Activation of the aryl hydrocarbon receptor improves allergen-specific immunotherapy of murine allergic airway inflammation: a novel adjuvant option?

Background: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed. Methods: A murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome. Results: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels. Conclusion: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.

Predicting the main pollen season of Broussonetia Papyrifera (paper mulberry) tree.

Paper mulberry pollen, declared a pest in several countries including Pakistan, can trigger severe allergies and cause asthma attacks. We aimed to develop an algorithm that could accurately predict high pollen days to underpin an alert system that would allow patients to take timely precautionary measures. We developed and validated two prediction models that take historical pollen and weather data as their input to predict the start date and peak date of the pollen season in Islamabad, the capital city of Pakistan. The first model is based on linear regression and the second one is based on phenological modelling. We tested our models on an original and comprehensive dataset from Islamabad. The mean absolute errors (MAEs) for the start day are 2.3 and 3.7 days for the linear and phenological models, respectively, while for the peak day, the MAEs are 3.3 and 4.0 days, respectively. These encouraging results could be used in a website or app to notify patients and healthcare providers to start preparing for the paper mulberry pollen season. Timely action could reduce the burden of symptoms, mitigate the risk of acute attacks and potentially prevent deaths due to acute pollen-induced allergy.

Phl p 5 levels more strongly associated than grass pollen counts with allergic respiratory health.

BACKGROUND: Studies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels. OBJECTIVE: We sought to assess associations of grass pollen counts and grass allergen levels (Phl p 5) with respiratory allergic health symptoms in a panel of 93 adults with moderate-severe allergic rhinitis and daily asthma hospital admissions in London, United Kingdom. METHODS: Daily symptom and medication scores were collected from adult participants in an allergy clinical trial. Daily counts of asthma hospital admissions in the London general population were obtained from Hospital Episode Statistics data. Daily grass pollen counts were measured using a volumetric air sampler, and novel Phl p 5 levels were measured using a ChemVol High Volume Cascade Impactor and ELISA analyses (May through August). Associations between the 2 pollen variables and daily health scores (dichotomized based on within-person 75th percentiles) were assessed using generalized estimating equation logistic models and with asthma hospital admissions using Poisson regression models. RESULTS: Daily pollen counts and Phl p 5 levels were each positively associated with reporting a high combined symptom and medication health score in separate models. However, in mutually adjusted models including terms for both pollen counts and Phl p 5 levels, associations remained for Phl p 5 levels (odds ratio [95% CI]: 1.18 [1.12, 1.24]), but were heavily attenuated for pollen counts (odds ratio [95% CI]: 1.00 [0.93, 1.07]). Similar trends were not observed for asthma hospital admissions in London. CONCLUSIONS: Grass allergen (Phl p 5) levels are more consistently associated with allergic respiratory symptoms than grass pollen counts.

Environmental exposure and sensitization patterns in a Swiss alpine pediatric cohort.

Background: The level of environmental exposure throughout life may contribute to the prevalence of allergic sensitization and allergic disease. The alpine climate has been considered a healthy climate with little allergen exposure and pollution. We conducted a cross-sectional study to investigate local environmental exposure and concomitant prevalence of allergic sensitization among local school children born and raised in an alpine environment. Methods: Clinical and demographic data were collected with a questionnaire. Allergen content was assessed in residential settled dust samples, lifetime exposure to pollen and air pollution was calculated using data from national pollen and air pollution monitoring stations, and the allergic sensitization profile was determined with component resolved diagnostics (ISAC®). Univariate and multivariate regression models were used to estimate the relation between exposure and sensitization. Results: In a cohort of children born and raised in an alpine environment, sensitization to aeroallergens is quite common (38%), especially to grass (33%) and cat (16%). House dust mite allergen was detected in up to 38% of residential dust samples, but sensitization to HDM was low (2.5%). Pollutant levels were low, but an increasing trend was observed in the amount of ozone and PM10. Living close to a busy road was associated with increased odds OR (95% CI) for being sensitized to any allergen 2.7 (1.0-7.2), to outdoor allergens 2.8 (1.1-7.1) and being sensitized plus reporting symptoms of rhinoconjunctivitis 4.4 (1.3-14.8) and asthma 5.5 (1.4-21). Indoor living conditions, including the presence of visible mold, increased the odds of being sensitized to indoor allergens (1.9 (1.1-3.2) and being sensitized plus reporting symptoms of rhinoconjunctivitis 1.9 (1.0-3.6) and asthma 2.1 (1.0-4.1). Conclusion: In a healthy alpine environment, pollution might still be an important factor contributing to allergic sensitization.

Impact of asthma in Europe: A comparison of web search data in 21 European countries.

Background: Asthma is a chronic inflammatory disorder of the airways and one of the most important non-communicable diseases worldwide. Analyzing crowdsourced data can help understand public interest and unmet needs as well as potential factors influencing search behavior. Objective: The study aimed to investigate asthma-related web search data in Europe to identify possible regional and seasonal variations and to assess public interest. Methods: Google Ads Keyword Planner was used to measure search volume for search terms related to asthma, allergic asthma, and bronchial asthma in 21 European countries between January 2018 and December 2021. The top 10 keywords of each country were categorized qualitatively. Search volume per 100 000 inhabitants was descriptively assessed in terms of regional and seasonal trends. Spearman correlations between search volume and pollen concentration as well as coronavirus disease (COVID-19) cases were investigated. Results: The median search volume per 100 000 inhabitants for asthma and allergic asthma was highest in Northern and Western Europe, while the highest search volume for bronchial asthma was observed in Western and Eastern regions. A seasonal trend was identified for all search terms and in all regions. Correlations were found between search frequency and pollen load and search behavior and COVID-19 cases. Overall, Europeans were most interested in the diseases in general, their treatment options, and symptoms. Conclusion: These results highlighted the need for reliable and region-specific information about the disease and for public campaigns to improve asthma control. The study also emphasizes the importance of using crowdsourced data for a more encompassing overview beyond conventional healthcare data.

Designing an automatic pollen monitoring network for direct usage of observations to reconstruct the concentration fields.

We consider several approaches to a design of a regional-to-continent-scale automatic pollen monitoring network in Europe. Practical challenges related to the arrangement of such a network limit the range of possible solutions. A hierarchical network is discussed, highlighting the necessity of a few reference sites that follow an extended observations protocol and have corresponding capabilities. Several theoretically rigorous approaches to a network design have been developed so far. However, before starting the process, a network purpose, a criterion of its performance, and a concept of the data usage should be formalized. For atmospheric composition monitoring, developments follow one of the two concepts: a network for direct representation of concentration fields and a network for model-based data assimilation, inverse problem solution, and forecasting. The current paper demonstrates the first approach, whereas the inverse problems are considered in a follow-up paper. We discuss the approaches for the network design from theoretical and practical standpoints, formulate criteria for the network optimality, and consider practical constraints for an automatic pollen network. An application of the methodology is demonstrated for a prominent example of Germany's pollen monitoring network. The multi-step method includes (i) the network representativeness and (ii) redundancy evaluation followed by (iii) fidelity evaluation and improvement using synthetic data.

Diurnal pattern of Poaceae and Betula pollen flight in Central Europe.

In Central Europe the most common allergies are provoked by grass or birch pollen allergens. We determined the intra-daily behavior of airborne pollen grains of grasses (Poaceae) and birch (Betula ssp.) in Central Europe, based on data obtained from a network of automatic pollen monitors over Europe (www.pollenscience.eu). Our aim was to determine the time of day when the lowest concentrations occur, to provide allergic individuals the optimal time to ventilate their homes. The study was carried out in three Central European capitals, Berlin (Germany), Paris-Saclay (France), and Luxembourg (Luxembourg), as well as in eight stations in Germany (Altötting, Feucht, Garmisch-Partenkirchen, Hof, Marktheidenfeld, Mindelheim, Munich and Viechtach). The diurnal rhythm of these eleven locations was analyzed for either the complete, first week, peak week, peak day and last week of the pollen season. The data studied were reported as pollen/m3 measured in 3 h periods. Stations were classified as city, semi-populated or countryside areas using land-use and population density criteria. Grass pollen has a more pronounced diurnal rhythm than birch pollen concentrations. A significant difference was observed when comparing day (6-21 h) versus night (21-6 h) for all stations. No difference was detected between city and countryside for both pollen types, although for Poaceae a longer period of maximum concentrations was observed in big cities and higher day/night-time differences were registered in the countryside (6.4) than in cities (3.0). The highest pollen concentrations were observed between 9 and 18 h for grass, but the rhythm was less pronounced for birch pollen. For allergic individuals who want to bring in fresh air in their homes, we recommend opening windows after 21 h, but even better early in the morning between 6 and 9 h before pollinations (re)starts.

Biological impact of sequential exposures to allergens and ultrafine particle-rich combustion aerosol on human bronchial epithelial BEAS-2B cells at the air liquid interface.

The prevalence of allergic diseases is constantly increasing since few decades. Anthropogenic ultrafine particles (UFPs) and allergenic aerosols is highly involved in this increase; however, the underlying cellular mechanisms are not yet understood. Studies observing these effects focused mainly on singular in vivo or in vitro exposures of single particle sources, while there is only limited evidence on their subsequent or combined effects. Our study aimed at evaluating the effect of subsequent exposures to allergy-related anthropogenic and biogenic aerosols on cellular mechanism exposed at air-liquid interface (ALI) conditions. Bronchial epithelial BEAS-2B cells were exposed to UFP-rich combustion aerosols for 2 h with or without allergen pre-exposure to birch pollen extract (BPE) or house dust mite extract (HDME). The physicochemical properties of the generated particles were characterized by state-of-the-art analytical instrumentation. We evaluated the cellular response in terms of cytotoxicity, oxidative stress, genotoxicity, and in-depth gene expression profiling. We observed that single exposures with UFP, BPE, and HDME cause genotoxicity. Exposure to UFP induced pro-inflammatory canonical pathways, shifting to a more xenobiotic-related response with longer preincubation time. With additional allergen exposure, the modulation of pro-inflammatory and xenobiotic signaling was more pronounced and appeared faster. Moreover, aryl hydrocarbon receptor (AhR) signaling activation showed to be an important feature of UFP toxicity, which was especially pronounced upon pre-exposure. In summary, we were able to demonstrate the importance of subsequent exposure studies to understand realistic exposure situations and to identify possible adjuvant allergic effects and the underlying molecular mechanisms.

Assessing the national burden of allergic asthma by web-search data, pollen counts, and drug prescriptions in Germany and Sweden.

Background: Asthma and its main phenotype allergic asthma are prevalent, chronic, and complex diseases affecting 4% of the population. One main trigger for allergic asthma exacerbations is pollen. Online health information search behavior by people is increasing, and analysis of web-search data can provide valuable insight into disease burden and risk factors of a population. Objectives: We sought to perform a web-search data analysis and correlation to climate factors and pollen in 2 European countries. Methods: We analyzed the national web-search volume for allergic asthma-related keywords in Germany and Sweden from 2018 to 2021 and correlated it to local pollen counts, climatic factors, and drug prescription rates. Results: Per capita, more searches were conducted in Sweden than in Germany. A complex geographic stratification within the countries was observed. Search results were seasonal with a peak in spring and correlated with pollen counts in both countries. However, anti-asthmatic drug prescription rates in Sweden, as well as temperature and precipitation in both countries, did not correlate with search volume. Conclusion: Our analysis offers population-level insights about this complex disease by reporting its needs and establishing the correlation to pollen counts, which enables a targeted approach in the public health management of allergic asthma. Local pollen counts, as opposed to temperature or precipitation, might be good predictors of allergic asthma disease burden.

Towards European automatic bioaerosol monitoring: Comparison of 9 automatic pollen observational instruments with classic Hirst-type traps.

To benefit allergy patients and the medical practitioners, pollen information should be available in both a reliable and timely manner; the latter is only recently possible due to automatic monitoring. To evaluate the performance of all currently available automatic instruments, an international intercomparison campaign was jointly organised by the EUMETNET AutoPollen Programme and the ADOPT COST Action in Munich, Germany (March-July 2021). The automatic systems (hardware plus identification algorithms) were compared with manual Hirst-type traps. Measurements were aggregated into 3-hourly or daily values to allow comparison across all devices. We report results for total pollen as well as for Betula, Fraxinus, Poaceae, and Quercus, for all instruments that provided these data. The results for daily averages compared better with Hirst observations than the 3-hourly values. For total pollen, there was a considerable spread among systems, with some reaching R2 > 0.6 (3 h) and R2 > 0.75 (daily) compared with Hirst-type traps, whilst other systems were not suitable to sample total pollen efficiently (R2 < 0.3). For individual pollen types, results similar to the Hirst were frequently shown by a small group of systems. For Betula, almost all systems performed well (R2 > 0.75 for 9 systems for 3-hourly data). Results for Fraxinus and Quercus were not as good for most systems, while for Poaceae (with some exceptions), the performance was weakest. For all pollen types and for most measurement systems, false positive classifications were observed outside of the main pollen season. Different algorithms applied to the same device also showed different results, highlighting the importance of this aspect of the measurement system. Overall, given the 30 % error on daily concentrations that is currently accepted for Hirst-type traps, several automatic systems are currently capable of being used operationally to provide real-time observations at high temporal resolutions. They provide distinct advantages compared to the manual Hirst-type measurements.

Alternaria spore exposure in Bavaria, Germany, measured using artificial intelligence algorithms in a network of BAA500 automatic pollen monitors.

Although Alternaria spores are well-known allergenic fungal spores, automatic bioaerosol recognition systems have not been trained to recognize these particles until now. Here we report the development of a new algorithm able to classify Alternaria spores with BAA500 automatic bioaerosol monitors. The best validation score was obtained when the model was trained on both data from the original dataset and artificially generated images, with a validation unweighted mean Intersection over Union (IoU), also called Jaccard Index, of 0.95. Data augmentation techniques were applied to the training set. While some particles were not recognized (false negatives), false positives were few. The results correlated well with manual counts (mean of four Hirst-type traps), with R2 = 0.78. Counts from BAA500 were 1.92 times lower than with Hirst-type traps. The algorithm was then used to re-analyze the historical automatic pollen monitoring network (ePIN) dataset (2018-2022), which lacked Alternaria spore counts. Re-analysis of past data showed that Alternaria spore exposure in Bavaria was very variable, with the highest counts in the North (Marktheidenfeld, 154 m a.s.l.), and the lowest values close to the mountains in the South (Garmisch-Partenkirchen, 735 m a.s.l.). This approach shows that in our network future algorithms can be run on past datasets. Over time, the use of different algorithms could lead to misinterpretations as stemming from climate change or other phenological causes. Our approach enables consistent, homogeneous treatment of long-term series, thus preventing variability in particle counts owing to changes in the algorithms.

Monitoring disease activity of pollen allergies: What crowdsourced data are telling us.

Background: Pollen allergies are a major public health concern worldwide. An IgE-mediated systemic inflammatory response to pollen allergens causes symptoms of allergic rhinitis or even asthma. They have a significant impact on individual quality of life and cause high socioeconomic strain. The aim of this study was to examine the value of pollen allergy-related web search data for public health. Methods: An in-depth analysis of search volumes and contents, and their correlation with factors of disease activity such as rates of dispensed medicine and pollen concentration, was conducted. In this retrospective longitudinal study, Google Ads Keyword Planner was used to determine the internet search volume of terms related to pollen allergies across Germany and Sweden as a whole and in each of the 16 German federal states and 21 Swedish provinces between January 2017 and December 2020. This search volume was converted into searches per 100,000 inhabitants and categorized qualitatively. Results: A total search volume of 7405 searches per 100,000 inhabitants in Germany and 17,592 searches per 100,000 inhabitants in Sweden was observed, with the total yearly search volume increasing continually in both countries during the study period. Regional search volume correlated with antihistamine dispensation rates (ρ = 0.848-0.960) and pollen concentration (ρ = 0.566-0.922). While overall search interest was higher in Sweden, a higher interest in treatment options was identified in Germany. Conclusion: Internet websearch data is an excellent proxy for disease activity of allergic rhinitis. In the 4-year study period, the interest in pollen allergies has increased and there are unmet medical needs in both countries.

Drivers of the release of the allergens Bet v 1 and Phl p 5 from birch and grass pollen.

The drivers affecting the Pollen Allergen Potency (PAP, amount of allergen released per pollen) are sparsely known. Betula and Poaceae airborne pollen are the two main allergenic pollen in the World. Airborne pollen and their allergens Bet v 1 and Phl p 5 were simultaneously measured from 2010 to 2015 in Davos (Switzerland) and Munich (Germany) by using volumetric traps and ChemVol cascade impactors. Daily variations in PAP were analysed in PM>10 and PM2.5-10 air fractions and generalized additive models were created to explain which factors determine PAP, including meteorological parameters and inorganic pollutants. 87.1 ± 13.9% of Bet v 1 and 88.8 ± 15.5% of Phl p 5 was detected in the fraction PM>10 where most pollen grains were collected. Significantly higher PAP for grasses (3.5 ± 1.9 pg Phl p 5/pollen grain) were observed in Munich than in Davos (2.4 ± 1.5 pg/pollen grain, p < 0.001), but not for Betula (2.5 ± 1.6 pg Bet v 1/pollen grain in Munich and 2.3 ± 1.7 in Davos, N.S.). PAP varied between days, years and location, and increased along the pollen season for Poaceae, but remaining constant for Betula. Free allergens (allergens observed in the fraction with limited pollen, PM2.5- 10) were recorded mostly at the beginning or at the end of the pollen season, being linked to higher humidity and rainy days. Also, PAP was higher when the airborne pollen concentrations increased rapidly after one day of low/moderate levels. Our findings show that pollen exposure explains allergen exposure only to a limited extend, and that day in the season, geographic location and some weather conditions need to be considered also to explain symptoms of allergic individuals.

Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation.

The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR-/- and CYP1B1-/- but not CYP1A1-/- or CYP1A2-/- animals display enhanced allergic airway inflammation compared to WT. Expression analysis, immunofluorescence staining of murine and human lung sections and bone marrow chimeras suggest an important role of CYP1B1 in non-hematopoietic lung epithelial cells to prevent exacerbation of allergic airway inflammation. Transcriptional analysis of murine and human lung epithelial cells indicates a functional link of AhR to barrier protection/inflammatory mediator signaling upon allergen challenge. In contrast, CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and to an increased availability of the AhR ligand kynurenic acid following allergen challenge. Thus, differential CYP1 family member expression and signaling via the AhR in epithelial cells represents an immunoregulatory layer protecting the lung from exacerbation of allergic airway inflammation.

Effect of air filtration on house dust mite, cat and dog allergens and particulate matter in homes.

Background: Indoor allergens (i.e. from mite, cat and dog) are carried by airborne particulate matter. Thus, removal of particles would reduce allergen exposure. This work aims to assess the performance of air filtration on particulate matter and thus allergen removal in 22 bedrooms. Methods: Indoor air was sampled (with and without air filtration) with a cascade impactor and allergens were measured using enzyme-linked immunosorbent assay (ELISA). Particulate matter (including ultrafine particles) was also monitored. Results: The median of allergen reduction was 75.2% for Der f 1 (p < 0.001, n = 20), 65.5% for Der p 1 (p = 0.066, n = 4), 76.6% for Fel d 1 (p < 0.01, n = 21) and 89.3% for Can f 1 (p < 0.01, n = 10). For size fractions, reductions were statistically significant for Der f 1 (all p < 0.001), Can f 1 (PM>10 and PM2.5-10, p < 0.01) and Fel d 1 (PM2.5-10, p < 0.01), but not for Der p 1 (all p > 0.05). PM was reduced in all fractions (p < 0.001). The allergens were found in all particle size fractions, higher mite allergens in the PM>10 and for pet allergens in the PM2.5-10. Conclusions: Air filtration was effective in removing mites, cat and dog allergens and also particulate matter from ambient indoor air, offering a fast and simple solution to mitigate allergen exposome.

The priming effect of diesel exhaust on native pollen exposure at the air-liquid interface.

Pollen related allergic diseases have been increasing for decades. The reasons for this increase are unknown, but environmental pollution like diesel exhaust seem to play a role. While previous studies explored the effects of pollen extracts, we studied here for the first time priming effects of diesel exhaust on native pollen exposure using a novel experimental setup. METHODS: Human bronchial epithelial BEAS-2B cells were exposed to native birch pollen (real life intact pollen, not pollen extracts) at the air-liquid interface (pollen-ALI). BEAS-2B cells were also pre-exposed in a diesel-ALI to diesel CAST for 2 h (a model for diesel exhaust) and then to pollen in the pollen-ALI 24 h later. Effects were analysed by genome wide transcriptome analysis after 2 h 25 min, 6 h 50 min and 24 h. Selected genes were confirmed by qRT-PCR. RESULTS: Bronchial epithelial cells exposed to native pollen showed the highest transcriptomic changes after about 24 h. About 3157 genes were significantly up- or down-regulated for all time points combined. After pre-exposure to diesel exhaust the maximum reaction to pollen had shifted to about 2.5 h after exposure, plus the reaction to pollen was desensitised as only 560 genes were differentially regulated. Only 97 genes were affected synergistically. Of these, enrichment analysis showed that genes involved in immune and inflammatory response were involved. CONCLUSION: Diesel exhaust seems to prime cells to react more rapidly to native pollen exposure, especially inflammation related genes, a factor known to facilitate the development of allergic sensitization. The marker genes here detected could guide studies in humans when investigating whether modern and outdoor diesel exhaust exposure is still detrimental for the development of allergic disease.

Non-pharmacological interventions for pollen-induced allergic symptoms: Systematic literature review.

BACKGROUND: Allergic diseases pose a health problem worldwide. Pollen are widespread aeroallergens which can cause symptoms like shortness of breath, cough, itchy eyes, or rhinitis. Apart from preventive measures and pharmacological treatment, also non-pharmacological interventions have been suggested to reduce symptoms. The objective of this work was to review studies investigating the effectiveness of non-pharmacologic interventions to reduce allergic symptoms. METHODS: PubMed, EMBASE, and CENTRAL were systematically reviewed in July 2018 and April 2020. Several authors worked on the screening of titles, abstracts, and full texts. One author for each literature search performed the data extraction and the risk of bias assessment. Studies were included if they met the inclusion criteria defined by the PECOs. Studies which investigating the effect of non-pharmacologic interventions on patients with allergic rhinitis were included. RESULTS: Twenty-nine studies investigating eleven types of non-pharmacologic interventions to avoid and reduce allergic symptoms due to pollen exposure were included in this review. Out of all studies, seven studies addressed nasal rinsing and 22 included acupuncture, air filtering, artisanal tears, individual allergen avoidance advice, various nasal applications, self-hypnosis, rhinophototherapy, and wraparound sunglasses. CONCLUSION: Most studies had a high risk of bias and small sample sizes. There were only a few high-quality studies that give hints about the effectiveness of non-pharmacological interventions. For future research, more high-quality studies are required to confirm the effectiveness of simple, safe, and cost-effective interventions.

Dosing intact birch pollen grains at the air-liquid interface (ALI) to the immortalized human bronchial epithelial cell line BEAS-2B.

In real life, humans are exposed to whole pollen grains at the air epithelial barrier. We developed a system for in vitro dosing of whole pollen grains at the Air-Liquid Interface (ALI) and studied their effect on the immortalized human bronchial epithelial cell line BEAS-2B. Pollen are sticky and large particles. Dosing pollen needs resuspension of single particles rather than clusters, and subsequent transportation to the cells with little loss to the walls of the instrumentation i.e. in a straight line. To avoid high speed impacting insults to cells we chose sedimentation by gravity as a delivery step. Pollen was resuspended into single particles by pressured air. A pollen dispersion unit including PTFE coating of the walls and reduced air pressure limited impaction loss to the walls. The loss of pollen to the system was still about 40%. A linear dose effect curve resulted in 327-2834 pollen/cm2 (± 6.1%), the latter concentration being calculated as the amount deposited on epithelial cells on high pollen days. After whole pollen exposure, the largest differential gene expression at the transcriptomic level was late, about 7 hours after exposure. Inflammatory and response to stimulus related genes were up-regulated. We developed a whole pollen exposure air-liquid interface system (Pollen-ALI), in which cells can be gently and reliably dosed.

Effects of future climate change on birch abundance and their pollen load.

Climate change impacts on the structure and function of ecosystems will worsen public health issues like allergic diseases. Birch trees (Betula spp.) are important sources of aeroallergens in Central and Northern Europe. Birches are vulnerable to climate change as these trees are sensitive to increased temperatures and summer droughts. This study aims to examine the effect of climate change on airborne birch pollen concentrations in Central Europe using Bavaria in Southern Germany as a case study. Pollen data from 28 monitoring stations in Bavaria were used in this study, with time series of up 30 years long. An integrative approach was used to model airborne birch pollen concentrations taking into account drivers influencing birch tree abundance and birch pollen production and projections made according to different climate change and socioeconomic scenarios. Birch tree abundance is projected to decrease in parts of Bavaria at different rates, depending on the climate scenario, particularly in current centres of the species distribution. Climate change is expected to result in initial increases in pollen load but, due to the reduction in birch trees, the amount of airborne birch pollen will decrease at lower altitudes. Conversely, higher altitude areas will experience expansions in birch tree distribution and subsequent increases in airborne birch pollen in the future. Even considering restrictions for migration rates, increases in pollen load are likely in Southwestern areas, where positive trends have already been detected during the last three decades. Integrating models for the distribution and abundance of pollen sources and the drivers that control birch pollen production allowed us to model airborne birch pollen concentrations in the future. The magnitude of changes depends on location and climate change scenario.