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.

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.

In the latest edition of medical headline hyperbole, many of us learned last week that “Fatal peanut allergies could be cured by probiotic bacteria, say Australian doctors” and “This Breakthrough Treatment Helped Over 80 Percent of Allergic Kids Tolerate Peanuts.”

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