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Objective: An Asian dust storm (ADS) contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil) in asthma model mice., Methods: Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df), and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured, and airway inflammation was examined histopathologically., Results: Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL)-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles., Conclusion: These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

Background: We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic endotoxin exposure in relation to asthma presence, and amongst children with asthma, we explored the association of these genetic variants and endotoxin exposure with hospital admissions due to asthma exacerbations., Methods: In a case-control study, we analysed data from 824 children (417 asthmatics, 407 controls; age 5-18 yr). Amongst asthmatics, we extracted data on hospitalization for asthma exacerbation from medical records. Endotoxin exposure was measured in dust samples collected from homes. We included 26 single-nucleotide polymorphisms (SNPs) in the final analysis (5 CD14, 7LY96 and 14 TLR4)., Results: Two variants remained significantly associated with hospital admissions with asthma exacerbations after correction for multiple testing: for CD14 SNP rs5744455, carriers of T allele had decreased risk of repeated hospital admissions compared with homozygotes for C allele [OR (95% CI), 0.42 (0.25-0.88), p = 0.01, False Discovery Rate (FDR) p = 0.02]; for LY96 SNP rs17226566, C-allele carriers were at a lower risk of hospital admissions compared with T-allele homozygotes [0.59 (0.38-0.90), p = 0.01, FDR p = 0.04]. We observed two interactions between SNPs in CD14 and LY96 with environmental endotoxin exposure in relation to hospital admissions due to asthma exacerbation which remained significant after correction for multiple testing (CD14 SNPs rs2915863 and LY96 SNP rs17226566)., Conclusion: Amongst children with asthma, genetic variants in CD14 and LY96 may increase the risk of hospital admissions with acute exacerbations. Polymorphisms in endotoxin pathway interact with domestic endotoxin exposure in further modification of the risk of hospitalization., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity., Methods: The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure., Results: Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS., Conclusion: Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.

Asian dust is a seasonal meteorological phenomenon caused by the displacement of atmospheric pollutants from the Mongolian and Chinese deserts. Although the frequency of Asian dust events and atmospheric dust levels have steadily increased in the eastern Asia region, the effects on human health remain poorly understood. In the present study, the impact of Asian dust on human health was determined in terms of allergic reactions. A total of 25 healthy volunteers were tested for a relationship between serum immunoglobulin E (IgE) levels and subjective symptoms during a 3-day Asian dust event recorded in April 2012. They filled daily questionnaires on the severity of nasal, pharyngeal, ocular, respiratory, and skin symptoms by a self-administered visual analog scale. Serum levels of non-specific IgE and 33 allergen-specific IgE molecules were analyzed. Spearman rank-correlation analysis revealed significant positive associations between nasal symptom scores and 2 microbial-specific IgE levels (Penicillium and Cladosporium). Microbes migrate vast distances during Asian dust events by attaching themselves to dust particles. Therefore, some of these symptoms may be associated with type 1 allergic reactions to certain type of microbes.

Objective: Asian dust storms frequently occur in northeast Asia and the dust occasionally even spreads as far as North America during spring. Asian dust can be harmful to human health and the environment, and thus has become one of the most serious problems for Asian countries. In the present study, we evaluated sensitization to Asian dust in Japanese patients with rhinoconjunctivitis., Methods: In March 2011, a prospective, non-randomized, cross-sectional study was conducted in 10 patients with allergic rhinoconjunctivitis (allergic group), 3 patients with atopic keratoconjunctivitis (atopic group), and 10 age- and sex-matched healthy control subjects (control group). Skin prick tests (SPT) were performed with untreated Asian dust, Asian dust extract, heat-sterilized Asian dust, silicon dioxide (SiO2), and phosphate-buffered saline (PBS). A panel of 14 allergen extracts was also tested, comprising extracts of pollens (cedar, orchard grass, ragweed, and mugwort), house dust (house dust mixture and Dermatophagoides pteronyssinus), animal dander (cat and dog), fungi (Alternaria tenuis, Candida, and Aspergillus), and foods (milk, egg, and wheat). Then the SPT-positive rate and the mean wheal diameter for each allergen were compared among the three groups., Results: The SPT-positive rates for untreated Asian dust, Asian dust extract, and sterilized Asian dust were significantly higher in the allergic and atopic groups than in the control group (all p<0.05). In the allergic group, there were a significant differences of the SPT-positive rates for untreated Asian dust (70%), Asian dust extract (50%), sterilized Asian dust (20%), SiO2 (20%), and PBS (0%) (p=0.0068). The SPT response to untreated Asian dust was correlated with the mean wheal diameters for four plant pollens (r=0.71, p=0.0104) and for three fungi (r=0.57, p=0.0426). Multivariate logistic regression analysis showed that significant predictors of the SPT reaction to untreated Asian dust were the mean wheal diameter for the four plant pollen (odds ratio=2.54, p=0.0138) and that for the three fungi (odds ratio=1.84, p=0.0273)., Conclusions: Asian dust may act as an adjuvant to promote allergic disease induced by inhaled allergens such as pollen and fungi., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Rationale: A low prevalence of asthma and atopy has been shown in farmers and agricultural workers. However, in these workers, a higher prevalence of respiratory symptoms has been reported, in which T helper 1 (Th1) and/or Th17 responses may play a role., Aim: We investigated the effect of exposure to dust extracts (DEs) from different farms on airway inflammation and T-cell polarisation in a mouse model and assessed T-cell polarisation in agricultural workers from the same farms., Methods: DEs were prepared from settled dust collected at cattle and pig farms and bulb and onion industries. Mice were exposed to phosphate-buffered saline (PBS), DEs, house dust mite (HDM) or HDM+DE via nasal instillation, four times per week during 5 weeks. Hyperresponsiveness, airway inflammation, IgE levels and T-cell polarisation were assessed. Th-cell and T cytotoxic (Tc)-cell subsets were investigated in peripheral blood samples from 33 agricultural workers and 9 non-exposed controls., Results: DEs induced interleukin(IL)-17, IL-1β and IL-6 in mouse lung homogenates. DE-exposed mice had more mixed inflammatory infiltrates in the lungs, and more neutrophils compared with PBS-exposed mice. DEs protected against the HDM-induced Th2 response and methacholine hyperresponsiveness. Interestingly, occupationally exposed humans had higher frequencies of Th cells spontaneously expressing IL-17 and interferon γ compared with controls., Conclusion: Chronic exposure to different types of farm dust induces a Th/Tc-17 inflammatory response in mice and agricultural workers. This may contribute to the low prevalence of Th2-related diseases but may constitute a risk for other chronic respiratory diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Glucan is a component of the fungal cell wall that is used as a marker of fungal exposure. Little is known about indoor glucan, atopy, and asthma exacerbations among children living in tropical environments such as Puerto Rico. Our objective was to examine whether glucan exposure is associated with degree of atopy or visits to the emergency department (ED)/urgent care for asthma in Puerto Rican children., Methods: This was a cross-sectional study of 317 children aged 6 to 14 years with (cases, n = 160) and without (control subjects, n = 157) asthma in San Juan, Puerto Rico. Our primary outcomes were the number of positive skin tests to allergens (range, 0-15) and (in cases only) having had at least one visit to the ED/urgent care for asthma in the prior year. Levels of glucan, endotoxin, peptidoglycan, and five allergens (Der p 1, Bla g 2, Fel d 1, Can f 1, and Mus m 1) were measured in samples of house dust. Linear or logistic regression was used for the multivariate analysis., Measurements and Main Results: In a multivariate analysis adjusting for case-control status, mouse allergen, and other covariates, children exposed to glucan levels in the second and third quartiles had approximately two more positive skin tests than those in the lowest quartile (P < 0.01 in both instances). Among children with asthma, exposure to the highest quartile of glucan was associated with nearly ninefold greater odds of one or more visits to the ED/urgent care for asthma (95% confidence interval for adjusted odds ratio, 2.7-28.4; P < 0.001)., Conclusions: Our results suggest that indoor fungal exposure leads to an increased degree of atopy and visits to the ED/urgent care for asthma in Puerto Rican children.

Unlabelled: Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture-based microbial analysis. In the low-income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years.The current analysis included 13 asthma cases and 28 controls. Next-generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio(OR) 4.80 (95% confidence interval (CI) 1.04–22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk (OR 21.0, 95% CI 2.16–204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next-generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community., Practical Implications: Early life exposure to low fungal diversity in house dust was associated with increased risk for later asthma developmen tin this low-income, immigrant community. No individual fungal taxon (species, genus, or class) was associated with asthma development, although exposure to low diversity within the genus Cryptococcus was associated with asthma development. Future asthma development studies should incorporate fungal diversity measurements, in addition to measuring individual fungal taxa. These results represent a step toward identifying the aspect(s) of indoor microbial populations that are associated with asthma development and suggest that understanding the factors that control diversity in the indoor environment may lead to public health recommendations for asthma prevention in the future.

Good's syndrome and common variable immune deficiency (CVID) are associated with chronic rhinosinusitis. Good's syndrome is characterized by hypogammaglobulinemia, B-cell depletion, variable defects in cellular immunity and thymoma. Immunodeficiency and recurrent infections can initially present after thymectomy. The pathogenesis can involve cytokines from bone marrow along with genetic defects. Intravenous gamma globulin (IVIG) restores defective signaling and can reestablish immune homeostasis. IVIG at regular intervals is the most effective way to improve the clinical symptoms and reduce patient mortality. Increased awareness of the clinical and immunological profile of this syndrome may increase its early recognition. CVID patients have hypogammaglobulinemia, respond to IVIG and have a dysregulated antimicrobial peptide response to pathogenic bacteria in the upper respiratory tract. This article reviewed selected literature on Good's syndrome, described an unusual case of Good's syndrome, CVID including SAD related to chronic rhinosinusitis.

Previous studies, often using data from questionnaires, have reported associations between various characteristics of indoor environments and allergic disease. The aim of this study has been to investigate possible associations between objectively assessed indoor environmental factors and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis. The study is a cross-sectional case-control study of 500 children aged 3-5 years from Odense, Denmark. The 200 cases had at least two parentally reported allergic diseases, while the 300 controls were randomly selected from 2835 participating families. A single physician conducted clinical examinations of all 500 children. Children from the initially random control group with clinically confirmed allergic disease were subsequently excluded from the control group and admitted in the case group, leaving 242 in the healthy control group. For most children, specific IgE's against various allergens were determined. In parallel, dust samples were collected and air change rates were measured in the children's bedrooms. The dust samples were analyzed for phthalate esters, polycyclic aromatic hydrocarbons (PAH), nicotine, and various allergens. Among children diagnosed with asthma, concentrations of nicotine were higher (P < 0.05) and cat allergens were lower (P < 0.05) compared with the healthy controls; air change rates were lower for those sensitized (specific IgE+) compared with those not sensitized (specific IgE-, P < 0.05); and dust mite allergens were higher for specific IgE+ cases compared with healthy controls (P < 0.05). When disease status was based solely on questionnaire responses (as opposed to physician diagnosis), significant associations were found between di(2-ethylhexyl) phthalate (DEHP) and dog allergens in dust and current wheeze., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP., Objectives: To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill., Methods: Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant., Results: At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved - paralleling the gradually reduced air levels of mold spores., Conclusions: In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored.

Background: Home characteristics and aeroallergen exposure in rural US children with asthma are poorly described., Objective: To examine the relationship between cockroach and mouse allergen concentrations and home characteristics of children with asthma in the rural Arkansas Delta., Methods: The home environments of rural children with asthma were examined using home environment questionnaire and home inspection. Bedroom and kitchen dust was analyzed for cockroach and mouse allergen concentrations., Results: The median age of participants was 9 years, and 84% were African American. Most participants (78%) resided in single-family homes. Evidence of cockroaches was detected in 13% of homes and evidence of rodents was detected in 23% of homes. Detectable Bla g 1 was found in 58% of kitchens and 43% of bedrooms, Bla g 2 was detected in 37% of kitchens and 28% of bedrooms, and Mus m 1 was found in 81% of kitchens and 97% of bedrooms. Evidence of cockroaches in any room was associated with Bla g 1 concentrations of ≥2 U/g (odds ratio 21.71, 95% confidence interval 4.26-118.39) and Bla g 2 concentrations of ≥2 U/g (odds ratio 21.90 95% confidence interval 4.30-138.91). Multifamily vs single-family dwellings were more likely to have Bla g 2 concentrations of ≥2 U/g (odds ratio 3.52, 95% confidence interval 1.0-11.82). Home characteristics were not associated with Mus m 1., Conclusion: Mouse and cockroach allergens were detected in most rural homes; however, concentrations were relatively low compared with those previously reported in inner-city homes. Few home characteristics predicted allergen concentrations. Further studies are needed to establish clinically relevant associations that might place rural children with asthma at risk for poor clinical outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT00590304., (Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with biphasic T cell-mediated abnormalities. Staphylococcal superantigens contribute to the exacerbation of inflammation in AD. The underlying immunopathological mechanisms are not fully understood., Objective: To determine whether epicutaneous application of recombinant staphylococcal enterotoxin A (rSEA) would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine model., Materials and Methods: We first established an AD-like model using BALB/c mice exposed to DNCB/DFE on the ear. Next, Staphylococcus (S.) aureus or rSEA were topically applied to the mice. We evaluated the clinical and histopathological features of the animals. Serum immunoglobulin levels were also measured. In addition, real-time PCR analysis of cytokines produced by T cell subsets in the ears was conducted., Results: Mice treated with S. aureus and rSEA had more severe clinical symptoms, including increased mean dermatitis scores and ear thickness, compared to animals with only AD-like lesions. Total IgE, IgG2a and serum histamine levels were increased in all groups except the normal control group. The S. aureus- and rSEA-treated groups showed increased levels of cytokines such as IL-4, IL-13, INF-γ, IL-17, and IL-18. In particular, increased cytokine expression was more conspicuous in the rSEA-treated group than in mice exposed to S. aureus., Conclusion: The results of this study showed that topical exposure to rSEA as well as SEA-producing S. aureus aggravate atopic skin inflammation. This may be associated with the induction of a mixed Th1/Th2 type dermatitis.

Objectives: Determine whether surface dust grab samples taken from a large military base in Iraq are toxic and respirable., Methods: X-ray diffraction for mineral content, x-ray fluorescence for elemental content, in vivo mouse dust challenges for assessment of histological changes, bronchoalveolar lavage for cytokines, polarizing light microscopy for crystals in lung tissue, and Fluorescence Activated Cell Sorting for cell surface and intracellular markers were utilized., Results: Camp Victory, Iraq dust taken during wartime contains respirable particles 2.5 microns in size, constituting particulate matter air pollution. Dust particles are angular and have sharp edges. Trace metals (including titanium) calcium and silicon are present. Mice with airway instillation of dust have polarizable crystals in lung and septate inflammation. Regulatory T cells (CD4⁺CD25⁺FOXP3⁺) are decreased in thymus and spleen. Interleukin-2 (IL-2) is upregulated in bronchoalveolar lavage., Conclusions: Respirable Iraq dust leads to lung inflammation in mice similar to that seen in patients with polarizable crystals, which seem to be titanium.

Respiratory diseases are responsible for a significant amount of animal morbidity and mortality in the swine industry, including the majority of nursery and grower/finisher deaths. Innate immunity, including the maintenance of lung macrophage health and function, is an important defense mechanism against respiratory pathogens and their associated losses. Chronic exposure of swine industry workers to airborne barn dust results in significant predisposition to airway diseases and impairment of alveolar macrophage (AMφ) function. Because of their importance in maintaining normal respiratory function, this study was designed to evaluate the impact of barn dust on swine macrophages. As measures of macrophage function, we evaluated the activation of NF-κB, cytokine production, cell surface marker expression and the phagocytic and antibacterial capabilities of porcine macrophages after in vitro exposure to an organic swine barn dust extract (ODE). ODE treatment induced AMφ secretion of both pro- and anti-inflammatory cytokines, suggesting a complex activation profile. Additionally, ODE induced expression of genes (TLR2, NOD2) involved in sensing Gram-positive bacteria, a major component of barn dust. ODE exposure also enhanced the expression of several cell surface markers of activation, including a receptor for the porcine reproductive and respiratory syndrome virus. Moreover, two key functions of AMϕ, phagocytosis and bacterial killing, were impaired after exposure to ODE. Treatment with ODE for the first 72 h of differentiation also inhibited the ability of monocyte-derived macrophages to translocate NF-κB to the nucleus following endotoxin stimulation. Taken together, these results demonstrate, for the first time, that organic dust extract exposure negatively affects pig macrophage activation and function, potentially enhancing host susceptibility to a variety of respiratory infections., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.

Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor- α (TNF- α ) compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ≤10  μ m in diameter provoked a greater inflammatory response than soil dust samples containing particles >10  μ m. In addition, Asian dust particles-induced TNF- α production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor- κ B and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages.

Background: Sensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment., Objective: The objective of this study was firstly to describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13-year-old adolescents and secondly to identify home characteristics associated with the presence of food allergen contamination in dust., Methods: Food allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analysed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models., Results: Fish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (< 100 m(2)) than larger dwellings (≥ 130 m(2)); 63-71% of the small dwellings (n = 24) had milk, peanut, and fish allergens in the samples compared with 33-44% of the larger dwellings (n = 95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors, with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens., Conclusions and Clinical Relevance: Food allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spent in the bedroom, mattress dust may be an important source of exposure to food allergens., (© 2013 John Wiley & Sons Ltd.)

Historically, horse dandruff was a favorite allergen source material. Today, however, allergic symptoms due to airborne mammalian allergens are mostly a result of indoor exposure, be it at home, at work or even at school. The relevance of mammalian allergens in relation to the allergenic activity of house dust extract is briefly discussed in the historical context of two other proposed sources of house dust allergenic activity: mites and Maillard-type lysine-sugar conjugates. Mammalian proteins involved in allergic reactions to airborne dust are largely found in only 2 protein families: lipocalins and secretoglobins (Fel d 1-like proteins), with a relatively minor contribution of serum albumins, cystatins and latherins. Both the lipocalin and the secretoglobin family are very complex. In some instances this results in a blurred separation between important and less important allergenic family members. The past 50 years have provided us with much detailed information on the genomic organization and protein structure of many of these allergens. However, the complex family relations, combined with the wide range of post-translational enzymatic and non-enzymatic modifications, make a proper qualitative and quantitative description of the important mammalian indoor airborne allergens still a significant proteomic challenge., (© 2014 S. Karger AG, Basel.)

It has been hypothesized that high environmental exposure to peanut allergens may be a potent risk factor for cutaneous sensitization. Therefore, we wanted to investigate whether peanut proteins are detectable in house dust of different household areas. Peanut levels of dust samples were measured with ELISA. Overall, peanut was detectable in 19 of 21 households in the eating area and/or in bed. The frequency of peanut consumption correlated with peanut levels. Forty-eight hours after intentional peanut consumption, peanut levels were highly increased. Nevertheless, further research is required to prove whether peanut allergen in house dust can cause sensitization via skin., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: While fungal exposures are assumed to provoke wheeze through irritant or allergenic mechanisms, little is known about the differential effects of indoor and outdoor fungi on early-life wheeze., Methods: In a Boston prospective birth cohort of 499 at-risk infants, culturable fungi in bedroom air and dust and outdoor air were measured at the age of 2-3 months. Wheeze was determined using bimonthly telephone questionnaires. Odds ratios were estimated for an interquartile increase in fungal natural log-transformed concentrations, adjusting for predictors of wheeze and potential confounders., Results: Increased odds of 'any wheeze' (≥1 vs 0 episodes) by age one were positively associated with indoor dust Alternaria [odds ratio (OR) = 1.83; 95% confidence interval (CI), 1.07-3.14], Penicillium [OR = 1.18; (0.98-1.43)], and Cladosporium [OR = 1.47; (1.16-1.85)]; indoor air Penicillium [OR = 1.26; (0.92-1.74)]; and outdoor air Cladosporium [OR = 1.68; (1.04-2.72)]. In contrast, indoor dust yeasts were protective [OR = 0.78; (0.66-0.93)]. 'Frequent wheeze' (≥2 vs <2 episodes) by age one was borderline associated with dust yeasts [OR = 0.86; (0.70-1.04)] and indoor air yeasts [OR = 1.53; (0.93-2.53)]. Alternaria concentration was associated with any wheeze for children with maternal mold sensitization [OR = 9.16; (1.37-61.22)], but not for those without maternal mold sensitization [OR = 1.32; (0.79-2.20)]., Conclusions: While wheeze rates were higher with exposures to fungal taxa considered to be irritant or allergenic in sensitive subjects, yeasts in the home had a strong protective association with wheeze in infancy. Molecular microbiologic studies may elucidate specific components of innate microbiologic stimulants that lead to contrasting effects on wheeze development., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Exposure to house dust mites (HDMs) is a major risk factor for the development of allergic symptoms. HDMs are worldwide in distribution. Assessing these allergens in each area is a critical step in evaluating the risk of sensitisation and controlling allergic symptoms. The aim of the present study was to evaluate the level of major HDMs, Der p 1 and Der f 1, in various parts of Iran., Methods: In 2009, 257 dust samples were obtained from living rooms' carpets in seven cities throughout Iran with different geoclimatic conditions. The level of Der p 1 and Der f 1 was measured by commercial ELISA., Results: Detectable level of Der p 1 and Der f 1 levels were only found in Gorgan and Sari, two cities near the Caspian Sea with moderate temperatures and high relative humidity. In both of these cities, Der f 1 was more frequent than Der p 1 (100% vs. 85%) and was found to be at a higher level than Der p 1 (geometric mean 3128 vs. 439ng/g dust, P<0.001)., Conclusion: The results of this study confirm that house dust mites in Iran are restricted to the Caspian Sea coastal areas, and in other parts, due to seasonal variations of temperature and humidity mites are not able to grow well and therefore are not an important risk factor for sensitisation and respiratory allergies., (Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: Forty million children are regularly exposed to environmental tobacco smoke (ETS) each year, increasing their risk for premature death and middle ear and acute respiratory infections. Early life exposure to ETS also is clearly associated with wheezing. However, there is no clear understanding of the influence of ETS on the development of allergic sensitization., Objective: To determine the association of combined exposure to ETS and indoor allergens on IgE sensitization to aeroallergens in children., Methods: This case-control study enrolled 116 cases and 121 controls from low-income families from Kansas City, Missouri. The adjusted odds ratio was calculated using a logistic model to assess the association between ETS and allergic sensitization using dust allergen levels as a covariate., Results: Thirty-six percent of atopic children and 39% of controls were exposed to ETS (P < .05). Unadjusted analyses showed no significant influence of ETS on IgE sensitization to indoor allergens. Logistic regression analyses also showed no significant influence of ETS on sensitization when adjusted for levels of allergens in the home dust and family history of allergic rhinitis., Conclusion: These data suggest that ETS exposure was not associated with IgE sensitization to indoor allergens, even when home allergen levels were taken into consideration. Further understanding of how components of tobacco smoke influence the immune response is necessary to interpret the disparate findings across studies., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. The immunological process underlying RAO is still unclear. Previous studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene in one Warmblood family (F1), but not in another (F2). It has also been shown that in F1, but not in F2, RAO is associated with resistance against parasites, suggesting that this association may have an immuno-genetic basis. Therefore, we hypothesized that the T helper (h)1/Th2/regulatory (Treg) cytokine profiles of RAO-associated antigen- and parasite-antigen-stimulated peripheral blood mononuclear cells (PBMC) differ between RAO-affected and healthy horses depending on their genetic background. In our study, PBMC from 17 RAO-affected and 14 healthy control horses of F1 and F2 were stimulated for 24h with antigens relevant to RAO [hay dust extract (HDE), Aspergillus fumigatus extract (AFE) and lipopolysaccharids (LPS)]; cyathostomin extract (CE) and recombinant cyathostomin antigen (RCA) or with concanavalin A (ConA). Total mRNA levels of IL-4, IL-4R, IL-13, interferon (INF)-γ and IL-10 were examined by qRT-PCR. Stimulation with either HDE or RCA resulted in significant differences in IL-4R mRNA levels between RAO-affected and control horses in F1, but not in F2. For IL-10 mRNA expression, a significant difference between RAO-affected and control horses in F1 but not in F2 was observed only following stimulation with HDE. In contrast to HDE, stimulation with CE resulted in a significant difference of IL-10 mRNA expression level between RAO-affected horses of F2 and healthy horses of F1. No significant differences were detected upon stimulation with any of the other challenge agents. These findings indicate that the immunological response, specifically IL-4R expression, in response to hay dust and cyathostomin antigens, differs between RAO-affected and healthy horses depending on their genetic background. This study shows that analysis of PBMC reveals systemic changes associated with RAO and helps to elucidate immunological pathways involved in this disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Home mouse allergen exposure is associated with asthma morbidity, but little is known about the shape of the dose-response relationship or the relevance of location of exposure within the home. Asthma outcome and allergen exposure data were collected every 3 months for 1 year in 150 urban children with asthma. Participants were stratified by mouse sensitization, and relationships between continuous measures of mouse allergen exposure and outcomes of interest were analyzed. Every tenfold increase in the bed mouse allergen level was associated with an 87% increase in the odds of any asthma-related health care use among mouse-sensitized [Odds Ratio (95% CI): 1.87 (1.21-2.88)], but not non-mouse-sensitized participants. Similar relationships were observed for emergency department visit and unscheduled doctor visit among mouse-sensitized participants. Kitchen floor and bedroom air mouse allergen concentrations were also associated with greater odds of asthma-related healthcare utilization; however, the magnitude of the association was less than that observed for bed mouse allergen concentrations. In this population of urban children with asthma, there is a linear dose-response relationship between mouse allergen concentrations and asthma morbidity among mouse-sensitized asthmatics. Bed and bedroom air mouse allergen exposure compartments may have a greater impact on asthma morbidity than other compartments., (© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Various studies have investigated the efficacies of mometasone furoate monohydrate (MFM) and fluticasone propionate (FP) nasal sprays for adults. However, research on their effectiveness for children is limited. This study compares the efficacies of MFM and FP nasal sprays in pediatric patients with perennial-allergic rhinitis., Materials and Methods: For this study, 94 perennial allergic rhinitis patients aged 6-12 years were randomly assigned to two treatment groups: an MFM group and an FP group. Treatment was provided for 4 weeks. The effects of the two agents were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire and total symptom scores (TSSs). Nasal-peak expiratory flow rates and eosinophil percentage in nasal smears were also compared between the two groups., Results: Patients in the MFM group exhibited significant improvement in their TSS (t = -2.65, p < 0.05). A detailed TSS analysis showed MFM to be more effective for relieving nasal symptoms, whereas FP was more effective for relieving non-nasal symptoms. Patient questionnaire scores suggested a significant reduction in symptoms for both the MFM (t = -7.23, p < 0.01) and FP (t = -5.43, p < 0.01) groups. The flow rate test results indicated significant improvements in the MFM group (t = 2.27, p < 0.05)., Conclusion: Following the 4-week therapy, MFM provided greater improvement compared to FP for symptoms of childhood perennial-allergic rhinitis. Based on their TSSs, the MFM group experienced more effective relief of nasal symptoms, whereas the FP group experienced more effective relief of non-nasal symptoms., (Copyright © 2013. Published by Elsevier B.V.)

Organic dust exposure within agricultural environments results in airway diseases. Toll-like receptor 2 (TLR2) and TLR4 only partly account for the innate response to these complex dust exposures. To determine the central pathway in mediating complex organic dust-induced airway inflammation, this study targeted the common adaptor protein, myeloid differentiation factor 88 (MyD88), and investigated the relative contributions of receptors upstream from this adaptor. Wild-type, MyD88, TLR9, TLR4, IL-1 receptor I (RI), and IL-18R knockout (KO) mice were challenged intranasally with organic dust extract (ODE) or saline, according to an established protocol. Airway hyperresponsiveness (AHR) was assessed by invasive pulmonary measurements. Bronchoalveolar lavage fluid was collected to quantitate leukocyte influx and cytokine/chemokine (TNF-α, IL-6, chemokine [C-X-C motif] ligands [CXCL1 and CXCL2]) concentrations. Lung tissue was collected for histopathology. Lung cell apoptosis was determined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and lymphocyte influx and intercellular adhesion molecule-1 (ICAM-1) expression were assessed by immunohistochemistry. ODE-induced AHR was significantly attenuated in MyD88 KO mice, and neutrophil influx and cytokine/chemokine production were nearly absent in MyD88 KO animals after ODE challenges. Despite a near-absent airspace inflammatory response, lung parenchymal inflammation was increased in MyD88 KO mice after repeated ODE exposures. ODE-induced epithelial-cell ICAM-1 expression was diminished in MyD88 KO mice. No difference was evident in the small degree of ODE-induced lung-cell apoptosis. Mice deficient in TLR9, TLR4, and IL-18R, but not IL-1IR, demonstrated partial protection against ODE-induced neutrophil influx and cytokine/chemokine production. Collectively, the acute organic dust-induced airway inflammatory response is highly dependent on MyD88 signaling, and is dictated, in part, by important contributions from upstream TLRs and IL-18R.

Background: It has been suggested that dust exposure causes airway inflammation among cement factory workers. However, there is limited information on the mechanisms of this effect. We explored any associations between total dust exposure and fractional exhaled nitric oxide (FENO) as a marker of airway eosinophilic inflammation among cement production workers in Tanzania. We also examined possible differences in FENO concentration between workers in different parts of the production line., Methodology: We examined 127 cement workers and 28 controls from a mineral water factory. An electrochemistry-based NIOX MINO device was used to examine FENO concentration. Personal total dust was collected from the breathing zone of the study participants using 37 mm cellulose acetate filters placed in three-piece plastic cassettes. Interviews on workers' background information were conducted in the Swahili language., Results: We found equal concentrations of FENO among exposed workers and controls (geometric mean (GM)=16 ppb). The GM for total dust among the exposed workers and controls was 5.0 and 0.6 mg/m(3), respectively. The FENO concentrations did not differ between the exposed workers with high (GM≥5 mg/m(3)) and low (GM<5 mg/m(3)) total dust exposure. There was no significant difference in FENO concentration between workers in the two main stages of the cement production process., Conclusions: We did not find any difference in FENO concentration between dust-exposed cement workers and controls, and there were similar FENO concentrations among workers in the two main stages of cement production.

Background: Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases., Objective: To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma., Methods: Indoor dust was collected from a bed mattress in an apartment. EV were prepared by sequential ultrafiltration and ultracentrifugation. Innate and adaptive immune responses were evaluated after airway exposure of EV., Results: Repeated intranasal application of indoor-dust-induced neutrophilic pulmonary inflammation accompanied by lung infiltration of both Th1 and Th17 cells. EV 50-200 nm in diameter were present (102.5 μg protein concentration/g dust) in indoor dust. These vesicles were internalized by airway epithelial cells and alveolar macrophages, and this process was blocked by treatment of polymyxin B (an antagonist of lipopolysaccharide, an outer-membrane component of Gram-negative bacteria). Intranasal application of 0.1 or 1 μg of these vesicles for 4 weeks elicited neutrophilic pulmonary inflammation. This phenotype was accompanied by lung infiltration of both Th1 and Th17 cells, which were reversed by treatment of polymyxin B. Serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis., Conclusion & Clinical Relevance: Indoor dust EV, especially derived from Gram-negative bacteria, is a possible causative agent of neutrophilic airway diseases., (© 2013 Blackwell Publishing Ltd.)

Objectives: To assess the effect of exposure to flour dust on pulmonary function tests, prevalence of symptoms (respiratory, allergic/irritating) and parameters of allergic sensitization in terms of skin prick test, and bronchial hyper-responsiveness., Material and Methods: 43 bakers (with at least 2 years of occupational exposure) working at different bakeries in Ismailia city, Egypt; and 64 control subjects of comparable socio demographic characteristics were compared. All participants were subjected to an interview questionnaire, clinical chest examination, skin prick test, bronchial hyper-responsiveness test and measurements of pulmonary function parameters., Results: All respiratory and allergic symptoms were more prevalent among bakers compared to the control group, with the highest odds ratio for allergic symptoms (OR = 6.9; p < 0.0001) and dyspnea (OR = 6.3; p = 0.0004). Bakers had a higher percentage of SPT positive results with statistically significant difference between the two groups (p < 0.0001). Bakers had lower observed values compared to the control group with statistically significant difference for FVC, FEV1/FVC ratio, FEF75%, and FEF25-75% parameters., Conclusion: The present study suggested that occupational exposure to flour dust may affect respiratory irritation and sensitization, and reduce the pulmonary function tests such as FVC, FEV1, and FEV1/FVC ratio and FEF25-75%.

Background: There are conflicting study results regarding the association of exposure to visible mould and fungal components in house dust with respiratory and allergic diseases in children. It has been suggested that functional polymorphisms of the GSTP1 gene may influence the risk for allergic disorders through an impaired defence against oxidant injury., Methods: We examined in six birth cohorts of over 14 000 children whether the association between early exposure to reported mould at home in relation to respiratory and allergic diseases is modified by a single nucleotide polymorphism of the GSTP1 gene., Results: We observed a positive association of mould exposure with nasal symptoms (2-10 year) aOR: 1.19 (1.02-11.38). Further, there was a borderline significant increased risk of rhinoconjunctivitis (6-8 year) in children homozygous for the minor allele Val/Val, aOR: 1.25 (0.98-1.60). In stratified analyses, subjects homozygous for the minor allele and exposed to mould at home were at increased risk for early wheezing aOR: 1.34 (1.03-1.75), whereas the major allele may confer susceptibility for later nasal outcomes, (6-8 year) aOR: 1.20 (1.00-1.45) and (2-10 year) aOR: 1.30 (1.04-1.61), respectively. For none of the health outcomes studied, we found gene by environment interactions., Conclusion: A genetic influence of the GSTP1 gene cannot be ruled out, but the magnitude of the effect is a matter of further research. In conclusion, the interplay between gene and environments is complex and remains subject of further study., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Lung epithelial cells can influence immune responses to airway allergens. Airway epithelial cells also undergo apoptosis after encountering environmental allergens; yet, relatively little is known about how these are cleared, and their effect on airway inflammation. Here we show that airway epithelial cells efficiently engulf apoptotic epithelial cells and secrete anti-inflammatory cytokines, dependent upon intracellular signalling by the small GTPase Rac1. Inducible deletion of Rac1 expression specifically in airway epithelial cells in a mouse model resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract or ovalbumin as allergens led to exacerbated inflammation, augmented Th2 cytokines and airway hyper-responsiveness, with decreased interleukin (IL)-10 in bronchial lavages. Rac1-deficient epithelial cells produced much higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of nuocyte-like cells. Administration of exogenous IL-10 'rescued' the airway inflammation phenotype in Rac1-deficient mice, with decreased IL-33. Collectively, these genetic and functional studies suggest a new role for Rac1-dependent engulfment by airway epithelial cells and in establishing the anti-inflammatory environment, and that defects in cell clearance in the airways could contribute to inflammatory responses towards common allergens.

Interleukin (IL)-13 genetic polymorphisms have shown adverse effects on respiratory health. However, few studies have explored the interactive effects between IL-13 haplotypes and environmental exposures on childhood asthma. The aims of our study are to evaluate the effects of IL-13 genetic variants on asthma phenotypes, and explore the potential interaction between IL-13 and household environmental exposures among Taiwanese children. We investigated 3,577 children in the Taiwan Children Health Study from 14 Taiwanese communities. Data regarding children's exposure and disease status were obtained from parents using a structured questionnaire. Four SNPs were tagged accounting for 100% of the variations in IL-13. Multiple logistic regression models with false-discovery rate (FDR) adjustments were fitted to estimate the effects of IL-13 variants on asthma phenotypes. SNP rs1800925, SNP rs20541 and SNP rs848 were significantly associated with increased risks on childhood wheeze with FDR of 0.03, 0.04 and 0.04, respectively. Children carrying two copies of h1011 haplotype showed increased susceptibility to wheeze. Compared to those without carpet use and h1011 haplotype, children carrying h1011 haplotype and using carpet at home had significantly synergistic risks of wheeze (OR, 2.5; 95% CI, 1.4-4.4; p for interaction, 0.01) and late-onset asthma (OR, 4.7; 95% CI, 2.0-10.9; p for interaction, 0.02). In conclusions, IL-13 genetic variants showed significant adverse effects on asthma phenotypes among children. The results also suggested that asthma pathogenesis might be mediated by household carpet use.

Background: Mites are the most common cause of respiratory allergy. Sensitization to house dust mites is estimated at 30%. Families Euroglyphus and Dermatophagoides, are the most important. Recently, storage mites, from the families Acaridae and Glyciphagidae, have become more important as a cause of allergic respiratory diseases., Objective: The aim of this study was to identify sensitization to house dust and storage mites by skin tests in adult patients with allergic respiratory diseases., Methods: This is a descriptive study in patients with asthma and/or allergic rhinitis, with the approval of the local research committee 2009-3601-46. Patients underwent skin prick tests, with seven standardized extracts of mites (IPI ASACR). The results were analyzed with descriptive statistics., Results: A total of 150 patients, 109 women and 41 men, with an average age 31 years (±11) were studied. The more common allergic diseases in this group of patients were: asthma and rhinitis 72 and 26%, respectively, and asthma plus rhinitis 3.2%. Positive skin tests for Dermatophagoides pteronyssinus and Dermatophagoides farinae were 82.1% 71.5%, respectively, and for storage mites: A. siro 51.7%, Tyrophagus 47.4%, Glycyphagus 47.7%, B. tropicalis 39.7% and Lepidoglyphus 39.1%. Storage mites produced greater sensitization than house dust mites, 32% vs 10%., Conclusions: The results show that adult patients with respiratory allergy, in southern Mexico City, have a higher rate of sensitization to storage mites than the one reported in the literature.

Allergic disorders are the most common childhood-related chronic diseases in developed countries. It is essential to assess the exposure, especially in schools, where children spend a large portion of their time. We aimed to investigate allergen and endotoxin levels in the air of schools and to observe seasonal variations of these factors. We evaluated airborne concentrations of house dust mites allergens (Der p 1, Der f 1), cat allergen (Fel d 1), and endotoxin in PM10 in 14 classrooms during the school days in the region of Munich, each over 20 consecutive days and in 1 classroom over the course of a year (at 83 days); we also tested outdoor air close to the schools. Endotoxin levels were quantified using two different analytical methods. In addition, indoor air climate parameters were measured. The median daily indoor CO2 and PM10 concentrations in the classrooms ranged from 423 to 3,135 ppm (median: 1,211 ppm) and 9 to 390 μg/m(3) (median: 127 μg/m(3)), respectively. Fel d 1 in the PM10 samples was the most frequently detected allergen, with levels from 0.02 to 1.15 ng/m(3) in a total of 301 samples (median: 0.19 ng/m(3), 95th percentile: 0.57 ng/m(3)). Der p 1 and Der f 1 were detected in only 51% and 19% of the samples, with 95th percentiles at 0.5 and 0.3 ng/m(3). Endotoxin levels in the PM10 and inhalable dust samples ranged from 0.5 to 84.1 EU/m(3) (median: 15.3 EU/m(3); 95th percentile: 58.2 EU/m(3)) and from 0.03 to 115 EU/m(3) (median: 8.4 EU/m(3); 95th percentile: 27.9 EU/m(3)). Fel d 1 and endotoxin were found in higher levels in the winter months. The results of the two different indoor sampling techniques for endotoxin were statistically significantly correlated. The results of airborne allergens indicate a generally low exposure level in classrooms. With regard to endotoxin, our study showed higher levels in schools compared with residences.

Mixed exposure to metals (including arsenic and lead) associated with the neurological and respiratory effects constitute one of the major health problems of copper smelting. Chemical composition of the dust, and the expected health effect of inhalation can be very diverse at different parts of the smelter plant. The aims of this study were to compare lung responses and behavioral effects in female Wistar rats after instillation of dust collected from different production processes at the same smelter department. Dusts collected at two different locations of furnace hall were sifted through 25-μm-mesh sieve. Obtained dust fractions, P-25(I) collected near stove, rich in heavy metals and arsenic, and P-25(II) collected near anode residue storage site, rich in aluminium, were instilled to rats. At 1, 7 and 30 days after dusts instillation, lung injury and inflammation were measured by analyzing sings of lung permeability in the bronchoalveolar lavage fluid (BALF), cell differentiation in BALF sediment and lung morphology. The behavioral studies were done 30 days after exposure. Results of biochemical tests showed a strong pro-inflammatory effect of P-25(I) fractions. Mostly characteristic effects after instillation of P-25(I) samples were 10× increased protein leakages in BALF. Both P-25(I) and P-25(II) fractions caused a reduction of Clara-cell 16 protein concentration (CC16) in BALF and activation of serum butyrylcholinesterase (BChE) at all time points. The morphological studies after exposure to P-25(I) fractions showed multi-focal infiltrations in the alveoli. The behavioral results, especially P-25(II) group rats (in open filed, passive avoidance and hot plate tests), indicated adverse effects in the nervous system, which may be related to changes in the dopaminergic and cholinergic pathway. The symptoms were noted in the form of persistent neurobehavioral changes which might be associated with the content of neurotoxic metals. e.g. Al, Mn and/or As. Decrease of CC16 concentration that occurred immediately after instillation of both dust samples, point out impaired anti-inflammatory potential, resulted in early harmful effect not only to the respiratory tract but also to the whole body, including the nervous system.

Background: Workers in swine operations are exposed to indoor dusts and gases and are at increased risk of respiratory problems. Toll-like receptor (TLR) 2 recognizes ligands from gram-positive bacteria, whereas TLR4 responds to endotoxin from gram-negative bacteria., Objective: To investigate the effects of TLR2 and TLR4 polymorphisms on lung function in workers from swine operations and nonfarming rural dwellers., Methods: A total of 374 full-time workers from large swine operations and 411 nonfarming rural dwellers from Saskatchewan were included. Information on demography, lifestyle, and occupation, lung function measurements, and blood samples for genotyping were obtained from the participants. Multiple regression analysis and Bonferroni correction were used in the statistical analysis., Results: Workers with TLR2-16933T/A polymorphism (AA) had significantly greater mean values of lung function than workers with wild-type genotypes (AT+TT) after controlling for potential confounders (forced expiratory volume in 1 second, 3.7 vs 3.5 L; P=.009; forced expiratory flow between 25% and 75%, 3.7 vs 3.3 L; P=.003; predicted forced expiratory volume in 1 second; 100.3% vs 95.6%; P=.005; forced expiratory flow between 25% and 75%, 92.4% vs 83.4%; P=.009). These results were also observed for TLR2Arg677Trp polymorphism among the workers. No such significant differences were observed among nonfarming rural dwellers. For Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene, no significant differences were observed in the mean lung function values between the polymorphic and wild-type groups in both workers and rural dwellers., Conclusion: Our study is the first, to our knowledge, to report protective effects of TLR2 polymorphisms on lung function among workers in swine operations and raises the possibility that TLR2 polymorphisms are protective of airway disease in individuals exposed to gram-positive organisms in the inhaled airborne dust., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Intranasal application of cowshed dust extract (CDE) during sensitisation in a murine model of experimental asthma leads to a significant alleviation of the clinical parameters of the allergic immune response. However, neither the immunological mechanisms underlying this protective effect nor all of the protective substances included in CDE have yet been described. Recently, complement factor 5a (C5a) receptor signalling has been identified to play a regulatory role in allergic airway disease. Thus we investigated whether CDE can activate the complement system to release biologically active C5a in the lung., Methods: Proteins included in CDE were identified by mass spectrometry. Complement cleaving activity of a serine protease identified in CDE was validated with the purified enzyme, and the biological activity of the released C5a was determined. C5a was applied in a murine model of allergy to prove its protective impact on allergic airway disease., Results: CDE induced the release of C5a in murine bronchoalveolar lavages (BAL). We identified a serine protease from the midgut of tenebrio molitor larvae in CDEs which was able to induce the release of biologically active C5a in murine BAL. We applied C5a in different doses to female Balb/c mice during the sensitisation phase and during the first antigen challenge and showed that C5a has the ability to dampen important parameters of allergic airway inflammation, such as infiltration of proinflammatory cells into lung tissue or Th2 cytokine secretion by lung cells., Conclusions: We conclude that the C5a generating enzyme included in CDE might account for some of the allergy protective effects of CDE by generation of C5a in murine lungs.

Background: Evaluation of the sensitisation and levels of exposure to grains and its pulmonary impact ina population of Brest port silo employees., Materials and Methods: We included exposed workers. The study consisted of clinical examination witha standardised questionnaire, blood samples, prick-tests, and spirometry tests. The atmospheric concentrationof total dust in the workplace was also associated., Results: Eight workers were included in the study. No case of occupational asthma was found, but 3 casesof occupational rhinitis were noted and occupational prick-tests were positive in 4 cases. The mean totaldust concentration in the three atmospheric samples was 4.87 mg/m3 for 8 hours but it was under thedetection limits for alveolar fractions., Conclusions: Port silo workers are exposed to total dust concentrations below the French legal limit (10 mg/m3) but higher than Canadian and American recommendations. Levels of exposure in our studyare similar to other studies developed in port silos. Symptoms developed by workers may be due to highexposure to dust with an irritant effect rather than an allergic effect. Despite this fact, a specific medicalsurvey is needed, and ventilation and respiratory masks have to be promoted for prevention.

Asian dust events result from displacement of atmospheric pollutants from the Chinese and Mongolian deserts, causing associated health issues throughout Northeast Asia. We investigated the relationship between skin symptoms in Asian dust events and contact allergy to Asian dust and associated metals. Increases in atmospheric levels of heavy metals such as Ni, Al, and Fe occurred during the severe Asian dust event on March 21, 2010. We conducted a case-control study (n = 62) with patch testing to compare skin symptoms on an Asian dust day with metal allergic reactions. Skin symptoms were observed in 18/62 subjects. Nine subjects with skin symptoms (group A) and 11 without (group B) were patch tested for six metals and Asian dust particles. Metal and dust samples were applied to the subjects' backs for 2 days and the reactions were scored according to the International Contact Dermatitis Research Group guidelines. Differences in the positive rates between the groups were analyzed. Skin reactions to ferric chloride (p = 0.015), aluminum chloride (p = 0.047), nickel sulfate (p = 0.008), and Asian dust particles (p = 0.047) were more common in group A than in group B. Skin symptoms during Asian dust events may be allergic reactions to Asian dust particle-bound metals.

Atopic dermatitis (AD) is a chronically relapsing, inflammatory skin disease characterized by severe itch, rash and dry skin. Hypersensitivity to aeroallergens is found in 40%-50% of children with AD and it is the cause of intensive skin lesions. The aim of the study was to assess the presence of hypersensitivity to aeroallergens in AD children. The study included 114 children (56 boys and 58 girls), median age 27.5 months, who had been diagnosed with AD according to Hanifin and Rajka criteria. The severity of the disease was assessed by the SCORAD index. To recognize hypersensitivity to aeroallergens, the following parameters were analyzed: medical history, values of absolute eosinophil count, total IgE antibodies, specific IgE antibodies to aeroallergens, and results of the skin prick test for aeroallergens. A moderate form of the disease was present in 61.4% of study children, with a median SCORAD index score of 28.5 points; 12.3% of study children showed hypersensitivity to aeroallergens (history of hypersensitivity to aeroallergens in 27.2%, increased absolute eosinophil count in 53.5%, increased total IgE antibodies in 56.1%, positive skin prick test in 20.2%, and positive specific IgE antibodies to aeroallergens in 12.3% of children). The most common aeroallergens responsible were house dust in 6.1% and Dermatophagoides pteronyssinus in 3.5% of children with AD. Hypersensitivity to aeroallergens was recorded in the same number of children with mild and severe forms of the disease and in 5.7% of children with a moderate form. In conclusion, the presence of hypersensitivity to aeroallergens in children with AD is significant. By discovering and removing the aeroallergens responsible, it is possible to achieve reduction in the intensity of skin lesions and frequency of exacerbations.

Objective: This study investigated environmental endotoxin exposure during early life, sensitization to aeroallergens, the production of cytokines by LPS-stimulated leukocytes, and the development of a wheezing phenotype in a prospective cohort of infants with high risk of developing allergic diseases., Materials and Methods: Eighty-four infants were followed from birth until 30 months of age. We assessed endotoxin concentration in house dust of their homes during the first 6 months of life. At age 30 months they were clinically evaluated to determine the development of wheezing and other clinical events, were skin prick tested, and had blood samples collected for the evaluation of cytokine release by LPS-stimulated peripheral blood mononuclear cells (PBMC)., Results: The level of endotoxin exposure during early life was not associated with development of a wheezing phenotype. On the other hand a higher incidence of respiratory infections occurred among recurrent wheezing (RW) infants. PBMC from RW children exposed to higher levels of environmental endotoxin (above 50 EU/mg) released less Interleukin (IL)-12p70 and IFN-γ compared to the non-RW group. TNF-α, IL-10, IL-4, IL-5, and IL17 production by LPS-stimulated PBMC from RW and non-RW children was equivalent in both groups of environmental endotoxin exposure., Conclusion: In this prospective cohort of infants with high risk of developing allergic diseases we observed that RW and non-RW children were exposed to similar levels of endotoxin early in life. LPS-stimulated PBMC from RW infants exposed to higher levels of endotoxin released significantly less IL-12 and IFN-γ compared to non-RW infants., (Copyright © 2012 Wiley Periodicals, Inc.)

Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction. Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria. The ability of bacterial products to act as adjuvants suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen-presenting dendritic cells (DCs) in vitro and promote allergic sensitization to inhaled innocuous proteins in vivo. It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen for adjuvant activity of microbial products revealed that the bacterial protein flagellin (FLA) stimulated strong allergic airway responses to an innocuous inhaled protein, ovalbumin (OVA). Moreover, Toll-like receptor 5 (TLR5), the mammalian receptor for FLA, was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, individuals with asthma have higher serum levels of FLA-specific antibodies as compared to nonasthmatic individuals. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens.

Organic dust exposure in the agricultural industry results in significant lung disease. Macrophage infiltrates are increased in the lungs after organic dust exposures, yet the phenotype and functional importance of these cells remain unclear. Using an established intranasal inhalation murine model of dust-induced lung inflammation, animals were treated once or daily for 3 weeks with swine confinement organic dust extract (DE). Repetitive DE treatment for 3 weeks resulted in significant increases in CD11c(+)/CD11b(+) macrophages in whole lung-associated tissue. These cells displayed increased costimulatory molecule (CD80 and CD86) expression, enhanced phagocytic ability, and an increased production of IL-6, CXCL1, and CXCL2. Similar findings were observed with the CD11c(+)/CD11b(+) macrophage infiltrate after repetitive exposure to peptidoglycan, a major DE component. To determine the functional importance of macrophages in mediating DE-induced airway inflammation, lung macrophages were selectively depleted using a well-established intranasal clodronate liposome depletion/suicide strategy. First, macrophage depletion by clodronate liposomes resulted in significant reductions in airway neutrophil influx and TNF-α and IL-6 production after a single exposure to DE. In contrast, after repetitive 3-week exposure to DE, airway lavage fluid and lung tissue neutrophils were significantly increased in clodronate liposome-treated mice compared with control mice. A histological examination of lung tissue demonstrated striking increases in alveolar and bronchiolar inflammation, as well as in the size and distribution of cellular aggregates in clodronate-liposome versus saline-liposome groups repetitively exposed to DE. These studies demonstrate that DE elicits activated CD11c(+)/CD11b(+) macrophages in the lung, which play a critical role in regulating the outcome of DE-induced airway inflammation.