Thursday, February 26, 2015

What makes the current peanut allergy prevention study so much better than past studies?

Update (2/27/15): Because of the concern among parents who have children with peanut allergies, the Kids with Food Allergies Foundation has issued the following statement. Please take a read. New Peanut Allergy Study Does Not Say Parents Are to Blame

Every now and again, a study comes along that changes things, and I truly believe that the Learning Early about Peanut Allergy (LEAP) study by Du Toit, et al.1 will usher in an era of solid evidence-based guidance in terms of infant dietary recommendations and a much needed "benchmark" for designing future studies addressing allergy prevention. This study is only the first step for re-writing the guidelines that have yet to make it into medical practice. Contrary to headlines, actions to “feed your infant peanuts” should not be changed overnight without working with a healthcare provider first.

Before I get into why I feel this study truly changes things, I want to convey my initial emotions surrounding this study because I know that I am not alone. Even though I am scientist, I am also a mom to two young boys. One has multiple life-threatening food allergies and the other is at high risk of developing life-threatening food allergies. My oldest guy with allergies, “JR,” who is a first grader this year, is the inspiration behind this blog. You could say that because of JR’s many life-threatening food allergies, fear has been my constant companion, both for JR who could violently react to traces of allergen and his younger brother, “Luke,” who is at risk for developing life-threatening food allergies himself.

As a parent, I want nothing more than to do everything in my power to prevent food allergies for Luke. The fact is, the current advice has always been a “best guess” with very little hard data backing it up or scientific understanding of how our immune system learns to tolerate harmless foods in the first place. Within the last month, Luke gleefully blew out the three birthday candles lighting his dinosaur cake. To me, those three candles represent more than just a third birthday. To me, they symbolize a tinge of regret in light of new evidence from the LEAP study. In spite of a few food allergy scares while introducing solid foods, Luke currently tolerates all foods he has tried.  Conspicuously missing from his palate are peanuts and tree nuts. Based on “best guess” medical advice from our allergist, we decided to wait until three years old to introduce peanuts and tree nuts. We did everything “right,” and yet…

For the “emotional” part of me, the results of this study feel like a double whammy of fear and regret. Rationally, I know we’re – and by we’re, I mean parents, caregivers, clinicians, scientists, etc. - just doing our best, following the best advice/evidence, hopefully preventing fears from manifesting into reality. There’s fear and regret that perhaps I haven’t done enough to prevent a second child from developing allergies.  Then there’s fear of even having those allergenic substances in the house for an already-allergic child who could react with just a tiny trace of peanut or tree nut. Could I live with the regret of causing a life-threatening reaction because I failed to adequately clean up after a messy toddler in the name of prevention in my own home?! Damned if I do, and damned if I don’t, I guess.

Beyond emotion.

As human beings, we tend to interpret information with our "hearts" first and let "reason" come later. And many people never even get beyond that initial "heart” interpretation.  I acknowledge it’s ok to have these feelings (and I hope that other allergy parents/caregivers out there do, too!), but I hope to illuminate those dark places where fear and regret lurk. This study was aimed at preventing peanut allergy in infants at high risk of developing food allergies. If you are already dealing with a food allergy, this study does not apply to your situation. Even though this new research can’t help my family or maybe even your family, I am overjoyed that we have the beginning of how to prevent allergies for other children! Refrain from reading any and all article commentary from non-experts to avoid the “I told you so” and “stupid, fearful parents for not feeding your kid our nation’s best, right-to-eat it anywhere, delicious, nutritious snack.” These comments are examples of ignorant people wrongfully interpreting scientific findings through a way too generalized media filter to support what they already “believe” to be true.  Science is not about what we “believe” to be true, but what we “know” to be true. And what we “know” to be true for an entire population of human infants is not determined by this one study. Far from it.

What makes this study so special?

Prospective, randomized controlled trial. Say what?! In terms of study designs, this type provides possible causal relationships. The researchers recruited a large, VERY defined population before the study began, and then they randomly assigned the participants to either the “avoid peanut” group or the “consume peanut” group. You can imagine it to be like putting 600 little pieces of paper with names into a hat, shaking all the pieces of paper, and then the first 300 chosen are assigned to the “avoid peanut group” and the remaining 300 individuals go to the “consume peanut” group.

Even though the study participants were highly defined upfront, it is possible that when you look across all participants included in the study, there may be other “factors” that could influence or “confound” the results. By doing this randomization process upfront, "treating" to an exact and defined protocol, and following those individuals over time, the hope is that these other potentially "confounding factors” will not be factors. Rather, a prospective, randomized trial aims to evenly distribute or shake out potentially confounding variables (i.e., sex, age, etc) between avoidance group and peanut consumption group so they are testing what they want to test – does introducing peanuts early or avoiding peanuts prevent peanut allergies from developing. Nothing more. Nothing less. This has NOTHING to do with reversing an already established food allergy. And the beauty of this study design is that they can ask all of their study participants for potential confounding information to later confirm that those potential “confounding” variables did in fact shake out evenly between the groups during the randomization process! How awesome is that?!

Many of the studies in the past rely on a different, less robust study design – observational and retrospective (looking back on what has already happened, i.e., peanut allergy vs. no peanut allergy correlated to when peanuts are typically introduced into the diet across a large population). This involves recruiting individuals who were “out in the wild” already consuming or avoiding peanut in who knows what kinds of quantities for one reason or another. While meaningful information may be gleaned, confounding variables are difficult to control. Observational and retrospective studies are a great starting point and often provide evidence to pursue those answers more definitively with a much better (much more expensive, I might add), prospective, randomized controlled trial. In fact, it was this same research group a few years back who did a study of this type showing that the prevalence of peanut allergy was much lower in Jewish children from Israel, where peanuts are introduced very early in infancy, compared to Jewish children in the United Kingdom, where peanut products, at the time, were not recommended for infants before a year old.2

What this does NOT mean

Because the study participants were a VERY defined population – they were between 4-11 months at the start of the study, and they were at risk of developing a peanut allergy (severe eczema, established egg allergy, or both severe egg allergy and eczema), we cannot safely extrapolate the findings beyond either the study population or the specific study parameters. The accompanying editorial published in the New England Journal of Medicine by Gruchalla and Sampson put it best:

"Given the results of this prospective, randomized
trial, which clearly indicates that the early
introduction of peanut dramatically decreases the
risk of development of peanut allergy (approximately
70 to 80%), should the guidelines be
changed? Should we recommend introducing
peanuts to all infants before they reach 11
months of age? Unfortunately, the answer is not
that simple, and many questions remain unanswered:
Do infants need to ingest 2 g of peanut
protein (approximately eight peanuts) three times
a week on a regular basis for 5 years, or will it
suffice to consume lesser amounts on a more
intermittent basis for a shorter period of time?
If regular peanut consumption is discontinued
for a prolonged period, will tolerance persist?
Can the findings of the LEAP study be applied to
other foods, such as milk, eggs, and tree nuts?"3

While many questions do remain, the same editorial goes on to say:

"…we believe that because the results of this trial are
so compelling, and the problem of the increasing
prevalence of peanut allergy so alarming, new
guidelines should be forthcoming very soon."3

They go on with suggestions for health care providers to follow for introduction of peanuts while we patiently wait for those new guidelines.

Where to go from here

In the words of pediatric allergist Dr. Dave Stukus, “This study may be called LEAP, but it’s still only one step.” This study provides a “benchmark” for many future studies. Being a basic scientist myself, I want nothing more than to take this information and understand how and why. What features of early immune system development impart tolerance when foods are introduced early? What changes happen to the immune system after you cross that critical period or window of opportunity? Along those same lines, how does prevention by early introduction differ from a child or adult who clearly tolerated a food for some time period, but went on to develop allergies much later on? We need to understand at a very fundamental level how we define immune tolerance at a cellular level, what establishes it, how it is maintained, and how it is lost.

Population studies such as the beautifully executed LEAP study give us guidance, but my hope is that by honing in on the how’s and why’s, we will move toward tailoring prevention and treatment strategies to the individual.

PS - Wish us luck as we trudge forward with introducing peanuts and tree nuts to Luke!

References

1. Du Toit G, Roberts G, Sayre PH, et al. Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy. N Engl J Med. 2015;372(9):150223141105002. doi:10.1056/NEJMoa1414850.

2. Du Toit G, Katz Y, Sasieni P, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122(5):984-991. doi:10.1016/j.jaci.2008.08.039.

3. Gruchalla RS, Sampson HA. Preventing Peanut Allergy through Early Consumption - Ready for Prime Time? N Engl J Med. 2015;372(9):875-877. doi:10.1056/NEJMe1500186.

Tuesday, February 10, 2015

Headline hyperbole - probiotics cure peanut allergy?

Note about study discussed below – please do not try oral immunotherapy (OIT) or OIT with probiotic supplements on your own! This is an experimental food allergy treatment to be performed under strict medical supervision.

Sigh… We all want a cure, and many scientists/clinicians are working tirelessly toward that goal (including the research group that performed the original peer-reviewed study(1)), but please, oh please media, stop overselling the scientific findings! I’m quite literally tired of having to explain the same thing over and over again! Unfortunately, there is a reason why one of my blog labels is now “Misleading Science Headlines.” I don’t necessarily want to go into the details of why this is so detrimental to both the science and food allergy communities, but rather I’d like to take the rest of this two part post to explain why the headlines got it wrong, what can actually be concluded from the study, and where the science may go from here. Lianne Mandelbaum, who founded No Nut Traveler, authored an excellent piece at the Huff Post Blog explaining why misleading headlines are such a problem when it comes to food allergies. I encourage you to take a read.

Brief summary of the study:

Mimi Tang, et al., from the Royal Children’s Hospital in Melbourne, Australia tested if the combination of oral immunotherapy (OIT) and a probiotic supplement could lead to “sustained unresponsiveness” in peanut allergic children compared to a placebo group  (peanut allergic children who did not receive peanut OIT or probiotic). They found that after stopping treatment (ranging from 2-5 weeks) over 80% of children who received OIT + probiotic maintained a “sustained unresponsiveness” to peanut compared to only 3.6% of the placebo group (1).


Study design: Randomized, double-blind, placebo-controlled

Saturday, December 20, 2014

Vegan pumpkin pie filling minus most of the gloopy starch (egg-free, milk-free, nut-free)

Introduction:
This may not be a cooking blog, but occasionally a little science can help solve a very real problem - a better vegan pumpkin pie filling! The starchy, gloopy, blobby pumpkin pie filling found in most vegan pumpkin pie recipes has much to be desired. In fact, I like to joke that I can chuck a scoop across the room and watch it slowly bleb down the wall. We deal with many allergies that won't allow using certain egg-replacing binders (e.g. flax seed gel, corn starch, tofu, etc.), so after coming up null with internet searches for workable recipes given our allergen set, necessity became the mother of invention! Welcome to my test kitchen!

Question: 
Could I use chia seed, some combination of chia seed and tapioca starch, or a combination of chia seed and course oat flour to improve the texture of the existing gloopy pumpkin pie filling (tapioca starch-based)?

Hypothesis: 
I predicted that either the combination of chia seed and oat flour or the combination of chia seeds and tapioca starch would significantly improve the texture of the gloopy pumpkin pie filling. I predicted that the chia seed alone would not provide enough binding to make an adequate filling.

Rationale: 
Chia is often touted as an egg substitute. Soaking 1 Tbsp of chia seeds in 3 Tbsp water for ~20 minutes makes a mucilaginous gel resembling the texture of raw egg in quantity. While the texture seems on par with raw egg, the real magic of egg binding in recipes doesn't happen until after it is cooked (think of a hard-boiled egg. The uncooked "white" is primarily protein, whose structure changes to the opaque, hard but slightly pliable white after cooking. Now imagine that same structure distributed throughout your pie filling!). Chia has a combination of polysaccharides (complex sugar chains - aka carbohydrates, some protein, and some fat). I reasoned that chia alone wouldn't have the same protein binding "magic" as an egg based on its protein content (1 large egg = 6.3 g of protein; 1 Tbsp chia seed = 3 g protein). Although it is possible that chia may compensate for a lack of protein a bit by providing more carbohydrates that can "gel" (1 large egg = 0.4 carbohydrates; 1 Tbsp chia seed = 5 g carbohydrates). Oats have a good deal of both protein and carbohydrates, though! So I figured grinding rolled oats into a coarse flour with a food processor may expose more of the protein/carbs contained within to serve a really good "binding" function (1/2 cup of rolled oats = 5 g protein, 27 g carbohydrates, 3 g fat).

Making chia seed gel. 1 egg substitute = 1 Tbsp chia seeds + 3 Tbsp water. Let sit ~20 minutes before using.
Materials and methods:
In order to waste as little food as possible, I mixed a large pumpkin pie base whose ingredients were common to all conditions and added 3/4 cup of the "base ingredients" to each of four tempered glass cups. 

Base ingredients common to all conditions
2 cups pureed pumpkin
1 cup light coconut milk
1/4 c. packed light brown sugar
1/4 c. maple syrup
1/4 tsp. sea salt
1 tsp. ground cinnamon
1/4 tsp. ground ginger
1/4 tsp. ground nutmeg

I then scaled down the unique ingredients I wanted to add to each of the four separate conditions, fully mixed, and baked in the oven at 375 deg. F for 45 minutes. Note, I would have loved to test additional conditions, but I didn't have enough ingredients to test them all! In theory, I should have included a proper "negative control" that would have baked the "base ingredients" with no additions. I would have also included an "egg based" version for good measure, but hey, we deal with an egg allergy in our house - it just didn't seem right. After baking and cooling, my husband and I taste-tested each condition to obtain results based on our personal texture preferences.


Results:
Chia seed + oat flour was the clear winner for binding and texture. Both the tapioca starch alone and the chia seed + tapioca starch had the gloopy starch binding texture instead of the soft texture associated with traditional egg-based pumpkin pie filling. Chia seed alone was quite delicious, but did did not have enough binding for pie filling. It makes a fabulous pudding, however! (Yes, two recipes in one!!!).

Pumpkin pie recipe:
Use your favorite crust recipe and line a 9 in. pie pan with crust. Mine happens to be Claire's quick and easy pie crust using spectrum organic shortening. You could easily substitute a different recipe to make this gluten-free.

Pumpkin pie filling ingredients:
2 c. pureed pumpkin (I used a can of Trader Joe's)
1/2 c. of coarsely ground oat flour (I used a food processor to grind rolled oats)
1 c. coconut milk light (I used canned from Trader Joe's)
Chia seed gel (1 Tbsp chia seed + 3 Tbsp water, sit for ~20 minutes before use)
1/4 c. light brown sugar, firmly packed
1/4 c. maple syrup
1/4 tsp. salt
1 tsp. ground cinnamon
1/4 tsp. ground ginger
1/4 tsp. ground nutmeg
Pumpkin pie filling thoroughly mixed.

Instructions:
1. Pre-heat oven to 375 deg. F. 
2. Combine all pumpkin pie filling ingredients and thoroughly mix.
2. Pour filling into pie shell (I covered my crust edges with aluminum foil for the first 30 minutes of baking and removed foil for the remainder of the bake time).
3. Bake for ~60 minutes (ovens may vary, so please check your pie sooner!).
4. Cool on rack and enjoy!





Monday, December 15, 2014

Why YOU should participate in a food allergy research study (Northwestern University currently seeking participants)


Research scientists must continually pitch their ideas.  Scientists “pitch” a funding agency when they write a grant – an elaborate document of their proposed studies, often including significant preliminary data to convince grant reviewers that their ideas are “going to work.” Writing grants is an essential part of a scientist’s job because without the money supplied by grants, research grinds to a halt (even for a university researcher!). And if that isn’t challenging enough, the scientists performing studies with human subjects must “pitch” their ideas to recruit a sufficient number of study participants to acquire enough data to draw trustworthy conclusions. It is true – the job of a scientist is part salesperson!

So here’s my pitch to all of you.

Share this post with as many people as you know because:
  1. It will help a great group of food allergy researchers at Northwestern University recruit participants to better understand a concerning problem for food allergies – what makes adolescents/young adults (14-22 year olds) more at risk from their food allergic reactions.
  2. Participating is easy – it is a short survey that can be accessed by internet (i.e. you don’t have to drive to Chicago to participate!).
  3. Answering the study questions will undoubtedly spin off many more questions that will help fund future grants, thus driving our understanding of this problem forward and ultimately improving the lives of those affected by food allergies.

I am including the details of the study with appropriate links below. If you’re already “sold” on sharing this widely or even participating, great! Scroll down to the section - STUDY OVERVIEW - to read the details provided directly by Dr. Ruchi Gupta’s team at Northwestern. If you need a little more “evidence,” I’ve got that, too. Read on.

Dr. Ruchi Gupta and her team with Illinois state Attorney General Lisa Madigan this past July. Dr. Gupta and her team helped advocate for a new law to expand Illinois' existing stock epinephrine for schools law.

Why I strongly support Dr. Gupta’s research group:

Any food allergy researcher who “pitches” their work to a funding agency, whether it is the federal government, a non-profit organization, or private investors must convince reviewers that food allergies are in fact a significant problem. Dr. Gupta’s group is behind many very solid studies that other researchers cite in their grant proposals to do just that – convince reviewers that yes, food allergies are in fact a large problem. Her group recently defined how prevalent food allergies are among U.S. children (1 in 13 children under 18 years of age)1 and just how enormous the economic burden of food allergies truly is on the U.S. economy (estimated at nearly $25 billion annually).2

I have no doubt that the outcome of the current study will serve as a research catalyst for herself and other researchers - a prominent citation in a grant proposal to justify further research funding to define why adolescents/young adults are more at risk of fatal anaphylaxis from their allergic reactions.3,4,5 While this is tragically a recognized problem, researchers still don’t fully understand why. Is it part psychology (e.g. teenagers/young adults tend to take more risks in general)?  Is it part biology (e.g. something about the biology of this age group drives stronger reactions)? Or is it some combination of both? Her work just may start to tease out the evidence to address those very questions in the future. If we understand the problem, we can design strategies to mitigate them.

Dr. Gupta “gets it.” As a mother to a child with food allergies herself, her work is not only driven by her scientific integrity, but also a very personal drive to make a difference in the lives of all who are touched by food allergies. The scientific questions she asks truly come from a deep understanding of food allergies. In addition to her busy job, Dr. Gupta lends her voice as a prominent researcher to advocate for and support the larger allergy community as a whole. She has written a book, The Food Allergy Experience, and regularly updates her blog, chronicling the many events where she has given back to the allergy community in very powerful ways.

Please help Dr. Gupta’s research group help all of us! Participate. Make a difference.

STUDY OVERVIEW:


Researchers at Northwestern Medicine are conducting a research study entitled “Risk Taking Behavior among Adolescents with Food Allergy," which is currently enrolling participants.  The goal of this study is to learn more about the risk taking behaviors of food allergic adolescents – both in regard to general risk taking and risk taking as it relates to food allergy.  In order to participate in the study, adolescents between the ages of 14 and 22 years who currently have a food allergy are being asked to complete an entirely anonymous and confidential electronic survey.  No protected health or identifying information is being collected.  No compensation is being offered in exchange for study participation. All aspects of this research study have been approved by the Northwestern Institutional Review Board, IRB STU00097291.


If you are between the ages of 18 and 22 and are interested in participating in this study, please click on this secure link to access the anonymous and confidential survey [https://redcap.nubic.northwestern.edu/redcap/surveys/?s=TcT8XLeZeA].

If you are a parent with a food allergic child between the ages of 14 and 17 and have no objections to your adolescent child participating in this study, please forward him/her this link [https://redcap.nubic.northwestern.edu/redcap/surveys/?s=TcT8XLeZeA].  The link will take him/her to the completely anonymous and confidential survey.

If you would prefer for your child not to participate, no further action is required.

If you have any questions prior to making your decision, please feel free to contact me directly at jacqueline.pence@northwestern.edu, or Dr. Gupta at r-gupta@northwestern.edu.

References:

1.           Gupta RS, Springston EE, Warrier MR, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128(1):e9-e17. doi:10.1542/peds.2011-0204.
2.           Gupta R, Holdford D, Bilaver L, Dyer A, Holl JL, Meltzer D. The economic impact of childhood food allergy in the United States. JAMA Pediatr. 2013;167(11):1026-1031. doi:10.1001/jamapediatrics.2013.2376.
3.           Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107(1):191-193. doi:10.1067/mai.2001.112031.
4.           Pumphrey R. Anaphylaxis: can we tell who is at risk of a fatal reaction? Curr Opin Allergy Clin Immunol. 2004;4(4):285-290. doi:10.1097/01.all.0000136762.89313.0b.
5.           Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327(6):380-384. doi:10.1056/NEJM199208063270603.




Thursday, September 25, 2014

Food Allergy Blogger's Conference 2014!

I'm thrilled to attend the Food Allergy Blogger's Conference (#FABlogCon) for the 2nd year in a row! Last year was truly a life-changing event for me, catalyzing many lasting, meaningful relationships across our food allergy community. The mutual understanding, support, and camaraderie of virtual friends meeting face-to-face was overwhelming in the best way possible for an introvert like me!

Look for me on Saturday morning at the break-out session on evidence-based blogging with Veronica LaFemina and Anna Luke from Food Allergy Research and Education (aka, FARE) and Henry Ehrlich, editor of Asthma Allergies Children and author of Food Allergies: Traditional Chinese Medicine, Western Science, and a Search for a Cure.

We hope to give lots of great advice and useful tips on blogging with integrity about food allergy science and discovery! I'll be leading the discussion on honest headlines and examining your personal bias. After all, how many times have you been frustrated by a misleading headline when it comes to food allergy research?!

If you can't make it, then please, please, please find me later and introduce yourself. I'm looking forward to meeting friends new and old (I'll be sure to give you one of my "business" post cards straight from Oregon!).

AND, if you can't make it to the conference, please follow along virtually on Twitter using the hashtag #FABlogCon. Selena at Amazing and Atopic did a wonderful job of explaining and providing a view of the Twitter feed, no Twitter account required!

See you soon!

My post on FABlogCon 2013