Maintenance OCS Were Used More Frequently Than Biologics in Patients with Uncontrolled GINA 4/5 Asthma in Germany in 2019.

Purpose: Asthma is affecting 4-5% of all adults (10% of children) in Germany, ≥ half are inadequately controlled. In 2019 up to 54 thousand patients suffered from severe uncontrolled asthma, 52% were treated/co-treated by pneumonologists. 45% of them had continuous oral corticosteroid (OCS)- and short-acting ß2-agonist (SABA) overuse for ≥2 years. The aim of the current study was to analyze the main treatments, escalation schemes and the adherence to the GINA recommendations. Patients and Methods: Retrospective analysis in 2021 based on data from January to December 2019 in Germany, using the IQVIA™ LRx prescription database and the IQVIA™ Disease Analyzer database containing anonymized electronic medical records as the main data sources. Results: In 2019 25,200 patients with severe, uncontrolled asthma treated in a pneumonologist´s practice in Germany received GINA 3 (0,4%), GINA 4 (76%) or GINA 5 therapy (24%) during the study year compared to 59% GINA 5 therapy in the 5-10% (1,500-3,000) co-treated in a specialized outpatient department. In Pneumonologists` practices the most frequent choice in GINA 5 was OCS in 69% of patients (biologicals 37%, long-acting muscarinic antagonist (LAMA) 20%) compared to 66% biologicals, 55% OCS, and 25% LAMA in the outpatient department. 54,958 of 613,000 GINA 4/5 patients were treated with OCS, 9,725 even with doses above the so called "Cushing threshold" for prednisolone of 2700 mg/year. After introduction of a biological treatment, patients reduced their SABA prescriptions by 28%, OCS by 55%, and OCS overall exposure by 40%, one-third did not need OCS anymore. Conclusion: In 75% of patients with uncontrolled asthma for ≥2 years therapy was not escalated beyond GINA 4 or low dose OCS was used as the most frequent add-on treatment in GINA 5 contradictory to treatment recommendations. Use of biologics reduced on demand rescue medication and OCS use.

[Medical clinical diagnostics for indoor mould exposure - Update 2023 (AWMF Register No. 161/001)]. / Medizinisch klinische Diagnostik bei Schimmelpilzexposition in Innenräumen ­ Update 2023 (AWMF-Register-Nr. 161/001).

This article is an abridged version of the updated AWMF mould guideline "Medical clinical diagnostics in case of indoor mould exposure - Update 2023", presented in July 2023 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin, GHUP), in collaboration with German and Austrian scientific medical societies, and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. There is no evidence for a causal relationship between moisture/mould damage and human diseases, mainly because of the ubiquitous presence of fungi and hitherto inadequate diagnostic methods. Sufficient evidence for an association between moisture/mould damage and the following health effects has been established for: allergic respiratory diseases, allergic rhinitis, allergic rhino-conjunctivitis, allergic bronchopulmonary aspergillosis (ABPA), other allergic bronchopulmonary mycosis (ABPM), aspergilloma, Aspergillus bronchitis, asthma (manifestation, progression, exacerbation), bronchitis (acute, chronic), community-acquired Aspergillus pneumonia, hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EEA)), invasive Aspergillosis, mycoses, organic dust toxic syndrome (ODTS) [workplace exposure], promotion of respiratory infections, pulmonary aspergillosis (subacute, chronic), and rhinosinusitis (acute, chronically invasive, or granulomatous, allergic). In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitization prevalence of 3-22,5 % in the general population across Europe. Limited or suspected evidence for an association exist with respect to atopic eczema (atopic dermatitis, neurodermatitis; manifestation), chronic obstructive pulmonary disease (COPD), mood disorders, mucous membrane irritation (MMI), odor effects, and sarcoidosis. (iv) Inadequate or insufficient evidence for an association exist for acute idiopathic pulmonary hemorrhage in infants, airborne transmitted mycotoxicosis, arthritis, autoimmune diseases, cancer, chronic fatigue syndrome (CFS), endocrinopathies, gastrointestinal effects, multiple chemical sensitivity (MCS), multiple sclerosis, neuropsychological effects, neurotoxic effects, renal effects, reproductive disorders, rheumatism, sick building syndrome (SBS), sudden infant death syndrome, teratogenicity, thyroid diseases, and urticaria.The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 (Aspergillus fumigatus, A. flavus) of the German Biological Agents Act (Biostoffverordnung). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, water activity, temperature and above all the growth substrates.In case of indoor moisture/mould damage, everyone can be affected by odor effects and/or mood disorders.However, this is not an acute health hazard. Predisposing factors for odor effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly regarding infection risk are immunocompromised persons according to the classification of the German Commission for Hospital Hygiene and Infection Prevention (Kommission für Krankenhaushygiene und Infektionsprävention, KRINKO) at the Robert Koch-Institute (RKI), persons suffering from severe influenza, persons suffering from severe COVID-19, and persons with cystic fibrosis (mucoviscidosis); with regard to allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma must be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections, the reader is referred to the specific guidelines. Regarding mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medical point of view, it is important that indoor mould infestation in relevant magnitudes cannot be tolerated for precautionary reasons.For evaluation of mould damage in the indoor environment and appropriate remedial procedures, the reader is referred to the mould guideline issued by the German Federal Environment Agency (Umweltbundesamt, UBA).

Safety of 300IR house dust mite sublingual tablet from pooled clinical trial and post-marketing data.

Background: The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data. Methods: Subjects (5-65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed. Results: Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised. Conclusion: Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status. Clinical trial registrations: NCT00674700; Retrospectively registered 06 May 2008.NCT01199133; Retrospectively registered 09 September 2010.NCT01527188; Retrospectively registered 01 February 2012.NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.jRCT2080222929/JapicCTI-15298; Registered 04 August 2015.

Disease modification in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

AWMF mold guideline "Medical clinical diagnostics for indoor mold exposure" - Update 2023 AWMF Register No. 161/001.

None.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

An emerging aeroallergen in Europe: Tree-of-Heaven (Ailanthus altissima [Mill.] Swingle) inventory and pollen concentrations - Taking a metropolitan region in Germany as an example.

Urban areas are often hotspots for the dissemination of non-native (invasive) plant species, some of which release (potentially) allergenic pollen. Given the high population density in cities, a considerable number of people can be regularly and potentially intensively exposed to the pollen from these plants. This study delves into the Tree-of-Heaven (Ailanthus altissima, [Mill.] Swingle), native to East Asia, which is known for its high invasiveness in temperate regions worldwide, particularly favoring urban colonization. This study explores the botanical and aerobiological dimensions of this species using the central European metropolitan region of Berlin, Germany, as a case study, and provides a comprehensive global overview of allergological insights. The number of Ailanthus trees decreased markedly from the center to the periphery of Berlin City, following a temperature gradient. The same spatial trend was mirrored by airborne Ailanthus pollen concentrations measured with volumetric spore traps (Hirst-type) at five sites using seven traps. Ailanthus pollen was most abundant around midday and in the afternoon, with concentrations tenfold higher at street level than at roof level. The Ailanthus flowering period in June and July coincided well with the pollen season. To the best of our knowledge this is the first study to investigate Ailanthus altissima pollen production. On average, 5539 pollen grains were found per anther. A literature review on the allergy relevance of Ailanthus altissima pollen indicates the high allergenic potential of pollen from this species. Considering the anticipated expansion of suitable habitats for Ailanthus owing to global warming and the allergological significance of its pollen, it is recommended to include Ailanthus pollen in routine pollen monitoring, particularly in areas colonized by this species. This comprehensive study provides new insights into a pollen taxon whose significance as an emerging aeroallergen should be factored into plant selection and greenspace management in all temperate regions.

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

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

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

Green Roof Gardens - Selecting Allergy-Friendly Vegetation: A Global Allergy and Asthma Excellence Network (GA²LEN) Position Paper.

Green roof gardens are important for planetary health by mitigating the effects of urbanization. Because of the nature of green roof gardens, only particular plants can be used. The allergologic impact of these plants remains ill-characterized and guidance on building allergy-friendly green roof gardens is missing. To address this gap, we investigated the plant spectrum of several German green roof companies and categorized plants based on their primary pollination mechanism. Except for grasses, most plants were insect-pollinated and of low allergenicity. In addition, we conducted a review on the allergologic impact of plants used for green roof gardens. Our aim was to provide landscape architects with guidance on how to develop allergy-friendly green roof gardens. We highlight the need for universally accepted standards for assessing the allergenicity of roof top plants. Also, we recommend the joint development, by green roof producers and allergists, of criteria for allergy-friendly roof gardens. Their implementation may help to reduce the risk of allergen sensitization and allergy exacerbation, such as by avoiding the use of wind-pollinated plants of proven allergenicity including grasses. Green infrastructure, such as green roofs, should benefit planetary health without increasing the prevalence and burden of allergies.

Initiation, response assessment, and switch of antibody therapies in patients with severe asthma - A survey among German specialists.

Background: For therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and switch. Objective: To assess current practice on all aspects of biologic therapy by specialists in Germany. Methods: A questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis. Results: Forty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between "responders", "partial responders" and "non-responders". Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP. Conclusion: This study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany.

Impact of climate change on allergic diseases in Germany.

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.

A temporally and spatially explicit, data-driven estimation of airborne ragweed pollen concentrations across Europe.

Ongoing and future climate change driven expansion of aeroallergen-producing plant species comprise a major human health problem across Europe and elsewhere. There is an urgent need to produce accurate, temporally dynamic maps at the continental level, especially in the context of climate uncertainty. This study aimed to restore missing daily ragweed pollen data sets for Europe, to produce phenological maps of ragweed pollen, resulting in the most complete and detailed high-resolution ragweed pollen concentration maps to date. To achieve this, we have developed two statistical procedures, a Gaussian method (GM) and deep learning (DL) for restoring missing daily ragweed pollen data sets, based on the plant's reproductive and growth (phenological, pollen production and frost-related) characteristics. DL model performances were consistently better for estimating seasonal pollen integrals than those of the GM approach. These are the first published modelled maps using altitude correction and flowering phenology to recover missing pollen information. We created a web page (http://euragweedpollen.gmf.u-szeged.hu/), including daily ragweed pollen concentration data sets of the stations examined and their restored daily data, allowing one to upload newly measured or recovered daily data. Generation of these maps provides a means to track pollen impacts in the context of climatic shifts, identify geographical regions with high pollen exposure, determine areas of future vulnerability, apply spatially-explicit mitigation measures and prioritize management interventions.

Health Care Situation in the Treatment of Uncontrolled GINA Step 4/5 Patients in Germany.

Purpose: It has been estimated that, in 2019, 54,000 patients in Germany had uncontrolled GINA step 4/5 asthma. In the current study we analyzed which health care providers were involved in the management of these patients and their role in disease phenotyping. Patients and Methods: The year 2019 was retrospectively analyzed using the IQVIATM LRx, a longitudinal anonymized prescription database, and the electronic, anonymized medical records database, the IQVIA Disease Analyzer. Results: Of 54,000 uncontrolled GINA step 4/5 asthma patients in Germany, 52% had consulted both general practitioners (GPs) and pulmonologists, and 48% were seen exclusively by a GP. Of these 54,000 patients, 45% were being prescribed and were thus overusing short-acting ß2-agonists (SABAs) and oral corticosteroids (OCS) for ≥2 years, 26% for ≥3 years, and 16% for ≥4 years. In most regions, pulmonologists saw one of their uncontrolled GINA step 4/5 asthma patients per week. Laboratory tests from consultations with a GP were available for only 10% of patients referred to a pulmonologist. In 50% of uncontrolled asthma patients treated according to GINA step 4/5, these were initiated by the pulmonologist, and 34% received laboratory testing within the first year (in GINA step 4/5 asthma, the numbers are 20% and 18%, respectively). Conclusion: Fifty percent of uncontrolled asthma patients treated according to GINA step 4/5 were regularly seen by pulmonologists, who performed most of the phenotyping confirming their importance in the management of severe, uncontrolled asthma in Germany. To understand treatment pathways for these patients, further studies are needed.

Designing an automatic pollen monitoring network for direct usage of observations to reconstruct the concentration fields.

We consider several approaches to a design of a regional-to-continent-scale automatic pollen monitoring network in Europe. Practical challenges related to the arrangement of such a network limit the range of possible solutions. A hierarchical network is discussed, highlighting the necessity of a few reference sites that follow an extended observations protocol and have corresponding capabilities. Several theoretically rigorous approaches to a network design have been developed so far. However, before starting the process, a network purpose, a criterion of its performance, and a concept of the data usage should be formalized. For atmospheric composition monitoring, developments follow one of the two concepts: a network for direct representation of concentration fields and a network for model-based data assimilation, inverse problem solution, and forecasting. The current paper demonstrates the first approach, whereas the inverse problems are considered in a follow-up paper. We discuss the approaches for the network design from theoretical and practical standpoints, formulate criteria for the network optimality, and consider practical constraints for an automatic pollen network. An application of the methodology is demonstrated for a prominent example of Germany's pollen monitoring network. The multi-step method includes (i) the network representativeness and (ii) redundancy evaluation followed by (iii) fidelity evaluation and improvement using synthetic data.

The holo beta-lactoglobulin lozenge reduces symptoms in cat allergy-Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge.

BACKGROUND: The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta-lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen-nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy. METHODS: A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3-month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min- constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure. RESULTS: 35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p < 0.001), as well as in median nasal flow by 20 L/min (p = 0.0035). 20% of patients reported late reactions after baseline exposure, but 0% after the final exposure. CONCLUSIONS: Cat allergic patients profited from targeted micronutrition with the holoBLG lozenge. As previously seen in other allergies, holoBLG supplementation also induced immune resilience in cat allergies, resulting in significant symptom amelioration.

Assessing the relevance of allergenic pollen in indoor environments-current knowledge base and research needs.

Airborne pollen allergens-a relevant component of bioaerosols and, therefore, of airborne particulate matter-are considered an important metric in air quality assessments. Although the measurement of airborne pollen allergen concentrations in outdoor environments (namely, in urban areas) has been recognized as a key environmental health indicator, no such obligation exists for indoor environments (dwellings or occupational settings). However, people spend most of their daily time (80-90%) indoors, where the majority of their exposure to air pollution, including pollen allergens, occurs. Nonetheless, the relative importance of airborne pollen allergen exposure indoors differs from outdoors because of differences in pollen loads, sources, dispersion, and degree of penetration from the outdoor surroundings, as well as the differences in the allergenic pollen profiles. In this brief review, we mined the literature over the last 10 years to summarize what existing measurements reveal about the relevance of airborne allergenic pollen in indoor environments. The research priorities on this topic are presented, highlighting the challenges and the motivations for obtaining pollen data in built environments which are key to understand the extent and mechanisms of human exposure to airborne pollen allergens. Thus, we provide a comprehensive assessment of the relevance of airborne allergenic pollen in indoor environments, highlighting knowledge gaps and research needs related to their health effects.

Oral mite anaphylaxis (pancake syndrome) caused by storage mite Acarus siro and its treatment with allergen immunotherapy.

A 10-year-old atopic patient with asthma, peanut, and house dust mite allergy developed frequent episodes with symptoms including abdominal pain, nausea, vomiting, dizziness, drop of blood pressure, and occasionally shortness of breath and wheezing. After detailed diagnostics including an ISAC test and several other specific IgE blood tests, which could not explain the symptoms, the patient tested positive for specific IgE to Acarus siro (flour mites) (9.2 kU/L). As no oral food challenge with Acarus siro was available, the patient's family implemented avoidance measures by storing food containing flour in the refrigerator, and the patient started subcutaneous immunotherapy (SCIT) with Depigoid Acarus siro. The implementation of avoidance measures led to an immediate improvement of symptoms, and after 3 years of treatment, products containing flour, stored at room temperature, are tolerated again.

Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients.

INTRODUCTION: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. METHODS: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. RESULTS: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. CONCLUSION: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.