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Background: There is evidence that global anthropogenic climate change may be impacting floral phenology and the temporal and spatial characteristics of aero-allergenic pollen. Given the extent of current and future climate uncertainty, there is a need to strengthen predictive pollen forecasts., Methods: The study aims to use CatBoost (CB) and deep learning (DL) models for predicting the daily total pollen concentration up to 14 days in advance for 23 cities, covering all five continents. The model includes the projected environmental parameters, recent concentrations (1, 2 and 4 weeks), and the past environmental explanatory variables, and their future values., Results: The best pollen forecasts include Mexico City (R 2 (DL_7) ≈ .7), and Santiago (R 2 (DL_7) ≈ .8) for the 7th forecast day, respectively; while the weakest pollen forecasts are made for Brisbane (R 2 (DL_7) ≈ .4) and Seoul (R 2 (DL_7) ≈ .1) for the 7th forecast day. The global order of the five most important environmental variables in determining the daily total pollen concentrations is, in decreasing order: the past daily total pollen concentration, future 2 m temperature, past 2 m temperature, past soil temperature in 28-100 cm depth, and past soil temperature in 0-7 cm depth. City-related clusters of the most similar distribution of feature importance values of the environmental variables only slightly change on consecutive forecast days for Caxias do Sul, Cape Town, Brisbane, and Mexico City, while they often change for Sydney, Santiago, and Busan., Conclusions: This new knowledge of the ecological relationships of the most remarkable variables importance for pollen forecast models according to clusters, cities and forecast days is important for developing and improving the accuracy of airborne pollen forecasts., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The EAACI Guidelines on the impact of short-term exposure to outdoor pollutants on asthma-related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence-informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short-term exposure to all pollutants evaluated increases the risk of asthma-related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of evidence at specific lag days). There is limited evidence for the impact of traffic-related air pollution and outdoor pesticides exposure as well as for the interventions to reduce emissions. Due to the quality of evidence, conditional recommendations were formulated for all pollutants and for the interventions reducing outdoor air pollution. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but global measures for clean air are needed to achieve significant impact., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Inflammatory skin diseases such as atopic eczema (atopic dermatitis [AD]) affect children and adults globally. In AD, the skin barrier is impaired on multiple levels. Underlying factors include genetic, chemical, immunologic, and microbial components. Increased skin pH in AD is part of the altered microbial microenvironment that promotes overgrowth of the skin microbiome with Staphylococcus aureus. The secretion of virulence factors, such as toxins and proteases, by S aureus further aggravates the skin barrier deficiency and additionally disrupts the balance of an already skewed immune response. Skin commensal bacteria, however, can inhibit the growth and pathogenicity of S aureus through quorum sensing. Therefore, restoring a healthy skin microbiome could contribute to remission induction in AD. This review discusses direct and indirect approaches to targeting the skin microbiome through modulation of the skin pH; UV treatment; and use of prebiotics, probiotics, and postbiotics. Furthermore, exploratory techniques such as skin microbiome transplantation, ozone therapy, and phage therapy are discussed. Finally, we summarize the latest findings on disease and microbiome modification through targeted immunomodulatory systemic treatments and biologics. We believe that targeting the skin microbiome should be considered a crucial component of successful AD treatment in the future., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: C. Traidl-Hoffmann reports institutes grants from Sebapharma, Germany, Beiersdorf, Germany, L’Oreal, Germany; personal fees from Novartis, Germany, Sanofi, Germany, Lilly pharma, Germany, grants and Töpfer GmbH, Bencard, Germany, Danone nutricia, Lancome, Germany, Loreal, Germany, outside the submitted work. M. Reiger reports personal fees from Novartis, Germany, Reviderm Germany, Bencard Allergy, La Roche Posay. C. Hülpüsch reports personal fees from Reviderm Germany. R. Rohayem reports personal fees from Novartis outside the submitted work., (Copyright © 2024. Published by Elsevier Inc.)

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO 2 , SO 2 , O 3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO 2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence)., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The high prevalence of hay fever in Europe has raised concerns about the implications of climate change-induced higher temperatures on pollen production. Our study focuses on downy birch pollen production across Europe by analyzing 456 catkins during 2019-2021 in 37 International Phenological Gardens (IPG) spanning a large geographic gradient. As IPGs rely on genetically identical plants, we were able to reduce the effects of genetic variability. We studied the potential association with masting behavior and three model specifications based on mean and quantile regression to assess the impact of meteorology (e.g., temperature and precipitation) and atmospheric gases (e.g., ozone (O 3 ) and carbon-dioxide (CO 2 )) on pollen and catkin production, while controlling for tree age approximated by stem circumference. The results revealed a substantial geographic variability in mean pollen production, ranging from 1.9 to 2.5 million pollen grains per catkin. Regression analyses indicated that elevated average temperatures of the previous summer corresponded to increased pollen production, while higher O 3 levels led to a reduction. Additionally, catkins number was positively influenced by preceding summer's temperature and precipitation but negatively by O 3 levels. The investigation of quantile effects revealed that the impacts of mean temperature and O 3 levels from the previous summer varied throughout the conditional response distribution. We found that temperature predominantly affected trees characterized by a high pollen production. We therefore suggest that birches modulate their physiological processes to optimize pollen production under varying temperature regimes. In turn, O 3 levels negatively affected trees with pollen production levels exceeding the conditional median. We conclude that future temperature increase might exacerbate pollen production while other factors may modify (decrease in the case of O 3 and amplify for precipitation) this effect. Our comprehensive study sheds light on potential impacts of climate change on downy birch pollen production, which is crucial for birch reproduction and human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new-onset asthma (incidence) and (ii) adverse asthma-related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new-onset asthma and critical and important asthma-related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new-onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new-onset asthma and with asthma severity (low level of certainty). Exposure to pesticides and VOCs may increase the risk of new-onset asthma (very low certainty evidence). The impact on asthma-related outcomes of all major indoor pollutants is uncertain. As the level of certainty is low or very low for most of the available evidence on the impact of indoor pollutants on asthma-related outcomes more rigorous research in the field is warranted., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background and Aims: In recent decades, nighttime temperatures have increased faster than daytime temperatures. The increasing prevalence of nocturnal heat exposure may pose a significant risk to cardiovascular health. This study investigated the association between nighttime heat exposure and stroke risk in the region of Augsburg, Germany, and examined its temporal variations over 15 years., Methods: Hourly meteorological parameters, including mean temperature, relative humidity, and barometric pressure, were acquired from a local meteorological station. A data set was obtained consisting of 11 037 clinical stroke cases diagnosed during warmer months (May to October) between the years 2006 and 2020. The average age of cases was 71.3 years. Among these cases, 642 were identified as haemorrhagic strokes, 7430 were classified as ischaemic strokes, and 2947 were transient ischaemic attacks. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the stroke risk associated with extreme nighttime heat, as measured by the hot night excess (HNE) index after controlling for the potential confounding effects of daily maximum temperature and other climatic variables. Subgroup analyses by age group, sex, stroke subtype, and stroke severity were performed to identify variations in susceptibility to nighttime heat., Results: Results suggested a significant increase in stroke risk on days with extreme nighttime heat (97.5% percentile of HNE) (odds ratio 1.07, 95% confidence interval 1.01-1.15) during the full study period. When comparing the results for 2013-20 with the results for 2006-12, there was a significant increase (P < .05) in HNE-related risk for all strokes and specifically for ischaemic strokes during the more recent period. Furthermore, older individuals, females, and patients with mild stroke symptoms exhibited a significantly increased vulnerability to nighttime heat., Conclusions: This study found nocturnal heat exposure to be related to elevated stroke risk after controlling for maximum daytime temperature, with increasing susceptibility between 2006 and 2020. These results underscore the importance of considering nocturnal heat as a critical trigger of stroke events in a warming climate., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Clinical data on the types of respiratory pathogens which are most frequently engaged in respiratory co-infections of children and adults are lacking. We analyzed 10 years of data on a total of over 15,000 tests for 16 viral and bacterial pathogens detected in clinical samples at the University Hospital of Augsburg, Germany. Co-infection frequencies and their seasonal patterns were examined using a proportional distribution model. Co-infections were detected in 7.3% of samples, with a higher incidence in children and males. The incidence of interbacterial and interviral co-infections was higher than expected, whereas bacterial-viral co-infections were less frequent. H. influenzae , S. pneumoniae , rhinovirus, and respiratory syncytial virus (RSV) were most frequently involved. Most co-infections occurred in winter, but distinct summer peaks were also observed, which occurred even in children, albeit less pronounced than in adults. Seasonality of respiratory (co-)infections decreased with age. Our results suggest to adjust existing testing strategies during high-incidence periods., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Importance: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown., Objective: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer., Design, Setting, and Participants: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started., Exposure: Adjuvant radiotherapy for breast cancer for 7 weeks., Main Outcomes and Measures: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration., Results: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load., Conclusions and Relevance: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

Background: The increase in allergies began worldwide with the onset of the Great Acceleration. Environmental pollution and climate change now threaten to cancel out decades of success in health research., Objective: A summary of environmental influences is provided, which not only shows the significant increase in the prevalence of allergies worldwide but also that of noncommunicable diseases. The effects of the climate crisis on allergies and the multifactorial and interfunctional relationships with other environmental changes are described in detail., Material and Methods: In order to obtain an overview of the possible effects of global environmental changes on allergies, a wide range of literature was evaluated and the study results were prepared and summarized., Results: A large number of allergens are influencing the human exposome on a daily basis. These allergens are triggered by environmental changes, such as air pollution in the ambient air and indoors, chemicals in everyday objects or residues in food. People are sensitized by the interaction of allergens and pollutants., Conclusion: The prevalence of allergies is stagnating in industrialized countries. This is probably just the calm before the storm. The accelerating effects of global warming could make pollen and air pollutants even more aggressive in the future. Urgent action is therefore needed to minimize environmental pollution and mitigate climate change., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The global burden of noncommunicable diseases (NCD) has seen a strong increase in recent decades and attributable to the influence of environmental factors. For a multitude of diseases an association with epithelial barrier damage has been reported., Objective: This article provides an overview of the health effects of environmental pollution in the context of the epithelial barrier hypothesis of Cezmi Akdis. Additionally, exemplary mechanisms of a barrier damage are described. Finally, possible preventive and therapeutic consequences are discussed., Material and Methods: The PubMed database was searched for the relevant topics and selected literature was reviewed., Results: A wide variety of substances can damage the epithelial barriers of the skin, lungs and gastrointestinal tract. The rise in the prevalences of atopic diseases could (partly) be due to an increased exposure to barrier-damaging substances, such as particulate matter and laundry detergents. A possible pathogenetic mechanism is the initiation and maintenance of an immune response by subepithelial penetration of microorganisms through damaged epithelia., Conclusion: Based on the epithelial barrier hypothesis new therapeutic and prevention strategies can be developed. The regulation of hazardous chemicals and the fight against environmental pollution and climate change are necessary to reduce the burden of disease., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

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 PM 10 . 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., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: Microbiome analysis is becoming a standard component in many scientific studies, but also requires extensive quality control of the 16S rRNA gene sequencing data prior to analysis. In particular, when investigating low-biomass microbial environments such as human skin, contaminants distort the true microbiome sample composition and need to be removed bioinformatically. We introduce MicrobIEM, a novel tool to bioinformatically remove contaminants using negative controls., Results: We benchmarked MicrobIEM against five established decontamination approaches in four 16S rRNA amplicon sequencing datasets: three serially diluted mock communities (10 8 -10 3 cells, 0.4-80% contamination) with even or staggered taxon compositions and a skin microbiome dataset. Results depended strongly on user-selected algorithm parameters. Overall, sample-based algorithms separated mock and contaminant sequences best in the even mock, whereas control-based algorithms performed better in the two staggered mocks, particularly in low-biomass samples (≤ 10 6 cells). We show that a correct decontamination benchmarking requires realistic staggered mock communities and unbiased evaluation measures such as Youden's index. In the skin dataset, the Decontam prevalence filter and MicrobIEM's ratio filter effectively reduced common contaminants while keeping skin-associated genera., Conclusions: MicrobIEM's ratio filter for decontamination performs better or as good as established bioinformatic decontamination tools. In contrast to established tools, MicrobIEM additionally provides interactive plots and supports selecting appropriate filtering parameters via a user-friendly graphical user interface. Therefore, MicrobIEM is the first quality control tool for microbiome experts without coding experience., (© 2023. The Author(s).)

Purpose: The development of a seroma after breast cancer surgery is a common postoperative complication seen after simple mastectomy and axillary surgery. We could recently demonstrate that breast cancer patients undergoing a simple mastectomy with subsequent seroma formation developed a T-helper cell increase within the aspirated fluid measured by flow cytometry. The same study revealed a Th2 and/or a Th17 immune response in peripheral blood and seroma fluid of the same patient. Based on these results and within the same study population, we now analyzed the Th2/Th17 cell associated cytokine content as well as the best known clinical important cytokine IL-6., Methods: Multiplex cytokine measurements (IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22) were done on 34 seroma fluids (Sf) after fine needle aspiration of patients who developed a seroma after a simple mastectomy. Serum of the same patient (Sp) and that of healthy volunteers (Sc) were used as controls., Results: We found the Sf to be highly cytokine rich. Almost all analyzed cytokines were significantly higher in abundance in the Sf compared to Sp and Sc, especially IL-6, which promotes Th17 differentiation as well as suppresses Th1 differentiation in favor of Th2 development., Conclusion: Our Sf cytokine measurements reflect a local immune event. In contrast, former study results on T-helper cell populations in both Sf and Sp tend to demonstrate a systemic immune process., (© 2023. The Author(s).)

Airborne pollen monitoring has been conducted for more than a century now, as knowledge of the quantity and periodicity of airborne pollen has diverse use cases, like reconstructing historic climates and tracking current climate change, forensic applications, and up to warning those affected by pollen-induced respiratory allergies. Hence, related work on automation of pollen classification already exists. In contrast, detection of pollen is still conducted manually, and it is the gold standard for accuracy. So, here we used a new-generation, automated, near-real-time pollen monitoring sampler, the BAA500, and we used data consisting of both raw and synthesised microscope images. Apart from the automatically generated, commercially-labelled data of all pollen taxa, we additionally used manual corrections to the pollen taxa, as well as a manually created test set of bounding boxes and pollen taxa, so as to more accurately evaluate the real-life performance. For the pollen detection, we employed two-stage deep neural network object detectors. We explored a semi-supervised training scheme to remedy the partial labelling. Using a teacher-student approach, the model can add pseudo-labels to complete the labelling during training. To evaluate the performance of our deep learning algorithms and to compare them to the commercial algorithm of the BAA500, we created a manual test set, in which an expert aerobiologist corrected automatically annotated labels. For the novel manual test set, both the supervised and semi-supervised approaches clearly outperform the commercial algorithm with an F1 score of up to 76.9 % compared to 61.3 %. On an automatically created and partially labelled test dataset, we obtain a maximum mAP of 92.7 %. Additional experiments on raw microscope images show comparable performance for the best models, which potentially justifies reducing the complexity of the image generation process. Our results bring automatic pollen monitoring a step forward, as they close the gap in pollen detection performance between manual and automated procedure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Obesity is associated with chronic low-grade inflammation, which is underpinned by the presence of elevated levels of circulating proinflammatory cytokines in obese individuals. Due to the close relationship between adipose tissue and the immune system, it can be speculated that the accumulation of fat may influence the frequency and phenotype of lymphocyte populations. The aim of our study was to investigate whether body fat distribution is associated with B lymphocyte composition in peripheral blood. We examined the association between visceral (VAT) and total body fat (TBF) and the frequencies of B-cell subsets in 238 subjects over a period of up to one year using random intercept models. B lymphocyte subsets were determined by fluorescence-based flow cytometry., Results: Inverse associations were found between body fat measurements and plasma blasts, memory B cells, and IgM - IgD - cells. VAT, but not TBF, was positively associated with naive CD19 cells. In our analyses, both VAT and TBF showed positive associations with IgD only B cells., Conclusions: In conclusion, body fat accumulation seems to be associated with a lower proportion of antibody-secreting plasma blasts and memory cells and an increasing amount of partially anergic, naive CD19 cells., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Allergic diseases, especially inhalation allergies, have reached epidemic levels and environmental factors play an important role in their development. Climate change influences the occurrence, frequency, and severity of allergic diseases., Methods: The contents of this article were selected by the authors and developed section by section according to their expertise and the current state of knowledge. The sections were then discussed and agreed upon amongst all authors., Results: The article highlights direct and indirect effects of climate change on allergies. It goes into detail about the connections between climate change and (new) pollen allergens as well as (new) occupational inhalation allergens, explains the effects of climate change on the clinical picture of atopic dermatitis, discusses the connections between air pollutants and allergies, and provides information about the phenomenon of thunderstorm asthma., Conclusions: There is a need for action in the field of pollen and fungal spore monitoring, allergy and sensitisation monitoring, urban planning from an allergological perspective, and changes in the working environment, among others., Competing Interests: Conflicts of interest Randolf Brehler declared lecturing activities (ALK, Allergopharma, Almirall, Astra Zeneca, Behring, Bencard, GlaxoSmithKline, HAL Allergie, Leti, MedUpdate, Merck, Novartis, Omnicuris, Oto-Rhino-Laryngologischer Verein, Sanofi, Stallergenes, Thermo-Fischer) and consulting activities (Allergopharma, Astra Zeneca, GlaxoSmithKline, HAL Allergie, Leti, Lofarma, Novartis). The other authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

Introduction: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems., Methods: The GA 2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL 2 EN ADCARE centres., Results: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD., Conclusion: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Based on scientific findings, the World Health Organization (WHO) has recommended stricter guideline values for air quality in 2021. Significant reductions in the annual mean values of particulate matter (particle size 2.5 µm or smaller, PM 2.5 ) and long-term exposure to nitrogen dioxide (NO 2 ) and ozone (O 3 ) were put forward. The risk of mortality already increases above the WHO guideline values, as shown in studies investigating low concentrations of air pollutants. In Germany, the 2021 WHO guideline values for PM 2.5 and NO 2 were clearly exceeded in 2022.In this position paper we give the following recommendations for the European Air Quality Directive: (1) set binding limit values according to WHO 2021, (2) apply the limit values to the whole of Europe, (3) continue and expand the established country-based monitoring networks, (4) expand air quality measurements for ultrafine particles and soot particles, and (5) link air pollution control and climate protection measures.Stricter limits for air pollutants require societal and political changes in areas such as mobility, energy use and generation, and urban and spatial planning. Implementation according to WHO 2021 would lead to a net economic benefit of 38 billion euros per year.Ambitious limit values for air pollutants also have an impact on climate change mitigation and its health impacts. The Environmental Public Health commission concludes that more ambitious limit values are crucial to enable effective health protection in Germany and calls for air pollutant limit values in line with the 2021 WHO recommendations to become binding in Europe., (© 2023. The Author(s).)

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., Competing Interests: HW, SZ, AK, CTH, GZ, ES, AD, MB, LS, MS, TT, NB, PC, JB, TB and AZ have no conflicts of interest to declare relating to this work. LT was employed by ViiV Healthcare after the study was conducted. JE has participated in Advisory Board for AstraZeneca., (© 2023 The Author(s).)

Background: Healthcare workers (HCWs) are at a high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate risk factors for SARS-CoV-2 infection among HCWs in medical disciplines with AGP., Methods: A nationwide questionnaire-based study in private practices and hospital settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCWs and potential risk factors of infection were investigated., Results: 2070 healthcare facilities with 25113 employees were included in the study. The overall infection rate among HCWs was 4.7%. Multivariate analysis showed that regions with higher incidence rates had a significantly increased risk of infection. Furthermore, hospital setting and HCWs in gastrointestinal endoscopy (GIE) had more than double the risk of infection (OR 2.63; 95% CI 2.50-2.82, p<0.01 and OR 2.35; 95% CI 2.25-2.50, p<0.01). For medical facilities who treated confirmed SARS-CoV-2 cases, there was a tendency towards higher risk of infection (OR 1.39; 95% CI 1.11-1.63, p=0.068)., Conclusion: Both factors within and outside medical facilities appear to be associated with an increased risk of infection among HCWs. Therefore, GIE and healthcare delivery setting were related to increased infection rates. Regions with higher SARS-CoV-2 incidence rates were also significantly associated with increased risk of infection., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls., Methods: We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic))., Results: We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controls non-atopic , aOR = 4.03 [1.20-13.45] vs. controls atopic ). Conjunctivitis showed a negative association versus controls atopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controls atopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters., Conclusions: The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with complex pathogenesis for which the cellular and molecular crosstalk in AD skin has not been fully understood., Methods: Skin tissues examined for spatial gene expression were derived from the upper arm of 6 healthy control (HC) donors and 7 AD patients (lesion and nonlesion). We performed spatial transcriptomics sequencing to characterize the cellular infiltrate in lesional skin. For single-cell analysis, we analyzed the single-cell data from suction blister material from AD lesions and HC skin at the antecubital fossa skin (4 ADs and 5 HCs) and full-thickness skin biopsies (4 ADs and 2 HCs). The multiple proximity extension assays were performed in the serum samples from 36 AD patients and 28 HCs., Results: The single-cell analysis identified unique clusters of fibroblasts, dendritic cells, and macrophages in the lesional AD skin. Spatial transcriptomics analysis showed the upregulation of COL6A5, COL4A1, TNC, and CCL19 in COL18A1-expressing fibroblasts in the leukocyte-infiltrated areas in AD skin. CCR7-expressing dendritic cells (DCs) showed a similar distribution in the lesions. Additionally, M2 macrophages expressed CCL13 and CCL18 in this area. Ligand-receptor interaction analysis of the spatial transcriptome identified neighboring infiltration and interaction between activated COL18A1-expressing fibroblasts, CCL13- and CCL18-expressing M2 macrophages, CCR7- and LAMP3-expressing DCs, and T cells. As observed in skin lesions, serum levels of TNC and CCL18 were significantly elevated in AD, and correlated with clinical disease severity., Conclusion: In this study, we show the unknown cellular crosstalk in leukocyte-infiltrated area in lesional skin. Our findings provide a comprehensive in-depth knowledge of the nature of AD skin lesions to guide the development of better treatments., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The collective of the SerMa pilot study included 100 cases of primary breast cancer or Carcinoma in situ who had undergone a mastectomy procedure with or without reconstruction of the breast using an implant or expander at Augsburg University Hospital between 12/2019 and 12/2022. The study aimed to investigate possible causes of seroma formation; reported here are the clinicopathological correlations between seroma formation and tumor biology and surgical procedures. Seroma occurred significantly more often in patients with older age (median patient age in cases with seroma was 73 years vs. 52 years without seroma; p < 0.001). In addition, patients with larger mastectomy specimen were significantly more likely to develop seroma (median ablation weight in cases with seroma 580 g vs. 330 g without seroma; p < 0.001). Other significant parameters for seroma formation were BMI ( p = 0.005), grading ( p = 0.015) and tumor size ( p = 0.036). In addition, with insertion of implant or expander, a seroma occurred significantly less frequently ( p < 0.001). In a binary logistic regression, age in particular was confirmed as a significant risk factor. In contrast, tumor biological characteristics, number of lymph nodes removed or affected showed no significant effect on seroma formation. The present study shows the need for patient education about the development of seroma in particular in older patients and patients with large breast volumes within the preoperative surgical clarification. These clinicopathological data support the previously published results hypothesizing that seroma formation is related to autoimmune/inflammatory processes and will be tested on a larger collective in the planned international multicenter SerMa study.

Pollen grains are among the main causes of respiratory allergies worldwide and hence they are routinely monitored in urban environments. However, their sources can be located farther, outside cities' borders. So, the fundamental question remains as to how frequent longer-range pollen transport incidents are and if they may actually comprise high-risk allergy cases. The aim was to study the pollen exposure on a high-altitude location where only scarce vegetation exists, by biomonitoring airborne pollen and symptoms of grass pollen allergic individuals, locally. The research was carried out in 2016 in the alpine research station UFS, located at 2650 m height, on the Zugspitze Mountain in Bavaria, Germany. Airborne pollen was monitored by use of portable Hirst-type volumetric traps. As a case study, grass pollen-allergic human volunteers were registering their symptoms daily during the peak of the grass pollen season in 2016, during a 2-week stay on Zugspitze, 13-24 June. The possible origin of some pollen types was identified using back trajectory model HYSPLIT for 27 air mass backward trajectories up to 24 h. We found that episodes of high aeroallergen concentrations may occur even at such a high-altitude location. More than 1000 pollen grains m -3 of air were measured on the UFS within only 4 days. It was confirmed that the locally detected bioaerosols originated from at least Switzerland, and up to northwest France, even eastern American Continent, because of frequent long-distance transport. Such far-transported pollen may explain the observed allergic symptoms in sensitized individuals at a remarkable rate of 87 % during the study period. Long-distance transport of aeroallergens can cause allergic symptoms in sensitized individuals, as evidenced in a sparse-vegetation, low-exposure, 'low-risk' alpine environment. We strongly suggest that we need cross-border pollen monitoring to investigate long-distance pollen transport, as its occurrence seems both frequent and clinically relevant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Non-allergenic, low molecular weight components of pollen grains are suspected to trigger changes in gut functions, sometimes leading to inflammatory conditions. Based on extensive neuroimmune communication in the gut wall, we investigated the effects of aqueous pollen extracts (APE) on enteric and spinal sensory neurons., Methods: Using Ca 2+ and fast potentiometric imaging, we recorded the responses of guinea-pig and human submucous and guinea-pig dorsal root ganglion (DRG) neurons to microejection of low (<3 kDa) and high (≥3 kDa) molecular weight APEs of birch, ragweed, and hazel. Histamine was determined pharmacologically and by mass spectrometry (LC-MS/MS)., Key Results: Birch APE <3kDa evoked strong [Ca +2 ] i signals in the vast majority of guinea-pig DRG neurons, and in guinea-pig and human enteric neurons. The effect of birch APE ≥3kDa was much weaker. Fast neuroimaging in human enteric neurons revealed an instantaneous spike discharge after microejection of birch, ragweed, and hazel APE <3kDa [median (interquartile range) at 7.0 Hz (6.2/9.8), 5.7 Hz (4.4/7.1), and 8.4 Hz (4.3/12.5), respectively]. The percentage of responding neurons per ganglion were similar [birch 40.0% (33.3/100.0), ragweed 50.8% (34.4/85.6), and hazel 83.3% (57.1/100.0)]. A mixture of histamine receptor (H1-H3) blockers significantly reduced nerve activation evoked by birch and ragweed APEs <3kDa , but was ineffective on hazel. Histamine concentrations in ragweed, birch and hazel APE's < 3 kDa were 0.764, 0.047, and 0.013 μM, respectively., Conclusions: Allergen-free APEs from birch, ragweed, and hazel evoked strong nerve activation. Altered nerve-immune signaling as a result of severe pollen exposure could be a pathophysiological feature of allergic and non-allergic gut inflammation., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large-scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer. Here we discuss the progress and further promise of applying artificial intelligence and machine-learning approaches to help unlock the power of complex environmental data sets toward providing causality models of exposure and intervention. We discuss a range of relevant machine-learning paradigms and models including the way such models are trained and validated together with examples of machine learning applied to allergic disease in the context of specific environmental exposures as well as attempts to tie these environmental data streams to the full representative exposome. We also discuss the promise of artificial intelligence in personalized medicine and the methodological approaches to healthcare with the final AI to improve public health., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Atopic dermatitis (AD) is an inflammatory skin disease with a microbiome dysbiosis towards a high relative abundance of Staphylococcus aureus . However, information is missing on the actual bacterial load on AD skin, which may affect the cell number driven release of pathogenic factors. Here, we combined the relative abundance results obtained by next-generation sequencing (NGS, 16S V1-V3) with bacterial quantification by targeted qPCR (total bacterial load = 16S, S. aureus = nuc gene). Skin swabs were sampled cross-sectionally ( n = 135 AD patients; n = 20 healthy) and longitudinally ( n = 6 AD patients; n = 6 healthy). NGS and qPCR yielded highly inter-correlated S. aureus relative abundances and S. aureus cell numbers. Additionally, intra-individual differences between body sides, skin status, and consecutive timepoints were also observed. Interestingly, a significantly higher total bacterial load, in addition to higher S. aureus relative abundance and cell numbers, was observed in AD patients in both lesional and non-lesional skin, as compared to healthy controls. Moreover, in the lesional skin of AD patients, higher S. aureus cell numbers significantly correlated with the higher total bacterial load. Furthermore, significantly more severe AD patients presented with higher S. aureus cell number and total bacterial load compared to patients with mild or moderate AD. Our results indicate that severe AD patients exhibit S. aureus driven increased bacterial skin colonization. Overall, bacterial quantification gives important insights in addition to microbiome composition by sequencing.

Viruses are frequently a microbial biocontaminant of healthy plants. The occurrence of the infection can be also due to environmental stress, like urbanisation, air pollution and increased air temperature, especially under the ongoing climate change. The aim of the present study was to investigate the hypothesis that worsened air quality and fewer green areas may favour the higher frequency of common viral infections, particularly in a common tree in temperate and continental climates, Betula pendula ROTH. We examined 18 trees, during the years 2015-2017, the same always for each year, in the region of Augsburg, Germany. By specific PCR, the frequency of two viruses, Cherry leaf roll virus (CLRV, genus Nepovirus, family Secoviridae), which is frequent in birch trees, and a novel virus tentatively named birch idaeovirus (BIV), which has been only recently described, were determined in pollen samples. The occurrence of the viruses was examined against the variables of urban index, air pollution (O 3 and NO 2 ), air temperature, and tree morphometrics (trunk perimeter, tree height, crown height and diameter). Generalized Non-linear models (binomial logit with backward stepwise removal of independent variables) were employed. During the study period, both CLRV and BIV were distributed widely throughout the investigated birch individuals. CLRV seemed to be rather cosmopolitan and was present independent of any abiotic factor. BIV's occurrence was mostly determined by higher values of the urban index and of NO 2 . Urban birch trees, located next to high-traffic roads with higher NO 2 levels, are more likely to be infected by BIV. Increased environmental stress may lead to more plant viral infections. Here we suggest that this is particularly true for urban spaces, near high-traffic roads, where plants may be more stressed, and we recommend taking mitigation measures for controlling negative human interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

High-altitude environments are highly susceptible to the effects of climate change. Thus, it is crucial to examine and understand the behaviour of specific plant traits along altitudinal gradients, which offer a real-life laboratory for analysing future impacts of climate change. The available information on how pollen production varies at different altitudes in mountainous areas is limited. In this study, we investigated pollen production of 17 birch (Betula pubescens Ehrh.) individuals along an altitudinal gradient in the European Alps. We sampled catkins at nine locations in the years 2020-2021 and monitored air temperatures. We investigated how birch pollen, flowers and inflorescences are produced in relation to thermal factors at various elevations. We found that mean pollen production of Betula pubescens Ehrh. varied between 0.4 and 8.3 million pollen grains per catkin. We did not observe any significant relationships between the studied reproductive metrics and altitude. However, minimum temperature of the previous summer was found to be significantly correlated to pollen (r s  = 0.504, p = 0.039), flower (r s  = 0.613, p = 0.009) and catkin (r s  = 0.642, p = 0.005) production per volume unit of crown. Therefore, we suggest that temperature variability even at such small scales is very important for studying the response related to pollen production., (© 2023. The Author(s).)

The assessment of persistence (P), bioaccumulation (B), and toxicity (T) of a chemical is a crucial first step at ensuring chemical safety and is a cornerstone of the European Union's chemicals regulation REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). Existing methods for PBT assessment are overly complex and cumbersome, have produced incorrect conclusions, and rely heavily on animal-intensive testing. We explore how new-approach methodologies (NAMs) can overcome the limitations of current PBT assessment. We propose two innovative hazard indicators, termed cumulative toxicity equivalents (CTE) and persistent toxicity equivalents (PTE). Together they are intended to replace existing PBT indicators and can also accommodate the emerging concept of PMT (where M stands for mobility). The proposed "toxicity equivalents" can be measured with high throughput in vitro bioassays. CTE refers to the toxic effects measured directly in any given sample, including single chemicals, substitution products, or mixtures. PTE is the equivalent measure of cumulative toxicity equivalents measured after simulated environmental degradation of the sample. With an appropriate panel of animal-free or alternative in vitro bioassays, CTE and PTE comprise key environmental and human health hazard indicators. CTE and PTE do not require analytical identification of transformation products and mixture components but instead prompt two key questions: is the chemical or mixture toxic, and is this toxicity persistent or can it be attenuated by environmental degradation? Taken together, the proposed hazard indicators CTE and PTE have the potential to integrate P, B/M and T assessment into one high-throughput experimental workflow that sidesteps the need for analytical measurements and will support the Chemicals Strategy for Sustainability of the European Union., (© 2023. The Author(s).)

Background: Atopic dermatitis (AD) is a heterogeneous, chronic inflammatory skin disease linked to skin microbiome dysbiosis with reduced bacterial diversity and elevated relative abundance of Staphylococcus aureus (S. aureus)., Objectives: We aimed to characterize the yet incompletely understood association between the skin microbiome and patients' demographic and clinical cofactors in relation to AD severity., Methods: The skin microbiome in 48 adult moderate-to-severe AD patients was investigated using next-generation deep sequencing (16S rRNA gene, V1-V3 region) followed by denoising (DADA2) to obtain amplicon sequence variant (ASV) composition., Results: In lesional skin, AD severity was associated with S. aureus relative abundance (r S  = 0.53, p < 0.001) and slightly better with the microbiome diversity measure Evenness (r S  = -0.58, p < 0.001), but not with Richness. Multiple regression confirmed the association of AD severity with microbiome diversity, including Shannon (in lesional skin, p < 0.001), Evenness (in non-lesional skin, p = 0.015) or S. aureus relative abundance (p < 0.012), and with patient's IgE levels (p < 0.001), race (p < 0.032), age (p < 0.034) and sex (p = 0.012). The lesional model explained 62% of the variation in AD severity, and the non-lesional model 50% of the variation., Conclusions: Our results specify the frequently reported "reduced diversity" of the AD-related skin microbiome to reduced Evenness, which was in turn mainly driven by S. aureus relative abundance, rather than to a reduced microbiome Richness. Finding associations between AD severity, the skin microbiome and patient's cofactors is a key aspect in developing new personalized AD treatments, particularly those targeting the AD microbiome., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The heterogeneous (endo)phenotypes of atopic dermatitis (AD) require precision medicine. Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI)≥16. Previous studies have demonstrated an improved treatment response to the anti-interleukin (IL)-13 antibody tralokinumab in AD subgroups with elevated levels of the IL-13-related biomarkers dipeptidyl-peptidase (DPP)-4 and periostin., Methods: Herein, 373 AD patients aged≥12 years were stratified by IL-13 high , periostin high and DPP-4 high endotypes using cross-sectional data from the ProRaD cohort Bonn. "High" was defined as >80 th quantile of 47 non-atopic controls. We analyzed endotype-phenotype associations using machine-learning gradient boosting compared to logistic regression., Results: AD severity and eosinophils correlated with IL-13 and periostin levels. Correlations of IL-13 with EASI were stronger in patients with increased (rs=0.482) than with normal (rs=0.342) periostin levels. We identified eosinophilia>6% and an EASI range of 5.5-17 dependent on the biomarker combination to be associated with increasing probabilities of biomarker high endotypes. Also patients with mild-to-low-moderate severity (EASI<16) featured increased biomarkers (IL-13 high : 41%, periostin high : 48.4%, DPP-4 high : 22.3%). Herthoge sign (adjusted Odds Ratio (aOR)=1.89, 95% Confidence Interval (CI) [1.14-3.14]) and maternal allergic rhinitis (aOR=2.79-4.47) increased the probability of an IL-13 high -endotype, "dirty neck" (aOR=2.83 [1.32-6.07]), orbital darkening (aOR=2.43 [1.08-5.50]), keratosis pilaris (aOR=2.21 [1.1-4.42]) and perleche (aOR=3.44 [1.72-6.86]) of a DPP-4 high -endotype., Conclusions: A substantial proportion of patients with EASI<16 featured high biomarker levels suggesting systemic impact of skin inflammation already below the current cut-off for systemic therapy. Our findings facilitate the identification of patients with distinct endotypes potentially linked to response to IL-13-targeted therapy., (This article is protected by copyright. All rights reserved.)

Higher incidences of asthma during thunderstorms can pose a serious health risk. In this study, we estimate the thunderstorm asthma risk using statistical methods, with special focus on Bavaria, Southern Germany. In this approach, a dataset of asthma-related emergency cases for the study region is combined with meteorological variables and aeroallergen data to identify statistical relationships between the occurrence of asthma (predictand) and different environmental parameters (set of predictors). On the one hand, the results provide evidence for a weak but significant relationship between atmospheric stability indices and asthma emergencies in the region, but also show that currently thunderstorm asthma is not a major concern in Bavaria due to overall low incidences. As thunderstorm asthma can have severe consequences for allergic patients, the presented approach can be important for the development of emergency strategies in regions affected by thunderstorm asthma and under present and future climate change conditions.

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 PM 2.5-10 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, PM 2.5- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The aim of this study was to create an overview on the COVID-associated burdens faced by the oral and maxillofacial surgery (OMS) workforce during 1 year of the pandemic. OMS hospitals and private practices nationwide were surveyed regarding health care worker (HCW) screening, infection status, pre-interventional testing, personal protective equipment (PPE), and economic impact. Participants were recruited via the German Society for Oral and Maxillofacial Surgery. A total of 11 hospitals (416 employees) and 55 private practices (744 employees) participated. The HCW infection rate was significantly higher in private practices than in clinics (4.7% vs. 1.4%, p<0.01), although most infections in HCW occurred in private environment (hospitals 88.2%, private practice 66.7%). Pre-interventional testing was performed significantly less for outpatients in private practices than in hospitals (90.7% vs. 36.4%, p<0.01). Polymerase chain reaction (PCR) was used significantly more for inpatients in hospitals than in private practices (100.0% vs. 27.3%, p<0.01). FFP2/3 use rose significantly in hospitals (0% in second quarter vs. 46% in fourth quarter, p<0.05) and private practices (15% in second quarter vs. 38% in fourth quarter, p<0.01). The decrease in procedures (≤50%) was significantly higher in hospitals than in private practices (90.9% vs. 40.0%, p<0.01). Despite higher infection rates in private practices, declining procedures and revenue affected hospitals more. Future COVID-related measures must adjust the infrastructure especially for hospitals to prevent further straining of staff and finances., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin.

Background: The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis., Methods: Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues., Results: We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1., Conclusions: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)