Opinions of children about participation in medical genetic research

Aims: The objective was to evaluate children's opinions about their participation in a large research project. Methods: Polish children between 6 and 14 years of age completed a questionnaire about their participation in the Polish Gabriel study (which aims to identify genetic and environmental causes of asthma). In total 706 questionnaires were collected. Results: Children's main motivation for participation was wanting to know whether they were healthy or not. Most children could think of no reasons to reconsider participation. Children aged 6-10 years might reconsider participating because they did not know what was going to happen. A third of the children were not informed by anybody about the study. Especially the youngest children indicated a need for a tailored letter (42%). The youngest children were less often asked for their opinion about participation. All children preferred that both parents and children are asked for consent or assent. Children who were not informed or not asked for their opinion seemed less emotionally involved in the study. Conclusion: While researchers and parents tend to focus their information provision to older children and include them in decision-making, especially the younger children expressed a need for more tailored information and involvement in their participation in research. Copyright © 2010 S. Karger AG, Basel

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

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

Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell‐mediated immunity in children

Background: Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression. Aims: In a 7-month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein-conjugate vaccine in children (2–11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC-O; n = 21) or a hydrocortisone ointment regimen (HC-O; n = 111). Methods: TAC-O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein-conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non-atopic dermatatits children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre 8 at the week 5 visit. Results: The response rate (patients with SBA titre 8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC-O, HC-O and control groups, respectively. Conclusions: The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC-O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell-mediated immunity.T Hofman, N Cranswick, P Kuna, A Boznanski, T Latos, M Gold, D F Murrell, K Gebauer, U Behre, E Machura, J Ólafsson, Z Szala

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

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

Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies

BACKGROUND: Evidence exists that a farming environment in childhood may provide protection against atopic respiratory disease. In the GABRIEL project based in Poland and Alpine regions of Germany, Austria and Switzerland, we aimed to assess whether a farming environment in childhood is protective against allergic diseases in Poland and whether specific exposures explain any protective effect. METHODS: In rural Poland, 23 331 families of schoolchildren completed a questionnaire enquiring into farming practices and allergic diseases (Phase I). A subsample (n = 2586) participated in Phase II involving a more detailed questionnaire on specific farm exposures with objective measures of atopy. RESULTS: Farming differed between Poland and the Alpine centres; in the latter, cattle farming was prevalent, whereas in Poland 18% of village farms kept ≥1 cow and 34% kept ≥1 pig. Polish children in villages had lower prevalences of asthma and hay fever than children from towns, and in the Phase II population, farm children had a reduced risk of atopy measured by IgE (aOR = 0.72, 95% CI 0.57, 0.91) and skin prick test (aOR = 0.65, 95% CI 0.50, 0.86). Early-life contact with grain was inversely related to the risk of atopy measured by IgE (aOR = 0.66, 95% CI 0.47, 0.92) and appeared to explain part of the farming effect. CONCLUSION: While farming in Poland differed from that in the Alpine areas as did the exposure-response associations, we found in communities engaged in small-scale, mixed farming, there was a protective farming effect against objective measures of atopy potentially related to contact with grain or associated farm activities

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

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

Safety and Efficacy of Pimecrolimus in Atopic Dermatitis: A 5-Year Randomized Trial

BACKGROUND AND OBJECTIVES: Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs. METHODS: A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear). RESULTS: Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity. CONCLUSIONS: Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children

Gene-environment interaction for childhood asthma and exposure to farming in Central Europe

BACKGROUND: Asthma is a disease in which both genetic and environmental factors play important roles. The farming environment has consistently been associated with protection from childhood asthma and atopy, and interactions have been reported with polymorphisms in innate immunity genes. OBJECTIVE: To detect gene-environment interactions for asthma and atopy in the farming environment. METHODS: We performed a genome-wide interaction analysis for asthma and atopy by using 500,000 genotyped single nucleotide polymorphisms (SNPs) and farm-related exposures in 1708 children from 4 rural regions of Central Europe. We also tested selectively for interactions between farm exposures and 7 SNPs that emerged as genome-wide significant in a large meta-analysis of childhood asthma and 5 SNPs that had been reported previously as interacting with farm exposures for asthma or atopy. RESULTS: Neither the asthma-associated SNPs nor the SNPs previously published for interactions with asthma showed significant interactions. The genome-wide interaction study did not reveal any significant interactions with SNPs within genes in the range of interacting allele frequencies from 30% to 70%, for which our study was well powered. Among rarer SNPs, we identified 15 genes with strong interactions for asthma or atopy in relation to farming, contact with cows and straw, or consumption of raw farm milk. CONCLUSION: Common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy, but rarer variants, particularly of the glutamate receptor, metabotropic 1 gene, may do so. Given the limited statistical power of our study, these findings should be interpreted with caution before being replicated in independent farm populations