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.

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.

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.

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.

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.

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.

Pollen season is reflected on symptom load for grass and birch pollen-induced allergic rhinitis in different geographic areas-An EAACI Task Force Report.

BACKGROUND: The effectiveness of allergen immunotherapy (AIT) in seasonal and perennial allergic rhinitis (AR) depends on the definition of pollen exposure intensity or time period. We recently evaluated pollen and symptom data from Germany to examine the new definitions of the European Academy of Allergy and Clinical Immunology (EAACI) on pollen season and peak pollen period start and end. Now, we aim to confirm the feasibility of these definitions to properly mirror symptom loads for grass and birch pollen-induced allergic rhinitis in other European geographical areas such as Austria, Finland and France, and therefore their suitability for AIT and clinical practice support. METHODS: Data from twenty-three pollen monitoring stations from three countries in Europe and for 3 years (2014-2016) were used to investigate the correlation between birch and grass pollen concentrations during the birch and grass pollen season defined via the EAACI criteria, and total nasal symptom and medication scores as reported with the aid of the patient's hay-fever diary (PHD). In addition, we conducted a statistical analysis, together with a graphical investigation, to reveal correlations and dependencies between the studied parameters. RESULTS: The analysis demonstrated that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to pollen-induced symptom loads reported by PHD users during birch and grass pollen season. A statistically significant correlation (slightly higher for birch) has been found between the Total Nasal Symptom and Medication Score (TNSMS) and the pollen concentration levels. Moreover, the maximum symptom levels occurred mostly within the peak pollen periods (PPP) following the EAACI criteria. CONCLUSIONS: Based on our analyses, we confirm the validity of the EAACI definitions on pollen season for both birch and grass and for a variety of geographical locations for the four European countries (including Germany from a previous publication) analyzed so far. On this basis, the use of the EAACI definitions is supported in future clinical trials on AIT as well as in daily routine for optimal patient care. Further evaluation of the EAACI criteria in other European regions is recommended.

The role of mobile health technologies in allergy care: An EAACI position paper.

Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.

An operational robotic pollen monitoring network based on automatic image recognition.

There is high demand for online, real-time and high-quality pollen data. To the moment pollen monitoring has been done manually by highly specialized experts. Here we evaluate the electronic Pollen Information Network (ePIN) comprising 8 automatic BAA500 pollen monitors in Bavaria, Germany. Automatic BAA500 and manual Hirst-type pollen traps were run simultaneously at the same locations for one pollen season. Classifications by BAA500 were checked by experts in pollen identification, which is traditionally considered to be the "gold standard" for pollen monitoring. BAA500 had a multiclass accuracy of over 90%. Correct identification of any individual pollen taxa was always >85%, except for Populus (73%) and Alnus (64%). The BAA500 was more precise than the manual method, with less discrepancies between determinations by pairs of automatic pollen monitors than between pairs of humans. The BAA500 was online for 97% of the time. There was a significant correlation of 0.84 between airborne pollen concentrations from the BAA500 and Hirst-type pollen traps. Due to the lack of calibration samples it is unknown which instrument gives the true concentration. The automatic BAA500 network delivered pollen data rapidly (3 h delay with real-time), reliably and online. We consider the ability to retrospectively check the accuracy of the reported classification essential for any automatic system.

Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke.

BACKGROUND: Wood combustion emissions have been studied previously either by in vitro or in vivo models using collected particles, yet most studies have neglected gaseous compounds. Furthermore, a more accurate and holistic view of the toxicity of aerosols can be gained with parallel in vitro and in vivo studies using direct exposure methods. Moreover, modern exposure techniques such as air-liquid interface (ALI) exposures enable better assessment of the toxicity of the applied aerosols than, for example, the previous state-of-the-art submerged cell exposure techniques. METHODS: We used three different ALI exposure systems in parallel to study the toxicological effects of spruce and pine combustion emissions in human alveolar epithelial (A549) and murine macrophage (RAW264.7) cell lines. A whole-body mouse inhalation system was also used to expose C57BL/6 J mice to aerosol emissions. Moreover, gaseous and particulate fractions were studied separately in one of the cell exposure systems. After exposure, the cells and animals were measured for various parameters of cytotoxicity, inflammation, genotoxicity, transcriptome and proteome. RESULTS: We found that diluted (1:15) exposure pine combustion emissions (PM1 mass 7.7 ± 6.5 mg m- 3, 41 mg MJ- 1) contained, on average, more PM and polycyclic aromatic hydrocarbons (PAHs) than spruce (PM1 mass 4.3 ± 5.1 mg m- 3, 26 mg MJ- 1) emissions, which instead showed a higher concentration of inorganic metals in the emission aerosol. Both A549 cells and mice exposed to these emissions showed low levels of inflammation but significantly increased genotoxicity. Gaseous emission compounds produced similar genotoxicity and a higher inflammatory response than the corresponding complete combustion emission in A549 cells. Systems biology approaches supported the findings, but we detected differing responses between in vivo and in vitro experiments. CONCLUSIONS: Comprehensive in vitro and in vivo exposure studies with emission characterization and systems biology approaches revealed further information on the effects of combustion aerosol toxicity than could be achieved with either method alone. Interestingly, in vitro and in vivo exposures showed the opposite order of the highest DNA damage. In vitro measurements also indicated that the gaseous fraction of emission aerosols may be more important in causing adverse toxicological effects. Combustion aerosols of different wood species result in mild but aerosol specific in vitro and in vivo effects.

Mixture Analyses of Air-sampled Pollen Extracts Can Accurately Differentiate Pollen Taxa.

The daily pollen forecast provides crucial information for allergic patients to avoid exposure to specific pollen. Pollen counts are typically measured with air samplers and analyzed with microscopy by trained experts. In contrast, this study evaluated the effectiveness of identifying the component pollens using the metabolites extracted from an air-sampled pollen mixture. Ambient air-sampled pollen from Munich in 2016 and 2017 was visually identified from reference pollens and extracts were prepared. The extracts were lyophilized, rehydrated in optimal NMR buffers, and filtered to remove large proteins. NMR spectra were analyzed for pollen associated metabolites. Regression and decision-tree based algorithms using the concentration of metabolites, calculated from the NMR spectra outperformed algorithms using the NMR spectra themselves as input data for pollen identification. Categorical prediction algorithms trained for low, medium, high, and very high pollen count groups had accuracies of 74% for the tree, 82% for the grass, and 93% for the weed pollen count. Deep learning models using convolutional neural networks performed better than regression models using NMR spectral input, and were the overall best method in terms of relative error and classification accuracy (86% for tree, 89% for grass, and 93% for weed pollen count). This study demonstrates that NMR spectra of air-sampled pollen extracts can be used in an automated fashion to provide taxa and type-specific measures of the daily pollen count.

Artemisia pollen is the main vector for airborne endotoxin.

BACKGROUND: Endotoxin (LPS) released from gram-negative bacteria causes strong immunologic and inflammatory effects and, when airborne, can contribute to respiratory conditions, such as allergic asthma. OBJECTIVES: We sought to identify the source of airborne endotoxin and the effect of this endotoxin on allergic sensitization. METHODS: We determined LPS levels in outdoor air on a daily basis for 4 consecutive years in Munich (Germany) and Davos (Switzerland). Air was sampled as particulate matter (PM) greater than 10 µm (PM > 10) and PM between 2.5 and 10 µm. LPS levels were determined by using the recombinant Factor C assay. RESULTS: More than 60% of the annual endotoxin exposure was detected in the PM > 10 fraction, showing that bacteria do not aerosolize as independent units or aggregates but adhered to large particles. In Munich 70% of annual exposure was detected between June 12th and August 28th. Multivariate modeling showed that endotoxin levels could be explained by phenological parameters (ie, plant growth). Indeed, days with high airborne endotoxin levels correlated well with the amount of Artemisia pollen in the air. Pollen collected from plants across Europe (100 locations) showed that the highest levels of endotoxin were detected on Artemisia vulgaris (mugwort) pollen, with little on other pollen. Microbiome analysis showed that LPS concentrations on mugwort pollen were related to the presence of Pseudomonas species and Pantoea species communities. In a mouse model of allergic disease, the presence of LPS on mugwort pollen was needed for allergic sensitization. CONCLUSIONS: The majority of airborne endotoxin stems from bacteria dispersed with pollen of only one plant: mugwort. This LPS was essential for inducing inflammation of the lung and allergic sensitization.

Near-ground effect of height on pollen exposure.

The effect of height on pollen concentration is not well documented and little is known about the near-ground vertical profile of airborne pollen. This is important as most measuring stations are on roofs, but patient exposure is at ground level. Our study used a big data approach to estimate the near-ground vertical profile of pollen concentrations based on a global study of paired stations located at different heights. We analyzed paired sampling stations located at different heights between 1.5 and 50 m above ground level (AGL). This provided pollen data from 59 Hirst-type volumetric traps from 25 different areas, mainly in Europe, but also covering North America and Australia, resulting in about 2,000,000 daily pollen concentrations analyzed. The daily ratio of the amounts of pollen from different heights per location was used, and the values of the lower station were divided by the higher station. The lower station of paired traps recorded more pollen than the higher trap. However, while the effect of height on pollen concentration was clear, it was also limited (average ratio 1.3, range 0.7-2.2). The standard deviation of the pollen ratio was highly variable when the lower station was located close to the ground level (below 10 m AGL). We show that pollen concentrations measured at >10 m are representative for background near-ground levels.

Variation of the group 5 grass pollen allergen content of airborne pollen in relation to geographic location and time in season.

BACKGROUND: Allergies to grass pollen are the number one cause of outdoor hay fever. The human immune system reacts with symptoms to allergen from pollen. OBJECTIVE: We investigated the natural variability in release of the major group 5 allergen from grass pollen across Europe. METHODS: Airborne pollen and allergens were simultaneously collected daily with a volumetric spore trap and a high-volume cascade impactor at 10 sites across Europe for 3 consecutive years. Group 5 allergen levels were determined with a Phl p 5-specific ELISA in 2 fractions of ambient air: particulate matter of greater than 10 µm in diameter and particulate matter greater than 2.5 µm and less than 10 µm in diameter. Mediator release by ambient air was determined in FcεRI-humanized basophils. The origin of pollen was modeled and condensed to pollen potency maps. RESULTS: On average, grass pollen released 2.3 pg of Phl p 5 per pollen. Allergen release per pollen (potency) varied substantially, ranging from less than 1 to 9 pg of Phl p 5 per pollen (5% to 95% percentile). The main variation was locally day to day. Average potency maps across Europe varied between years. Mediator release from basophilic granulocytes correlated better with allergen levels per cubic meter (r(2) = 0.80, P < .001) than with pollen grains per cubic meter (r(2) = 0.61, P < .001). In addition, pollen released different amounts of allergen in the non-pollen-bearing fraction of ambient air, depending on humidity. CONCLUSION: Across Europe, the same amount of pollen released substantially different amounts of group 5 grass pollen allergen. This variation in allergen release is in addition to variations in pollen counts. Molecular aerobiology (ie, determining allergen in ambient air) might be a valuable addition to pollen counting.

Automatic and Online Pollen Monitoring.

BACKGROUND: Pollen are monitored in Europe by a network of about 400 pollen traps, all operated manually. To date, automated pollen monitoring has only been feasible in areas with limited variability in pollen species. There is a need for rapid reporting of airborne pollen as well as for alleviating the workload of manual operation. We report our experience with a fully automated, image recognition-based pollen monitoring system, BAA500. METHODS: The BAA500 sampled ambient air intermittently with a 3-stage virtual impactor at 60 m3/h in Munich, Germany. Pollen is deposited on a sticky surface that was regularly moved to a microscope equipped with a CCD camera. Images of the pollen were constructed and compared with a library of known samples. A Hirst-type pollen trap was operated simultaneously. RESULTS: Over 480,000 particles sampled with the BAA500 were both manually and automatically identified, of which about 46,000 were pollen. Of the automatically reported pollen, 93.3% were correctly recognized. However, compared with manual identification, 27.8% of the captured pollen were missing in the automatic report, with most reported as unknown pollen. Salix pollen grains were not identified satisfactorily. The daily pollen concentrations reported by a Hirst-type pollen trap and the BAA500 were highly correlated (r = 0.98). CONCLUSIONS: The BAA500 is a functional automated pollen counter. Its software can be upgraded, and so we expected its performance to improve upon training. Automated pollen counting has great potential for workload reduction and rapid online pollen reporting.