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Study on Possibility of Preventing Peanut Allergies

October 12, 2015
Written by Elise

In the last 10 years, peanut allergies have begun to be found more commonly in Africa and Asia, and its occurrence among children in Western countries has doubled. Peanut allergies have been given a lot of attention by the scientific and medical communities because, of all food allergies, being allergic to peanuts most frequently leads to death.



For people who are allergic to peanuts, the allergy usually develops early in their lives and it is rarely outgrown. It is not currently curable. Additionally, because roasted peanuts are nutritious and known in the food industry as having a unique and pleasant taste, they are used quite ubiquitously for added flavor or protein in foods. It then becomes quite dangerous and difficult for people who have a peanut allergy (especially a severe one) to avoid accidentally eating peanuts. Due to the danger of peanut allergies, multiple different kinds of suggestions have been made throughout the last few years to parents of children who might have the allergy, including to avoid them until the child was 3 years old.

In 2008, a study was published on the rates of peanut allergies in Jewish children of Ashkenazi heritage who lived in London compared with those who lived in Tel Aviv. Two differences were found: 10X more of the children in London were allergic to peanuts than the children in Tel Aviv; and most of the children in London started eating peanuts at about 3 years old, where 80-90% of the children in Tel Aviv had started eating them by the time they were 9 months old. This 2008 study inspired the same group of researchers to embark on a second study that was published earlier this year.

Read beginning below for a basic outline of the study. Scroll to the "Technical" section below for a more technical account of the study. Throughout this post, clicking on words that are bolded and underlined will expand an explanation of that word or concept. Click the word again to make the explanation disappear.


Basic:

The study, Learning Early About Peanut allergy (LEAP), hailed as a "landmark" study which will "[revolutionize] the care of children at high risk for peanut allergy" placed high risk infants between the ages of 4 and 11 months old into 2 cohorts
(a name for sample groups in a study) based on the results of a skin-prick test (an allergy test in which a medical professional places a drop of a potential allergen onto the skin of a patient, then slightly pricks the skin below with a needle to allow the potential allergen to enter just slightly below the surface) (children initially showing a small reaction to peanuts and children initially showing no reaction to peanuts) and again into 2 other groups within those cohorts (each cohort had a group assigned to eat peanuts and a group assigned to avoid them) and all study participants were followed up with when they reached the age of 5 years old.

Allergies work like this: in the blood stream is an antibody (a protein your body produces in your bloodstream in response to a specific antigen in order to counteract it) called immunoglobulin E (IgE), which acts in response to antigens (chemical substances your body recognizes as alien and therefore attacks in order to destroy them or weaken their effects; this process forms the basis of immunity). The body's ability to produce IgE is genetic. The first time a person who is genetically predisposed to produce IgE in response to a certain food eats that food, the IgE already in their bloodstream has not yet been modified to react to it. This change in the IgE cells happens as the cells come into contact for the first time with the antigens (that come from the food). This can also trigger the body to produce large amounts of these newly modified IgE cells. The IgE cells that are now structured to respond when a certain kind of food is eaten spread throughout the bloodstream and attach to mast cells (a very common type of cell in the body that releases histamine and other substances during allergic reactions and other inflammatory events). These mast cells are especially common in the skin, pharynx (the tube that forms your throat), bronchii and bronchioles (the smallest structures in your lungs), as well as the gastrointestinal tract (includes the mouth, esophagus, stomach, small intestine, large intestine, rectum, anus). The next time this food is eaten, the newly specific IgE cells trigger histamine (a compound released by mast cells in response to an immune signal that causes, among other things, increased blood flow; this in turn causes swelling) production in the mast cells they've attached to. As histamine takes effect in the areas where mast cells are very common, people experience symptoms like itching in the mouth, difficulty breathing, difficulty swallowing, vomiting, diarrhea, abdominal pain, decreased blood pressure, eczema, and rashes on the skin.

At the study's follow-up, 617 children participated in an oral food challenge (This is the most accurate test we currently have for food allergies. A patient is safely given measure doses of a potential allergen, starting with small dosages and working their way up to large ones that are more likely to cause a reaction. They are then observed to do if they do exhibit symptoms of an allergic reaction. If one occurs, it is generally mild due to the safe, graded structure of the test.) with the peanuts administered in standard dose-escalation procedures for safety. Children who initially didn't show conclusive signs of allergy were found to have developed allergies in 13.7% of the group who avoided peanuts and 1.9% of the group who regularly ate them. For children who did initially show signs of peanut allergy, 35.3% of the avoidance group developed allergies while only 10.6% of the consumption group developed them.

The study concludes that "early environmental exposure (through the skin) to peanut may account for early sensitization, whereas early oral exposure may lead to immune tolerance". Because the results showed a significant decrease in allergy rates for children who ate peanuts earlier as compared to children who avoided them, new questions have been raised about the efficacy of advising parents to avoid exposing their children to peanuts while they are young as a strategy to prevent peanut allergies. Though researchers don't know from this study if these effects would be lasting in children if they stopped consuming peanuts as often, this has sparked a third study for them, the LEAP-On study, which is designed to answer that precise question.



Technical:


Peanut allergy is a dangerous IgE-mediated food allergy common in Western countries. In the U.S., the American Academy of Pediatrics indicated for about 8 years that children at high-risk for peanut allergy should not have peanuts as a part of their diet until they had reached about 3 years of age. However, studies attempting to prove this indication to be a helpful intervention consistently failed until, in 2008, the association revised their stance to outline that the helpfulness of a delay in peanut consumption past the age of 4-6 months in children at high-risk was not backed by evidence. Parents were counseled to consult with a specialist on an individual basis. The study in London and Tel Aviv sparked the question of whether or not the opposite (consuming peanuts from an early age) could actually be the useful intervention for these children.

Because it is not well studied, oral tolerance is an immunologic phenomenon scientists don't understand well. The Learning Early about Peanut Allergy (LEAP) study was designed to be a relatively large scale trial to determine whether preventing peanut allergy by way of early introduction and regular consumption of peanuts in high-risk children would work as both a primary and secondary strategy. High risk infants between the ages of 4 and 11 months old were placed into 2 cohorts based on the results of a skin-prick test (children initially showing a small reaction to peanuts and children initially showing no reaction to peanuts) and again into 2 other groups within those cohorts (each cohort had a group assigned to eat peanuts and a group assigned to avoid them) and all study participants were followed up with when they reached the age of 5 years old. Adherence to the assigned diets was assessed by means of parental reporting and analysis of dust samples from the participant's beds. 423 of 640 study participants submitted to dust sample analysis. Participants in the consumption groups consumed at least 6g of peanuts a week. During the course of the study, rate of hospitalization or serious allergic events between the avoidance groups and consumption groups did not show a significant difference. 99% of the participants, whether or not they consumed peanuts, reported at least one allergic event. No deaths occurred.

At the time of final consultation for the study, 617 children participated in an oral food challenge. If a child showed no indication of allergic symptoms throughout the course of the study, they were given 5g of peanut protein in a single dosage. The rest of the participants followed standard dose-escalation procedures. In the 11 cases where results of the oral food challenge were inconclusive, researchers determined whether or not they had an allergy through use of clinical history, a skin-prick test, tested levels of specific IgE production, and a diagnostic algorithm.

Children who initially didn't show conclusive signs of allergy were found to have developed allergies in 13.7% of the group who avoided peanuts and 1.9% of the group who regularly ate them. For children who did initially show signs of peanut allergy, 35.3% of the avoidance group developed allergies while only 10.6% of the consumption group developed them.

The study concludes that, "Among infants with high-risk atopic disease, sustained peanut consumption beginning in the first 11 months of life, as compared with peanut avoidance, resulted in a significantly smaller proportion of children with peanut allergy at the age of 60 months. This intervention was safe, tolerated, and highly efficacious." Because the results showed a significant decrease in allergy rates for children who ate peanuts earlier as compared to children who avoided them, new questions have been raised about the efficacy of advising parents to avoid exposing their children to peanuts while they are young as a strategy to prevent peanut allergies. Though researchers don't know from this study if these effects would be lasting in children if they stopped consuming them as often, this has sparked a third study for them, the LEAP-On study, which is designed to answer that precise question. Researchers note there is some question as to whether it would be ethical to withhold this intervention from people in future studies, given its effectiveness and potential to change lives. 


Sources:
Du Toit, George, Graham Roberts, Peter H. Sayre, Marshall Plaut, Henry T. Bahnson, Herman Mitchell, Suzana Radulovic et al. "Identifying infants at high risk of peanut allergy: the Learning Early About Peanut Allergy (LEAP) screening study." Journal of Allergy and Clinical Immunology 131, no. 1 (2013): 135-143. at http://www.jacionline.org/article/S0091-6749(12)01510-2/fulltext

 Scudder, Laurie, and Matthew J Greenhawt. "Peanut Allergy: The Paradigm-Changing Research." MedScape. August 18, 2015. Accessed September 2, 2015. 

 Galli, Stephen J, and Mindy Tsai. "Figure 1: Allergen Sensitization and IgE Production." Nature Medicine, 2012, 693–704. Accessed October 1, 2015. doi:10.1038. at http://www.nature.com/nm/journal/v18/n5/fig_tab/nm.2755_F1.html

"How Allergic Reactions Work." How Allergic Reactions Work. July 29, 2001. Accessed September 2, 2015. http://www.wakemed.org/adam/careguides/allergy/allergy_reactions.html

Scanning Electron Microscope photo of mast cell from Hale, Laura P. "Introduction to Systemic Histology." Duke University Pathology. Accessed October 1, 2015. http://pathology.mc.duke.edu/research/histo_course/mastcell_em2.jpg.

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