SYMPOSIUM
the possibility of recall bias. Moreover, they have held up when adjustments have been made for parental atopy, as it was thought those families with allergy would be less likely to have pets.37-43
Proposed mechanisms have
included the possibility that pet expo- sure may lead to increased exposure to infectious agents such as Toxoplas- ma and Bartonella, which may skew to Th1 development, increased en- dotoxin exposure, and the induction of an altered Th2 response, i.e., the production of IgG antibodies without development of an allergic response or asthma.44-49 With fewer people now living on
farms, it has been of interest to exam- ine farm exposure and its association with decreased atopic disease preva- lence in many North American coun- tries, Europe, and Australia.50-52
A Ger-
man study of 5- to 7-year-old children showed that within the same villages, those children raised on a farm ver- sus those not raised on a farm had lower rates of allergic rhinitis.50
Even
in larger scale studies that adjusted for potential confounding variables including pet exposure, parental his- tory of allergy, number of siblings, and severe respiratory infections in child- hood, living on a farm in childhood was associated with a reduced risk of atopic sensitization as an adult.53
No
protective effect was seen on asthma or wheezing. Another study found that clini- cal disease indeed may be modified by farm exposures and that timing is important. Reidler et al. found chil- dren younger than 1 year who were exposed to stables and those who consumed farm milk demonstrated less asthma, hay fever, and atopic sensitization than children ages 1 to 5 years who were similarly exposed.54 In contrast to some earlier studies that didn’t show a protective effect of farm exposure on asthma, Ege et al. showed that children raised on farms had lower asthma and atopy preva- lence and that they were exposed to a greater variety of environmental mi-
croorganisms than the children in the reference group.55 The reasons that farm exposures
may protect against atopy remain un- clear, but it is thought that exposure to livestock and to materials found in high amounts in stables (molds, am- monia, feces, animal proteins, con- stituents of feed, and endotoxin) may render individuals less susceptible to the development of Th2 responses. Moreover, the exposure to raw milk, which contains more gram-negative bacteria and lipopolysaccharide than pasteurized milk, may lead to altera- tions in the commensal gut flora that are not favorable to the development of Th2 responses.54,56
Endotoxin has
been found in higher levels in house dust and mattresses of children raised in farm families,56
and some reports
suggest higher levels of endotoxin exposure may downregulate Th2 im- mune responses.57
POLLUTION
A big undue consequence of the push for industrialization has been air pol- lution, which has been implicated as a cause of increasing asthma rates, but the literature also is somewhat controversial. If pollution was a sig- nificant driver, one would expect to see higher asthma rates in large cit- ies with air pollution compared with other less-polluted areas. However, as Platts-Mills points out, asthma also has increased in areas were pollu- tion is not a problem, such as coastal towns in New Zealand, or in other areas where pollution has decreased, such as London.7 In Katowice, Poland, where pol-
lution is a significant problem, likely from coal smoke, higher asthma rates were not demonstrated.7,58
However,
studies have shown associations par- ticularly with diesel exhaust particles and atopic sensitization. Diesel ex- haust particles have been thought to act as adjuvants to the immune sys- tem,59
and some studies have shown
specific synergistic effects between diesel exhaust particles and ragweed
February 2017 TEXAS MEDICINE 57
pollen with increases in IgE and mRNA for Th2 cytokines.60
These
studies suggest an environmental fac- tor such as diesel exhaust particles may cause genetically susceptible individuals to become sensitized to allergens that ordinarily would not af- fect them.61
CONCLUSION
Although many have sought to offer explanations for the relatively rapid rise in atopic diseases, it is clear that complex interactions between genetic factors and multiple environmental factors are likely contributing to this trend. Strachan’s early hypothesis re- garding the role of family size and ex- posure to early childhood infections in the development of atopic diseases has clearly evolved to integrate the possible effects of hygiene, eradica- tion of parasitic infections, immuniza- tions, improvements in home heating and ventilation, dust mite exposure, breastfeeding duration, diet, parental smoking, pollution, and exposure to pets and farm animals. However, as most of our current understanding still comes from observational and ep- idemiologic studies, further prospec- tive investigations will be needed to help uncover which of these genetic and environmental factors are indeed the causes behind the increase in al- lergic disease. Once this information is known, preventive strategies hope- fully can be developed.
Sheenal V. Patel, MD, is a second-year allergy and immunology fellow at The University of Texas Medical Center at Dallas.
Southwestern
Rebecca S. Gruchalla, MD, is a profes- sor of internal medicine and pediatrics and director of the Division of Allergy and Immunology at UT-Southwestern.
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