What is the treatment for triad asthma (aspirin-exacerbated respiratory disease, AERD)?

Treatment of Aspirin-Exacerbated Respiratory Disease (AERD)

The cornerstone of AERD management involves strict avoidance of aspirin and NSAIDs combined with aggressive medical treatment of underlying asthma and rhinosinusitis, with aspirin desensitization followed by daily maintenance aspirin therapy being the most important therapeutic option for patients with poorly controlled disease despite standard medications. 1

Initial Management Strategy

Medication Avoidance and Safe Alternatives

• All COX-1 inhibiting NSAIDs must be strictly avoided, as they universally cross-react and trigger respiratory reactions in AERD patients 1, 2
• Selective COX-2 inhibitors (celecoxib, etoricoxib) are extremely safe and can be used as alternative analgesics, as reactions to these agents are extremely rare in AERD 1, 2
• Acetaminophen up to 650 mg is safe for analgesic or antipyretic relief in AERD patients 3
• Weak COX-1 inhibitors such as sodium salicylate or choline magnesium trisalicylate can also be used safely 3

Aggressive Medical Management of Underlying Disease

• Inhaled corticosteroid/long-acting beta-agonist combinations are mandatory for optimizing asthma control and should be used at higher doses than typical asthma management 1
• Leukotriene-modifying agents (montelukast, zafirlukast) have an established role in long-term management and should be considered first-line therapy 2
• Intranasal corticosteroids are effective, with twice-daily dosing being superior to once-daily dosing for controlling rhinosinusitis symptoms 2
• Systemic corticosteroids may be required for patients with severe, refractory disease 1

Surgical Intervention

• Endoscopic sinus surgery with debulking polypectomy is often necessary for recurrent or intractable nasal polyps, though polyps typically recur despite avoidance of aspirin/NSAIDs 1, 4

Aspirin Desensitization: The Definitive Therapeutic Option

Indications for Aspirin Desensitization

Aspirin desensitization should be strongly considered for patients with:

• Poorly controlled upper and/or lower airway disease despite appropriate medications 1
• Requirement for long-term systemic corticosteroids to control respiratory disease 1
• Recurrent nasal polyps requiring repeated surgical interventions 1
• Need for cardioprotection or pain relief requiring aspirin therapy 1

Pre-Desensitization Preparation

• Leukotriene-modifying agents are recommended as pretreatment for patients not already taking them, as they diminish the lower respiratory asthmatic response during desensitization 1
• Inhaled corticosteroid/long-acting beta-agonist inhalers should be optimized prior to desensitization to diminish the severity of NSAID-induced bronchospasm 1
• Asthma must be well-controlled before attempting desensitization 1

Desensitization Protocol

The standard aspirin desensitization protocol involves:

• Starting with low doses (20.25-40.5 mg) and gradually escalating over 1-2 days 1
• Most patients react at doses between 40.25 mg and 120 mg of aspirin 1
• When a reaction occurs, the protocol is paused until the reaction resolves, then the triggering dose is repeated before up-dosing 1
• The target maintenance dose is typically 325 mg daily initially, then increased to 650 mg twice daily for optimal control of nasal polyps and airway inflammation 1

Maintenance Therapy and Long-Term Outcomes

• Daily aspirin must be continued indefinitely to maintain the desensitized state, with at least 325 mg once daily required 1
• Gaps in aspirin doses >48 hours may lead to loss of tolerance, and after 5 days all patients will react and require repeat desensitization 1
• Once desensitized, universal tolerance to all COX-1 inhibiting NSAIDs is achieved 1

Clinical outcomes with long-term aspirin therapy:

• 67% of patients improve in their clinical course while decreasing systemic and topical corticosteroids 5
• Significant improvement in sense of smell, asthma, sinus, and allergic rhinitis symptoms occurs in patients remaining on aspirin therapy 6
• 68% of patients have a positive response and do not require further sinus surgery 6
• Nearly 85% of AERD patients on aspirin therapy find it helpful in improving airway disease and quality of life 6
• Aspirin desensitization is cost-effective at $6,768 per quality-adjusted life-year 1
• Long-term use beyond 10 years appears safe and effective 6

Managing Aspirin Interruption for Surgery

• If surgery can be performed within a 48-hour window, aspirin can be restarted immediately at the previous dose without loss of tolerance 1
• For longer interruptions, reduce aspirin to 325 mg daily for 7 days before surgery, hold the day before and day of surgery, then restart immediately postoperatively 1
• Ibuprofen can be used as a "bridge" during surgery to reduce bleeding complications while maintaining tolerance 1
• For interruptions >48 hours, desensitization must be repeated 1

Gastrointestinal Protection

• Enteric-coated aspirin and gastrointestinal prophylaxis (proton pump inhibitors) should be considered, as aspirin therapy may cause gastritis, epigastric pain, or gastrointestinal bleeding 1
• Approximately 14% of patients stop aspirin due to intractable gastrointestinal side effects 5

Emerging Biologic Therapies

• Dupilumab shows benefit in AERD patients with nasal polyposis, though its effect on NSAID hypersensitivity remains to be fully determined 1
• Omalizumab may affect NSAID-induced hypersensitivity and could lead to negative challenges in some patients 1

Common Pitfalls to Avoid

• Do not perform aspirin challenge solely to confirm diagnosis in patients with ≥2 respiratory reactions to different NSAIDs or a respiratory reaction requiring hospitalization, as the diagnosis is already established 1
• Do not abruptly substitute aspirin desensitization for inhaled or oral corticosteroids without gradual tapering under medical supervision 7
• Do not expect aspirin desensitization to prevent bronchoconstrictor response to aspirin or NSAIDs during the desensitization procedure itself—this is expected and managed by pausing the protocol 7
• Do not discontinue daily aspirin maintenance therapy without understanding that tolerance will be lost within 48 hours 1