Something old, something new: indoor endotoxin, allergens and asthma

Abstract

Endotoxin and allergen exposure have been explored in the context of asthma for more than a century. Building upon a pyramid of knowledge are recent observations that provide new insights to the effect of these exposures on the development of asthma. Some of these studies challenge some previously held concepts of the role of these exposures in asthma inception. Indoor allergens are well established as the basis of inflammation in sensitised asthmatics, contributing to disease severity. Then does greater exposure to indoor allergens cause allergen sensitisation and asthma as well? While risk of sensitisation to house dust mites generally increases with higher levels of exposure, this does not seem to hold for cats, where higher levels of cat allergen exposure are associated with less sensitisation. Indeed, several recent studies suggest that early childhood exposure to animals, as indoor pets or in farming stables, are associated with a lower prevalence of asthma, hay fever, and inhalant allergen sensitisation. Endotoxin in asthma provides a similar paradox. Endotoxin is a potent immune-stimulatory component of the bacterial cell wall of all gram-negative bacteria. As such, endotoxin is ubiquitous in our environment. Endotoxin exposure has been well demonstrated to underlie "Monday Asthma" or byssinosis in cotton workers, and has since emerged as a frequent cause of asthma-like symptoms in a wide range of occupational settings. Asthmatics are particularly sensitive to inhaled endotoxin, and inhalation induces both immediate and sustained airflow obstruction. The paradox of endotoxin exposure is that higher levels of exposure in early life might mitigate the development of allergy and persistent asthma. With endotoxin exposure being significantly higher in homes with animals and in farming households, where allergy and asthma are less likely to develop, endotoxin and other microbial exposures in early life may keep allergen sensitisation and asthma from developing by promoting Th1-type immune development. These observations, consistent with the "Hygiene Hypothesis" of allergy and asthma, are an encouraging glimpse of the potential for early immune modulatory approaches to asthma therapy and prevention.