The GABRIEL Advanced Surveys: study design, participation and evaluation of bias

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease. The GABRIEL Advanced Surveys have a multi-phase stratified design. In a first-screening phase, a comprehensive population-based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103,219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15,255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in-depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895). Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour. The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective 'farm effect' on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research.

[Alban Köhler (1874-1947): Inventor of grid therapy]

Grid (or sieve) therapy ("Gitter-" oder "Siebtherapie"), spatially fractionated kilo- and megavolt X-ray therapy, was invented in 1909 by Alban Köhler, a radiologist in Wiesbaden, Germany. He tested it on several patients before 1913 using approximately 60-70kV Hittorf-Crookes tubes. Köhler pushed the X-ray tube's lead-shielded housing against a stiff grid of 1 mm-square iron wires woven 3.0-3.5mm on center, taped tightly to the skin over a thin chamois. Numerous islets unshielded by iron in the pressure-blanched skin were irradiated with up to about 6 erythema doses (ED). The skin was then thoroughly cleansed, disinfected, and bandaged; delayed punctate necrosis healed in several weeks. Although grid therapy was disparaged or ignored until the 1930s, it has been used successfully since then to shrink bulky malignancies. Also, advanced cancers in rats and mice have been mitigated or ablated using Köhler's concept since the early 1990s by unidirectional or stereotactic exposure to an array of nearly parallel microplanar (25-75μm-wide) beams of very intense, moderately hard (median energy approximately 100 keV) synchrotron-generated X rays spaced 0.1-0.4mm on center. Such beams maintain sharp edges at high doses well beneath the skin yet confer little toxicity. They could palliate some otherwise intractable malignancies, perhaps in young children too, with tolerable sequelae. There are plans for such studies in larger animals.