Protection from childhood asthma and allergy in Alpine farm environments—the GABRIEL Advanced Studies Sabina Illi, PhD, Martin Depner, PhD, Jon Genuneit,

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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, MSc, Christine Strunz-Lehner, MPH, Gisela Büchele, PhD, Andrzej Boznanski, MD, PhD, Hanna Danielewicz, MD, Paul Cullinan, MD, Dick Heederik, PhD, Charlotte Braun- Fahrländer, MD, Erika von Mutius, MD, MSc Journal of Allergy and Clinical Immunology Volume 129, Issue 6, Pages 1470-1477.e6 (June 2012) DOI: 10.1016/j.jaci.2012.03.013 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Study population and design. *Completed phase I recruiting questionnaire. †Completed phase I recruiting questionnaire and signed a consent form for analyses and all additional investigations in phase II. §Random selection stratified for exposure. ‡Completed phase II questionnaire. ¶Completed phase II questionnaire and participated in blood sampling and analysis of specific IgE levels. Journal of Allergy and Clinical Immunology 2012 129, 1470-1477.e6DOI: (10.1016/j.jaci.2012.03.013) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Types of farms based on farm characteristics. Results of LCA with 3-class solution are shown. Farm characteristics assessed in the phase I recruitment questionnaire are shown (n = 9611 farm children). Journal of Allergy and Clinical Immunology 2012 129, 1470-1477.e6DOI: (10.1016/j.jaci.2012.03.013) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Timing of the first exposure to farm characteristics. Most children experienced their first exposure through their mothers in pregnancy. *Computations are based on 5 groups of children ever exposed to cows, cow sheds, straw, barns, fodder storage rooms, or farm milk. The bars show the proportion of children with first-time contact with the respective farm exposure per age category. Proportions of the 5 age categories add up to 100%. Journal of Allergy and Clinical Immunology 2012 129, 1470-1477.e6DOI: (10.1016/j.jaci.2012.03.013) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Specific farm exposures that best explain the overall effect of farming. Results of multivariate stepwise weighted regression models. *Mutually adjusted and additionally adjusted for center and potential confounders (family atopy, ≥2 siblings, sex, maternal smoking in pregnancy, and parental education). §Compared with the reference group (neither contact with cows nor straw). Odds ratios for intermediate categories (contact with cows or straw) are shown in Table E2. Journal of Allergy and Clinical Immunology 2012 129, 1470-1477.e6DOI: (10.1016/j.jaci.2012.03.013) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Frequency of exposure and risk of asthma, hay fever, and atopic sensitization. Frequency of exposure is defined as the maximum exposure of the 3 time periods (pregnancy, first year of life, and second to third year of life). aORs and 95% CIs are adjusted for farming and potential confounders. Journal of Allergy and Clinical Immunology 2012 129, 1470-1477.e6DOI: (10.1016/j.jaci.2012.03.013) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions