To what extent is allergen exposure a risk factor for the development of allergic disease?

The role of allergen exposure in the development of allergic disease has been a matter of considerable debate, and our understanding of the importance of allergens has evolved over the last 25 years. Several observational and primary prevention studies have investigated these relationships, and different studies reported inconsistent, and sometimes opposite findings. It has to be emphasized that a clear understanding of how aeroallergen exposure occurs, and accurate and reproducible measurement of exposure are essential prerequisites for understanding the role of exposure. However, our current understanding of how we get exposed to allergens is not based on solid evidence, but on a number of assumptions, and we urgently need to develop better proxy measures (or indices) of exposure. In addition, the relative importance of the timing of exposure (e.g. early compared to exposure in later life) is unknown. It is also unclear which route of exposure is the most relevant (e.g. inhaled vs. oral vs. transcutaneous). Available data suggest that the dose-response relationship between allergen exposure and allergic disease may differ between different allergens, dose ranges and exposure patterns, and these relationships may further differ between different populations and geographical areas. It is increasingly clear that childhood asthma and atopy are not single phenotypes, and it is likely that allergen exposure has different effect on distinct subgroups under the umbrella terms of 'sensitization' and 'asthma'. Susceptibility to allergen exposure, other environmental exposures and their interactions may also differ between individuals with different genetic predispositions. However, the precise nature of these complex relationships is unclear. We need a holistic approach offered by systems biology, with integration of information on the standardized and reliable measures of exposures (including allergens and other relevant exposures) with genetic and biological data to fully understand the role of allergens in the development of allergic disease.