Aspirin-induced asthma

Samter's triad

Aspirin in tablets
Classification and external resources
Specialty pulmonology
ICD-10 J45.1, J45.8
ICD-9-CM 493.1
OMIM 208550
MeSH D055963

Aspirin-induced asthma is also termed Samter's triad, Samter's syndrome, aspirin-exacerbated respiratory disease (AERD),[1] and recently by an appointed task force of the European Academy of Allergy and Clinical Immunology/World Allergy Organization (EAACI/WAO) Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD).[1] The syndrome, which EAACI/WHO classifies as one of 5 types of non-steroidal anti-inflammatory drug hypersensitivity or NSAID hypersensitivity reactions, is a medical condition initially defined as consisting of three key features viz., asthma, respiratory symptoms exacerbated by aspirin, and nasal/ethmoidal polyposis; however, the syndrome's symptoms are exacerbated by a large variety of other NSAID besides aspirin.[2][3][4] The symptoms of respiratory reactions in this syndrome are hypersensitivity reactions to NSAIDs rather than the typically described true allergic reactions that trigger other common allergen-induced asthma, rhinitis, or hives. The NSAID-induced reactions do not appear to involve the common mediators of true allergic reactions, immunoglobulin E or T cells.[4] Rather, AERD is a type of NSAID-induced hypersensitivity syndrome.

Signs and symptoms

The various non-allergic NSAID hypersensitivity syndromes affect 0.5-1.9% of the general population, with AERD affecting about 7% of all asthmatics and about 14% of patients with severe asthma. [5] AERD, which is more prevalent in women, usually begins in young adulthood[6] (twenties and thirties are the most common onset times although children are afflicted with it and present a diagnostic problem in pediatrics)[7][8] and may not include any other allergies. Most commonly the first symptom is rhinitis (inflammation or irritation of the nasal mucosa), which can manifest as sneezing, runny nose, or congestion. The disorder typically progresses to asthma, then nasal polyposis, with aspirin sensitivity coming last. Anosmia (lack of smell) is also common, as inflammation within the nose and sinuses likely reaches the olfactory receptors.[9]

The respiratory reactions to aspirin vary in severity, ranging from mild nasal congestion and eye watering to lower respiratory symptoms including wheezing, coughing, an asthma attack, and in rare cases, anaphylaxis. In addition to the typical respiratory reactions, about 10% of patients with AERD manifest skin symptoms like urticaria and/or gastrointestinal symptoms such as abdominal pain or vomiting during their reactions to aspirin.[2] In addition to aspirin, patients usually also react to other NSAIDs such as ibuprofen, and to any medication that inhibits the cyclooxygenase-1 (COX-1) enzyme, although paracetamol (acetaminophen) in low doses[10] is generally considered safe. NSAID that are highly selective in blocking COX-2 and do not block its closely related paralog, COX-1, such as the COX-2 inhibitors celecoxib and rofecoxib, are also regarded as safe.[11] Nonetheless, recent studies do find that these types of drugs, e.g. acetaminophen and celecoxib, may trigger adverse reactions in these patients; caution is recommended in using any COX inhibitors.[12] In addition to aspirin and NSAIDs, consumption of even small amounts of alcohol also produces uncomfortable respiratory reactions in many patients.[13]


The disorder is thought to be caused by an anomaly in the arachidonic acid metabolizing cascade which leads to increased production of pro-inflammatory cysteinyl leukotrienes, a series of chemicals involved in the body's inflammatory response. When medications like NSAIDs or aspirin block the COX-1 enzyme, production of thromboxane and some anti-inflammatory prostaglandins is decreased, and in patients with aspirin-induced asthma this results in the overproduction of pro-inflammatory leukotrienes to causes severe exacerbations of asthma and allergy-like symptoms.[14][15][16][17][18][19] The underlying cause of the disorder is not fully understood, but there have been several important findings:



Urinary cystyl-leukotriene or urinary LTE4 can be used after a supervised challenge with aspirin. In aspirin sensitivity, no change in N-methylhistamine is observed; while LTE4 levels are increased. This test however lacks sensitivity and has a 25 percent false negative rate among affected persons.[27]


The preferred treatment for many patients is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. In the United States, the Scripps Clinic in San Diego, CA,[28] the Massachusetts General Hospital in Boston, MA,[29] the Brigham and Women's Hospital in Boston, MA,[30] National Jewish Hospital in Denver [31] and Stanford University Adult ENT Clinic have allergists who routinely perform aspirin desensitization procedures for patients with aspirin-induced asthma. Patients who are desensitized then take a maintenance dose of aspirin daily and while on daily aspirin they often have reduced need for supporting medications, fewer asthma and sinusitis symptoms than previously, and many have an improved sense of smell. Desensitization to aspirin reduces the chance of nasal polyp recurrence, and can slow the regrowth of nasal polyps. Even patients desensitized to aspirin may continue to need other medications including nasal steroids, inhaled steroids, and leukotriene antagonists.

Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) are often helpful in treating the symptoms of aspirin-induced asthma. Some patients require oral steroids to alleviate asthma and congestion, and most patients will have recurring or chronic sinusitis due to the nasal inflammation.


Often surgery is required to remove nasal polyps,[32] although they typically recur, particularly if aspirin desensitization is not undertaken.


Some people have reported relief of symptoms by following a low-salicylate diet such as the Feingold diet. Aspirin is quickly converted in the body to salicylic acid, also known as 2-Hydroxybenzoic acid. However, there is little evidence that a low-salicylate diet is beneficial for patients with AERD.[33] Current clinical trials are underway to determine whether or not the difficult dietary changes needed for a low-salicylate diet truly provide worthwhile therapeutic improvement for these patients.[34]

A diet low in omega-6 oils (precursors of arachidonic acid), and high in omega-3 oils, may also help. In a small study, aspirin-sensitive asthma patients taking 10 grams of fish oil daily reported relief of most symptoms after six weeks, however symptoms returned if the supplement was stopped.[35]

Alternate and related names

Samter's triad goes by several other names:

A sufferer who has not yet experienced asthma or aspirin sensitivity might be diagnosed as having:


It is named for Max Samter.[40]

Initial reports on the link between asthma, aspirin and nasal polyposis were made by Widal in 1922.[41] Further studies were done by Samter & Beers in reports published in 1968.[42]

See also


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  3. Kim JE, Kountakis SE (July 2007). "The prevalence of Samter's triad in patients undergoing functional endoscopic sinus surgery". Ear Nose Throat J. 86 (7): 396–9. PMID 17702319.
  4. 1 2 Allergy. 2011 Jul;66(7):818-29. doi: 10.1111/j.1398-9995.2011.02557
  5. J Allergy Clin Immunol. 2015 Mar;135(3):676-81
  6. "Nasal Polyps – The Current Management Process". Retrieved 2014-12-13.
  7. Welch, Kevin C. "Aspirin Desensitization". American Rhinologic Society.
  8. Int J Pediatr Otorhinolaryngol. 2013 Feb;77(2):281-3. doi: 10.1016/j.ijporl.2012.10.017
  9. Clin Rev Allergy Immunol. 2003 Apr;24(2):113-24
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  11. Lancet Neurol. 2008 Sep;7(9):812-26. doi: 10.1016/S1474-4422(08)70169-8
  12. Allergy Asthma Immunol Res. 2014 Mar;6(2):156-62. doi: 10.4168/aair.2014.6.2.156
  13. Cardet JC, White AA, Barrett NA, et al. (2014). "Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease". J Allergy Clin Immunol Pract. 2 (2): 208–13. doi:10.1016/j.jaip.2013.12.003. PMID 24607050.
  14. Narayanankutty A, Reséndiz-Hernández JM, Falfán-Valencia R, Teran LM (May 2013). "Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD)". Clin. Biochem. 46 (7-8): 566–78. doi:10.1016/j.clinbiochem.2012.12.005. PMID 23246457.
  15. Prostaglandins Other Lipid Mediat. 2009 Sep;89(3-4):120-5. doi: 10.1016/j.prostaglandins.2008.12.003.
  16. Respir Med. 2010 Oct;104(10):1404-9. doi: 10.1016/j.rmed.2010.04.017
  17. Allergy. 2011 Jul;66(7):818-29. doi: 10.1111/j.1398-9995.2011.02557.x.
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  19. Curr Opin Allergy Clin Immunol. 2014 Feb;14(1):1-6. doi: 10.1097/ACI.0000000000000021
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  23. Sousa AR, Parikh A, Scadding G, Corrigan CJ, Lee TH (November 2002). "Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis". N. Engl. J. Med. 347 (19): 1493–9. doi:10.1056/NEJMoa013508. PMID 12421891.
  24. Cowburn AS, Sladek K, Soja J, et al. (February 1998). "Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma". J. Clin. Invest. 101 (4): 834–46. doi:10.1172/JCI620. PMC 508632Freely accessible. PMID 9466979.
  25. Laidlaw TM, Kidder MS, Bhattacharyya N, et al. (April 2012). "Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes". Blood. 119 (16): 3790–8. doi:10.1182/blood-2011-10-384826. PMC 3335383Freely accessible. PMID 22262771.
  26. Online Mendelian Inheritance in Man (OMIM) Asthma, Nasal Polyps, and Aspirin Intolerance -208550
  27. Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients. Di Lorenzo G, Pacor ML, Vignola AM, Profita M, Esposito-Pellitteri M, Biasi D, Corrocher R, Caruso C. Allergy. 2002 Dec;57(12):1180-6. PMID 12464047
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  40. Samter's syndrome at Who Named It?
  41. Widal MF (1922). "Anaphylaxie et idiosyncraise". Press Med (in French). 119: 48–51.
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