Reviews and Feature ArticlesAspirin-induced asthma: Advances in pathogenesis, diagnosis, and management☆,☆☆
Section snippets
Definition
The term ASA-exacerbated respiratory disease4 is the best description of the aggressive and continuous inflammatory disease of the airways, combined with exacerbation of asthma and rhinitis attacks, after ingestion of ASA and most nonsteroidal anti-inflammatory drugs (NSAIDs). However, most physicians refer to this condition as ASA-induced asthma (AIA), the aspirin triad , ASA sensitivity , or ASA-intolerant asthma . We will use the term ASA-induced asthma because of its widespread use and
Prevalence
Based on patients' histories alone, the incidence of ASA sensitivity in asthmatic adults is 3% to 5%, but this percentage doubles or triples when adult asthmatic patients are prospectively challenged with ASA. Three large population-based sampling studies, using specifically designed questionnaires, were recently concluded. In a random sample of 4300 adult women and men in southern Finland,5 the prevalence of reported ASA intolerance causing shortness of breath or attacks of asthma was 1.2%,
Clinical Presentation
The natural history and clinical characteristics of AIA were recently described in 500 patients from 10 European countries, each having a diagnosis of AIA confirmed by ASA provocation tests.8 AIA developed according to a characteristic sequence of symptoms: persistent rhinitis appeared at an average age of 30 years and was followed by asthma, ASA sensitivity, and nasal polyposis. In women, who outnumbered men at a ratio of2.3:1, the onset of symptoms occurred significantly earlier and the
Diagnosis
The presence of AIA should be suspected in cases presenting (a) a history of attacks of dyspnea (asthma) associated with ingestion of ASA and other NSAIDs, (b) chronic and intractable nasal congestion and watery rhinorrhea, particularly if allergy skin tests are negative, (c) nasal polyposis, (d) pansinusitis by computed tomography scanning, and (e) severe attacks of asthma without apparent cause requiring hospitalization in an intensive care unit.
Diagnosis can be established with certainty
Cyclooxygenase pathways
Twenty-eight years ago it was proposed29 that ASA-precipitated attacks of asthma are not due to an allergic reaction but result from inhibition of cyclooxygenase (COX) by ASA-like drugs in the airways of sensitive patients. Confirmation of this proposition by various groups3 led to the formulation of the COX theory.30
It is now well recognized that there are at least 2 COX enzymes, COX-1 and COX-2, coded by 2 different genes. Their role in asthma has been reviewed previously.31 Most recently,
Prevention
To prevent life-threatening reactions, patients with AIA should avoid ASA, all products containing it, and other analgesics that inhibit COX-1. Thus, the education of physicians, pharmacists, and patients is important in the survival of patients with AIA.
Patients with AIA can safely ingest sodium salicylate, salicylamide, choline magnesium trisalicylate, benzydamine, chloroquine, azapropazone, and dextropropoxyphen.3, 75 Unfortunately, all of these are poor analgesics and have only mild
Treatment
The general rules concerning treatment of the asthma associated with AIA do not differ from the accepted guidelines for the management of asthma.77 Most patients have moderate or severe persistent asthma, and approximately one half of them require chronic treatment with systemic corticosteroids to control the disease.8
Conclusions
AIA, or ASA-exacerbated respiratory disease, characterizes a relatively common subgroup of asthma patients, accounting for 10% to 15% of all asthmatic individuals. Despite this observation, the disorder is underrecognized and undiagnosed patients are particularly vulnerable to catastrophic asthma attacks after ingesting ASA and the older NSAIDs. LT modifier drugs prevent ASA-induced asthma attacks only in some patients, leaving other patients with AIA unprotected. There is complete
References (102)
- et al.
Aspirin-induced asthma: advances in pathogenesis and management
J Allergy Clin Immunol
(1999) - et al.
Classification of allergic and pseudoallergic reactions to drugs that inhibit cyclooxygenase enzymes
Ann Allergy Asthma Immunol
(2001) - et al.
Myocardial ischemia possibly mediated by cysteinyl leukotrienes
J Allergy Clin Immunol
(2002) - et al.
Nasal provocation test for diagnosis of aspirin-induced asthma
J Allergy Clin Immunol
(1998) - et al.
Association of urinary leukotriene E4 excretion during aspirin challenges with severity of respiratory responses
J Allergy Clin Immunol
(1999) - et al.
Selective cyclo-oxygenase 2 inhibitor in patients with aspirin-induced asthma
J Allergy Clin Immunol
(2000) - et al.
Lack of cross-reactivity between rofecoxib and aspirin-sensitive patients with asthma
J Allergy Clin Immunol
(2001) - et al.
Aspirin-sensitive asthma: the effect of aspirin on the release of prostaglandin from nasal polyps
Pharmacol Res Commun
(1977) - et al.
Cyclooxygenase 1 and cyclooxygenase 2 expression in abnormally regulated in human nasal polyps
J Allergy Clin Immunol
(2002) Prostaglandin E2 and aspirin-induced asthma
Lancet
(1995)
Bronchoprotective role for endogenous prostaglandin E2
Lancet
Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients with special reference to aspirin-induced asthma
J Allergy Clin Immunol
Effects of pranlukast on chemical mediators in induced sputum on provocation tests in atopic and aspirin-intolerant asthmatic patients
Chest
Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma
J Allergy Clin Immunol
Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma
Lancet
5′Flanking region polymorphism of the gene encoding leukotriene C4 synthase does not correlate with the aspirin-intolerant asthma phenotype in the United States
J Allergy Clin Immunol
Leukotriene C4 synthase polymorphism and aspirin-induced asthma
J Allergy Clin Immunol
Cell-specific transcription of leukotriene C4 synthase involves a Kruppel-like transcription factor and Sp1
J Biol Chem
The molecular characterisation and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor
Biochem Biophys Res Commun
Increased urinary excretion of the prostaglandin D2 metabolite 9α, 11β-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction
J Allergy Clin Immunol
Effect of acyclovir on bronchoconstriction and urinary leukotriene E4 excretion in aspirin-induced asthma
J Allergy Clin Immunol
Clinical patterns of hypersensitivity to nonsteroidal antiinflammatory drugs and their pathogenesis
J Allergy Clin Immunol
Cross-sensitivity with acetaminophen in aspirin sensitive subjects with asthma
J Allergy Clin Immunol
Asthma
Lancet
Refractory period to aspirin in a patient with aspirin-induced asthma
J Allergy Clin Immunol
Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges
J Allergy Clin Immunol
Aspirin desensitization in aspirin sensitive asthmatic patients: clinical manifestations and characterization of the refractory period
J Allergy Clin Immunol
Treatment with aspirin desensitization in patients with aspirin exacerbated respiratory disease
J Allergy Clin Immunol
Inhibition of monocyte leukotriene B4 production following aspirin desensitization
J Allergy Clin Immunol
Montelukast is only partially effective in inhibiting aspirin responses in aspirin-sensitive asthmatics
Ann Allergy Asthma Immunol
Montelukast for persistent asthma
Lancet
Anaphylaxie et idiosyncrasie
Presse Med
Intolerance to aspirin. Clinical studies and consideration of its pathogenesis
Ann Int Med
Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study
Int J Epidemiol
Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland
Allergy
The prevalence of aspirin-intolerant asthma (AIA) in Australian asthmatic patients
Thorax
: Natural history of aspirin-induced asthma
Eur Respir J
The atopy trait in hypersensitivity to nonsteroidal anti-inflammatory drugs
Allergy
Occurrence of allergic conditions in asthmatic with analgesic intolerance
Allergy
Atopy and intolerance of antimicrobial drugs increase the risk of reactions to acetaminophen and nimesulide in patients allergic to nonsteroidal anti-inflammatory drugs
Allergy
The natural history and clinical characteristics of aspirin exacerbated respiratory disease
Ann Allergy Asthma Immunol
Sensitivity to aspirin and nonsteroidal anti-inflammatory drugs
NSAIDs sensitivity in chronic idiopathic urticaria: selective involvement of cyclooxygenase-1 and overproduction of cysteinyl-leukotrienes
J Allergy Clin Immunol
Testing for aspirin hypersensitivity
Allergy
Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma
Eur Respir J
Aspirin-induced tolerance in aspirin-induced asthma detected by a new challenge technique
IRCS J Med Sci
Report of the INTERASMA Working Group on standardization of inhalation provocation tests in aspirin-induced asthma
Allergy
Nasal provocation test (NPT) with aspirin: a sensitive and safe method to diagnose aspirin-induced asthma (AIA)
Allergy
Leukotrienes in aspirin-sensitive asthma
Cellular antigen stimulation test (CAST): a new dimension in allergy diagnosis
Allergy Clin Immunol News
Cited by (420)
Inhaled drug delivery for the targeted treatment of asthma
2023, Advanced Drug Delivery ReviewsA novel drug delivery system —— Drug crystallization encapsulated liquid crystal emulsion
2021, International Journal of PharmaceuticsAn endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis
2020, Journal of Allergy and Clinical ImmunologyThe Saudi initiative for asthma – 2024 update: Guidelines for the diagnosis and management of asthma in adults and children
2024, Annals of Thoracic Medicine
- ☆
This activity is available for CME credit. See page 37A for important information.
- ☆☆
Reprint requests: Donald D. Stevenson, MD, Division of Allergy, Asthma and Immunology, Department of Medicine, Scripps Clinic and The Scripps Research Institute, 10066 N Torrey Pines Road, La Jolla, CA 92037.