Ten-year retrospective data analysis reveals frequent respiratory co-infections in hospitalized patients in Augsburg.

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.

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

During the birch pollen season an enhanced incidence of virus infections is noticed, raising the question whether pollen can affect anti-viral responses independent of allergic reactions. We previously showed that birch pollen-treatment of monocyte-derived dendritic cells (moDC) enhances human cytomegalovirus (HCMV) infection. Here we addressed how in moDC the relatively weak pollen response can affect the comparably strong response to HCMV. To this end, moDC were stimulated with aqueous birch pollen extract (APE), HCMV, and APE with HCMV, and transcriptomic signatures were determined after 6 and 24 h of incubation. Infection was monitored upon exposure of moDC to GFP expressing HCMV by flow cytometric analysis of GFP expressing cells. Principle component analysis of RNA sequencing data revealed close clustering of mock and APE treated moDC, whereas HCMV as well as APE with HCMV treated moDC clustered separately after 6 and 24 h of incubation, respectively. Communally induced genes were detected in APE, HCMV and APE with HCMV treated moDC. In APE with HCMV treated moDC, the comparably weak APE induced signatures were maintained after HCMV exposure. In particular, NF-κB/RELA and PI3K/AKT/MAPK signaling were altered upon APE with HCMV exposure. Earlier, we discovered that NF-κB inhibition alleviated APE induced enhancement of HCMV infection. Here we additionally found that impairment of PI3K signaling reduced HCMV infection in HCMV and APE with HCMV treated moDC. APE treated moDC that were exposed to HCMV show a unique host gene signature, which to a large extent is regulated by NF-κB activation and PI3K/AKT/MAPK signaling.

Continental-scale evaluation of downy birch pollen production: Estimating the impacts of global change.

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 (O3) and carbon-dioxide (CO2)) 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 O3 levels led to a reduction. Additionally, catkins number was positively influenced by preceding summer's temperature and precipitation but negatively by O3 levels. The investigation of quantile effects revealed that the impacts of mean temperature and O3 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, O3 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 O3 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.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

EAACI guidelines on environmental science for allergy and asthma: The impact of short-term exposure to outdoor air pollutants on asthma-related outcomes and recommendations for mitigation measures.

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.

The impact of outdoor pollution and extreme temperatures on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

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, NO2, SO2, O3, 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 NO2 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).

The impact of indoor pollution on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

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.

Pollen production of downy birch (Betula pubescens Ehrh.) along an altitudinal gradient in the European Alps.

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 (rs = 0.504, p = 0.039), flower (rs = 0.613, p = 0.009) and catkin (rs = 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.

Pollen long-distance transport associated with symptoms in pollen allergics on the German Alps: An old story with a new ending?

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.

Tissue-specific antigen-presenting cells contribute to distinct phenotypes of allergy.

Antigen-presenting cells (APCs) are critical cells bridging innate and adaptive immune responses by taking up, processing, and presenting antigens to naïve T cells. At steady state, APCs thus control both tissue homeostasis and the induction of tolerance. In allergies however, APCs drive a Th2-biased immune response that is directed against otherwise harmless antigens from the environment. The main types of APCs involved in the induction of allergy are dendritic cells, monocytes, and macrophages. However, these cell types can be further divided into local, tissue-specific populations that differ in their phenotype, migratory capacity, T-cell activating potential, and production of effector molecules. Understanding if distinct populations of APCs contribute to either tissue-specific immune tolerance, allergen sensitization, or allergic inflammation will allow us to better understand disease pathology and develop targeted treatment options for different stages of allergic disease. Therefore, this review describes the main characteristics, phenotypes, and effector molecules of the APCs involved in the induction of allergen-specific Th2 responses in affected barrier sites, such as the skin, nose, lung, and gastrointestinal tract. Furthermore, we highlight open questions that remain to be addressed to fully understand the contribution of different APCs to allergic disease.

Betula pendula trees infected by birch idaeovirus and cherry leaf roll virus: Impacts of urbanisation and NO2 levels.

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 (O3 and NO2), 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 NO2. Urban birch trees, located next to high-traffic roads with higher NO2 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.

Allergen-free extracts from birch, ragweed, and hazel pollen activate human and guinea-pig submucous and spinal sensory neurons.

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 Ca2+ 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.

Is exposure to pollen a risk factor for moderate and severe asthma exacerbations?

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.

Is Pollen Production of Birch Controlled by Genetics and Local Conditions?

Intraspecific genetic variation might limit the relevance of environmental factors on plant traits. For example, the interaction between genetics and (a-)biotic factors regulating pollen production are still poorly understood. In this study, we investigated pollen production of 28 birch (Betula pendula Roth) individuals in the years 2019−2021. We sampled catkins of eleven groups of genetically identical trees, which were partially topped, but of the same age and located in a seed plantation in southern Germany characterized by similar microclimatic conditions. Furthermore, we monitored environmental factors such as air temperature, characterized air quality (NO2, NOx and O3), and assessed potential solar radiation. We especially checked for differences between years as well as between and within clones and assessed the synchronicity of years with high/low pollen production. We present a robust mean for the pollen production of Betula pendula (1.66 million pollen grains per catkin). Our findings show temporal (H(2) = 46.29, p < 0.001) and clonal variations (H(4) = 21.44, p < 0.001) in pollen production. We conclude that synchronized high or low pollen production is not utterly site-specific and, in addition, not strictly dependent on genotypes. We suggest that appropriate clone selection based on application (seed plantation, urban planting) might be advantageous and encourage a long-term monitoring.

Allergy: Type I, II, III, and IV.

Hypersensitivity reactions are overreactions of the immune system clinically seen as allergic and autoimmune diseases. Gell and Coombs originally described four different types of hypersensitivity reactions almost 60 years ago, and their description still applies in large parts. However, some modifications and extensions have been included in original definition. Especially in allergic diseases, it became clear that often, multiple types of hypersensitivity reaction can occur simultaneously. This improved insight is not only important for a better understanding of hypersensitivity disorders, but is especially of importance for improved diagnostics and directing therapeutic interventions.