Gert Doekes

Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm

Background Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non‐farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the ‘protective’ effect of a farm environment can also be found in adults.

Fungal extracellular polysaccharides in house dust as a marker for exposure to fungi: Relations with culturable fungi, reported home dampness, and respiratory symptoms☆☆☆

BACKGROUND Epidemiologic studies have demonstrated an association between indoor fungal growth and respiratory symptoms. However, in only a few studies was fungal exposure actually measured. OBJECTIVE The purpose of this study was to evaluate the measurement by enzyme immunoassay of extracellular polysaccharides of Aspergillus and Penicillium species (EPS-Asp/Pen ) in house dust as a marker for fungal exposure and to study the relations between EPS-Asp/Pen levels and home dampness and respiratory symptoms in children. METHODS Extracts of house dust samples from bedroom and living room floors and mattresses from homes of 31 children with chronic respiratory symptoms and 29 children with no chronic respiratory symptoms were analyzed for EPS-Asp/Pen. RESULTS EPS-Asp/Pen were readily detectable (40 to 46,513 nanogram equivalent/g dust) in 161 house dust extracts, with highest concentrations in living room floor dust. EPS-Asp/Pen levels were 2 to 3 times higher on carpeted floors than on smooth floors. EPS-Asp/Pen were significantly correlated with total culturable fungi (r = 0.3 to 0.5) and with house dust mite allergens (r = 0.3 to 0.5). EPS-Asp/Pen levels in living room floor dust were positively associated with occupant-reported home dampness. This was not observed for EPS-Asp/Pen in bedroom floor and mattress dust. EPS-Asp/Pen levels in living room floor dust were positively associated with respiratory symptoms. EPS-Asp/Pen in bedroom floor and mattress dust showed a reversed association with respiratory symptoms, possibly because of allergen-avoidance measures taken in the bedroom. CONCLUSION The enzyme immunoassay for fungal EPS-Asp/Pen may be a useful method for exposure assessment of indoor fungi.

Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study

Background Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents.

Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens : results from a pooled study

BACKGROUND Recent studies in a few industries have shown that the likelihood of IgE-mediated sensitization increases with increasing exposure. The shape of the exposure-response relationships and modification by age, sex, and smoking habit has hardly been studied. OBJECTIVE The purpose of this study was to determine exposure sensitization relationships for rat sensitization and to evaluate the influence of atopy, smoking habits, and sex. METHODS Data from 3 cross-sectional studies in The Netherlands, the United Kingdom, and Sweden were used and involved 1062 animal laboratory workers. Selection criteria were harmonized, and this resulted in a study population of 650 animal laboratory workers (60.6% female) with less than 4 years of exposure. Air allergen levels were assessed previously and converted on the basis of an interlaboratory allergen analysis comparison. Available sera were analyzed for the presence of specific antibodies against common allergens (house dust mite, cat, dog, and grass and birch pollen) and work-related allergens (rat and mouse urinary proteins). Questionnaire items on work-related respiratory symptoms, hours worked with rats per week, job performed, smoking habits, and sex were used in this analysis RESULTS The prevalence of work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as specific IgE to 1 of the common allergens). The sensitization rate increased with increasing air allergen exposure. Atopic workers exposed to low levels of allergen had a more than 3-fold increased sensitization risk compared with nonexposed atopic workers. For atopic subjects, the risk increased little with increasing exposure, whereas for nonatopic subjects, a steadily increasing risk was observed. Smoking and sex did not modify the sensitization risk. CONCLUSION Rat urinary allergen-sensitization risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitization risk at low allergen exposure levels.

Bacterial and fungal components in house dust of farm children, Rudolf Steiner school children and reference children – the PARSIFAL Study

Background:  Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. It has been suggested that the enhanced exposure to endotoxin is an important protective factor of farm environments. Little is known about exposure to other microbial components on farms and exposure in anthroposophic families.

Evaluation of a low-cost electrostatic dust fall collector for indoor air endotoxin exposure assessment.

ABSTRACT Exposure to endotoxin in home environments has become a key issue in asthma and allergy research. Most studies have analyzed floor or mattress dust endotoxin, but its validity as a proxy for airborne exposure is unknown, while active airborne dust sampling is not feasible in large-scale population studies because of logistic and financial limitations. We therefore developed and evaluated a simple passive airborne dust collection method for airborne endotoxin exposure assessment. We explored an electrostatic dust fall collector (EDC), consisting of a 42- by 29.6-cm-sized folder with four electrostatic cloths exposed to the air. The EDC was tested during two 14-day periods in seven nonfarm and nine farm homes and in farm stables. In parallel, active airborne dust sampling was performed with Harvard impactors and floor dust collected by vacuuming, using nylon sampling socks. The endotoxin levels could be measured in all EDC cloth extracts. The levels (in EU/m2) between EDCs used simultaneously or in different sampling periods in the same home correlated strongly (r > 0.8). EDC endotoxin also correlated moderately to strongly (r = 0.6 to 0.8) with the endotoxin measured by active airborne dust sampling and living room floor dust sampling and—in farm homes—with the endotoxin captured by the EDC in stables. In contrast, endotoxin levels measured by floor dust sampling showed only a poor correlation with the levels measured by active airborne dust sampling. We therefore conclude that measuring endotoxin levels with the EDC is a valid measure of average airborne endotoxin exposure, while reproducibility over time is at least equivalent to that of reservoir dust analyses.

Occupational respiratory allergy in bakery workers: a review of the literature.

Bakers asthma has long been recognized as a serious disease among workers in the bakery industry and the number of cases with bakers asthma is steadily increasing. This paper presents a review of the available literature on bakers allergy with a special focus on the allergens involved, the epidemiologic research and issues on exposure assessment, evidence of exposure-response-relationships, and possible prevention strategies. A large number of potential allergens have been identified and are described here. At present little is known about the incidence of bakers allergy. On the other hand, a large number of cross-sectional studies have been performed, showing that sensitization and work-related symptoms are common among bakery workers. Only atopy and exposure level have consistently been reported as determinants of this occupational disease. Age, gender, and smoking habits do not seem to be associated with sensitization or work-related respiratory symptoms. Recently, immunochemical methods have been developed to measure specific allergens in the bakery industry, which have been used to unravel the role of allergen exposure in the development of bakers asthma. Clear exposure-response-relationships have been found. The implications of these recent findings for prevention strategies and standard setting are discussed.

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.

Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood

BACKGROUND European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. OBJECTIVE We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. METHODS From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctors diagnosis. RESULTS Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. CONCLUSIONS Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.

Cat and dog allergy and total IgE as risk factors of laboratory animal allergy

BACKGROUND Laboratory animal workers are at high risk of developing occupational allergy. In many cases the severity of allergy symptoms makes further work with laboratory animals impossible. OBJECTIVE This study was designed to estimate prevalence rates of sensitization and symptoms of allergy in a population of laboratory animal workers and to determine the association between various host factors and these prevalence rates. METHODS A cross-sectional survey was undertaken in 540 workers at eight facilities in the Netherlands. All participants completed a questionnaire and underwent skin prick testing with common and occupational allergens. In addition, total and specific IgE measurements were obtained. RESULTS Prevalence rates of allergy symptoms caused by working with rats and mice were 19% and 10%, respectively. Symptoms, especially chest tightness, were strongly related to sensitization. Rat and mouse allergy, defined as symptoms of allergy accompanied by specific atopic sensitization, were highly associated with elevated total IgE, reported adverse reactions, and positive skin prick test responses to common allergens. This relationship could be explained by a response to cat or dog allergens. CONCLUSIONS Allergy to cats or dogs seemed to be an important risk factor for laboratory animal allergy, whereas allergy to pollen or house dust mite, in the absence of cat and dog allergy, appeared to be insignificant. More conclusive evidence about cat and dog allergy preceding laboratory animal allergy can only be provided after analysis of follow-up data.