Tanya M. Laidlaw, MD
Aspirin exacerbated respiratory disease, which we refer to as AERD, has gone by several other names, including Samter's triad and aspirin triad. And the three symptoms that really come together to form that syndrome are asthma, nasal polyps and respiratory reactions to aspirin or other medications like aspirin, things like ibuprofen and naprosyn that are in the same group as aspirin.
AERD affects about seven percent of all adults with asthma. So we suspect that there are about a million patients in the United States who have AERD; although not necessarily all of them have been properly diagnosed yet, because it can be difficult to diagnose.
Patients who have asthma and nasal polyps and can tell you that they had a reaction to either aspirin or ibuprofen or naprosyn, they clearly have the disease.
For patients who have asthma and nasal polyps, but either don't take medications like aspirin or ibuprofen, or can't remember if they've ever had a reaction to one of them, those are the more challenging patients. And those are patients where we actually need to bring them into the clinic and, under safe conditions, give them a dose or two of aspirin to see if they will have a reaction. We do this under very controlled conditions and do it safely.
It turns out that these patients can be desensitized to aspirin. And we can do that because giving them high doses of aspirin, once they're able to tolerate the medication, can act as a therapy for them. It's really the only medication that we have available to us right now that will prevent their nasal polyps from growing back and can provide by far the best standard of care for them.
The desensitization procedure begins with half of a baby dose of aspirin, a very small dose. And then every one to three hours, we increase the dose of aspirin, until they start to get a bit of a reaction. And we're able to treat them through the reaction. And once the reaction has finished, their body has already begun to tolerate the medication, and we can continue to give them increasing doses of aspirin that same day to complete the desensitization.
The doses of aspirin that we need to treat them are actually quite high. So patients will take up to one to two grams of aspirin per day, every day, as one of their regular medical therapies for this treatment. The unfortunate part about the treatment is that if you lapse in taking the aspirin for just three or four days, you both become re-sensitive and re-allergic to it, and you lose the therapeutic benefit. So it becomes a lifelong therapy for our patients.
It turns out that the side effects of taking high dose aspirin are almost exactly the same as taking low dose aspirin. So our patients are at slightly increased risk of bruising and bleeding, but so are patients who take a simple low dose aspirin every day. One of the only side effects that increases in patients who take higher dose aspirin are the GI side effects – the gastrointestinal symptoms.
Our Brigham and Women's Hospital AERD Center consists of a team of allergists and otolaryngology specialists who are able to clinically evaluate and treat patients with AERD quickly and with a lot of expertise. So we are able to provide aspirin challenges and aspirin desensitization procedures, both in the outpatient clinic setting or in the inpatient clinic setting if it is safer for that patient. We're also able to refer quickly to ENT specialists in case those patients need nasal polyp surgeries or advice from the nasal surgeon in terms of what would be best for treating their nasal symptoms as well.
So we currently have two clinical trials ongoing at the Brigham and Women's Hospital AERD Center. The first one is a clinical trial that involves trying to decrease the contribution of platelets to the inflammation in the disease.
When we looked into the nasal polyp tissue of patients with AERD, we found many more platelets attached to their immune cells than we did in the sinus tissue of healthier patients. We also looked in their blood and again found many more platelets attached to the immune cells in the blood of patients with AERD than in healthy controls.
With that new discovery in mind, we were able to take advantage of existing anti-platelet therapies that act to decrease the activation of the platelet and decrease the inflammation that platelets can cause.
And we're now using one of those anti-platelet therapies to determine whether or not it will help decrease the inflammation overall in our patients enough to help their symptoms or to completely block their reactions to aspirin.
The second clinical trial we have ongoing is actually a non-medical intervention. It's one that involves dietary control. It turns out that one of the main causes of inflammation in our patients with AERD is that they overproduce two pro-inflammatory chemicals called prostaglandins and leukotrienes, which are general classes of inflammatory chemicals.
Those chemicals cannot be made by the human body unless we eat the amino acids that are the building blocks for those chemicals. And those amino acid building blocks exist only in omega-6 fatty acids.
And so, we have created a dietary intervention where we help patients reduce the amount of omega-6 fatty acids they eat every day and instead increase the amount of omega-3 fatty acids in their diet. And then we test to see whether or not their symptoms have improved after the dietary intervention or whether or not the amount of chemicals – of prostaglandins and leukotrienes – they’re making have decreased in their blood.
So we made an observation in our clinic just a couple of years ago that many of our patients with AERD also reported that they had similar symptoms when they drank alcohol.
We found that more than half of our patients with AERD report that many forms of alcohol will cause respiratory symptoms, and it is often within less than one glass of alcohol, and it is not something that any of our current standard therapies seems to improve.
Our group at the Brigham and Women's Hospital AERD Center now has the largest registry in the country of patients who are clinically diagnosed with AERD and are willing and interested in participating in research. We're also able to use this registry of patients to understand many of the clinical trends in the disease that had not previously been known. Understanding better who would be at risk for the disease, understanding better what the normal clinical trajectory or clinical course of the disease would be can really help shape the field in terms of what areas of interest would be best for research in the future.