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It is now well established that the exposure to certain environments such as farms has the potential to protect from the development of allergies later in life. This protection is achieved when repeated exposure to the farming environment occurs early in life, but persists when children spend sufficient amount of time in contact with livestock and hay, and drink unpasteurized milk. The capacity of farm dust to protect from allergy development lies, amongst others, in the microbe composition in the farm. These protective microbes release various metabolites and cell wall components that change farmers' home dust composition, when compared to urbanized home dust. Additionally, they can colonize various barrier sites (skin, lung, intestine) in farmers' children, leading to persistent changes in the way their immune system and their barrier cells respond to environmental allergens.

Objective: In epidemiological and clinical studies, whole blood assay (WBA) has been used as a measure to characterize inter-individual differences in the cytokine response of individuals exposed to inflammatory agents, such as endotoxins. Several short-time repeatability studies have shown stable cytokine levels in individuals over periods of days, weeks or months, but little is known about the long-term stability of cytokine reactivity.Methods: We studied cytokine response levels in LPS-stimulated whole blood in a cohort of 193 farmers and agricultural industry workers at two time points with a five-year interval.Results: IL-10 and IL-1 beta responses measured with a five-year time interval showed a weak positive correlation (r = 0.22 and 0.27, respectively), whereas no correlation was observed for TNF alpha (r = 0.06). Cytokine reactivity measured repeatedly at the same time point showed high correlations (IL-10 r = 0.80, IL-1 beta r = 0.53 and TNF alpha r = 0.74), suggesting that the observed weak correlations over time are reflective of actual variations in cytokine reactivity over time.Conclusions: Repeatability of ex vivo cytokine reactivity showed to be differential for the measured cytokines, being more stable for IL-10 and IL-1 beta than for TNF alpha. However, in general, repeatability of ex vivo cytokine reactivity was weak, reflecting that cytokine reactivity can mostly be explained by (short term) intra-individual (immunological) or time varying environmental factors and less by genetic or other time-invariant factors. Therefore, WBA should be regarded as a viable tool to study relationships with current health status and exposure, and only partially as a predictor for a future response.

Airborne bacterial communities are subject to conditions ill-suited to microbial activity and growth. In spite of this, air is an important transfer medium for bacteria, with the bacteria in indoor air having potentially major consequences for the health of a building's occupants. A major example is the decreased diversity and altered composition of indoor airborne microbial communities as a proposed explanation for the increasing prevalence of asthma and allergies worldwide. Previous research has shown that living on a farm confers protection against development of asthma and allergies, with airborne bacteria suggested as playing a role in this protective effect. However, the composition of this beneficial microbial community has still not been identified. We sampled settled airborne dust using a passive dust sampler from Danish pig stables, associated farmers' homes, and from suburban homes (267 samples in total) and carried out quantitative PCR measurements of bacterial abundance and MiSeq sequencing of the V3-V4 region of bacterial 16S rRNA genes found in these samples. Airborne bacteria had a greater diversity and were significantly more abundant in pig stables and farmers' homes than suburban homes (Wilcoxon rank sum test P < 0.05). Moreover, bacterial taxa previously suggested to contribute to a protective effect had significantly higher relative and absolute abundance in pig stables and farmers' homes than in suburban homes (ALDEx2 with P < 0.05), including Firmicutes, Peptostreptococcaceae, Prevotellaceae, Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, and Lactobacillus. Pig stables had significantly lower airborne bacterial diversity than farmers' homes, and there was no discernable direct transfer of airborne bacteria from stable to home. This study identifies differences in indoor airborne bacterial communities that may be an important component of this putative protective effect, while showing that pig stables themselves do not appear to directly contribute to the airborne bacterial communities in the homes of farmers. These findings improve our understanding of the role of airborne bacteria in the increasing prevalence of asthma and allergy.

Objectives: The inhaled endotoxin is considered as a causative factor in the process of acute bronchial obstruction, which can be measured by a decrease in forced expiratory volume in 1 s (FEV1). The aim of this study was to assess endotoxin exposure among sewage treatment plant workers (STPW) and its effect on across-shift changes in respiratory airflow. Material and Methods: A group of 78 STPW from a large sewage treatment plant was studied. Inhalable dust for endotoxin assessment was collected using personal aerosol samplers. Endotoxin was assayed with the kinetic, chromogenic Limulus amebocyte lysate test. Across-shift spirometric measurements were performed on Mondays, after 2-days absence from work, with the use of portable spirometer. The forced vital capacity (FVC), and FEV1 parameters were analyzed. Multifactor regression modeling was performed to determine parameters significantly associated with endotoxin exposure. Results: The concentration of inhalable dust and endotoxin ranged from 0.01–1.38 mg/m3 and 0.68–214 endotoxin units per cubic meter of air (EU/m3), respectively. Endotoxins were characterized with the skewed distribution (arithmetic mean (AM) = 38.8 EU/m3, geometric mean (GM) = 15.4 EU/m3, geometric standard deviation (GSD) = 4.21). Through the use of multifactor analysis, which excluded the main confounders (inhalable dust and smoking habit) it was found that, despite low levels of endotoxin, it had significant impact on the observed across-shift decline in FEV1 (p = 0.044). For this parameter, the regression slope was additionally calculated (r = –0.017, p = 0.071). Conclusions: Relatively low levels of endotoxin among sewage treatment plant workers may cause small, but significant across-shift declines in FEV1. The observed relationship was independent of organic dust concentrations and smoking habit. The respiratory protection should be provided for STPW. Award Number 5D43 TW000621-10 from the Fogarty International Center

Background: Greenhouse workers are exposed to organic dusts, and they are thereby at risk of developing airway disorders. This study aims to measure personal endotoxin exposure, assess respiratory symptoms and measure fractional exhaled nitric oxide (FeNO) among female flower farm workers in Ethiopia. Methods: A cross-sectional study involving female workers (n = 248) from four flower farms was conducted. The workers were interviewed for respiratory symptoms using a standard questionnaire. Workers from two of these farms also participated in personal endotoxin sampling (46 workers, 75 measurements) on glass fiber filters (0.2 μm pore size) inside conductive 25 mm Millipore cassettes for sampling of the “total dust” fraction. They also participated in FeNO (n = 114) measurements with a portable electrochemistry-based sensor. Chi-square and independent t-tests were used to compare categorical and continuous variables respectively. A mixed-effects model was used to analyze exposure determinants. Results: Endotoxin exposure had a geometric mean (GM) of 22.8 endotoxin units (EU)/m3 with a maximum of 180 EU/m3. Greenhouse workers had significantly higher endotoxin exposure than workers outside the greenhouses (GM= 26.7 vs. 19.3 EU/m3 respectively; p < 0.05). The mean age of the workers was 24 years, and their mean working time in the flower farm was 21 months. Greenhouse workers had higher prevalence of self-reported respiratory symptoms than those outside greenhouses. However, after adjusting for education only blocked nose remained significant. The FeNO concentration ranged 5–166 ppb (GM = 14 ppb). Two workers had FeNO concentration above 50 ppb. FeNO levels differs significantly between the farms but there was no difference between workers inside and outside greenhouses. Conclusion: Greenhouse workers at flower farms had higher prevalence of blocked nose than workers outside, which may indicate the presence of rhinitis. Endotoxin exposure was low. There were few workers with objective signs of airway inflammation; this might be because the mean working time in the greenhouses was only two years. We suggest further studies to evaluate the effect of longer employment and exposure time as well as to investigate possible exposure to pesticides and other components in the bio-aerosols. publishedVersion

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.

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.

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.

Objectives: Workers in many industries are exposed to endotoxins, which may cause adverse health effects. In exposure assessment, information about exposure variability is essential. However, variability in exposure has rarely been investigated for biological agents and more specifically for endotoxin. Therefore, variance components and determinants of exposure were studied in a large database with >2000 endotoxin measurements. Methods: Data from 10 individual studies were combined to create a database with 2010 personal inhalable dust and endotoxin measurements, of which 1650 were repeated measurements. Exposure groups were defined based on job codes. Between- and within-worker variance components were estimated for different grouping strategies, and determinants of exposure were studied using mixed effects models. Results: Inhalable dust and endotoxin exposure levels are summarized for 46 industries and 4 broadly defined sectors. The between-worker variability exceeded the within-worker variability overall and within sectors and subsectors, and variance components were larger for endotoxin than for dust. Between-worker variability also exceeded within-worker variability in nearly half of the exposure groups based upon industries or job code within industries for endotoxin exposure and in 10% of the groups for dust exposure. Among other things, dustiness of the process, contact with animals, bulk production, presence of plant material or a cyclic process appeared as determinants of exposure, which largely explained the between-worker variability. Conclusions: Exposure groups were much less homogeneous for endotoxin exposure than for dust exposure. This is distinctly different than for chemical exposure. Large variability in measured exposure levels is inherent to endotoxin exposure, which is caused in part by determinants that influence growth of microorganisms. These findings have major consequences for the design of future occupational intervention and epidemiological studies. The measurement effort needs to be greater than exposure assessment for chemical agents which demonstrate lower exposure variability, especially when evaluating endotoxin exposure for compliance testing. The established determinants of exposure give direction for potential exposure control, although more information about determinants of day-to-day variability in exposure is still needed to be able to effectively control endotoxin exposure. © The Author 2008. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Objectives High microbial exposures in farmers and agricultural workers are associated with less atopy. Although it has been speculated that healthy worker survival could be an explanation, this has not been studied so far. Therefore, we investigated the presence of healthy worker survival in a five-year follow-up study of an occupational cohort of Dutch farmers and agricultural industry (company) workers. Methods We compared baseline demographic characteristics, respiratory health, atopy and endotoxin exposure of 259 workers followed up with 124 workers lost to follow-up. Additionally, baseline health status of 31 participants who had changed to lower exposure jobs at follow-up was compared to those with similar or higher exposure jobs at follow-up. Results In general, no major healthy worker survival effect was found. Nonetheless, small differences were observed between subjects included in follow-up and those lost to follow-up. Those lost to follow-up were older, had a lower peak expiratory flow, and were less often raised on a farm. Company workers lost to follow-up with a farm childhood had more often self-reported allergy, but this was not observed for subjects with atopic sensitization or other respiratory symptoms. No differences were found for any of the studied characteristics in participants with lower exposure at follow-up compared to participants with similar or higher exposure at follow-up. Conclusions No major healthy worker survival is present in this organic dust exposed cohort. Differences between participants lost to follow-up and participants included in follow-up with regard to health characteristics are small and unlikely to explain the previously reported inverse associations between endotoxin exposure and atopy. Electronic supplementary material The online version of this article (doi:10.1007/s00420-015-1047-9) contains supplementary material, which is available to authorized users.

Studies have presented conflicting associations between cat allergen exposure and sensitisation and atopic disease. We therefore investigated the association between the observed domestic cat allergen level and cat sensitisation in young children in four study populations from three European countries. We recruited children from a nested case-control study, which is composed of four ongoing birth cohorts conducted in three European countries. Children at 2-4 years of age in the four cohorts who were sensitised to cat allergens (n = 106) were compared with 554 non-sensitised children (controls). House dust samples were collected when the children were 5 to 7 years old, and cat allergen levels were measured in ng/g dust and ng/m(2) surface area. In the German study population we found a positive association between domestic cat allergen in house dust and cat sensitisation (OR (CI) = 3.01 (1.16, 7.99)) while in the Swedish study population, we found a negative association (OR (CI) = 0.41 (0.16, 0.98)). No association was found in the Dutch study population (OR (CI) = 0.83 (0.22, 2.93)). Looking into the family history of cat keeping, we found the lowest prevalence of cat sensitisation in children who were cat owners at the age of blood sampling (11%) and the highest prevalence was found in those who have had a cat but not anymore, at the age of blood sampling (41%). The mixed results may be explained by differences in age and avoidance patterns. (C) 2007 Elsevier GmbH. All rights reserved.