input data for the temperature-time phenological model of birch dusting. Within the framework of the joint model, a test technology was developed for seasonal forecasting of the timing of the beginning of birch dusting in the European territory of Russia. Verification of this technology on seasonal retrospective forecasts of the INM-CM5 model (1991–2019) showed an adequate reproduction of the birch dusting start dates calculated for the same period according to the ERA5 reanalysis. The mean systematic errors are ±2 days, and the spatial correlation coefficients are above +0.84. The forecasts of the date of dusting start in 2022, calculated from the experimental operational seasonal forecasts of the INM-CM5 model with a monthly lead-time and with a zero lead-time, are also evaluated. It is shown that the errors in forecasting the beginning of dusting are ±5–10 days, and the forecasts with a one-month lead-time have fewer errors. The obtained results allow us to conclude that the seasonal forecast of the surface temperature of the INM-CM5 model can be used as input information for the temperature-time phenological model for the operational forecast of the timing of the start of birch dusting in the European territory of Russia.

In the Polish population, the most common cause of allergic rhinitis (AR) in the spring is birch pollen. The aim of this study was to assess the basic characteristics of the birch pollen season in selected cities in central and northern Poland including Warsaw, Piotrkow Trybunalski, and Bydgoszcz in 2022, considering their clinical implications. Pollen monitoring was conducted using the volumetric method with the Hirst-type continuous volumetric sampler. Measurements were taken in 7-day cycles, and the microscopic analysis was performed for each 24-hour period. Results During the studied period, birch pollen posed a threat in the 2nd and 3rd decades of April and the 1st and 2nd decades of May. The birch pollination intensity was reflected by the very high values of maximum average daily pollen concentration 4102 pollen/m3 in Warsaw, 4389 pollen/m3 in Piotrkow Trybunalski, 3832 pollen/m3 in Bydgoszcz and the sum of the average daily pollen concentrations (i.e. Annual Pollen Integral, APIn) from 32439 in Bydgoszcz to 37638 in Warsaw, and long periods of exposure to high concentrations (2930 days). The pollen season 2022 is part of an alternating 2-year cycle of the birch pollen season intensity. The variability of parameters describing the dynamics of pollen seasons over years makes it necessary to monitor information on the pollen concentration in the air during the pollen season, both by the patients with inhalant allergy and their physicians.

BackgroundBirch pollen‐related apple allergy is the most frequent IgE‐mediated food allergy in Central‐Northern Europe with Mal d 1 as major allergen. Its concentration in apples varies with the cultivar and storage time. Year‐round appealing, hypoallergenic cultivars still are needed to satisfy the nutritional needs of affected individuals. We characterized three promising cultivars by multidisciplinary in vitro assays including long‐term storage and by clinical challenges of allergic individuals before and after the birch pollen season.MethodsProteins were extracted from fruits of ‘Santana’, ‘Golden Delicious’ (GD), and three genuine cultivars in November 2018 and April 2019. Mal d 1‐levels were analysed by mass spectrometry, SDS‐PAGE, immunoblotting, competitive ELISA, and basophil activation tests. Twenty‐eight allergic individuals underwent single‐blinded open food challenges and skin testing with the cultivars and birch pollen in November 2018 and May 2019. Allergen‐specific IgE‐levels were determined.ResultsAfter storage all cultivars except ‘Santana’ were of appealing appearance and taste. Their Mal d 1 content had increased, also reflected by significantly amplified basophil activation and stronger reactions in clinical challenges. Besides, individuals showed boosted reactivity after pollen exposure indicated by enhanced allergen‐specific IgE‐levels and skin reactions to birch pollen. Still, all cultivars remained significantly less allergenic than GD and comparable to Santana in November 2018 in all assessments except for skin testing.ConclusionsCombined expertise in pomology and allergology identified promising new cultivars for allergic consumers. The evaluation of hypoallergenic apples should incorporate long‐term storage and birch pollen exposure. Basophil activation tests may be suitable in the selection of promising cultivars for oral challenges.

IntroductionThere is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.MethodsPatients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5‐grass allergen extracts (10,000 SQ units/ml, ALK‐Abelló), or birch and placebo or 5‐grass and placebo by ultrasound‐guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen‐induced cytokine and chemokine production were analysed by flow cytometry and Luminex.ResultsThe three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch‐induced IL‐10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.ConclusionsIntralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.Clinical Trial Registration: EudraCT (2013‐004726‐28).

The study aims to monitor the birch pollen season in selected Polish cities: Bialystok, Bydgoszcz, Cracow, Lublin, Olsztyn, Opole, Sosnowiec, Szczecin, Warsaw, Wroclaw and Zielona Gora in 2021. Pollen concentrations were recorded using a Burkard type sampler operating in a continuous volumetric mode. The birch pollen season of 2021 started during the first and second decade of April. In south-western Poland it began about 10 days earlier (April 7th or 10th) than in north-eastern regions (April 18th or 19th). The average length of the season was 31 days. The highest daily concentrations and annual pollen grains sum (seasonal pollen integral) were the most variable season characteristics. The maximum concentrations of birch pollen were recorded between April 21st (in Wroclaw) and May 1st (in Sosnowiec and Warsaw). It ranged from 222 p/m3 in Cracow up to 1997 p/m3 in Wroclaw. SPI was the lowest in Cracow (1573) and Sosnowiec (1763) and the highest in Bydgoszcz (5474) and Wroclaw (5072). The longest exposure to high concentrations of birch pollen, lasting 16–18 days, was detected in Szczecin, Olsztyn and Bydgoszcz. The abundance of birch pollen in Poland in 2021 was not as high as in 2019 and 2020, which, combined with the protective effect of mouth and nose masks due to COVID-19 pandemic, may have resulted in less severe allergy symptoms in sensitized individuals than in previous years.

In this work, the HYSPLIT model was used to reproduce birch pollen concentrations in Poland for the years 2015 and 2016, where there was significant variation in terms of pollen concentrations and start/end dates of the pollen season. The analysis of pollen observations showed that the seasonal pollen integral (SPIn) was low in 2015 with a shorter season compared to 2016. In 2016, SPIn was unusually high. The HYSPLIT model simulation, with a one-hour temporal resolution, was conducted during the birch pollen season (from March to May) for 2015 and 2016. Meteorological data were obtained from the WRF model. The birch coverage map of the European Forest Institute was used. The emission, introduced to the model, covered Central Europe with a resolution of 0.3° × 0.3°. The results were compared to data from 11 observation stations in Poland. The measured birch pollen concentrations for 2015 were overestimated by HYSPLIT at 8 of the 11 stations (normalized mean bias/NMB from 0.13 to 2.53) and underestimated for three stations (NMB from − 0.44 to − 0.15). For 2016, the model highly underestimated the pollen concentrations, with NMB ranging from − 0.45 to − 0.93. In general, the results show that the model can resolve the main peaks of pollen concentrations, which is a step forward in the application of the HYSPLIT model for birch pollen forecasting over Poland. We suggest the application of methods that can reduce the bias of temperature such as meteorological data assimilation or bias correction, which could improve calculation of the start of emissions and consequently the start of the pollen season as well as pollen concentrations.

BackgroundPollen from grasses and trees can trigger allergic rhinitis (AR), where the symptoms and associated consequences can negatively affect quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) is frequently used in clinical trials of AR to assess QoL. To help interpret RQLQ data, the minimal important difference (MID) can be used to assess whether a mean difference in QoL between treatment groups is clinically meaningful. In seasonal allergy, an MID differs according to the allergen, pollen exposure, symptom severity, patient age and treatment; the same MID cannot be applied to all scenarios.MethodsUsing data from four Phase III clinical trials of SQ sublingual immunotherapy‐tablets in adults with moderate‐to‐severe allergy, between‐group MIDs were derived for the RQLQ in grass pollen allergy (during the peak [n = 501] and entire [n = 514] pollen seasons), and in tree pollen allergy (during the birch [n = 516] and tree [n = 518] pollen seasons), using anchor‐based methodology, supported by distribution‐based methods.ResultsFor grass pollen allergy, anchor‐based derived between‐group MIDs were 0.22 for the entire pollen season (n = 343) and 0.10 for the peak pollen season (n = 335). For tree pollen allergy, anchor‐based derived between‐group MIDs were 0.26 for the tree pollen season (n = 306) and 0.16 for the birch pollen season (n = 305) (representative of peak season). Distribution‐based derived MIDs were supportive of the anchor‐based values.ConclusionsThis analysis has derived between‐group MIDs specific to the trial populations evaluated and to the conditions under which the data were obtained, and highlights the need for a range of MIDs to reflect the unique nature of seasonal allergic disease.

The study's main objective was to specify the extent to which weather conditions were related to the course of birch pollen seasons in the years 1997–2020. The impact of atmospheric conditions on the daily concentrations of birch pollen grains, the Annual pollen integral (APIn), and the length of pollen seasons were studied. The dependency between each meteorological condition and various features of the birch pollen season was determined using Spearman’s rho correlation, the Kruskal–Wallis test, and cluster analysis with the k-means method. It has been shown that the duration of sunshine and average air temperature occurring within 14 days preceding the season has the most significant influence on the beginning of a birch pollen season. The value of daily birch pollen concentrations in Sosnowiec showed a statistically significant positive correlation with the duration of sunlight and the average and maximum wind speed. The daily concentration also depended on the synoptic situation: the mass airflow direction, the type of air mass inflow, and the type of weather front. The near-ground temperature influenced the APIn of birch pollen grains during the period of 14 days before the beginning of the season and the meteorological conditions occurring in the summer of the preceding year such as the maximum temperature, duration of sunlight, the maximum and average wind speed, and the relative air humidity. It was concluded that the length of birch pollen seasons decreased year by year.

We analyse the impact of ground-based data assimilation to the Weather Research and Forecasting (WRF) meteorological model on parameters relevant for birch pollen emission calculations. Then, we use two different emission databases (BASE – no data assimilation, OBSNUD – data assimilation for the meteorological model) in the chemical transport model and evaluate birch pollen concentrations. Finally, we apply a scaling factor for the emissions (BASE and OBSNUD), based on the ratio between simulated and observed seasonal pollen integral (SPIn) to analyse its impact on birch concentrations over Central Europe. Assimilation of observational data significantly reduces model overestimation of air temperature, which is the main parameter responsible for the start of pollen emission and amount of released pollen. The results also show that a relatively small bias in air temperature from the model can lead to significant differences in heating degree days (HDD) value. This may cause the HDD threshold to be attained several days earlier/later than indicated from observational data which has further impact on the start of pollen emission. Even though the bias for air temperature was reduced for OBSNUD, the model indicates a start for the birch pollen season that is too early compared to observations. The start date of the season was improved at two of the 11 stations in Poland. Data assimilation does not have a significant impact on the season's end or SPIn value. The application of the SPIn factor for the emissions results in a much closer birch pollen concentration level to observations even though the factor does not improve the start or end of the pollen season. The post-processing of modelled meteorological fields, such as the application of bias correction, can be considered as a way to further improve the pollen emission modelling.

Birch belongs to the most important allergenic taxa in Europe, therefore information on the start dates of the pollen season is very important for allergists and their patients as well as for climatologists. The study examined changes in the start of the birch pollen season as well as determined the trend of these changes. Pollen monitoring was performed in Lublin (eastern Poland) in the period 2001–2019 using the volumetric method. The Makra-test was used to detect periods with significantly higher or lower average of the onset than the average for the whole dataset. Two significant falls in the average of the pollen season start were found in 2007 and 2014. Besides, taking into account the 2-3-year rhythm of high and low concentrations of birch pollen in the atmospheric air, linear trends were fitted for the subsets of high and low abundance seasons. Significant changes in Betula pollen season start dates were only determined for the highly abundance seasons, while the results for seasons with a low concentration did not allow rejecting the hypothesis about the lack of a linear trend in the changes in the studied parameter. Moreover, a significant polynomial relationship was found between the beginning of a pollen season and the average values of monthly temperatures preceded a season. These analyses show that the start dates of the Betula pollen season are getting significantly earlier. The dynamics of changes differ between seasons with high and low concentrations of pollen.

Environmental exposure unit simulates natural seasonal birch pollen exposures while maximizing change in allergic symptoms