Aspirin-exacerbated respiratory disease: NSAID challenge and desensitization
- Ronald A Simon, MD
Ronald A Simon, MD
- Adjunct Professor, Department of Molecular and Experimental Medicine
- Scripps Research Institute, La Jolla, CA
Patients with aspirin-exacerbated respiratory disease (AERD) present with one or more of the following disorders:
●Chronic rhinosinusitis with nasal polyposis
●Reactions to aspirin (acetylsalicylic acid [ASA]) and other cyclooxygenase-1 (COX-1)-inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs), in which symptoms begin 30 minutes to 3 hours after ingestion and characteristically involve the upper and lower airways (eg, nasal congestion and bronchospasm)
AERD is also called NSAID-exacerbated respiratory disease (NERD). NSAID challenge protocols involve cautiously administering gradually increasing doses of an NSAID, usually aspirin, in an appropriately monitored medical setting. These procedures are used to diagnose NSAID pseudoallergy and also to desensitize AERD patients to NSAIDs, when indicated. The safety and technical aspects of these protocols, as well as the efficacy of aspirin therapy for AERD, are discussed here. The clinical manifestations and management of AERD and a general discussion of allergic and pseudoallergic reactions to NSAIDs are reviewed separately. (See "Aspirin-exacerbated respiratory disease" and "NSAIDs (including aspirin): Allergic and pseudoallergic reactions".)
- White A, Bigby T, Stevenson D. Intranasal ketorolac challenge for the diagnosis of aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol 2006; 97:190.
- Lee RU, White AA, Ding D, et al. Use of intranasal ketorolac and modified oral aspirin challenge for desensitization of aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol 2010; 105:130.
- Casadevall J, Ventura PJ, Mullol J, Picado C. Intranasal challenge with aspirin in the diagnosis of aspirin intolerant asthma: evaluation of nasal response by acoustic rhinometry. Thorax 2000; 55:921.
- White AA, Stevenson DD, Simon RA. The blocking effect of essential controller medications during aspirin challenges in patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol 2005; 95:330.
- Berges-Gimeno MP, Simon RA, Stevenson DD. The effect of leukotriene-modifier drugs on aspirin-induced asthma and rhinitis reactions. Clin Exp Allergy 2002; 32:1491.
- Lee DK, Haggart K, Robb FM, Lipworth BJ. Montelukast protects against nasal lysine-aspirin challenge in patients with aspirin-induced asthma. Eur Respir J 2004; 24:226.
- Stevenson DD, Simon RA, Mathison DA, Christiansen SC. Montelukast is only partially effective in inhibiting aspirin responses in aspirin-sensitive asthmatics. Ann Allergy Asthma Immunol 2000; 85:477.
- Szczeklik A, Serwonska M. Inhibition of idiosyncratic reactions to aspirin in asthmatic patients by clemastine. Thorax 1979; 34:654.
- Dahl R. Oral and inhaled sodium cromoglycate in challenge test with food allergens or acetylsalicylic acid. Allergy 1981; 36:161.
- Simon RA, Scripps Clinic, personal communication.
- Macy E, Bernstein JA, Castells MC, et al. Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: a practice paper. Ann Allergy Asthma Immunol 2007; 98:172.
- Hope AP, Woessner KA, Simon RA, Stevenson DD. Rational approach to aspirin dosing during oral challenges and desensitization of patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2009; 123:406.
- Chen JR, Buchmiller BL, Khan DA. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract 2015; 3:926.
- Morwood K, Gillis D, Smith W, Kette F. Aspirin-sensitive asthma. Intern Med J 2005; 35:240.
- Milewski M, Mastalerz L, Nizankowska E, Szczeklik A. Nasal provocation test with lysine-aspirin for diagnosis of aspirin-sensitive asthma. J Allergy Clin Immunol 1998; 101:581.
- Alonso-Llamazares A, Martinez-Cócera C, Domínguez-Ortega J, et al. Nasal provocation test (NPT) with aspirin: a sensitive and safe method to diagnose aspirin-induced asthma (AIA). Allergy 2002; 57:632.
- Bianco S, Robuschi M, Petrigni G. Aspirin-induced tolerance in aspirin induced asthma detected by a new challenge technique. IRCS J Med Sci 1977; 5:129.
- Dahlén B, Zetterström O. Comparison of bronchial and per oral provocation with aspirin in aspirin-sensitive asthmatics. Eur Respir J 1990; 3:527.
- Nizankowska E, Bestyńska-Krypel A, Cmiel A, Szczeklik A. Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma. Eur Respir J 2000; 15:863.
- The Scripps Clinic, San Diego, California. Dr. Simon may be reached at email@example.com.
- Mathison DA, Lumry WR, Stevenson DD, et al. Aspirin in chronic urticaria and/or angioedema: Studies of sensitivity and desensitization. J Allergy Clin Immunol 1982; 69:135.
- Stevenson DD, Pleskow WW, Simon RA, et al. Aspirin-sensitive rhinosinusitis asthma: a double-blind crossover study of treatment with aspirin. J Allergy Clin Immunol 1984; 73:500.
- Sweet JM, Stevenson DD, Simon RA, Mathison DA. Long-term effects of aspirin desensitization--treatment for aspirin-sensitive rhinosinusitis-asthma. J Allergy Clin Immunol 1990; 85:59.
- Williams AN, Woessner KM. The clinical effectiveness of aspirin desensitization in chronic rhinosinusitis. Curr Allergy Asthma Rep 2008; 8:245.
- Rozsasi A, Polzehl D, Deutschle T, et al. Long-term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily. Allergy 2008; 63:1228.
- Stevenson DD, Hankammer MA, Mathison DA, et al. Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes. J Allergy Clin Immunol 1996; 98:751.
- McMains KC, Kountakis SE. Medical and surgical considerations in patients with Samter's triad. Am J Rhinol 2006; 20:573.
- Berges-Gimeno MP, Simon RA, Stevenson DD. Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2003; 111:180.
- Berges-Gimeno MP, Simon RA, Stevenson DD. Early effects of aspirin desensitization treatment in asthmatic patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol 2003; 90:338.
- Lee JY, Simon RA, Stevenson DD. Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2007; 119:157.
- Świerczyńska-Krępa M, Sanak M, Bochenek G, et al. Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study. J Allergy Clin Immunol 2014; 134:883.
- Cho KS, Soudry E, Psaltis AJ, et al. Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease. Otolaryngol Head Neck Surg 2014; 151:575.
- Fruth K, Pogorzelski B, Schmidtmann I, et al. Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease. Allergy 2013; 68:659.
- Hoyte FC, Weber RW, Katial RK. Pancreatitis as a novel complication of aspirin therapy in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2012; 129:1684.
- Stevenson DD, White AA, Simon RA. Aspirin as a cause of pancreatitis in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2012; 129:1687.
- OVERVIEW OF NSAID CHALLENGE
- Indications for challenge
- Contraindications to challenge
- TYPES OF CHALLENGES
- CHALLENGE PROTOCOLS AND PROCEDURES
- Oral aspirin challenge and desensitization
- - Use of placebo doses
- - Procedure
- - Provocation of symptoms
- - Treatment of symptoms during challenge
- Inhalational challenge and desensitization
- - Ketorolac nasal provocation
- Definition of a positive nasal challenge
- - Aspirin-lysine bronchial provocation
- Definition of a positive inhalational challenge
- Comparison of oral and inhalational challenge
- Outcomes of desensitization
- - Cross-desensitization to other NSAIDs
- - Missed doses
- - Breakthrough symptoms
- EFFICACY OF ASPIRIN THERAPY IN AERD
- Optimal aspirin dose for AERD
- Other issues of aspirin dosing after desensitization
- Prevention of gastrointestinal toxicity from NSAIDs
- Reasons for discontinuation
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS