What is Aspirin Triad (AERD)?
Aspirin triad, now termed Aspirin-Exacerbated Respiratory Disease (AERD), is a clinical syndrome characterized by three defining features: asthma, chronic rhinosinusitis with nasal polyps, and acute respiratory reactions triggered by aspirin or other COX-1 inhibiting NSAIDs. 1, 2
The Classic Triad Components
The three essential elements that define AERD are:
Asthma: Typically severe and difficult-to-control, often requiring higher doses of inhaled corticosteroids and more frequent systemic corticosteroid courses compared to non-AERD asthma patients 2, 3
Chronic rhinosinusitis with nasal polyps: The nasal polyps are characteristically refractory to treatment and regrow rapidly after surgical removal, often accompanied by anosmia (loss of smell) and severe nasal congestion 2, 4, 5
Acute respiratory reactions to aspirin/NSAIDs: Within 30 minutes to 3 hours of ingesting COX-1 inhibiting NSAIDs, patients develop sudden onset of bronchoconstriction, severe asthma exacerbation, profuse rhinorrhea, nasal congestion, and sometimes laryngospasm 2, 6
Key Pathophysiologic Mechanism
AERD is NOT a true IgE-mediated allergy but rather a pseudoallergic reaction caused by COX-1 inhibition. 2 When COX-1 is blocked, arachidonic acid metabolism is diverted to the leukotriene pathway, resulting in massive overproduction of pro-inflammatory cysteinyl leukotrienes while simultaneously decreasing protective prostaglandin E2 1, 2, 6
Cross-Reactivity Pattern
All COX-1 inhibiting NSAIDs cross-react and trigger reactions in AERD patients—this is not drug-specific but mechanism-specific. 1 This includes:
- Aspirin, ibuprofen, naproxen, indomethacin, ketorolac, and other traditional NSAIDs 1, 6
- Selective COX-2 inhibitors (celecoxib) are extremely safe and rarely cause reactions in AERD patients 1
Epidemiology and Clinical Presentation
- AERD affects approximately 7% of adults with asthma, but prevalence increases to 25% in patients with severe, persistent asthma 2, 3
- The condition is extremely rare in children and typically develops in adulthood 2
- The typical progression begins with perennial rhinitis, followed by nasal polyposis, then asthma, with aspirin sensitivity often manifesting last 2
Diagnostic Approach
The diagnosis is primarily clinical, established by history alone in most cases, with 80-100% probability of a positive reaction on formal aspirin challenge when the history is typical. 1, 2
Formal oral aspirin challenge is reserved for cases of diagnostic uncertainty:
- Remote or unclear NSAID reaction history 1
- Atypical reaction descriptions (cutaneous-only symptoms, reactions >3 hours after ingestion, or prolonged symptoms lasting >8-10 hours) 1
- Patients who never take NSAIDs and have no exposure history 1
Important diagnostic pearls:
- Skin testing and in vitro tests are completely useless for AERD diagnosis 1
- Patients with ≥2 respiratory reactions to different NSAIDs or a single reaction requiring hospitalization do NOT need confirmatory aspirin challenge—the diagnosis is established by history alone 1
Common Pitfalls to Avoid
Do not confuse AERD with IgE-mediated drug allergy—AERD patients can safely use selective COX-2 inhibitors, whereas true aspirin allergy would preclude all aspirin-containing products regardless of COX selectivity 1, 2
Do not assume avoidance of aspirin/NSAIDs will improve the underlying disease—AERD is a chronic progressive condition that continues to worsen even with complete NSAID avoidance 6
Recognize that AERD represents more recalcitrant underlying disease—making this diagnosis provides critical insight that the patient's nasal polyps and asthma will likely be more difficult to control and may require more aggressive therapy including consideration of aspirin desensitization or biologic agents 1, 7