Those who face aspirin-exacerbated respiratory disease (AERD)--also known as Samter's Triad or aspirin sensitive asthma--may not know it for possibly decades, if ever.
Symptoms often do not develop until the person hits their 30s or 40s. "The typical patient is a middle-aged to young adult who has a decreased sense of smell, progressive sinus disease, and may not know they have polyps," says John Anderson, MD with Alabama Allergy & Asthma Center.
AERD is an acquired condition. The patient will manifest three primary symptoms: asthma, sinus inflammation with nasal polyps, and a sensitivity to aspirin and other non-steroidal, anti-inflammatory drugs (NSAIDs). "What causes this cluster of symptoms to occur together is still be being researched," Anderson says.
People with Samter's Triad often develop asthma after they have developed sinus disease. They may also complain of facial pain and sometimes have other associated problems, like a constant nasal drip, persistent cough, or ear pressure. "Then they usually end up with an allergist because they took aspirin and had an acute asthma attack that leads to emergency care," Anderson says. "It's at this point that aspirin-allergy is discovered."
As a distinct subset of asthma, AERD is not a common affliction. According to a 2015 meta-analysis of literature, it afflicts seven percent of typical adult asthmatic patients and twice that number in patients with severe asthma. This percentage rises to 25 percent among those with both asthma and nasal polyps, according to The Samter's Society, which estimates that over a million people in the United States have AERD.
"We can't say aspirin causes Samter's Triad," Anderson says. "The chronic asthma symptoms usually begin while the patient is tolerating aspirin or even without using aspirin. So the cause is not aspirin, but aspirin unmasks it for us."
An alternative to perpetually medicating the symptoms and avoiding NSAIDs is aspirin desensitization. The process takes two to three day-long sessions in an allergist's office. During office hours, the patient receives small oral doses of aspirin that gradually increase in three-hour increments. For severe patients with a history of life-threating reactions or very severe asthma, the process is performed in a hospital.
"It's different from other desensitizations, which are done in 30 minute increments, because aspirin patients will invariably develop a flare of respiratory symptoms during the desensitization," Anderson says. "They will react before they get better."
Most often the flare symptoms are mild, such as a slight drop in lung function or an increased sinus symptom. "We halt the desensitization then and treat them until they feel better. Then we re-challenge them at the same dose they flared with until they don't react to that dose," Anderson says. Flares usually happen once or twice.
The process ends when the patient can tolerate 650 milligrams of aspirin. But they must continue taking a daily dose of 650 milligrams twice daily in perpetuity. "We usually inch the dosage down if they're responding, because of the potential side effects," Anderson says.
The lowest dose prescribed might be one regular-dose aspirin of 325 milligrams once or twice daily. "The problem is that the lower we go, the more we risk insufficient suppression of this pathway and polyp regrowth," Anderson says.
The downside to the daily aspirin dosage includes indigestion or gastrointestinal (GI) bleeding if the patient develops ulcerations. "If they have any underlying GI problems of heartburn or reflux before we do this procedure we often make sure they're on an anti-reflux regimen, like proton pump inhibitors," Anderson says.
The maintenance dosage is required because, unlike with allergy shots, desensitization does not induce long-term tolerance to a substance at a level where exposure no longer causes an inflammatory response. "So if these patients withhold their daily aspirin, they will be re-sensitized to it. The desensitization is a temporary physiologic state," Anderson says.
This leads to a potentially significant fail rate for the protocol. Some patients cannot maintain the needed consistency. And in others, it may not work. In one trial, 24 (14 percent) of the 172 patients discontinued the medication because of side effects. For those who tolerated a year or more of treatment, 87 percent experienced improvement. Aspirin desensitization offers patients a chance to be free of polyp regrowth and the chronic asthma symptoms by taking two inexpensive pills a day.
"If the patient is a candidate for desensitization, then that's the gold standard approach for the moment, but we have an eye toward the biologic medications," Anderson says. Xolair, Nucala, and Dupixent have had promising results in small studies. "And they are doing larger studies as we speak," he says, adding that Alabama Allergy participates in those clinical trials.
Anderson says the most helpful change that can be made for those with potential AERD right now is the advice they hear. "People with reactions to aspirin are told not to take that medicine again,'" he says. "What they should be told is, 'Go see an allergist.'"