What is Aspirin-Exacerbated Respiratory Disease (AERD)?

Aspirin-Exacerbated Respiratory Disease (AERD)

Aspirin-Exacerbated Respiratory Disease (AERD) is a clinical entity characterized by the triad of chronic rhinosinusitis with nasal polyps, bronchial asthma, and hypersensitivity to aspirin and other NSAIDs that inhibit the COX-1 enzyme. 1

Definition and Epidemiology

• AERD is a unique syndrome that typically develops following an upper respiratory infection, with onset of perennial rhinitis followed by sinonasal polyposis, and progression to asthma 1
• The condition affects approximately 7% of adults with asthma and one-third of patients with asthma and nasal polyposis 1, 2
• AERD is rare in children with asthma and becomes increasingly more common in adults 1
• The condition has historically been known by various names including "aspirin sensitivity," "aspirin intolerance," "aspirin idiosyncrasy," "aspirin-induced asthma," "NSAID-exacerbated respiratory disease (N-ERD)," "aspirin triad," "Widal triad," and "Samter's triad" 1, 2
• Although N-ERD is commonly used, AERD is the preferred terminology in the United States 1

Pathophysiology

• AERD reactions occur through COX-1 inhibition and are not IgE-mediated or drug-specific 1
• The condition involves dysregulation of arachidonic acid metabolism with increased production of cysteinyl leukotrienes 1, 3
• High-dose aspirin exposure in AERD patients causes decreased prostaglandin E2, increased cysteinyl leukotrienes, increased tryptase, continued 5-lipoxygenase activity, and other immune effects 1

Clinical Presentation

• Rhinitis is often complicated by chronic sinusitis, anosmia, and nasal polyposis 1
• Asthma and hypersensitivity to NSAIDs usually develop several years after the onset of rhinitis 1
• Upper and lower respiratory tract symptoms are frequently sudden and often severe after administration of aspirin or any NSAID that inhibits the COX-1 enzyme 1
• Despite avoidance of aspirin and cross-reacting drugs, patients typically experience refractory rhinosinusitis and asthma 1, 4
• Many patients require repeated sinus surgeries and frequent or chronic administration of systemic corticosteroids 1, 4

Diagnosis

• The diagnosis of AERD is usually established by history, with the probability of reacting to a formal challenge ranging from 80% to 100% in patients with a typical history 1
• Neither skin testing nor in vitro tests are useful for diagnosing AERD 1
• When patients with a history of multiple reactions to structurally dissimilar NSAIDs (e.g., ibuprofen and aspirin) are challenged with aspirin, approximately 80% will have a respiratory reaction confirming the diagnosis 1
• In patients with ≥2 respiratory reactions to different NSAIDs or a respiratory reaction requiring hospitalization, further diagnostic testing with aspirin challenge is unnecessary 1
• An oral aspirin challenge may be suggested to confirm the diagnosis of AERD in cases of diagnostic uncertainty 1

Management

• Avoidance of all COX-1 inhibiting NSAIDs is recommended 4
• Selective COX-2 inhibitors may be used as alternative analgesics in patients with AERD when an NSAID is needed 1
• Reactions to selective COX-2 inhibitors are extremely rare in patients with AERD 1
• Intranasal corticosteroids are a mainstay of treatment for controlling nasal symptoms and polyp growth 4, 5
• Leukotriene receptor antagonists (e.g., montelukast) may provide subjective improvement when administered alongside intranasal corticosteroids 4
• Endoscopic sinus surgery is often required for patients with refractory nasal polyposis 4
• Aspirin desensitization followed by daily aspirin therapy may be considered for post-surgical or persistent disease 4, 3
• Newer biologic therapies targeting IL-4Rα, IL-5, IL-5Rα, and IgE have shown efficacy in treating CRSwNP and asthma in patients with AERD 6, 7

Common Pitfalls and Caveats

• AERD is often underdiagnosed due to its relative rarity and complex presentation 8
• Patients with AERD can typically take up to 650 mg of acetaminophen for analgesic or antipyretic relief 3
• Patients with AERD can safely use intranasal corticosteroids like fluticasone (Flonase) despite their NSAID sensitivity 5
• The condition is chronic and does not improve with avoidance of COX-1 inhibitors alone 3
• Management requires a comprehensive approach addressing both upper and lower airway disease 4, 7