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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Pulmonology · Aspirin-Exacerbated Respiratory Disease

The Science of the Shutdown: Biology and Diagnosis

At a Glance

Aspirin-Exacerbated Respiratory Disease (AERD) is caused by a metabolic imbalance of inflammatory chemicals, not an allergy. While a clinical history of asthma and nasal polyps provides clues, the only definitive way to diagnose AERD is through a medically supervised aspirin challenge.

If you have AERD, your body is essentially “short-circuited” at a metabolic level. While it may feel like an allergy, the root cause is a fundamental imbalance in how your body processes certain fats to manage inflammation [1][2].

The Biology of Imbalance: Brake and Gas

To understand AERD, it helps to think of two opposing chemicals in your body: Prostaglandin E2 (PGE2) and Cysteinyl Leukotrienes [3][4].

  • The “Brake” (PGE2): In a healthy body, PGE2 acts as a natural anti-inflammatory “brake.” It keeps your airways open and prevents your immune cells from becoming overactive [3][5]. People with AERD have a chronic deficiency of this protective chemical [3][6].
  • The “Gas” (Leukotrienes): Leukotrienes are the “gas” that drives inflammation. They are incredibly powerful—far more potent than histamine—at causing the swelling, mucus production, and airway tightening that lead to asthma and nasal polyps [1][4].

In AERD, the “brake” is broken, and the “gas” is stuck on high. When you take aspirin or an NSAID (like ibuprofen), it blocks an enzyme called COX-1. In most people, this is harmless. But in someone with AERD, blocking COX-1 causes the already-low PGE2 to crash, which triggers a massive, sudden release of leukotrienes—leading to a severe respiratory reaction [3][7].

How Doctors Confirm AERD

Diagnosing AERD can be tricky because there is currently no simple blood test that can tell you “yes” or “no” [8][9].

1. Clinical History

Your doctor will first look for the “triad”: adult-onset asthma, recurring nasal polyps, and any history of reacting to aspirin [10][11]. However, many patients have avoided these drugs for years, making their history “equivocal” or unclear [12][13].

2. The Gold Standard: The Aspirin Challenge

The only definitive way to diagnose AERD is through a medically supervised aspirin challenge [14][15].

  • What happens: You are given tiny, gradually increasing doses of aspirin (oral or intranasal) over several hours or two days [14][16].
  • Safety: This is performed in a specialized clinic equipped to handle respiratory reactions. Doctors monitor your lung function (using a spirometer to measure FEV1) and nasal symptoms throughout the process [17][18].
  • The Goal: A “positive” result—meaning a controlled reaction occurs—confirms the diagnosis and often leads directly into aspirin desensitization treatment [14][19].

CRITICAL WARNING: You should never attempt to test your own aspirin sensitivity or conduct an “at-home challenge.” Because the reaction can cause severe, sudden airway closure (bronchospasm), this test must only be performed in a specialized medical facility with emergency resuscitation equipment and rescue medications immediately available [18][15].

3. Biomarkers: The uLTE4 Test

You may hear about the Urinary Leukotriene E4 (uLTE4) test. This measures the amount of leukotrienes in your urine. While AERD patients typically have higher levels than those with standard asthma, the levels can overlap between the two groups [20][21]. Therefore, while uLTE4 is a helpful “hint” or biomarker for disease severity, it is not currently used as a standalone diagnostic tool [20][22]. Your clinical history and the aspirin challenge remain the most reliable ways to get an answer [20].

Common questions in this guide

How do doctors diagnose AERD?
Doctors look for a clinical history of adult-onset asthma, recurring nasal polyps, and respiratory reactions to aspirin or NSAIDs. However, the only definitive way to confirm an AERD diagnosis is through a medically supervised aspirin challenge in a clinic.
What happens during an aspirin challenge test?
During the test, you are given tiny, gradually increasing doses of aspirin over several hours or days in a specialized clinic. Doctors closely monitor your lung function and nasal symptoms to safely confirm if a controlled reaction occurs.
Is it safe to test my aspirin sensitivity at home?
You should never attempt to test your aspirin sensitivity at home. The reaction can cause severe and sudden airway closure, so this test must only be performed in a specialized medical facility with emergency resuscitation equipment and rescue medications available.
Can a blood or urine test diagnose AERD?
There is no simple blood test that can say exactly whether or not you have AERD. While doctors can measure urinary leukotriene E4 (uLTE4) levels as a biomarker for disease severity, it cannot definitively diagnose the condition on its own.
Why do aspirin and NSAIDs cause an asthma attack in people with AERD?
If you have AERD, taking an NSAID blocks an enzyme called COX-1, which causes your body's already-low protective anti-inflammatory chemicals to crash. This triggers a massive, sudden release of inflammatory leukotrienes that lead to a severe respiratory reaction.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my history, do you think I need a supervised aspirin challenge to confirm my diagnosis, or is my clinical history clear enough?
  2. 2.How do you ensure my safety during an aspirin challenge, especially since I have a history of severe asthma?
  3. 3.Can we test my urinary leukotriene E4 (uLTE4) levels to see if they are elevated, and how would that result change my treatment?
  4. 4.If I have an aspirin challenge, can we transition directly into aspirin desensitization?
  5. 5.Are there certain medications, like Singulair (montelukast), that I need to stop before undergoing a challenge?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (22)
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    Lipid Mediators in Aspirin-Exacerbated Respiratory Disease.

    Parker AR, Ayars AG, Altman MC, Henderson WR

    Immunology and allergy clinics of North America 2016; (36(4)):749-763 doi:10.1016/j.iac.2016.06.009.

    PMID: 27712768
  2. 2

    Cysteinyl Leukotrienes in Allergic Inflammation.

    Lee M, Boyce JA, Barrett NA

    Annual review of pathology 2025; (20(1)):115-141 doi:10.1146/annurev-pathmechdis-111523-023509.

    PMID: 39374430
  3. 3

    Low Prostaglandin E2 but High Prostaglandin D2, a Paradoxical Dissociation in Arachidonic Acid Metabolism in Aspirin-Exacerbated Airway Disease: Role of Airway Epithelium.

    Picado C, Machado-Carvalho L, Roca-Ferrer J

    Journal of clinical medicine 2024; (13(23)) doi:10.3390/jcm13237416.

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    Epithelial folliculin enhances airway inflammation in aspirin-exacerbated respiratory disease.

    Trinh HKT, Pham DL, Choi Y, et al.

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    Prostaglandin E2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin.

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    Mediator production and severity of aspirin-induced respiratory reactions: Impact of sampling site and body mass index.

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    What's New in the Diagnosis and Treatment of Aspirin-Exacerbated Respiratory Disease: A Brief Review.

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    A novel treatment adjunct for aspirin exacerbated respiratory disease: the low-salicylate diet: a multicenter randomized control crossover trial.

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    Diagnostic Role of Aspirin Challenge in NSAID-Exacerbated Respiratory Disease: A Prospective Single-Center Study in China.

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This page explains the biology and diagnosis of Aspirin-Exacerbated Respiratory Disease for informational purposes only. Never attempt an aspirin challenge at home; it must always be conducted under strict medical supervision.

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