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1.
Handb Exp Pharmacol ; 268: 101-115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34236520

RESUMO

Atopic eczema (AE) is a chronic inflammatory disease hallmarked by intense pruritus and eczematous lesions. It depicts one of the most common skin diseases affecting a major part of children and several percentages of adults.Both pathogenesis and pathophysiology are based on complex orchestrated interactions of skin barrier defects, immunological changes, the environment, and an abundance of other contributing factors. Frequently, AE displays the starting point for other allergic diseases such as allergic asthma and rhinoconjunctivitis. Additionally, the risk of developing food allergy is increased. Furthermore, the disease is accompanied by a susceptibility to bacterial, fungal, and viral infections. The development of new therapies received great impetus by an ample research of the pathophysiological mechanisms, leading to a new era in the treatment of severe atopic eczema due to targeted treatments, e.g. the IL-4R alpha specific monoclonal antibody dupilumab.This article provides an overview of the causative and pathophysiological characteristics, the clinical and diagnostic aspects as well as current and future therapeutical possibilities focusing allergic aspects contributing to the course of the disease.


Assuntos
Asma , Dermatite Atópica , Eczema , Hipersensibilidade , Adulto , Criança , Dermatite Atópica/tratamento farmacológico , Humanos
2.
Dtsch Med Wochenschr ; 146(24-25): 1636-1641, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34879414

RESUMO

The climate crisis and its consequences represent the greatest challenge facing human health and health care system in the 21st century. It threatens to undermine the last decades of health gains. Rising temperatures, fires, floods and droughts can directly and indirectly cause human pathologies, that are physical and mental. Extreme weather events lead to loss of life, basic life resources and cause severe mental burden. More intense and frequent heat waves due to global warming impact human health and increase mortality, especially for those most vulnerable. The heat-related health risk depends on individual state of health as well as environmental and socioeconomic characteristics of residential areas. Increasing exposure to air pollutants, due to wildfires and anthropogenic emissions, raises respiratory and cardiovascular mortality. Climate warming changes ecosystems and enhances biological invasions that can better adapt to warm environments. Pathogen profiles are changing, transmission and spread of vector-borne diseases as Malaria or Dengue are increasing. Further, rising temperatures and air pollution increase the production and allergenicity of pollen, associated with higher prevalence of allergic diseases. Protective environmental factors, as biodiversity or diverse microbiome, should be given greater consideration in future research.Health sector has the central responsibility as the fifth-largest greenhouse gas emitter to transform in a climate-neutral and sustainable way, e. g. by efficient use of resources. Further education and training in this area should be intensified and included in curricula for medical staff. Furthermore, medical professionals must educate patients about the burden of climate change, climate resilience, and the benefits of CO2 reduction - for human but also for planetary health.

3.
JAMA Dermatol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757407

RESUMO

Importance: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and is driven by a complex pathophysiology underlying highly heterogeneous phenotypes. Current advances in precision medicine emphasize the need for stratification. Objective: To perform deep phenotyping and identification of severity-associated factors in adolescent and adult patients with AD. Design, Setting, and Participants: Cross-sectional data from the baseline visit of a prospective longitudinal study investigating the phenotype among inpatients and outpatients with AD from the Department of Dermatology and Allergy of the University Hospital Bonn enrolled between November 2016 and February 2020. Main Outcomes and Measures: Patients were stratified by severity groups using the Eczema Area and Severity Index (EASI). The associations of 130 factors with AD severity were analyzed applying a machine learning-gradient boosting approach with cross-validation-based tuning as well as multinomial logistic regression. Results: A total of 367 patients (157 male [42.8%]; mean [SD] age, 39 [17] years; 94% adults) were analyzed. Among the participants, 177 (48.2%) had mild disease (EASI ≤7), 120 (32.7%) had moderate disease (EASI >7 and ≤ 21), and 70 (19.1%) had severe disease (EASI >21). Atopic stigmata (cheilitis: odds ratio [OR], 8.10; 95% CI, 3.35-10.59; white dermographism: OR, 4.42; 95% CI, 1.68-11.64; Hertoghe sign: OR, 2.75; 95% CI, 1.27-5.93; nipple eczema: OR, 4.97; 95% CI, 1.56-15.78) was associated with increased probability of severe AD, while female sex was associated with reduced probability (OR, 0.30; 95% CI, 0.13-0.66). The probability of severe AD was associated with total serum immunoglobulin E levels greater than 1708 IU/mL and eosinophil values greater than 6.8%. Patients aged 12 to 21 years or older than 52 years had an elevated probability of severe AD; patients aged 22 to 51 years had an elevated probability of mild AD. Age at AD onset older than 12 years was associated with increased probability of severe AD up to a peak at 30 years; age at onset older than 33 years was associated with moderate to severe AD; and childhood onset was associated with mild AD (peak, 7 years). Lifestyle factors associated with severe AD were physical activity less than once per week and (former) smoking. Alopecia areata was associated with moderate (OR, 5.23; 95% CI, 1.53-17.88) and severe (OR, 4.67; 95% CI, 1.01-21.56) AD. Predictive performance of machine learning-gradient boosting vs multinomial logistic regression differed only slightly (mean multiclass area under the curve value: 0.71 [95% CI, 0.69-0.72] vs 0.68 [0.66-0.70], respectively). Conclusions and Relevance: The associations found in this cross-sectional study among patients with AD might contribute to a deeper disease understanding, closer monitoring of predisposed patients, and personalized prevention and therapy.

4.
Int J Environ Health Res ; : 1-17, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607495

RESUMO

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.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34639625

RESUMO

Flowering and pollen seasons are sensitive to environmental variability and are considered climate change indicators. However, it has not been concluded to what extent flowering phenology is indeed reflected in airborne pollen season locally. The aim of this study was to investigate, for the commonly represented in temperate climates and with highly allergenic pollen Betula pendula Roth, the responsiveness of flowering to different environmental regimes and also to check for commensurate changes in the respective pollen seasons. The region of Augsburg, Bavaria, Germany, was initially screened for birch trees, which were geolocated at a radius of 25 km. Random trees across the city were then investigated during three full flowering years, 2015-2017. Flowering observations were made 3-7 times a week, from flower differentiation to flower desiccation, in a total of 43 plant individuals. Data were regressed against meteorological parameters and air pollutant levels in an attempt to identify the driving factors of flowering onset and offset. Flowering dates were compared with dates of the related airborne pollen seasons per taxon; airborne pollen monitoring took place daily using a Hirst-type volumetric sampler. The salient finding was that flowering occurred earlier during warmer years; it also started earlier at locations with higher urbanity, and peaked and ended earlier at sites with higher NO2 concentrations. Airborne pollen season of Betula spp. frequently did not coincide locally with the flowering period of Betula pendula: while flowering and pollen season were synchronized particularly in their onset, local flowering phenology alone could explain only 57.3% of the pollen season variability. This raises questions about the relationship between flowering times and airborne pollen seasons and on the rather underestimated role of the long-distance transport of pollen.


Assuntos
Betula , Dióxido de Nitrogênio , Alérgenos , Alemanha , Humanos , Pólen , Estações do Ano , Temperatura
6.
Z Gastroenterol ; 59(12): 1278-1287, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34687033

RESUMO

BACKGROUND: Practices and hospitals are facing great challenges in coping with the COVID-19-pandemic. So far, data on the impact of the pandemic on gastroenterological facilities are lacking, especially on a temporal course. A database is lacking, especially for the outpatient care sector. University Hospital of Augsburg was commissioned to generate data on this as a part of the collaborative project B-FAST of the Network of University Medicine (NUM). METHODS: Gastroenterological institutions nationwide were surveyed by an online questionnaire. Recruitment was carried out via the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the Professional Association of Gastroenterologists in Private Practice (bng). This manuscript provides an overview of data on the use of protective equipment, pre-interventional testing of patients, staff screening and economic impact over the course of the pandemic. RESULTS: 429 facilities answered the questionnaire. Practices tested their patients pre-interventionally significantly less often than clinics (7.8% vs. 82.6%). In clinics, inpatients (93.1%) were tested significantly more often than outpatients (72.2%). The use of personal protective equipment (PPE) increased significantly during the pandemic. It was shown that over 70% of facilities screened their staff for SARS-CoV-2 without cause. Clinics cancelled elective procedures significantly more often than practices in quarter 4/2020. Procedures and turnover decreased in 2020 compared to the previous year. However, fewer facilities were affected by a loss of revenue than expected in previous studies. CONCLUSION: Our data demonstrate the variable implementation of pre-interventional SARS-CoV-2 testing in outpatient and inpatient care. The use of adequate PPE and staff screening increased during the pandemic.

7.
MMW Fortschr Med ; 163(18): 28-29, 2021 10.
Artigo em Alemão | MEDLINE | ID: mdl-34652651
8.
Allergol Select ; 5: 244-250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476334

RESUMO

It is obvious that social, biogenic, and anthropogenic environmental factors, as well as nutrition contribute to the development and course of atopic eczema. Social deprivation and stress have a negative impact on atopic eczema symptoms, and social change in recent decades has led to a "westernized" lifestyle associated with high prevalence of atopic eczema in industrialized countries. Urbanization leads to an increase in air pollution and a decrease in biodiversity, which negatively affects atopic eczema. Climate change alters the allergenicity of pollen, which increases atopic eczema symptoms in some patients during the pollen season. Protective natural and social factors for the prevention of atopic eczema and for the promotion of "climate resilience" should be given greater consideration in future research.

10.
Allergy ; 76(11): 3408-3421, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34407212

RESUMO

Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment are essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research.


Assuntos
Dermatite Atópica , Microbiota , Administração Cutânea , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Disbiose , Humanos , Staphylococcus aureus
11.
Exp Dermatol ; 30(10): 1517-1531, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34387406

RESUMO

The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis.

12.
Contact Dermatitis ; 85(6): 615-626, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34420214

RESUMO

The "epithelial barrier hypothesis" proposes that the exposure to various epithelial barrier-damaging agents linked to industrialization and urbanization underlies the increase in allergic diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defense against environmental factors. Recent reports have shown that industrial products disrupt the epithelial barriers. Innate and adaptive immune responses play an important role in epithelial barrier damage. In addition, recent studies suggest that epithelial barrier dysfunction plays an essential role in the pathogenesis of the atopic march by allergen sensitization through the transcutaneous route. It is evident that external factors interact with the immune system, triggering a cascade of complex reactions that damage the epithelial barrier. Epigenetic and microbiome changes modulate the integrity of the epithelial barrier. Robust and simple measurements of the skin barrier dysfunction at the point-of-care are of significant value as a biomarker, as recently reported using electrical impedance spectroscopy to directly measure barrier defects. Understanding epithelial barrier dysfunction and its mechanism is key to developing novel strategies for the prevention and treatment of allergic diseases. The aim of this review is to summarize recent studies on the pathophysiological mechanisms triggered by environmental factors that contribute to the dysregulation of epithelial barrier function.

14.
Glob Chang Biol ; 27(22): 5934-5949, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34363285

RESUMO

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


Assuntos
Betula , Mudança Climática , Alérgenos , Ecossistema , Pólen
15.
Sci Total Environ ; 796: 148932, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34273827

RESUMO

Allergic diseases have been the epidemic of the century among chronic diseases. Particularly for pollen allergies, and in the context of climate change, as airborne pollen seasons have been shifting earlier and abundances have been becoming higher, pollen monitoring plays an important role in generating high-risk allergy alerts. However, this task requires labour-intensive and time-consuming manual classification via optical microscopy. Even new-generation, automatic, monitoring devices require manual pollen labelling to increase accuracy and to advance to genuinely operational devices. Deep Learning-based models have the potential to increase the accuracy of automated pollen monitoring systems. In the current research, transfer learning-based convolutional neural networks were employed to classify pollen grains from microscopic images. Given a high imbalance in the dataset, we incorporated class weighted loss, focal loss and weight vector normalisation for class balancing as well as data augmentation and weight penalties for regularisation. Airborne pollen has been routinely recorded by a Bio-Aerosol Analyzer (BAA500, Hund GmbH) located in Augsburg, Germany. Here we utilised a database referring to manually classified airborne pollen images of the whole pollen diversity throughout an annual pollen season. By using the cropped pollen images collected by this device, we achieved an unweighted average F1 score of 93.8% across 15 classes and an unweighted average F1 score of 75.9% across 31 classes. The majority of taxa (9 of 15), being also the most abundant and allergenic, showed a recall of at least 95%, reaching up to a remarkable 100% in pollen from Taxus and Urticaceae. The recent introduction of novel pollen monitoring devices worldwide has pointed to the necessity for real-time, automatic measurements of airborne pollen and fungal spores. Thus, we may improve everyday clinical practice and achieve the most efficient prophylaxis of allergic patients.


Assuntos
Aprendizado Profundo , Rinite Alérgica Sazonal , Alérgenos , Monitoramento Ambiental , Humanos , Pólen , Estações do Ano
17.
Metabolites ; 11(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202850

RESUMO

Our skin influences our physical and mental health, and its chemical composition can reflect environmental and disease conditions. Therefore, through sampling the skin metabolome, we can provide a promising window into the mechanisms of the body. However, the broad application of skin metabolomics has recently been hampered by a lack of easy and widely applicable sampling methods. Here, we present a novel rapid, simple, and, most importantly, painless and non-invasive sampling technique suitable for clinical studies of fragile or weakened skin. The method is called WET PREP and is simply a lavage of the skin which focuses on capturing the metabolome. We systematically evaluate WET PREPs in comparison with the non-invasive method of choice in skin metabolomics, swab collection, using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS2) on two complementary chromatographic columns (C18 reversed phase and hydrophilic interaction chromatography). We also integrate targeted analyses of key metabolites of skin relevance. Overall, WET PREP provides a strikingly more stable shared metabolome across sampled individuals, while also being able to capture unique individual metabolites with a high consistency in intra-individual reproducibility. With the exception of (phospho-)lipidomic studies, we recommend WET PREPs as the preferred skin metabolome sampling technique due to the quick preparation time, low cost, and gentleness for the patient.

18.
Cells ; 10(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206914

RESUMO

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.


Assuntos
Inflamação/imunologia , Inflamação/patologia , Queratinócitos/patologia , Linfócitos T/imunologia , Apresentação do Antígeno/imunologia , Biomarcadores/metabolismo , Comunicação Celular , Proliferação de Células , Forma Celular , Microambiente Celular , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Queratinócitos/ultraestrutura , Modelos Biológicos , Pele/imunologia , Pele/patologia , Solubilidade , Linfócitos T/ultraestrutura
20.
Sci Total Environ ; 793: 148509, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175598

RESUMO

Ganoderma comprises a common bracket fungal genus that causes basal stem rot in deciduous and coniferous trees and palms, thus having a large economic impact on forestry production. We estimated pathogen abundance using long-term, daily spore concentration data collected in five biogeographic regions in Europe and SW Asia. We hypothesized that pathogen abundance in the air depends on the density of potential hosts (trees) in the surrounding area, and that its spores originate locally. We tested this hypothesis by (1) calculating tree cover density, (2) assessing the impact of local meteorological variables on spore concentration, (3) computing back trajectories, (4) developing random forest models predicting daily spore concentration. The area covered by trees was calculated based on Tree Density Datasets within a 30 km radius from sampling sites. Variations in daily and seasonal spore concentrations were cross-examined between sites using a selection of statistical tools including HYSPLIT and random forest models. Our results showed that spore concentrations were higher in Northern and Central Europe than in South Europe and SW Asia. High and unusually high spore concentrations (> 90th and > 98th percentile, respectively) were partially associated with long distance transported spores: at least 33% of Ganoderma spores recorded in Madeira during days with high concentrations originated from the Iberian Peninsula located >900 km away. Random forest models developed on local meteorological data performed better in sites where the contribution of long distance transported spores was lower. We found that high concentrations were recorded in sites with low host density (Leicester, Worcester), and low concentrations in Kastamonu with high host density. This suggests that south European and SW Asian forests may be less severely affected by Ganoderma. This study highlights the effectiveness of monitoring airborne Ganoderma spore concentrations as a tool for assessing local Ganoderma pathogen infection levels.


Assuntos
Ganoderma , Árvores , Microbiologia do Ar , Monitoramento Ambiental , Europa (Continente) , Esporos Fúngicos
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