Skip to main content
Log in

The mechanisms of aspirin-intolerant asthma and its management

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Aspirin is one of the most widely used medications in the world. Adverse effects related to aspirin use were described almost concurrently with its first use. The most common side effects are gastrointestinal and renal, but adverse respiratory effects are not uncommon, and approximately 10% of adult asthmatics are aspirin intolerant. Many of these patients present with the so-called aspirin triad of aspirin sensitivity, chronic rhinosinusitis with associated nasal polyposis, and severe asthma. This paper provides a review of recent investigations into the pathogenesis of this process, which have furthered our understanding of the mechanisms and management of aspirin-induced asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Vane SJ: Aspirin and other anti-inflammatory drugs. Thorax 2000, 55(suppl_2):S3-S9. A concise review of the mechanism of action of aspirin from the author who won the 1982 Nobel Prize in Medicine for his work relating to prostaglandins.

    Article  PubMed  Google Scholar 

  2. Stevenson DD, Simon RA: Sensitivity to aspirin and nonsteroidal antiinflammatory drugs. In Allergy Principles and Practice. Edited by Middleton E, Reed CE, Ellis EF, et al. St. Louis: Mosby; 1998:1225–1234.

    Google Scholar 

  3. Szczeklik A, Sanak M: Genetic mechanisms in aspirin-induced asthma. Am J Respir Crit Care Med 2000, 161:S142-S146.

    PubMed  CAS  Google Scholar 

  4. Cooke RA: Allergy in drug idiosyncrasy. JAMA 1911, 72:759–760.

    Google Scholar 

  5. Settipane GA: Landmark commentary: history of aspirin intolerance. Allergy Proc 1990, 11:251–252.

    Article  Google Scholar 

  6. Widal F: Anaphylaxis et idiosyncrasie. Presse Med 1922, 30:189–193.

    CAS  Google Scholar 

  7. Samter M, Beers RF Jr: Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med 1968, 68:975–983.

    PubMed  CAS  Google Scholar 

  8. Settipane GA: Aspirin and allergic diseases: a review. Am J Med 1983, 74:102–109.

    Article  PubMed  CAS  Google Scholar 

  9. Mathison DA, Stevenson DD: Aspirin sensitivity in rhinosinusitis and asthma. Immunol Allergy Proc 1983, 5:17–26.

    Google Scholar 

  10. Stevenson DD: Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal antiinflammatory drugs. J Allergy Clin Immunol 1984, 74:617–622.

    Article  PubMed  CAS  Google Scholar 

  11. Lumry WR, Curd JG, Stevenson DD: Aspirin-sensitive asthma and rhinosinusitis: current concepts and recent advances. Ear Nose Throat J 1984, 63:66, 68–70, 72–74 passim.

    PubMed  CAS  Google Scholar 

  12. Pleskow WW, Stevenson DD, Mathison DA, et al.: Aspirinsensitive rhinosinusitis/asthma: spectrum of adverse reactions to aspirin. J Allergy Clin Immunol 1983, 71:574–579.

    Article  PubMed  CAS  Google Scholar 

  13. Castillo JA, Picado C: Prevalence of aspirin intolerance in asthmatics treated in a hospital. Respiration 1986, 50:153–157.

    PubMed  CAS  Google Scholar 

  14. Szczeklik A, Nizankowska E, Duplaga M: Natural history of aspirin-induced asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma. Eur Respir J 2000, 16:432–436. An important study of the natural history of this condition conducted in more than 500 patients.

    Article  PubMed  CAS  Google Scholar 

  15. Ameisen JC, Capron A: Aspirin-sensitive asthma. Clin Exp Allergy 1990, 20:127–129.

    Article  PubMed  CAS  Google Scholar 

  16. Pleskow WW, Chenoweth DE, Simon RA, et al.: The absence of detectable complement activation in aspirin-sensitive asthmatic patients during aspirin challenge. J Allergy Clin Immunol 1983, 72:462–468.

    Article  PubMed  CAS  Google Scholar 

  17. Szczeklik A: The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J 1990, 3:588–593.

    PubMed  CAS  Google Scholar 

  18. Restivo C, Paulus HE: Anaphylaxis from tolmetin. JAMA 1978, 240:246.

    Article  PubMed  CAS  Google Scholar 

  19. Marks F, Harrell K, Fischer R: Successful use of cyclooxygenase-2 inhibitor in a patient with aspirin-induced asthma. South Med J 2001, 94:256–257.

    PubMed  CAS  Google Scholar 

  20. Stevenson DD: Lack of cross-reactivity between selective COX-2 inhibitors and aspirin in aspirin sensitive asthmatic subjects [abstract]. J Allergy Clin Immunol 2000, 105(1 pt 2):5273.

    Google Scholar 

  21. Yoshida S, Ishizaki Y, Onuma K, et al.: Selective cyclooxygenase 2 inhibitor in patients with aspirin-induced asthma. J Allergy Clin Immunol 2000, 106:1201–1202. The first controlled study documenting safety and efficacy of the COX-2 selective agent rofecoxib in AIA patients. The results are important to clinical practice and also in reinforcing recent thoughts on the pathogenesis of AIA.

    Article  PubMed  CAS  Google Scholar 

  22. Szczeklik A, Nizankowska E, Bochenek G, et al.: Safety of a specific COX-2 inhibitor in aspirin-induced asthma. Clin Exp Allergy 2001, 31:219–225.

    Article  PubMed  CAS  Google Scholar 

  23. Szczeklik A, Gryglewski RJ, Olszewski E, et al.: Aspirin-sensitive asthma: the effect of aspirin on the release of prostaglandins from nasal polyps. Pharmacol Res Commun 1977, 9:415–425.

    Article  PubMed  CAS  Google Scholar 

  24. Picado C, Fernandez-Morata JC, Juan M, et al.: Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirinsensitive asthmatics. Am J Respir Crit Care Med 1999, 160:291–296.

    PubMed  CAS  Google Scholar 

  25. Kowalski ML, Pawliczak R, Wozniak J, et al.: Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients. Am J Respir Crit Care Med 2000, 161:391–398.

    PubMed  CAS  Google Scholar 

  26. Babu KS, Salvi SS: Aspirin and asthma. Chest 2000, 118:1470–1476.

    Article  PubMed  CAS  Google Scholar 

  27. Kumlin M, Dahlen B, Bjorck T, et al.: Urinary excretion of leukotriene E4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and histamine in asthmatics. Am Rev Respir Dis 1992, 146:96–103.

    PubMed  CAS  Google Scholar 

  28. Daffern PJ, Muilenburg D, Hugli TE, Stevenson DD: Association of urinary leukotriene E4 excretion during aspirin challenges with severity of respiratory responses. J Allergy Clin Immunol 1999, 104:559–564.

    Article  PubMed  CAS  Google Scholar 

  29. Knapp HR, Sladek K, Fitzgerald GA: Increased excretion of leukotriene E4 during aspirin-induced asthma. J Lab Clin Med 1992, 119:48–51.

    PubMed  CAS  Google Scholar 

  30. Christie PE, Tagari P, Ford-Hutchinson AW, et al.: Urinary leukotriene E4 concentrations increase after aspirin challenge in aspirin-sensitive asthmatic subjects. Am Rev Respir Dis 1991, 143:1025–1029.

    PubMed  CAS  Google Scholar 

  31. Szczeklik A, Sladek K, Dworski R, et al.: Bronchial aspirin challenge causes specific eicosanoid response in aspirinsensitive asthmatics. Am J Respir Crit Care Med 1996, 154:1608–1614.

    PubMed  CAS  Google Scholar 

  32. Arm JP, O’Hickey SP, Spur BW, Lee TH: Airway responsiveness to histamine and leukotriene E4 in subjects with aspirininduced asthma. Am Rev Respir Dis 1989, 140:148–153.

    PubMed  CAS  Google Scholar 

  33. Lee TH: Mechanism of bronchospasm in aspirin-sensitive asthma. Am Rev Respir Dis 1993, 148:1442–1443.

    PubMed  CAS  Google Scholar 

  34. Christie PE, Smith CM, Lee TH: The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma. Am Rev Respir Dis 1991, 144:957–958.

    PubMed  CAS  Google Scholar 

  35. Israel E, Fischer AR, Rosenberg MA, et al.: The pivotal role of 5-lipoxygenase products in the reaction of aspirinsensitive asthmatics to aspirin. Am Rev Respir Dis 1993, 148:1447–1451.

    PubMed  CAS  Google Scholar 

  36. Nasser SM, Bell GS, Foster S, et al.: Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma. Thorax 1994, 49:749–756.

    Article  PubMed  CAS  Google Scholar 

  37. Nasser SM, Pfister R, Christie PE, et al.: Inflammatory cell populations in bronchial biopsies from aspirin-sensitive asthmatic subjects. Am J Respir Crit Care Med 1996, 153:90–96.

    PubMed  CAS  Google Scholar 

  38. Cowburn AS, Sladek K, Soja J, et al.: Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest 1998, 101:834–846. An important contribution to the pathogenesis of AIA in terms of leukotriene excess.

    Article  PubMed  CAS  Google Scholar 

  39. Sanak M, Simon HU, Szczeklik A: Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet 1997, 350:1599–1600.

    Article  PubMed  CAS  Google Scholar 

  40. Mullarkey MF, Thomas PS, Hansen JA, et al.: Association of aspirin-sensitive asthma with HLA-DQw2. Am Rev Respir Dis 1986, 133:261–263.

    PubMed  CAS  Google Scholar 

  41. Manning ME, Stevenson DD: Aspirin sensitivity. A distressing reaction that is now often treatable. Postgrad Med 1991, 90:227–233.

    PubMed  CAS  Google Scholar 

  42. Phillips GD, Foord R, Holgate ST: Inhaled lysine-aspirin as a bronchoprovocation procedure in aspirin-sensitive asthma: its repeatability, absence of a late-phase reaction, and the role of histamine. J Allergy Clin Immunol 1989, 84:232–241.

    Article  PubMed  CAS  Google Scholar 

  43. Zeiss CR, Lockey RF: Refractory period to aspirin in a patient with aspirin-induced asthma. J Allergy Clin Immunol 1976, 57:440–448.

    Article  PubMed  CAS  Google Scholar 

  44. Bianco S, Robuschi M, Petrigni G: Aspirin induced tolerance in aspirin-asthma detected by a new challenge test. IRCSJ Med Sci 1977, 5:129.

    Google Scholar 

  45. Stevenson DD, Simon RA, Mathison DA: Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges. J Allergy Clin Immunol 1980, 66:82–88.

    Article  PubMed  CAS  Google Scholar 

  46. Pleskow WW, Stevenson DD, Mathison DA, et al.: Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol 1982, 69:11–19.

    Article  PubMed  CAS  Google Scholar 

  47. Chiu JT: Improvement in aspirin-sensitive asthmatic subjects after rapid aspirin desensitization and aspirin maintenance (ADAM) treatment. J Allergy Clin Immunol 1983, 71:560–567.

    Article  PubMed  CAS  Google Scholar 

  48. Lumry WR, Curd JG, Zeiger RS, et al.: Aspirin-sensitive rhinosinusitis: the clinical syndrome and effects of aspirin administration. J Allergy Clin Immunol 1983, 71:580–587.

    Article  PubMed  CAS  Google Scholar 

  49. Stevenson DD: Aspirin desensitization. N Engl Reg Allergy Proc 1986, 7:101–104.

    Article  PubMed  CAS  Google Scholar 

  50. Sweet JM, Stevenson DD, Simon RA, Mathison DA: Long-term effects of aspirin desensitization—treatment for aspirinsensitive rhinosinusitis-asthma. J Allergy Clin Immunol 1990, 85:59–65.

    Article  PubMed  CAS  Google Scholar 

  51. 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, 98:751–758.

    Article  PubMed  CAS  Google Scholar 

  52. Dor PJ, Vervloet D, Baldocchi G, Charpin J: Aspirin intolerance and asthmal induction of a tolerance and long-term monitoring. Clin Allergy 1985, 15:37–42.

    Article  PubMed  CAS  Google Scholar 

  53. Dankner RE, Wedner HJ: Aspirin desensitization in aspirinsensitive asthma: failure to maintain a desensitized state during prolonged therapy. Am Rev Respir Dis 1983, 128:953–955.

    PubMed  CAS  Google Scholar 

  54. 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, 73:500–507.

    Article  PubMed  CAS  Google Scholar 

  55. Schaefer OP, Gore JM: Aspirin sensitivity: the role for aspirin challenge and desensitization in postmyocardial infarction patients. Cardiology 1999, 91:8–13.

    Article  PubMed  CAS  Google Scholar 

  56. 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, 85:477–482.

    Article  PubMed  CAS  Google Scholar 

  57. Nelson RP, Stablein JJ, Lockey RF: Asthma improved by acetylsalicylic acid and other nonsteroidal anti-inflammatory agents. N Engl Reg Allergy Proc 1986, 7:117–121.

    Article  PubMed  CAS  Google Scholar 

  58. Fernandez-Rivas M, Cesar JM, Losada E: Asthma relieved by aspirin: clinical studies, platelet function, and arachidonate metabolism. J Allergy Clin Immunol 1992, 89:141–143.

    Article  PubMed  CAS  Google Scholar 

  59. Sheehan GJ, Kutzner MR, Chin WD: Acute asthma attack due to ophthalmic indomethacin. Ann Intern Med 1989, 111:337–338.

    PubMed  CAS  Google Scholar 

  60. Settipane RA, Stevenson DD: Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. J Allergy Clin Immunol 1989, 84:26–33.

    Article  PubMed  CAS  Google Scholar 

  61. Stevenson DD, Hougham AJ, Schrank PJ, et al.: Salsalate cross-sensitivity in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 1990, 86:749–758.

    Article  PubMed  CAS  Google Scholar 

  62. 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, 73:500–507.

    Article  PubMed  CAS  Google Scholar 

  63. Szczeklik A, Nizankowska E, Czerniawska-Mysik G, Sek S: Hydrocortisone and airflow impairment in aspirin-induced asthma. J Allergy Clin Immunol 1985, 76:530–536.

    Article  PubMed  CAS  Google Scholar 

  64. Feigenbaum BA, Stevenson DD, Simon RA: Hydrocortisone sodium succinate does not cross-react with aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 1995, 96:545–548.

    Article  PubMed  CAS  Google Scholar 

  65. Bush RK, Asbury D: Aspirin-sensitive asthma. In Asthma and Rhinitis. Edited by Busse WW, Holgate ST. Boston: Blackwell Scientific; 1995:1429–1439.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

McGeehan, M., Bush, R.K. The mechanisms of aspirin-intolerant asthma and its management. Curr Allergy Asthma Rep 2, 117–125 (2002). https://doi.org/10.1007/s11882-002-0006-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-002-0006-1

Keywords

Navigation