Metropolitan Endotoxin Exposure, Allergy and Asthma
Metropolitan Endotoxin Exposure, Allergy and Asthma
Purpose of Review: To review the role of metropolitan endotoxin exposure in asthma and allergy, emphasizing recently published articles (i.e. April 2002-June 2003).
Recent Findings: In infants and toddlers in metropolitan communities, higher endotoxin levels in house dust are associated with less atopy and increased wheezing in infancy, but this increased risk may normalize by age 4 years. Increased endotoxin levels and exposure in metropolitan households with dogs and sometimes cats is intriguing in light of recent studies suggesting that animal exposure early in life is associated with less allergen sensitization and asthma. Dust endotoxin also appears to serve as a marker for other similar innate immune-stimulatory microbial components called pathogen-associated molecular patterns. Pathogen-associated molecular patterns, such as bacterial DNA, may augment and steer endotoxin-initiated immune responses in an immune-regulatory direction. These findings support the premise that the differences in health outcomes from endotoxin exposure are due to important moderating variables, such as age of exposure, timing of exposure relative to disease development, dose and frequency of exposure, co-exposures, and genetic predispositions in response to endotoxin.
Summary: We will discuss (1) endotoxin's ability to exacerbate established atopic disease and asthma; (2) factors influencing endotoxin levels in metropolitan homes; (3) relationships between endotoxin, pet exposure, and atopic disease; (4) endotoxin's paradoxical potential to both abrogate as well as exacerbate asthma; and (5) endotoxin's role as a marker for other similar pathogen-associated molecular patterns.
The hygiene hypothesis originally theorized that increased infections tended to protect against atopy. Over time, this theory has evolved such that harmful infections per se may not be as critical as exposure to microbial burden. Simply stated, the lack of microbial exposure in metropolitan cities is associated with increased atopic disease. Endotoxin may be a reliable marker for measuring this microbial load. Thus, the ubiquitously present endotoxin, an outer layer cell wall component of all Gram-negative bacteria, has been implicated in the development of atopic diseases and asthma. However, endotoxin's influence over atopy and asthma pathogenesis is far from clear, direct or linear. Recent studies have begun to elucidate its complex role.
Purpose of Review: To review the role of metropolitan endotoxin exposure in asthma and allergy, emphasizing recently published articles (i.e. April 2002-June 2003).
Recent Findings: In infants and toddlers in metropolitan communities, higher endotoxin levels in house dust are associated with less atopy and increased wheezing in infancy, but this increased risk may normalize by age 4 years. Increased endotoxin levels and exposure in metropolitan households with dogs and sometimes cats is intriguing in light of recent studies suggesting that animal exposure early in life is associated with less allergen sensitization and asthma. Dust endotoxin also appears to serve as a marker for other similar innate immune-stimulatory microbial components called pathogen-associated molecular patterns. Pathogen-associated molecular patterns, such as bacterial DNA, may augment and steer endotoxin-initiated immune responses in an immune-regulatory direction. These findings support the premise that the differences in health outcomes from endotoxin exposure are due to important moderating variables, such as age of exposure, timing of exposure relative to disease development, dose and frequency of exposure, co-exposures, and genetic predispositions in response to endotoxin.
Summary: We will discuss (1) endotoxin's ability to exacerbate established atopic disease and asthma; (2) factors influencing endotoxin levels in metropolitan homes; (3) relationships between endotoxin, pet exposure, and atopic disease; (4) endotoxin's paradoxical potential to both abrogate as well as exacerbate asthma; and (5) endotoxin's role as a marker for other similar pathogen-associated molecular patterns.
The hygiene hypothesis originally theorized that increased infections tended to protect against atopy. Over time, this theory has evolved such that harmful infections per se may not be as critical as exposure to microbial burden. Simply stated, the lack of microbial exposure in metropolitan cities is associated with increased atopic disease. Endotoxin may be a reliable marker for measuring this microbial load. Thus, the ubiquitously present endotoxin, an outer layer cell wall component of all Gram-negative bacteria, has been implicated in the development of atopic diseases and asthma. However, endotoxin's influence over atopy and asthma pathogenesis is far from clear, direct or linear. Recent studies have begun to elucidate its complex role.
