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Agriculture dust contains many organic immunogenic compounds, and organic dust exposure is strongly associated with the development of immune-mediated chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD). Chronic organic dust exposure from agriculture sources induces chronic lung inflammatory diseases and organic dust exposure has recently been linked to an increased risk of developing dementia. The cytokine interleukin-22 (IL-22) has been established as an important mediator in the resolution and repair of lung tissues. The omega-3 fatty acid metabolite aspirin-triggered Resolvin D1 (AT-RvD1) has shown efficacy in modulating the immune response in both pulmonary and neurological inflammation but has not been explored as a therapeutic in organic dust exposure-induced neuroinflammation. Investigating the link between IL-22 and AT-RvD1 may help in developing effective therapies for these immune-mediated diseases. We aimed to investigate the link between organic dust exposure and neuroinflammation, the role of IL-22 in the pulmonary and neurological immune response to organic dust exposure, and the immune-modulating therapeutic applications of AT-RvD1 in an IL-22 knock-out mouse model of organic dust exposure. C57BL/6J (WT) and IL-22 knock-out (KO) mice were repetitively exposed to aqueous agriculture organic dust extract (DE) 5 days per week for 3 weeks (15 total instillations) and treated with AT-RvD1 either once per week (3 total injections) or 5 times per week (15 total injections) for 3 weeks and allowed to recover for 3 days. We observed a significant pulmonary and neurological immune response to DE characterized by the development of inducible bronchus associated lymphoid tissue in the lung and gliosis in the frontal areas of the brain. We also observed that IL-22 knock-out increased pulmonary and neurological inflammation severity. Animals exposed to DE and treated with AT-RvD1 displayed reduced lung pathology severity and gliosis. Our data demonstrate that DE exposure contributes to neurological inflammation and that IL-22 is crucial to effective tissue repair processes. Our data further suggest that AT-RvD1 may have potential as a novel therapeutic for organic dust exposure-induced, immune-mediated pulmonary and neurological inflammation, improving outcomes of those with these diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AU declared a past co-authorship with the author TN to the handling editor., (Copyright © 2024 Threatt, White, Klepper, Brier, Dean, Ibarra, Harris, Jones, Wahl, Barahona, Oyewole, Pauly, Moreno and Nordgren.)

Background: Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described., Objective: Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures., Methods: Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n = 120) or age 36 months (n = 142) and paired house dust samples collected at 3 months (12-month, n = 73; 36-month, n = 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort., Results: In these high-risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ß = 2.04; P = .006). Age-related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P = .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness (R 2  = 0.055; P = .0001) and dominant bacterial genus (R 2  = 0.59; P = .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high-wheeze respiratory phenotypes. By age 36 months, nasal microbiota was significantly associated with respiratory phenotypes (R 2  = 0.019; P = .0376), and Moraxella-dominated microbiota was associated specifically with atopy-associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment., Conclusion: Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early-life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years., (Copyright © 2024. Published by Elsevier Inc.)

The patient was a 3-year-old girl whose father was employed sorting and washing soybeans. She exhibited transient respiratory distress and loss of activity on the same day or the next day after her father came home wearing work clothes with soybean dust on them. One day, she developed anaphylaxis after being lifted into her father's arms while he was wearing his work clothes. Although a blood test was positive for soybean and Gly m 4-specific IgE antibodies, the girl was able to consume soy products (not including soy milk, which she had never consumed) without any issues. The father was instructed to change clothes before leaving work and bathe immediately upon returning home, and the girl has not had any further episodes of respiratory distress, loss of activity, or anaphylaxis. Though reports of anaphylaxis from soybean antigen inhalation are extremely rare, it is very likely that inhalation of soybean dust from the father's work clothes induced anaphylaxis in this case.

Background: The prevalence of allergic respiratory disease (ARD) is increasing worldwide during the last few decades, causing a great disease burden especially for children. Air pollution has been increasingly considered as a potential contributor to this trend, but its role in ARD induced by house dust mite (HDM-ARD) remains unclear, especially in time-series study., Methods: A positive reporting of respiratory allergy to named allergens was included by serum specific IgE testing. A time series Quasi-Poisson regression with distributed lag non-linear model, combined with generalized linear model was used to examine the effects of air pollutants on ARD, HDM-ARD and ARD induced by non-house dust mite (NHDM-ARD)., Results: A total of 16,249 cases of ARD, including 8,719 HDM-ARD and 8,070 NHDM-ARD from 1 Jan 2013 to 31 Dec 2017 were involved in this study. Air pollutants were significantly associated with clinical visits for childhood ARD and HDM-ARD. Exposure to higher O 3 and interquartile range (IQR) increment in O 3 (40.6 µg/m 3 ) increased the risks of clinical visits for childhood HDM-ARD (RR lag0-5 for the 95th percentile of O 3 : 1.26, 95% confidence interval (CI): 1.03, 1.55; RR lag0-5 for IQR increment (40.6 µg/m 3 ): 1.09, 95% CI: 1.01, 1.17) and ARD (RR lag0-5 for the 95th percentile of O 3 : 1.19, 95% CI: 1.03, 1.38; RR lag0-5 for IQR increment (40.6 µg/m 3 ): 1.06, 95% CI: 1.01, 1.12). In addition, higher O 3 was associated with increased RR of boys with ARD (RR lag0-5 for the 95th percentile: 1.26, 95% CI: 1.05, 1.51; RR lag0-5 for IQR increment (40.6 µg/m 3 ): 1.09, 95% CI: 1.02, 1.16) and HDM-ARD (RR lag0-5 for the 95th percentile: 1.36, 95% CI: 1.06, 1.75; RR lag0-5 for IQR increment (40.6 µg/m 3 ): 1.11, 95% CI: 1.02, 1.22), but not in girls., Conclusions: Exposure to O 3 appeared to be a trigger of clinical visits for childhood ARD, especially for HDM-ARD and boys. These findings provide novel evidence on the impact of air pollution on HDM-ARD, which may have significant implications for designing effective intervention programs to control and prevent childhood ARD, especially HDM-ARD, in China and other similar developing countries., (© 2022. The Author(s).)

Rationale: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. Objectives: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. Methods: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. Measurements and Main Results: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV 1 of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (β, -8.29; 95% confidence interval [CI], -14.80 to -1.77), higher St. George's Respiratory Questionnaire Total Score (β, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. Conclusions: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD outcomes.

Inflammatory response in patients with COPD secondary to organic dust exposure (OD-COPD) is poorly understood. We therefore aimed to characterize inflammatory and immune profile from peripheral blood mononuclear cells (PBMC) in a group of patients with mild-to-moderate COPD secondary to organic dust exposure (OD-COPD), tobacco smoking (T-COPD), or both. We compared T, B and NK cells distribution and inflammatory (TNF-α, Il-1β, IL-6), type 1 (IFN-γ), type 2 (IL-4, IL-13) and type 3 (IL-17) immunity related cytokines at baseline, and after stimulation with LPS, flagellin and CD3/CD28 beads in all COPD groups. OD-COPD displayed significantly lower NK cells and CD8+ T cells compared with controls. After flagellin stimulation, T-COPD had significantly lower IL-13 levels than OD-COPD and controls (p < 0.05) whereas IFN-γ tended to be lower in OD-COPD. All COPD groups displayed higher IL-1β and IL-17 than controls after CD3/CD28 stimulation. Inflammatory responses in OD-COPD were different from T-COPD. OD-COPD displayed higher levels of type 2 immunity related cytokines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Identifying allergen distribution is meaningful and significant for effective diagnosis and treatment of allergic diseases. This study compared the allergen sensitivity in four southern China cities. We enrolled 55,432 participants (27,408 male, 28,024 female) between 2007 and 2019. The allergen-specific IgE levels were compared by the χ2 test. The five prevalent sensitivities were for mite mix (10,985, 19.82%), cockroach (4,860, 8.77%), crab (4,450, 8.03%), fish mix (3,874, 6.99%), and house dust (3,486, 6.29%). Almost all allergen sensitivities decreased with age, particularly from infant to middle aged participants (p < 0.05). An exception was Shenzhen, where food allergen positive rates remained constant in all age groups studied. The proportion of male sensitive to at least one food allergen (OR 1.130; 95% CI 1.088-1.174, p < 0.0025) or aeroallergen (OR, 1.117; 95% CI, 1.078-1.158, p < 0.0025) was higher than female in all four cities. Except for dog dander and tree mix, all aeroallergens differed significantly between seasons (p < 0.05). Liuzhou had the highest rates of food allergen- and aeroallergen-positive participants. The allergen-specific IgE distribution differed among the studied cities, with significant seasonal differences. Young age, male sex, and aeroallergens were risk factors for allergic disease.

The Southwestern United States has a legacy of industrial mining due to the presence of rich mineral ore deposits. The relationship between environmental inhaled particulate matter (PM) exposures and neurological outcomes within an autoimmune context is understudied. The aim of this study was to compare two regionally-relevant dusts from high-priority abandoned mine-sites, Claim 28 PM, from Blue Gap Tachee, AZ and St. Anthony mine PM, from the Pueblo of Laguna, NM and to expose autoimmune-prone mice (NZBWF1/J). Mice were randomly assigned to one of three groups (n = 8/group): DM (dispersion media, control), Claim 28 PM, or St. Anthony PM, subjected to oropharyngeal aspiration of (100 µg/50 µl), once per week for a total of 4 consecutive doses. A battery of immunological and neurological endpoints was assessed at 24 weeks of age including: bronchoalveolar lavage cell counts, lung gene expression, brain immunohistochemistry, behavioral tasks and serum autoimmune biomarkers. Bronchoalveolar lavage results demonstrated a significant increase in number of polymorphonuclear neutrophils following Claim 28 and St. Anthony mine PM aspiration. Lung mRNA expression showed significant upregulation in CCL-2 and IL-1ß following St. Anthony mine PM aspiration. In addition, neuroinflammation was present in both Claim 28 and St. Anthony mine-site derived PM exposure groups. Behavioral tasks resulted in significant deficits as determined by Y-maze new arm frequency following Claim 28 aspiration. Neutrophil elastase was significantly upregulated in the St. Anthony mine exposure group. Interestingly, there were no significant changes in serum autoantigens suggesting systemic inflammatory effects may be mediated through other molecular mechanisms following low-dose PM exposures.

Workplaces with elevated organic dust levels such as animal feed barns also commonly have elevated levels of gasses, such as CO 2 . Workers exposed to such complex environments often experience respiratory effects that may be due to a combination of respirable factors. We examined the effects of CO 2 on lung innate immune responses in mice co-exposed to the inflammatory agents lipopolysaccharide (LPS) and organic dust. We evaluated CO 2 levels at the building recommended limit (1000 ppm) as well as the exposure limit (5000 ppm). Mice were nasally instilled with dust extracts or LPS and immediately put into chambers with a constant flow of room air (avg. 430 ppm CO 2 ), 1000 ppm, or 5000 ppm CO 2 enriched air. Results reveal that organic dust exposures tended to show decreased inflammatory responses with 1000 ppm CO 2 and increased responses at 5000 ppm CO 2 . Conversely, LPS with addition of CO 2 as low as 1000 ppm tended to inhibit several inflammatory markers. In most cases saline treated animals showed few changes with CO 2 exposure, though some changes in mRNA levels were present. This shows that CO 2 as low as 1000 ppm CO 2 was capable of altering innate immune responses to both LPS and organic dust extracts, but each response was altered in a different fashion.

The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation., Competing Interests: The authors have declared that no competing interests exist.

Background: Bacterial exposure from house dust has been associated with asthma and atopy in children but whether these relationships are present in adults remains unclear., Objective: We sought to examine associations of house dust microbiota with adult asthma, atopy, and hay fever., Methods: Vacuumed bedroom dust samples from the homes of 879 participants (average age, 62 years) in the Agricultural Lung Health Study, a case-control study of asthma nested within a farming cohort, were subjected to 16S rRNA amplicon sequencing to characterize bacterial communities. We defined current asthma and hay fever using questionnaires and current atopy by blood specific IgE level > 0.70 IU/mL to 1 or more of 10 common allergens. We used linear regression to examine whether overall within-sample bacterial diversity differed by outcome, microbiome regression-based kernel association test to evaluate whether between-sample bacterial community compositions differed by outcome, and analysis of composition of microbiomes to identify differentially abundant bacterial taxa., Results: Overall diversity of bacterial communities in house dust was similar by asthma status but was lower (P < .05) with atopy or hay fever. Many individual bacterial taxa were differentially abundant (false-discovery rate, <0.05) by asthma, atopy, or hay fever. Several taxa from Cyanobacteria, Bacteroidetes, and Fusobacteria were more abundant with asthma, atopy, or hay fever. In contrast, several taxa from Firmicutes were more abundant in homes of individuals with adequately controlled asthma (vs inadequately controlled asthma), individuals without atopy, or individuals without hay fever., Conclusions: Microbial composition of house dust may influence allergic outcomes in adults., (Published by Elsevier Inc.)

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, autoreactive/suppressor), 5 macrophages (airspace, differentiating/recruited, recruited, resident/interstitial, and proliferative airspace), 2 T-cells (differentiating and effector), and a single cluster each of inflammatory monocytes, dendritic cells, B-cells and natural killer cells. Inflammatory monocytes, autoreactive/suppressor neutrophils, and recruited/differentiating macrophages were predominant with arthritis induction (CIA and CIA+ODE). By specific lung cell isolation, several interferon-related and autoimmune genes were disproportionately expressed among CIA and CIA+ODE (e.g. Oasl1, Oas2, Ifit3, Gbp2, Ifi44, and Zbp1), corresponding to RA and RA-associated lung disease. Monocytic myeloid-derived suppressor cells were reduced, while complement genes (e.g. C1s1 and Cfb) were uniquely increased in CIA+ODE mice across cell populations. Recruited and inflammatory macrophages/monocytes and neutrophils expressing interferon-, autoimmune-, and complement-related genes might contribute towards pro-fibrotic inflammatory lung responses following airborne biohazard exposures in setting of autoimmune arthritis and could be predictive and/or targeted to reduce disease burden., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Wheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved., Methods: Of the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010-2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models., Results: The prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (p<0.001). The risk of work-related asthma-like symptoms was more than doubled in bakers using additives without or with multigrain than in shop assistants (OR 2.3, 95% CI 1.0 to 5.5 and OR 3.4, 95% CI 1.1 to 10.8, respectively). Making bread with additives alone or with multigrain significantly increased the risk of work-related nasal symptoms in shop assistants, while the risk of skin symptoms was not significantly affected., Conclusions: Bakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Allergic airway disease models use laboratory mice housed in highly controlled and hygienic environments, which provide a barrier between the mice and a predetermined list of specific pathogens excluded from the facility. In this study, we hypothesized that differences in facility barrier level and, consequently, the hygienic quality of the environment that mice inhabit impact the severity of pulmonary inflammation and lung function. Allergen-naive animals housed in the cleaner, high barrier (HB) specific pathogen-free facility had increased levels of inflammatory cytokines and higher infiltration of immune cells in the lung tissue but not in the bronchoalveolar lavage compared with mice housed in the less hygienic, low barrier specific pathogen-free facility. In both genders, house dust mite-induced airway disease was more severe in the HB than the low barrier facility. Within each barrier facility, female mice developed the most severe inflammation. However, allergen-naive male mice had worse lung function, regardless of the housing environment, and in the HB, the lung function in female mice was higher in the house dust mite model. Severe disease in the HB was associated with reduced lung microbiome diversity. The lung microbiome was altered across housing barriers, gender, and allergen-exposed groups. Thus, the housing barrier level impacts microbial-driven disease and gender phenotypes in allergic asthma. The housing of laboratory mice in more clean HB facilities aggravates lung immunity and causes a more severe allergic lung disease., (Copyright © 2021 The Authors.)

House dust mites (HDMs) are one of the major causes of allergies in the world. The group 23 allergen, Der p 23, from Dermatophagoides pteronyssinus, is a major allergen amongst HDM-sensitized individuals. This study aims to determine the specific immunoglobulin E (sIgE) binding frequency and IgE-binding residues of recombinant Der p 23 (rDer p 23) allergen amongst a cohort of consecutive atopic individuals in a tropical region. We performed site-directed mutagenesis and carried out immuno-dot blot assays using 65 atopic sera. The immuno-dot blot assays results indicated that the two residues K44 and E46 which are located at the N-terminal region are the major IgE-binding residues. The rDerp-23 sIgE titers are strongly correlated to the number of IgE-binding residues for rDer p 23 (P < 0.001). Atopic individuals who were only sensitized to HDM have a significantly higher number of IgE-binding residues than the individuals who were polysensitized to HDM and other crude allergens (P < 0.05). Individuals with allergic multimorbidity and moderate-to-severe allergic rhinitis also have a higher number of IgE-binding residues compared to those with single allergic disease and mild allergic rhinitis. The results prompt us to hypothesize that the individuals who have a higher number of IgE-binding residues may face a bigger challenge to be treated through immunotherapy due to the complexity in designing an effective hypoallergen with a high number of IgE-binding residues. We propose that the development of a refined molecular diagnostic assay, which includes alanine substitution of surface-exposed residues could be a more precise diagnostic strategy to identify all the IgE-binding residues of a major allergen for an atopic individual and the development could be another new dimension in allergy diagnosis and allergen immunotherapy treatment.

Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFα through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated in vitro with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced in vivo lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in in vivo HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. In vitro rIL-10 treatment reduced HDE-stimulated TNFα release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (ζ) activity and increased TNFα following in vitro HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFα and decreased IL-10 and PKCζ activation. PKCζ inhibitors blocked HDE-stimulated IL-10, but not TNFα. Collectively, HDE stimulates IL-10 by an SRA- and PKCζ-dependent mechanism to regulate TNFα. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions.

Asthma is one of the most common childhood chronic diseases worldwide. Subcutaneous immunotherapy (SCIT) is commonly used in the treatment of house dust mite (HDM)‑related asthma in children. However, the therapeutic mechanism of SCIT in asthma remains unclear. The present study aimed to investigate the molecular biomarkers associated with HDM‑related asthma in asthmatic children prior and subsequent to SCIT treatment compared with those in healthy children via proteomic analysis. The study included a control group (30 healthy children), ‑Treatment group (30 children with HDM‑related allergic asthma) and +Treatment group (30 children with HDM‑related allergic asthma treated with SCIT). An isobaric labeling with relative and absolute quantification‑based method was used to analyze serum proteome changes to detect differentially expressed proteins, while functional enrichment and protein‑protein interaction network analysis were used to select candidate biomarkers. A total of 72 differentially expressed proteins were detected in the ‑Treatment, +Treatment and control groups. A total of 33 and 57 differentially expressed proteins were observed in the ‑Treatment vs. control and +Treatment vs. control groups, respectively. Through bioinformatics analysis, 5 candidate proteins [keratin 1 (KRT1), apolipoprotein B (APOB), fibronectin 1, antithrombin III (SERPINC1) and α‑1‑antitrypsin (SERPINA1)] were selected for validation by western blotting; among them, 4 proteins (KRT1, APOB, SERPINC1 and SERPINA1) showed robust reproducibility in asthma and control samples. This study illustrated the changes in proteome regulation following SCIT treatment for asthma. The 4 identified proteins may serve as potential biomarkers prior and subsequent to SCIT treatment, and help elucidate the molecular regulation mechanisms of SCIT to treat HDM‑related asthma.

Air pollution, especially that initiated by particulate matter (PM), has been implicated as a risk factor for several inflammatory diseases. Previously, it was reported that PM enhances immune responses. PM includes the tar fraction that contains polycyclic aromatic hydrocarbons (PAHs), which produce adverse health effects in exposed individuals. However, the influence of the tar fraction (as a component of PM) on splenocytes is not fully understood. The aim of this study was to determine the effects of the tar fraction extracted from PM collected from the atmosphere in Fukuoka, Japan, on mouse splenocytes. ICR mice were administered tar (1 or 5 μg/mouse) intratracheally 4 times at 2-week intervals, and splenocytes from the tar-treated mice were extracted and examined. The parameters determined were proliferation, cytokine concentrations and transcription factors activation. Following tar treatment, splenocyte proliferation increased relative to controls. Concanavalin A (ConA)-induced interleukin (IL)-2 formation and ConA- or lipopolysaccharide (LPS)-induced interferon-γ production were elevated in splenocytes from tar-exposed mice. However, the production of tumor necrosis factor-α and IL-6 induced by LPS was not markedly changed following tar treatment. Further, nuclear factor of activated T cells, but not nuclear factor-κB, was enhanced in splenocytes of tar-exposed mice. Data indicate that tar-activated splenocytes and PM-bound PAHs might contribute to T cell activation in the spleen.

Background: Various inflammatory biomarkers have been used in asthma cases for evaluating inflammation, however it has been determined that the majority of these biomarkers are insufficient for putting forth the course and severity of the disease. Osteoprotegerin is a glycoprotein mediator in the lung and macrophages. As far as we know, there are no studies about the role played by osteoprotegerin in child patients with asthma., Objective: It was planned to examine the relationship between osteoprotegerin levels in childhood asthma and respiratory functions and airway inflammation and to assess its use as a biomarker., Methods: The study included patients aged 6-16 years who were diagnosed with asthma at the pediatric allergy outpatient clinic of Bagcilar Training and Research Hospital in Turkey. The correlation analyses for the osteoprotegerin levels of asthma patients and their respiratory functions were examined., Results: The age average of asthma cases was 10.61±3.04 years and 51.2 % were female. No statistically significant difference was observed between the osteoprotegerin levels of the groups (p>0.05). A negative and statistically significant correlation was observed between the FEV1 and FVC values and osteoprotegerin levels (p=0.015, p=0.003)., Conclusions: This was the first study to examine the relationship between osteoprotegerin levels and airway inflammation in children with asthma. We believe that there is a need for wider scale studies in which clinical symptoms and more parameters are evaluated for defining the role played by osteoprotegerin level in children with asthma and for determining its usability as a biomarker., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: House dust endotoxin may have beneficial effects on allergic sensitization and asthma in children. Evidence is scarce for adolescents and most studies so far have been cross-sectional and limited to a single exposure measurement., Objective: We assessed associations of house dust endotoxin with asthma and allergic sensitization from birth to age 17 years longitudinally taking into account exposure early in life and at primary school age., Methods: We used data of 854 participants of the prospective Dutch PIAMA birth cohort study with house dust endotoxin measurements at 3 months and/or 5-6 years and data on asthma and/or allergic sensitization from at least one of 11 follow-ups until age 17. We assessed overall and age-specific associations of the prevalence of asthma and sensitization with mattress and living room floor dust concentrations (per gram of dust) and loads (per m 2 of sampling surface)., Results: Higher living room floor dust endotoxin concentrations at 3 months were associated with lower odds of asthma until age 4 [odds ratio (95% confidence interval) ranging from 0.70 (0.51-0.97) at age 1 to 0.76 (0.57-1.00) at age 3 per interquartile range increase], but not thereafter in children of allergic mothers. Higher living room floor dust endotoxin at 5-6 years was associated with higher odds of sensitization at 8-16 years [eg odds ratio (95% confidence interval) 1.70 (1.17-2.47) per interquartile range increase in endotoxin load]., Conclusions and Clinical Relevance: House dust endotoxin may have beneficial effects on asthma in preschool children of allergic mothers, which do not persist into adolescence. Beneficial associations with allergic sensitization could not be confirmed., (© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Pantoea agglomerans is gram-negative bacteria widely distributed in nature. It predominates in inhalable dust from grain, herbs, and flax, and was identified as the most important cause of hypersensitivity pneumonitis (HP) in eastern Poland. To better understand the molecular mechanism of HP development studies focused on the interactions between P. agglomerans and alveolar epithelial cells as well as lung tissue with particular emphasis on the epithelial-mesenchymal transition (EMT). The studies were conducted on human normal lung epithelial NL20 cells and mice strain C57BL/6J. Cells and mice underwent chronic exposure to saline extract of P. agglomerans (SE-PA). Morphological changes were evaluated under light microscopy, the concentration of fibrosis markers was examined by the ELISA method, while the expression of genes involved in EMT was evaluated by RealTime PCR. During incubation with SE-PA epithelial cells underwent conversion and assumed fibroblast phenotype characterized by a decrease in epithelial cells markers (CDH1, CLDN1, JUP) and increase in mesenchymal cells markers (FN1, VIM, CDH2). Mice lungs collected after 14 days of SE-PA treatment revealed inflammation with marked lymphocytes infiltration. The intensified inflammatory process accompanied by increased proliferation of fibrous connective tissue was noted in mice lungs after 28 days of SE-PA exposure. Histological changes correlated with an increase of fibrosis markers (hydroxyproline, collagens), downregulation of epithelial markers (Cdh1, Cldn1, Jup, Ocln) and upregulation of myofibroblasts markers (Acta2, Cdh2, Fn1, Vim). Obtained results revealed SE-PA ability to induce EMT in human lung epithelial cells and mice lung tissue, with the scale of changes proportional to the time of treatment., Competing Interests: Declaration of competing interests ☒ 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. ☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Baker's allergy and asthma continue to represent an important contributor of occupational asthma globally. This review identified recent studies related to the prevention of baker's allergy and asthma., Recent Findings: Studies with respect to regulatory exposure standards, workplace control measures aimed at reduction of flour dust exposures, surveillance programmes (exposure monitoring, medical surveillance) and workplace information, education and training programmes were identified., Summary: Detailed knowledge on risk factors and detection methods to assess exposure and early identification of high-risk workers exist, but workplace control measures remain sub-optimal because they are rarely multifaceted. This is compounded by the lack of health-based exposure standards globally. Exposure level monitoring and medical surveillance are integral to assessing effectiveness of preventive strategies. Triage systems for optimizing the efficiency of medical surveillance programmes show promise, but need replication in different contexts. Future studies need to focus on evaluating the relevance and quantification of peak exposures in increasing risk; developing standardized respiratory questionnaires for medical surveillance; and further exploration of serial fractional exhaled nitric oxide (FeNO) measurements as an adjunct to allergic sensitization for the early identification of baker's asthma and assessing the long-term impact of interventions.

Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4-25 μg ml-1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.

Because the alveolar macrophage (AM) phenotype of horses with severe equine asthma (SEA) is unknown, the cytokines expressed by M1- and M2-polarized AM were determined and the hypothesis that natural hay/straw challenge (NC) induces divergent AM phenotypes in control horses and horses with SEA was tested. Macrophages from control horses were activated either with eIFNγ + lipolysaccharide (LPS) or eIL-4 to characterize M1- or M2-polarized AM gene expression, respectively and determine the response of polarized cells to pathogen-associated molecular patterns (PAMPS): LPS, zymosan, peptidoglycan and hay dust. Subsequently, gene expression was explored in AM of control horses and horses with SEA at pasture and after NC. M1 polarization increased expression of pro-inflammatory cytokines (TNFα, IL-8, IL-12p40), IL-10, and CD80. M2 polarization increased CD206 and down-regulated arginase-II and IL-10. Expression of pro-inflammatory cytokines and CD80 in response to PAMPS was further increased by M1 pre-polarization whereas M2 pre-polarization down-regulated expression of pro-inflammatory cytokines and IL-10 but increased CD206. In horses with SEA, AMs had elevated expression of IL-10 both at pasture and after NC, but only after NC in control horses. CD206 expression increased in both groups during NC. At pasture, stimulation by PAMPS augmented expression of IL-8 and IL-10 in horses with SEA compared to control horses. NC eliminated this difference by selectively increasing expression of IL-10 in control horses. A fundamental shift in the macrophage phenotype in SEA is supported by consistently elevated production of IL-10. A similar non-canonical phenotype develops temporarily in control horses upon NC suggesting that AMs in horses with SEA have lost the ability to respond dynamically to environmental cues., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The development of food allergies is thought to involve multiple factors, and it is unclear which conveys the most risk regarding this process. Since food allergy is a chronic disease without a cure at this time, understanding its development could provide an avenue for preventive practices and development of a curative treatment. Both historical and current data implicate maternal factors, genetics, and environmental exposures as major risk factors in the development of food allergy. An immature gut of the infant has been hypothesized as a possible route of sensitization. Breastfeeding until at least 6 months of age has been shown to have protective factors for the newborn and may possibly improve gut permeability. Newer studies such as the LEAP and EAT investigations also looked at early exposure and prevention of food allergies; their long-term results are critical in understanding early introduction and tolerance. Cutaneous exposure, oral exposure, and food protein exposure in house dust with their relation to the food allergy course are also a path of interest. Current research has shown sensitization can occur through impaired skin such as those with eczema and a filaggrin mutation. Tropomyosin and alpha-gal also are related to the complicated immunomodulatory factors involved in food allergy and allergic response. Cross-reactivity with plant allergens, sensitization to house dust mite and cockroach, and lone star tick bites can also induce food allergens in children and adults. Together, these factors provide a cohesive beginning to understanding how food allergies can occur and can influence further investigation into prevention, treatment, and eventual cure of food allergies.

Objectives: We estimated the association between occupational exposures to five different organic dusts: wood, animal, paper, textile and flour dust and the risk of developing rheumatoid arthritis (RA)., Methods: This population-based case-control study analysed 12 582 incident cases and 129 335 controls. Participants were identified from national public authority and quality registers. Census data on occupations were collected 1960-2010 and we estimated the exposure to organic dust with the help of job-exposure matrices. We used logistic regression to assess the OR of seropositive or seronegative RA. Estimates were adjusted for the matching variables (sex, county, age and index year), education and occupational silica exposure., Results: Exposure to animal dust was associated with an increased risk of RA among both men and women. The OR was 1.2 (95% CI=1.1 to 1.4) for seropositive RA and 1.3 (95% CI=1.1 to 1.5) for seronegative RA among ever exposed participants compared with unexposed. The risk increased with duration of exposure for seropositive RA, and participants who had been exposed in five or more censuses had an OR of 1.6 (95% CI=1.1 to 2.2, p for trend=0.003). Exposure to textile dust also generated a significant dose-response relationship for seropositive RA (p for trend=0.014). We detected no association between exposure to wood, paper or flour dust and risk of RA., Conclusions: Overall, exposure to animal dust and textile dust was associated with an increased risk of developing RA. These observations give further support to the notion that airborne exposures are involved in the aetiology of RA., Competing Interests: Competing interests: LA have for the EIRA study been supported by research grants from the Swedish Medical Research Council; the Swedish Council for Health, Working Life and Welfare; King Gustaf V:s 80-year foundation; the Swedish Rheumatism Foundation; Stockholm County Council; the insurance company AFA Insurance and the IMI-supported RTCure projects, unrelated to the submitted work. PW has received research grants from AFA Insurance, unrelated to the submitted work. PG has received research grants from the Swedish Research Council for Health, Working Life and Welfare, unrelated to the submitted work. LA received grants from the Swedish Research Council for Health, Working Life and Welfare (grant no: 2013-0194) and AFA Insurance (grant number 120299) to support the present study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Household dust often contains aeroallergens, such as the house dust mite antigen Der p 1. It has been proposed that overnight exposure to particulate matter from bedding and other sources may be an important driver of atopic asthma. Whether variability in overnight particulate matter exposure is a significant determinant of asthma control is unknown., Objective: To test the hypothesis that overnight particulate matter exposure is associated with day-to-day symptoms, lung function, and airway inflammation in patients with asthma who are sensitized to house dust mite., Methods: We undertook a prospective, single-center panel study in 28 adults with asthma and house dust mite sensitization. Overnight exposure to particulate matter was measured using a commercially available indoor air quality monitor. Symptom scores, peak expiratory flow, and exhaled nitric oxide were measured and electronically recorded daily. Participants were followed up for 12 weeks and attended study visits every 4 weeks, at which they underwent spirometry and completed the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire. Data were analyzed using cross-correlation and linear mixed-effects models., Results: No significant associations were observed between overnight particulate matter exposure and clinical outcomes measured daily or at study visits., Conclusion: Natural variability in overnight particulate matter exposure does not appear to be a major determinant of daily asthma control in patients with asthma and house dust mite sensitization., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Exposure to dust in agricultural and animal environments, known as organic dust, is associated with the development of respiratory symptoms and respiratory diseases. Inflammation is a key feature of lung pathologies associated with organic dust exposure, and exposure to organic dust induces the expression of several immune and inflammatory mediators. However, information on transcription factors and cellular and molecular mechanisms controlling the production of immune and inflammatory mediators induced by organic dust is limited. In this study, we have identified STAT-3 as an important transcription factor controlling the induction of expression of immune and inflammatory mediators by poultry dust extracts in airway epithelial cells and in mouse lungs and delineated the cellular pathway for STAT-3 activation. Poultry dust extract activated STAT-3 phosphorylation in Beas2B and normal human bronchial epithelial cells and in mouse lungs. Chemical inhibition and siRNA knockdown of STAT-3 suppressed induction of immune and inflammatory mediator expression. Antioxidants suppressed the increase of STAT-3 phosphorylation induced by poultry dust extract indicating that oxidative stress [elevated reactive oxygen species (ROS) levels] is important for the activation. Chemical inhibition and siRNA knockdown experiments demonstrated that STAT-3 activation is dependent on the activation of nonreceptor tyrosine-protein kinase 2 (TYK2) and epidermal growth factor receptor (EGFR) tyrosine kinases. Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator expression via a cellular pathway involving oxidative stress-mediated STAT-3 activation by TYK2 and EGFR tyrosine kinases.

Introduction: To assess the across-shift changes of cytokine concentrations in nasal lavage (NAL) samples were collected from workers exposed to bacterial cell wall components present in organic dust in three different occupational environments., Material and Methods: The study was conducted in 38 employees including 10 workers from a municipal waste sorting plant (WSP), 20 from a sewage treatment plant (STP) and 8 from an office building (OB), who were established as a reference group, not exposed to organic dust. Interleukins 1β (IL-1β), 6 (IL-6), 8 (IL-8) and tumour necrosis factor alpha (TNF-α) were examined in NAL before and after work shift on Wednesdays. Bioaerosol exposure was determined by personal measurements and analysed for organic dust, endotoxins (END) and peptidoglycans (PGN)., Results: The analysis included the results for IL-8 only, because for the other cytokines their concentrations in 80% of cases were below the detection level. The most polluted were the workplaces in WSP with average concentrations of organic dust - 3.47 mg/m 3 , END - 96.31 ng/m 3 and PGN - 571.88 ng/m 3 . The results of IL-8 showed a significant difference between the studied groups after the work shift (p=0.007). Among WSP workers concentrations of IL-8 increased also significantly (p=0.015) during the work shift. Multivariate analysis showed that organic dust and END were the factors that in the most distinct way (p<0.001) influenced changes of IL-8 levels in NAL., Conclusions: Each alteration in the composition of bioaerosols will probably determine the changes in the mechanisms responsible for both formation and modulation of inflammatory reactions in exposed workers.

Background: Individuals often report allergy to specific aeroallergens, but allergy testing can reveal disparate sensitization., Objective: To characterize the agreement between perceived and actual sensitization to individual aeroallergens in an urban pediatric population., Methods: A total of 253 children were enrolled from pediatric clinics in New York, NY. Detailed questionnaires regarding perceived sensitization and serum specific IgE measurements to 10 common aeroallergens were completed. Agreement between perceived and actual sensitization (sIgE ≥ 0.35 kU A /L) to individual aeroallergens was assessed by Cohen's kappa. Multivariable logistic regression models adjusted for potential confounders were used to test for associations between perceived and actual sensitization., Results: A total of 161 (63.6%) of 253 children reported perceived sensitization to 1 or more aeroallergen, and 203 (80.2%) were actually sensitized to 1 or more aeroallergen. Agreement between perceived and actual aeroallergen sensitization was fair for most aeroallergens, with greatest agreement for cat dander (κ, 0.42; 95% CI, 0.32-0.53) and dust (κ, 0.32; 95% CI, 0.20-0.44). Models adjusted for potential confounders showed nearly 6-fold odds of sensitization to cat dander given perceived cat allergy (adjusted odds ratio, 5.82; 95% CI, 2.91-11.64), and over 2-fold odds of sensitization to Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog dander, or grass pollen given perceived sensitization to their respective allergens. Among children with no perceived sensitization, actual sensitization ranged from 5.4% to 30.4%, and was more common for indoor versus outdoor allergens, including cockroach., Conclusions: Children who perceive allergen sensitization to cat, dog, dust, or grass are likely to demonstrate actual sensitization to these individual allergens. Children with no perceived sensitization to allergens are nonetheless frequently sensitized., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Allergen specific immunoglobulin E (spIgE) in the nasal mucosa is a biomarker for local allergic rhinitis. Inferior turbinate tissue biopsy is a sensitive method to detect nasal spIgE but is invasive. Nasal brushing is a relatively noninvasive method to detect nasal spIgE that may be of comparable diagnostic utility. Objective: To assess the performance of nasal brushing to obtain a nasal spIgE sample compared with an inferior turbinate tissue biopsy among patients who underwent turbinate surgery. Methods: A diagnostic cross-sectional study that involved participants who were undergoing turbinate surgery was performed. Nasal brushing, inferior turbinate tissue biopsy, blood collection, and skin-prick test (SPT) were performed perioperatively and tested for house-dust allergens. A receiver operating curve was used to assess the performance of the nasal brushings to obtain nasal spIgE samples compared with the inferior turbinate tissue biopsy. The diagnostic utility of nasal brushings of spIgE compared with serum spIgE testing and SPT was also assessed. Results: A total of 157 patients (41.61 ± 14.83 years; 37.6% women) were included. Nasal brushing was an excellent method to sample for nasal spIgE compared with inferior turbinate tissue biopsy (Area under curve (AUC) 0.87 [95% confidence interval {CI}, 0.81-0.93], p < 0.01). Positive house-dust allergen spIgE results of nasal brushings was defined as > 0.1 kUA/L. Nasal brushings for spIgE sampling was also able to predict the presence of serum spIgE (AUC 0.93 [95% CI, 0.89-0.97], p < 0.01) and SPT (AUC 0.80 [95% CI, 0.72-0.87], p < 0.01). Conclusion: Nasal brushing constituted an easy and relatively noninvasive method to sample nasal epithelium. This sampling technique was comparable with an inferior turbinate tissue biopsy and may be developed as a diagnostic tool for the diagnosis of local allergic rhinitis.

Background: Vitamin D has been reported to affect both innate, and acquired immunity with immune cells such as dendritic cells having the vitamin D receptors. The co-occurrence of the high prevalence of allergic diseases and vitamin D deficiency globally documented in recent decades, has prompted a hypothesis on whether there is a reasonable association between them., Objective: To investigate the association between serum vitamin D deficiency and allergic symptoms., Methods: Historical cohort. On a cohort study for the association between desert dust exposure and allergic symptoms in 3,327 pregnant women during spring and fall in 2011-2013 in Japan conducted as an adjunct study to the Japan Environment and Children's Study, we promptly acquired subjects' daily allergic symptom scores by sending a web-based questionnaire to each participant on some days. Of the 29,434 answers provided by 3,327 participating pregnant women, we extracted 13,356 answers from 1,475 pregnant women that were answered within a 3-month period after blood samplings. And we measured 25(OH)D levels on those samples to investigate the association between their vitamin D deficiency (serum 25(OH)D < 20ng/mL) and the occurrence of any allergic symptom (allergic symptom score> 0) within 3 months., Results: Serum 25(OH)D was less than 20ng/mL in 1,233 of 1,745 samples (70.7%). The adjusted odds ratio (aOR) for occurrence of any allergic symptom in deficient cases compared with non-deficient cases was 1.33 (95% CI: 1.07-1.64, p = 0.01). Further, vitamin D deficiency significantly enhanced the risk increase at desert dust events and at pollen exposure (p-values for interaction <0.1)., Conclusion: We confirmed the association between serum vitamin D deficiency and allergic symptoms in Japanese pregnant women., Competing Interests: The authors have declared that no competing interests exist.

Background: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease with frequent hypersensitivity to allergens. However, the role of exposure to indoor allergens on AD severity is unclear., Methods: Children aged 0-17 years with active AD from central Chile were recruited; disease severity was evaluated with SCORAD and POEM scores. A home environment survey was applied to parents. Bedroom dust samples were collected for all subjects and analyzed by multiplex assay to quantify dust mite (Der p1, Der f1), dog (Can f1), cat (Fel d1), and alternaria alternata (Alt a1) allergens., Results: Twenty-five children aged 3.9 ± 3.8 years were included. Fifty-two percent were female. Mean SCORAD was 29 ± 14 (range 11-61), and mean POEM was 10.7 ± 6.2. No direct association was found between tobacco exposure, pet ownership, aerosol use, visible dust, or home carpets/rugs with SCORAD (all P > 0.05). Dust samples from all homes had Can f1 and Fel d1 allergens, regardless of pet ownership. Homes that had indoor dogs or cats had significantly higher amounts of these allergens (P < 0.001). Forty percent of homes had dust mite allergens, and none had alternaria alternata. Children with AD living in homes with elevated dust mite and animal dander allergen concentrations had higher SCORAD than those from homes with low allergen concentrations (40 ± 13 vs. 26 ± 13, P = 0.025)., Conclusions: High concentrations of indoor allergens may influence AD severity in children. Further studies assessing indoor allergens and allergen sensitization are warranted to fully evaluate the role of indoor allergens on AD., (© 2018 The International Society of Dermatology.)

During the 2000s, Asian sand dust (ASD) was implicated in the increasing prevalence of respiratory disorders, including asthma. We previously demonstrated that a fungus from ASD aerosol exacerbated ovalbumin (OVA)-induced airways inflammation. Exposure to heat-inactivated ASD (H-ASD) and either Zymosan A (ZymA, containing β-glucan) or lipopolysaccharide (LPS) exacerbated allergic airways inflammation in a mouse model, but the effects of co-exposure of LPS and β-glucan are unclear. We investigated the effects of co-exposure of LPS and ZymA in OVA-induced allergic airways inflammation with ASD using BALB/c mice. Exposure to OVA + LPS enhanced the recruitment of inflammatory cells to the lungs, particularly neutrophils; exposure to OVA + LPS + H-ASD potentiated this effect. Exposure to OVA + ZymA + H-ASD stimulated the recruitment of inflammatory cells to the lungs, particularly eosinophils, and serum levels of OVA-specific IgE and IgG1 antibodies, whereas exposure to OVA + ZymA did not affect most indicators of lung inflammation. Although exposure to OVA + LPS + ZymA + H-ASD affected a few allergic parameters additively or synergistically, most allergic parameters in this group indicated the same level of exposure to OVA + LPS + H-ASD or OVA + ZymA + H-ASD. These results suggest that LPS and ZymA play different roles in allergic airways inflammation with ASD; LPS mainly enhances neutrophil recruitment through H-ASD, and ZymA enhances eosinophil recruitment through H-ASD., (© 2018 John Wiley & Sons, Ltd.)

Objective: Some evidences indicate that exposure to molds or their products can be relevant for the loss of asthma control. Thus, we measured the mold burden present inside houses of subjects with asthma, and evaluated its relationship with asthma control., Methods: Markers of asthma control in adult patients residing in Mexico City were evaluated through questionnaires and spirometry. Dust was collected from the patients' houses and its fungal content was determined by mold specific quantitative PCR (MSQPCR) for 36 fungal species., Results: Forty-two patients with asthma (12 males, 30 females) with a mean age of 45 years (18-76 years) were included in the study. The level of asthma control measured through the Asthma Control Test ranged from 9 to 25 (mean 20.9). The FEV 1 /FVC ratio fluctuated from 38 to 106 %predicted (mean, 87.4 %predicted). Associations between mold burden and asthma control differed between males and females. Thus, concentrations of some molds, particularly Aspergillus fumigatus, Aureobasidium pullulans, Stachybotrys chartarum, Alternaria alternata, Cladosporium cladosporioides 2, Cladosporium herbarum, and Epicoccum nigrum, were negatively associated with parameters of asthma control in male subjects, but not in female patients., Conclusion: Our results showed that potential indoor exposure to some molds is associated with less asthma control in male subjects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Agriculture exposures are associated with reducing the risk of allergy and asthma in early life; yet, repeated exposures later in life are associated with chronic bronchitis and obstructive pulmonary diseases. The objective of this study was to investigate the airway inflammatory response to organic dust extract (ODE) in mice with established ovalbumin (OVA)-induced experimental asthma. C57BL/6 mice were either OVA sensitized/aerosol-exposed or saline (Sal) sensitized/aerosol-challenged. Both groups were then subsequently challenged once with intranasal saline or swine confinement ODE to obtain 4 treatment groups of Sal-Sal, Sal-ODE, OVA-Sal, and OVA-ODE. Airway hyper-responsiveness (AHR) to methacholine, bronchiolar lavage fluid, lung tissues, and serum were collected. Intranasal inhalation of ODE in OVA-treated (asthmatic) mice (OVA-ODE) increased AHR and total cellular influx marked by elevated neutrophil and eosinophil counts. Flow cytometry analysis further demonstrated that populations of CD11c hi dendritic cells (DC), CD3 + T cells, CD19 + B cells, and NKp46 + group 3 innate lymphoid cells (ILC3) were increased in lavage fluid of OVA-ODE mice as compared to ODE or OVA alone. Alveolar macrophages, DC, and T cells were significantly increased with co-exposure to OVA-ODE as compared to OVA alone. Lung ILC2 and ILC3 were only increased in OVA-Sal mice. Cytokine/chemokine levels varied with exposure to OVA-ODE reflecting an additive mixture of the pro- and allergic-inflammatory profiles. Collectively, ODE increased airway inflammatory cells and chemotactic mediator release in allergic (OVA) sensitized mice to suggest that persons with allergy/asthma be identified and warned prior to the occupational exposure of potentially worsening airway disease.

Helminth infections and allergies are characterized by a predominant type-2 immune response. In schistosomiasis, the Th-2 response is usually accompanied by induction of immunoregulatory mechanisms that contribute to worm survival and less severe schistosomiasis. Although helminth-induced immunomodulatory mechanisms seem to affect atopy, epidemiological studies on the relationship between helminths and allergy have been inconsistent, and data suggest that the modulatory effects may be influenced by helminth species, chronicity of infection, and parasite burden. Here we performed a cross-sectional study to investigate the effects of Schistosoma mansoni parasite burden and immune response on allergic reactivity of individuals living in a schistosomiasis endemic area in Brazil. Fecal samples from the participants were collected for extensive parasitological examinations by spontaneous sedimentation, Kato-Katz, Helmintex and Saline Gradient tests and molecular detection of S. mansoni by qPCR. Additionally, the concentrations of cytokines and chemokines, total IgE and IgE-reactivity to common house dust allergens were quantified from serum samples. IgE reactivity to dust allergens was detected in 47 individuals (23.8%), and 140 individuals (54.4%) were diagnosed with S. mansoni infection. Most of the infected population (108 individuals) presented very low parasite burden (≤12 eggs/g of feces). The frequency and intensity ( p ≤ 0.03) of allergic reactivity were lower in S. mansoni- infected compared with non-infected individuals. Multivariable logistic regression models adjusted by age revealed that allergic reactivity was positively associated with low IL-10 response (OR, 4.55, 95% CI, 0.56-7.36) and high concentration of the inflammatory mediators IL-33 (OR, 2.70, 95% CI, 1.02-7.15) or TNF-α (OR, 6.88, 95% CI, 0.32-143.39) in serum, and inversely associated with S. mansoni infection (OR, 0.38, 95% CI, 0.16-0.87). Most importantly, the logistic regression demonstrated that the modulatory effects of Schistosoma infection depend on parasite burden, with individuals infected with ≤12 eggs/g of feces showing allergic IgE-reactivity similar to non-infected individuals Altogether, our data show that immunomodulation of allergic reactivity depends on S. mansoni burden, low type-2 inflammatory response, and high level of IL-10.

Background: Pets are major contributors of endotoxin in homes, but whether they influence endotoxin association with respiratory outcomes is unclear., Objective: To examine whether exposure and sensitization to dog and cat modify the relationship between endotoxin exposure and asthma and wheeze., Methods: We analyzed data from 6051 participants in the 2005-2006 cycle of the National Health and Nutrition Examination Survey (NHANES). House dust from bedroom floor and bedding was evaluated for endotoxin and for dog (Canis familiaris 1) and cat (Feline domesticus 1) allergens. The NHANES also collected data on respiratory outcomes and measured IgE specific to allergens. Associations of log-endotoxin and pet exposure with respiratory outcomes were examined, adjusting for covariates including pet avoidance., Results: Dog and cat ownership among participants was 48.3% and 37.5%, respectively. Endotoxin geometric mean (SE) was 15.49 (0.50) EU/mg. Endotoxin and pet allergen levels were significantly higher in households with a dog or cat. Overall, endotoxin was positively associated with wheeze (odds ratio [OR], 1.30; 95% CI, 1.04-1.62), but not with asthma. However, in participants nonsensitized to dog, the odds of endotoxin association with wheeze were higher with exposure to dog allergen (OR, 1.80; 95% CI, 1.27-2.53; P interaction  = .048). In participants sensitized to cat and exposed to cat allergen, endotoxin became positively associated with asthma (OR, 1.92; 95% CI, 1.21-3.0; P interaction  = .040). With coexposure to dog and cat allergens, endotoxin association with asthma and wheeze was exacerbated (OR, 2.00; 95% CI, 1.04-3.83; P interaction  = .012 and OR, 1.88; 95% CI, 1.32-2.66; P interaction  = .016, respectively)., Conclusions: Exposure to dog and cat allergens enhances the association of endotoxin with asthma and wheeze., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Allergies are usually referred to as type I hypersensitivity reactions against innocuous environmental antigens, characterized by a Th2/IgE-dominated inflammation. They can manifest themselves in various organs, such as skin, gastrointestinal and respiratory tract, and comprise diseases as diverse as allergic rhinitis and conjunctivitis, bronchial asthma, oral allergy syndrome, food allergy, urticaria and atopic eczema, but also anaphylactic shock. Within the last decades, there was a significant global increase in allergy prevalence, which has been mostly attributed to changes in environment and lifestyle. But which, among all factors discussed, are the most relevant, and what are the mechanisms by which these factors promote or prevent the development of allergic diseases? To answer this, it is necessary to go back to the two key questions that have occupied allergy researchers for the last decades: Firstly, what makes an allergen an allergen? Secondly, why are more and more individuals affected? Within the last decade, we have made considerable progress in answering these questions. This review gives an overview over scientific progress in the field, summarizes latest findings and points out future prospective and research needs., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In current practice, allergens in vacuum-collected dust are used as surrogates for inhalable allergens. We developed an air-sampling device that can be used by patients for direct measurement of airborne allergen concentrations in their own homes., Objective: To demonstrate the use of this device to establish allergen concentration reference ranges in a target population and to evaluate associations between patient-reported information and measured allergen concentrations., Methods: Patients from 5 allergist's practices in the Chicagoland region were provided with instructions, questionnaires, informed consent forms, and samplers to run for 5 days in their bedrooms. Samples were collected from cartridges and assayed by multiplex immunoassays for 12 common household allergens and enzyme-linked immunosorbent assay for ragweed., Results: Unique allergen profiles were obtained for 102 patient homes. Samples with allergen concentrations above the limit of detection were as follows: total dust mite, 28%; cat, 61%; dog, 64%; mouse, 12%; rat, 0%; cockroach, 4%; Alternaria, 6%; Aspergillus, 21%; birch pollen 1%; grass, 8%; and ragweed, 5%. Of those, 75 completed questionnaires, providing meta-data for further analysis. Pet allergens correlated significantly with number of pets owned. Humidity correlated with dust mite allergens, open windows with Alternaria and mouse allergens, and high-efficiency particulate air filter use with reduced levels of several allergens. Many other variables showed no significant correlations., Conclusion: The combination of ease of use, high air-sampling rate, and sensitive immunoassays permitted the measurement of airborne allergen concentrations in homes and establishment of reference ranges. Patient-reported information permitted identification of factors that could relate to allergen concentrations and suggested remedial measures., (Copyright © 2018 American College of Allergy, Asthma 8 Immunology. Published by Elsevier Inc. All rights reserved.)

Exacerbated inflammation upon persistent barn organic dust exposure is a key contributor to the pathogenesis of lung inflammation and lung function decline. Barn dust constituents and the mechanisms contributing to the exacerbated inflammation are not clearly known. We set out to understand the inflammatory effects of Swine Barn Dust Extracts (SBDE) on human lung epithelial (BEAS2B) and macrophage (THP-1 monocyte derived) cell lines on a kinome array to determine phosphorylation events in the inflammatory signaling pathways. Upon identifying events unique to SBDE or those induced by innate immune ligands in each cell line, we validated the signaling pathway activation by transcriptional analyses of downstream inflammatory cytokines. Our findings indicate that SBDE-mediated pro-inflammatory effects are predominantly due to the induction of neutrophilic chemokine IL-8. Differentially phosphorylated peptides implicated in IL-8 induction in BEAS2B cell line include, TLR2, 4, 5, 7, 8, 9, PKC, MAP kinases (p38, JNK), inflammasomes (NLRP1, NLRP3), NF-κB and AP-1. In the THP-1 cell line, in addition to the aforementioned peptides, peptides corresponding to RIG-I-like receptors (RIG-I, MDA5) were found. This is the first report to demonstrate the application of a kinome array to delineate key inflammatory signaling pathways activated upon SBDE exposure in vitro.

Background: Early-life sensitization to indoor allergens predicts asthma development. The aim of this study was to compare allergen concentrations in day-care centers (DCC) with those in private homes., Methods: Settled airborne dust was collected 4 times a year from 20 German DCC (620 samples) and from the homes of children and day-care workers (602 samples) using electrostatic dust collectors (EDC). The samples were analyzed with fluorescence enzyme immunoassays recognizing domestic mite allergens (DM), Fel d 1, Can f 1, and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs from those without were calculated using receiver-operating characteristics. Influences on allergen levels were analyzed using multilevel models., Results: Allergen loads were on average higher in DCC than in homes. In DCC, 96% of the samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and the threshold level for homes with cats was 46 ng/m² Fel d 1 (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence., Conclusions: Mite, mouse, cat, and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objectives: To quantify exposure to vapour, gas, dust and fumes (VGDF) and smoking in male rheumatoid arthritis (RA) and investigate impact on rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels., Design: A retrospective observational study., Setting: The Royal Cornwall Hospital Trust, UK. A single university hospital setting., Participants: 726 men followed up between February 2015 and August 2016, fulfilling RA diagnostic criteria., Main Outcome Measures: Prevalence of VGDF exposure and smoking prior to RA diagnosis. Determination of association between VGDF, smoking and autoantibody levels., Results: 546/726 (75%) had been exposed to VGDF for >1 year. 561/726 (77%) had been smokers. Only 58/726 (8%) had no exposure to VGDF and had never smoked. A significant difference in RF levels was observed between unexposed and VGDF exposed never smokers (median RF 24 vs 36, p=0.03), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 24 vs 57, p=0.02). A significant difference in RF levels was also observed between unexposed and VGDF exposed smokers (median RF 71 vs RF 95, p=0.04), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 71 vs RF 113, p=0.01). A significant difference in RF titre was observed between never smokers >2 VGDF exposures and smokers with >2 VGDF exposures (RF 57 vs RF 113, p=0.02). No association of ACPA seropositivity rates or titres with VGDF exposure was observed. Smokers with >2 VGDF exposures had a significantly lower age of RA diagnosis than smokers with no VGDF exposure (53 years vs 57 years, p=0.03). All results remained similar when corrected for social class., Conclusions: VGDF exposure increases RF levels. Combination exposure to smoking and VDGF results in higher RF levels, particularly with multiple exposures. These compelling findings demonstrate the importance of combined inhaled exposures in RF generation., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The highly consistent association of growing up on a farm with a reduced asthma risk has so far been attributed to direct farm exposure. In contrast, geographic determinants of the larger environment have never been assessed. In this study, the effects of proximity to farms and environmental variables in relation to the residential address on asthma and atopy were assessed., Methods: Addresses of 2265 children of the Bavarian arm of the GABRIELA study were converted into geocodes. Proximity to the nearest cow farm was calculated, and environmental characteristics were derived from satellite data or terrestrial monitoring. Bacterial diversity in mattress dust samples was assessed in 501 children by sequencing of the 16S rRNA amplicons. Logistic regression models were used to calculate associations between outcomes and exposure variables., Results: Asthma and atopy were inversely associated with the presence of a farm within a radius of maximum 100 m. The environmental variables greenness, tree cover, soil sealing, altitude, air pollution differed not only between farm and non-farm children but also between farm children with and without another farm nearby. The latter distinction revealed strong associations with characteristics of traditional farms including a broader diversity of microbial exposure, which mainly contributed to the protective effect on asthma. In non-farm children, the protective effect of a farm nearby was completely explained by consumption of farm milk., Conclusions: Clustering of farms within a neighborhood of 100 m is strongly associated with the protective effect on asthma and may represent a more traditional style of farming with broader microbial exposure., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)