What is the treatment for a patient presenting with acute aspirin-exacerbated respiratory disease (AERD)?

Management of Acute Aspirin-Exacerbated Respiratory Disease (AERD)

For acute presentations of AERD, immediately administer short-acting inhaled beta-agonists for bronchospasm, provide systemic corticosteroids if severe, and ensure strict avoidance of all COX-1 inhibiting NSAIDs while initiating high-dose inhaled corticosteroid/long-acting beta-agonist therapy. 1, 2

Immediate Acute Management

• Bronchodilator therapy is the cornerstone of acute management—patients must have short-acting inhaled beta-agonists available for rescue during any acute exacerbation, as leukotriene modifiers and aspirin desensitization do not reverse acute bronchospasm 2

• Systemic corticosteroids (oral prednisone or IV methylprednisolone) should be administered for moderate-to-severe acute exacerbations, as AERD patients typically require higher and more frequent corticosteroid courses than non-AERD asthmatics 3

• All COX-1 inhibiting NSAIDs must be strictly avoided during acute presentations, as they universally cross-react and trigger respiratory reactions—this includes aspirin, ibuprofen, naproxen, ketorolac, and indomethacin 1, 4

Transitioning to Chronic Disease Control

• High-dose inhaled corticosteroid/long-acting beta-agonist combinations are mandatory and should be optimized at higher doses than typical asthma management, as AERD represents more severe eosinophilic airway disease 1

• Leukotriene modifiers (montelukast or zileuton) provide additional benefit—zileuton specifically improved smell, reduced rhinorrhea, and showed trends toward improved nasal flow in 40 AERD patients 3

• Selective COX-2 inhibitors (celecoxib) are extremely safe alternatives for analgesia, with reactions being extremely rare in AERD patients 1

Definitive Long-Term Treatment Options

Aspirin Desensitization Followed by Daily Aspirin Therapy (ATAD)

• ATAD should be strongly considered for patients with poorly controlled upper/lower airway disease despite appropriate medications, requirement for long-term systemic corticosteroids, or recurrent nasal polyps 1

• The 2023 Joint Task Force guidelines provide a conditional recommendation for ATAD in AERD based on moderate certainty evidence showing significant improvements in SNOT-22 scores (mean difference -11.9 points), total symptom scores, and FEV1 3

• Clinical efficacy is substantial: In 172 AERD patients desensitized and treated with aspirin, 87% experienced improvement by 1 year, with significant reductions in sinus infections, prednisone courses, and improvements in smell and nasal-sinus symptoms 3

• Daily aspirin must be continued indefinitely at doses of at least 325 mg once daily (typically 650 mg twice daily in studies) to maintain the desensitized state—gaps >48 hours may lead to loss of tolerance requiring repeat desensitization 1, 5

• Desensitization protocols involve gradual dose escalation over 1-2 days, starting with low doses (typically 40.25-60 mg) and increasing to 325 mg, with most patients reacting between 40.25-120 mg during the procedure 1, 6

Biologic Therapies

• The 2023 guidelines suggest biologics over no biologics for CRSwNP (conditional recommendation, moderate certainty evidence), with dupilumab and omalizumab showing the most benefit across patient-important outcomes 3

• Biologics may be preferred over ATAD for patients with increased bleeding risk (elderly, male, low BMI, hypertension, diabetes, smoking, prednisone use, prior GI/intracranial bleed), those valuing most efficacious therapies, or those wishing to avoid daily oral medication regimens 3, 1

• Dupilumab shows particular benefit in AERD patients with nasal polyposis, though its effect on NSAID hypersensitivity remains incompletely determined 1

Critical Safety Considerations

• Enteric-coated aspirin and proton pump inhibitor prophylaxis should be used with ATAD to prevent gastritis, epigastric pain, or gastrointestinal bleeding 1

• Aspirin desensitization carries contraindications: absolute in pregnancy, relative in history of GI bleeding, and should only be performed in stable coronary disease if needed for cardioprotection due to risk of anaphylactoid reaction increasing cardiac demand 1

• Severe poorly controlled asthma is a contraindication to performing aspirin desensitization until asthma is optimized 3

• Side effects leading to ATAD discontinuation occur in approximately 14% of patients (24/172 in one large series), primarily from intractable gastritis or urticaria 5

Common Pitfalls to Avoid

• Do not confuse aspirin desensitization with acute treatment—the desensitization procedure itself provides no immediate clinical benefit and is only the means to enable daily aspirin therapy 3

• Do not use montelukast as monotherapy for acute exacerbations—it is not indicated for reversal of acute bronchospasm and cannot substitute for rescue bronchodilators 2

• Do not abruptly substitute leukotriene modifiers for inhaled or oral corticosteroids—corticosteroid doses must be reduced gradually under medical supervision 2

• Do not assume aspirin desensitization prevents reactions to NSAIDs during the procedure—it has not been shown to truncate the bronchoconstrictor response during initial challenges 2, 4