Exposure and sensitization in infants and children.
The complex relationship between allergen exposure, atopic sensitization and asthma in individuals and in populations has recently been a subject of controversy. A number of studies have demonstrated that allergen exposure in sensitized asthmatic individuals increases the severity of disease. A simple dose-response relationship between mite allergen exposure and specific sensitization in infants and children has been confirmed. However, the concept that there is a direct relationship between allergen exposure and the initiation of asthma has been challenged. The relationship between allergen exposure and subsequent disease development is complex, and is confounded by a number of important factors. Populations and individuals are exposed to a mixture of several allergens, irritants and pollutants, and we know very little about the impact of these mixtures and their possible synergistic effect. The dose-response relationship between allergen exposure and allergic disease may not be linear, and may be different for different allergens. For example, a protective effect of cat ownership on sensitization and allergic disease has been reported, raising the question of whether the dose-response relationship between exposure and sensitization may be different for cat compared with mite allergen. It has been suggested that many children who are exposed to a high level of cat allergen make a modified T helper type 2 response, characterized by the presence of IgG4 antibody to cat proteins without becoming allergic (i.e. no IgE response), which could be regarded as a form of tolerance. This could explain a decreased risk of asthma in children living in homes with cats, without invoking a concept of a shift in the balance of T helper types 1 and 2 responses. Cat allergen is ubiquitous, and passive exposure (e.g. home without cats and public places) may induce specific IgE responses in non-cat owners, whereas those exposed to very high levels of cat allergen may initially mount an IgE response, which may be replaced by a modified T helper type 2 response (tolerance). It is likely that the population susceptibility to allergic sensitization and also end-organ responsiveness has altered, and allergen exposure may still be important in initiating disease in an increasingly susceptible population, although the pattern may differ for different allergens.
Custovic
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North West Lung Centre, Wythenshawe Hospital, Southmoor Road, Manchester, UK. acustovic@fs1.with.man.ac.uk
Woodcock
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D000293:Adolescent; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000829:Animals, Domestic; D001249:Asthma / Q000453:epidemiology / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000209:etiology*; D007073:Immunoglobulin E / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D015995:Prevalence; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D007073:Immunoglobulin E