The hapten-atopy hypothesis III: the potential role of airborne chemicals

Abstract

One explanation for the large increase in the prevalence of atopic disease in developed countries during the last 50 years is the 'hygiene hypothesis'. This proposes that a reduced exposure to pathogenic microorganisms at a key period(s) during development results in the maintenance or acquisition of an atopic phenotype. Alternatively, or additionally, we have postulated that increased exposure to chemicals generally, and to irritant/haptenic chemicals in particular, during critical windows of maternal pregnancy/early life have also contributed to changes in the prevalence of atopic disease. Having previously reviewed the potential roles of oral and cutaneous exposure to chemicals on the subsequent diagnosis of atopic disease, we here consider possible evidence of a role for exposure to airborne chemicals as a contributory factor in acquired susceptibility to atopic allergy. After controlling for known confounders, five specific maternal occupations during pregnancy have been implicated as being associated with subsequent atopic disease in the offspring. Each of these occupations is characterized by high and persistent exposure to airborne chemicals. High-level exposure to volatile organic compounds in the domestic environment, either during pregnancy or in early life, is also associated with development of childhood atopic disease. Similarly, sustained exposure to airborne chlorinated chemicals from swimming pools during childhood has been associated with the development of atopic allergy. A possible immunological basis for these associations is that exposure to certain airborne chemicals, even at low levels, can result in the delivery of 'danger' signals that, in turn, bias the immune response towards the selective induction or maintenance of preferential T helper 2-type immune responses consistent with the acquisition of allergic sensitization.

Indoor total volatile organic compounds exposure at 6 months followed by atopic dermatitis at 3 years in children

“…It may have been insufficient to elicit some relationships or confirm some results that were close to the significant level. Higher air humidity and higher temperature also correlated with higher levels of these volatile organic chemicals , we, however, could not control for these factors in our study. The health data were self‐reported which could have been a limiting factor in the present study.…”

T helper cell 2 immune skewing in pregnancy/early life: chemical exposure and the development of atopic disease and allergy

“…We have postulated that personal exposure to chemicals through the skin, gut and airways, and, in particular, to chemical allergens (haptens) or to irritant chemicals, has contributed to the remarkable increase in prevalence in atopic allergy that has been witnessed in recent decades in Westernized countries (the ‘hapten–atopy’ hypothesis) . Although chemical allergens cause skin sensitization and allergic contact dermatitis, and irritant chemicals cause irritant contact dermatitis, both of which are associated primarily with Th1 activity, repeated low‐dose exposure via the skin to such chemicals may result in a Th2‐type immunological bias .…”

“…Although chemical allergens cause skin sensitization and allergic contact dermatitis, and irritant chemicals cause irritant contact dermatitis, both of which are associated primarily with Th1 activity, repeated low‐dose exposure via the skin to such chemicals may result in a Th2‐type immunological bias . This is probably mediated via innate ‘danger’ signalling rather than by a direct influence on the adaptive immune system . Chemical allergens and irritants can produce oxidative stress leading to release of damage‐associated molecular pattern molecules that, like PAMPS, are known to serve as danger signals and to be required for the elicitation of optimal adaptive immune responses …”

“…One of the commonly employed animal models of AD involves repeated topical exposure to a chemical allergen that causes a gradual shift from Th1 dominance to Th2 dominance . It has also been argued that airway exposure to chemicals may induce a Th2 shift . Recent investigations have demonstrated that experimental food allergy and gut‐associated Th2 skewing is promoted by low‐dose oral hapten exposure .…”

“…There is emerging evidence that certain chemical exposure over the critical time of maternal pregnancy and early life is associated with subsequent atopic disease. Ingestion of haptenic drugs in maternal pregnancy and early life is associated with the development of atopic disease . A large study found that five maternal occupations during pregnancy, all associated with exposure to specific airborne chemicals, significantly correlated with atopic disease at the age of 18 years in the subsequent child .…”