Respiratory diseases and allergy in farmers working with livestock: a EAACI position paper.

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.

Allergy and respiratory health effects of dampness and dampness-related agents in schools and homes: a cross-sectional study in Danish pupils.

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 (zFEV1 ), forced vital capacity (zFVC) and the ratio zFEV1 /zFVC 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 (ß-coef. -0.71; 95% CI -1.17 to -0.23) and zFVC (ß-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 zFEV1 (ß-coef. -0.22; 95% CI -0.42 to -0.02) and zFEV1 /zFVCratio (ß-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.

Determinants of house dust, endotoxin, and ß-(1→3)-D-glucan in homes of Danish children.

Little is known about the geographic variation and determinants of bacterial endotoxin and ß-(1,3)-D-glucan in Danish house dust. In a population of 317 children, we: (i) described loads and concentrations of floor dust, endotoxin, and ß-(1→3)-D-glucan and (ii) their correlations and (iii) assessed their determinants; (iv) Finally, we compared our findings with previous European studies. Bedroom floor dust was analyzed for endotoxin content by the kinetic limulus amoebocyte lysate assay and for ß-(1→3)-D-glucan by the inhibition enzyme immunoassay. The parents answered questions regarding potential determinants. We found: geometric means (geometric standard deviations) 186 mg/m(2) (4.3) for dust; 5.46 × 10(3) EU/m(2) (8.0) and 31.1 × 10(3) EU/g (2.6) for endotoxin; and 142 µg/m(2) (14.3) and 0.71 × 10(3) µg/g (7.3) for ß-(1→3)-D-glucan. High correlations (r > 0.75) were found between floor dust and endotoxin and ß-(1→3)-D-glucan loads, while endotoxin and ß-(1→3)-D-glucan concentrations were moderately correlated (r = 0.36-0.41) with the dust load. Having a carpet was positively associated with dust load and with endotoxin and ß-(1→3)-D-glucan concentrations. Pet keeping, dwelling type, and dwelling location were determinants of endotoxin concentrations. No other determinants were associated with ß-(1→3)-D-glucan concentrations. Compared with other European studies, we found lower ß-(1→3)-D-glucan loads and concentrations but higher endotoxin loads and concentrations suggesting a geographically determined different composition of Danish floor dust compared with other European regions.

Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology & Air Pollution.

Exposure to high molecular weight sensitizers of biological origin is an important risk factor for the development of asthma and rhinitis. Most of the causal allergens have been defined based on their reactivity with IgE antibodies, and in many cases, the molecular structure and function of the allergens have been established. Significant information on allergen levels that cause sensitization and allergic symptoms for several major environmental and occupational allergens has been reported. Monitoring of high molecular weight allergens and allergen carrier particles is an important part of the management of allergic respiratory diseases and requires standardized allergen assessment methods for occupational and environmental (indoor and outdoor) allergen exposure. The aim of this EAACI task force was to review the essential points for monitoring environmental and occupational allergen exposure including sampling strategies and methods, processing of dust samples, allergen analysis, and quantification. The paper includes a summary of different methods for sampling and allergen quantification, as well as their pros and cons for various exposure settings. Recommendations are being made for different exposure scenarios.

Quantity and diversity of environmental microbial exposure and development of asthma: a birth cohort study.

BACKGROUND: Early-life exposure to environmental microbial agents may be associated with the development of allergies. The aim of the study was to identify better ways to characterize microbial exposure as a predictor of respiratory symptoms and allergies. METHODS: A birth cohort of 410 children was followed up until 6 years of age. Bacterial endotoxin, 3-hydroxy fatty acids, N-acetyl-muramic acid, fungal extracellular polysaccharides (EPS) from Penicillium and Aspergillus spp., ß-D-glucan, ergosterol, and bacterial or fungal quantitative polymerase chain reactions (qPCRs) were analyzed from dust samples collected at 2 months of age. Asthma, wheezing, cough, and atopic dermatitis were assessed using repeated questionnaires. Specific IgEs were determined at the age of 1 and 6 years. RESULTS: Only few associations were found between single microbial markers and the studied outcomes. In contrast, a score for the total quantity of microbial exposure, that is, sum of indicators for fungi (ergosterol), Gram-positive (muramic acid) bacteria, and Gram-negative (endotoxin) bacteria, was significantly (inverted-U shape) associated with asthma incidence (P < 0.001): the highest risk was found at medium levels (adjusted odds ratio (aOR) 2.24, 95% confidence interval (95% CI) 0.87-5.75 for 3rd quintile) and the lowest risk at the highest level (aOR 0.34, 95% CI 0.09-1.36 for 5th quintile). The microbial diversity score, that is, sum of detected qPCRs, was inversely associated with risk of wheezing and was significantly (inverted-U shape) associated with sensitization to inhalant allergens. CONCLUSION: Score for quantity of microbial exposure predicted asthma better than single microbial markers independently of microbial diversity and amount of dust. Better indicators of total quantity and diversity of microbial exposure are needed in studies on the development of asthma.

Endotoxin levels in settled airborne dust in European schools: the HITEA school study.

Indoor exposure to microbial agents is known to influence respiratory health. Besides home exposure, exposure in schools can affect respiratory health. In this study, we measured endotoxin in settled dust in primary schools in three European countries from three different geographical regions with different climates. Our aim was to characterize endotoxin levels in primary schools and evaluate associations with potential determinants. Endotoxin levels were repeatedly assessed in 23 schools in Spain (n = 7), the Netherlands (n = 10), and Finland (n = 6) using electrostatic dustfall collectors. In total, 645 measurements were taken in 237 classrooms. Endotoxin levels differed significantly between countries; Dutch schools had the highest levels, while Finnish schools showed the lowest levels. In each country, differences in endotoxin levels were observed between schools and over the sampling periods. Estimates improved after adjustment for sampling period. Factors affecting endotoxin levels in a school differed per country. In general, endotoxin levels were higher in lower grades and in classrooms with higher occupancy. School endotoxin levels may contribute significantly to total endotoxin exposure in children and teachers. As the correlation between the repeated measurements is reasonable, single endotoxin measurements form a reasonable basis for estimating annual endotoxin levels in schools.

Endotoxin, extracellular polysaccharides, and ß(1-3)-glucan concentrations in dust and their determinants in four European birth cohorts: results from the HITEA project.

UNLABELLED: Early-life exposure to microbial agents may play a protective role in asthma and allergies development. Geographical differences in the prevalence of these diseases exist, but the differences in early-life indoor microbial agent levels and their determinants have been hardly studied. We aimed to describe the early-life levels of endotoxin, extracellular polysaccharides (EPS), and ß(1-3)-glucans in living room dust of four geographically spread European birth cohorts (LISA in Germany, PIAMA in the Netherlands, INMA in Spain, and LUKAS2 in Finland) and to assess their determinants. A total of 1572 dust samples from living rooms of participants were analyzed for endotoxin, Penicillium/Aspergillus EPS, and ß(1-3)-glucans. Information on potential determinants was obtained through questionnaires. Concentrations of endotoxin, EPS, and ß(1-3)-glucans were different across cohorts. Concentrations of endotoxin and EPS were respectively lower and higher in INMA than in other cohorts, while glucans were higher in LUKAS2. Season of sampling, dog ownership, dampness, and the number of people living at home were significantly associated with concentrations of at least one microbial agent, with heterogeneity of effect estimates of the determinants across cohorts. In conclusion, both early-life microbial exposure levels and exposure determinants differ across cohorts derived from diverse European countries. PRACTICAL IMPLICATIONS: This study adds evidence of variability in the levels of indoor endotoxin, extracellular polysaccharide, and ß(1-3)-glucans across four geographically spread European regions. Furthermore, we observed heterogeneity across regions in the effect of exposure determinants. We hypothesize that the variations observed in our study may play a role in the differences in asthma and allergies prevalences across countries.

Exposure to microbial agents in house dust and wheezing, atopic dermatitis and atopic sensitization in early childhood: a birth cohort study in rural areas.

BACKGROUND: Early-life exposure to environmental microbial agents may be associated with development of wheezing and allergic diseases. OBJECTIVE: To assess the association of microbial exposure in rural homes with the risk of asthma, wheezing, atopic dermatitis and sensitization. METHODS: Birth cohorts of rural children (n = 1133), half from farmer families, were followed up from birth to 2 years of age by questionnaires in five European centres. Endotoxin and extracellular polysaccharides (EPS) of Penicillium and Aspergillus spp. were determined from living room floor and mother's mattress dust samples collected at 2 months of age. Specific IgE against 19 allergens was measured at 1 year of age. Discrete-time hazard models, generalized estimations equations (GEE) and logistic regression were used for statistical analyses. RESULTS: The incidence of asthma was inversely associated with the amount of dust (adjusted odds ratio (aOR) 0.73, 95% CI 0.58-0.93) and the loads (units/m(2)) of EPS (aOR 0.75, 95% CI 0.55-1.04) and endotoxin (aOR 0.79, 95% CI 0.60-1.05) in the mother's mattress. Similar associations were seen with wheezing and with living room floor dust. The microbial markers were highly correlated and their effects could not be clearly separated. The inverse associations were seen especially among non-farmers. The risk of sensitization to inhalant allergens increased with increasing endotoxin exposure from mattress dust. No associations were observed with concentrations (units/g) or with atopic dermatitis. CONCLUSION AND CLINICAL RELEVANCE: The amount and microbial content of house dust were inversely associated with asthma and wheezing, but due to high correlations between microbial agents and amount of dust, it was not possible to disentangle their individual effects. New ways to better measure and represent exposure to environmental microbes, including indexes of biodiversity, are needed especially among farmers.

Geographical variation and the determinants of domestic endotoxin levels in mattress dust in Europe.

UNLABELLED: Endotoxin exposures have manifold effects on human health. The geographical variation and determinants of domestic endotoxin levels in Europe have not yet been extensively described. To investigate the geographical variation and determinants of domestic endotoxin concentrations in mattress dust in Europe using data collected in the European Community Respiratory Health Survey follow-up (ECRHS II). Endotoxin levels were measured in mattress dust from 974 ECRHS II participants from 22 study centers using an immunoassay. Information on demographic, lifestyle, and housing characteristics of the participants was obtained in face-to-face interviews. The median endotoxin concentration in mattress dust ranged from 772 endotoxin units per gram (EU/g) dust in Reykjavik, Iceland, to 4806 EU/g in Turin, Italy. High average outdoor summer temperature of study center, cat or dog keeping, a high household crowding index, and visible damp patches in the bedroom were significantly associated with a higher endotoxin concentrations in mattress dust. There is a large variability in domestic endotoxin levels across Europe. Average outdoor summer temperature of study center, which explains only 10% of the variation in domestic endotoxin level by center, is the strongest meteorological determinant. The observed variation needs to be taken into account when evaluating the health effects of endotoxin exposures in international contexts. PRACTICAL IMPLICATIONS: The incoherent observations of the health effects of endotoxin may be partly owing to the geographical heterogeneity of endotoxin exposure. Therefore, the observed variation should be considered in further studies. Measurements of indoor endotoxin are recommended as an indicator for the level of exposures of individual domestic environments.

Respiratory health and endotoxin: associations and modification by CD14/-260 genotype.

Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14. Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels varied from 0.1 to 402.6 EU · mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels. In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.

IgG4 antibodies against rodents in laboratory animal workers do not protect against allergic sensitization.

BACKGROUND: The modified Th2 response, defined as an IgG4 response in the absence of IgE, is suggested to protect against the development of allergic sensitization. However, studies suggesting this protective effect all had a cross-sectional design, making it impossible to study the development of both responses. AIM OF THE STUDY: We aimed to study the dynamics in IgG4 antibodies in relation to allergic sensitization in an occupational cohort of starting laboratory animal workers. Moreover, we studied the relation between exposure, antibody responses, atopy and self reported allergic symptoms. METHODS: A total of 110 starting animal workers were followed for 2 years. IgG4 antibodies against rats and mice were assessed. Workers were tested for allergic sensitization and exposure to animal allergens was estimated. Symptom status was assessed using questionnaires. RESULTS: Rat and mouse specific IgG4 antibodies were present before the development of allergy and did not significantly change over time. Allergic sensitization was related to exposure and atopic status but high levels of IgG4 showed no protective effect. In contrary, workers that developed mouse specific sensitization during follow up had higher levels of mouse specific IgG4. Symptoms were related to allergic sensitization and IgG4 levels did not influence that relationship. CONCLUSIONS: IgG4 antibodies are present before IgE antibodies develop and IgG4 levels are stable over time. In our occupational cohort, the modified Th2 response had no protective effect on development of sensitization or allergic symptoms.

Childhood asthma and early life exposure to indoor allergens, endotoxin and beta(1,3)-glucans.

BACKGROUND: Divergent results have been reported regarding early life exposure to indoor environmental agents and the risk of asthma and allergic sensitization later in life. OBJECTIVE: To assess whether early exposure to indoor allergens, beta(1,3)-glucans and endotoxin modifies the risk of allergic diseases at 10 years of age. METHODS: The concentrations of mite, cat and dog allergens, endotoxin and beta(1,3)-glucans were determined in dust from the homes of 260 two-year-old children with lung function measured at birth (tidal flow volume loops) in the Environment and Childhood Asthma study in Oslo. At 10 years, the health status was assessed in a follow-up study including a structured interview of the parents and an extended clinical examination. RESULTS: Cat and dog keeping at 2 years of age was reported in 6.5% and 5.5% of the families, respectively. Mite allergens were detected in only 4/260 dust samples. The adjusted odds ratio for asthma at age 10 was 1.20 (95% confidence interval: 1.01-1.43) and 1.22 (1.02-1.46) for bronchial hyperresponsiveness (BHR) per 10 microg/g dust increase in cat allergen exposure at 2 years of age. No association was seen with allergic sensitization. Moreover, endotoxin and beta(1,3)-glucan exposure did not modify the risk of asthma or allergic sensitization. None of the measured environmental factors were associated with lung function at 10 years of age or a relative change in lung function from birth. CONCLUSION: In a community with a low prevalence of pet keeping and low mite allergen levels, exposure to cat allergens early in life increased the risk of late childhood asthma and BHR, but not the risk of allergic sensitization. No risk modification was seen for dog allergens, endotoxin and beta(1,3)-glucans.

International variations in associations of allergic markers and diseases in children: ISAAC Phase Two.

BACKGROUND: Circulating allergen-specific IgE (sIgE) and skin prick tests (SPT) are used to define atopy. Downregulation of local inflammatory responsiveness has been proposed to explain a low prevalence of positive SPTs in less affluent countries. We analysed the association between SPTs, total and allergen-specific IgE and their relationships to allergic symptoms in centres with diverse living conditions. METHODS: Cross-sectional studies of stratified random samples of 8 to 12-year-old children (n = 7461) used the standardized methodology of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema were ascertained by parental questionnaires. Skin examination, hypertonic saline bronchial challenge, six aeroallergen SPTs and measurements of serum total IgE and sIgE were performed. RESULTS: In nonaffluent countries, a higher proportion of children with positive SPT had no detectable sIgE (range 37-61%) than in affluent countries (0-37%). Total serum IgE was associated with all disease outcomes among children with both positive SPT and sIgE (P < 0.001), but only with self-reported eczema in children with negative SPTs and negative sIgE. CONCLUSIONS: The international pattern of discordance between SPT and sIgE results did not support the downregulation hypothesis. Among children with no evidence of sensitization to common aeroallergens, increased total IgE contributes little to the risk of wheeze and rhinitis in the general population but may play a role in eczema.

Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure.

Not everyone exposed to endotoxin develops respiratory symptoms, even at very high exposure levels. The aim was to investigate whether ex vivo lipopolysaccharide (LPS)-induced cytokine release may be predictive of individual sensitivity to occupational endotoxin exposure. In 412 agricultural workers, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 release was measured in supernatants from LPS-stimulated whole blood, lung function was measured, and respiratory symptoms were assessed by questionnaire. For each cytokine, the population was dichotomised into low and high responders according to median cytokine concentrations. Endotoxin exposure levels were determined based on 249 personal exposure measurements. High IL-10 responders had a higher prevalence of airway symptoms than low IL-10 responders (odds ratios between 2.03 and 5.10; p<0.05). TNF-alpha response was positively, but not significantly, associated with symptoms, whereas no relationship was found between IL-1beta response and symptoms. For all three cytokines, subjects with above-median responses showed significant positive dose-response relationships between endotoxin exposure and asthma symptoms, and significant associations between endotoxin exposure and a lower forced expiratory volume in 1 s (p<0.05). In contrast, exposure-response relationships were weak and statistically nonsignificant for low responders. The ex vivo inflammatory response to LPS reflects, to a large extent, whether individuals are susceptible to adverse respiratory effects induced by high occupational endotoxin exposure.

Different respiratory phenotypes are associated with isocyanate exposure in spray painters.

Associations have been observed between exposure to isocyanates, consisting mainly of oligomers, and respiratory symptoms and isocyanate specific sensitisation in spray painters. The aim of the present study was to assess associations between isocyanate exposure and more objective respiratory effect measures such as bronchial hyperresponsiveness (BHR), baseline spirometry and exhaled nitric oxide (eNO) in a subset of spray painters. Methacholine challenge and eNO measurements were performed in 229 workers. Questionnaires and blood samples were obtained. Specific immunoglobulin (Ig)E and IgG to hexamethylene di-isocyanate were assessed in serum using various assays. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and time-activity information. Workers with higher isocyanate exposure were more often hyperresponsive (prevalence ratio comparing the 75th versus 25th percentile of exposure 1.8). In addition, significant exposure-related decreased forced expiratory volume in one second (FEV(1)), FEV(1)/forced vital capacity ratio and flow-volume parameters independent of BHR were found. BHR was more prevalent among sensitised workers. This was statistically significant for only IgG-ImmunoCAP (Phadia, Uppsala, Sweden) positive workers. eNO was not associated with exposure although slightly elevated eNO levels in specific IgG positive subjects were found. The current study provides evidence that exposure to isocyanate oligomers is related to asthma with bronchial hyperresponsiveness as a hallmark, but also shows independent chronic obstructive respiratory effects resulting from isocyanate exposure.

Exhaled nitric oxide in endotoxin-exposed adults: effect modification by smoking and atopy.

OBJECTIVES: Occupational exposure to endotoxin is associated with non-allergic asthma and other airway inflammatory reactions. Little is known about the role of mucosal nitric oxide (NO) production in endotoxin-induced airway inflammation. The objective was to explore exposure-response relationships between occupational endotoxin exposure and fractional concentrations of exhaled NO (FE(NO)) and study the role of FE(NO) as an intermediate factor in the relationship between endotoxin exposure and asthma-like symptoms. METHODS: FE(NO) was measured online in 425 farmers and agricultural processing workers. For each participant (cumulative) endotoxin level was modelled on the basis of 249 personal measurements and job history. Atopy was assessed as specific serum IgE to common inhalant allergens, and other health data and personal characteristics by standardised questionnaires. RESULTS: A significant positive exposure-response relationship was found between endotoxin and FE(NO), but only in non-atopic, non-smoking subjects (p = 0.001). FE(NO) was significantly associated with current wheeze and other asthma-like symptoms irrespective of atopy and current smoking. Associations between endotoxin exposure and symptoms changed slightly after adjusting for FE(NO). CONCLUSIONS: A positive association was found between occupational endotoxin exposure and exhaled nitric oxide in non-smoking, non-atopic adults. Increased FE(NO) was associated with asthma-like symptoms, but the role of FE(NO) as an intermediate factor between endotoxin exposure and airway symptoms appears to be limited.

The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms.

BACKGROUND: Little is known about the asthma candidate gene neuropeptide S receptor 1 (NPSR1) in relation to environmental exposures, but recent evidences suggest its role as an effect modifier. OBJECTIVES: To explore the interaction between NPSR1 polymorphisms and environmental exposures related to farming lifestyle and to study the in vitro effects of lipopolysaccharide (LPS) stimulation on NPSR1 expression levels. METHODS: We studied 3113 children from PARSIFAL, a European cross-sectional study on environmental/lifestyle factors and childhood allergy, partly focused on children brought up on a farm. Information on exposures and outcomes was primarily obtained from parental questionnaires. Seven tagging polymorphisms were analysed in a conserved haplotype block of NPSR1. Multivariate logistic regression was used to evaluate a multiplicative model of interaction. NPSR1 protein and messenger RNA (mRNA) levels in monocytes were measured after LPS stimulation by fluorescence activated cell sorting (FACS) and quantitative real-time polymerase chain reaction (PCR). RESULTS: A strong interaction was seen between current regular contact to farm animals and several NPSR1 polymorphisms, particularly rs323922 and rs324377 (p<0.005), with respect to allergic symptoms. Considering the timing of initiation of such current regular farm animal contact, significant interactions with these and two additional polymorphisms (SNP546333, rs740347) were revealed. In response to LPS, NPSR1-A protein levels in monocytes were upregulated (p = 0.002), as were NPSR1-A mRNA levels (p = 0.02). CONCLUSIONS: The effect of farm animal contact on the development of allergic symptoms in children is modified by NPSR1 genetic background.

Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II).

BACKGROUND: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. OBJECTIVES: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. METHODS: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. RESULTS: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. CONCLUSION: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.

Exposure-response analysis of allergy and respiratory symptoms in endotoxin-exposed adults.

The objective of the present study was to investigate exposure-response relationships between current endotoxin exposure and allergic and respiratory symptoms in adults, taking into account farming exposures during childhood. A cross-sectional study was conducted among 877 Dutch farmers and agricultural industry workers in 2006. Based on 249 full-shift personal airborne endotoxin samples, a job-exposure matrix was constructed to assign endotoxin exposure levels to all participants. Associations between endotoxin exposure and questionnaire data on symptoms were studied by multiple logistic regression. Adjusted odds ratios (OR) for an interquartile range increase in endotoxin level were elevated for respiratory symptoms such as wheezing (OR 1.41 (95% confidence interval 1.16-1.72)), wheezing with shortness of breath (1.50 (1.18-1.90)) and daily cough (1.29 (1.03-1.62)). In contrast, endotoxin was strongly associated with a decreased prevalence of hay fever (0.62 (0.49-0.78)). Workers who had grown up on a farm had a lower prevalence of hay fever, but no evidence was found of effect modification by farm childhood. In conclusion, occupational endotoxin exposure in adulthood is associated with an increased risk of asthma-like symptoms but a reduced prevalence of hay fever.

Inhalable beta(1->3)glucans as a non-allergenic exposure factor in Dutch bakeries.

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.