eSign Food Allergy Chart Made Easy

E sign food allergy chart

good morning i'm dr christina chacho i'm the chief of allergy at the university of chicago and an associate professor of pediatrics in medicine so this morning i am going to just kick off the topic of the pathogenesis of allergic disease and i'm going to be followed by three absolutely fantastic speakers who are each going to dive into one of the hypotheses of why food allergy is so highly prevalent in the united states today so i am going to talk about adverse food reactions with a slide that we i think all hold near and dear to our heart of course for the sake of this meeting we are going to be talking about immune mediated adverse food reactions and for the most part i am assuming the following speakers are going to be specifically talking about ige mediated food allergy into a much lesser extent non-ige mated food allergies such as f pies or things that may be non-ige mediated or mixed such as eoi so why do we care about food allergy well we care because we know that children with food allergy and the families of these children have a decreased quality of life it goes certainly beyond just the the fear of a reaction or the reaction itself but we know that children with food allergies are bullied we know that family social activities can be negatively impacted it becomes much more difficult to dine out and attend sporting events children's social activities also become limited accommodations are needed for play dates birthday parties and camps that aren't needed for other children and children require special food and that food can be hard to come by it can be extremely expensive and it's not available for all populations in the united states right now very unfortunately leading to a disparity and food allergy and at times children can be separated from their peers at meal times and during social activities because there is anxiety about an accidental reaction which can be very isolating for the children in one study the quality of life those with peanut allergy were compared to those with insulin dependent diabetes and what they saw was that the overall mean score was higher for peanut allergy which means that the quality of life of those with peanut allergy was more highly impacted than those with insulin dependent diabetes the children with peanut allergy were more afraid of an accidental ingestion of peanut than children with insulin dependent diabetes of having a hypoglycemic event although both reactions can be fatal and can lead to a hospitalization the pean allergy group in this study had high anxiety at social activities and they felt restricted in their physical activities so why do we need to understand the disease development or the pathogenesis of this atopic condition well if we want even a crack at being able to come up with preventive strategies or safe and effective treatment options we need to i have an understanding but of course the ultimate goal for me will always still remain finding a way to reset the immune system so we're no longer living with these chronic non-infectious inflammatory diseases but getting to a state where a children and adults with food allergy may be cured or maybe in a remission or a state of tolerance or whatever that looks like or word you want to describe it getting them to a place where it does not become a worry and they don't have to do anything special on a day-to-day basis to maintain the state of tolerance what is the pathogenesis of food allergy it is the failure of oral tolerance and to better understand what food allergy comes from we have to understand where oral tolerance is failing so what oral tolerance is it typically happens in the gut immune system of course the luminous barriers at a significant player as is the extensive lymphoid tissue throughout the gastrointestinal tract and the key components include the antigen degradation that happens with enzymes as soon as food antigen enters the mouth and as it goes into the stomach it has additional degradation from the acidic environment and then as it leaves towards the duodenum and small intestine of course the antigens are selectively taken up and presented to the immune system the antigen presentation of course happens from cd103 positive dendritic cells and then the effector cells when oral tolerance goes correctly will produce t regulatory cells in a high amount that keep the immune system in check and send overall a signal that this antigen should be tolerated and allergic reactions should not occur so what are things that affect oral tolerance well the nature of the antigen the dose of the antigen are both very important the frequency of administration of the antigen the age at the first exposure we know and the immunological state of the host at that time all play a critical role in oral tolerance the dietary exposure that the mother has during pregnancy as well as while she's breastfeeding because we know antigens are transmitted via breast milk and the route of first exposure and bacterial colonization all seem to be critically important for oral tolerance to happen correctly so what specifically signals for oral tolerance well the nature of the anagen soluble antigens tend to signal more strongly for tolerance whereas particulate antigens do not the dose of the antigen as in a low dose versus a high dose can make a difference however both low-dose doses of antigen as well as high doses of antigen can signal for oral tolerance but in distinct pathways so the exact right dose at the right time we still need to do work to figure out exactly where this is of course with the frequency of administration of anagen the more frequent exposure tends to lead to tolerance and of course this makes sense if you think of many generations throughout the time of humans we would not have traveled to the extent that we do now we would not have been able to transport foods so the foods that would have been available to feed to a child would have been in the close proximity of where they were born and it would have been certainly a much more limited repertoire than what we have now so children would have probably exposure to the foods that they were going to eat their entire life when they were very young and they would have had them eaten them frequently of course the age at first exposure we certainly know from the leap trial seems to make a difference the early exposure was highly significant in preventing peanut allergy and i think studies continue to be on the way to see if other allergens is also effective technique and of course the immunologic status of the host this food allergy is a chronic non-infectious inflammatory disease of course with skewing to the th2 a side of inflammation but it is still a chronic inflammatory disease and the host the child's immune system needs to be in a state of preparedness for the antigen when we introduce it of course the dietary exposure of mother and the antigen transmission via breast milk is important because in this situation igg and iga can be bound to the antigen and can be presented to the mucosal immune system in a way that directs it very clearly how it should be processed and can certainly be more likely to signal towards tolerance and of course the route of first exposure so if it's extra intestinal we worry very much about the loss of oral tolerance we really want to be that first exposure to be through the mouth our oral tolerance can be signal and not through the skin for example and then of course more and more we have been thinking about bacterial colonization not only in the gut but throughout the child's body and we are paying attention to both the gamma diversity and specific bacteria namely those that are butyrate producing as mechanisms for promoting oral tolerance so several hypotheses have been proposed at why oral tolerance is lost but what i would like to drive home this morning is that these hypotheses are not independent of each other so there are many but they can all be at play they all signal a different part of a loss of oral tolerance and certainly may all be a part of the big picture so the microbiome hypothesis of course is one that we're going to hear more about today it originally started in the 80s as the hygiene hypothesis but the hygiene hypothesis as it was originally written fell apart fairly easily but now that we've learned more and more about the exact bacteria that live in the gut this has certainly become a viable hypothesis again and speaks to how we have co-evolved with bacteria throughout time and these bacteria have been immunoregulatory for us so the loss of the correct bacteria has led to inflammation that may lead then not only to food allergy but if genetics dictated also may lead to other chronic non-infectious inflammatory diseases such as diabetes of course there's the omega-3 fatty acid hypothesis and this hypothesis briefly it says that the amount of omega-3 fatty acids has been skewed since the 1960s very strongly towards a more omega-6 fatty acid-rich diet here in the united states and because of that the omega-6 is more likely to produce arachidonic acid and lead to a state of inflammation in the host of course that would cause a signal loss of oral tolerance there's of course vitamin d hypothesis that says that we are certainly outside less our vitamin d levels are lower there's been some thought actually to low vitamin d and extremely high vitamin d exposure both skewing the immune system and signaling a loss of tolerance and a very important one that we're looking at now is the dual allergen exposure hypothesis so this one says that if you have an allergen that goes through the epithelial barrier and is not presented through the mouth then again you can lead to oral tolerance loss of oral tolerance of course the food processing hypothesis that we are processing our foods differently we're growing them differently an example of this would be peanuts of course which are boiled we think are less allergenic than those that are fried or more allergenic or in the case of shellfish those that are boiled may be less allergenic and those are fried may be more allergenic and then of course maternal stress is a hypothesis that is gaining intense interest particularly as we look more and more at the disparity of food allergy and atopic burden across the country we can see that there are certain areas that are blighted and families have less access and increased stressors really just to get through day-to-day life this is showing that it's significant to the immune system and certainly may be something that is important as we think about the development of atopic disease but all of these hypotheses again can work together because they all target a different part of oral tolerance and it certainly may be that this is a multi-generational phenomena and as things change different parts of oral tolerance have been affected and we've come to this point there have been too many hits and we have been left with this state of inflammation so of course the microbiome hygiene hypothesis speaks to the bacterial colonization importance of oral tolerance the omega-3 speaks to the immunologic status of the host as does the vitamin d hypothesis of course the dual allergen exposure hypothesis speaks both to the point of entry of the first exposure as well as the age and frequency of exposure the food processing speaks to the nature of the antigen and then of course maternal stress speaks to immunologic status of the host as well so again in combination all of these things play a part in oral tolerance they're all important and i think as we move forward we need to look to see if in combination we can get the oral tolerance again to a place where we can prevent food allergy which of these pan outs so of course we look at genetics whenever we're talking about the pathogenesis of disease and food allergy there's been certainly a gut instinct that there is a genetic component and this has been shown by some great studies one a twin study of peanut allergy that included 14 monozygotic twin pairs and 44 dizygotic twin pairs and they showed a 64 concordance in peanut allergy in the monozygotic twin pairs compared to a 6.8 concordance in the dizygotic twin pairs this led to a heritability estimate for peanut allergy of 81 so of course this is a strong genetic association in the sibling study of food allergy included 581 families and food allergy in one child diagnosis was based on clinical history and ige level predicted food allergy and other siblings with an odds ratio of 2.6 so what genes play a role well we do know that there are some monogenetic disorders that are associated with food allergy to a greater extent than the average population so lloyd's syndrome which is associated with mutations in tgf beta doc 8 pgm3 nethertons ipex and wiscon aldridge all have a predisposition to food allergy but these genes of course these mutations are in a very small amount of population and hardly are an explanation for why the prevalence is so high across the united states but when we look at chiwa studies we can see some significant loci that seem to be affected including serpent b flagrant hla a cytokine gene cluster and lrc 32 of course which is at the start of tgf gene the first two which play a critical role in the epithelial barrier function so again speaks to the route of first transmission and the latter three speak to inflammation in the host all these are our key components of the immune system and within mutations certainly may predispose the host on that first exposure to tolerate the antigen but genetics alone does not seem to be the explanation or the whole explanation that can get us to where we need to be we've watched the prevalence increase over the past several decades the case of peanut allergy in 1997 a phone survey estimated the prevalence to be 0.4 and as different methods of course can't directly be compared we're done the estimate did seem to increase until very recently in 2015 2016 a survey estimated a prevalence at 2.2 percent so this same study said overall there was a 7.6 prevalence of convincing food allergy in children over 40 percent of these had experienced a severe allergic reaction and the predominant foods were peanut milk and shellfish but it wasn't just in children it was in adults and certainly i think many people would have guessed decades ago that very few adults had food allergy there's not a lot of data to compare this but in the 2015-2016 study they concluded that 11 of adults had a convincing food allergy the most common of being shellfish but greater than 50 percent at some time in their life had experienced severe allergic reaction so this increase in prevalence really speaks to the environment playing a strong role too and there are many things that have happened in the past several generations that would influence many of these components of oral tolerance including an increase in c-sections and decrease in breastfeeding and increase in simple sugars in our diets with a decrease in fibrous plants an increased use of antibiotics large move from rural environments to urban areas a decrease in family size increased use of bactericidal soaps and detergents in the home not only on surfaces but on skin increased sanitization of the food we're eating and certainly water contaminants we're drinking city water more frequently than ever before move away from well water to exemplify this dramatic shift i have found a picture that is not actually of my home but this from what i could steal on the internet since i didn't have anything from home this is actually very similar to the road i grew up on and this is actually a photo of my older brother in front of him is our breakfast table our baby would eat breakfast and dinner at as a matter of fact and this of course is our horse saying hi to him through the window as he's having a snack or breakfast one morning my father came from a very large italian family there were eight siblings in his family also grew up in a rural environment and two generations later this is actually a view from where i live now in the city you can see in the background the university so it's like i never leave work at all but this is the environment my kids are growing up in which is a substantially different we have a small family i have two children and we have very little green space to be outside of course we do we're very lucky in hyde park to have many trees but in just two generations there has been significant changes in just my family all of which can have had a significant impact on the environment that my kids have grown up in and so that brings us to some important hypotheses that are going to be discussed further in the next presentation but the first is near and dear to my heart it's something that i believe in as a potential for therapy with microbiome modulators but it's the microbiome hypothesis and in this one again it says that we have co-evolved with bacteria for millennia and we have lost some of these bacteria or it's certainly changed in composition over the past several generations but what we want is to live in a symbiosis with these bacteria so it may be things like an increase in prebiotics so those fibrous fruits and vegetables that we eat or potentially exploiting different probiotics can lead either to the colonization or the increase of beneficial microbes that will secrete postbiotics such as the short chain fatty acids specifically butyrate which then feed back to our immune systems and keep it under control by maintaining a nice tight barrier function and certainly influencing the immune system to a state of tolerance in a way from a state of inflammation another hypothesis that we're going to hear about today is the dual antigen exposure hypothesis so we are certainly starting to think very strongly about a tight epithelial skin barrier function and what we know is that as soon as eczema starts there is a pathway for allergens to be introduced to the body for the first time instead of through oral tolerance so kids certainly who have peanut dust in their floors and maybe active examineus lesions on their arms if they crawl across the carpet and maybe get an antigen exposure in this way there are probably other influences on the skin that can lead to the state of inflammation but in general if these allergens are introduced through the skin the signal to the immune system is going to fight them instead of tolerate them and we i think are going to be looking very intensely in coming years of whether there is a way to improve the barrier function of the skin to prevent the development of food allergy and the last thing we're going to hear about is the gut brain access and certainly very intriguing as a potential player in food allergy we certainly know that both maternal and childhood stress is increasing certainly in certain populations and when we talk about this we're referring to stress that is transmitted partially via cortisol from the central nervous system down to the gut nervous system the entire nervous system and these signals can actually have some of the same effects that we see when we change the microbiome we can see an increase in intestinal permeability and effects on motility as well but this pursuit is certainly worth all the effort that we're putting into we've had two huge successes in recent years one in prevention and one in treatment that has resulted from our understanding of oral tolerance and the pathogenesis of food allergy one of course is the leap study that showed us that it's very powerful to get the timing right of introduction of a highly allergenic food such as peanuts and then of course just in 2020 we had our first fda approval of a food allergy treatment ever and this again speaks volumes to how we are influencing oral tolerance by the timing and the amount of introduction of an allergen so my hope is that in coming years we can expand upon this that we can continue to bring new treatments to market with this knowledge we've gained and certainly continue to work on preventive strategies so there may be a point where we don't even need treatment for children any longer and of course with a long-term cure of having something for every kid who has a food allergy so that they can live the quality of life that they want to live so with that i just want to thank you very much and i will turn it over to the team that is going to go in depth and talk a little bit about disease development so thank you very much