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Investigates the occurrence of chronic respiratory effects of exposure to organic dust in the potato processing industry. Method used to investigate the relationship between exposure concentrations and respiratory health variables; Technique used to assess atopy; Conclusions derived after determining the levels of exposure to endotoxin.

BACKGROUND: It has been suggested that vitamin E can counteract the age-associated decline in cellular immune responsiveness (CIR). Particularly, T helper cell type 1 (Th1) activity, ie, interferon (IFN) gamma-producing Th1 activity and, hence, delayed-type hypersensitivity (DTH) would be enhanced by vitamin E supplementation. OBJECTIVE: Our aim was to study the effects of 6 mo supplementation with 50 and 100 mg vitamin E on CIR in the elderly. DESIGN: A double-blind, placebo-controlled trial was conducted in 161 healthy elderly subjects aged 65-80 y. CIR was measured in vivo by means of DTH skin tests and in vitro by assessing the production of interleukin (IL) 2, IFN-gamma (a typical Th1 cytokine), and IL-4 (a typical Th2 cytokine) by peripheral blood mononuclear cells after stimulation with phytohemagglutinin. RESULTS: Both DTH and IL-2 production showed a trend toward increased responsiveness with increasing dose of vitamin E. However, IFN-gamma production decreased whereas IL-4 production increased in the groups receiving vitamin E. Only the change in the number of positive DTH reactions was borderline significantly larger in the 100-mg vitamin E group than in the placebo group (P = 0.06, Bonferroni adjusted). Subjects receiving 100 mg vitamin E with low baseline DTH reactivity or who were physically less active had a significantly larger increase in the cumulative diameter of the skin induration resulting from the DTH test than did the placebo group (P = 0.03), although this difference was not significant after Bonferroni correction (P = 0.07). CONCLUSION: Possible beneficial effects of 100-mg vitamin E supplementation may be more pronounced in particular subgroups of elderly subjects. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

The influence of IgM-rheumatoid factor (IgM-RF) on the activation of isolated Cl by soluble IgG aggregates (AIgG) and immune complexes was studied. IgM preparations obtained from the sera of four patients with seropositive rheumatoid arthritis markedly reduced the Cl activation capacity of AIgO, especially when large aggregates were tested. The results of parallel experiments with radiolabelled AIgU indicated that this inhibitory effect of IgM-RF was accompanied by a very large increase of the aggregate size. A comparable IgM preparation isolated from pooled normal human serum influenced neither the size nor the Cl activation capacity of AIgO. The inhibitory effect of IgM-RF on Cl activation was also demonstrated for soluble tetanus-anti-tetanus immune complexes. Thus, in spite of the established C activation ability of IgM-RF and the fact that, in general, larger IgO aggregates and immune complexes activate C I more efficiently, cross- linking and size enlargement of soluble lgG complexes and aggregates by IgM-RF lead to a decrease of the Cl activation capacity. As a consequence, IgM-RF may reduce plasma complement activation by soluble IgO complexes in the circulation of patients with seropositive rheumatic diseases. [ABSTRACT FROM AUTHOR]

The role of C&1macr; inactivator (C&1macr;-In) during activation of the classical complement pathway by soluble immune complexes was studied using purified human complement components C1, C4 and C&1macr;-In, and stabilized soluble aggregates of normal human IgG as a model for soluble immune complexes. The C4-consuming ability that could be generated by incubation of precursor C1 with IgG aggregates was abolished completely by the presence of a large excess of C&1macr;-In during the C1 activation step. Kinetic studies confirmed that this inhibition was due to a second-order reaction between C&1macr; and C&1macr;-In resulting in the irreversible inactivation of C&1macr;. When aggregates of various sizes were enabled to induce C4 conversion in mixtures of C1, C4 and a variable concentration of C&1macr;-In, the presence of C&1macr;-In had two effects. Firstly, the efficiency of the aggregates in causing C4 consumption was reduced remarkably. At a C&1macr;-In:C1 ratio of 8, which can be found in normal human serum, approximately eight to ten times as many aggregates were required for a given level of C4 consumption as when no C&1macr; -In was present. Secondly, C&1macr;-In diminished the maximum C4 consumption that could be achieved, especially with smaller aggregates. Thus, a complete or partial C&1macr;-In deficiency probably facilitates complement activation by soluble immune complexes in two ways: it may enhance the efficiency of classical pathway activation by all C1-activating complexes, and it may enable small complexes, which normally cannot overcome the C&1macr;-In bather, to activate the classical pathway to the C4 level. [ABSTRACT FROM AUTHOR]

The interaction between small aggregates of human IgG and the first component of human complement was studied. Stabilized soluble IgG aggregates of restricted size were prepared by heat aggregation of human IgG, followed by sucrose-density ultracentrifugation. Human C1 was isolated in its precursor form by euglobulin precipitation, followed by gel filtration and immunoadsorption. A C1 preparation was obtained of which more than 90% was still in its unactivated form. Soluble aggregates containing 20, 10 or 5 molecules IgG, and monomeric IgG were tested for their ability to bind and to activate C1. The binding of C1 was determined by C1 consumption, whereas the activation of C1 was measured as the increased ability of the C1 preparation to consume purified human C4 after the incubation with the aggregates. The three aggregates tested and monomeric IgG were all able to bind and to activate C1, but the efficiency of both processes markedly increased with increasing aggregate-size. Furthermore, it was found that all four preparations activated an appreciable amount of C1 at concentrations that did not result in any detectable C1 fixation. These results confirm earlier suggestions that C1 can be activated during a short, transient binding to small aggregates or immune complexes that have a low avidity for C1, after which the activated form, C&1sline;, is released into the medium. [ABSTRACT FROM AUTHOR]

An enzyme-linked immunosorbent assay (ELISA) was developed to assess serum IgE antibodies directed against Pityrosporum ovale in patients with atopic dermatitis (AD), atopic patients with allergic respiratory disease (ARD: rhinitis or asthma) but without eczema, and in healthy controls. IgE binding to P. ovale extract was demonstrated in 49% (35/72) of AD patients. In contrast. anti-R ovule IgE was found in only one of 27 atopic controls without eczema: all healthy control sera (n=17) were negative. Of 37 AD patients tested intracutaneously with P. ovale. 31 showed immediate-type reactivity, and 20 of these 3 1 patients had anti-P. ovale IgE detectable by ELISA, while sera from the six non-responders were all negative. Levels of anti-P. ovale IgE were highest in AD patients aged 20–30 years. No correlation was found with the severity of AD, but there was a non-significant tendency (P = 0.06) to higher levels in AD patients with concomittant respiratory allergy. Anti-P. ovale IgE was significantly correlated with total serum IgE, with specific IgE against various aeroallergens as measured by RAST, and with levels of anti-Candida albicans IgE, measured with a similar ELISA. Thus, production of IgE antibodies against P. ovale occurs very frequently in AD. and rarely in patients with atopic disease without skin involvement. [ABSTRACT FROM AUTHOR]

Background Allergen exposure in early childhood is thought to be important for sensitization and subsequent development of asthma. Not much is known, however, about exposure of young children to allergens in the home. Objectives This study was designed to document dust mite allergen exposure in young children, and to determine whether infants from atopic mothers (='high-risk' infants) are exposed lo lower concentrations of house dust mite allergen than infants from nonatopic parents ( ='low-risk' infants). Methods Dust samples were taken in the homes of 104 infants (48 'high-risk' and 56 'low-risk' infants, selected by questionnaire) aged 3-15 months, from floors in different rooms and from the child's mattress surface. Results The majority of the infants were found to be exposed to Der p I concentrations of more than 2000 ng/g in dust collected from the surface of their mattresses. Lower Der p I concentrations were found in mattress surface dust from the beds of infants from atopic mothers than of infants from non-atopic parents. Also, lower Der p I concentrations were found in floor dust from the homes of infants from atopic mothers. Infant beds equipped with new mattresses, new blankets and top plastic sheeting had significantly lower Der p I concentrations than beds equipped with used mattresses and blankets, without top plastic sheeting. Conclusions Young children in the Netherlands are exposed to significant concentrations of Der p 1 in mattress surface dust. Allergic parents appear to provide their children with environments somewhat less rich in mite allergen than non-allergic parents. [ABSTRACT FROM AUTHOR]

Pityrosporum ovale has recently been recognized as a source of allergens to which many patients with atopic dermatitis (AD) show type I skin reactions and specific IgE antibodies. In this study the IgE-binding components and/or epitopes in P. ovale extract were shown to be partially sensitive to pronase or trypsin treatment, whereas periodate oxidation resulted in a complete loss of IgE-binding capacity, thus suggesting the involvement of carbohydrate structures. In Con A affinity chromatography most of the IgE-binding capacity of crude P. ovale extract bound to the column, and could be eluted with mannoside. Gel filtration on Sephacryl S-400 revealed a marked heterogeneity with respect to molecular mass, with most of the IgE-binding activity associated with high-mol.-mass fractions (from 5 × 104 up to 2 × 106 Da). A similar heterogeneity was found after chromatofocusing, with IgE-binding in the whole pI-range from 7.0 to 4.0. Essentially identical results were obtained with extracts of Candida albicans, in agreement with the previously shown cross-reactivity of IgE-binding components in the two yeast extracts. In inhibition ELISA, gel filtration and chromatofocusing fractions containing components with widely different mol. mass or pI showed complete reciprocal cross-inhibition, and were all capable of inhibiting the binding of IgE to unfractionated extracts. We therefore conclude that the cross-reacting anti-P. ovale/anti-C. albicans IgE antibodies in the sera of AD patients are mainly directed at a restricted number of carbohydrate epitopes that are expressed on a heterodisperse range of high-mol.-mass components, probably mannans or mannoproteins. [ABSTRACT FROM AUTHOR]

In atopic dermatitis (AD), a high prevalence has been reported of type I reactions and specific IgE to extracts of the commensal lipophilic skin yeast Pityrosporum ovale. In the present study, a highly significant correlation (r= 0.77) was found between levels of anti-P. ovale IgE and of IgE reacting with extracts of Candida albicans, both measured by a sensitive ELISA method. In a series of 128 AD sera, 34 sera reacted positively with both yeast extracts, 38 reacted with P. ovale but not with C. albicans, and only one of the 56 anti-P. ovale-negative sera showed a very weak reaction with C. albicans. The correlation was due to a marked cross-reactivity, as shown by inhibition ELISA. Fluid-phase preincubation of double-positive sera with either of the two yeast extracts resulted in a dose-dependent, and at high concentrations complete, inhibition of the IgE reactions with both coated P. ovale and C. albicans allergens. Mutual inhibition of IgE-binding could also be achieved with pools of glycoproteins and/or polysaccharides isolated from the crude extracts by Con A affinity chromatography. P. ovale allergens were, however, more potent fluid-phase inhibitors than the corresponding C. albicans components. The apparently higher avidity for P. ovale allergens suggests that these antiyeast IgE antibodies in AD result from sensitization to P. ovale and cross-react with C. albicans. [ABSTRACT FROM AUTHOR]

The interaction between soluble complexes and the first component of complement (C1) was studied. Complexes were prepared from purified bovine thyroglobulin (BTg) or tetanus toxoid (TT) and immunospecific rabbit IgG antibodies. Purified human precursor C1 was incubated with dilutions of the preparations, and the inhibition of C1 haemolytic activity was determined as a measure of C1-binding. The activation of C1 was assessed by measuring the amount of C4 consumed by generated C1. The molar antibody/antigen (Ab/Ag) ratio of BTg—anti-BTg mixtures strongly influenced their C1-binding and C1-activating capacities: mixtures with high Ab/Ag ratios were by far the most efficient. On the other hand, the Ab/Ag ratio had only a limited influence on the activity of TT-anti-TT complexes. The effect of complex size was investigated by ultracentrifugation of antibody—antigen mixtures on calibrated sucrose density gradients followed by C1-binding and -activation experiments with the fractions obtained. For both types of immune complex, the C1-binding and -activating capacities increased markedly with increasing complex size. Thus, both the size and the Ab/Ag ratio of soluble immune complexes influence their capacity to activate the classical complement pathway. The effect of the Ab/Ag ratio. however, may also be dependent on the antigen molecule(s) present in the complexes. [ABSTRACT FROM AUTHOR]

Spontaneous production of immunoglobulins (Igs) by peripheral blood mononuclear cells (PBMC) in vitro was investigated to assess B cell activity in a group of 24 patients with rheumatoid arthritis (RA) with or without active joint disease and with or without rheumatoid vasculitis (RV) at the time of study. PBMC of patients with active arthritis (Ritchie index above 16) produced significantly more IgG and IgA than those of patients with inactive joint disease or those of 12 healthy controls. Enhanced production of IgG was found mainly among RA patients with concomitant RV, whereas markedly enhanced IgA production could also be found in patients without symptoms of RV. IgM production was only enhanced in two patients who had both active arthritis and RV. High production of IgG and IgA was probably due to increased numbers of Ig-secreting cells among freshly isolated PBMC, since the concentrations of Ig produced in vitro rose steadily, starting on day 0 and persisting throughout the entire culture period. Moreover, IgG and IgA concentrations measured after 7 days of culture showed significant correlations with the numbers of IgG- and IgA-containing plasma cells in PBMC on day 0. Comparison of the spontaneous production of Igs by PBMC with the levels of circulating immune complexes (CIC), showed that CIC levels were also significantly higher in active arthritis and in RV, but that there was no correlation between the CIC levels in individual patients and Ig production by their PBMC in vitro. This indicates that no direct relationship exists between the occurrence of high CIC levels in RA and the presence of a systemic B-cell hyperreactivity which had been suggested by the enhanced Ig production by PBMC. [ABSTRACT FROM AUTHOR]

Immunofluorescence on polymorphonuclear cells (PMN) of patients with Felty syndrome (FS) revealed increased amounts of IgG, IgA, and IgM bound to the PMN surface compared with PMN of patients with rheumatoid arthritis alone. A positve correlation was found between the score for surface-bound immunoglobulins on FS-PMN and the results of the C1q binding assay in FS sera. After preincubation with sera from 20 patients with FS, immunofluorescence on PMN from healthy controls (HC) showed that these cells had bound IgG, IgA, and IgM. However F(ab') fragments of IgG from FS sera did not bind to PMN, although the antigen-binding reactivity of the F(ab') fragments was maintained as shown by control experiments. Immunoglobulins eluted from FS-PMN failed to bind to HC-PMN, whereas the corresponding IgG of patients with autoimmune neutropenia was bound. Gel filtration of FS sera on Sepharose 4B showed that the binding of IgG in FS sera to PMN did not coincide with the 7S peak but occurred mainly in fractions containing larger material. No binding of IgA and IgM to HC-PMN was found after incubation with FS sera pretreated with polyethylene glycol (PEG) to precipitate immune complexes. These results indicate that in sera of patients with FS the PMN-binding reactivity of IgG, IgA, and IgM is due to the binding of immune complexes containing these immunoglobulins and not to presence of autoantibodies directed to antigens on the neutrophil surface. [ABSTRACT FROM AUTHOR]

Objectives: To obtain an overview of inhalable β(1→3)glucans levels in Dutch industrial bakeries and explore possible associations with reported respiratory health effects in bakery workers. Methods: β(1→3)glucan levels were analysed in 186 personal inhalable dust measurements obtained from a random population of bakery workers. Association between respiratory health effects and exposure to β(1→3)glucan was explored in a population of industrial bakery workers participating in a Health Surveillance System for flour processing sectors. Based on their job, bakery workers were assigned to low or high exposure categories given the average job exposure estimates obtained from the measurement study. Results: Bread bakers and dough makers had the highest exposures to β(1→3)glucans (GM 1.48 μg/m3 and 1.37 μg/m3 respectively(. Strong correlations were found between airborne levels of inhalable dust and β3(1→3)glucans, and between β(1→3)glucans and wheat allergens (Pearson correlation coefficients were 0.74 and 0.68 respectively). No significant associations could be identified between β(1→3)glucan exposure and work-related respiratory symptoms. Conclusion: This study has shown that bakery workers are exposed to inhalable β(1→)glucan levels comparable with exposure levels found in other occupational settings. More refined exposure assessment is necessary to fully understand the role of β(1→3)glucan exposure on respiratory health in bakery workers. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To obtain an overview of inhalable beta(1-->3)glucans levels in Dutch industrial bakeries and explore possible associations with reported respiratory health effects in bakery workers. METHODS: beta(1-->3)glucan levels were analysed in 186 personal inhalable dust measurements obtained from a random population of bakery workers. Association between respiratory health effects and exposure to beta(1-->3)glucan was explored in a population of industrial bakery workers participating in a Health Surveillance System for flour processing sectors. Based on their job, bakery workers were assigned to low or high exposure categories given the average job exposure estimates obtained from the measurement study. RESULTS: Bread bakers and dough makers had the highest exposures to beta(1-->3)glucans (GM 1.48 mug/m3 and 1.37 mug/m3 respectively). Strong correlations were found between airborne levels of inhalable dust and beta(1-->3)glucans, and between beta(1-->3)glucans and wheat allergens (Pearson correlation coefficients were 0.74 and 0.68 respectively). No significant associations could be identified between beta(1-->3)glucan exposure and work-related respiratory symptoms. CONCLUSION: This study has shown that bakery workers are exposed to inhalable beta(1-->3)glucan levels comparable with exposure levels found in other occupational settings. More refined exposure assessment is necessary to fully understand the role of beta(1-->3)glucan exposure on respiratory health in bakery workers. [ABSTRACT FROM AUTHOR]

Farmers constitute a large professional group worldwide. In developed countries farms tend to become larger, with a concentration of farm operations. Animal farming has been associated with negative respiratory effects such as work-related asthma and rhinitis. However, being born and raised or working on a farm reduces the risk of atopic asthma and rhinitis later in life. A risk of chronic bronchitis and bronchial obstruction/COPD has been reported in confinement buildings and livestock farmers. This position paper reviews the literature linking exposure information to intensive animal farming and the risk of work-related respiratory diseases and focuses on prevention. Animal farming is associated with exposure to organic dust containing allergens and microbial matter including alive microorganisms and viruses, endotoxins and other factors like irritant gases such as ammonia and disinfectants. These exposures have been identified as specific agents/risk factors of asthma, rhinitis, chronic bronchitis, COPD and reduced FEV1. Published studies on dust and endotoxin exposure in livestock farmers do not show a downward trend in exposure over the last 30 years, suggesting that the workforce in these industries is still overexposed and at risk of developing respiratory disease. In cases of occupational asthma and rhinitis, avoidance of further exposure to causal agents is recommended, but it may not be obtainable in agriculture, mainly due to socio-economic considerations. Hence, there is an urgent need for focus on farming exposure in order to protect farmers and others at work in these and related industries from developing respiratory diseases and allergy. [ABSTRACT FROM AUTHOR]

Little is known about the health effects of school-related indoor dampness and microbial exposures. In this study, we investigated dampness and dampness-related agents in both homes and schools and their association with allergy and respiratory health effects in 330 Danish pupils. Classroom dampness was identified based on technical inspection and bedroom dampness on parents' self-report. Classroom and bedroom dust was analyzed for seven microbial components. Skin prick testing determined atopic sensitization. Lung function was expressed as z-scores for forced expiratory volume in one-second (z FEV1), forced vital capacity (z FVC) and the ratio z FEV1/z FVC using GLI-2012 prediction equations. The parents reported children's allergies, airway symptoms, and doctor-diagnosed asthma. High classroom dampness, but not bedroom dampness, was negatively associated with zFEV1 ( β-coef. −0.71; 95% CI −1.17 to −0.23) and z FVC ( β-coef. −0.52; 95% CI −0.98 to −0.06) and positively with wheezing ( OR 8.09; 95% CI 1.49 to 43.97). No consistent findings were found between any individual microbial components or combination of microbial components and health outcomes. Among other indoor risk factors, environmental tobacco smoke ( ETS) decreased z FEV1 ( β-coef. −0.22; 95% CI −0.42 to −0.02) and z FEV1/z FVCratio ( β-coef. −0.26; 95% CI −0.44 to −0.07) and increased upper airway symptoms ( OR 1.66; 95% CI 1.03-2.66). In conclusion, dampness in classrooms may have adverse respiratory health effects in pupils, but microbial agents responsible for this effect remain unknown. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about risk factors for new onset and loss of atopic sensitisation in adulthood. The aim is to examine the longitudinal effect of quantitatively assessed endotoxin exposures on changes in specific allergen sensitisation in young adults., Methods: The cohort consisted of 1113 young Danish farmers and rural controls, with a mean age of 19 years at baseline. Sensitisation to birch pollen, grass pollen, cat dander and house dust mite was measured by specific IgE levels in serum samples from baseline and at 15 years' follow-up. Changes in sensitisation were analysed in relation to cumulative endotoxin exposure during follow-up, considering early life farm exposure., Results: Endotoxin exposure during follow-up was significantly associated with less new onset of specifically grass and birch pollen sensitisation. For the highest versus lowest quartile of cumulative endotoxin exposure, the OR for new-onset IgE sensitisation was 0.35 (0.13-0.91) for birch and 0.14 (0.05-0.50) for grass. On the other hand, loss of pollen sensitisation showed a positive, although mostly non-significant, association with increased levels of endotoxin exposure. Endotoxin exposure was not associated with significant changes in cat dander and house dust mite sensitisation., Conclusions: High exposure to endotoxin during young adulthood appears to protect against new onset of pollen sensitisation, independent of childhood farm exposure., 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: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease., Objective: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role., Methods: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice., Results: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17 + T-cell numbers and supported differentiation of regulatory T cells., Conclusions: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking., Objective: To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases., Design, Setting, and Participants: The Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included., Exposures: Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years., Main Outcomes and Measures: The latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases., Results: We included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95% CI, 1.31-6.31). The late phenotype was only positively associated with allergic rhinitis., Conclusions and Relevance: Using latent class analysis, 4 phenotypes of atopic dermatitis were identified depending on the onset and course of the disease. The prevalence of asthma and food allergy by 6 years of age was strongly increased among children with early phenotypes (within age 2 years), especially with persistent symptoms. These findings are important for the development of strategies in allergy prevention.

Background: Sensitization to wheat flour plays an important role in the development and diagnosis of baker's asthma., Objectives: We evaluated wheat allergen components as sensitizers for bakers with work-related complaints, with consideration of cross-reactivity to grass pollen., Methods: Nineteen recombinant wheat flour proteins and 2 cross-reactive carbohydrate determinants were tested by using CAP-FEIA in sera of 101 bakers with wheat flour allergy (40 German, 37 Dutch, and 24 Spanish) and 29 pollen-sensitized control subjects with wheat-specific IgE but without occupational exposure. IgE binding to the single components was inhibited with wheat flour, rye flour, and grass pollen. The diagnostic efficiencies of IgE tests with single allergens and combinations were evaluated by assessing their ability to discriminate between patients with baker's allergy and control subjects based on receiver operating characteristic analyses., Results: Eighty percent of bakers had specific IgE levels of 0.35 kUA/L or greater and 91% had specific IgE levels of 0.1 kUA/L or greater to at least one of the 21 allergens. The highest frequencies of IgE binding were found for thiol reductase (Tri a 27) and the wheat dimeric α-amylase inhibitor 0.19 (Tri a 28). Cross-reactivity to grass pollen was proved for 9 components, and cross-reactivity to rye flour was proved for 18 components. A combination of IgE tests to 5 components, Tri a 27, Tri a 28, tetrameric α-amylase inhibitor CM2 (Tri a 29.02), serine protease inhibitor-like allergen (Tri a 39), and 1-cys-peroxiredoxin (Tri a 32), produced the maximal area under the curve (AUC = 0.84) in receiver operating characteristic analyses, but this was still lower than the AUC for wheat- or rye flour-specific IgE (AUC = 0.89 or 0.88, respectively)., Conclusions: Component-resolved diagnostics help to distinguish between sensitization caused by occupational flour exposure and wheat seropositivity based on cross-reactivity to grass pollen. For routine diagnosis of baker's allergy, however, allergen-specific IgE tests with whole wheat and rye flour extracts remain mandatory because of superior diagnostic sensitivity., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Dampness and mould exposure have been repeatedly associated with respiratory health. However, less is known about the specific agents provoking or arresting health effects in adult populations. We aimed to assess predictors of microbial agents in mattress dust throughout Europe and to investigate associations between microbial exposures, home characteristics and respiratory health., Methods: Seven different fungal and bacterial parameters were assessed in mattress dust from 956 adult ECRHS II participants in addition to interview based home characteristics. Associations between microbial parameters and the asthma score and lung function were examined using mixed negative binomial regression and linear mixed models, respectively., Results: Indoor dampness and pet keeping were significant predictors for higher microbial agent concentrations in mattress dust. Current mould and condensation in the bedroom were significantly associated with lung function decline and current mould at home was positively associated with the asthma score. Higher concentrations of muramic acid were associated with higher mean ratios of the asthma score (aMR 1.37, 95%CI 1.17-1.61). There was no evidence for any association between fungal and bacterial components and lung function., Conclusion: Indoor dampness was associated with microbial levels in mattress dust which in turn was positively associated with asthma symptoms.

Inverse associations have been found between exposure to bio-contaminants and asthma and allergies. The aim of this study was to prospectively assess whether early exposure to bio-contaminants in dust is associated with asthma and allergy later in childhood among children from (sub)-urban areas. In subsets of three European birth cohorts (PIAMA: n=553; INMA: n=481; and LISAplus: n=395), endotoxin, (1,3,)-β-d-glucan and extracellular polysaccharide were measured in dust from living rooms shortly after birth. Current asthma at 6 years and 10 years of age and ever asthma up to 10 years of age were assessed by parental questionnaires. Specific IgE levels at 8 years (PIAMA) and 10 years (LISAplus) were available. Adjusted, cohort-specific logistic regression analyses were performed. Higher endotoxin concentrations were positively associated with current asthma at 6 years of age in PIAMA (adjusted OR 1.96, 95% CI 1.07-3.58), but were inversely related with ever asthma up to 10 years of age in INMA (adjusted OR 0.39, 95% CI 0.16-0.94). No associations with asthma were found for LISAplus. No associations were observed with atopic sensitisation in all cohorts. All associations with (1,3)-β-d-glucan and extracellular polysaccharide were statistically nonsignificant. The suggested immunological mechanisms of early exposure to bio-contaminants with regards to asthma and allergy might be different for children growing up in (sub)-urban environments., (Copyright ©ERS 2015.)

Background: Respiratory health effects of damp housing are well recognised, but less is known about the effect of dampness and water damage in schools. The HITEA study previously reported a higher prevalence of respiratory symptoms in pupils from moisture damaged schools, but the role of specific microbial exposures remained unclear., Objectives: To study associations between school dampness, levels of fungal and bacterial markers, respiratory symptoms and lung function in children., Methods: Primary schools in Spain, the Netherlands and Finland were selected on the basis of the observed presence (n=15) or absence (n=10) of moisture, dampness and/or mould. Settled dust was repeatedly sampled in 232 classrooms and levels of 14 different microbial markers and groups of microbes were determined. Parental reports of respiratory symptoms were available from 3843 children aged 6-12 years, of whom 2736 provided acceptable forced spirometry testing. Country-specific associations between exposure and respiratory health were evaluated by multilevel mixed-effects logistic and linear regression models and combined using random-effects meta-analysis., Results: The prevalence of respiratory symptoms was higher in moisture damaged schools, being more pronounced in Finnish pupils. Effects on lung function were not apparent. Levels of microbial markers were generally higher in moisture damaged schools, varied by season and were lower in Finnish schools. Wheeze tended to be inversely associated with microbial levels. All other respiratory symptoms were not consistently associated with microbial marker levels., Conclusions: Health effects of moisture and microbial exposures may vary between countries, but this requires further study., (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: Isocyanate asthma is one of the most frequently identified forms of occupational asthma in industrialised countries. The underlying mechanisms have not been clarified. There is only limited information about the relationship between exhaled nitric oxide (eNO) and occupational exposure to isocyanates and asthma., Objectives: To investigate the association between isocyanate exposure and eNO levels in isocyanate-exposed workers and to elucidate whether eNO acts as a marker of airway inflammation controlling for smoking and atopy in an industry-wide survey., Methods: Information on estimated personal isocyanate exposure, measured eNO levels, health effects and sensitisation were analysed in 229 workers from a cross-sectional study. Univariate and multiple regression analyses were used to explore the exposure-response relationships between isocyanate exposure and eNO, stratified by smoking and atopy., Results: A marginally significant exposure-response relationship was found between isocyanate exposure and eNO in atopic, non-smokers (p=0.054). eNO was significantly associated with atopy and smoking, bronchial hyper-responsiveness (BHR), work-related conjunctivitis and rhinitis after adjustment for age, gender, atopy and smoking (p<0.05). A borderline significant association was found between eNO and asthma-like symptoms after adjustment for age, gender, atopy and current smoking (p=0.055). In a small group of isocyanate-exposed workers with positive serum-specific immunoglobulin E (IgE) antibodies to hexamethylene diisocyanate (HDI), elevated eNO levels were clearly exposure related. eNO was associated with the positive specific IgG antibodies to HDI in non-atopic, non-smokers (p=0.03)., Conclusions: Increased eNO levels may indicate increased airway inflammation in atopic, non-smokers exposed to isocyanates especially at higher levels of isocyanate exposure.