SYMPOSIUM
fections or other environmental fac- tors that would lead to decreased pro- duction of cytokines that favor Th1 development, a predominance of Th2 cells may develop, leading to atopic disease.
FAMILY SIZE AND EARLY CHILDHOOD INFECTIONS
Strachan’s observations published in 1989 with respect to family size be- came the initial basis for his expla- nation of the rise in atopic diseases, later known as “the hygiene hypoth- esis.” He studied a British birth co- hort and found an inverse correlation between rates of allergic rhinitis and the number of children within the household.13
Strachan et al. in 1997
also showed factors related to smaller families (reduced number of older siblings) and higher socioeconomic status in childhood were associated with higher rates of atopic sensitiza- tion to a variety of aeroallergens in adulthood. This suggested the earlier observations of higher prevalence of allergic rhinitis in smaller, more af- fluent families were not just an arti- fact of symptom recognition, paren- tal recall, or diagnostic labelling but indicated the underlying epidemiol- ogy of atopy.14
Other studies of West
German schoolchildren and Finnish adolescents also showed inverse as- sociations between numbers of siblings and atopic sensitiza- tion and incidence of allergic rhinitis, respectively.15,16 The predominant the-
ory to explain these find- ings was that the pres- ence of older siblings was a marker of exposure to more early childhood infections that thereby influenced immune sys- tem development. If this was the case, attendance at
Source: Bufford JD, Gern JE. The hygiene hypothesis revisited. Immunol Allergy Clin N Am. 2005;25:247-262.
FIGURE 1. THE HYGIENE HYPOTHESIS ILLUSTRATED
Birth Th2
Day care Older siblings
Infections (Th1) Microbes Animals
Allergen exposure
Few infections “sterile” environment
Only child
day care should have a similar effect. Ball et al. evaluated a birth cohort as part of the Tucson Children’s Respiratory Study and showed an association between the presence of one or more older siblings at home or day care during the first six months of life with lower relative risks of atopic disease and asthma. They pro- posed a possible mechanism of a shifting of the Th2 phenotype to Th1 phenotype in the presence of early infections.17 More recently, Lynch et al. exam- ined a birth cohort at high risk for developing asthma in multiple U.S. cities and determined the extent of early allergen and microbial expo- sure. They showed that exposure to certain allergens from cockroaches, mice, and cats and specific bacteria in house dust in the first year of life was inversely associated with recurrent wheezing at age 3 years.18
However,
other studies have shown conflict- ing results with respect to the influ- ence of early bacterial exposure (in the form of colonization). Bisgaard et al. evaluated children of asthmatic mothers in Denmark who were part of a prospective birth cohort. They found neonates colonized with Strep- tococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis,
or with a combination of these organ- isms at 1 month of age were associ- ated with persistent wheeze, acute severe exacerbations of wheeze, and hospitalization for wheeze. Blood eo- sinophil counts, total IgE at 4 years of age, and the prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization.19 Additional studies also have sug-
gested there are genetic factors such as maternal history of asthma that in- fluence the relationship between day care attendance and risk of wheezing. Celedon et al. showed that in children without maternal history of asthma, day care attendance within the first year of life was associated with a de- creased risk of asthma and recurrent wheezing at age 6 years and was as- sociated with a decreased risk of any wheezing after the age of 4 years. However, in children with a maternal history of asthma who attended day care in the first year of life, the oppo- site was actually seen; there was an increased risk of wheezing in the first six years of life.20
MICROBIAL EXPOSURE
Further studies continue to ex- amine the effects of various infections on atopic disease development, but overall the role of infection and development of atopic disease remains some- what controversial. A history of tubercu- losis infection has been associated with de- creased rates of asthma and atopic disease. Von
Th1 or tolerance Healthy
Still Th2 Allergies Asthma
Mutius et al. evaluated data from the Internation- al Study of Asthma and Al-
lergies in Childhood (that ex- amined prevalence of symptoms of asthma, rhinitis, and eczema in
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