Total bacterial count and somatic cell count in bulk and individual goat milk around kidding: two longitudinal observational studies.

Total bacterial count (TBC) and somatic cell count (SCC) are important quality parameters in goat milk. Exceeding the bulk milk TBC (BMTBC) thresholds leads to price penalties for Dutch dairy goat farmers. Controlling these milk quality parameters can be challenging, especially around kidding. First, we describe the variation and the peaks around kidding of TBC and SCC in census data on Dutch bulk milk over the last 22 years. Second, to explore causes of these elevations, we studied the variation of TBC and SCC in individual goat milk from 3 weeks before to 5 weeks after kidding and their association with systemic response markers interferon-γ (IFN-γ), calprotectin, ß-hydroxybutyrate (BHB), body condition score (BCS) and fecal consistency. We visited 4 Dutch dairy goat farms weekly for 10 to 16 weeks around kidding. Some of the goats had been dried off, other goats were milked continuously throughout pregnancy. A total of 1,886 milk samples from 141 goats were collected for automated flowcytometric quantification of TBC and SCC measurement. IFN-γ, calprotectin and BHB were determined twice in blood of the same goats, most samples were collected after kidding. The BCS and fecal consistency were scored visually before and after kidding. We found a strong correlation between TBC and SCC (Spearman's rho = 0.87) around kidding. Furthermore, in the third week before kidding, the average TBC (5.67 log10 cfu/mL) and SCC (6.70 log10 cells/mL) were significantly higher compared with the fifth week after kidding, where the average TBC decreased to 4.20 log10 cfu/mL and the average SCC decreased to 5.92 log10 cells/mL. In multivariable linear regression models, farm and stage of lactation were significantly associated with TBC and SCC, but none of the systemic response markers correlated with TBC or SCC. In conclusion, TBC and SCC in dairy goats were high in late lactation and decreased shortly after parturition. For SCC, the dilution effect might have caused the decrease, but this was not plausible for TBC. Moreover, the excretion of bacteria and cells in goat milk was not associated with the selected systemic response markers that were chosen as a read out for general immunity status, intestinal health and metabolic diseases. Therefore, we assume that the TBC increase before kidding and the decrease after parturition is caused by other systemic, possibly hormonal, processes. To reduce BMTBC and BMSCC, it would be advisable to keep milk of goats with highest numbers of bacteria and cells in their milk out of the bulk milk during end lactation. Further studies are needed to investigate the effects of withholding this end lactation milk from the bulk tank.

[Food hypes and claims to superior health]. / Superieure gezondheid door superfoods en diëten.

Food hypes can be described as a food, nutrient or diet that is popularized by (social) media or a person with a large following, often only popular for a short period of time. We discuss the historical context of one of the most popular food hypes: weight-loss diets based on carbohydrate reduction. Supporters of these low-carbohydrate diets claim that they suppress appetite, increase energy expenditure, stimulate fat loss and are superior to other diets in terms of weight loss. We checked these claims against the available scientific evidence and put them into context of a whole-foods based approach. Studies show that low-carbohydrate diets are no more effective than other energy-restricted diets for weight loss. Furthermore, few popular weight-loss hypes are successful in the long term. We propose that the focus on macronutrients is counterproductive in efforts to promote a healthy diet and sustained weight loss.

Prevalence of non-specific health symptoms in livestock dense areas: Looking beyond respiratory conditions.

The aim of this study was to gain more insight in the association between prevalence of diverse acute non-specific symptoms (NSS) and livestock density as a possible risk factor among residents of livestock-dense and non-dense regions, taking into account socio-demographic factors and psychological morbidity. Prevalence of NSS and psychological morbidity were assessed for the year 2017, based on electronic health records from 39 general practices in the Netherlands. The study group consisted of people who lived in rural areas with high numbers of livestock (n = 74093), while the control group included people in rural areas with low numbers of livestock (n = 50139). For a large portion of the study group, exposure estimates (to livestock) were calculated. Multiple logistic multilevel regression analyses were performed. Two methods were used: 1) area comparisons between study and control areas in relation to health problems, and 2) estimates of livestock exposure (to goats, poultry, pigs, and cattle) within the study area. It was found that prevalence of diarrhea, headache, sleep disturbance, respiratory symptoms, and skin problems were higher in the study group. The data suggest that there may be a protective effect of livestock exposure: in general, there was a lower risk of NSS closer to livestock (within the exposure analyses). The study suggests that the previously identified higher risk of respiratory health problems in livestock dense areas might also apply to the prevalence of various other NSS. Longitudinal research taking into account different or more individual and contextual characteristics could possibly elucidate why prevalence of NSS in closer proximity to livestock is lower compared to people who live further away, whilst a more overarching analysis indicated that living in livestock dense areas was associated with more NSS.

Stability of individual LPS-induced ex vivo cytokine release in a whole blood assay over a five-year interval.

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-1ß 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 TNFα (r = 0.06). Cytokine reactivity measured repeatedly at the same time point showed high correlations (IL-10 r = 0.80, IL-1ß r = 0.53 and TNFα 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-1ß than for TNFα. 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.

Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion gene confirmed (mammary analogue) secretory carcinoma of salivary glands.

OBJECTIVES: In 2010, a new subtype of salivary gland cancer (SGC), (mammary analogue) secretory carcinoma (SC), was defined, characterized by the ETV6-NTRK3 fusion gene. As clinical behavior and outcome data of this histological subtype tumor are still sparse, we aimed to describe the clinicopathological course and outcome of a series of translocation positive SC patients. PATIENT AND METHODS: We re-evaluated the pathological diagnosis of a subset of SGCs, diagnosed in 4 of 8 Dutch head and neck centers. Subsequently, tumors with a morphological resemblance to SC were tested for the ETV6-NTRK3 fusion gene using RT-PCR. Furthermore, patients prospectively diagnosed with SC were included. The clinical characteristics and outcomes were retrieved from the patient files. RESULTS: Thirty-one patients with ETV6-NTRK3 fusion gene positive SC were included. The median age was 49 years, 17 patients (55%) were male. Eighteen tumors (58%) arose in the parotid gland. One patient presented with lymph node metastasis. All patients underwent tumor resection and 4 patients had a neck dissection. Four patients had re-resection and 15 patients (48%) received postoperative radiotherapy. One patient developed a local recurrence, no regional recurrences or distant metastases were observed. After a median follow-up of 49 months the 5- and 10-year overall survival were 95%, the 5- and 10-year disease free survival were 89%. CONCLUSION: The clinical course of SC is favorable with a low rate of locoregional recurrence and excellent survival. Given the low incidence of nodal metastases, elective neck treatment, i.e. surgery and/or radiotherapy, does not seem to be indicated.

Prevalence and risk factors for colonization of Clostridium difficile among adults living near livestock farms in the Netherlands.

A cross-sectional study was performed among 2494 adults not living or working on a farm to assess prevalence of Clostridium difficile (CD) colonization and risk factors in a livestock dense area. CD prevalence was 1·2%. Twenty-one persons were colonized with a toxigenic strain and nine with a non-toxigenic strain. CD-positive persons did not live closer to livestock farms than individuals negative for CD. Antibiotic exposure in the preceding 3 months was a risk factor for CD colonization (odds ratio 3·70; 95% confidence interval 1·25-10·95).

Extended-spectrum ß-lactamase- and pAmpC-producing Enterobacteriaceae among the general population in a livestock-dense area.

OBJECTIVES: In the Netherlands there is an ongoing debate regarding environmental health risks of livestock farming for neighbouring residents. This explorative study aims to determine the prevalence of carriage of extended-spectrum ß-lactamase and/or plasmid-mediated AmpC-producing Enterobacteriaceae (ESBL/pAmpC-E) in the general population living in a livestock-dense area, and to study associations between determinants, including exposure through contact with animals and the environment, and human carriage of ESBL/pAmpC-E. METHODS: A cross-sectional study was performed among 2432 adults (aged 20-72 years) in 12 temporary research centres in the south of the Netherlands, consisting of a questionnaire and analysis of a faecal sample to assess carriage of ESBL/pAmpC-E. Risk factors were analysed using logistic regression. RESULTS: The prevalence for carriage of ESBL/pAmpC-E was 4.5% (109/2432; 95% CI 3.7-5.4) ranging from 1.4% to 10.9% among the research centres. ESBL/pAmpC resistance genes were detected in Escherichia coli and Klebsiella pneumoniae isolates obtained from these 109 persons and the most common ESBL-resistance genes were blaCTX-M-15, blaCTX-M-14/17 and blaCTX-M-1, originating from 76 participants. Travel in the previous 12 months to Africa, Asia or Latin America (OR 2.82; 95% CI 1.71-4.63), having kept cows for a hobby in the previous 5 years (OR 3.77; 95% CI 1.22-11.64), usage of proton-pump inhibitors (OR 1.84; 95% CI 1.05-3.23), and living within 1000 m of a mink farm (OR 2.26; 95% CI 1.28-3.98) were identified as risk factors. Exposure to poultry was not identified as a risk factor. CONCLUSIONS: Overall, living in close proximity to livestock animals and farms does not seem to be a risk factor for carriage of ESBL/pAmpC-E.

Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations.

BACKGROUND: A high prevalence of contact dermatitis (CD) and respiratory symptoms has been observed in the construction industry, probably due to widespread exposure to irritants and allergens. It is unknown whether carriers of loss-of-function mutations in the gene encoding filaggrin (FLG), a known risk gene for eczema and asthma, are at increased risk. OBJECTIVES: To investigate associations of FLG mutations with CD and respiratory symptoms in Dutch construction workers. METHODS: A questionnaire including items on dermal and respiratory symptoms such as wheeze, shortness of breath and asthma was administered to construction workers. Total and specific serum IgE was analysed by enzyme immunoassays. Four FLG loss-of-function mutations were genotyped. CD was diagnosed by a team of a dermatologist and a clinical occupational medicine specialist using photographs of the subjects' hands and self-reported questionnaire data. RESULTS: Of the 506 participating workers, 6·3% carried at least one FLG mutation. Mild CD was diagnosed by the specialists in 34·0%, and severe CD in an additional 24·3%. CD was considered work related in 282 of 295 subjects (95·6%). Carriers of FLG variants had an increased risk of CD compared with subjects carrying wild-type alleles [mild CD: odds ratio (OR) 5·71, 95% confidence interval (CI) 1·63-20·06; severe CD: OR 8·26, 95% CI 2·32-29·39]. FLG variants and the presence of CD were not associated with respiratory symptoms and atopy. CONCLUSIONS: Contact dermatitis prevalence in construction workers is high. FLG loss-of-function mutations increase the risk of CD even further. FLG mutations were not associated with respiratory symptoms or atopy.

The relation between modeled odor exposure from livestock farming and odor annoyance among neighboring residents.

PURPOSE: Odor annoyance is an important environmental stressor for neighboring residents of livestock farms and may affect their quality of life and health. However, little is known about the relation between odor exposure due to livestock farming and odor annoyance. Even more, the relation between odor exposure and odor annoyance is rather complicated due to variable responses among individuals to comparable exposure levels and a large number of factors (such as age, gender, education) that may affect the relation. In this study, we (1) investigated the relation between modeled odor exposure and odor annoyance; (2) investigated whether other factors can affect this relation; and (3) compared our dose-response relation to a dose-response relation established in a previous study carried out in the Netherlands, more than 10 years ago, in order to investigate changes in odor perception and appreciation over time. METHODS: We used data from 582 respondents who participated in a questionnaire survey among neighboring residents of livestock farms in the south of the Netherlands. Odor annoyance was established by two close-ended questions in a questionnaire; odor exposure was estimated using the Stacks dispersion model. RESULTS: The results of our study indicate a statistically significant and positive relation between modeled odor exposure and reported odor annoyance from livestock farming (OR 1.92; 95 % CI 1.53-2.41). Furthermore, age, asthma, education and perceived air pollution in the environment are all related to odor annoyance, although they hardly affect the relation between estimated livestock odor exposure and reported odor annoyance. We also found relatively more odor annoyance reported among neighboring residents than in a previous study conducted in the Netherlands. CONCLUSIONS: We found a strong relation between modeled odor exposure and odor annoyance. However, due to some uncertainties and small number of studies on this topic, further research and replication of results is recommended.

Evaluation of Patients with Community-Acquired Pneumonia Caused by Zoonotic Pathogens in an Area with a High Density of Animal Farms.

Intensive animal farming could potentially lead to outbreaks of infectious diseases. Clinicians are at the forefront of detecting unusual diseases, but the lack of specificity of zoonotic disease symptoms makes this a challenging task. We evaluated patients with community-acquired pneumonia (CAP) with known and unknown aetiology in an area with a high livestock density and a potential association with animal farms in the proximity. Between 2008 and 2009, a period coinciding with a large Q fever outbreak in the Netherlands, patients with CAP were tested for the presence of possible respiratory pathogens. The presence and number of farm animals within 1 km of the patients' home address were assessed using geographic information system (GIS) and were compared between cases and age-matched control subjects. Of 408 patients with CAP, pathogens were detected in 275 (67.4%) patients. The presence of sheep and the number of goats were associated with CAP caused by Coxiella burnetii in a multiple logistic regression model (P < 0.05). CAP with unknown aetiology was not associated with the presence of animal farms (P > 0.10). The use of GIS in combination with aetiology of CAP could be potentially used to target diagnostics and to identify outbreaks of rare zoonotic disease.

[Genetic and environmental factors of asthma and allergy: Results of the EGEA study]. / Facteurs génétiques et environnementaux de l'asthme et de l'allergie: synthèse des résultats de l'étude EGEA.

INTRODUCTION AND METHODS: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). RESULTS: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. CONCLUSION: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.

Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children.

BACKGROUND: Emerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children. We aimed to the explore associations of prenatal exposures to a large set of environmental chemical contaminants with asthma and eczema in school-age children. METHODS: We studied 1024 mother-child pairs from Greenland and Ukraine from the INUENDO birth cohort. Data were collected by means of an interview-based questionnaire when the children were 5-9 years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and p,p'-DDE. Scores of five principal components (PCs) explaining 70% of the variance were included in multiple logistic regression models. RESULTS: In a meta-analysis that included both populations, the PC2 score, reflecting exposure to DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52-0.96). Other associations were not consistent between the two populations. In Ukrainian children, the PC3 score (DEHP) was positively associated with current wheeze (adjusted OR 1.56, 95% CI 1.03-2.37), whereas the PC5 score, dominated by perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR 0.64, 0.41-0.99). In Greenlandic children, a negative association of PC4 (organochlorines) with ever eczema (OR 0.78, 0.61-0.99) was found. CONCLUSIONS: We found limited evidence to support a link between prenatal exposure to environmental chemical contaminants and childhood asthma and eczema.

Healthy worker survivor analysis in an occupational cohort study of Dutch agricultural workers.

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.

Do young adults with childhood asthma avoid occupational exposures at first hire?

Information on the healthy worker hire effect in relation to asthma is scant. We aimed to assess whether and how childhood asthma-related characteristics (before hire) relate to occupational exposures at first hire. Analyses were conducted in 298 children examined at the first survey of the Epidemiological Study on the Genetics and Environment of Asthma (1991-1995), who reported a training period or a job at follow-up in 2003-2007 (aged 17-29 yrs; 53% males). Exposure likelihood to dust, gases and/or fumes in their first occupation was estimated by the ALOHA job exposure matrix. Asthma before the first occupation and two asthma classifications for severity (Global Initiative for Asthma 2002 guidelines) and symptoms were defined by questionnaire. In their first job, 47% of subjects were exposed. After adjustment (age, sex and education), pre-hire onset asthmatics (59%) were nonsignificantly less likely to be exposed (OR 0.67, 95% CI 0.41-1.11). Associations were stronger when considering those with severe asthma or high symptom score in childhood (OR 0.27 (95% CI 0.11-0.63) and OR 0.49 (95% CI 0.25-0.99), respectively). The association was observed in those who completed a university degree (OR 0.55, 95% CI 0.29-1.04) but not in the others (OR 0.98, 95% CI 0.44-2.22), with consistent results for all asthma characteristics. Results suggest a healthy worker hire effect in subjects with more severe or more symptomatic asthma in childhood. Education may modulate self-selection.

17q21 variants modify the association between early respiratory infections and asthma.

Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify associations between early respiratory infections and asthma. Association analysis was conducted in 499 children (268 with asthma, median age 11 yrs) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The 12-yr follow-up data were used to assess persistent or remittent asthma in young adulthood. Respiratory infection before 2 yrs of age was assessed retrospectively. For the 12 17q21 SNPs studied, the odds ratios (OR) for association between infection and early-onset asthma (age at onset

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.

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.

A cross-sectional study of lung function and respiratory symptoms among chemical workers producing diacetyl for food flavourings.

OBJECTIVES: Four diacetyl workers were found to have bronchiolitis obliterans syndrome. Exposures, respiratory symptoms, lung function and exposure-response relationships were investigated. METHODS: 175 workers from a plant producing diacetyl between 1960 and 2003 were investigated. Exposure data were used to model diacetyl exposure. Lung function and questionnaire data on respiratory symptoms were compared to a general population sample and respiratory symptoms to an internal reference group. RESULTS: Workers were potentially exposed to acetoin, diacetyl, acetaldehyde and acetic acid. Historic diacetyl exposure ranged from 1.8 to 351 mg/m(3), and from 3 to 396 mg/m(3) for specific tasks. Diacetyl workers reported significantly more respiratory symptoms compared to the general population sample (continuous trouble with breathing (prevalence ratio (PR) = 2.6; 95% CI 1.3 to 5.1), daily cough (PR = 1.5; 95% CI 1.1 to 2.1), asthma attack (ever) (PR = 2.0; 95% CI 1.2 to 3.4), doctor diagnosed asthma (PR = 2.2; 95% CI 1.3 to 3.8) and asthma attack in the last year (PR = 4.7; 95% CI 1.9 to 11.4)) and to a minimally exposed internal reference group (ever trouble with breathing (PR = 2.8; 95% CI 1.1 to 7.0) and work-related shortness of breath in the last year (PR = 7.5; 95% CI 1.1 to 52.9)). Lung function did not differ between groups. A positive relationship between exposure and FEV(1) was found. CONCLUSION: The excess of respiratory symptoms in this retrospective cohort suggests that diacetyl production poses an occupational hazard. Limited historical exposure data did not support a quantitative individual diacetyl exposure-response relationship, but our findings suggest that preventive measures are prudent.

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.

Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study.

BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We genotyped 100 new-onset asthma cases and 88 control subjects for three CD14 SNPs, three TLR2 SNPs, and two TLR4 SNPs. Atopy at baseline (defined as a positive skin prick test to one or more common inhalant allergens) was found in 17 asthma cases (17.0%) and in 17 controls (19.3%). RESULTS: The CD14/-260T allele was significantly associated with less atopy [odds ratio (OR) 0.39; 95% confidence interval (CI) 0.21-0.72, additive genetic model], whereas the CD14/-651T allele was positively associated with atopy (OR 2.53; 95% CI 1.33-4.80). Similar results were obtained by haplotype analysis. Stratified analysis by farm childhood showed stronger effects of both CD14 SNPs on atopy among farmers who were born and raised on a farm, although no significant interaction was found. No associations between CD14, TLR2, or TLR4 genotypes and new-onset asthma were found. CONCLUSION: The CD14/-260 and CD14/-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments.