What is Triad Asthma (Aspirin-Exacerbated Respiratory Disease)?
Triad asthma, formally known as Aspirin-Exacerbated Respiratory Disease (AERD), is a clinical syndrome characterized by the classic triad of chronic rhinosinusitis with nasal polyps, asthma, and acute respiratory reactions triggered by aspirin or NSAIDs that inhibit COX-1. 1, 2
Core Clinical Features
The three defining components of AERD are:
- Chronic rhinosinusitis with nasal polyps that is typically severe and refractory to standard treatment 1, 2
- Asthma that is often difficult to control and more severe than in patients without AERD 2, 3
- Respiratory reactions to aspirin/NSAIDs including bronchoconstriction, severe asthma exacerbation, profuse rhinorrhea, and nasal congestion occurring within minutes to hours after ingestion 1, 2
Pathophysiology
AERD is not a true IgE-mediated allergy but rather a pseudoallergic reaction related to COX-1 inhibition. 2 When COX-1 is inhibited, arachidonic acid metabolism is diverted to the leukotriene pathway, resulting in overproduction of cysteinyl leukotrienes that drive the respiratory inflammation 2. This explains why patients react to all COX-1 inhibiting NSAIDs regardless of chemical structure, not just aspirin 1.
Epidemiology
- AERD affects approximately 7% of adults with asthma and up to one-third of patients with both asthma and nasal polyps 2, 4
- The condition is extremely rare in children, typically developing in the third decade of life or later 2, 5
- The typical progression begins with perennial rhinitis, followed by nasal polyps, then asthma, with aspirin sensitivity often recognized last 2
Diagnosis
The diagnosis is primarily established by clinical history, with an 80-100% probability of positive reaction on formal challenge testing when the history is typical. 1, 2
When Challenge Testing is Needed:
- Oral aspirin challenge should be performed when diagnostic uncertainty exists 1
- Challenge testing is NOT required in patients with ≥2 respiratory reactions to different NSAIDs or a respiratory reaction requiring hospitalization 1
- Skin testing and in vitro tests are not useful for AERD diagnosis 1, 2
Challenge Testing Methods:
- Nasal challenge with lysine aspirin is a safe alternative to oral/bronchial methods with good sensitivity and specificity 1
- Oral provocation starts with low doses (typically 30 mg aspirin) with gradual escalation 1
- A positive response includes ≥25% decrease in nasal airway volume or ≥20% drop in FEV1 1
Key Clinical Pitfalls
A critical caveat: respiratory inflammation persists in AERD even when patients avoid NSAIDs entirely. 4, 6 Simply avoiding aspirin and NSAIDs does not control the underlying disease—patients typically continue to experience refractory rhinosinusitis and asthma requiring aggressive medical and often surgical management 4.
Safe Medication Alternatives
- Selective COX-2 inhibitors are extremely safe and can be used as alternative analgesics in AERD patients 1, 2
- Acetaminophen (paracetamol) is the safest alternative analgesic, though high doses (650-1000 mg) may cause mild reactions in highly sensitive individuals 1, 2
- All non-selective COX-1 inhibiting NSAIDs must be avoided due to high cross-reactivity 2
Management Implications
Making the AERD diagnosis is critical because it provides opportunities for aspirin desensitization therapy, guides NSAID avoidance counseling, and signals that the underlying polypoid disease and asthma will likely be more recalcitrant to standard therapy 1. These patients often require repeated sinus surgeries, chronic systemic corticosteroids, and more aggressive management strategies than typical chronic rhinosinusitis or asthma patients 4, 3.