Birch Pollen Research Articles

Characteristics of the molecular sensitization profiles in patients with birch pollen allergy and cross-reactive food allergy to PR-10 proteins

BACKGROUND: Birch pollen allergy is widespread and is the main allergic disease in Russia. Cross-reactive food allergy, often found in patients with birch pollen allergy, is an underestimated problem that complicates the course of pollinosis and requires further study to improve the quality of diagnosis and personalized recommendations for such patients.
 AIM: To study the features of the molecular sensitization profile of adult patients with birch pollen allergy and cross-reactive food allergy to PR-10 proteins.
 MATERIALS AND METHODS: Twenty-five adult patients with confirmed birch pollen allergy, with or without cross-reactive food allergy, were included in an open single-center interventional prospective controlled nonrandomized study. Specific IgE to 112 allergens was determined by multiplex analysis using ImmunoCAP ISAC (ThermoFisher, Sweden). Patients with cross-reactive food allergy completed a validated questionnaire on cross-reactive food allergy symptoms and causative allergens. The primary endpoint of the study was the assessment of the sensitization profile to Bet v 1 and PR-10 proteins (Mal d 1, Ara h 8, Cor a 1.0101, Cor a 1.0401, Act d 8, Api g 1, Pru p 1, and Gly m 4) and the clinical characteristics of the sensitized patients. The secondary endpoint was the comparison of patients with and without cross-reactive food allergy and the evaluation of how sensitization to Bet v 1 and PR-10 homologs can affect clinical manifestations of cross-reactive food allergy in patients.
 RESULTS: The study included 25 patients aged 18–55 years, from which two comparable groups were formed: group 1 consisted of 13 patients with cross-reactive food allergy symptoms and group 2 (without cross-reactive food allergy) consisted of 12 patients who had never experienced cross-reactive food allergy symptoms. Analysis of the sensitization profile to PR-10 allergens revealed similar patterns in both groups; however, sIgE concentrations to all allergens were significantly higher in group 1. A strong correlation was found between the number of triggering products and total IgE level with PR-10 proteins (r=0.81; p=0.001). The severity of cross-reactive food allergy symptoms correlated with the total level of IgE to PR-10 proteins (r=0.97; p 0.0001). The cutoff level for total sIgE to food PR-10 proteins, equal to 70 ISU-E, allowed us to distinguish patients with only oral allergic syndrome from those with systemic manifestations of cross-reactive food allergy.
 CONCLUSION: The results of the study are applicable in clinical practice and have prognostic value in determining the severity of cross-reactive food allergy.

Uncovering a Severe Patient Group With Pollen-Related Extrarespiratory Allergic Symptoms: A Year-Long Diary Survey in Japan

BackgroundThe most common symptoms of pollen allergy are rhinitis and conjunctivitis. However, in real-world clinical practice, we sometimes encounter patients with pollen allergy suffering from severe extrarespiratory symptoms including skin, gastrointestinal, or flu-like symptoms in relation to exposure to sensitized pollen. ObjectiveThe aim of this study was to elucidate the extrarespiratory symptoms in patients with pollen allergy MethodsWe performed a non-drug-focused, prospective study of patients with pollen allergy (n=384). During the 1-year observational period, they were asked to complete a weekly e-diary consisting of visual analogue scale (VAS) scores to assess all symptoms experienced in various organs over the past week. An association between seasonal pollen levels and seasonal increase in VAS scores was evaluated using a mixed-effect model for repeated measures. A k-means cluster analysis was performed to identify a group of patients experiencing stronger extrarespiratory symptoms. ResultsIn patients sensitized to grass or birch pollen, higher seasonal levels of these pollen grains were associated with higher VAS scores for headache, gastrointestinal symptoms, skin symptoms, and fatigue. A cluster analysis identified a group of severe pollen-allergic patients with higher extrarespiratory symptoms (n=42). This group was characterized by a higher frequency of comorbid food allergy/atopic dermatitis, higher rate of IgE-sensitization to pollens, and higher impaired activity and work productivity. ConclusionThis 1-year survey identified a small but non-negligible group of patients with pollen-related extrarespiratory symptoms. More attention should be paid to this patient group considering their impaired activity and work productivity.

Individual wearable air purifier protects against pollen, house dust mite, and cat allergens: Report from anallergen exposure chamber.

Evaluation of a new individual wearable air purifier (Respiray Wear A+) for birch pollen, house dust mite (HDM), and cat-allergic rhinoconjunctivitis (ARC) patients in a standardized allergen exposure chamber (AEC). Eligible allergic patients were exposed to birch pollen, HDM raw material, and cat allergen in an AEC for 60 minutes without (V1) and with (V3) the use of the Respiray device. Nasal, ocular, bronchial, and other symptoms were rated by the patients every 10 minutes, and their wellbeing, peak nasal inspiratory flow (PNIF), and lung function parameters were assessed every 30 minutes. The primary endpoint was the change in the median of the total symptom score (TSS) at V3 compared to V1 at 60 minutes of exposure. The secondary endpoints consisted of the total nasal symptom score (TNSS) and total eye symptom score (TESS). 23 patients with birch pollen allergy, 37 patients with HDM allergy, and 41 patients with cat allergy were included in the analysis. Significant reduced symptom scores of ~49% were observed when using Respiray Wea A+ under birch pollen exposure (p<0.05) in the primary endpoint TSS (V3 2.43 compared to V1 4.78). An 48% reduction of symptoms was seen in TSS in case of HDM exposure (V3 3.59; V1 6.92, (t-test: p<0.01)) and the highest reduction of TSS (60%) under Respiray A+ using cat allergens (V3 2.95, V1 7.44, (t-test p<0.01) after 60 minutes of exposure. The personal wellbeing revealed clinically meaningful improvements over time in all three studies which manifested in a lower symptom increase during the final allergen exposures. The individual wearable air purifier Respiray Wear A+ protects significantly against airborne pollen, HDM, and cat allergens and may be a very useful device for avoiding indoor allergens in a new way.

Soybean, Gly m 4, and Birch Pollen Allergy

Several types of soy foods are consumed worldwide. Soybean products have shown some potential benefits for health, but soy allergy can cause life-threatening allergic reactions. Pollens of birch trees can be associated with food allergy-related disease such as pollen/food allergy syndrome.

Analysis on epidemiological characteristics of allergens with allergic skin diseases in a hospital in Beijing City from 2017 to 2021

Objectives: In order to provide valuable information for the diagnosis and treatment of dermatitis, the prevalence rate and trend changes of common allergens in patients with allergic skin diseases in Beijing City were investigated and analyzed. Methods: This study was a retrospective data collection study. A total of 2 822 patients diagnosed with moderate to severe atopic dermatitis with allergen examinations were collected from Peking University First Hospital from 2017 to 2021, most of them were adults, and 83%(2 340/2 822) were over 18 years old. The ImmunoCAP fluorescent enzyme-linked immunoassay system was used to quantify specific IgE. The positive rate of each allergen was counted according to age, gender and year. The epidemiological characteristics and trends were analyzed. Results: In the past five years, 22 503 allergen-specific IgE test data were collected, and the positive rate of allergens in 40%(1 122/2 822) of the 2 822 patients was mainly multiple sensitization, the positive rate of allergens and multiple sensitization rates were the highest in people aged 13-18 years old. The 2 822 patients were dominated by inhaled allergens, and the highest positive rate was inhaled mixture (29.3%). The top five positive rates of inhaled allergens were Dermatophagoides farina (26.7%), Dermatophagoides pteronyssinus (25.5%), Mugwort (23.9%), Birch pollen (19.2%) and Siberian cocklebur (18.2%). The top five positive rates of food allergens were shrimp (15.2%), peanut (14.8%), sesame (14.7%), wheat (13.2%) and milk (13.1%). Analysis of the positive rate of allergens in different age groups showed except for the positive rate of birch pollen peaked at 3-12 years old, other inhaled allergens were the highest food allergens in 13-18 years old. Among food allergens, the positive rates of fx5, milk, egg and wheat were the highest in <3 years old, the positive rate decreased gradually with age, and the positive rate of other food allergens peaked at 13-18 years old, and the shrimp and crab was the highest in adult. The positive rate of various allergens in the 2 822 patients showed little difference between male and female and the male was slightly higher than female. In the past five years, the positive rate of allergens has been on the rise. The changes of inhaled allergens in cat/dog hair dander, Dermatophagoides farina and cicadas were large, while the positive rate of food allergens was stable. Conclusions: The etiology of the allergic skin diseases is complex, which may be related to allergen exposure, heredity, immunity, environmental factors, abnormal skin barrier function, etc. This study showed the distribution of allergens in patients with allergic skin diseases in Beijing City to a certain extent. It provided epidemiological data and clinical evidence for the prevention and treatment of allergic diseases.

Oligomerization and tyrosine nitration enhance the allergenic potential of the birch and grass pollen allergens Bet v 1 and Phl p 5.

Protein modifications such as oligomerization and tyrosine nitration alter the immune response to allergens and may contribute to the increasing prevalence of allergic diseases. In this mini-review, we summarize and discuss relevant findings for the major birch and grass pollen allergens Bet v 1 and Phl p 5 modified with tetranitromethane (laboratory studies), peroxynitrite (physiological processes), and ozone and nitrogen dioxide (environmental conditions). We focus on tyrosine nitration and the formation of protein dimers and higher oligomers via dityrosine cross-linking and the immunological effects studied.

T cells specific to multiple Bet v 1 peptides are highly cross-reactive toward the corresponding peptides from the homologous group of tree pollens.

Allergens from Fagales trees frequently cause spring allergy in Europe, North America, and some parts of Asia. The definition of the birch homologous group, which includes birch (Bet v), oak (Que a), alder (Aln g), hazel (Cor a), hornbeam (Car b), beech (Fag s), and chestnut (Cas s), is based on high allergen sequence identity and extensive IgE cross-reactivity. Clinical effect was seen during the alder/hazel, birch, and oak pollen seasons after treatment with tree SLIT-tablets containing only birch allergen extract. Here, we characterize T-cell reactivity with respect to epitope specificities and cross-reactivity toward various Bet v 1 family members, (PR-10/group 1 major allergens). This cross-reactivity may be part of the immunological basis of clinical effect or cross-protection when exposed to birch homologous tree species. T-cell lines were generated from 29 birch-allergic individuals through stimulation of peripheral blood mononuclear cells (PBMCs) with birch/Bet v or oak/Que a allergen extracts. T-cell responses to allergen extracts, purified group 1 allergens, and overlapping 20-mer peptides (Bet v 1, Aln g 1, Cor a 1, and Que a 1) were investigated by T-cell proliferation and cytokine production. Cross-reactivity was evaluated based on Pearson's correlations of response strength and further investigated by flow cytometry using tetramer staining for homologous peptide pairs. T-cell reactivity toward extracts and group 1 allergens from across the birch homologous group was observed for birch/Bet v as well as oak/Que a T-cell lines. T-cell lines responded to multiple Bet v 1 homologous peptides from Aln g 1 and Cor a 1 and a subset of Que a 1 peptides. Significant Pearson's correlations between frequently recognized peptides derived from Bet v 1 and the corresponding peptides derived from alder, hazel, and oak strongly supported the T-cell cross-reactivity toward these allergens. Cross-reactivity between birch and birch homologous peptides was confirmed by pMHCII tetramer staining. T cells from birch tree pollen allergic individuals respond to multiple trees within the birch homologous group in accordance with the level of sequence homology between Bet v 1 family members, (PR-10 allergens) from these allergen sources, confirming the basis for clinical cross-protection.

Limited beneficial effects of systemic steroids when added to standard of care treatment of seasonal allergic rhinitis

Intramuscular injections with methylprednisolone treating allergic rhinitis (AR) have a long history. Modern guidelines are designed to dissuade this treatment, but it´s frequently used, especially in primary care. This despite of concern for side effects and lack of modern placebo-controlled studies. This study was designed to evaluate if methylprednisolone, could significantly improve symptoms of birch pollen induced AR and reduce the concomitant use of standard of care medication. Forty-two patients with birch pollen induced AR were randomized to treatment with methylprednisolone (80 mg) or placebo (NaCl 0.9%). Daily symptom- and medication scores was registered for 3 weeks. Quality of life questionnaires Sino-nasal Outcome Test-22 (SNOT-22) and Juniper Rhinoconjunctivitis Quality of Life Questionaire (Juniper RQLQ) were registered at trial start and at the end of the 3 weeks period. The combined symptom- and medication scores indicate that the methylprednisolone treated group [mean Area Under the Curve (AUC) 37.1 (SD 16.2 (95% CI 29.9–44.6))] was significantly better off than the placebo group [mean AUC 49.1 (SD 10.1 (95% CI 44.5–53.7))], p = 0.008. No significant difference between the groups were found in the SNOT-22 and Juniper RQLQ analysis. Registered side effects were few and mild. The limited beneficial effects of systemic steroids when added to standard of care in combination of its potential risk for side effects, speaks against its use for treatment of severe seasonal allergic rhinitis. The lack of difference in quality-of-life further underscores this result.

Profiles of Birch Allergen Component Sensitization and Its Association with Pollen Food Allergy Syndrome in Northern China.

To investigate the major allergen components associated with birch pollen allergy in northern China and elucidate clinical relevance to pollen food allergy syndrome (PFAS). Fifty-eight patients were recruited for a cross-sectional study and categorized into two groups: PFAS group and non-PFAS group, as well as apple allergy group and non-apple allergy group. The sIgE levels of birch pollen and its components, namely Bet v 1, Bet v 2, Bet v 4, and Bet v 6, were analyzed. Among 58 participants, 44 individuals (75.9%) reported PFAS. 32 out of 44 (72.7%) participants reported apple allergy. Bet v 1 exhibited the highest sensitization rate at 82.8%, followed by Bet v 2 (29.3%) and Bet v 6 (1.7%). The combined sensitization rate for Bet v 1 and/or Bet v 2 was 93.1%. A total of 77.6% of the subjects demonstrated sensitization to single component, while 19.0% exhibited sensitization to two components. The sIgE levels of birch pollen and Bet v 1 were significantly elevated in PFAS group compared to non-PFAS group (p=0.001, p<0.001, respectively), as well as in apple-allergic and non-apple-allergic group (p<0.001, p<0.001, respectively). The optimal cut-off values for birch pollen and Bet v 1 sIgE were determined to be 7.09 kUA/L (with a sensitivity of 84.1% and specificity of 78.6%) and 5.11 kUA/L (with a sensitivity of 75.0% and specificity of 85.7%) when diagnosing PFAS. In terms of apple allergy, the optimal cut-off value were 9.40 kUA/L (with a sensitivity of 81.3% and specificity of 76.9%) and 6.53 kUA/L (with a sensitivity of 84.4% and specificity of 84.6%), respectively. The predominant sensitization pattern is mono-sensitization to Bet v 1, but when considering immunotherapy, Bet v 2 should also be taken into account. Bet v 1 serves as a valuable biomarker for diagnosing PFAS and apple allergy.

Skin Prick Automated Test device offers more reliable allergy test results compared to a manual skin prick test.

The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed. The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

A high-dose, depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy has a favourable efficacy/safety ratio.

Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose-dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch-pollen-induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma. A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double-blind, parallel-group, dose-ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose-level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up-dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT. Three hundred forty-three patients were included (mean (range) age: 42.6 (19-70)). The highest CPT responder rates were seen in the higher dose-level groups. In the intention-to-treat analysis, the difference between the 100 and 10,000 groups was statistically significant (p=0.0118). Although the proportion of patients with ≥1 treatment-emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%). Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high-dose-level preparation of a DPP birch pollen extract.

Structural Basis of the Immunological Cross-Reactivity between Kiwi and Birch Pollen.

Allergies related to kiwi consumption have become a growing health concern, with their prevalence on the rise. Many of these allergic reactions are attributed to cross-reactivity, particularly with the major allergen found in birch pollen. This cross-reactivity is associated with proteins belonging to the pathogenesis-related class 10 (PR-10) protein family. In our study, we determined the three-dimensional structures of the two PR-10 proteins in gold and green kiwi fruits, Act c 8 and Act d 8, using nuclear magnetic resonance (NMR) spectroscopy. The structures of both kiwi proteins closely resemble the major birch pollen allergen, Bet v 1, providing a molecular explanation for the observed immunological cross-reactivity between kiwi and birch pollen. Compared to Act d 11, however, a kiwi allergen that shares the same architecture as PR-10 proteins, structural differences are apparent. Moreover, despite both Act c 8 and Act d 8 containing multiple cysteine residues, no disulfide bridges are present within their structures. Instead, all the cysteines are accessible on the protein's surface and exposed to the surrounding solvent, where they are available for reactions with components of the natural food matrix. This structural characteristic sets Act c 8 and Act d 8 apart from other kiwi proteins with a high cysteine content. Furthermore, we demonstrate that pyrogallol, the most abundant phenolic compound found in kiwi, binds into the internal cavities of these two proteins, albeit with low affinity. Our research offers a foundation for further studies aimed at understanding allergic reactions associated with this fruit and exploring how interactions with the natural food matrix might be employed to enhance food safety.

Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy.

IgE cross-sensitization to major birch pollen allergen Bet v 1 and pathogenesis-related (PR10) plant food allergens is responsible for the pollen-food allergy syndrome. We designed a recombinant protein, AB-PreS, consisting of non-allergenic peptides derived from the IgE-binding sites of Bet v 1 and the cross-reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB-PreS was expressed in E.coli and purified by chromatography. The allergenic and inflammatory activity of AB-PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB-PreS and birch pollen extract-based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA. IgE-binding experiments and basophil activation test revealed the hypoallergenic nature of AB-PreS. AB-PreS induced lower T-cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB-PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract-based vaccines. Additionally, immunization with AB-PreS induced HBV-specific antibodies potentially protecting from infection with HBV. The recombinant AB-PreS-based vaccine is hypoallergenic and superior over currently registered allergen extract-based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.

Association between ambient temperature and common allergenic pollen and fungal spores: A 52-year analysis in central England, United Kingdom

Exposure to pollen and fungal spores can trigger asthma/allergic symptoms and affect health. Rising temperatures from climate change have been associated with earlier seasons and increasing intensity for some pollen, with weaker evidence for fungal spores. It is unclear whether climate change has resulted in changes in the exposure-response function between temperature and pollen/fungal spore concentrations over time. This study examined associations between temperature and pollen/fungal spores in different time periods and assessed potential adaptation using the longest pollen/fungal spore dataset in existence (52 years). Daily concentrations of pollen (birch and grass) and fungal spores (Cladosporium, Alternaria, Sporobolomyces and Tilletiopsis) collected between April and October from Derby (1970–2005) and Leicester (2006–2021), UK, were analysed. Cumulative seasonal concentrations (seasonal integral) and start-of-season were calculated and linked to seasonal mean temperatures (Tmeans) using generalized additive models. Daily concentrations were evaluated against daily Tmean with distributed lagged nonlinear models. Models were adjusted for precipitation, relative humidity, long-term trend and location. Seasonal and daily analyses were respectively stratified into two periods (1970–1995, 1997–2021) and five decades. Warmer seasonal Tmeans were associated with higher seasonal integral for birch, Cladosporium and Alternaria, as well as earlier start-of-season for birch, grass and Cladosporium. There were indications of changing associations with temperature in the recent decades. A warmer January was associated with higher seasonal integral for grass in 1997–2021, but not in 1970–1995. In 2000–2021, daily concentrations of birch pollen tended to remain at higher levels, vs. decrease during 1990s, when Tmean was between 13 and 15 °C. Our study suggests higher temperatures experienced in recent decades are associated with higher overall abundance of some pollen/fungal spores, which may increase future disease burdens of allergies. The changing responses of some pollen to higher temperatures over time may indicate adaptation to increasing temperatures and should be considered in climate change mitigation and adaptation planning.

Detection of Bet v 1 Homologous Proteins and Plant Profilins by Indirect ELISA.

Allergies are an ever-increasing health problem in developed societies. Cross-allergies caused by panallergens are a particularly difficult issue. Proteins similar to the main birch pollen Bet v 1 allergen and profilin are some of the most common allergens. These proteins have a very conservative structure and are present in many distinct organisms. Hence, the knowledge of their natural occurrence is very important for the prevention of allergic reactions. The immunometric method is the most useful approach for determining these allergens. The requirement of reliability and simplicity is fulfilled by enzyme-linked immunosorbent assay (ELISA). In this chapter, detailed procedures are described for the determination of Bet v 1 homologous proteins and plant profilins with the use of indirect, noncompetitive ELISA.

Assessing IgE sensitization profiles to birch and timothy grass pollen allergens in birch pollen allergic blood donors using an oligoplex specific IgE assay

IgE sensitization profiles to single birch allergens in birch-sensitized patients differ among European countries. The aim of this study was to determine the distribution of specific IgE antibodies to major and minor birch pollen allergens in a population of allergic Norwegian individuals by using a birch allergic blood donor population as a surrogate sample. Sixty blood donors were recruited and sampled based on birch allergy symptoms such as rhinitis, rhinoconjunctivitis and/or mild asthma in previous seasons. All sera were collected before start of the pollen season and tested using a line blot assay (Euroimmun AG, Lübeck, Germany) for IgE to birch and timothy pollen. Both extracts, single allergens, and cross-reacting carbohydrate determinants (CCD) were analysed. Only donors with specific IgE to birch and/or timothy grass were further evaluated. Specific IgE to birch pollen extract was found in 52 sera, and sensitization to timothy grass in 40 sera. Specific IgE to Bet v 1 was predominant in contrast to Bet v 4 which was absent. However, sensitization to the minor allergens Bet v 2 and 6 was always found together with high levels of IgE to Bet v 1. Subjects sensitized to the profilin Bet v 2 from birch were also sensitized to Phl p 12 from timothy grass. In conclusion, there was predominantly Bet v 1 sensitization in this cohort and low sensitization to minor allergens and cross-reactive allergens (Bet v 2, Bet v 4, Phl p 7 and Phl p 12).

Estimation of historical daily airborne pollen concentrations across Switzerland using a spatio temporal random forest model

High concentrations of airborne pollen trigger seasonal allergies and possibly more severe adverse respiratory and cardiovascular health events. Predicting pollen concentration accurately is valuable for epidemiological studies, in order to study the effects of pollen exposure. We aimed to develop a spatiotemporal machine learning model predicting daily pollen concentrations at a spatial resolution of 1 × 1 km across Switzerland between 2000 and 2019. Daily pollen concentrations for five common, highly allergenic pollen types (hazel, alder, birch ash, and grasses) were available from fourteen measurement sites across Switzerland. We considered several predictors such as elevation, species distribution, wind speed, wind direction, temperature, precipitation, relative humidity, satellite-observed Normalized Difference Vegetation Index, and land-use (CORINE, Landsat satellite) to explain variation in pollen concentration. We employed feature engineering techniques to encode categorical variables and fill in missing values. We applied a random forest machine learning model with 5-fold cross-validation. The 5th–99th percentiles for concentrations of hazel, alder, birch, ash, and grass pollen at the pollen monitoring stations were 0–298, 0–306, 0–1153, 0–800, and 0–290 pollen grains/m3, respectively. The results of a predictive model for these concentrations yielded overall R2 values of 0.87, 0.84, 0.89, 0.88, and 0.91, and temporal root mean squared errors (RMSEs) of 16.07, 16.72, 69.04, 41.50, and 22.45 pollen grains/m3. An analysis of predictor variable importance indicates that the average national daily pollen concentration is the most important predictor of pollen concentrations for all pollen types. Furthermore, meteorological variables including temperature, total precipitation, humidity, boundary layer height, wind speed, and wind direction, as well as date and satellite features, are important factors in pollen concentration prediction. These spatiotemporal pollen models will serve to estimate individual residential pollen exposure for epidemiological studies. Resulting estimates will enable us to study respiratory and cardiovascular mortality and hospital admissions in Switzerland.

Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes.

The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail. To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation. Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG1 and IgG4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis. The ability of Bet v 1-specific serum antibodies from non-allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1-derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non-allergic subjects to modulate Bet v 1-induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients. IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG1 and IgG4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen-containing food. Natural Bet v 1-specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1-specific basophil activation. IgE and IgG antibodies from BPA patients and birch pollen-exposed non-sensitized subjects recognize different epitopes. These findings explain why natural allergen-specific IgG do not protect against allergic symptoms and suggest that allergen-specific IgE and IgG have different clonal origin.

Tolerability and Safety of Sublingual Immunotherapy in Patients with Tree Pollen Allergy in Daily Practice-An Open, Prospective, Non-Interventional Study.

To investigate the tolerability and safety of two sublingual tree pollen extracts approved in 2018, a non-interventional study (NIS) was performed. This NIS was an 8-month observational study conducted at 84 sites throughout Germany. Study participants received either a sublingual liquid allergen extract of birch pollen (SBPE) or a liquid allergen extract consisting of a mixture of birch, hazel, and alder tree pollen (STPE). Data from 432 patients were analyzed for the occurrence of adverse events and patient compliance. At least one local reaction occurred in 69 (22.2%) patients, whereas systemic reactions were only observed in 27 (6.3%) patients. STPE-treated patients developed systemic reactions more frequently than SBPE-treated patients (SBPE: 9 (4.3%) vs. STPE: 18 (8.0%)). Only one patient developed a systemic grade III reaction. Severe systemic grade IV reactions were not observed. A total of 348 (98.6%) of the patients who completed all visits were satisfied or very satisfied with the sublingual immunotherapy (SLIT), and 322 (71%) patients completed all visits. Both investigated products were well tolerated by the patients and demonstrated a good safety profile. AEs were observed less frequently than in the preceding clinical phase III trial, and no new safety concerns were identified.

Circulating mast cell progenitors increase during natural birch pollen exposure in allergic asthma patients.

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.