Airborne Alt a 1 Dynamic and Its Relationship with the Airborne Dynamics of Alternaria Conidia and Pleosporales Spores

This research was carried out within the framework of the research projects funded by the Ministry of Science and Technology I + D + I of Spain CGL2012-39523-C02-01 and CTM2017-89565-C2-1-P. This research contributes to the "Maria de Maeztu" Programme for Units of Excellence of the Spanish Ministry of Science and Innovation (CEX2019-000940-M).Fungal spores are universal atmospheric components associated to allergic reactions. Alternaria (Ascomycota) is considered the most allergenic spore taxa. Alt a 1 is the major allergen of Alternaria and is present also in other Pleosporales. In this study, standard Hirst-based sampling and analyzing methods for measuring spore daily concentrations of Alternaria, Curvularia, Drechslera- Helminthosporium, Epicoccum, Leptosphaeria, Pithomyces, Pleospora and Stemphylium (all included in the taxon Pleosporales) have been used as well as two high-volume samplers, Burkard Cyclone (2017) and MCV CAV-A/mb (2019–2020), and ELISA kits for measuring the allergen. The detection and quantification of Alt a 1 was only possible in the samples from the MCV sampler. Although Alt a 1 was better correlated with Alternaria spores than with Pleosporales spores, the three of them showed high correlations. It is shown that there is a high and significant correlation of Alt a 1 with temperature, a negative correlation with relative humidity and no correlation with precipitation. The aerobiological monitoring of these three elements ensures the best information for understanding the affectation to allergy sufferers, but, if this is not possible, as a minimum public health service aimed at the detection, treatment and prevention of allergies, the study of the airborne Alternaria spores should be ensured.Ministry of Science and Technology I + D + I of Spain CGL2012-39523-C02-01 CTM2017-89565-C2-1-P"Maria de Maeztu" Programme for Units of Excellence of the Spanish Ministry of Science and Innovation CEX2019-000940-

Aspergillus Conidia and Allergens in Outdoor Environment: A Health Hazard?

Aspergillus is a genus of saprophytic fungus widely distributed in the environment and associated with soil, decaying vegetation, or seeds. However, some species, such as A. fumigatus, are considered opportunistic pathogens in humans. Their conidia (asexual spores) and mycelia are associated with clinical diseases known as invasive aspergillosis (IA), mainly related to the respiratory tract, such as allergic asthma, allergic bronchopulmonary aspergillosis (ABPA), or hypersensitivity. However, they can also disseminate to other organs, particularly the central nervous system. Due to the dispersal mechanism of the conidia through the air, airborne fungal particle measurement should be used to prevent and control this mold. This study aims to measure the outdoor airborne concentration of Aspergillus conidia and the Asp f 1 allergen concentration in Bellaterra (Barcelona, Spain) during 2021 and 2022, and to compare their dynamics to improve the understanding of the biology of this genus and contribute to a better diagnosis, prevention, and therapeutic measures in the face of possible health problems. The results show that both particles were airborne nearly all year round, but their concentrations showed no correlation. Due to Asp f 1 not being present in the conidia itself but being detectable during their germination and in hyphal fragments, we report the relevance of the aero-immunological analysis as a methodology to detect the potential pathogenic hazard of this fungus.Ministry of Science and Technology I + D + I of Spain CGL2012-39523-C02-01CTM2017-89565- C2-1-P

Potential contribution of distant sources to airborne Betula pollen levels in Northeastern Iberian Peninsula

We acknowledge the financial support of the European Commission for ENV4-CT98-0755; the Spanish Government for CGL2004-21166-E, CGL2005-07543/CLI, CGL2009-11205, CGL2012-39523-C02-01/CLI, CGL2012-39523-C02-02, CGL2016-75996-R, CTM2017-89565-C2-1, CTM2017-89565-C2-2, and CSD 2007-00067; the Catalan Government for 2005SGR00519, 2009SGR1102, and 2017SGR1692; Diputacio de Tarragona; Servei Meteorologic de Catalunya; Sociedad Espanola de Alergologia e Inmunologia Clinica (SEAIC); Laboratorios LETI PHARMA; Societat Catalana d'Allergia i Immunologia Clinica (SCAIC); J Uriach y Compania; S.A. This research contributes to the Maria de Maeztu Programme for Units of Excellence of the Spanish Ministry of Science and Innovation (CEX2019-000940-M). The authors gratefully acknowledge the NOAA Air Resources Laboratory (ARL) for their HYSPLIT transport and dispersion model and the synoptic charts used in this publication.Betula (birch) pollen is one of the most important causes of respiratory allergy in Northern and Central Europe. While birch trees are abundant in Central, Northern, and Eastern Europe, they are scarce in the Mediterranean territories, especially in the Iberian Peninsula (IP), where they grow only in the northern regions and as ornamental trees in urban areas. However, the airborne birch pollen patterns in Catalonia (Northeastern IP) show abrupt high concentrations in areas with usually low local influence. The intensity of the derived health problems can be increased by outbreaks due to long-range pollen transport. The present work evaluates the different potential contributions to Catalonia from the main source regions: Pyrenees, Cantabria, and the forests of France and Central Europe. To this end, we computed the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) back trajectories of air masses associated with the main Betula pollen peaks occurring simultaneously over different Catalan monitoring stations, and we studied their provenance over a 15-year period. The Vielha aerobiological station on the northern slopes of the Central Pyrenees was used to identify the dates of the pollen season in the Pyrenean region. In order to better understand the role of the Pyrenees, which is the nearest of the four birch forested regions, we classified the pollen peaks in the other Catalan stations into three groups based on the relationship between the peak and the pollen season in the Pyrenees. Our analysis of back-trajectory residence time, combined with the associated pollen concentration, reveals that two principal routes other than the Pyrenean forest sustain the northerly fluxes that enter Catalonia and carry significant concentrations of Betula pollen. This study has also allowed quantifying the differentiated contributions of the potential source regions. In addition, theWeather Research Forecast (WRF) mesoscale model has been used to study three specific episodes. Both models, HYSPLIT and WRF, complement each other and have allowed for better understanding of the main mechanisms governing the entry of birch pollen to the region.European Commission European Commission Joint Research Centre ENV4-CT98-0755Spanish GovernmentEuropean Commission CGL2004-21166-E CGL2005-07543/CLI CGL2009-11205 CGL2012-39523-C02-01/CLI CGL2012-39523-C02-02 CGL2016-75996-R CTM2017-89565-C2-1 CTM2017-89565-C2-2 CSD 2007-00067Diputacio de TarragonaSociedad Espanola de Alergologia e Inmunologia Clinica (SEAIC)Laboratorios LETI PHARMASocietat Catalana d'Allergia i Immunologia Clinica (SCAIC)J Uriach y CompaniaMaria de Maeztu Programme for Units of Excellence of the Spanish Ministry of Science and Innovation CEX2019-000940-MCatalan Government 2005SGR00519 2009SGR1102 2017SGR169

Aerobiological and allergenic analysis of Cupressaceae pollen in Granada (Southern Spain)

Cupressaceae pollen has been cited in recent years as one of the major airborne allergens of the Mediterranean region, prompting us to conduct an exhaustive analysis on the aerobiological behaviour of this pollen in the Iberian Peninsula and the repercussion that it has had on the atopic population. The aerobiological study, performed from 1996 to 2003 in the city of Granada (S. Spain), used a volumetric Hirst collector. The results indicate that this pollen is present in the air most of the year, registering a high incidence during the winter months. This type of pollen behaved irregularly in the air, fluctuating yearly, seasonally, and within the same day. Temperature and humidity were the parameters that most directly influence the variability of this allergen, while rainfall prior to flowering increased pollen production. The predictive models used estimated a high percentage of the levels reached over the short term by this pollen in the atmosphere of Granada. The clinical study performed with atopic patients showed that some 30% of the population with pollinosis are sensitive to Cupressaceae pollen, affecting people of both genders equally. On the other hand, the most sensitive age group was 21-40 years of age, while children and the elderly registered almost negligible values. Most of the sensitive subjects resided within the city or in the metropolitan area, where environmental pollution reached high levels, while the pathology was found to be less frequent in rural zones. The most frequent symptoms were upper-respiratory ailments and an asthmatic profile.En los últimos años el polen de Cupressaceae se ha considerado uno de los principales alérgenos aéreos de la región Mediterránea, lo que motivó la realización de un análisis exhaustivo del comportamiento aerobiológico de este polen en la Península Ibérica y de la repercusión que tenía en la población atópica. En el estudio aerobiológico, llevado a cabo entre 1996 y 2003 en la ciudad de Granada (sur de España), se utilizó un captador volumétrico tipo Hirst. Los resultados indican que este polen se encuentra presente en el aire la mayor parte del año, pero registra una alta incidencia en los meses de invierno. Este tipo de polen mostró un comportamiento irregular en el aire, con fluctuaciones anuales, estacionales y en un mismo día. La temperatura y la humedad fueron los parámetros que influyeron más directamente en la variabilidad de este alérgeno, mientras que la lluvia antes de la floración incrementó la producción de polen. Los modelos predictivos utilizados estimaron un porcentaje elevado de los niveles alcanzados a corto plazo por este polen en la atmósfera de Granada. El estudio clínico realizado con pacientes atópicos mostró que un 30% de la población con polinosis es sensible al polen de Cupressaceae, afectando a ambos sexos por igual. Por otra parte, el grupo de edad más sensible fue el de 21 a 40 años, mientras que los niños y los ancianos registraron valores casi insignificantes. La mayoría de los sujetos sensibles residían en el núcleo urbano o en el área metropolitana, donde la contaminación ambiental alcanza niveles elevados, mientras que la patología fue menos frecuente en la zona rural. Los síntomas más frecuentes fueron afecciones de las vías respiratorias altas y un perfil asmático.The authors wish to thank the Spanish Ministry of Science and Technology for financing this study with the “Análisis de la actividad alergénica de la atmósfera” project (BOS2002-03474)

A Comparison of Models for the Forecast of Daily Concentration Thresholds of Airborne Fungal Spores

Altres ajuts: Ministerio de Ciencia y Tecnología AMB97-0457-CO7-021, REN2001-10659-CO3-01, BOS2002-03474, CGL2004-21166-E, GGL2006-12648-CO3-02Unidad de excelencia María de Maeztu CEX2019-000940-MAerobiological predictive model development is of increasing interest, despite the distribution and variability of data and the limitations of statistical methods making it highly challenging. The use of concentration thresholds and models, where a binary response allows one to establish the occurrence or non-occurrence of the threshold, have been proposed to reduce difficulties. In this paper, we use logistic regression (logit) and regression trees to predict the daily concentration thresholds (low, medium, high, and very high) of six airborne fungal spore taxa (Alternaria, Cladosporium, Agaricus, Ganoderma, Leptosphaeria, and Pleospora) in eight localities in Catalonia (NE Spain) using data from 1995 to 2014. The predictive potential of these models was analyzed through sensitivity and specificity. The models showed similar results regarding the relationship and influence of the meteorological parameters and fungal spores. Ascospores showed a strong relationship with precipitation and basidiospores with minimum temperature, while conidiospores did not indicate any preferences. Sensitivity (true-positive) and specificity (false-positive) presented highly satisfactory validation results for both models in all thresholds, with an average of 73%. However, seeing as logit offers greater precision when attempting to establish the exceedance of a concentration threshold and is easier to apply, it is proposed as the best predictive model

Airborne Cupressaceae Pollen and Its Major Allergen, Cup a 1, in Urban Green Areas of Southern Iberian Peninsula

Cupressaceae pollen is responsible for winter respiratory allergies in the Mediterranean area. Pollen grains of this diverse family share the same characteristics under light microscopy. Consequently, the partial contribution of each Cupressaceae species to the airborne pollen spectrum cannot be determined with conventional aerobiological methods. Studies on major aeroallergens offer better information on the allergic sensitization and appearance of symptoms in patients sensitized to airborne pollen and spores. Our aim was to determine if airborne Cupressaceae pollen concentrations correspond to aerodynamics of the major allergen of Cupressus (Cup a 1), as well as the aeroallergen correlation with different-sized particles. The air was sampled in two cities of Southern Spain (Granada and Córdoba) using the Hirst-type volumetric sampler for airborne pollen detection during 2006 to 2008 and the Andersen Cascade Impactor for aeroallergen detection during the main pollination period of Cupressaceae in the same period. The samples were analyzed by the methodology proposed by the Spanish Aerobiology Network (REA), the minimum requirements of the European Aeroallergen Society (EAS) for pollen, and by ELISA immunoassay to detect airborne Cup a 1. The distribution patterns of airborne Cupressaceae pollen and Cup a 1 were observed throughout the sampling period, although with some irregular oscillations. Cupressaceae pollen and Cup a 1 showed positive and significant correlation during the period of maximum concentrations (January to March). However, the results of this study showed that the period of exposure of aeroallergens depends on the Cupressus species and their abundance in cities. According to the allergy potential obtained, species like C. arizonica could release more allergens than other species like C. sempervirens.Ministry of Science and Technology I + D + I of Spain CGL2006-1648-CO3-02Andalusian Government RNM 011

Building-integrated agriculture : a first assessment of aerobiological air quality in rooftop greenhouses (i-RTGs)

Unidad de excelencia María de Maeztu MdM-2015-0552Building-integrated rooftop greenhouse (i-RTG) agriculture has intensified in recent years, due to the growing interest in the development of new agricultural spaces and in the promotion of food self-sufficiency in urban areas. This paper provides a first assessment of the indoor dynamics of bioaerosols in an i-RTG, with the aim of evaluating biological air quality in a tomato greenhouse near Barcelona. It evaluates the greenhouse workers' exposure to airborne pollen and fungal spores in order to prevent allergy problems associated with occupational tasks. Moreover, it evaluates whether the quality of the hot air accumulated in the i-RTG is adequate for recirculation to heat the building. Daily airborne pollen and fungal spore concentrations were measured simultaneously in the indoor and outdoor environments during the warm season. A total of 4,924 pollen grains/m3 were observed in the i-RTG, with a peak of 334 pollen grains/m3day, and a total of 295,038 fungal spores were observed, reaching a maximum concentration of 26,185 spores/m3day. In general, the results showed that the most important source of pollen grains and fungal spores observed indoors was the outdoor environment. However, Solanaceae pollen and several fungal spore taxa, such as the allergenic Aspergillus/Penicillium, largely originated inside the greenhouses or were able to colonize the indoor environment under favourable growing conditions. Specific meteorological conditions and agricultural management tasks are related to the highest observed indoor concentrations of pollen grains and fungal spores. Therefore, preventive measures have been suggested in order to reduce or control the levels of bioaerosols indoors (to install a system to interrupt the recirculation of air to the building during critical periods or to implement appropriate air filters in ventilation air ducts). This first evaluation could help in making decisions to prevent the development of fungal diseases, specifically those due to Oidium and Torula

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Serum profiling identifies CCL8, CXCL13, and IL-1RA as markers of active disease in patients with systemic lupus erythematosus

IntroductionSystemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).MethodsSerum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121). Cytokine levels were determined using Luminex panels, and autoantibodies using different immunoassays.ResultsOf the 83 cytokines analysed, 29 differed significantly between patients with SLE and HC. Specifically, CCL8, CXCL13, and IL-1RA levels were elevated in patients with active, but not inactive, SLE versus HC, as well as in patients with SLE versus other AIDs. The levels of these cytokines also correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores, among five other cytokines. Overall, the occurrence of autoantibodies was similar across SLEDAI-2K organ domains, and the correlations between autoantibodies and activity in different organ domains were weak.DiscussionOur findings suggest that, upon validation, CCL8, CXCL13, and IL-1RA could serve as promising serum biomarkers of activity in SLE