Monday, December 27, 2010

Threshold Research

University of Nebraska Lincoln has a division called the Food Allergy Research and Resource Program. Their program has done a number interesting projects. One of their current projects is studying how much of a food allergen is too much--in other words, how much can an allergic person ingest before an adverse reaction occurs?

I know from Sophie's experiences that not every exposure results in a bad reaction--some exposures result in no discernible reaction. So how do you go about finding what the exposure threshold is?

The FARRP team has analyzed data based on challenges at a large food allergy clinic to begin determining what the threshold may be for peanut allergies. Obviously there's a great deal of additional research and analysis necessary in order to come to any real conclusions about allergic thresholds.

I had a few questions as I read about the study, and I was able to contact Professor Stephen Taylor for some additional information.
Me: Is the threshold different for different people?

Professor Taylor: Yes, absolutely. The range of individual thresholds is amazingly broad. For peanuts where we have the most information, individual thresholds (as defined by lowest dose provoking a mild objective reaction) range from 0.4 mg up to above 8 g (expressed as whole peanut). Since an "average" peanut weighs about 350 mg, some with an individual threshold would have to eat 20 peanuts to experience symptoms.
Individual thresholds may also vary with age over time. This does not appear to happen for peanut in most individuals so it is a life-long affliction. But many infants with milk allergy will ultimately become tolerant - outgrow their allergy (not all of them do unfortunately).

Me: What symptoms are considered a "reaction" and is this standard being universally applied?

Professor Taylor: Great question. Not everyone uses the same definition of a reaction. We are currently seeking consensus. But, our group uses the first signs of an objective reaction (something the physician can see such as a hive or two, lip swelling, flare of eczema, etc.). We have one exception to that definition and we also recognize abdominal pain (a subjective symptom) as a credible sign especially in infants. Other groups use the first subjective symptom (mouth itching, stuffiness, etc.) as the definition of a reaction. We know of one group that requires 3 or more hives as opposed to just one (which is fine in our definition).
In all of these definition, the signs and symptoms would spontaneously resolve within 15 minutes without any pharmacological treatment. It would be quite unethical to continue with challenge doses to determine the amount needed to provoke a more serious reaction.
In our opinion, the first sign of a mild objective reaction is the most universal and consistent definition. Subjective symptoms appear to be more dependent and variable depending upon the physician/nurse doing the challenge.

Me: If thresholds are established for each allergen, in what ways will this complicate the process of consumers determining safe foods? Since allergies tend to have a cumulative effect (for example, a consumer may eat more than one food at a single meal with a "below threshold: does of their allergen), will consumers opt to maintain their zero exposure standard, rather than risking a reaction based on the cumulative effects of eating multiple foods?

Professor Taylor: For most IgE-mediated reactions, symptoms are immediate (within 2 hrs) and not cumulative. We are only seeking to define thresholds for these immediate hypersensitivity type of reactions. This approach would not be applicable to more delayed conditions where cumulative doses might matter (still unclear) such as eosinophilic esophagitis, ulcerative colitis, celiac disease, etc.
The idea is to establish population thresholds (e.g. for all peanut-allergic individuals) that would be safe for the vast majority of all consumers with a particular food allergy. We are currently in the research phase. Consensus has not been reached on any of those population thresholds. Obviously, this must be approached with great care and consensus must be sought. Consumer groups such as the Food Allergy & Anaphylaxis Network must be included in reaching consensus but we have only now initiated the beginning of that process because we are still in the research phase. Scientists have a lot of individual threshold data for peanut, milk, and egg but lesser amounts of data for other allergenic foods. Thus, we may need to generate data before we can even think about thresholds for all allergenic foods.
How will thresholds affect consumers? I cannot be sure at this point. Our goal at the moment is to use population thresholds to guide industry use of precautionary/advisory labels (e.g. may contain peanuts and the like). With no guidance on thresholds, the food industry tends to apply such labels to products on a rather wide scale. Many of these products contain no detectable peanut or milk (the ones that we have looked for) using assays that would detect amounts below any known threshold dose for individuals.
Consumer behavior regarding thresholds is another unknown. Obviously, consumers will need to trust that these levels are safe. That is why widespread consensus is so important. We recognize that communication with allergic consumers is ultra-important on this subject but it is probably premature to make a major effort here until the scientists reach some level of consensus. But ultimately the consensus needs to include consumers, physicians (allergists), public health agencies (e.g. FDA), the food industry, and the research scientists.
I realize that consumers make every attempt to adopt a zero exposure standard. Until thresholds are established, they have no other choice to stay safe. But, recognize that the real goal is safe and not zero.
As we establish thresholds, we do need to take many factors into account - individual differences, possible exacerbating factors (such as other illnesses, exercise, medications, pollen season, etc.), and certainly the ingestion of multiple foods in a meal. All of that is part of the ongoing discussion. Again, rest assured that everyone has the exact same goal - safe foods for allergic consumers.

I am thrilled by this research and eagerly look forward to watching the progress of this group.

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