Aspirin Exacerbated Respiratory Disease — ED Care and Long Term Options

Key Points

• AERD consists of asthma, chronic rhinosinusitis with nasal polyps, and respiratory reactions to strong COX-1-inhibiting NSAIDs.
• The mechanism is pharmacologic dysregulation of arachidonic-acid metabolism rather than classic drug-specific IgE allergy.
• Untreated patients generally cross-react with multiple strong COX-1 NSAIDs.
• Acute bronchospasm is treated as an asthma exacerbation, and epinephrine is used when anaphylaxis or life-threatening multisystem compromise is present.
• Lower-dose acetaminophen is often tolerated, while higher doses can provoke symptoms in sensitive patients.
• Selective COX-2 inhibitors are tolerated by most patients with AERD.
• Long-term therapy includes asthma treatment, intranasal therapy, leukotriene modifiers, sinus surgery, biologics, and selected aspirin desensitization.
• Aspirin desensitization requires continued aspirin dosing to maintain tolerance.

Algorithm

1. Suspect AERD in an adult with asthma, recurrent nasal polyps or anosmia, and reproducible respiratory symptoms after aspirin or NSAIDs.
2. During an acute reaction, stop the NSAID and assess airway, breathing, circulation, and asthma severity.
3. Treat bronchospasm with inhaled bronchodilator therapy and systemic corticosteroid when indicated.
4. Give IM epinephrine for anaphylaxis, severe upper-airway compromise, hypotension, or rapidly progressive multisystem reaction.
5. After stabilization, advise avoidance of strong COX-1 inhibitors unless the patient has been desensitized.
6. Optimize chronic asthma and nasal-polyp therapy, including leukotriene-directed treatment when appropriate.
7. Refer to allergy and ENT for diagnostic challenge when needed and for coordinated chronic management.
8. Consider biologic therapy or aspirin desensitization with maintenance aspirin in selected patients using shared decision-making.

Clinical Synopsis & Reasoning

Aspirin-exacerbated respiratory disease, also called NSAID-exacerbated respiratory disease, is characterized by asthma, chronic rhinosinusitis with nasal polyps, and reproducible respiratory reactions after aspirin or another strong cyclooxygenase-1 inhibitor. It is not a classic drug-specific IgE allergy. COX-1 inhibition shifts arachidonic-acid metabolism toward excessive cysteinyl leukotriene signaling and can trigger nasal congestion, rhinorrhea, ocular symptoms, bronchospasm, and sometimes systemic symptoms.

AERD often begins in adulthood. Patients may describe progressive nasal congestion and loss of smell, recurrent nasal polyps requiring surgery, difficult asthma, and then a striking episode of wheezing or severe congestion after ibuprofen, naproxen, aspirin, or another nonselective NSAID. Reactions typically begin within minutes to a few hours of ingestion. Some patients have never recognized the association because they have avoided NSAIDs or because prior reactions were attributed to asthma alone.

The diagnosis can be made clinically when the triad and repeated convincing NSAID reactions are present. A supervised aspirin challenge is the diagnostic standard when the history is uncertain, but it should be performed in a specialized setting capable of treating significant bronchospasm and systemic reactions. Routine aspirin challenge during an acute ED visit is inappropriate.

The emergency clinician should distinguish an AERD respiratory reaction from other causes of acute asthma and from IgE-mediated single-NSAID allergy. AERD usually cross-reacts among strong COX-1 inhibitors, whereas a patient with selective IgE-mediated allergy to one NSAID may tolerate unrelated NSAIDs. Chronic upper-airway disease is also a major clue. Alcohol, especially wine or beer, can provoke respiratory symptoms in many patients with AERD and may be a useful historical detail.

Because AERD is a chronic inflammatory syndrome, simply avoiding NSAIDs does not cure the asthma or sinus disease. Patients often continue to have severe nasal obstruction, recurrent polyps, and asthma unless the underlying airway inflammation is treated.

Treatment Strategy & Disposition

During an acute NSAID-triggered reaction, stop further exposure and assess airway, breathing, circulation, oxygenation, and peak expiratory flow when feasible. Treat bronchospasm with inhaled short-acting beta-agonist and add inhaled anticholinergic therapy for severe exacerbation. Systemic corticosteroids are appropriate for a significant asthma exacerbation. Give intramuscular epinephrine when the reaction meets anaphylaxis criteria or there is severe upper-airway edema, hypotension, or rapidly progressive multisystem disease. Epinephrine should not be withheld simply because AERD is non-IgE mediated when the clinical syndrome is life-threatening.

Patients who have not been desensitized should avoid aspirin and other strong COX-1-inhibiting NSAIDs. Acetaminophen is usually tolerated at lower single doses, with AAAAI patient guidance noting tolerance is generally better at doses up to 500 mg at a time, although sensitive patients can react, especially at higher doses. Selective COX-2 inhibitors such as celecoxib are tolerated by most patients with AERD, but a supervised first dose can be considered when the history is severe or uncertain.

Long-term treatment addresses both lower and upper airways. Use guideline-directed asthma therapy, usually including inhaled corticosteroid-containing treatment. Intranasal corticosteroids, saline irrigation, and often corticosteroid sinus rinses help chronic rhinosinusitis. Leukotriene receptor antagonists such as montelukast or zafirlukast and the 5-lipoxygenase inhibitor zileuton directly target the leukotriene pathway and can improve symptoms in selected patients. Recurrent obstructive polyps frequently require endoscopic sinus surgery.

Aspirin desensitization followed by daily aspirin therapy is an established option for selected patients, particularly those with recurrent polyps, difficult upper-airway disease, a cardiovascular need for aspirin, or inadequate control with other approaches. Desensitization must be performed in a specialist-supervised setting. Continued daily aspirin is required to maintain desensitization; interruption can allow reactivity to return. Biologic therapies used for asthma and chronic rhinosinusitis with nasal polyps, including agents targeting type 2 inflammatory pathways, are another important option. Contemporary practice uses shared decision-making among biologic therapy, surgery, and aspirin desensitization based on disease pattern, contraindications, cost, access, and patient preference.

Epidemiology / Risk Factors

• AERD occurs in a minority of all patients with asthma but is enriched among patients with severe asthma and recurrent nasal polyps.
• Symptoms often begin in early to middle adulthood rather than childhood.
• Loss of smell and recurrent polyp surgery are characteristic upper-airway burdens.
• Alcohol-triggered respiratory symptoms are reported frequently in this population.
• Disease burden persists despite NSAID avoidance because the underlying airway inflammation is chronic.

Investigations

Analgesic Choices

Pharmacology

Prognosis / Complications

• Acute NSAID reactions usually resolve with prompt bronchodilator and supportive treatment, with epinephrine when clinically indicated.
• Chronic disease can cause recurrent polyps, anosmia, asthma exacerbations, repeated surgery, and substantial quality-of-life impairment.
• Leukotriene modifiers, biologics, and aspirin therapy after desensitization can substantially improve control in selected patients.
• Sinus surgery alone does not eliminate the underlying inflammatory tendency and polyps may recur.
• Coordinated allergy, pulmonary, and ENT care offers the best long-term control for severe disease.

Patient Education / Counseling

• Avoid aspirin, ibuprofen, naproxen, and other strong COX-1 NSAIDs unless a clinician has established a safe alternative or completed desensitization.
• Check combination cold, pain, and menstrual products because NSAIDs may be hidden ingredients.
• Lower-dose acetaminophen is often safer but is not guaranteed to be tolerated at all doses.
• Discuss celecoxib or another selective COX-2 inhibitor with the treating clinician when anti-inflammatory therapy is needed.
• Keep asthma rescue medication available and seek urgent care for severe wheezing, throat symptoms, faintness, or rapidly progressive reactions.
• If taking daily aspirin after desensitization, do not interrupt therapy without discussing how loss of desensitization will be managed.

Notes

AERD is a useful example of why every drug reaction should not be called an IgE allergy. The cross-reactivity is driven by COX-1 inhibition, so a patient may react to several chemically unrelated NSAIDs while tolerating a selective COX-2 inhibitor.

Treatment has evolved beyond aspirin avoidance. Modern care treats AERD as combined lower- and upper-airway inflammatory disease, with surgery, leukotriene-directed therapy, biologics, and aspirin desensitization selected according to the individual disease burden and patient goals.

References

1. AAAAI Aspirin-Exacerbated Respiratory Disease — Link
2. AAAAI 2025 Expert Review: Role of Aspirin Desensitization — Link