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Asthma attacks induced by low doses of celecoxib, aspirin, and acetaminophen

2005; Elsevier BV; Volume: 117; Issue: 1 Linguagem: Inglês

10.1016/j.jaci.2005.10.021

1097-6825

S Baldassarre, L SCHANDENE, Georges Choufani, Alain Michils,

Asthma and respiratory diseases

To the Editor:Coxibs are a new class of potent nonsteroidal anti-inflammatory drugs that selectively inhibit the COX-2 enzyme.1Hawkey C.J. COX-2 inhibitors.Lancet. 1999; 353: 307-314Abstract Full Text Full Text PDF PubMed Scopus (1049) Google Scholar This characteristic allows them to be administered safely to most patients with intolerance to aspirin or other conventional nonsteroidal anti-inflammatory drugs, which is thought to be precipitated by the COX-1 inhibition of these drugs.2Szczeklik A. Stevenson D.D. Aspirin-induced asthma: advances in pathogenesis and management.J Allergy Clin Immunol. 2003; 111: 913-921Abstract Full Text PDF PubMed Scopus (407) Google Scholar However, anaphylaxis to celecoxib has been reported.3Levy M.B. Fink J.N. Anaphylaxis to celecoxib.Ann Allergy Asthma Immunol. 2001; 87: 72-73Abstract Full Text PDF PubMed Scopus (63) Google Scholar In addition, urticarial reactions have been reported after ingestion of coxibs.4Kelkar P.S. Butterfield J.H. Teaford H.G. Urticaria and angioedema from cyclooxygenase-2 inhibitors.J Rheumatol. 2001; 28: 2553-2554PubMed Google Scholar, 5Murr D. Bocquet H. Lelouet H. Fischer R.M. Revuz J. Cosnes A. Adverse cutaneous reaction to celexocib: 6 cases.Ann Dermatol Venereol. 2003; 130: 519-521PubMed Google ScholarWe report the case of a 45-year-old woman with a known sensitivity to aspirin who was referred to the allergy clinic for treatment of severe arthrosis. The patient was suffering from nonallergic asthma that had been diagnosed at 12 years of age when she had developed a severe bronchospasm after ingesting aspirin (1 g) for a common cold. She had also experienced difficulty with breathing after ingesting paracetamol (500 mg) for a headache. More recently, her asthma had become more difficult to control, requiring frequent courses of oral steroids in addition to high doses of inhaled corticosteroids, long-acting β2-agonists, and leukotriene (LT) antagonists.Nasal polyps and chronic sinusitis had previously been surgically treated, but sinus computed tomography conducted in our clinic revealed persistent signs of sinusitis. This was treated with a course of antibiotics as well as oral and nasal steroids.Before prescribing anything, we subjected the patient to a single-blind placebo-controlled challenge with acetylsalicylic acid (ASA; 10 mg, 30 mg, 120 mg, 300 mg) and celecoxib (15 mg, 60 mg, 130 mg), according to procedures previously described.6Woessener K.M. Simon R.A. Stevenson D.D. Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.Ann Allergy Asthma Immunol. 2004; 93: 339-344Abstract Full Text PDF PubMed Scopus (35) Google ScholarInhaled corticosteroids were continued, but LT antagonists and long-acting β2-agonists were discontinued 5 days before the challenge procedure. The use of short-acting β2-agonists was not allowed from 8 hours before the challenge.No reaction was observed during the placebo procedure. Keeping the previous reaction to a relatively low dose of acetaminophen (500 mg) in mind, the ASA challenge was started using a low dose of aspirin (10 mg). Indeed, about 1 hour and a half after the ingestion of this first provocative dose, the patient did experience an asthma attack, confirming the diagnosis of aspirin-exacerbated repiratory disease (AERD; Fig 1). In addition, she also developed a severe bronchospasm when challenged 2 weeks later with celecoxib (provocative dose, 15 mg; Fig 1).Fig 1 shows that the urinary levels of LTE4—determined by an ELISA (CAST-200; Buhlman, Allschwill, Switzerland)—increased from 368 pg/mg creatinine and 180 pg/mg creatinine to 1283 pg/mg creatinine and 1318 pg/mg creatinine when the patient experienced bronchospasms after ingestion of ASA and celecoxib, respectively. No change in urinary LTE4 levels was observed during placebo challenge.As far as we are aware, this is the first documented report of an asthma attack precipitated by celecoxib through its pharmacological mode of action, even though a double-blind challenge would have been more appropriate to establish the reaction firmly. Indeed, an increase in leukotriene production—thought to play a key role in the onset of bronchospasm induced by ASA in patients with AERD—was also observed when the patient was challenged with celecoxib. Whether this reaction could be expected is unclear. Indeed, even though the increase of urinary LTE4 (× ∼3.49) observed during the ASA challenge was within the range usually observed when ASA patients undergo such procedures, the provocative dose of ASA was strikingly low (10 mg), clearly below the usual threshold doses (30-150 mg).7Szczeklik A. Nizankowska E. Bochenek G. Nagraba K. Mejza F. Swierczynska M. Safety of a specific COX-2 inhibitor in aspirin-induced asthma.Clin Exp Allergy. 2001; 31: 219-225Crossref PubMed Scopus (195) Google Scholar This, together with the reaction previously noted in this patient after the ingestion of a relatively low dose of paracetamol (which has only a limited inhibitory effect on COX-1 activity at usual dosage, with the provocative dose averaging 1000-1500 mg2), suggested an exquisite sensitivity of CysLT production to COX-1 inhibition. Alternatively, considering that celecoxib only inhibits COX-1 at high concentration, some unknown mechanism unrelated to COX-1 inhibition could induce synthesis of leukotrienes by direct stimulation of mast cells (a new mast cell receptor?) with low doses of ASA, acetaminophen, and coxibs.As mentioned, occasional reactions caused by intolerance to celecoxib (mainly skin reactions, but also rare cases of true anaphylactic reactions) have already been reported.3Levy M.B. Fink J.N. Anaphylaxis to celecoxib.Ann Allergy Asthma Immunol. 2001; 87: 72-73Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 4Kelkar P.S. Butterfield J.H. Teaford H.G. Urticaria and angioedema from cyclooxygenase-2 inhibitors.J Rheumatol. 2001; 28: 2553-2554PubMed Google Scholar, 5Murr D. Bocquet H. Lelouet H. Fischer R.M. Revuz J. Cosnes A. Adverse cutaneous reaction to celexocib: 6 cases.Ann Dermatol Venereol. 2003; 130: 519-521PubMed Google Scholar Similarly, a few cases of urticaria and 1 attack of asthma have been reported with the use of rofecoxib,8Passero M. Cyclooxygenase-2 inhibitors in aspirin sensitive asthma.Chest. 2003; 123: 2155-2156Crossref PubMed Scopus (14) Google Scholar, 9Bavbek S. Celik G. Ozer F. Mungan D. Misirligil Z. Safety of selective COX-2 inhibitors in aspirin/nonsteroidal anti-inflammatory drug-intolerant patients: comparison of nimesulide, meloxicam, and rofecoxib.J Asthma. 2004; 41: 67-75Crossref PubMed Scopus (68) Google Scholar—an even more selective COX-2 inhibitor. These reactions are quite rare6Woessener K.M. Simon R.A. Stevenson D.D. Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.Ann Allergy Asthma Immunol. 2004; 93: 339-344Abstract Full Text PDF PubMed Scopus (35) Google Scholar and do not challenge the view that COX-2 inhibitors provide a safe alternative for treatment of inflammatory states in patients with AERD. However, the severity of some reactions5Murr D. Bocquet H. Lelouet H. Fischer R.M. Revuz J. Cosnes A. Adverse cutaneous reaction to celexocib: 6 cases.Ann Dermatol Venereol. 2003; 130: 519-521PubMed Google Scholar, 7Szczeklik A. Nizankowska E. Bochenek G. Nagraba K. Mejza F. Swierczynska M. Safety of a specific COX-2 inhibitor in aspirin-induced asthma.Clin Exp Allergy. 2001; 31: 219-225Crossref PubMed Scopus (195) Google Scholar also suggests that the first dose ingestion should be in a medical doctor's office. To the Editor: Coxibs are a new class of potent nonsteroidal anti-inflammatory drugs that selectively inhibit the COX-2 enzyme.1Hawkey C.J. COX-2 inhibitors.Lancet. 1999; 353: 307-314Abstract Full Text Full Text PDF PubMed Scopus (1049) Google Scholar This characteristic allows them to be administered safely to most patients with intolerance to aspirin or other conventional nonsteroidal anti-inflammatory drugs, which is thought to be precipitated by the COX-1 inhibition of these drugs.2Szczeklik A. Stevenson D.D. Aspirin-induced asthma: advances in pathogenesis and management.J Allergy Clin Immunol. 2003; 111: 913-921Abstract Full Text PDF PubMed Scopus (407) Google Scholar However, anaphylaxis to celecoxib has been reported.3Levy M.B. Fink J.N. Anaphylaxis to celecoxib.Ann Allergy Asthma Immunol. 2001; 87: 72-73Abstract Full Text PDF PubMed Scopus (63) Google Scholar In addition, urticarial reactions have been reported after ingestion of coxibs.4Kelkar P.S. Butterfield J.H. Teaford H.G. Urticaria and angioedema from cyclooxygenase-2 inhibitors.J Rheumatol. 2001; 28: 2553-2554PubMed Google Scholar, 5Murr D. Bocquet H. Lelouet H. Fischer R.M. Revuz J. Cosnes A. Adverse cutaneous reaction to celexocib: 6 cases.Ann Dermatol Venereol. 2003; 130: 519-521PubMed Google Scholar We report the case of a 45-year-old woman with a known sensitivity to aspirin who was referred to the allergy clinic for treatment of severe arthrosis. The patient was suffering from nonallergic asthma that had been diagnosed at 12 years of age when she had developed a severe bronchospasm after ingesting aspirin (1 g) for a common cold. She had also experienced difficulty with breathing after ingesting paracetamol (500 mg) for a headache. More recently, her asthma had become more difficult to control, requiring frequent courses of oral steroids in addition to high doses of inhaled corticosteroids, long-acting β2-agonists, and leukotriene (LT) antagonists. Nasal polyps and chronic sinusitis had previously been surgically treated, but sinus computed tomography conducted in our clinic revealed persistent signs of sinusitis. This was treated with a course of antibiotics as well as oral and nasal steroids. Before prescribing anything, we subjected the patient to a single-blind placebo-controlled challenge with acetylsalicylic acid (ASA; 10 mg, 30 mg, 120 mg, 300 mg) and celecoxib (15 mg, 60 mg, 130 mg), according to procedures previously described.6Woessener K.M. Simon R.A. Stevenson D.D. Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.Ann Allergy Asthma Immunol. 2004; 93: 339-344Abstract Full Text PDF PubMed Scopus (35) Google Scholar Inhaled corticosteroids were continued, but LT antagonists and long-acting β2-agonists were discontinued 5 days before the challenge procedure. The use of short-acting β2-agonists was not allowed from 8 hours before the challenge. No reaction was observed during the placebo procedure. Keeping the previous reaction to a relatively low dose of acetaminophen (500 mg) in mind, the ASA challenge was started using a low dose of aspirin (10 mg). Indeed, about 1 hour and a half after the ingestion of this first provocative dose, the patient did experience an asthma attack, confirming the diagnosis of aspirin-exacerbated repiratory disease (AERD; Fig 1). In addition, she also developed a severe bronchospasm when challenged 2 weeks later with celecoxib (provocative dose, 15 mg; Fig 1). Fig 1 shows that the urinary levels of LTE4—determined by an ELISA (CAST-200; Buhlman, Allschwill, Switzerland)—increased from 368 pg/mg creatinine and 180 pg/mg creatinine to 1283 pg/mg creatinine and 1318 pg/mg creatinine when the patient experienced bronchospasms after ingestion of ASA and celecoxib, respectively. No change in urinary LTE4 levels was observed during placebo challenge. As far as we are aware, this is the first documented report of an asthma attack precipitated by celecoxib through its pharmacological mode of action, even though a double-blind challenge would have been more appropriate to establish the reaction firmly. Indeed, an increase in leukotriene production—thought to play a key role in the onset of bronchospasm induced by ASA in patients with AERD—was also observed when the patient was challenged with celecoxib. Whether this reaction could be expected is unclear. Indeed, even though the increase of urinary LTE4 (× ∼3.49) observed during the ASA challenge was within the range usually observed when ASA patients undergo such procedures, the provocative dose of ASA was strikingly low (10 mg), clearly below the usual threshold doses (30-150 mg).7Szczeklik A. Nizankowska E. Bochenek G. Nagraba K. Mejza F. Swierczynska M. Safety of a specific COX-2 inhibitor in aspirin-induced asthma.Clin Exp Allergy. 2001; 31: 219-225Crossref PubMed Scopus (195) Google Scholar This, together with the reaction previously noted in this patient after the ingestion of a relatively low dose of paracetamol (which has only a limited inhibitory effect on COX-1 activity at usual dosage, with the provocative dose averaging 1000-1500 mg2), suggested an exquisite sensitivity of CysLT production to COX-1 inhibition. Alternatively, considering that celecoxib only inhibits COX-1 at high concentration, some unknown mechanism unrelated to COX-1 inhibition could induce synthesis of leukotrienes by direct stimulation of mast cells (a new mast cell receptor?) with low doses of ASA, acetaminophen, and coxibs. As mentioned, occasional reactions caused by intolerance to celecoxib (mainly skin reactions, but also rare cases of true anaphylactic reactions) have already been reported.3Levy M.B. Fink J.N. Anaphylaxis to celecoxib.Ann Allergy Asthma Immunol. 2001; 87: 72-73Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 4Kelkar P.S. Butterfield J.H. Teaford H.G. Urticaria and angioedema from cyclooxygenase-2 inhibitors.J Rheumatol. 2001; 28: 2553-2554PubMed Google Scholar, 5Murr D. Bocquet H. Lelouet H. Fischer R.M. Revuz J. Cosnes A. Adverse cutaneous reaction to celexocib: 6 cases.Ann Dermatol Venereol. 2003; 130: 519-521PubMed Google Scholar Similarly, a few cases of urticaria and 1 attack of asthma have been reported with the use of rofecoxib,8Passero M. Cyclooxygenase-2 inhibitors in aspirin sensitive asthma.Chest. 2003; 123: 2155-2156Crossref PubMed Scopus (14) Google Scholar, 9Bavbek S. Celik G. Ozer F. Mungan D. Misirligil Z. Safety of selective COX-2 inhibitors in aspirin/nonsteroidal anti-inflammatory drug-intolerant patients: comparison of nimesulide, meloxicam, and rofecoxib.J Asthma. 2004; 41: 67-75Crossref PubMed Scopus (68) Google Scholar—an even more selective COX-2 inhibitor. These reactions are quite rare6Woessener K.M. Simon R.A. Stevenson D.D. Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.Ann Allergy Asthma Immunol. 2004; 93: 339-344Abstract Full Text PDF PubMed Scopus (35) Google Scholar and do not challenge the view that COX-2 inhibitors provide a safe alternative for treatment of inflammatory states in patients with AERD. However, the severity of some reactions5Murr D. Bocquet H. Lelouet H. Fischer R.M. Revuz J. Cosnes A. Adverse cutaneous reaction to celexocib: 6 cases.Ann Dermatol Venereol. 2003; 130: 519-521PubMed Google Scholar, 7Szczeklik A. Nizankowska E. Bochenek G. Nagraba K. Mejza F. Swierczynska M. Safety of a specific COX-2 inhibitor in aspirin-induced asthma.Clin Exp Allergy. 2001; 31: 219-225Crossref PubMed Scopus (195) Google Scholar also suggests that the first dose ingestion should be in a medical doctor's office. We thank Alain Van Muylen, Irène Delvaux (chest department, Cliniques Universitaires De Bruxelles Erasme), and David Young from Cline, Davis and Mann for their help in preparing the manuscript.