Skip to main content

Advertisement

SpringerLink
Log in

Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs

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

Abstract

Aspirin-exacerbated respiratory disease (AERD) is an adultonset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Stevenson D, Simon RA, Zuraw B: Sensitivity to aspirin and non-steroidal anti-inflammatory drugs. In Allergy: Principles and Practice, edn 6. Edited by Middleton E Jr, Ellis EF, Yunginer JW, et al. St. Louis: Mosby; 2003. This reference is a current and comprehensive review of the topic of respiratory but also other reactions (especially cutaneous reactions to aspirin and other NSAIDs) that inhibit cyclooxygenase.

    Google Scholar 

  2. Stevenson D, Szczeklik A: Classification of allergic and pseudoallergic reactions to drugs that inhibit cyclooxygenase enzymes. Ann Allergy 2001, 87:177–180.

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. Giraldo B, Blumenthal MN, Spink WW: Aspirin intolerance and asthma: a clinical and immunological study. Ann Intern Med 1969, 71:479–496.

    CAS  PubMed  Google Scholar 

  5. McDonald JR, Mathison DA, Stevenson DD: Aspirin intolerance in asthma, detection by oral challenge. J Allergy Clin Immunol 1972, 50:198–207.

    Article  CAS  PubMed  Google Scholar 

  6. Berges-Gimeno MP, Simon RA, Stevenson DD: The natural history and clinical characteristics of aspirin exacerbated respiratory disease. Ann Allergy Asthma Immunol 2002, 89:474–478. Presents the up-to-date Scripps Clinic experience in the clinical presentation of AERD and its natural history. Should help clinicians identify these individuals.

    PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Stevenson D: Adverse reactions to nonsteroidal anti-inflammatory drugs. Immunol Allergy Clin North Am 1998, 18:773–798.

    Article  Google Scholar 

  9. 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  CAS  PubMed  Google Scholar 

  10. Weber JCP, Eissigman WK: Pulmonary alveolitis and NSAIDs: fact or fiction. Br J Rheumatol 1986, 25:5–6.

    Article  CAS  PubMed  Google Scholar 

  11. Nader DA, Schillaci RF: Pulmonary infiltrates with eosinophilia due to naproxene. Chest 1983, 83:280–282.

    CAS  PubMed  Google Scholar 

  12. Buscaglia AJ, Cowden FE: Pulmonary infiltrates associated with naproxene. JAMA 1984, 1:65–66.

    Article  Google Scholar 

  13. Goodwin SD, Glenny RW: Nonsteroidal anti-inflammatory drug-associated pulmonary infiltrates with eosinophilia: review of the literature and Food and Drug Administration Adverse Drug Reaction reports. Arch Intern Med 1992, 152:1521–1524.

    Article  CAS  PubMed  Google Scholar 

  14. Londino AV, Wolf GL, Calabro JJ: Naproxen and pneumonitis. JAMA 1984, 252:1853–1854.

    Article  PubMed  Google Scholar 

  15. Pauls JD, Simon RA, Daffern PJ, et al.: Lack of effect of the 5-lipoxygenase inhibitor zileuton in blocking oral aspirin challenges in aspirin-sensitive asthmatics. Ann Allergy Asthma Immunol 2000, 85:40–45.

    CAS  PubMed  Google Scholar 

  16. Stevenson D, Simon RA, Mathison DA, et al.: Montelukast is only partially effective in inhibiting aspirin responses in aspirin sensitive asthmatics. Ann Allergy Asthma Immunol 2000, 85:477–482.

    CAS  PubMed  Google Scholar 

  17. Nizankowska E, Szczeklik A: Glucocorticosteroids attenuate aspirin-precipitated adverse reactions in aspirin-intolerant patients with asthma. Ann Allergy 1989, 63:159–162.

    CAS  PubMed  Google Scholar 

  18. Szczeklik A, Serwonska M: Inhibition of idiosyncratic reactions to aspirin in asthmatic patients by clemastine. Thorax 1979, 34:654–657.

    Article  CAS  PubMed  Google Scholar 

  19. Dahl R: Oral and inhaled sodium cromoglycate in challenges with food and acetylsalicylic acid. Allergy 1981, 36:161–172.

    Article  CAS  PubMed  Google Scholar 

  20. Stevenson DD: Oral challenges to detect aspirin and sulfite sensitivity in asthma. N Engl Reg Allergy Proc 1988, 9:135–142.

    Article  CAS  PubMed  Google Scholar 

  21. Bianco SR, Robuschi M, Petrigni G: Aspirin-induced tolerance in aspirin-asthma detected by a new challenge test. IRCS J Med Sci 1977, 5:129–136.

    Google Scholar 

  22. Phillips GD, Foord R, Holgate ST: Inhaled lysine-aspirin as a broncho-provocation procedure with aspirin in aspirinsensitive asthma. J Allergy Clin Immunol 1989, 84:232–241.

    Article  CAS  PubMed  Google Scholar 

  23. Dahlen B, Zetterstrom O: Comparison of bronchial and per oral provocation with aspirin in aspirin-sensitive asthmatics. Eur Respir J 1990, 3:527–534.

    CAS  PubMed  Google Scholar 

  24. Milewski M, Mastalerz L, Nizankowska E, et al.: Nasal provocation test with lysine-aspirin for diagnosis of aspirinsensitive asthma. J Allergy Clin Immunol 1998, 101:581–586.

    Article  CAS  PubMed  Google Scholar 

  25. Widal MF, Abrami P, Lermeyez J: Anaphylaxie et idiosyncrasie. Presse Med 1922, 30:189–192.

    CAS  Google Scholar 

  26. Stevenson DD, Simon RA, Mathison DA: Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges. J Allergy Clin Immunol 1980, 66:82–85.

    Article  CAS  PubMed  Google Scholar 

  27. 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  CAS  PubMed  Google Scholar 

  28. Stevenson DD, Hankammer MA, Mathison DA: Long-term ASA desensitization-treatment of aspirin-sensitive asthmatic patients: Clinical outcome studies. J Allergy Clin Immunol 1996, 98:751–758.

    Article  CAS  PubMed  Google Scholar 

  29. Szczeklik A, Gryglewski RJ, Czernigwska-Mysik G: Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. J Allergy Clin Immunol 1977, 60:276–284.

    Article  CAS  PubMed  Google Scholar 

  30. Delaney JC: The diagnosis of aspirin idiosyncrasy by analgesic challenge. Clin Allergy 1976, 6:177–184.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Stevenson DD: Cross-reactivity between aspirin and other drugs/dietary chemicals: a critical review. In Progress in Allergy and Clinical Immunology. Edited by Pichler WJ, Stadler MM, Dahinden CA, et al. Lewiston, NY: Hogrefe and Huber; 1989:462–473.

    Google Scholar 

  33. Feigenbaum BA, Stevenson DD, Simon RA: Lack of crosssensitivity to IV hydrocortisone in aspirin-sensitive subjects with asthma. J Allergy Clin Immunol 1995, 96:545–548.

    Article  CAS  PubMed  Google Scholar 

  34. Stevenson DD, Simon R: Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 2001, 108:47–51. First comprehensive report describing the safety of COX-2 inhibitors in a large number of patients with AERD who underwent blinded, placebo-controlled challenges with rofecoxib.

    Article  CAS  PubMed  Google Scholar 

  35. Woessner KM, Simon RA, Stevenson DD: The safety of celecoxib in patients with aspirin sensitive asthma. Arthritis Rheum 2002, 46:2201–2206.

    Article  CAS  PubMed  Google Scholar 

  36. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 1971, 231:232–235.

    CAS  Google Scholar 

  37. Moneret-Vautrin DA, Hsieh V, Wayoff M, et al.: Nonallergic rhinitis with eosinophilia syndrome a precursor of the triad: nasal polyposis, intrinsic asthma, and intolerance to aspirin. Ann Allergy 1990, 64:513–518.

    CAS  PubMed  Google Scholar 

  38. Sladek K, Dworski R, Soja J, et al.: Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge. Am J Respir Care Med 1994, 149:940–946.

    CAS  Google Scholar 

  39. Yamashita T, Tsuyi H, Maeda N, et al.: Etiology of nasal polyps associated with aspirin-sensitive asthmatic subjects. Rhinology 1989, 8:15–24.

    CAS  Google Scholar 

  40. Samuelsson B, Hammarstroem S, Murphy RC, et al.: Leukotrienes and slow reacting substance of anaphylaxis. Allergy 1980, 35:375–381.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    CAS  PubMed  Google Scholar 

  42. Smith DM, Hawksworth RJ, Thien FC, et al.: Urinary leukotriene E4 in bronchial asthma. Eur Respir J 1992, 5:693–699.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  44. Szczeklik A, Stevenson DD: Aspirin-induced asthma: advances in pathogenesis and management. J Allergy Clin Immunol 1999, 104:5–13.

    Article  CAS  PubMed  Google Scholar 

  45. Juergens UR, Christiansen SC, Stevenson DD, et al.: Arachidonic acid metabolism in monocytes of aspirinsensitive patients before and after oral aspirin challenge. J Allergy Clin Immunol 1992, 90:636–645.

    Article  CAS  PubMed  Google Scholar 

  46. 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.

    CAS  PubMed  Google Scholar 

  47. Pierzchalska M, Szabo Z, Sanak M, et al.: Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma. J Allergy Clin Immunol 2003, 111:1041–1048.

    Article  CAS  PubMed  Google Scholar 

  48. Sousa AR, Parikh A, Scadding G, et al.: Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirinsensitive rhinosinusitis. N Engl J Med 2002, 347:1493–1499.

    Article  CAS  PubMed  Google Scholar 

  49. 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.

    CAS  PubMed  Google Scholar 

  50. Sladek K, Dworski R, Soja J, et al.: Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge. Am J Resp Crit Care Med 1994, 149:940–946.

    CAS  PubMed  Google Scholar 

  51. Bochenek G, Nagraba K, Nizankowska E, et al.: A controlled study of 9a, 11b-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls alter aspirin challenge. J Allergy Clin Immunol 2003, 111:743–749.

    Article  CAS  PubMed  Google Scholar 

  52. Sestini P, Armetti L, Gambaro G, et al.: Inhaled PEG2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma. Am J Respir Crit Care Med 1996, 153:572–575.

    CAS  PubMed  Google Scholar 

  53. Juergens UR, Christiansen SC, Stevenson DD, et al.: Inhibition of monocyte leukotriene B4 production following aspirin desensitization. J Allergy Clin Immunol 1995, 96:148–156.

    Article  CAS  PubMed  Google Scholar 

  54. Dahlen B, Nizankowska E, Szczeklik A: Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics. Am J Respir Crit Care Med 1998, 157:1187–1194.

    CAS  PubMed  Google Scholar 

  55. Kuna P, Malmstrom K, Dahlen SE, et al.: Montelukast (MK-0476) a cysLT1 receptor antagonist improves asthma control in aspirin-intolerant asthmatic patients. Am J Respir Care Med 1997, 155:A975.

    Google Scholar 

  56. Sweet JA, Stevenson DD, Simon RA, et al.: Long-term effects of aspirin desensitization treatment for aspirin sensitive rhinosinusitis asthma. J Allergy Clin Immunol 1990, 86:59–65.

    Article  Google Scholar 

  57. Stevenson DD, Hankammer MA, Mathison DA, et al.: Longterm ASA desensitization-treatment of aspirin sensitive asthmatic patients: clinical outcome studies. J Allergy Clin Immunol 1996, 98:751–758.

    Article  CAS  PubMed  Google Scholar 

  58. 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, 111:180–186. This report presents a tremendous amount of data on the effectiveness of aspirin desensitization treatment. Presents data, for the first time, on percent responders and also percent drop outs (and why).

    Article  CAS  PubMed  Google Scholar 

  59. 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, 90:338–341. First look at how soon one can expect to see benefit from aspirin desensitization treatment with aspirin in AERD.

    Article  CAS  PubMed  Google Scholar 

  60. Berges-Gimeno MP, Simon RA, Stevenson DD: The effect of leukotriene modifier drugs on aspirin-induced asthma and rhinitis. Clin Exp Allergy 2002, 32:1491–1496.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Allergy, Asthma and Immunology, Scripps Clinic, 10666 North Torrey Pines Road, 205W, 92037, La Jolla, CA, USA

    Ronald A. Simon MD

Authors
  1. Ronald A. Simon MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simon, R.A. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs. Curr Allergy Asthma Rep 4, 17–24 (2004). https://doi.org/10.1007/s11882-004-0037-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-004-0037-x

Keywords

Search

Navigation