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Sept. 10, 2026

Otolaryngologists at Mayo Clinic are leading efforts to recognize aspirin-exacerbated respiratory disease (AERD) early, from identifying biomarkers to developing diagnostic screening questions that empower primary care physicians. Formerly known as Samter triad, AERD remains underrecognized, frequently resulting in delayed diagnosis, recurrent nasal polyps and repeat sinus surgeries before initiation of a targeted, multimodal treatment.

"The key and first thing you can do is ask the patient if they have ever taken aspirin or aspirin-related products and if they have ever had a reaction to it," says Angela M. Donaldson, M.D., an otolaryngologist at Mayo Clinic in Jacksonville, Florida. "For our practice, these are standard questions whenever we have a patient with chronic sinusitis."

Differentiating AERD from chronic rhinosinusitis with asthma

Doctors diagnose AERD using the current or historical presence of three defining clinical characteristics:

• Allergy to aspirin or aspirin-related products, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or high-salicylate foods and alcohol.
• Asthma.
• Chronic rhinosinusitis with nasal polyps.

"Asking a detailed history about subtle responses or reactions to aspirin can help delineate a potential aspirin-related condition from the run-of-the-mill chronic rhinosinusitis with polyps," Dr. Donaldson says.

Aspirin reactions can range from wheezing and shortness of breath to abdominal cramping and increased nasal congestion or drainage.

Alongside a history of aspirin reactions, strong indications for AERD include severe asthma, an extensive nasal polyp burden affecting most sinuses, and inspissated material on a sinus CT scan.

Compared with individuals who have chronic rhinosinusitis and asthma, patients with AERD generally experience more severe sinus symptoms and undergo a greater number of sinus surgeries. They also are more likely to develop oral corticosteroid-dependent disease, often receiving repeated courses of oral corticosteroids annually.

Recommended diagnostic labs and AERD biomarkers

To help establish a history of aspirin allergy and confirm an AERD diagnosis, physicians should evaluate:

• Complete blood count with differential to assess for elevated eosinophils.
• Serum immunoglobulin E to distinguish from environmental allergies or eosinophilic granulomatosis with polyangiitis.
• Urinary leukotriene E4 (LTE₄) to detect overproduction of cysteinyl leukotrienes.

Urinary LTE₄ measurement, validated and described by Mayo Clinic researchers in The Journal of Allergy and Clinical Immunology: In Practice, serves as a potential biomarker for distinguishing AERD from other respiratory phenotypes. Mayo Clinic otolaryngologists use urinary LTE₄ to help assess for AERD in patients who have chronic rhinosinusitis with nasal polyps and initiate multidisciplinary care as needed. They also employ intraoperative tissue biopsy to evaluate elevated tissue eosinophils, which informs treatment plans as an indicator of disease severity and predictor of disease recurrence.

Mayo Clinic otolaryngologists and allergists are currently investigating additional biomarkers to improve AERD diagnostic accuracy and guide personalized treatment selection, including whether urinary LTE₄ levels can determine when to de-escalate medical therapies.

Referring to a tertiary center for AERD aspirin challenge and treatment

Physicians should consider referring patients with suspected AERD to a center that can provide tertiary care, given the disease complexity and severity. When required for diagnostic confirmation, aspirin challenge testing is most safely performed in centers equipped with allergists, experienced nursing staff and immediate access to an intensive care unit due to the risk of anaphylaxis or an asthma attack.

Tertiary centers also provide access to specialists experienced in comprehensive functional endoscopic sinus surgery, particularly for patients with complex frontal sinus disease and extensive eosinophilic disease. Additionally, dedicated asthma management resources help optimize postoperative outcomes and minimize complications.

"It is not only the preoperative collaboration, but also the multidisciplinary aspect of postoperative care that I think Mayo Clinic is really well set up to provide for these patients," Dr. Donaldson says. "There are many different treatments for this condition, and conversations between otolaryngology, allergy and pulmonology allow for disease control and treatment de-escalation over time in a safe and stepwise fashion."

Optimizing medical therapies and sinus surgery for AERD

Managing AERD requires a multimodal and individualized approach, integrating medical therapies and surgical interventions. At Mayo Clinic, AERD treatment strategies may include:

• Topical steroids administered pre- and postoperatively, with steroid irrigation preferred to nasal sprays for the greatest effect on severe polyps.
• Primary endoscopic sinus surgery to debulk polyps, remove eosinophilic tissue and open all sinuses.
• Nasal endoscopic monitoring of polyps and eosinophils to guide medical therapy changes.
• Aspirin desensitization with daily high-dose aspirin therapy in select patients to decrease airway inflammation and improve asthma control.
• Biologics to control eosinophil production postoperatively or in patients who are not surgical candidates, which help reduce polyps, inflammation and respiratory symptoms.
• Revision endoscopic sinus surgery when necessary to manage recurrent disease and improve direct delivery of topical steroids.

"Every person with AERD deserves a full endoscopic sinus surgery where all of their sinuses have been addressed, especially if it is their primary surgery," Dr. Donaldson says. "There is also a discussion of whether aspirin therapy makes sense in the day and age of biologics. But I think there is a subset of people it works well for when it comes to financial access and ability to safely take NSAIDs as needed."

As biologics continue to evolve, researchers aim to develop faster acting, more cost-effective therapies that provide quality-of-life improvements comparable to sinus surgery.

Long-term AERD control and patient adherence

Postoperative AERD management typically requires lifelong, daily medical therapy. Although the frequency or dose of medication may be reduced over time in patients whose symptoms are well controlled, adherence is critical to prevent inflammation and disease recurrence.

"When people feel well for a reasonable amount of time, they tend to forget what it was like to feel ill, and so then they stop taking medicine," Dr. Donaldson says. "It is important to educate patients about the fact that AERD is a chronic condition. Patients should understand that, with good multidisciplinary care, they can become asymptomatic from this condition, but it requires control with some form of medication, as we understand the disease now."

For more information

Divekar R, et al. Diagnostic utility of urinary LTE₄ in asthma, allergic rhinitis, chronic rhinosinusitis, nasal polyps, and aspirin sensitivity. The Journal of Allergy and Clinical Immunology: In Practice. 2016;4:665.

Refer a patient to Mayo Clinic.