Hope for the hygiene hypothesis: when the dirt hits the fan.

The hygiene hypothesis was developed in response to data suggesting that the increase in allergic diseases as well as asthma was secondary to a reduced exposure to infectious stimuli. Indeed, the epidemiologic changes, resulting in an increase in atopic disease, have been impressive and intriguing. Furthermore, although there clearly is a genetic component to atopic diseases, genetics cannot account for a marked increase in the incidence and prevalence of allergic manifestations within a few generations. Thus, environmental factors have been suggested as responsible for the changing prevalence. There are two--not mutually exclusive--possibilities, namely, that substances that promote atopy have been added to the environment or that factors that provided protection from allergic disease were lost from the environment. Both outdoor and indoor pollution, along with a long list of other environmental factors, have been proposed. It is of interest that in many developed countries, certain types of pollution have decreased, whereas the prevalence of atopic disease has increased. In this review, we have explored a detailed analysis of a large number of studies that have focused on this issue and suggest that, although the hygiene hypothesis has merit, the stimuli responsible for the new epidemiology remain enigmatic.