SYMPOSIUM
children aged 13–14 years) in combi- nation with tuberculosis notifications rates from the World Health Orga- nization. They showed tuberculosis notification rates were significantly inversely associated with the lifetime prevalence of wheeze, asthma, and symptoms of allergic rhinoconjuncti- vitis.21
Matricardi et al. also showed in
multiple studies hepatitis A seroposi- tivity was inversely associated with atopic disease.22-24 On the other hand, studies with
respect to history of measles infec- tion have been conflicting. In a study of young adults from a semirural dis- trict of Guinea-Bissau in Africa, Sha- heen et al. showed 12.8 percent who had had measles infection were atopic compared with 25.6 percent of those who had been vaccinated and not had measles (adjusted odds ratio=0.36).25 Measles infection also was associated with a large reduction in the risk of skin-prick test positivity to house dust mites. However, Paunio et al. showed the opposite in a cross-sectional study of Finnish residents aged 14 months to 19 years. They showed that history of measles infection was positively as- sociated with eczema, allergic rhinitis, and asthma.26
PARASITIC INFECTIONS
Parasitic infections also have been as- sociated with decreased rates of asth- ma. Infections with parasites, particu- larly intestinal helminths, result in a similar immunologic response as is seen in atopic diseases involving IgE production, Th2 cells, and eosinophil- ia. In fact, it is believed that humans evolved an immediate hypersensitiv- ity in response to the parasitic envi- ronment to which they were exposed. In the absence of parasites, an IgE response to common aeroallergens develops by default.27 Epidemiologic studies have gen-
erally shown an inverse relationship between parasitic infections and asthma prevalence. For example, in rural areas of Africa where parasitic infections are common, asthma is
56 TEXAS MEDICINE February 2017
exceedingly rare. However, no causal relationships can be implied as many other differences are also at play, in- cluding diet, animal exposure, other infections, antibiotic use, etc.27
Specif-
ic studies of parasitic infections, such as one examining urinary schistoso- miasis in Gabonese schoolchildren, showed lower prevalence of a positive skin reaction to house dust mites com- pared with those free of this infection. In a subset of children who under- went further study, infected children were
shown to have significantly
higher Schistosoma-antigen-specific concentrations of interleukin-10, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with skin test reactivity to dust mites. The authors therefore suggested Schistosoma- induced IL-10 appears central to sup- pressing atopy in African children.28
GUT MICROFLORA
Recent attention has focused on a po- tential role of gut microflora and links to atopic disease, as well. Some have hypothesized that specific microbes in the commensal gut microflora may play a more important role than spo- radic infections in preventing atopic disease or in altering immune system development. Studies comparing chil- dren from Sweden and Estonia have shown differences in intestinal micro- flora with a high prevalence of aller- gies in Sweden and a low prevalence in Estonia. Counts of aerobic bacteria were 10- to 1,000-fold higher in stool samples in Estonian than in Swedish newborn babies during the first week of life.29
Lactobacilli were more com-
monly found in Estonian children at 1 month30
and 1 year.31 Kalliomaki et al. provided further
support by performing a double-blind, randomized, placebo-controlled trial that involved giving Lactobacillus GG (a probiotic culture of healthy gut mi- croflora) prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, al- lergic rhinitis, or asthma, and postna-
tally for six months to their infants at high risk for atopy.32
The frequency
of atopic eczema at age 4 years in the probiotic group was half that of the placebo group; however, no dif- ference in allergic sensitization was shown. This study suggests gut mi- croflora might be a potential source of natural immunomodulators and pro- biotics may play a role in the preven- tion of atopic disease.
VACCINES
Studies examining associations be- tween vaccines and atopic diseases also have been conflicting. A study of Japanese schoolchildren given the BCG (tuberculosis) vaccine after birth and at ages 6 years and 12 years showed a strong inverse association between delayed hypersensitivity to Mycobacterium tuberculosis and at- opy.33
Positive tuberculin responses
predicted a lower incidence of asthma, lower serum IgE levels, and cytokine profiles biased toward a Th1 type. A study on measles vaccination did not show any significant effect on atopy development.34 A retrospective telephone survey performed after the completion of a randomized trial examining the ef- ficacy of various acellular pertussis vaccines revealed no differences in re- ported wheeze, itching, or sneezing at age 2 years among the groups.35
While
another study showed pertussis vac- cination increased the risk of diag- nosed asthma, the study also involved a retrospective phone interview only, and confirmatory prospective data have not been provided to support this finding.36
Overall, no convincing
evidence exists that childhood vac- cinations have any impact on atopic disease development.
PET AND FARM EXPOSURE
With respect to pet exposure, many studies have shown inverse associa- tions between early cat and dog expo- sure and atopic sensitization and/or asthma. These associations have held up in prospective studies, eliminating
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