Newsletter 2012/2013:

A Great Big Thank You to all of you for continuing to take part in the Manchester Asthma and Allergy Study. This round of the study means we would like to see your child between their 13th and 16th birthday. We are analyzing the data collected from all the previous visits to try to get a better idea of why some children get asthma and allergies and others don’t. We know that these diseases occur because of both genetic and environmental factors, but it is very complicated trying to work out which environmental exposures are important in different people.

For example, we have investigated whether attending nursery affects the likelihood of developing wheeze in school age children. Overall we found that attending nursery was associated with a reduced risk of wheezing (at age 5 years) and that the protective effect appeared strongest if children started nursery between 6 and 12 months of age (1). We subsequently found that the protective effect of nursery was seen only in the ~ 75 % of children with a particular genetic marker (known as TLR2/-16934). Those who carried a different version of this gene appeared to be at increased risk of allergies and wheeze if they attended nursery (2). We cannot recommend that parents use this type of information to try to prevent allergies and asthma at this stage as it is too preliminary. However, this does confirm our suspicion that the environment affects different people in different ways and what appears protective for one person may be harmful for another. The interaction between our genes and our environment is hugely complex and we are continuing to study these effects.

A new gene for eczema (called Filaggrin) was discovered in 2006; we have found that children who carry ‘weak’ copies of this gene (about 10% of the population) are about twice as likely to get eczema as a baby, particularly if they have a cat (3). Again, it is too early to use these kind of results to change the way we live; they need to be confirmed in other studies first. We have also been involved in a very large project which included results from thousands of children from around the world to identify genes that increase the risk of eczema. Three new genes were identified, but lots of work is needed before this sort of information can help children suffering from eczema (4).

We have been investigating peanut allergy and thanks to your valuable contribution to this study have helped to develop a new and more accurate blood test (5). A positive result to this new test (called Ara h 2) can diagnose true peanut allergy with more than 95% certainty. The standard skin tests and blood tests for peanut allergy were positive in lots of children who could safely eat peanuts (particularly those with hay fever). Following on from our results in MAAS, this new test is now widely used in clinics across Europe.

At the age 11 visit, we asked you to complete extra questionnaires about your journey to school and also about your home environment as we are studying the effects of both indoor and outdoor pollutants on the risk of asthma and lung function. We had to check that the questionnaires that we used give us good information about pollution, particularly Nitrogen dioxide (NO2) by getting another group children of the same age to help us, as we didn’t want to give you extra things to do! These children wore pollution monitors on their lapels for 24 hours and also completed the questionnaires so that we can compare measured levels to the levels we would estimate using the questionnaire (6). Fortunately, we found that the questionnaires give a good indication of exposure to pollutants and so we are in the process of analyzing the effects of pollutant exposure on lung function and risk of asthma.

Many of the parents of our MAAS children attended clinics to have skin testing and lung function measurements too. We have now completed some genetic testing and have shown that variation in genes on Chromosome 17 are associated with asthma, especially in cigarette smokers (7).

As many of you will remember we have been asking you for a number of years now about what your children eat. From the dietary questionnaires that you have completed we have been able to look at specific nutrients consumed, for example vitamins and minerals. We have found that children who eat more vitamins, particularly β-carotene (the strongly-coloured red-orange pigment abundant in plants and fruits) seem to be at less risk of becoming allergic (8). We are now looking at patterns of diet, rather than individual nutrients, and suspect we will have some interesting results to share with you soon.
Other researchers have suggested that the increase in asthma that we have seen in our population is related to the increase in obesity that has also occurred. We have investigated this within the Manchester Asthma and Allergy Study (9). We found that increasing weight was associated with an increased risk of wheeze, but as children got older the effect was only seen in girls. We found that children who were overweight at 3 years of age were at higher risk of both persistent wheeze and persistent eczema (up to age 8 years). It is hard to be sure as yet whether children who are overweight are more likely to get wheezy or whether wheezy children are more likely to get overweight. We hope that by continuing to follow up everyone we will be able to answer questions like this.

References
1. Day –care attendance, position in sibship, and early childhood wheezing: a population-based birth cohort study. J Allergy Clin Immunol. 2008; 122(3):500-6.e5.
2. Effect of day care attendance on sensitization and atopic wheezing differs by Toll-like receptor 2 genotype in 2 population-based birth cohort studies. Custovic A, Rothers J, Stern D, Simpson A, Woodcock A, Wright AL, Nicolaou NC, Hankinson J, Halonen M, Martinez FD. J Allergy Clin Immunol. 2011 Feb;127(2):390-397.
3. Bisgaard H, Simpson A, Palmer CNA, Bønnelykke K, Mclean I, Mukhopadhyay S, Pipper CB, Halkjaer LB, Lipworth B, Hankinson J, Woodcock A, Custovic A. Gene-environment interaction in the onset of eczema in infancy: Filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Medicine 2008;5(6):0934-40.
3. Bisgaard H, Simpson A, Palmer CNA, Bønnelykke K, Mclean I, Mukhopadhyay S, Pipper CB, Halkjaer LB, Lipworth B, Hankinson J, Woodcock A, Custovic A. Gene-environment interaction in the onset of eczema in infancy: Filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Medicine 2008;5(6):0934-40.
4. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. The Genetics of Overweight Young Adults (GOYA) Consortium, Strachan DP, Martin NG, Jarvelin MR, Heinrich J, Evans DM; the EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium, Weidinger S. Nat Genet. 2011 Dec 25. doi: 10.1038/ng.1017.
5. Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component resolved diagnostics. J Allergy Clin Immunol 2010 Jan; 125 (1): 191-7.el-133.
6. Mölter A, Lindley S, de Vocht F, Agius R, Kerry G, Johnson K, Ashmore M, Terry A, i Dimitroulopoulou S, Simpson A. Performance of a microenviromental model for estimating personal NO2 exposure in children. Atmospheric Environment 2012 in press.
7. Marinho S, Marsden P, Smith J, Custovic A, Simpson A.17q12-21 Variants Are Associated With Asthma and Interact With Active Smoking in an Adult Population from the UK. Annals of Allergy, Asthma & Immunology 2012 in press.
8. Dietary antioxidant intake, allergic sensitization and allergic diseases in young children. Allergy.2009 Dec; 64 (12):1766-72.
9 .Body mass index in young children and allergic disease: gender differences in a longitudinal study. Clin Exp Allergy 2011; 41 (1):78-85