Allergy Asthma Immunol Res.  2016 Jul;8(4):298-304. 10.4168/aair.2016.8.4.298.

Update on the Management of Aspirin-Exacerbated Respiratory Disease

Affiliations
  • 1Department of Medicine, Harvard Medical School, Boston, MA, USA. kbuchheit@partners.org
  • 2Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, USA.

Abstract

Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD.

Keyword

Aspirin-exacerbated respiratory disease; Samter's triad; nasal polyps; aspirin desensitization

MeSH Terms

Aspirin
Asthma
Cyclooxygenase 1
Eosinophils
Humans
Nasal Polyps
Aspirin
Cyclooxygenase 1

Cited by  2 articles

Which Factors Associated With Activated Eosinophils Contribute to the Pathogenesis of Aspirin-Exacerbated Respiratory Disease?
Youngwoo Choi, Youngsoo Lee, Hae-Sim Park
Allergy Asthma Immunol Res. 2019;11(3):320-329.    doi: 10.4168/aair.2019.11.3.320.

Therapeutic Effect of Omalizumab in Severe Asthma: A Real-World Study in Korea
Ji-Ho Lee, Hyun Young Lee, Chang-Gyu Jung, Ga-Young Ban, Yoo Seob Shin, Young-Min Ye, Dong-Ho Nahm, Hae-Sim Park
Allergy Asthma Immunol Res. 2018;10(2):121-130.    doi: 10.4168/aair.2018.10.2.121.


Reference

1. Rajan JP, Wineinger NE, Stevenson DD, White AA. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: a meta-analysis of the literature. J Allergy Clin Immunol. 2015; 135:676–681.e1.
2. 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.
3. 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.
4. Cahill KN, Bensko JC, Boyce JA, Laidlaw TM. Prostaglandin D(2): a dominant mediator of aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2015; 135:245–252.
5. Kowalski ML, Makowska JS. Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new classification in real practice? Allergy Asthma Immunol Res. 2015; 7:312–320.
6. Cahill KN, Laidlaw TM. Aspirin exacerbated respiratory disease: the search for a biomarker. Ann Allergy Asthma Immunol. 2014; 113:500–501.
7. Christie PE, Tagari P, Ford-Hutchinson AW, Charlesson S, Chee P, Arm JP, et al. Urinary leukotriene E4 concentrations increase after aspirin challenge in aspirin-sensitive asthmatic subjects. Am Rev Respir Dis. 1991; 143:1025–1029.
8. Kanaoka Y, Boyce JA. Cysteinyl leukotrienes and their receptors; emerging concepts. Allergy Asthma Immunol Res. 2014; 6:288–295.
9. Sladek K, Dworski R, Soja J, Sheller JR, Nizankowska E, Oates JA, et al. Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge. Am J Respir Crit Care Med. 1994; 149:940–946.
10. Bochenek G, Nagraba K, Nizankowska E, Szczeklik A. A controlled study of 9alpha,11beta-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls after aspirin challenge. J Allergy Clin Immunol. 2003; 111:743–749.
11. Yoshimura T, Yoshikawa M, Otori N, Haruna S, Moriyama H. Correlation between the prostaglandin D(2)/E(2) ratio in nasal polyps and the recalcitrant pathophysiology of chronic rhinosinusitis associated with bronchial asthma. Allergol Int. 2008; 57:429–436.
12. Cowburn AS, Sladek K, Soja J, Adamek L, Nizankowska E, Szczeklik A, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest. 1998; 101:834–846.
13. Payne SC, Early SB, Huyett P, Han JK, Borish L, Steinke JW. Evidence for distinct histologic profile of nasal polyps with and without eosinophilia. Laryngoscope. 2011; 121:2262–2267.
14. Laidlaw TM, Kidder MS, Bhattacharyya N, Xing W, Shen S, Milne GL, et al. Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes. Blood. 2012; 119:3790–3798.
15. Sestini P, Armetti L, Gambaro G, Pieroni MG, Refini RM, Sala A, et al. Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma. Am J Respir Crit Care Med. 1996; 153:572–575.
16. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007; 120:S94–S138.
17. Peters AT, Spector S, Hsu J, Hamilos DL, Baroody FM, Chandra RK, et al. Diagnosis and management of rhinosinusitis: a practice parameter update. Ann Allergy Asthma Immunol. 2014; 113:347–385.
18. Macy E, Bernstein JA, Castells MC, Gawchik SM, Lee TH, Settipane RA, et al. Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: a practice paper. Ann Allergy Asthma Immunol. 2007; 98:172–174.
19. Gollapudi RR, Teirstein PS, Stevenson DD, Simon RA. Aspirin sensitivity: implications for patients with coronary artery disease. JAMA. 2004; 292:3017–3023.
20. Woessner KM, Simon RA. Cardiovascular prophylaxis and aspirin "allergy". Immunol Allergy Clin North Am. 2013; 33:263–274.
21. Kim YJ, Lim KH, Kim MY, Jo EJ, Lee SY, Lee SE, et al. Cross-reactivity to acetaminophen and celecoxib according to the type of nonsteroidal anti-inflammatory drug hypersensitivity. Allergy Asthma Immunol Res. 2014; 6:156–162.
22. Stevenson DD, Pleskow WW, Simon RA, Mathison DA, Lumry WR, Schatz M, et al. Aspirin-sensitive rhinosinusitis asthma: a double-blind crossover study of treatment with aspirin. J Allergy Clin Immunol. 1984; 73:500–507.
23. McMains KC, Kountakis SE. Medical and surgical considerations in patients with Samter's triad. Am J Rhinol. 2006; 20:573–576.
24. 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.
25. 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.
26. Stevenson DD, Hankammer MA, Mathison DA, Christiansen SC, Simon RA. Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes. J Allergy Clin Immunol. 1996; 98:751–758.
27. Świerczyńska-Krępa M, Sanak M, Bochenek G, Stręk P, Ćmiel A, Gielicz A, et al. Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study. J Allergy Clin Immunol. 2014; 134:883–890.
28. Rozsasi A, Polzehl D, Deutschle T, Smith E, Wiesmiller K, Riechelmann H, et al. Long-term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily. Allergy. 2008; 63:1228–1234.
29. Shaker M, Lobb A, Jenkins P, O'Rourke D, Takemoto SK, Sheth S, et al. An economic analysis of aspirin desensitization in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2008; 121:81–87.
30. 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; 119:157–164.
31. Dahlén SE, Malmström K, Nizankowska E, Dahlén B, Kuna P, Kowalski M, et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2002; 165:9–14.
32. 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; 24:226–230.
33. Kieff DA, Busaba NY. Efficacy of montelukast in the treatment of nasal polyposis. Ann Otol Rhinol Laryngol. 2005; 114:941–945.
34. Ta V, White AA. Survey-defined patient experiences with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2015; 3:711–718.
35. Watkins PB, Dube LM, Walton-Bowen K, Cameron CM, Kasten LE. Clinical pattern of zileuton-associated liver injury: results of a 12-month study in patients with chronic asthma. Drug Saf. 2007; 30:805–815.
36. Wenzel S, Busse W, Calhoun W, Panettieri R Jr, Peters-Golden M, Dube L, et al. The safety and efficacy of zileuton controlled-release tablets as adjunctive therapy to usual care in the treatment of moderate persistent asthma: a 6-month randomized controlled study. J Asthma. 2007; 44:305–310.
37. Bobolea I, Barranco P, Fiandor A, Cabañas R, Quirce S. Omalizumab: a potential new therapeutic approach for aspirin-exacerbated respiratory disease. J Investig Allergol Clin Immunol. 2010; 20:448–449.
38. Bergmann KC, Zuberbier T, Church MK. Omalizumab in the treatment of aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2015; 3:459–460.
39. Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013; 131:110–116.e1.
40. Johns CB, Laidlaw TM. Elevated total serum IgE in nonatopic patients with aspirin-exacerbated respiratory disease. Am J Rhinol Allergy. 2014; 28:287–289.
41. Klinkhardt U, Bauersachs R, Adams J, Graff J, Lindhoff-Last E, Harder S. Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther. 2003; 73:232–241.
42. Paruchuri S, Tashimo H, Feng C, Maekawa A, Xing W, Jiang Y, et al. Leukotriene E4-induced pulmonary inflammation is mediated by the P2Y12 receptor. J Exp Med. 2009; 206:2543–2555.
43. Cummings HE, Liu T, Feng C, Laidlaw TM, Conley PB, Kanaoka Y, et al. Cutting edge: Leukotriene C4 activates mouse platelets in plasma exclusively through the type 2 cysteinyl leukotriene receptor. J Immunol. 2013; 191:5807–5810.
44. Liu T, Laidlaw TM, Katz HR, Boyce JA. Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes. Proc Natl Acad Sci U S A. 2013; 110:16987–16992.
45. Kim SH, Choi JH, Park HS, Holloway JW, Lee SK, Park CS, et al. Association of thromboxane A2 receptor gene polymorphism with the phenotype of acetyl salicylic acid-intolerant asthma. Clin Exp Allergy. 2005; 35:585–590.
46. Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007; 176:1062–1071.
47. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014; 371:1189–1197.
48. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009; 360:985–993.
49. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009; 360:973–984.
50. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014; 371:1198–1207.
51. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012; 380:651–659.
52. Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F, et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011; 128:989–995.e1-8.
53. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013; 368:2455–2466.
54. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014; 371:130–139.
55. Chudwin DS, Strub M, Golden HE, Frey C, Richmond GW, Luskin AT. Sensitivity to non-acetylated salicylates in a patient with asthma, nasal polyps, and rheumatoid arthritis. Ann Allergy. 1986; 57:133–134.
56. Park HS, Lim YS, Suh JE, Rhu NS, Cho DI, Kim JW. Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity. J Korean Med Sci. 1991; 6:113–117.
57. Sommer DD, Hoffbauer S, Au M, Sowerby LJ, Gupta MK, Nayan S. Treatment of aspirin exacerbated respiratory disease with a low salicylate diet: a pilot crossover study. Otolaryngol Head Neck Surg. 2015; 152:42–47.
58. Healy E, Newell L, Howarth P, Friedmann PS. Control of salicylate intolerance with fish oils. Br J Dermatol. 2008; 159:1368–1369.
Full Text Links
  • AAIR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr