Dr. Peter Vadas is the Head of the Division of Allergy and Clinical Immunology at St. Michael’s Hospital, a teaching hospital affiliated with the University of Toronto. He is also a senior scientist at the Li Ka Shing Knowledge Institute and the Hospital for Sick Children Research Institute, in Toronto, focusing on identifying mechanisms and risk factors for severe and life-threatening anaphylaxis.
We recently spoke with him about his current research study looking at the causes of severe, near-fatal, or fatal anaphylaxis. In other words, looking at what the risk factors may be to cause a severe allergic reaction in someone.
In the pilot trials of his study, Dr. Vadas and his team studied both adult and pediatric patients who visited the emergency department due to an anaphylactic reaction to a variety of triggers, including food allergens, medications, insect stings, or unknown allergens.
As he describes it, reaction severity was graded, or scored, based on the involvement of different bodily systems, from skin involvement through “more severe cardio-pulmonary involvement.”
Ultimately, the research looked at two biochemical markers (a biochemical marker is any hormone, enzyme, antibody, or other substance that is detected in the urine, blood, or other body fluids or tissues that may serve as a sign of a disease or abnormality). One marker is called platelet activating factor (PAF), and the other is an enzyme that breaks down PAF, called platelet-activating factor acetyl hydrolase (PAF-AH). What the team found in that cohort of patients was that anaphylaxis severity was “directly proportional to the level of circulating PAF in their bloodstream. So, the higher the levels of PAF, the more severe the anaphylactic reaction.”
Because PAF-AH inactivates PAF, the team expected that the higher the levels of PAF-AH would be inversely proportional to the severity of anaphylaxis, “the more quickly PAF would be inactivated, the less severe the allergic reaction would be.” And this proved to be correct. In fact, the people who had the lowest levels of PAF-AH also had the most severe allergic reactions. “So, in other words, a deficiency of PAF-AH predisposed these individuals to severe anaphylaxis.”
As a part of the research, the team also looked at the following:
- A retrospective study, where they looked at a cohort of individuals who previously had anaphylactic reactions which were also graded by relative severity. And here too, they noted the same response – the lowest PAF-AH levels existed in patients with severe anaphylaxis, while those with normal or higher levels of PAF-AH had milder anaphylactic reactions.
- A cohort of individuals who had, sadly, died of anaphylaxis. When they measured the PAF-AH levels in blood samples, they were very low, indicating a PAF-AH deficiency. The team also sampled the blood of control group members – healthy adults and children with mild allergies, but not anaphylaxis, as well as individuals who had died of causes unrelated to anaphylaxis. What they found was telling: all the control groups had normal levels of PAF-AH.
According to Dr. Vadas, this means that, “the severity of anaphylaxis correlates directly to PAF levels, and its severity correlates inversely with PAF-AH.” This data has also been confirmed by other studies, pointing to the ability of PAF and PAF-AH to predict anaphylaxis severity. These aren’t the only markers or causes of severe or fatal anaphylaxis, but they are certainly among them.
Currently, his research involves working with Dr. Julia Upton at SickKids Hospital in Toronto to collect serum samples from patients who have visited emergency departments with anaphylactic reactions. The researchers are currently collecting serum first, during acute anaphylaxis, and once again a few weeks later, when they’ve recovered. The team will then look at these patients’ PAF-AH levels to see whether their baseline PAF-AH predicts severe anaphylaxis. “And our expectation,” he states, “is that our answer will be yes.”
The study itself began around 2006, but, as Dr. Vadas notes, it hasn’t always been easy, as the investigation itself is “very fidgety,” calling for stringency in lab conditions to ensure that the researchers obtain reliable results. “But because these same results have been confirmed on two other continents, I’m confident and comfortable with our findings.”
Research goals for the future
The “number one” aim of this research “is to establish a validated risk factor which is measurable, so that we can send off a blood test for patients. Because right now, we don’t have good biochemical markers of severity.” This might offer doctors a way to identify patients at higher risk of severe anaphylaxis, and allow them to manage their conditions more effectively. Another goal is to develop potential PAF and PAF-AH-related therapies for at-risk patients. This could lead to “a medication that blocks PAF receptors, either acutely, during acute anaphylaxis, as a rescue therapy, or to use daily on a long-term basis to prevent anaphylaxis.”
There are different approaches within the field of anaphylaxis research. Desensitization protocols such as patch desensitization and oral immunotherapy, for example, are among them. Summarizing his own research approach, Dr. Vadas notes that he is doing “something different, which is to take a condition which is life-threatening, like anaphylaxis, and convert it into a non-life-threatening condition.”
This is exciting research with eventual potential benefits for individuals with anaphylaxis not only in Canada, but worldwide. Wishing Dr. Vadas and his research team much success.