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Pollen allergies, such as allergic rhinitis, are triggered by exposure to airborne pollen. They are a considerable global health burden, with their numbers expected to rise in the coming decades due to the advent of climate change and air pollution. The relationships that exist between pollens, meteorological, and environmental conditions are complex due to a lack of clarity on the nature and conditions associated with these interactions; therefore, it is challenging to describe their direct impacts on allergenic potential clearly. This article attempts to review evidence pertaining to the possible influence of meteorological factors and air pollutants on the allergic potential of pollen by studying the interactions that pollen undergoes, from its inception to atmospheric traversal to human exposure. This study classifies the evidence based on the nature of these interactions as physical, chemical, source, and biological, thereby simplifying the complexities in describing these interactions. Physical conditions facilitating pollen rupturing for tree, grass, and weed pollen, along with their mechanisms, are studied. The effects of pollen exposure to air pollutants and their impact on pollen allergenic potential are presented along with the possible outcomes following these interactions, such as pollen fragmentation (SPP generation), deposition of particulate matter on pollen exine, and modification of protein levels in-situ of pollen. This study also delves into evidence on plant-based (source and biological) interactions, which could indirectly influence the allergic potential of pollen. The current state of knowledge, open questions, and a brief overview of future research directions are outlined and discussed. We suggest that future studies should utilise a multi-disciplinary approach to better understand this complex system of pollen interactions that occur in nature., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sudharsun Venkatesan reports administrative support and writing assistance were provided by Deakin University. Svetlana Stevanovic reports a relationship with Deakin University that includes: employment. If there are other authors, they 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. Published by Elsevier B.V.)

Background: Immunoglobulin E (IgE) is a diagnostic biomarker for allergic diseases. While some metal exposure has been found to be associated with allergic diseases, there are still a lot of knowledge gaps regarding the relationship between metal exposure and allergen-specific IgE antibodies, particularly in adults., Methods: We included a total of 1433 adult participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), all of whom had concentrations of 10 metals (including Barium (Ba), Cadmium (Cd), Cobalt (Co), Cesium (Cs), Molybdenum (Mo), Lead (Pb), Antimony (Sb), Thallium (Tl), Tungsten (Tu), and Uranium (Ur)) in urine, as well as measurements of 19 allergen-specific IgE and total IgE antibodies. Linear regression, logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to estimate associations between metals and total and allergen-specific IgE., Results: Linear regression models revealed a positive correlation between Pb and Cd levels and the total IgE levels. Furthermore, the WQS and BKMR models suggested a positive association between mixed metals and total IgE levels, with the WQS model highlighting Pb and Cd as the major contributors. Logistic regression models showed positive correlations between Pb and food sensitization, Ur and plant sensitization, negative correlations between Cs and plant sensitization, Co and dust mite and pet sensitization, Mo and dust mite and cockroach sensitization, and Tl and mold sensitization. Moreover, the BKMR results indicated a statistically significant negative correlation between mixed metals and mold sensitization., Conclusion: According to the research findings, exposure to metals is associated with total and allergen-specific IgE in American adults. Further assessment of these relationships is necessary in representative populations of other countries., 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.)

The study is aimed at determining the potential spatiotemporal risk of the co-occurrence of airborne pollen and fungal spores high concentrations in different bio-climatic zones in Europe. Birch, grass, mugwort, ragweed, olive pollen and Alternaria and Cladosporium fungal spores were investigated at 16 sites in Europe, in 2005-2019. In Central and northern Europe, pollen and fungal spore seasons mainly overlap in June and July, while in South Europe, the highest pollen concentrations occur frequently outside of the spore seasons. In the coldest climate, no allergy thresholds were exceeded simultaneously by two spore or pollen taxa, while in the warmest climate most of the days with at least two pollen taxa exceeding threshold values were observed. The annual air temperature amplitude seems to be the main bioclimatic factor influencing the accumulation of days in which Alternaria and Cladosporium spores simultaneously exceed allergy thresholds. The phenomenon of co-occurrence of airborne allergen concentrations gets increasingly common in Europe and is proposed to be present on other continents, especially in temperate climate., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

One of the traditional methods of treating allergy is to avoid the allergen, protocol that has long been used in high altitude clinics. It has been hypothesized that the therapeutic effect of high altitude on allergy is due to allergen avoidance, exposure to sunlight and reduced stress. However, the contribution of environmental elements like low oxygen pressure and hypoxia remains underexplored. In this study, we examined the role of hypoxia in the development of type 2 lung inflammation. Mice were administered with papain or recombinant IL-33 intra-nasally to induce type 2 lung inflammation. Some of them were treated additionally with the prolyl hydroxylase (PHD) inhibitor DMOG, which mimics hypoxia. DMOG treatment exhibited an inhibitory effect on the lung inflammation induced by papain or IL-33, operating in a manner independent of T and B cells. The anti-inflammatory effect of DMOG was accompanied by a downregulation of IL-5 and IL-13 in innate lymphoid cells (ILCs), which was abolished in HIF-1α deficient mice. Collectively, our findings suggest that DMOG's modulatory effect on IL-5 and IL-13 operates through the HIF-1 pathway, resulting in a reduction in type 2 lung inflammation. These findings underscore the role of the PHD-HIF pathway in IL-5 and IL-13 expression in lung ILCs and pharmacological inhibition of PHD might be a novel therapeutic candidate for type 2 lung inflammation., 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 Inc. All rights reserved.)

In Central Europe the most common allergies are provoked by grass or birch pollen allergens. We determined the intra-daily behavior of airborne pollen grains of grasses (Poaceae) and birch (Betula ssp.) in Central Europe, based on data obtained from a network of automatic pollen monitors over Europe (www.pollenscience.eu). Our aim was to determine the time of day when the lowest concentrations occur, to provide allergic individuals the optimal time to ventilate their homes. The study was carried out in three Central European capitals, Berlin (Germany), Paris-Saclay (France), and Luxembourg (Luxembourg), as well as in eight stations in Germany (Altötting, Feucht, Garmisch-Partenkirchen, Hof, Marktheidenfeld, Mindelheim, Munich and Viechtach). The diurnal rhythm of these eleven locations was analyzed for either the complete, first week, peak week, peak day and last week of the pollen season. The data studied were reported as pollen/m 3 measured in 3 h periods. Stations were classified as city, semi-populated or countryside areas using land-use and population density criteria. Grass pollen has a more pronounced diurnal rhythm than birch pollen concentrations. A significant difference was observed when comparing day (6-21 h) versus night (21-6 h) for all stations. No difference was detected between city and countryside for both pollen types, although for Poaceae a longer period of maximum concentrations was observed in big cities and higher day/night-time differences were registered in the countryside (6.4) than in cities (3.0). The highest pollen concentrations were observed between 9 and 18 h for grass, but the rhythm was less pronounced for birch pollen. For allergic individuals who want to bring in fresh air in their homes, we recommend opening windows after 21 h, but even better early in the morning between 6 and 9 h before pollinations (re)starts., 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. Published by Elsevier B.V.)

The grass family is responsible for most of peoples pollen allergies, and the severity of pollen-based asthma and allergies is expected to increase with global climate change. Identifying grass species through standard pollen monitoring techniques have limitations due to challenges in species-specific pollen identification. As a result, these monitoring methods end up grouping all Poaceae species together, even though there are hundreds of grass species in Europe with flowering times that may vary drastically among species. Given this lack of specificity, it is hard to know which grass species are responsible for causing allergies over the pollen season, and how different species are affected by climate change. To address these issues, we obtained phenological data from thousands of herbarium specimens collected across Denmark spanning 190 years and used pollen monitoring data collected over the last four decades to determine the response of flowering time to climate change for 12 allergenic grass species, and identify which species are likely the biggest contributors to grass pollen loads throughout the pollen season. We find that pollen season duration is lasting longer and starting earlier, and the maximum pollen loads are occurring earlier in response to climate warming. Herbarium specimens provide taxonomic resolution and reveal that many grass species are flowering earlier in response to warmer spring temperatures. Seven out of the 12 species studied in Denmark are identified as major contributors to airborne pollen based on their flowering times, relative abundance and overlap with the time of the year when maximum pollen loads are detected. Four species (Poa pratensis, Dactylis glomerata, Festuca rubra, Holcus lanatus) significantly shifted their flowering time in response to warming temperatures and are flagged as of particular concern to allergy sufferers. Using data derived from natural history collections can contribute to the advancement of pollen forecasting for asthma and allergy patients under both current conditions and amidst future global changes., 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 B.V. All rights reserved.)

Grass pollen is a leading cause of allergy in many countries, particularly Europe. Although many elements of grass pollen production and dispersal are quite well researched, gaps still remain around the grass species that are predominant in the air and which of those are most likely to trigger allergy. In this comprehensive review we isolate the species aspect in grass pollen allergy by exploring the interdisciplinary interdependencies between plant ecology, public health, aerobiology, reproductive phenology and molecular ecology. We further identify current research gaps and provide open ended questions and recommendations for future research in an effort to focus the research community to develop novel strategies to combat grass pollen allergy. We emphasise the role of separating temperate and subtropical grasses, identified through divergence in evolutionary history, climate adaptations and flowering times. However, allergen cross-reactivity and the degree of IgE connectivity in sufferers between the two groups remains an area of active research. The importance of future research to identify allergen homology through biomolecular similarity and the connection to species taxonomy and practical implications of this to allergenicity is further emphasised. We also discuss the relevance of eDNA and molecular ecological techniques (DNA metabarcoding, qPCR and ELISA) as important tools in quantifying the connection between the biosphere with the atmosphere. By gaining more understanding of the connection between species-specific atmospheric eDNA and flowering phenology we will further elucidate the importance of species in releasing grass pollen and allergens to the atmosphere and their individual role in grass pollen allergy., Competing Interests: Declaration of competing interest The authors declare that they do not have any inappropriate financial or personal relationships that would bias or influence the research in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.)

To benefit allergy patients and the medical practitioners, pollen information should be available in both a reliable and timely manner; the latter is only recently possible due to automatic monitoring. To evaluate the performance of all currently available automatic instruments, an international intercomparison campaign was jointly organised by the EUMETNET AutoPollen Programme and the ADOPT COST Action in Munich, Germany (March-July 2021). The automatic systems (hardware plus identification algorithms) were compared with manual Hirst-type traps. Measurements were aggregated into 3-hourly or daily values to allow comparison across all devices. We report results for total pollen as well as for Betula, Fraxinus, Poaceae, and Quercus, for all instruments that provided these data. The results for daily averages compared better with Hirst observations than the 3-hourly values. For total pollen, there was a considerable spread among systems, with some reaching R 2 > 0.6 (3 h) and R 2 > 0.75 (daily) compared with Hirst-type traps, whilst other systems were not suitable to sample total pollen efficiently (R 2 < 0.3). For individual pollen types, results similar to the Hirst were frequently shown by a small group of systems. For Betula, almost all systems performed well (R 2 > 0.75 for 9 systems for 3-hourly data). Results for Fraxinus and Quercus were not as good for most systems, while for Poaceae (with some exceptions), the performance was weakest. For all pollen types and for most measurement systems, false positive classifications were observed outside of the main pollen season. Different algorithms applied to the same device also showed different results, highlighting the importance of this aspect of the measurement system. Overall, given the 30 % error on daily concentrations that is currently accepted for Hirst-type traps, several automatic systems are currently capable of being used operationally to provide real-time observations at high temporal resolutions. They provide distinct advantages compared to the manual Hirst-type measurements., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeroen Buters, Jose M. Maya Manzano, Carsten B. Schmidt-Weber and Marina Triviño report financial support, administrative support, equipment, drugs, or supplies, and travel were provided by Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit (LGL) and EUMETNET. Carsten Skjoth reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and travel were provided by COST Action CA18226 ADOPT – New approaches in detection of pathogens and aeroallergens. Bernard Clot and Fiona Tummon report financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and travel were provided by European Meteorological Society and the EUMETNET AutoPollen Programme. Branko Sikoparija and Predrag Matavulj report financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and travel were provided by BREATHE project from the Science Fund of the Republic of Serbia PROMIS program, under grant agreement no. 6039613 and by the Ministry of Education, Science and Technological Development of the Republic of Serbia (grant agreement number 451–03-68/2022–14/200358). Evgeny Kadantsev and Julia Palamarchuk report financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and travel were provided by Academy of Finland PS4A (grant 318,194). Mikhail Sofiev reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and travel were provided by Academy of Finland project ALL-Impress (grant 329,215). Mikhail Sofiev reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and travel were provided by European Social Fund (project no. 09.3.3-LMT-K-712-01-0066) and Research Council of Lithuania (LMTLT). Nathan Allan, Landon Bunderson, Richard W. Lucas (Pollen science TM), Jorg Haus, Stefan Schaefer, Martin Schnitzler and Tom Stemmler (Helmut Hund Wetzlar), Reto Abt, Elias Graf, Erny Niederberger and Yanick Zeder (Swisens AG) report a relationship with Pollen science TM, Helmut Hund Wetzlar and Swisens AG respectively, that includes: board membership, employment, and travel reimbursement. The investigations were carried out in compliance with good scientific practices and the support provided by these companies in terms of instrumentation had no effect on the results presented., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In vivo animal models can provide worthy information on various aspects of asthma mechanism and pathogenesis. The genetic predisposition and phenotype of mice may affect the immune response itself. Here we compare the early immune response to Der p 2 or HDM allergen extract upon injection and inhalation in BALB/c and C57BL/6 mice. Female C57BL/6 and BALB/c mice were immunized with Der p 2 allergen subcutaneously followed by inhalation of Der p 2 or HDM extract. After challenge, the mice were euthanized; blood, bronchoalveolar lavage (BAL), spleens and lungs were collected. Cells from BAL were identified by May-Grünwald Giemsa staining and lung leukocyte populations were analyzed by flow cytometry. Serum antibody levels of Der p 2 specific IgE, IgG, IgG1 and IgG2a were assessed by ELISA, and cytokine secretion (IL-4, IFN-γ and IL-10) was evaluated upon stimulation with Der p 2 or HDM extract. The Th2 immune response was confirmed by elevated allergen-specific immunoglobulin E (IgE) and the allergic reaction was evidenced by infiltration of eosinophils and/or neutrophils into BAL. We found that BALB/c mice were inefficient in integrating local with systemic immune response, evidenced by almost no IgG or IgE production upon one subcutaneous injection and subsequent inhalation of Der p 2 allergen; also, the bronchoalveolar lavage infiltrate in these mice consisted of neutrophil infiltration, unlike C57BL/6 mice in which eosinophilic infiltrate predominated. The differences between BALB/c and C57BL/6 mice strains could be exploited for generating different types of responses to the Der p 2 allergen., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Innovations in oral immunotherapy have greatly advanced the therapeutic control of allergies. However, these therapeutic effects suffer from the fact that the amount of antigen delivered to antigen-presenting cells is limited given the formulations that are currently available. We recently designed a cell-penetrating albumin and found that this modified albumin enters cells via the induction of macropinocytosis. Herein, we report on a novel system for delivering antigens based on cell-penetrating albumin-inducible macropinocytosis that allows larger amounts of antigens to be delivered to antigen-presenting cells. A treatment with cell-penetrating albumin significantly increased the permeability of ovalbumin (45 kDa) or dextran (2000 kDa) on monolayers derived from human oral squamous carcinoma cells. Flow cytometric analyses showed that the cell-penetrating albumin treatment resulted in a significant elevation in the amount of dextran that was delivered to two types of antigen-presenting cells. Finally, mice that had been sensitized by Japanese cedar pollen extract (JCPE) and cell-penetrating albumin showed a decline in the frequency of nose-rubbing against a subsequent intranasal administration of JCPE. These findings suggest that the sublingual administration of cell-penetrating albumin efficiently delivers antigens to antigen-presenting cells via the induction of macropinocytosis, resulting in an enhancement in the therapeutic effect of sublingual immunotherapy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

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.)

Asthma affects over 300 million people globally and is a cause of substantial burden of disease, including both premature death and reduced quality of life in people of all ages. Although both genetic and environmental factors play an important role in the pathogenesis of asthma, the rising trend of asthma and other allergic diseases over recent decades is thought to be largely caused by alteration in environmental conditions. Thus, a considerable amount of attention has been paid to environmental modification for the treatment and management of asthma, including household allergen reduction and/or irritant removal. More advanced environmental modification strategies (e.g., health resort medical rehabilitation, high-altitude climate therapy and multiple-hit interventions) have also been suggested. Research advances have been made over the past decades, but major challenges and opportunities coexist in this emerging field. Concerted efforts are required to tackle these formidable challenges., 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 Elsevier Inc. All rights reserved.)

Indoor dust is the main carrier of indoor pollutants, especially dust mite allergens and bacteria, they can trigger asthma, rhinitis, eczema and other allergic diseases. However, the interactions between dust mite allergens and bacterial communities in different types of indoor dust are not clear. The study focused on particulate and flocculent fibrous dust, explored the concentrations of Der p 1 (Dermatophagoides pteronyssinus) and Der f 1 (D. farinae) in 46 households in Changchun and their environmental influences, characterized the bacterial communities by high-throughput sequencing, and the interactions between Der p 1, Der f 1 and bacterial communities were explored. The results showed that Der p 1 and Der f 1 tended to accumulate more in flocculent fibrous dust, and Der p 1 predominated in the indoor dust samples. The floor height, years of housing occupancy and the living areas all affected the concentrations of dust mite allergens. In bacterial community, Proteobacteria, Firmicutes and Actinobacteria were leading phyla in the two types of dust. Kocuria, Blastococcus and Massilia were dominating genera in particulate dust and Acinetobacter, Lactobacillus, Corynebacterium&#95;1 were dominating genera in flocculent fibrous dust. The overall diversity and species richness of bacteria in particulate dust were significantly higher than those in flocculent dust (p < 0.001). The living area was an important environmental factor affecting the bacterial community in flocculent fibrous dust (p < 0.01). The interaction between the relative abundance of Proteobacteria, Firmicutes and Actinobacteria and dust mite allergen concentrations significantly differed between the two dust types, indicating that bacteria could be used both as food and to establish symbiotic relationships with household dust mites (HDMs) hosts and provide nutrition., 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 Elsevier B.V. All rights reserved.)

Aims: In our clinical work, some patients with type I hypersensitivity could be detected protein in their urine. This study focused on the early renal injury in patients with type I hypersensitivity., Main Methods: From 43 type I hypersensitivity patients with proteinuria, 10 patients were randomly selected for mass spectrometry analysis of 24-h urine together with 5 healthy volunteers. Mice were vaccinated with Dermatophagoides farina (Der f) and ovalbumin (OVA) were used as antigen to establish the type I hypersensitivity animal models., Key Findings: The urine protein of hypersensitivity patients was significantly increased in the alpha-1-microglobulin/ bikunin precursor (Protein AMBP) (t = 3.140, P = 0.008), retinol binding protein 4 (RBP4) (t = 2.426, P = 0.031), kininogen-1 (t = 2.501, P = 0.027), and transferrin appeared only in patients' urine. After immunizing mice with antigens, significant increases of the total serum immunoglobulin E (IgE) were observed in both Der f (86.92 ± 36.01 U/mL, t = 5.231, P = 0.0004) and OVA group (34.65 ± 24.72 U/mL, t = 2.891, P = 0.0161) compared with the negative control group (2.68 ± 0.47 U/mL). Meanwhile, definite eosinophil infiltration around the impaired renal tubules as well as the bronchus in Der f mice were observed, and urine protein appeared. After stopping the allergen stimulation, proteinuria disappeared. Instead, when the mice were treated with the antigen again, proteinuria reappeared., Significance: Our findings suggest that renal tubular damage in patients with type I hypersensitivity is reversible, and proteinuria disappears with allergy symptoms remission., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The total amount of immunoglobulin E (IgE) in human serum is an important parameter in diagnosing allergies. To reduce the false diagnosis of allergies and better assist in therapy, clinical studies can be performed to obtain accurate and reliable measurements of IgE. A magnetic beads (MBs)-based ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for total IgE measurement and the diagnosis of food allergies in serum was developed in this study. First, IgE was extracted by MBs coupled with anti-IgE antibody from serum. The extracted IgE was quantified by a specific signal peptide after digestion. A spiked linear IgE concentration ranging from 400 to 5000 ng mL -1 was used for quantification. The limits of detection and quantification were 400 ng mL -1 and 800 ng mL -1 , respectively, for the developed method. Additionally, the combined capacity of the extracted IgE with different allergic proteins was evaluated by a binding experiment in vitro. The combining capacity of IgE with different allergens was used to speculate the kind of allergens that induce allergies in patients. Overall, a new method was developed that could be used to quantify the amount of IgE and simultaneously diagnose which allergen causes an allergic reaction, and this method may provide a powerful new tool in the clinical detection of allergies. Moreover, the developed method was applied to analyze IgE in four samples of patient serum and four serum samples from healthy individuals., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The peripheral nervous system and the immune system are virtually distributed in all organs in mouse and human. They act in concert to constitute an exceptional sensory system capable of sensing threatening stimuli, including allergens, and triggering appropriate biological responses. Recent advances in the field have revealed that tissue-resident mast cells and nearby sensory neurons could form functional neuroimmune clusters driven by bidirectional interactions and predisposed to significantly influence major allergic conditions. In this review, we highlight recent discoveries that paved the way toward a better understanding of how mast cells and sensory neurons can communicate to regulate basic features of allergic disorders in different organs., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood., Methods: This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles., Results: The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels., Conclusions: The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy., Methods: Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined., Results: Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ, IL-10, and TGF-β expression were increased. Moreover, OVA-specific IgE levels were also decreased., Conclusion: These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Considering the important role of Der f 2 in house dust mites mediating allergic diseases and allergic adverse effects during allergen-specific immunotherapy (AIT), we intend to develop a candidate of desensitization vaccines against Der f 2 without allergenicity. According to the reported immunoglobulin E (IgE)-binding B and T cell epitopes of Der f 2, four candidates of desensitization vaccines against Der f 2 were developed. Recombinant wild-type Der f 2 (rWt-Der f 2) preserved conformational and linear IgE-binding B epitopes. rWt-Der f 2 linearized by reduction and alkylation reactions (rWt-Der f 2 (red/alk)) and recombinant modified-type Der f 2 (rMt-Der f 2) were developed via destroying conformational and linear IgE-binding B epitopes respectively. rMt-Der f 2 linearized by reduction and alkylation reactions (rMt-Der f 2 (red/alk)) was developed by destroying conformational and linear IgE-binding B epitopes. T cell epitopes of 4 candidates were preserved. The change of their IgE-binding activity was determined by enzyme linked immunosorbent assay (ELISA), western blot and inhibition ELISA. Compared with rWt-Der f 2, the IgE-binding activity of rWt-Der f 2 (red/alk), rMt-Der f 2 and rMt-Der f 2 (red/alk) all decreased, which was consistent with the result of western blot. The IgE-binding activity of rMt-Der f 2 and rMt-Der f 2 (red/alk) was not significantly different (P = 0.0863 > 0.05), which was comparable to that of their corresponding negative controls (P = 0.3488 and 0.4459, both > 0.05). The result of inhibition ELISA also showed that their IgE-binding activity decreased, and rMt-Der f 2 (red/alk) was the lowest. Conclusively, we developed the candidate of desensitization vaccines against Der f 2, rMt-Der f 2 or rMt-Der f 2 (red/alk), nearly without allergenicity, which would potentially prevent HDM allergic patients from allergic adverse effects caused by AIT., (Copyright © 2022. Published by Elsevier GmbH.)

The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

The relatively easy access to fish worldwide, alongside the increase of aquaculture production contributes to increased fish consumption which result in higher prevalence of respective allergies. Allergies to fish constitute a significant concern worldwide. β-parvalbumin is the main elicitor for IgE-mediated reactions. Creatine, involved in the muscle energy metabolism, and ethylenediamine tetraacetic acid (EDTA), a calcium chelator, are potential molecules to modulate parvalbumin. The purpose of this study was to test creatine (2, 5 and 8%) and EDTA (1.5, 3 and 4.5%) supplementation in fish diets to modulate β-parvalbumin expression and structure and its allergenicity in farmed European seabass (Dicentrarchus labrax) while assessing its effects on the end-product quality. Fish welfare and muscle quality parameters were evaluated by plasma metabolites, rigor mortis, muscle pH and sensory and texture analysis. Proteomics was used to assess alterations in muscle proteome profile and metabolic fingerprinting by Fourier transform infrared spectroscopy was used to assess the liver metabolic profile. In addition, IgE-reactivity to parvalbumin was analysed using fish allergic patient sera. Metabolic fingerprinting of liver tissue revealed no major alterations in infrared spectra with creatine supplementation, while with EDTA, only absorption bands characteristic of lipids were altered. Comparative proteomics showed up regulation of (tropo) myosin and phosphoglycerate mutase 2 with Creatine supplementation. In the case of EDTA proteomics showed up regulation of proteins involved in cellular and ion homeostasis. Allergenicity seems not to be modulated with creatine or EDTA supplementation as no decreased expression levels were found and IgE-binding reactivity showed no quantitative differences., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Dendritic cells of the innate immune system and sensory neurons of the peripheral nervous system are embedded in barrier tissues and gather information about an organisms' environment. While the mechanisms by which dendritic cells recognize and initiate adaptive immune responses to pathogens is well defined, how they sense allergens is poorly understood. Indeed, allergens induce dendritic cell maturation and migration in vivo, but not in vitro. How are adaptive immune responses to allergens initiated if dendritic cells do not directly sense allergens? Sensory neurons release neuropeptides within minutes of allergen exposure. Recent evidence demonstrated that while neuropeptides modify dendritic cell function during pathogen responses, they are required for dendritic cell function during allergic responses. These emerging studies suggest that sensory neurons do not just pass information along to the central nervous system, but also to dendritic cells, particularly during the initiation of adaptive immunity to allergens., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Potential triggers for equine asthma are allergens from hay and straw dusts, mold spores and storage mites. The contribution of these environmental trigger factors to equine asthma is still largely uncertain. The aim of this study was to compare results of four allergy tests from healthy and asthma-affected horses, and to evaluate the clinical relevance of allergens tested positive via specific inhalation provocation test. Fifteen horses were classified using a clinical scoring system as asthmatic (n = 9) or control (n = 6). Four different allergy tests (functional in vitro test, intradermal test, Fc-epsilon receptor test, and ELISA for allergen-specific IgE) were compared. A histamine inhalation provocation test as positive control was performed in all horses and the interpleural pressure was measured. In addition, two individual allergens were chosen for the allergen inhalation provocation test based on the results of the allergy tests and inhaled in increasing concentrations, until signs of dyspnea occurred. None of the four allergy tests could differentiate reliably between controls and asthma-affected horses. There was no agreement among the results of the four allergy tests. The interpleural pressure results showed a large individual variability. A clear positive reaction on the allergen inhalation provocation test was only detected in two asthma-affected horses 6 hours after allergen inhalation with Aspergillus fumigatus and Cladosporium herbarum. In most cases a purely type I immediate reaction is unlikely to be involved in causing the clinical signs of equine asthma. Because of a delayed reaction after allergen provocation in two horses, the involvement of cell-mediated type III or IV hypersensitivity may be possible. As all allergy tests used in this study can only detect IgE-mediated hypersensitivity, these tests are probably not suitable for an etiological diagnosis of equine asthma., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent research showed that plant secondary metabolites in pollen may exacerbate the protein-mediated allergic reaction in pollen allergy. It was found that allergenic pollen from various plant families contain significant amounts of electrophiles which may covalently bind to nucleophilic groups of proteins, such as thiol moieties. Electrophiles in pollen of the Asteraceae species are typically sesquiterpene lactones, but the nature of electrophilic metabolites in allergenic pollen of other plant families is unknown. We developed a solid-supported cysteinyl probe in order to selectively extract physiologically relevant electrophiles from pollen extracts, and to enable their subsequent characterization by on-line and off-line spectroscopic analysis. The validity of this approach was evaluated with a selection of structurally different model compounds and with a spiked model extract., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The increase in childhood allergic disease in recent decades has coincided with increased folic acid intakes during pregnancy. Circulating unmetabolized folic acid (UMFA) has been proposed as a biomarker of excessive folic acid intake., Objective: We aimed to determine if late-pregnancy serum UMFA and total folate concentrations were associated with allergic disease risk in the offspring at 1 y of age in a population at high risk of allergy., Methods: The cohort consisted of 561 mother-infant pairs from Western Australia. To be eligible the infant had to have a first-degree relative (mother, father, or sibling) with a history of medically diagnosed allergic disease. Maternal venous blood was collected between 36 and 40 wk of gestation. Serum UMFA was measured by LC-tandem MS. Serum total folate was determined using a microbiological method with chloramphenicol-resistant Lactobacillus rhamnosus as the test organism, and was collected between 36 and 40 wk of gestation. UMFA concentrations were measured by tandem MS using stable isotope dilution; folate concentrations were determined using the microbiological method with standardized kits. Infant allergic disease outcomes of medically diagnosed eczema, steroid-treated eczema, atopic eczema, IgE-mediated food allergy, allergen sensitization, and medically diagnosed wheeze were assessed at 1 y of age., Results: Median (IQR) concentrations for UMFA and serum folate were 1.6 (0.6-4.7) and 53.2 (32.6-74.5) nmol/L, respectively. Of the infants, 34.6% had medically diagnosed eczema, 26.4% allergen sensitization, and 14.9% had an IgE-mediated food allergy. In both adjusted and unadjusted models there was little evidence of association between UMFA or serum folate and any of the infant allergy outcomes., Conclusions: In this cohort of children at high risk of allergic disease there was no association between maternal UMFA or serum folate concentrations measured in late pregnancy and allergic disease outcomes at 1 y of age., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Ornamental trees bring benefits for human health, including reducing urban pollution. However, some species, such as plane trees (Platanus sp.), produce allergenic pollen. Consequently, urban maps are a valuable tool for allergic patients and allergists, but they often fail to include variables that contribute to the "building downwash effect", such as the width and shape of streets and the height of buildings. Other factors that directly influence pollen dispersion (slopes and other geographical features) also have not traditionally been discussed. The LiDAR (Laser Imaging Detection and Ranging) technique enables one to consider these variables with high accuracy. This work proposes an Aerobiological Index to create Risk maps for Ornamental Trees (AIROT) and the establishment of potential areas of risk of exposure to Platanus pollen. LiDAR data from five urban areas were used to create the DEM and DSM (Digital Elevation and Surface Models) needed to perform further analysis. GIS software was used to map the points for each city and to create risk maps by Kriging, with stable (3 cases) and exponential function (2 cases) as the optimal models. In short, the AIROT index was a useful tool to map possible biological risks in cities. Since AIROT allows each city to consider its own characteristics, including geographical specifications, by using remote sensing and geostatistics techniques, the establishment of risk maps and healthy itineraries is valuable for allergic patients, allergists, architects and urban planners. This new aerobiological index provides a new decision-making tool related to urban planning and allergenicity assessment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

New techniques in equine veterinary allergy testing include multiple allergen simultaneous tests (MASTs) that cover insect bite hypersensitivity (IBH), respiratory and atopic allergic diseases. The in vivo intradermal test (IDT) method is one of the most widely used techniques in veterinary practice, but recently, in vitro methods have been introduced as possible alternatives. This study was designed to assess the correlation between IDTs and MASTs based on IgE determination in serum. The study was performed on Malopolski breed horses with IBH (n = 26). IDTs were performed, and allergen-specific IgE serum concentrations were measured using a monoclonal anti-IgE antibody during the years 2008-2016. An allergen panel containing Tabanus spp., Culicoides nubeculosus, mosquito (Culex spp.), Simulium equinum, and Stomoxys calcitrans was used. This study shows good agreement and correlation (correlation coefficient rho, 0.413-0.589) between the two tests for four (Tabanus spp, Culicoides nubeculosus, Culex spp., Simulium equinum) of the five tested allergens in horses with IBH. The overall sensitivity (Se) of the allergen-specific IgE insect horse panel was 72.6% (range, 30.8%-91.3%), the specificity (Sp) was 63.6% (range, 50%-70.1%), and the accuracy (Acc) was 73.3% (range, 48%-88.5%) compared with IDTs. This study found good agreement and correlation between IDTs and serological MASTs based on monoclonal antibodies for most of the determined allergens for horses with IBH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Conjugation of avian IgY antibodies to nanosensors has been extensively explored for the diagnostics of virus and parasite infection, as well as for the detection of pharmaceutically and toxicologically relevant molecules. However, to date this strategy has only been minimally applied the detection of allergens. In this study, gold nanoparticles (GNPs) were conjugated to a polyvalent IgY antibodies raised against Dermatophagoides group I allergens. GNPs were synthesized by HAuCL 4 reduction using 1% trisodium citrate, and characterized them by absorption spectroscopy and transmission electron microscopy (TEM). The most stable immunoconjugates were obtained with 18-nm monodisperse GNPs and a minimal concentration of 12.5 μg/mL of IgY at pH 7.5. The immunoconjugate was capable of detecting up to 1.5 μg of a total Dermatophagoides farinae protein extract in an immuno-dot blot assay. This immunoreactant conjugate represents a new tool for the detection and control of indoor dust mite allergens., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to examine potential allergic reactions to different materials in oral and perioral diseases., Study Design: The study included 230 consenting subjects in total-180 patients with oral and perioral diseases (30 patients each in the following groups: angioedema, oral lichenoid reactions [OLRs], burning mouth syndrome [BMS], gingivostomatitis, cheilitis, and perioral dermatitis) and 50 healthy controls. Comprehensive diagnostic workups were performed prior to patch testing with standard series allergens and with specific dental materials and skin prick testing (SPT) for food, preservatives and additives, and inhalants., Results: Positive allergy test results were more common in patients with oral diseases than in controls, with significantly greater frequency of contact allergies in the cheilitis group (P = .048). The most common allergens in the majority patients were cobalt chloride (13.3% in BMS vs 10% in controls) and nickel sulfate (10% in gingivostomatitis and 6.7% in cheilitis vs 3.3% in controls), and preservatives (23.3% in angioedema and BMS)., Conclusions: Allergy skin tests are reliable and justified for diagnosing allergies in cases of persistent or recurrent oral diseases. This is the only way to confirm allergies and is the basis for consequent allergen avoidance for the benefit of the patient., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: In Portugal, data on the role of Der p 1 and Der p 2 in patients with house dust mite (HDM) allergy are scarce. Allergen-specific immunotherapy (sIT) is the only treatment that improves symptoms, reduces the need for pharmacological therapy and modifies the natural history of the disease. With this study, the authors aim to understand the local epidemiology and to clarify if the molecular assay of major allergens is advantageous in deciding and/or modifying the decision to initiate sIT in children with clinical indication which are sensitized to Dermatophagoides pteronyssinus., Methods: Retrospective study with analysis of patients with asthma and/or rhinitis., Study Period: January/2013-December/2016., Inclusion Criteria: 1) positive prick-test to Dermatophagoides pteronyssinus; and 2) clinically relevant disease under treatment. Assay Der p 1 and Der p 2 values ≥0.35 kUA/L were considered positive. Statistical significance was set at P<.05., Results: The clinical files of 279 patients. Mean ages 9.55 years (min.4-max.17). Asthma was present in 199 children (71.3%) and rhinitis in 245 (87.8%). Der p 1 and Der p 2 was <0.35kUA/L in 29 (10,4%) patients. The value of Der p 1/Der p 2 correlated with the size of the prick-test papule, the value of the eosinophils and the total IgE., Conclusions: Der p 1 and Der p 2 are dominant allergens in our population and there may be benefits in determining these molecular allergen levels in patients with a positive prick-test and a clinical indication for sIT prior to a decision of initiating sIT or not., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Several methods have been developed to detect allergen-specific IgE in sera. The passive IgE sensitization assay using human IgE receptor-expressing rat cell line RBL-2H3 is a powerful tool to detect biologically active allergen-specific IgE in serum samples. However, one disadvantage is that RBL-2H3 cells are vulnerable to high concentrations of human sera. Only a few human cultured cell lines are easily applicable to the passive IgE sensitization assay. However, the use of human induced pluripotent stem cells (iPSCs) to generate human mast cells (MCs) has not yet been reported., Methods: The nuclear factor-kappa B (NF-κB)-responsive luciferase reporter gene was stably introduced into a human iPSC line 201B7, and the transfectants were induced to differentiate into MCs (iPSC-MCs). The iPSC-MCs were sensitized overnight with sera from subjects who were allergic to cedar pollen, ragweed pollen, mites, or house dust, and then stimulated with an extract of corresponding allergens. Activation of iPSC-MCs was evaluated by β-hexosaminidase release, histamine release, or luciferase intensity., Results: iPSCs-MCs stably expressed high-affinity IgE receptor and functionally responded to various allergens when sensitized with human sera from relevant allergic subjects. This passive IgE sensitization system, which we termed the induced mast cell activation test (iMAT), worked well even with undiluted human sera., Conclusions: iMAT may serve as a novel determining system for IgE/allergens in the clinical and research settings., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Allergic sensitization results from a complex interaction between genetic and environmental factors. Earlier studies have shown that highly polymorphic HLA genes are associated with a variety of allergies. Several important respiratory allergens belong to the family of lipocalin proteins. These include occupational sensitizers, such as cow Bos d 2 or rat Rat n 1, and prevalent indoor sensitizers, such as dog Can f 1 or cockroach Bla g 4. HLA associations with sensitization to lipocalin allergens are incompletely known. In the present study we have investigated an association between HLA alleles and sensitization to the major cow allergen Bos d 2. The HLA-DR/DQ genotypes of 40 Bos d 2-sensitized subjects having occupational asthma were determined by polymerase chain reaction (PCR) and the results were compared with the genotypes of 151 unrelated Finnish subjects. The frequencies of HLA class II alleles DRB1*0101, DRB1*0404, DQB1*0302, and DQB1*0501 were significantly higher among Bos d 2-sensitized than among control subjects. In addition, the allergic subjects expressed significantly lower frequencies of HLA-DRB1*0301 and DQB1*0201 alleles than did the control subjects. These data suggest that the HLA class II alleles DRB1*0101, DRB1*0404, DQB1*0302, and DQB1*0501, and the haplotypes that include them, are associated with sensitization to the major cow allergen Bos d 2, whereas HLA-DRB1*0301 and DQB1*0201 are dissociated with it. Amino acid analysis provides a biologically plausible explanation for the HLA associations., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Objective: The purpose of this study was to investigate the presence of allergy in patients with benign migratory glossitis (BMG) using patch and prick tests., Patients and Methods: Eighty patients (40 BMG and 40 healthy controls) received patch and prick tests. If at least one test result was positive, patients were considered to be allergic., Results: The prick test was positive in 10 patients (25.0%) of the study group and in 4 patients (10.0%) of the control group. The patch test was positive in 12 patients (30.0%) of the study group and in 6 patients (15.0%) of the control group. When results of both tests were evaluated together, the study group showed a positive rate of 47.5% (n = 19), whereas the control group showed a positive rate of 22.5% (n = 9) (P = .02)., Conclusion: Our results revealed that a combination of prick and patch tests can significantly enhance the diagnostic accuracy of predisposition of allergy in patients with BMG., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Respiratory and/or food allergy is common in children. Serous otitis media is also very frequent in children, especially those between 3 and 6 years of age. On the other hand, in spite of promising animal studies, a cause-and-effect relation between these two conditions in man has not been established. Concerning the treatment, avoidance of food allergens may be as efficacious for an active serous otitis media as for avoidance of a new episode. Conversely, antihistamines do not appear to be efficacious, at least with respect to being curative.

Mosquito bites may induce allergic reactions in children. Usually underestimated, these reactions are often cutaneous and difficult to distinguish from non-specific histaminic phenomena. Recently, the identification of major allergens in mosquito saliva has allowed the achievement of recombinant allergens, which should facilitate the diagnosis and treatment of allergic reactions. Preventive cares must be performed in all children with large reactions, allergic or even non-allergic. Prevention consists in cutaneous protection, the use of repellents (with special attention to their toxicity), and antihistamines. A practical sheet for patient is provided.

Exposure to high ambient levels of nitrogen dioxide (NO2) enhances the airway reaction in humans to allergen, measured as decreased pulmonary function. We tested whether this NO2 effect is associated with an increased inflammatory response to allergen in the airways. To mimic real-life conditions, in which exposure to high ambient levels of NO2 occurs only during short periods of time but often several times a day, we used a repeated-exposure model. On day 1, 18 subjects with allergic asthma were exposed, in randomized order, to purified air or to 500 microg/m3 NO2 for 15 min, and on day 2 for 2 x 15 min. Allergen was inhaled 3-4h after the NO2 exposures on both days. Symptoms, pulmonary function, and inflammatory response in sputum and blood were measured daily. Eosinophil cationic protein in both sputum and blood increased more from day 1 to day 3 after NO2+allergen than after air+allergen, whereas eosinophil counts did not differ. The change in myeloperoxidase was significantly greater after NO2+allergen than after air+allergen in blood but not in sputum. This finding was not accompanied by raised levels of neutrophils in sputum and blood. Symptoms and pulmonary function were equally affected by NO2+allergen and air+allergen. We conclude that two to three brief exposures to ambient levels of NO2 can prime circulating eosinophils and enhance the eosinophilic activity in sputum in response to inhaled allergen. This might be an important mechanism by which air pollutants amplify the inflammatory reactions in the airways.

Background: Breastfeeding is widely advocated to reduce risk of atopy and asthma, but the evidence for such an effect is conflicting. We aimed to assess long-term outcomes of asthma and atopy related to breastfeeding in a New Zealand birth cohort., Methods: Our cohort consisted of 1037 of 1139 children born in Dunedin, New Zealand, between April, 1972, and March, 1973, and residing in Otago province at age 3 years. Children were assessed every 2-5 years from ages 9 to 26 years with respiratory questionnaires, pulmonary function, bronchial challenge, and allergy skin tests. History of breastfeeding had been independently recorded in early childhood., Findings: 504 (49%) of 1037 eligible children were breastfed (4 weeks or longer) and 533 (51%) were not. More children who were breastfed were atopic at all ages from 13 to 21 years to cats (p=0.0001), house dust mites (p=0.0010), and grass pollen (p<0.0001) than those who were not. More children who were breastfed reported current asthma at each assessment between age 9 (p=0.0008) and 26 years (p=0.0008) than those who were not. Breastfeeding effects were not affected by parental history of hayfever or asthma. Multifactor analysis controlling for socioeconomic status, parental smoking, birth order, and use of sheepskin bedding in infancy, showed odds ratios of 1.94 (95% CI 1.42-2.65, p<0.0001) for any allergen positive at age 13 years, 2.40 (1.36-4.26, p=0.0003) for current asthma at 9 years, and 1.83 (1.35-2.47, p<0.0001) for current asthma at 9-26 years by repeated-measures analysis., Interpretation: Breastfeeding does not protect children against atopy and asthma and may even increase the risk.

Children of atopic parents are recognised as being at higher risk of developing bronchial asthma, drawing the attention of prevention strategies towards this population. Due to recent advances, lung function abnormalities in asthmatic children may now be measured early in life. The aim ofthis investigation was to examine possible predictors of lung function development in a sub sample of high-risk infants who took part in an allergy avoidance study In 60 babies of atopic parents, measurements of upper airways inflammation were performed at 4 weeks of age, respiratory symptoms were assessed at 6 and 12 months of age, and lung function (Vmax, FRC) was measured at 18 months by the rapid thoracoabdominal compression technique. Twenty-eight babies were enrolled in an allergen avoidance program, and 32 recruited as controls. No significant differences were detected for V'max,FRC between the intervention group (mean 331 ml s(-1)) and the control group (359 ml s(-1)), P = 0.382. A multiple linear regression model could explain levels of V'max FRC by weight gain since birth (beta = -35.35 ml s(-1) kg(-1), P = 0.022) and by eosinophilic cationic protein (ECP) (beta = -0.95 ml s(-1) microl(-1), P = 0.044), but not by intervention. Lung function measured at the age of 18 months in high-risk children is associated with weight gain and nasal ECF.

Background: Some recent studies suggest that regular beta(2)-agonist use may result in inadequate control of asthma. It has been hypothesized that this occurs particularly in allergic asthmatic patients exposed to relevant allergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting beta(2)-agonists., Methods: Asthmatic patients (n = 145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting beta(2)-agonist (SA; n = 48), a long-acting beta(2)-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introduction of allergen avoidance measures (active/placebo treatment) to lower HDM exposure in the active group, and an 8-week washout period to adjust patients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter, spirometric measurements (FEV(1) and provocative concentration of histamine causing a 20% fall in FEV(1) [PC(20)]) were performed. Peak flow and asthma symptoms were recorded daily. Additionally, at the start and every 6 weeks thereafter, dust samples were collected from mattresses and living room and bedroom floors to assess HDM (der p 1) concentrations. Effects on FEV(1), PC(20), peak flow, and asthma symptoms were analyzed with repeated-measurement analysis and corrected for the exposure to HDM allergens., Results: There were no significant differences among the three medication groups after 12 weeks for FEV(1). However, a significant decrease in mean FEV(1) percent predicted (95% confidence interval [CI]) was observed within the SA group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002). A decrease in geometric mean PC(20) (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was observed within the SA group (p = 0.05). No significant changes in FEV(1) and PC(20) were observed > 12 weeks within the LA group or the placebo group. There were neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Moreover, none of the parameters showed interactive effects with allergen exposure., Conclusion: There were no significant differences among the three medication groups for FEV(1) and PC(20). The within-treatment group comparison showed a significant small decline in FEV(1) for the SA group (but not for the LA group), which could indicate that monotherapy with SAs might have negative effects on FEV(1). This was not seen during regular use of LAS: No clear pathophysiologic mechanism can explain these findings at the moment. Relatively high or low exposure to allergens did not alter these findings.

Control of the asthmatic child's environment forms an integral part of therapeutic care. This requires knowing what the main allergens in the child's habitat are and how they arise: eg, acarids, animal teguments, insects and fungi. The overall measures for reducing them chiefly entail controlling humidity: regular airing, or even ventilation, and eliminating sources of humidity can be recommended. Control of acarids will require modifying furnishings (no mats or carpeting, non hangings or heavy curtains, a slatted not interior spring bed base). Acarid-repellent loose covers seem to be more effective than acaricides, which give conflicting results. Physical processes, although necessary, are seldom sufficient. Animals should be evicted. If this is impossible, certain measures have proved effective, however. Insects and moulds are controlled by specific sanitary measures. A practical approach is proposed that takes into account both theoretical demands and everyday realities.

Extracts from ragweed pollen grains contain novel trypsin and chymotrypsin-like serine peptidases which are described in this report. The molecular mass of the chymotrypsin-like enzyme was 82 kDa, had a pH optimum near 9.0, and its activity was unaffected by chelating or reducing agents. It was inhibited by diisopropyl fluorophosphate (DFP), a general serine class inhibitor, and more specifically N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a chymotrypsin-like proteinase inhibitor. In addition to various synthetic substrates, the neuropeptides, vasoactive intestinal peptide (VIP) and substance P, which are required for normalized lung functions, were also rapidly hydrolysed. Activity toward protein substrates was not detected with the exception of the inactivation of alpha-1-proteinase inhibitor (alpha-1-PI) which occurred through cleavage within the reactive site loop. The 'trypsin-like' enzyme has a molecular mass near 80 kDa, a blocked N-terminus, a pH optimum near 9.0, and requires Ca++ for stability and activity, but not reducing agents. It is inhibited by DFP, and more specifically the trypsin-like proteinase inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK). Again, activity toward protein substrates was not detected, but various synthetic substrates and biologically active peptides were efficiently cleaved. Significantly, atrial natriuretic peptide (ANP) and angiotensin 2 (ATII), whose degradation would amplify kinin activity and influence inflammatory diseases of the respiratory tract and nasal passages, were also rapidly hydrolyzed.