Abstract
Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) exert their clinical effect through inhibition of prostaglandin H synthases 1 and 2, also known as cyclooxygenase. This shared effect of COX-inhibition is also the mechanism for shared adverse effects. Much of our understanding of cross-reacting drugs and chemicals with aspirin comes from studying asthmatics with aspirin-exacerbated respiratory disease (AERD). Aspirin exacerbated respiratory disease is characterized by recalcitrant sinusitis/polyposis, asthma and precipitation of asthma after ingestion of aspirin and most NSAIDs. Cross-reactions between ASA and NSAIDs occur with first exposure unlike IgE-mediated allergic drug reactions. Cross-reactions between aspirin and other drugs are dependent upon inhibition of the cyclooxygenase-1 isoenzyme. Desensitization to aspirin will result in cross-desensitization to all NSATDs that inhibit COX-1. Despite reports in the literature, there does not appear to he cross-reactions between food coloring, hydrocortisone succinate and monosodium glutamate in individuals with aspirin exacerbated respiratory disease. The new highly selective cyclooxygenase 2 inhibitors are well tolerated in AERD asthmatics who have not been desensitized to aspirin. Because low-dose ASA exerts a cardioprotective effect by irreversible inhibition of COX-1, AERD patients who are at risk for coronary artery disease should be considered for aspirin desensitization.
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Hamberg, M., Svensson, J., and Samuelsson, B. (1974), Novel transformation of arachidonic acid in human platelets. Proc. Natl. Acad. Sci. USA 71, 3400–3404.
Stevenson, D. D. and Simon R. A. Sensitivity to aspirin and nonsteroidal antiinflammatory drugs, in: Allergy: Principles and Practice, Middleton, R. C. W., and Busse, W. W., eds., 5th ed. Mosby St. Louis, 1998, pp. 1225–1234.
Vane, J. R., Bakhle, Y. S., and Botting, R. M. (1998). Cyclooxygenases 1 and 2. Annu. Rev. Pharmacol. Toxicol. 38, 91–120.
Kraemer, S. A., Meade, C. A., and DeWitt, D. L. (1992), Prostaglandin endoperoxidase synthase gene structure: identification of the transcriptional start site and 5' flanking regulatory sequences. Arch. Biochem. Biophys. 293, 391–400.
Hinz, B., and Brune, K. (2002), Cyclooxygenase-2–10 years later. J. Pharmacol. Exp. Ther. 300, 357–375.
Berg, D. J., Zhang, J., Lauricella, D. M., and Moore, S. A. (2001), IL-10 is a central regulator of cyclo-oxygenase-2 expression and prostaglandin production. J. Immunol. 166, 2674–2680.
Gierse, J. K., Hauser, S. D., Creely, D. P., Koboldt, C., Rangwala, S. H., Isakson, P. C., et al. (1993) Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem. J. 305 (Pt 2) 479–484.
Picot, D., Loll, P. J., and Garavito, R. M. (1994), The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature 367, 243–249.
Picot, D., Loll, P. J., and Garavito, R. M. (1997), X-ray crystallographic study of the structure of prostaglandin H synthase. Adv. Exp. Med. Biol. 400A, 107–111.
Roth, G. J., Stanford, N., and Majerus, P. W. (1975). Acetylation of prostaglandin synthase by aspirin. Proc. Natl. Acad. Sci. USA 72, 3073–3076.
Luong, C., Miller, M., Barnett, J., Chow, J., Ramesha, C., and Browner, M. F. (1996), Flexibility of NSAID binding site in the structure of human cyclooxygenase 2 Nat. Struct. Biol. 3, 927–933.
Kurambail, R. G., Stevens, A. M., Gierse, J. K., McDonald, J. J., Stegeman, R. A., Pak, J. Y., et al. (1996), Structural basis for selective inhibition of cyclooxygenase-2 by antiinflammatory agents. Nature 384, 644–648.
Stevenson, D. D. (1984), Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal antiinflammatory drugs. J. Allergy Clin. Immunol. 74, 617–622.
Funk, C. D. (2001), Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871–1875.
Demoly, P., Jaffuel, D., Lequeux, N., Weksler, B., Creminon, C. H., Michel, F.-B., et al. (1997), Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of asthmatics. Am. J. Respir. Crit. Care Med. 155, 670–675.
Szczeklik, A., and Stevenson, D. D. (1999), Aspirin-induced asthma: advances in pathogenesis and management. J. Allergy Clin. Immunol. 104, 5–13.
Szczeklik, A. (1990), The cylcooxygenase theory of aspirin-induced asthma. Eur. Respir. J. 3, 588–593.
Fischer, A. R., Rosenberg, M. A., Lilly, C. M., Callergy, J. C., Rubin, P., Cohn, J., et al. (1994), Direct evidence for a role of the mast cell in the nasal response to aspirin in aspirin-sensitive asthma. J. Allergy Clin. Immunol. 94, 1046–1056.
Vanselow, N. A., and Smith, J. R. (1967), Bronchial asthma induced by indomethacin. Ann. Intern. Med. 66, 568–573.
Samter, M. and Beers, R. J. (1968), Intolerance to aspirin: clinical studies and consideration of its pathogenesis. Ann. Intern. Med. 68, 975–983.
Szczeklik, A., Gryglewski, R. J., and Czerniawska-Mysik, G. (1977), Clinical patterns of hypersensitivity to nonsteroidal antiinflammatory drugs and their pathogenesis. J. Allergy Clin. Immunol. 60, 276–284.
Szczeklik, A. and Gryglewski, R. J. (1983), Asthma and antiinflammatory drugs: mechanisms and clinical patterns. Drugs 25, 533–543.
Mathison, D. A., and Stevenson, D. D. (1979), Hypersensitivity to nonsteroidal antiinflammatory drugs: indications and methods for oral challenges. J. Allergy Clin. Immunol. 64, 669–674.
Stevenson, D. D., Hougham, A., Schrank, P., and Goldlust, M. B. (1990), Disalcid cross-sensitivity in aspirin-sensitive asthmatic patients. J. Allergy Clin. Immunol. 86, 749–758.
Sheehan, G. J., Kutzner, M. R., and Chin, W. D. (1989), Acute asthma attack due to ophthalmic indomethacin. Ann. Intern. Med. 11, 337–338.
Stevenson, D. D. (1986), Aspirin desensitization. N. Engl. Reg. Allergy Proc. 7, 101–104.
Stevenson, D. D. (1987), Aspirin sensitivity: new approaches to detection and desensitization. Int. Med. Spec. 8, 60–68.
Pleskow, W. W., Stevenson D. D., Mathison, D. A., Simon, R. A., Schatz, M., and Zeiger, R. S. (1982), Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J. Allergy Clin. Immunol. 69, 11–19.
Bosso, J. V., Creighton, D., and Stevenson, D. D. (1992), Fluriprofen (Ansaid) cross-sensitivity in an aspirin-sensitive asthmatic patient. Chest 101, 856–858.
Szmidt, M., Grzelewska-Rzymowska, I., and Rozniecki, J. (1993), Tolerance to aspirin in aspirin-sensitive asthmatics. Methods of inducing the tolerance state and its influence on the course of asthma and rhinosinusitis. J. Investig. Allergol. Clin. Immunol. 3, 156–159.
Szmidt, M., Grzelewska-Rzymowska, I., Kowalski, M., et al. (1987) Tolerance to acetylsalicylic acid (ASA) induced in ASA-sensitive asthmatics does not depend on initial adverse reaction. Allergy 42, 182–185.
Falliers, C. J. (1983), Acetaminophen and aspirin challenges in subgroups of asthmatics. J. Asthma 20 (Suppl 1), 39–49.
Schwarz, N., and Ham Pong, A. (1996), Acetaminophen anaphylaxis with aspirin and sodium salicylate sensitivity: a case report. Ann. Allergy Asthma Immunol. 77, 473–474.
Settipane, R. A. and Stevenson, D. D. (1989), Cross sensitivity with acetaminophen in aspirinsensitive subjects with asthma. J. Allergy Clin. Immunol. 84, 26–33.
Settipane, R. A., Schrank, P. J., Simon, R. A., Mathison, D. A., Christiansen, S. C., and Stevenson, D. D. (1995), Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J. Allergy Clin. Immunol. 96, 480–485.
Delaney, J. C. (1976) The diagnosis of aspirin idiosyncrasy by analgesic challenge. Clin. Allergy 6, 177–181.
Andri, L., Senna, G., Betteli, C., Givanni, S., Scaricabarozzi, I., Mezzelani, P., et al. (1994), Tolerability of nimesulide in aspirin-sensitive patients. Ann. Allergy 72, 29–32.
Asero, R. (1998), Aspirin and paracetamol tolerance in patients with nimesulide-induced urticaria. Ann. Allergy Asthma Immunol. 81, 237–238.
Bavbek, S., Celik, G., Ediger, D., Mungan, D., Demirel, Y. S., and Misirligil, Z. (1999), The use of nimesulide in patients with acetylsalicylic acid and nonsteroidal antiinflammatory drug intolerance. J. Asthma 36, 657–663.
Quaratino, D., Romano, A., Di Fonso, M., Papa, G., Perrone, M. R., D’Ambrosio, F. P. et al. (2000), Tolerability of meloxicam in patients with histories of adverse reactions to nonsteroidal antiinflammatory drugs.—Ann. Allergy Asthma Immunol. 84, 613–617.
Kosnik, M., Music, E., Matjaz, F., and Suskovic, S. (1998), Relative safety of meloxicam in NSAID-intolerant patients. Allergy 53, 1231–1233.
Szczeklik, A., Nizankowska, E., Bochenek, G., Nagraba, K., Mejza, F., and Swiercznska, M. (2001), Safety of a specific COX-2 inhibitor in aspirin-induced asthma. Clin. Exp. Allergy 31, 219–225.
Stevenson, D. D., and Simon, R. A. (2001), Lack of crossreactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J. Allergy Clin. Immunol. 108, 47–51.
Yoshida, S., Ishizaki, Y., Onuma, K., Shoji, T., Nakagawa, H., and Amayasu, H. (2000), Selective cyclo-oxygenase 2 inhibitor in patients with asthma and aspirin intolerance [letter]. J. Allergy Clin. Immunol. 106, 1203–1204.
Dahlen, B., Szczeklik, A., and Murray, J. J. (2001), Celecoxib in patients with asthma and aspirin intolerance [letter]. N. Engl. J. Med. 344, 142.
Woessner, K. M., and Simon, R. A. (2002), The safety of celecoxib in patients with aspirin sensitive asthma. Arthritis Rheum. 46, 2201–2206.
Physicians Desk Reference, 55th ed. Medical Economics Company, Montvale, NJ, 2001, pp. 2213–2676.
Levy, M. B., and Fink, J. N. (2001), Anaphylaxis to celecoxib. Ann. Allergy Asthma Immunol. 87, 72–73.
Schellenberg, R. R., ISH, (2001), Anaphylactoid reaction to a cyclooxygenase-2 inhibitor in a patient who had a reaction to a cyclooxygenase-1 inhibitor. N. Engl. J. Med. 345, 1856.
Spector, S. L., Wangaard, C. H., and Farr, D. S. (1979), Aspirin and concomitant idiosyncrasies in adult asthmatic patients. J. Allergy Clin. Immunol. 64, 500–506.
Freedman, B. (1977), Asthma induced by sulfur dioxide, benzoate and tartrazine contained in orange drinks. Clin. Allergy 7, 407–411.
Juhlin, L., Michaelsson, G., and Zetterstrom, O. (1972), Urticaria and asthma induced by food and drug additives in patients with aspirin sensitivity. J. Allergy Clin. Immunol. 50, 92–102.
Allen, D. H., Delohery, J., and Baker, G. (1987), Monosodium L-glutamate-induced asthma. J. Allergy Clin. Immunol. 80, 530–537.
Weber, R. W., Hoffman, M., Raine, D. A., Jr., and Nelson, H. S. (1979), Incidence of bronchocon-striction due to aspirin, azo dyes, non-azo dyes, and preservatives in a population of perennial asthmatics. J. Allergy Clin. Immunol. 64, 32–37.
Ardern, K. D. and Ram, F. S. (2001), Tartrazine exclusion for allergic asthma (Cochrane Review). Cochrane Database Syst. Rev. 4, CD000460.
Stevenson, D. D., Simon, R. A., Lumry, W. R., and Mathison, D. A. (1986), Adverse reactions to tartrazine. J. Allergy Clin. Immunol. 78, 182–191.
Szczeklik, A., Nizankowska, E., and Sanak, M. (1998), New insights into the pathogenesis and management of aspirin-induced asthma. Clin. Asthma Reviews 2, 79–86.
Dajani, B. M., Sliman, N. A., and Shubair, K. S. (1981), Bronchospasm caused by intravenous hydrocortisone succinate (Solu-Cortef) in aspirinsensitive asthmatics. J. Allergy Clin. Immunol. 68, 201–204.
Szczeklik, A., Nizankowska, E., Czerniawska-Mysik, G., and Sek, S. (1985)) Hydrocortisone and airflow impairment in aspirin-induced asthma. J. Allergy Clin. Immunol. 76, 530–536.
Feigenbaum, B. A., Stevenson, D. D., and Simon, R. A. (1995), Lack of cross-sensitivity to IV hydrocortisone in aspirin-sensitive subjects with asthma. J. Allergy Clin. Immunol., 96, 545–548.
Moneret-Vautrin, D. A. (1987), Monosodium glutamate induced asthma: study of the potential risk in 30 asthmatics and a review of the literature. Alergie et Immunol. 19, 29–35.
Stevenson, D. D. (2000), Monosodium glutamate and asthma. J. Nutrition 130, 1067–1073.
Schwartzstein, R., Kelleher, M., Weingerger, S. E., Weiss, J. W., and Drazen, J. M. (1987), Airway effects of monosodium glutamate in subjects with chronic stable asthma. J. Asthma 24, 167–172.
Germano, P., Cohen, S. G., Hahn, B., and Metcalfe, D. D. (1991), An evaluation of clinical reactions to monosodium glutamate (MSG) in asthmatics, using a blinded placebo-controlled challenge. J. Allergy. Clin. Immunol. 87, 177.
Woods, R., Weiner, J., Thien, F., Abramson, M., and Walters, E. (1998), The effects of monosodium glutamate in adults with asthma who perceive themselves to be monosodium glutamate-intolerant. J. Allergy Clin. Immunol. 101, 762–771.
Woessner, K. M., Simon, R. A., and Stevenson, D. D. (1999), Monosodium glutamate sensitivity in asthma. J. Allergy Clin. Immunol. 104, 305–310.
Stevenson, D. D., and Simon, R. A. (1981), Sensitivity to ingested metabisulfite in asthmatic subjects. J. Allergy Clin. Immunol. 68, 26–20.
Szczeklik, A., Nizankowska, E., and Dworski, R. (1990), Choline magnesium trisalicylate in patients with aspirin-induced asthma. Eur. Respir. J. 3, 535–539.
Patrono, C. (2001), Efficacy and safety of aspirin in the long-term management of atherothrombosis. Haematologica 86, 19–21.
Patrono, C., Patrignani P., and Garcia Rodriguez, L. A. (2001), Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs. J. Clin. Investig. 108, 7–13.
Schaefer, O. P., and Gore, J. M. (1999), Aspirin sensitivity: the role for aspirin challenge and desensitization in postmyocardial infarction patients. Cardiology 91, 8–13.
Parks, W. M., Hoak, J. C., and Czervionke, R. L. (1981), Comparative effect of ibuprofen on endothelial and platelet prostaglandin synthesis. J. Pharmacol Exp. Ther. 219, 415–419.
Rao, G. H., Johnson, G. G., Reddy, K. R., and White, J. G. (1983), Ibuprofen protects platelet cyclo-oxygenase from irreversible inhibition by aspirin. Arteriosclerosis 3, 383–388.
Cerletti, C. (1985), Interaction of non-steroidal anti-inflammatory drugs on platelet cyclo-oxygenase and lipoxygenase activity. Int. J. Tissue React. 7, 309–312.
Catella-Lawson, F., Reilly, M. P., Kapoor, S. C., Cucchiara, A. J., DeMarco, S., Tournier, B., et al. (2001), Cyclooxygenase inhibitors and the anti-platelet effects of aspirin. N. Engl. J. Med. 345, 1809–1817.
Copeland, R. A., Williams, J. M., Giannaras, J., Nurnberg, S., Covington, M., Pinto, D., et al. (1994), Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc. Natl. Acad. Sci. USA 91, 11,202–11,206.
Ouellet, M., and Percival, M. D. (1995), Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem. J. 306 (Pt 1), 247–251.
Reilly, I. A., and FitzGerald, G. A. (1987), Blood 69, 180–186.
Ouellet, M., Riendeau, D., and Percival, M. D. (2001), A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin. Proc. Natl. Acad. Sci. USA 98, 14,583–14,588.
Greenberg, H. E., Gottesdiener, K., Huntington, M. Wong, P., Larson, P., Wildonger, L., et al. (2000), A new cyclooxygenase-2 inhibitor rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers. J. Clin. Pharmacol. 40, 1509–1515.
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Woessner, K.M. Crossreacting drugs and chemicals. Clinic Rev Allerg Immunol 24, 149–158 (2003). https://doi.org/10.1385/CRIAI:24:2:149
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DOI: https://doi.org/10.1385/CRIAI:24:2:149