Recent Research Activities from the EOM Working Groups

Sensitisation to common allergens and respiratory symptoms in endotoxin exposed workers: a pooled analysis

Ioannis Basinas, Vivi Schlünssen, Dick Heederik, Torben Sigsgaard, Lidwien A M Smit, Sadegh Samadi, Øyvind Omland, Charlotte Hjort, Anne Mette Madsen, Simon Skov, Inge M Wouters

Occup Environ Med 2012;69:99-106 doi:10.1136/oem.2011.065169

Objective To test the hypotheses that current endotoxin exposure is inversely associated with allergic sensitisation and positively associated with non-allergic respiratory diseases in four occupationally exposed populations using a standardised analytical approach.

Methods Data were pooled from four epidemiological studies including 3883 Dutch and Danish employees in veterinary medicine, agriculture and power plants using biofuel. Endotoxin exposure was estimated by quantitative job-exposure matrices specific for the study populations. Dose–response relationships between exposure, IgE-mediated sensitisation to common allergens and self-reported health symptoms were assessed using logistic regression and generalised additive modelling. Adjustments were made for study, age, sex, atopic predisposition, smoking habit and farm childhood. Heterogeneity was assessed by analysis stratified by study.

Results Current endotoxin exposure was dose-dependently associated with a reduced prevalence of allergic sensitisation (ORs of 0.92, 0.81 and 0.66 for low mediate, high mediate and high exposure) and hay fever (ORs of 1.16, 0.81 and 0.58). Endotoxin exposure was a risk factor for organic dust toxic syndrome, and levels above 100?EU/m3 significantly increased the risk of chronic bronchitis (p<0.0001). Stratification by farm childhood showed no effect modification except for allergic sensitisation. Only among workers without a farm childhood, endotoxin exposure was inversely associated with allergic sensitisation. Heterogeneity was primarily present for biofuel workers.

Conclusions Occupational endotoxin exposure has a protective effect on allergic sensitisation and hay fever but increases the risk for organic dust toxic syndrome and chronic bronchitis. Endotoxin's protective effects are most clearly observed among agricultural workers.

The combined effects of family size and farm exposure on childhood hay fever and atopy

Jon Genuneit, David P. Strachan, Gisela Büchele, Juliane Weber, Georg Loss , Barbara Sozanska, Andrzej Boznanski, Elisabeth Horak, Dick Heederik, Charlotte Braun-Fahrländer, Erika von Mutius

Pediatric Allergy and Immunology, Volume 24, Issue 3, pages 293–298, May 2013

Background: Exposure to farming environments and siblings is associated with reduced risks of childhood hay fever and atopy. We explored the independence and interaction of these protective effects in the GABRIELA study.

Methods: Questionnaire surveys on farming, asthma, and allergies were conducted in four central European areas among 79,888 6–12-yr-old children. Aeroallergen-specific serum IgE was measured in a stratified sample of 8,023 children. Multiple logistic regression was used to compare gradients in allergy prevalence by sibship size across three categories of exposure to farming environments.

Results: The prevalence of hay fever ranged from 2% (95% confidence interval 1.6%; 2.7%) among farmers' children with more than two siblings to 12% (11.2%; 13.0%) among children with no farm exposure and no siblings. Farming families were larger on average. More siblings and exposure to farming environments independently conferred protection from hay fever and atopy. There was no substantial effect modification between family size and exposure to farming environments. The odds ratios for hay fever per additional sibling were 0.79 among unexposed non-farm children, 0.77 among farm-exposed non-farm children, and 0.72 among children from farming families (2df interaction test: p = 0.41).

Conclusion: The inverse association of exposure to farming environments with hay fever is found in all sizes of family, with no substantial tendency to saturation or synergism. This suggests that different biological mechanisms may underlie these two protective factors. Combinations of a large family and exposure to farming environments markedly reduce the prevalence of hay fever and indicate the strength of its environmental determinants.

Protection from childhood asthma and allergy in Alpine farm environments - the GABRIEL Advanced Studies

Sabina Illi, PhD, Martin Depner, PhD, Jon Genuneit, MD, Elisabeth Horak, MD, Georg Loss, MS, Christine Strunz-Lehner, MPH, Gisela Büchele, PhD, Andrzej Boznanski, MD, PhD, Hanna Danielewicz, MD, Paul Cullinan, MD, Dick Heederik, PhD, Charlotte Braun-Fahrländer, MDd, Erika von Mutius, MD, MSc

Journal of Allergy and Clinical Immunology, Volume 129, Issue 6, June 2012, Pages 1470–1477.e6

Background: Studies on the association of farm environments with asthma and atopy have repeatedly observed a protective effect of farming. However, no single specific farm-related exposure explaining this protective farm effect has consistently been identified.

Objective: We sought to determine distinct farm exposures that account for the protective effect of farming on asthma and atopy.

Methods: In rural regions of Austria, Germany, and Switzerland, 79,888 school-aged children answered a recruiting questionnaire (phase I). In phase II a stratified random subsample of 8,419 children answered a detailed questionnaire on farming environment. Blood samples and specific IgE levels were available for 7,682 of these children. A broad asthma definition was used, comprising symptoms, diagnosis, or treatment ever.

Results: Children living on a farm were at significantly reduced risk of asthma (adjusted odds ratio [aOR], 0.68; 95% CI, 0.59-0.78; P < .001), hay fever (aOR, 0.43; 95% CI, 0.36-0.52; P < .001), atopic dermatitis (aOR, 0.80; 95% CI, 0.69-0.93; P = .004), and atopic sensitization (aOR, 0.54; 95% CI, 0.48-0.61; P < .001) compared with nonfarm children. Whereas this overall farm effect could be explained by specific exposures to cows, straw, and farm milk for asthma and exposure to fodder storage rooms and manure for atopic dermatitis, the farm effect on hay fever and atopic sensitization could not be completely explained by the questionnaire items themselves or their diversity.

Conclusion: A specific type of farm typical for traditional farming (ie, with cows and cultivation) was protective against asthma, hay fever, and atopy. However, whereas the farm effect on asthma could be explained by specific farm characteristics, there is a link still missing for hay fever and atopy.

The management of work-related asthma guidelines: a broader perspective

Xaver Baur, Tor Brøvig Aasen, P. Sherwood Burge, Dick Heederik, Paul K. Henneberger, Piero Maestrellif, Vivi Schlünssen, Olivier Vandenplas and Dennis Wilken

Eur Respir Rev June 1, 2012 vol. 21 no. 124 125-139

The aim of the European Respiratory Society work-related asthma guidelines is to present the management and prevention options of work-related asthma and their effectiveness.

Work-related asthma accounts for 5–25% of all adult asthma cases and is responsible for a significant socioeconomic burden. Several hundred occupational agents, mainly allergens but also irritants and substances with unknown pathological mechanisms, have been identified as causing work-related asthma.

The essential message of these guidelines is that the management of work-related asthma can be considerably optimised based on the present knowledge of causes, risk factors, pathomechanisms, and realistic and effective interventions. To reach this goal we urgently require greatly intensified primary preventive measures and improved case management. There is now a substantial body of evidence supporting the implementation of comprehensive medical surveillance programmes for workers at risk. Those workers who fail surveillance programmes need to be referred to a clinician who can confirm or exclude an occupational cause. Once work-related asthma is confirmed, a revised risk assessment in the workplace is needed to prevent further cases. These new guidelines confirm and extend already existing statements and recommendations. 

We hope that these guidelines will initiate the much-needed research that is required to fill the gaps in our knowledge and to initiate substantial improvements in preventative measures.