New Strategies May Halt the Atopic March

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Newswise — Potential new strategies may be on the horizon for halting the atopic march, a term which refers to the natural history of allergic or atopic manifestations that often begin in early infancy and are commonly associated with food allergy and atopic eczema. Subsequently, the development of asthma and allergic rhinitis may occur, but according to research presented at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Anaheim, it may be possible to prevent the atopic march before it has begun.

Our thinking about allergic diseases has changed," said Erika Isolauri, M.D., D. Med. Sc., a professor of pediatrics at the University of Turku, Finland. "It is no longer only seen as an immediate IgE associated condition. The pattern of sensitization has changed, and we are seeing patients who are sensitized at a very young age."

Several studies have suggested that probiotics may have an immunomodulatory effect, and might be able to reduce the risk of atopic disease. A probiotic is a live microbial food supplement that beneficially and safely alters the intestinal microbial balance. The gastrointestinal tract functions as a barrier against antigens from microorganisms and food, and specific strains of healthy gut microbiota may aid in regulating the secretion of inflammatory mediators, as well as directing immune system development during the period of life when the risk of allergic disease is very high.

We used to believe that the relationship between the human host and microbes was commensal, in that the host was unaffected and unharmed, said Dr. Isolauri. There are ten times the number of bacteria in the human body than cells, and it was assumed that the bacteria were neither beneficial nor harmful.

"Now we speak of a host-microbe interaction, in that there is a benefit to the host by the microbial presence, and we need the microbes in our intestines," Dr. Isolauri said.

A study that looked at allergy development and intestinal flora during the first year of life found that infants who developed allergies often had lower levels of enterococci colonization during the first month following birth (72 percent vs. 96 percent in healthy infants). In addition, infants will allergies were also less apt to be colonized with bifidobacteria during their first year (17-39 percent vs. 42-69 percent in healthy infants).

In our study, we found that perinatal administration of probiotics was able to reduce the risk of atopic eczema in half, said Dr. Isolauri. These rates were also seen in other cohorts as well.

"The beneficial effects continued beyond infancy," she added. At four years of age, 46 percent of the placecbo group had atopic eczema, compared with 26 percent who had received antenatal probiotics.

The perinatal administration of probiotics was also found to be safe, and had no influence on the height and weight of children at 48 months. There was no permanent colonization, and no long-term effects in microbial flora.

"Vaginal delivery provides first bacterial exposure, and then breast feeding provides the beneficial bacteria in the child's intestines," said Dr. Isolauri. The diet of the mother also affects the composition of breast milk.

Our dietary thinking must change, she added, as food is a source of protectors against allergy.

"It's quite clear that the atopic march is a lot more complex than just moving from eczema, to allergic rhinitis, and to asthma," said John O. Warner, M.D., a professor of child health at the University of Southampton, UK. "We have to think about the march and how it starts."

There is evidence which suggests that changes to the immune response may begin occurring while the fetus is still inutero. "If we really want to prevent the disease, it may well be that we are going have to look at what happens before the child is born," said Dr. Warner. "And we are going to have to understand the interaction of genes, maternal nutrition, the way in which the mother is exposed to allergens, whether the mother has infections, and also the interaction of various pollutants of which the most important is maternal smoking."

One misconception is the assumed relationship between the amount of allergen exposure and the risk of becoming sensitized. "As far as allergies are concerned, there has been an assumption that there is a linear relationship as to the amount you're exposed to and the probability of being sensitized," said Dr. Warner. "The higher the exposure, the higher the probability of being sensitized. But that is not the case, as it is quite clear now that there is a bell shaped curve."

Studies have suggested that both extremely low and very high levels of exposure lead to a reduced probability of sensitization, and it is the middle range that has the highest probability of sensitization.

Research that has looked at the avoidance of allergens has produced mixed results. Allergen avoidance is probably not the strategy for the future, pointed out Dr. Warner.

Caesarian sections, and maternal exposure to pollutants, antibiotics, cigarette smoke and acetaminophen have all been associated with subsequent allergies in the child. Genes, the health of both the mother and grandmother, and good nutrition during pregnancy may also affect the onset of allergies.

There are some potential strategies for active interventions during pregnancy. One of these is anti-IgE, as there is some evidence that the fetus is exposed to maternal IgE in the amniotic fluid, said Dr. Warner. "Giving the mother anti-IgE might improve results, but we don't know right now if it is safe to give in pregnancy."

Other possibilities include allergen immunotherapy and nutritional supplements such as fish oil and selenium. Low levels of selenium in the cord blood have been associated with a higher probability of persistent wheezing throughout infancy and childhood. Supplementation with fish oil during pregnancy has been shown to alter allergen induced cytokine production from cord blood cells and reduce the severity of subsequent eczema. Pre- and probiotics may also have a role.

Finally, antihistamines may also play a role with children who already have atopic eczema or allergies, but have not yet developed asthma. "Babies with eczema and who were already showing sensitization to grass allergy, were much less likely to develop asthma if given a second-generation antihistamine regularly every day for 12 to 18 months," said Dr. Warner. "The effect was present after the treatment period. One study, where the treatment had been given for 18 months, showed a sustained effect even 18 months after stopping the treatment."

The ACAAI is a professional medical organization, headquartered in Arlington Heights, Ill., comprising nearly 5,000 qualified allergists-immunologists and related health care professionals. The College is dedicated to the clinical practice of allergy, asthma and immunology through education and research to promote the highest quality of patient care.

For more ACAAI Annual Meeting news, visit the online press room at http://www.acaai.org.


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