Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice
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《英国医生杂志》
1 Woolcock Institute of Medical Research, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia, 2 King's College Hospital, London SE5 9RS, 3 Asthma Centre, Royal Prince Alfred Hospital
Correspondence to: C Jenkins, Suite 702, 26 Ridge Street, North Sydney, NSW 2060, Australia crj@med.usyd.edu.au
Abstract
Aspirin induced asthma is a distinct clinical syndrome affecting some asthmatic patients. It is characterised by the onset of asthma 30 minutes to three hours after the ingestion of aspirin. Although the name of the condition relates to aspirin, it is well established that affected patients are cross sensitive to all non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclo-oxygenase (COX) enzymes.1 2 Paracetamol (acetaminophen), however, is seldom associated with cross sensitivity in patients with aspirin induced asthma. Emerging evidence shows that paracetamol may exert at least part of its analgesic effect through a newly identified COX-3 isoenzyme, whereas aspirin induced asthma is believed to involve inhibition of COX-1.3-5
Despite a wealth of literature on aspirin induced asthma, controversy remains as to its prevalence, with published data ranging from 4% to 44%. Differences in populations studied, methods used, definitions of outcomes, and criteria for defining sensitivity reactions may all be responsible for the variations in reported rates.6-8 A greater understanding of aspirin induced asthma is desirable, particularly given the increasing trend for consumers to treat themselves for minor painful conditions and the lack of association by many consumers between asthma and some analgesics. We performed a systematic review to reassess the prevalence of aspirin induced asthma in the general asthma population and to understand better the cross sensitivity of these individuals to commonly used non-prescription analgesics.
Methods
Prevalence in adults
A total of 66 papers were identified that gave the prevalence for aspirin induced asthma. Only 21 (15 in adults and six in children) were eligible for inclusion in our analysis (fig 1).8 10-29 Although a double blind trial would produce more robust data, this is not the usual method employed for studies of aspirin induced asthma owing to the high risk of life threatening reactions. Only four of the trials were double blind.
Fig 1 Inclusion of studies
The pooled incidence of aspirin induced asthma was 21% (95% confidence interval 14% to 29%), regardless of whether the patients had a history of aspirin induced asthma or markers for an increased risk of the syndrome (table 1). Prevalence of aspirin induced asthma also seemed to depend on the method used to determine it, with history alone resulting in a much lower prevalence (2.7%). Four of the studies in adults gave data on the number of patients reacting to different doses of aspirin.12 14 15 17 Around half (57/113) of those who had positive reactions, did so at low doses of aspirin ( 80 mg), indicating that they were highly sensitive.
Table 1 Prevalence of aspirin induced asthma in adults, analysed by population and test method. Values are numbers (percentages) unless stated otherwise
Prevalence in children
Aspirin induced asthma has been considered rare in children, yet we found that although it is less common in children than in adults, prevalence is still around 5% (0% to 14%) when children are subject to oral provocation testing (table 2).21 23 25 Although only one of the studies was a double blind, randomised controlled trial, it accounted for almost half of the patients in our analysis.21 As with adults, the use of history alone gave a lower estimate of prevalence (2%, 1% to 3%) than determined by oral provocation testing.
Table 2 Prevalence of aspirin induced asthma in children, analysed by population and test method. Values are numbers (percentages) unless stated otherwise
Incidence of cross sensitivity
Over the counter NSAIDs
Ten studies reported the incidence of cross sensitivity to three commonly used NSAIDs (ibuprofen, naproxen, diclofenac). Only three of these were level 1 studies eligible for inclusion.1 30 31 Based on these, the incidence of cross sensitivity was: 400 mg ibuprofen, 98% (95% CI 90% to 100%); 100 mg naproxen, 100% (83% to 100); and 40 mg diclofenac, 93% (76% to 100%; table 3). 1 30 31
Table 3 Incidence of cross sensitivity to NSAIDs among patients with aspirin induced asthma
Cross sensitivity to paracetamol
Each article on cross sensitivity to paracetamol was classified according to its methods. Ten of 52 identified papers were of level 1 studies.1 12 14 17 24 32-36 Table 4 summarises the data for these studies, except for one in which the authors report the number of oral provocation tests and reactions but not the number of patients with a positive reaction.36 Of 268 adults and children with aspirin induced asthma who underwent oral challenge, only 32 had a positive respiratory reaction to paracetamol (pooled incidence 7%, 0% to 16%).
Table 4 Incidence of cross sensitivity to paracetamol among patients with aspirin induced asthma
Discussion
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. J Allergy Clin Immunol 1977;60: 276-84.
Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol 1984;74: 617-22.
Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Nat Acad Sci USA 2002;99: 13926-31.
Schwab JM, Schluesener HJ, Laufer S. COX-3: just another COX or the solitary elusive target of paracetamol? Lancet 2003;361: 981-2.
Stevenson DD, Simon RA. Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 2001;108: 47-51.
Kwoh CK, Feinstein AR. Rates of sensitivity reactions to aspirin: problems in interpreting the data. Clin Pharmacol Ther 1986;40: 494-505.
Levy S, Volans G. The use of analgesics in patients with asthma. Drug Safety 2001;24: 829-41.
Vally H, Taylor ML, Thompson PJ. The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients. Thorax 2002;57: 569-74.
Nizankowska E, Bestynska-Krypel A, Cmiel A, Szczeklik A. Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma. Eur Respir J 2000;15: 863-9.
McDonald JR, Mathison DA, Stevenson DD. Aspirin intolerance in asthma. Detection by oral challenge. J Allergy Clin Immunol 1972;50: 198-207.
Stevenson DD, Mathison DA, Tan EM, Vaughan JH. Provoking factors in bronchial asthma. Arch Intern Med 1975;135: 777-83.
Delaney JC. The diagnosis of aspirin idiosyncrasy by analgesic challenge. Clin Allergy 1976;6: 177-81.
Stenius BSM, Lemola M. Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma. Clin Allergy 1976;6: 119-29.
Spector SL, Wangaard CH, Farr RS. Aspirin and concomitant idiosyncrasies in adult asthmatic patients. J Allergy Clin Immunol 1979;64: 500-6.
Weber RW, Hoffman M, Raine DAJ, Nelson HS. Incidence of bronchoconstriction due to aspirin, azo dyes, non-azo dyes, and preservatives in a population of perennial asthmatics. J Allergy Clin Immunol 1979;64: 32-7.
Picado C, Castillo JA, Vennera MC, Gistau C, Burgos F, Agusti A. Aspirin intolerance: relationship with severity of clinical characteristics of asthma (abstract). Eur J Respir Dis 1982;63: 226.
Falliers CJ. Acetaminophen and aspirin challenges in subgroups of asthmatics. J Asthma 1983;20: 39-49.
Castillo J, Picado C. Prevalence of aspirin intolerance in asthmatics treated in a hospital. Respiration 1986;50: 153-7.
Milosevic D. Intoleranz und allergie gegen analgetika. Allergologie Jahrgang 1990;13: 205-9.
Marquette CH, Saulnier F, Leroy O, Wallaert B, Chopin C, Demarcq JM, et al. Long-term prognosis of near-fatal asthma: a 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992;146: 76-81.
Rachelefsky GS, Coulson A, Siegel SC, Stiehm ER. Aspirin intolerance in chronic childhood asthma: detected by oral challenge. Pediatrics 1975;56: 443-8.
Vedanthan PK, Menon MM, Bell TD, Bergin D. Aspirin and tartrazine oral challenge: incidence of adverse response in chronic childhood asthma. J Allergy Clin Immunol 1997;60: 8-13.
Schuhl JF, Pereyra JG. Oral acetylsalicylic acid (aspirin) challenge in asthmatic children. Clin Allergy 1979;9: 83-8.
Fischer TJ, Guilfoile TD, Kesarwala HH, Winant JGJ, Kearns GL, Gartside PS, et al. Adverse pulmonary responses to aspirin and acetaminophen in chronic childhood asthma. Pediatrics 1983;71: 313-8.
Towns SJ, Mellis CM. Role of acetyl salicylic acid and sodium metabisulfite in chronic childhood asthma. Pediatrics 1984;73: 631-7.
Walton CHA, Randle DL. Aspirin allergy. Can Med Assoc J 1957;76: 1016-8.
Pearson RSB. Hypersensitivity to aspirin. In: Dixon A, Martin KB, eds. Salicylates: an international symposium. London: Churchill, 1963: 170-3.
Chafee FH, Settipane GA. Aspirin intolerance I. Frequency in an allergic population. J Allergy Clin Immunol 1974;53: 193-9.
Falliers CJ. Aspirin and subtypes of asthma: risk factor analysis. J Allergy Clin Immunol 1973;52: 141-7.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G, Zmuda A. Aspirin-induced asthma. Hypersensitivity to fenoprofen and ibuprofen in relation to their inhibitory action on prostaglandin generation by different microsomal enzymatic preparations. J Allergy Clin Immunol 1976;58: 10-8.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G, Pieton R. Asthmatic attacks induced in aspirin-sensitive patients by diclofenac and naproxen. BMJ 1977;2: 231-2.
Quiralte J. Intolerance to nonsteroidal antiinflammatory drugs: results of controlled drug challenges in 98 patients. J Allergy Clin Immunol 1996;98: 678-85.
Settipane RA, Schrank PJ, Simon RA, Mathison DA, Christiansen SC, Stevenson DD. Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol 1995;96: 480-5.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. BMJ 1975;1: 67-9.
Barles PG, Duce GF, Portillo OJ, Perez AJ, Escuer AJ. Adverse reaction of acetaminophen as an alternative analgesic in AAS triad. Allergol Immunopathol (Madr) 1988;16: 321-5.
Ispano M, Fontana A, Scibilia J, Ortolani C. Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents. Drugs 1993;46: 253-6.
Szczeklik A, Sanak M. Molecular mechanisms in aspirin-induced asthma. Allergy Clin Immunol Int 2000;12: 171-6.
Szczeklik A, Nizankowska E, Duplaga M. Natural history of aspirin-induced asthma. Eur Respir J 2000;16: 432-6.(Christine Jenkins, head, )
Correspondence to: C Jenkins, Suite 702, 26 Ridge Street, North Sydney, NSW 2060, Australia crj@med.usyd.edu.au
Abstract
Aspirin induced asthma is a distinct clinical syndrome affecting some asthmatic patients. It is characterised by the onset of asthma 30 minutes to three hours after the ingestion of aspirin. Although the name of the condition relates to aspirin, it is well established that affected patients are cross sensitive to all non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclo-oxygenase (COX) enzymes.1 2 Paracetamol (acetaminophen), however, is seldom associated with cross sensitivity in patients with aspirin induced asthma. Emerging evidence shows that paracetamol may exert at least part of its analgesic effect through a newly identified COX-3 isoenzyme, whereas aspirin induced asthma is believed to involve inhibition of COX-1.3-5
Despite a wealth of literature on aspirin induced asthma, controversy remains as to its prevalence, with published data ranging from 4% to 44%. Differences in populations studied, methods used, definitions of outcomes, and criteria for defining sensitivity reactions may all be responsible for the variations in reported rates.6-8 A greater understanding of aspirin induced asthma is desirable, particularly given the increasing trend for consumers to treat themselves for minor painful conditions and the lack of association by many consumers between asthma and some analgesics. We performed a systematic review to reassess the prevalence of aspirin induced asthma in the general asthma population and to understand better the cross sensitivity of these individuals to commonly used non-prescription analgesics.
Methods
Prevalence in adults
A total of 66 papers were identified that gave the prevalence for aspirin induced asthma. Only 21 (15 in adults and six in children) were eligible for inclusion in our analysis (fig 1).8 10-29 Although a double blind trial would produce more robust data, this is not the usual method employed for studies of aspirin induced asthma owing to the high risk of life threatening reactions. Only four of the trials were double blind.
Fig 1 Inclusion of studies
The pooled incidence of aspirin induced asthma was 21% (95% confidence interval 14% to 29%), regardless of whether the patients had a history of aspirin induced asthma or markers for an increased risk of the syndrome (table 1). Prevalence of aspirin induced asthma also seemed to depend on the method used to determine it, with history alone resulting in a much lower prevalence (2.7%). Four of the studies in adults gave data on the number of patients reacting to different doses of aspirin.12 14 15 17 Around half (57/113) of those who had positive reactions, did so at low doses of aspirin ( 80 mg), indicating that they were highly sensitive.
Table 1 Prevalence of aspirin induced asthma in adults, analysed by population and test method. Values are numbers (percentages) unless stated otherwise
Prevalence in children
Aspirin induced asthma has been considered rare in children, yet we found that although it is less common in children than in adults, prevalence is still around 5% (0% to 14%) when children are subject to oral provocation testing (table 2).21 23 25 Although only one of the studies was a double blind, randomised controlled trial, it accounted for almost half of the patients in our analysis.21 As with adults, the use of history alone gave a lower estimate of prevalence (2%, 1% to 3%) than determined by oral provocation testing.
Table 2 Prevalence of aspirin induced asthma in children, analysed by population and test method. Values are numbers (percentages) unless stated otherwise
Incidence of cross sensitivity
Over the counter NSAIDs
Ten studies reported the incidence of cross sensitivity to three commonly used NSAIDs (ibuprofen, naproxen, diclofenac). Only three of these were level 1 studies eligible for inclusion.1 30 31 Based on these, the incidence of cross sensitivity was: 400 mg ibuprofen, 98% (95% CI 90% to 100%); 100 mg naproxen, 100% (83% to 100); and 40 mg diclofenac, 93% (76% to 100%; table 3). 1 30 31
Table 3 Incidence of cross sensitivity to NSAIDs among patients with aspirin induced asthma
Cross sensitivity to paracetamol
Each article on cross sensitivity to paracetamol was classified according to its methods. Ten of 52 identified papers were of level 1 studies.1 12 14 17 24 32-36 Table 4 summarises the data for these studies, except for one in which the authors report the number of oral provocation tests and reactions but not the number of patients with a positive reaction.36 Of 268 adults and children with aspirin induced asthma who underwent oral challenge, only 32 had a positive respiratory reaction to paracetamol (pooled incidence 7%, 0% to 16%).
Table 4 Incidence of cross sensitivity to paracetamol among patients with aspirin induced asthma
Discussion
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. J Allergy Clin Immunol 1977;60: 276-84.
Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol 1984;74: 617-22.
Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Nat Acad Sci USA 2002;99: 13926-31.
Schwab JM, Schluesener HJ, Laufer S. COX-3: just another COX or the solitary elusive target of paracetamol? Lancet 2003;361: 981-2.
Stevenson DD, Simon RA. Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 2001;108: 47-51.
Kwoh CK, Feinstein AR. Rates of sensitivity reactions to aspirin: problems in interpreting the data. Clin Pharmacol Ther 1986;40: 494-505.
Levy S, Volans G. The use of analgesics in patients with asthma. Drug Safety 2001;24: 829-41.
Vally H, Taylor ML, Thompson PJ. The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients. Thorax 2002;57: 569-74.
Nizankowska E, Bestynska-Krypel A, Cmiel A, Szczeklik A. Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma. Eur Respir J 2000;15: 863-9.
McDonald JR, Mathison DA, Stevenson DD. Aspirin intolerance in asthma. Detection by oral challenge. J Allergy Clin Immunol 1972;50: 198-207.
Stevenson DD, Mathison DA, Tan EM, Vaughan JH. Provoking factors in bronchial asthma. Arch Intern Med 1975;135: 777-83.
Delaney JC. The diagnosis of aspirin idiosyncrasy by analgesic challenge. Clin Allergy 1976;6: 177-81.
Stenius BSM, Lemola M. Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma. Clin Allergy 1976;6: 119-29.
Spector SL, Wangaard CH, Farr RS. Aspirin and concomitant idiosyncrasies in adult asthmatic patients. J Allergy Clin Immunol 1979;64: 500-6.
Weber RW, Hoffman M, Raine DAJ, Nelson HS. Incidence of bronchoconstriction due to aspirin, azo dyes, non-azo dyes, and preservatives in a population of perennial asthmatics. J Allergy Clin Immunol 1979;64: 32-7.
Picado C, Castillo JA, Vennera MC, Gistau C, Burgos F, Agusti A. Aspirin intolerance: relationship with severity of clinical characteristics of asthma (abstract). Eur J Respir Dis 1982;63: 226.
Falliers CJ. Acetaminophen and aspirin challenges in subgroups of asthmatics. J Asthma 1983;20: 39-49.
Castillo J, Picado C. Prevalence of aspirin intolerance in asthmatics treated in a hospital. Respiration 1986;50: 153-7.
Milosevic D. Intoleranz und allergie gegen analgetika. Allergologie Jahrgang 1990;13: 205-9.
Marquette CH, Saulnier F, Leroy O, Wallaert B, Chopin C, Demarcq JM, et al. Long-term prognosis of near-fatal asthma: a 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992;146: 76-81.
Rachelefsky GS, Coulson A, Siegel SC, Stiehm ER. Aspirin intolerance in chronic childhood asthma: detected by oral challenge. Pediatrics 1975;56: 443-8.
Vedanthan PK, Menon MM, Bell TD, Bergin D. Aspirin and tartrazine oral challenge: incidence of adverse response in chronic childhood asthma. J Allergy Clin Immunol 1997;60: 8-13.
Schuhl JF, Pereyra JG. Oral acetylsalicylic acid (aspirin) challenge in asthmatic children. Clin Allergy 1979;9: 83-8.
Fischer TJ, Guilfoile TD, Kesarwala HH, Winant JGJ, Kearns GL, Gartside PS, et al. Adverse pulmonary responses to aspirin and acetaminophen in chronic childhood asthma. Pediatrics 1983;71: 313-8.
Towns SJ, Mellis CM. Role of acetyl salicylic acid and sodium metabisulfite in chronic childhood asthma. Pediatrics 1984;73: 631-7.
Walton CHA, Randle DL. Aspirin allergy. Can Med Assoc J 1957;76: 1016-8.
Pearson RSB. Hypersensitivity to aspirin. In: Dixon A, Martin KB, eds. Salicylates: an international symposium. London: Churchill, 1963: 170-3.
Chafee FH, Settipane GA. Aspirin intolerance I. Frequency in an allergic population. J Allergy Clin Immunol 1974;53: 193-9.
Falliers CJ. Aspirin and subtypes of asthma: risk factor analysis. J Allergy Clin Immunol 1973;52: 141-7.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G, Zmuda A. Aspirin-induced asthma. Hypersensitivity to fenoprofen and ibuprofen in relation to their inhibitory action on prostaglandin generation by different microsomal enzymatic preparations. J Allergy Clin Immunol 1976;58: 10-8.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G, Pieton R. Asthmatic attacks induced in aspirin-sensitive patients by diclofenac and naproxen. BMJ 1977;2: 231-2.
Quiralte J. Intolerance to nonsteroidal antiinflammatory drugs: results of controlled drug challenges in 98 patients. J Allergy Clin Immunol 1996;98: 678-85.
Settipane RA, Schrank PJ, Simon RA, Mathison DA, Christiansen SC, Stevenson DD. Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol 1995;96: 480-5.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. BMJ 1975;1: 67-9.
Barles PG, Duce GF, Portillo OJ, Perez AJ, Escuer AJ. Adverse reaction of acetaminophen as an alternative analgesic in AAS triad. Allergol Immunopathol (Madr) 1988;16: 321-5.
Ispano M, Fontana A, Scibilia J, Ortolani C. Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents. Drugs 1993;46: 253-6.
Szczeklik A, Sanak M. Molecular mechanisms in aspirin-induced asthma. Allergy Clin Immunol Int 2000;12: 171-6.
Szczeklik A, Nizankowska E, Duplaga M. Natural history of aspirin-induced asthma. Eur Respir J 2000;16: 432-6.(Christine Jenkins, head, )