Skip to main content

Aspirin-Exacerbated Asthma


This review focuses on aspirin-exacerbated asthma (AEA). The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1). Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2). The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO). Leukotriene C4 (LTC4) synthase is the enzyme responsible for the production of leukotriene C4, the chief cysteinyl leukotriene responsible for AEA. There have been familial occurences of AEA. An allele of the LTC4 synthase gene in AEA is known as allele C. Allele C has a higher frequency in AEA. Clinical presentation includes a history of asthma after ingestion of aspirin, nasal congestion, watery rhinorrhea and nasal polyposis. Treatment includes leukotriene receptor antagonists, leukotriene inhibitors, aspirin desinsitaztion and surgery. AEA is the most well-defined phenotype of asthma. Although AEA affects adults and children with physician-diagnosed asthma, in some cases there is no history of asthma and AEA often goes unrecognized and underdiagnosed.

Acetylsalicylic acid (aspirin) is one of the most prescribed and frequently used over-the-counter medications of all time. Aspirin-exacerbated asthma (AEA) was first reported 84 years ago after severe bronchospasm in an individual with asthma was observed following aspirin ingestion and is characterized by eosinophilic rhinosinusitis, nasal polyposis, aspirin sensitivity, and asthma[1, 2]. All cyclooxygenase-1 (COX-1) inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, induce bronchospasm, rhinorrhea, and nasal obstruction in these subjects [24]. In addition, the ocular administration of the COX-1-inhibiting NSAID ketorolac has been linked to AEA[4]. Individuals with AEA usually have moderate to severe persistent asthma and often require treatment with high-dose inhaled corticosteroids and even systemic corticosteroids in some instances[2, 5]. Although the exact mechanism causing the AEA has yet to be fully elucidated, there is considerable evidence that an alteration in the metabolism of arachidonic acid is responsible [58].

Another clinical entity, chronic idiopathic urticaria with aspirin sensitivity, although perhaps similar at a biochemical level to AEA, is clinically different as this reaction is confined to the skin and subcutaneous tissues[9]. This review focuses on AEA.

Historical Perspective and Background

The medicinal properties of the group of alkali metal salts and esters known as salicylates have been known since ancient times. Records dating back to the time of Hippocrates (460 BC) describe powders derived from the bark of the white willow tree (Salix alba) used for pain relief; the name salicylic acid is derived from Salix, the Latin name for this tree [1013]. In 1853, the French chemist Gerhardt neutralized salicylic acid by buffering it with sodium salicylate and acetylchloride, creating acetylsalicylic acid or aspirin. The discovery of aspirin by Gerhardt was abandoned until Felix Hoffman, a German chemist, rediscovered it in 1887 and learned of its unique property of reduced gastrointestinal irritation compared with salicylic acid. Shortly afterward, "aspirin" was patented by Bayer in 1889 as a new analgesic wonder drug. The reduced gastrointestinal irritation can be attributed to the acetylation of the phenolic hydroxyl group (-OH) of sodium acetylate[14].

Salicylic acid was synthesized by Kolbe, a German chemist, in 1874 and was used as a analgesic; however, severe gastrointestinal irritation was a common side effect. In 1876, MacLagan and Stricker demonstrated that salicylic acid was an effective treatment for rheumatic fever; it was used later for chronic rheumatoid arthritis and gout[15].

Today salicylic acid and its derivatives have a variety of clinical uses. Salicylic acid is often used because of its keratinolytic properties as a topical solution for acne, cutaneous exfoliation in chemical skin peels, and psoriasis and for treatment of cutaneous fungal infections[16]. Aspirin is used as an analgesic and to treat fever, migraine, rheumatic fever (drug of choice), Kawasaki disease (along with intravenous immunoglobulin), pericarditis, and even ulcerative colitis (5-acetylsalicylic acid or mesalamine)[17]. In addition, it is used to prevent coronary artery disease and for both primary and secondary prevention of cerebrovascular accidents[18].

However, serious side effects are associated with its use, such as occurs in AEA. There are both short- and long-term side effects of aspirin, such as nephropathy, gastritis, peptic ulcer disease, prolonged bleeding, and Reye syndrome[19, 20]. AEA was first described by Widal and colleagues in 1922. In 1967, Samter and Beers reported and popularized the phenomenon of AEA (Table 1)[21].

Table 1 Historical Perspective of Aspirin and Aspirin-Exacerbated Asthma


Over the past several decades, AEA has also been referred to as the Samter triad, aspirin triad, aspirin-sensitive asthma, aspirin-intolerant asthma (ATA), aspirin sensitivity, and aspirin-exacerbated respiratory disease. AEA best defines this phenomenon as this term describes the disease in which the exacerbation of asthma occurs following the ingestion of aspirin and other COX-1 inhibiting NSAIDs. AEA is used to refer to this syndrome throughout this article[22, 23].


Jenkins and colleagues found that prevalence rates are 21% and 5% for asthmatic adults and children, respectively, when examining primarily unblinded oral provocation tests in a systematic review of 66 articles on AEA [24]. Prevalence was dependent on the method used to diagnose AEA, with patients' histories alone giving a much lower prevalence rate of 2.7% in adults and 2% in children. In 1967, Vanselow first reported AEA exacerbated by indomethacin[3]. Jenkins and colleagues confirmed the finding that some other NSAIDs also exacerbated AEA by reporting the sensitivity to ibuprofen, <400 mg, of 98%; naproxen, 100 mg, of 100%; and diclofenac, <40 mg, of 76 to 100% [24]. Vally and colleagues reported that the prevalence of respiratory symptoms triggered by aspirin in three different asthma study populations surveyed in Australia was 10 to 11% [25]. In a random sample by postal survey of 4,300 adults in southern Finland, the prevalence of AEA reported in the general population was 1.2%; however, individuals with pre-existing physician-diagnosed asthma had reported prevalence rates of 8.8% [26]. A database study from Poland in which 12,971 adults were randomly selected showed a prevalence of AEA of 0.6% in the general population and 4.3% of subjects with a known diagnosis of asthma[27]. With nasal polyps, aspirin sensitivity may be as high as 14 to 22%, and with chronic rhinitis, it is 0.7 to 2.6% [28]. AEA may be widely underdiagnosed; for example, in the European Network of Aspirin-Induced Asthma (AIANE), 18% of participants were unaware of aspirin sensitivity before undergoing unblinded aspirin provocation tests. The reasons for underdiagnosis may be the lack of recognition by the AEA individual of mild symptoms induced by aspirin and low clinical awareness of this syndrome among health care professionals[29]. A study by Lockey and colleagues showed that if subjects are not double-blind challenged, the results may be falsely positive. Only one of three of the individuals challenged had positive results when tested using double-blind, controlled challenges. Therefore, without double-blinded challenges, the true prevalence of AEA cannot be ensured[30].


An immunoglobulin E (IgE) mechanism does not explain the AEA phenomena. An elevated total IgE, dermographism, and increased sensitivity to antibiotics were associated with AEA in one study, but skin test responses with lysine-aspirin were negative. No antibodies against aspirin or other NSAIDs have been consistently detected in this disease[2, 3135].

In 1971, Vane added credence to the theory that aspirin-precipitated attacks are not due to an allergic reaction but to inhibition of COX-1 in the airways when he discovered that aspirin inhibited the COX-1 enzyme [3641]. That discovery led to the AEA COX pathway theory.

Some studies demonstrated an increase in the number of bronchial submucosal mast cells in AEA compared with ATA, whereas others have not confirmed this finding[42, 43]. The cytokine profile of the mast cell was investigated in another study and reported an increase in bronchial submucosal mast cells expressing interleukin-5 and granulocyte-macrophage colony-stimulating factor[44]. Cowburn and colleagues did not report any significant differences in bronchial mucosal mast after lysine-aspirin challenges between ATA and AEA individuals even though the number of mast cells was lower in both groups when compared with healthy controls[45].

Cyclooxygenase Pathway

Phospholipids are a class of lipids formed from four components: a fatty acid, a negatively charged phosphate group, nitrogen-containing alcohol, and a backbone of either glycerol or sphingosine. Four different groups of phospholipases exist, A, B, C, and D, with each group serving a unique function. Phospholipase A2 produces arachidonic acid. It is from arachidonic acid that various eicosanoids are produced from the action of lipoxygenase and cycloxygenase, namely leukotrienes and prostanoids.

There are two main COX enzymes, COX-1 and COX-2, encoded by two specific genes on chromosomes 9q32 and 1q25, respectively. COX-3 also exists, and two smaller forms of COX-1, derived from alternative splicing of COX-1 messenger ribonucleic acid (mRNA), have been identified[46]. COX-2 is activated during periods of inflammation, whereas COX-1 is active during periods of quiescence.

The inhibition of COX-1 by aspirin causes the reactions associated with AEA, and this inhibition leads to a decrease in the production of prostaglandin E2 (PGE2), which acts like a brake on the uncontrolled synthesis of cysteinyl leukotrienes (Cys-LTs) [4753]. Picado and colleagues found decreased COX-2 mRNA expression by analysis of nasal polyps in subjects suffering from AEA[48]. Since COX-2 was found to be underexpressed, inadequate COX-2 regulation may also be involved in the pathogenesis of AEA.

NSAIDs that are highly selective for COX-2, for example, celecoxib and rofecoxib, do not cause acute exacerbations of asthma in AEA[54, 55]. Cowburn and colleagues demonstrated that although aspirin removes PGE2-dependent suppression in all subjects, only in AEA is there an increase in leukotriene C4 (LTC4) synthase, leading to a marked overproduction of Cys-LTs[45].

Lipoxygenase Pathway and Production of Cys-LTs

Arachidonic acid is first converted by 5-lipoxygenase (5-LO) into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and then into leukotriene A4 (LTA4). LTA4 is converted into leukotriene B4 (LTB4) by the enzyme LTA4 epoxide hydrolase. Eosinophils, mast cells, and alveolar macrophages use the enzyme LTC4 synthase to conjugate glutathione with LTA4 to make LTC4. LTC4 can be transported out of the cell and its glutamic acid moiety removed by ubiquitous enzymes to make leukotriene D4 (LTD4). LTD4, in turn, can be cleaved by dipeptidases to make leukotriene E4 (LTE4). LTC4, LTD4, and LTE4 make up the Cys-LTs. The Cys-LTs cause bronchoconstriction, mucus plugging and edema, and cellular infiltration and recruitment in the airways. The overexpression of Cys-LTs occurs in both bronchial and nasal mucosa in AEA [4753].

In a study by Adamjee and colleagues, eosinophils from nasal polyps, immunopositive for LTC4 synthase, were fourfold more numerous in AEA than in ATA. There were also threefold more cells expressing 5-LO in the nasal polyp mucosa. These investigators found that fivefold higher eosinophil counts accounted for the increased LTC4 synthase expression in polyps from AEA[53].

The inhibitory effect of PGE2 in AEA was also investigated in a study that showed that inhaled PGE2 affords almost complete protection in AEA by blocking aspirin-induced bronchoconstriction. The inhibitory effect, however, is still controversial as PGE2 levels have been found to be both increased and decreased in nasal and bronchial lavages (Figure 1)[52, 56, 57].

Figure 1

Cox-1 = cyclooxygenase-1; Cys-LT = cysteinyl leukotriene; LTC 4 = leukotriene C 4 ; LTD 4 = leukotreine D 4 ; LTE 4 = leukotriene E 4 ; PGE-2 = prostaglandin E 2 .

Familial Inheritance

Lockey and colleagues in 1973 described four members of a Mennonite family with AEA, three of whom were first cousins[58]. One of the cousins, whose husband was a member of the isolate, had twin daughters, one with AEA and another with allergic rhinitis and extrinsic asthma but no AEA. The twin with AEA and her husband shared common ancestors in the eighth ancestral generation. The presence of AEA in relatives, influenced by the presence of consanguinity, suggests an autosomal recessive mode of inheritance. It also suggests that the discordance seen in the twins may be an indication of environmental influences on the phenotypic expression of this phenomenon[58]. Also mentioned in this article was a report of two sisters of a non-Mennonite family who had AEA and a third sibling with intrinsic asthma who improved after aspirin ingestion. Curiously, there are other case reports of AEA improving after aspirin ingestion[30].

Miller described a pair of sisters with the AEA in another report of familial inheritance[59]. Von Maur and colleagues described a family with mild AEA and suggested a dominant mode of inheritance[60]. In this study, an early onset of asthma in most affected members of the family and a lack of symptoms of sinusitis or nasal polyposis predominated.

Familial occurrence of AEA was reported in 5.1% of 400 subjects studied in AIANE[29]. In these families, affected individuals were usually siblings. Szczeklik and Sanak reported on two sisters, aged 20 and 27 years, who, after being given unblinded aspirin challenges, had widely different reactions, with the older sibling experiencing an asthma exacerbation and the younger marked nasal congestion [61]. Both sisters shared the variant allele of LTC4 synthase associated with AEA. The parents of the twins and some other family members who were atopic or had moderate eosinophilia were challenged with aspirin and had negative responses.

LTC4 Synthase

LTC4, one of the Cys-LTs, is proposed as the primary leukotriene that causes bronchospasm in AEA[48]. Cys-LTs are first synthesized by 5-LO and 5-lipoxygenaseassociated protein (FLAP 5). Expression of 5-LO is modulated by a genetic variation in the transcription factor binding motif of the 5-LO gene. No association between the allelic variants of 5-LO gene promoter and AEA has been observed, nor has there been any difference in the results from immunostaining of bronchial biopsy specimens for 5-LO and FLAP 5[53, 62].

LTC4 synthase is a terminal enzyme that mediates production of Cys-LTs[45, 53, 63]. This enzyme is expressed in eosinophils, basophils, and macrophages. In these cells LTC4 synthase alternatively converts LTC4 from LTA4. LTC4 is rendered powerless owing to the lack of concomitant 5-LO expression in platelets and epithelial and endothelial cells. Production of LTC4 synthase depends on external sources of LTA4.

LTC4 synthase has been cloned by Lam and colleagues[68] and its function and sequence studied. An allelic variant of the LTC4 synthase gene has been identified and is referred to as allele C. This allele has a 39% to 50% or higher frequency in AEA, 26% in ATA, and 25% in normal individuals. Allele C is formed by the transversion of adenine to cytosine, 444 bases from the translation start. Semiquantitative studies by Sanak and colleagues of LTC4 synthase transcripts in peripheral blood eosinophils showed increased numbers of mRNA copies in individuals with AEA[64]. The increased transcripts correlated with the allelic C variant.

The nature of this interaction has yet to be fully elucidated. Of note, the transient increase in urinary LTE4 in AEA following oral aspirin provocation has been observed only in allele C variants[64]. A Japanese study also showed that the variant C allele is higher in AEA than in ATA[65].

Clinical Presentation

The age at onset of 300 subjects with AEA in the United States was, on average, 34 years. In women, the age at onset is usually earlier than in men, and severity is usually classified in the moderate to severe persistent category. Presentation in one European study showed a characteristic sequence of symptoms, first beginning with persistent rhinitis at around age 30 years of age and followed by asthma, aspirin sensitivity, and then nasal polyposis. Atopy was reported in one-third of cases[66].

Rhinorrhea and nasal congestion are usually the first symptoms of AEA and are commonly refractory to pharmacologic therapy. It becomes perennial and more difficult to treat and then becomes associated with anosmia, recurrent and chronic sinusitis, and nasal polyposis[5, 6, 66, 67].

After the ingestion of aspirin or other COX-1 inhibitors, bronchospasm occurs within 1 to 3 hours. Care must be taken to differentiate selective COX-2 inhibitors from preferentially selective COX-2 inhibitors such as rofecoxib, meloxicam, and ibuprofen.

Preferentially selective COX-2 inhibitors are selective for COX-2 at low doses but at higher doses also inhibit COX-1 [6870]. However, despite their overall safety profile, caution must be used with these medications as several cases have been described in which bronchospasm occurred with their use[71]. Bronchospasm with COX-1 challenge can be accompanied by profuse rhinorrhea, conjunctival injection, a scarlet flushing of the head and neck, periorbital edema, abdominal pain, and even urticaria[5, 6].

A refractory period to the administration of aspirin or other COX-1 inhibitors develops after sufficient quantities of one or another of these medications is given to an AEA subject. This refractory period lasts for an average of 2 to 4 days[30, 7274].


AEA should be suspected when the following exists:

  1. 1.

    A history of exacerbation of asthma after ingestion of aspirin or other non-NSAIDs

  2. 2.

    Chronic and intractable nasal congestion and watery rhinorrhea, especially if specific IgE tests are negative

  3. 3.

    Nasal polyposis

  4. 4.

    Total or near-total opacification of the sinus cavities as demonstrated by computed tomography

  5. 5.

    An individual with the rapid onset of a severe attack of asthma with no previous insult who necessitates acute emergency care, intensive care unit admission, or endotracheal intubation[2, 5, 6]

The oral challenge, beginning with small amounts of aspirin and increasing the dose, is commonly used to confirm the diagnosis. Threshold doses of 30 to 150 mg (averaging 60-75 mg) evoke positive reactions and are the most sensitive diagnostic tool. Inhaled bronchial challenged with acetylsalicylic acid-lysine is also used to detect this syndrome. So, too, is nasal provocation with aspirin-lysine, but this technique is much less sensitive than bronchial challenge. Urinary LTE4 can also be measured following aspirin challenge as an adjunctive measure to confirm a positive bronchial challenge[75]. Preferably, aspirin challenge tests should be preceded by a "placebo challenge" to exclude the variability of bronchial responsiveness; however, as with any study, double-blinded control studies are ideal[2, 5, 6, 66]. Stevenson and colleagues also reported that intranasal ketorolac administration is a reasonably accurate and safe method to diagnose AEA[76].


AEA subjects should avoid all aspirin-containing compounds and other analgesics that have the potential to inhibit the COX-1 enzyme. They can safely ingest sodium salicylate, salicylamide, choline magnesium trisalicylate, benzydamine, chloroquine, azapropazone, and dextropropoxyphene. However, these drugs are poor analgesics and have little anti-inflammatory effect[77]. Most individuals can ingest acetaminophen, which primarily inhibits COX-3 while weakly inhibiting COX-1 and COX-2. However, in some subjects, very sensitive to low provoking doses of aspirin, acetaminophen-induced asthma is more common. It can cause bronchoconstriction at doses greater than 1,000 mg in 34% of individuals with this syndrome[78].


The guidelines used to treat and manage AEA are no different from those used to treat moderate to severe persistent ATA asthma. Individuals with AEA occasionally require systemic corticosteroids in addition to their regular maintenance therapy.

Leukotriene inhibitors, such as zileuton, which inhibits 5-LO, and leukotriene receptor antagonists, such as montelukast and zafirlukast, are used to treat AEA. However, ATA and AEA subjects on leukotriene inhibitors have similar clinical outcomes, and urinary LTE4 cannot be used to determine responses to these medications[79, 80]. AEA subjects with the C allele appear to have a better response with leukotriene receptor antagonists[81].

Surgery for nasal polyposis associated with AEA results in an 80% subjective improvement rate with a 40% chance or more of recurrence of nasal polyps and persistence of nasal symptoms. Thus, following sinus surgery, treatment with topical and systemic corticosteroids, aspirin desensitization, and leukotriene inhibitors is recommended[88, 89]. Mild to marked improvement in quality of life was reported in individuals with AEA following sinus surgery in a Japanese study[82]. McFadden and colleagues also reported improvements in quality of life and pulmonary function tests (PFTs) and a reduction in systemic and topical corticosteroid requirements[83]. Simple polypectomy alone does not seem to be as useful as endoscopic surgery owing to the excessive amount of polypoid tissue burden in AEA[2, 84, 85].

Aspirin Desensitization

Desensitization became possible because of the discovery of the refractory period in AEA[30, 72]. Stevenson and colleagues, in 1980, reported on two individuals with AEA who were successfully desensitized to aspirin[86]. They were continuously treated with daily aspirin, and both individuals reported improvement in nasal patency, with one regaining her sense of smell. Therapy with aspirin was continued for months, with persistent nasal airway patency and a diminished growth in nasal polyps, with an overall reduction of half in the use of systemic corticosteroids and improvement in rhinitis and asthma.

In another study by the same investigators, published in 2003, of 172 subjects, 67% experienced a reduction in their nasal airway symptoms and systemic and corticosteroid requirements as long as they maintained their daily intake of aspirin. In 126 subjects who completed a year or more of such treatment, 87% experienced good or excellent improvement in sense of smell and general assessment of nasal-sinus and asthma symptoms. This study suggests that aspirin desensitization be used for those who do not respond to topical glucocorticoids or oral leukotriene antagonists. Those ideal for desensitization have nasal polyposis, necessitating treatment with systemic corticosteroids[86, 87].

Sousa and colleagues reported that desensitization is associated with a reduction in the number of inflammatory cells in the nasal mucosa expressing the Cys-LT1 receptor and that downregulation of receptor expression after aspirin desensitization is the likely mechanism of action[88]. Pretreatment with Cys-LT receptor antagonists prior to aspirin desensitization significantly decreases the risk of AEA[89, 90].

Other new modalities are under investigation, some involving high-dose aspirin therapy for emergent desensitization using oral protocols based on rapidly escalating doses of aspirin. In individuals with aspirin-induced urticaria-angioedema, a separate clinical entity with perhaps similar pathogenic mechanisms, Wong and colleagues reported the safe, rapid oral challenge desensitization to aspirin[91]. In this study, aspirin administration permitted individuals with coronary artery disease to receive aspirin. Some other promising treatments, such as tacrolimus, have proven ineffective[92].


AEA is perhaps the most well-defined asthma phenotype compared with other asthma phenotypes, such as allergic, non-allergic, exercise-induced, and infectious asthma. It is a relatively common phenotype of asthma, affecting primarily adults but also children with physician-diagnosed asthma and, in some cases, subjects with no previous history of asthma. It is often unrecognized and underdiagnosed.

Subjects with moderate to severe asthma who have severe nasal congestion, nasal polyposis, and radiologic evidence of opacification of sinuses and who require emergent care and/or intubation should be suspected to have this form of asthma. A history of exacerbation associated with the ingestion of aspirin or other COX-1 NSAIDs can be diagnostic for the phenotype. A refractory period following aspirin challenge during which no additional symptoms occur with additional aspirin or other COX-1 NSAIDs may last up to 2 to 4 days.

PGE2 acts as a brake on LTC4 synthase, which moderates the production of Cys-LTs. Individuals with AEA have decreased levels of PGE2, which, in turn, causes an overproduction of Cys-LTs, which theoretically causes AEA. Genetic mechanism studies suggest that there is a familial incidence; however, the exact mode of inheritance is unknown.

Treatment of AEA primarily involves use of systemic and inhaled glucocorticosteroids, short- and long-acting β-agonists, leukotriene-modifying agents, and medical and sometimes surgical treatment of the rhinitis and/or nasal polyposis.

Leukotriene-modifying agents and inhaled corticosteroids, often in high doses, are the mainstay of therapy. Aspirin desensitization is also a useful tool and in up to 60 to 70% of these patients, and the response sometimes can be dramatic in reducing the overall dependence on inhaled and/or systemic glucocorticosteroids.


  1. 1.

    Widal MF, Abrami P, Lemoyez J: Anaphylaxie et idiosyncrasie. Presse Med. 1922, 30: 189-92.

    CAS  Google Scholar 

  2. 2.

    Szczeklik A, Stevenson DD: Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol. 2003, 111: 913-21. 10.1067/mai.2003.1487.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Vanselow N: Bronchial asthma induced by indomethacin. Ann Intern Med. 1967, 66: 568-72.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Sitenga GL, Ing EB, Van Dellen RG: Asthma caused by topical application of ketorolac. Ophthalmology. 1996, 103: 890-2.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Stevenson DD, Szczeklik A: Clinical and pathologic perspectives on aspirin sensitivity and asthma. Allergy Clin Immunol. 2006, 118: 773-86. 10.1016/j.jaci.2006.07.024.

    CAS  Article  Google Scholar 

  6. 6.

    Szczeklik A, Niankowska E: Clinical features and diagnosis of aspirin induced asthma. Thorax. 2000, 55 (Suppl 2): S42-4. 10.1136/thorax.55.suppl_2.S42.

    PubMed Central  Article  PubMed  Google Scholar 

  7. 7.

    Sanak M, Szczeklik A: Genetics of aspirin induced asthma. Thorax. 2000, 55 (Suppl 2): S45-7. 10.1136/thorax.55.suppl_2.S45.

    PubMed Central  Article  PubMed  Google Scholar 

  8. 8.

    Mastalerz L, Setkowicz M, Sczceklik A: Mechanism of chronic urticaria exacerbation by aspirin. Curr Allergy Asthma Rep. 2005, 5: 277-83. 10.1007/s11882-005-0067-z.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Kim SH, Ye YM, Lee SK, Park HS: Genetic mechanism of aspirin-induced urticaria/angioedema. Curr Opin Allergy Clin Immunol. 2006, 6: 266-70. 10.1097/01.all.0000235899.57182.d4.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Chiej R: Encyclopaedia of medicinal plants. 1984, MacDonald

    Google Scholar 

  11. 11.

    Rainsford KD: Aspirin and the salicylates. 1984, London: Butterworths

    Google Scholar 

  12. 12.

    Vane JR, Botting RM: Aspirin and other salicylates. 1992, London: Chapman and Hall Medical Publishers

    Google Scholar 

  13. 13.

    Verg E, Plumpe G, Schultheis H: Meilensteine: the official Bayer publication in commemoration of the centenary of aspirin's release. 1989

    Google Scholar 

  14. 14.

    McTavish J: What's in a name? Aspirin and the American Medical Association. Bull Hist Med. 1987, 61: 364-5.

    Google Scholar 

  15. 15.

    Buselmeier TJ: Combination urea and salicyclic acid ointment nail avulsion in nondystrophic nails. Cutis. 1980, 25: 397-405.

    CAS  PubMed  Google Scholar 

  16. 16.

    Pullman H, Lennartz KJ, Steigleder GK: Effect of salicylic acid on epidermal cell proliferation kinetics in psoriasis. Arch Dermatol Forsch. 1975, 251: 271-5.

    Article  Google Scholar 

  17. 17.

    Regueiro M, Loftus EV, Steinhart AH, Cohen RD: Clinical guidelines for the medical management of left sided ulcerative colitis and ulcerative proctitis. Inflamm Bowel Dis. 2006, 12: 972-8. 10.1097/01.mib.0000231496.92013.85.

    Article  PubMed  Google Scholar 

  18. 18.

    Berger JS, Roncaglioni MC, Avanzini F: Aspirin for the primary prevention of cardiovascular events in women and men. JAMA. 2006, 295: 306-13. 10.1001/jama.295.3.306.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Lanas A, Hunt R: Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies. Ann Med. 2006, 38: 415-28. 10.1080/07853890600925843.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Aaron TH, Muttitt EL: Reactions to acetylsalicylic acid. Can Med Assoc J. 1982, 126: 609-11.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. 21.

    Samter M, Beers RF: Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med. 1968, 68: 975-83.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Kalyoncu AF: Aspirin-induced asthma needs a classification. Allergol Immunopathol (Madr). 2000, 28: 334-5.

    CAS  Google Scholar 

  23. 23.

    Szczeklik A, Stevenson DD: Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol. 2003, 111: 913-21. 10.1067/mai.2003.1487.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Jenkins C, Costello J, Hodge L: Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ. 2004, 328: 434-10.1136/bmj.328.7437.434.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  25. 25.

    Vally H, Taylor ML, Thompson PJ: The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients. Thorax. 2002, 57: 569-74. 10.1136/thorax.57.7.569.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  26. 26.

    Hedman J, Kaprio J, Poussa T, Nieminen MM: Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. Int J Epidemiol. 1999, 28: 717-22. 10.1093/ije/28.4.717.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Kasper L, Sladek K, Duplaga M: Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland. Allergy. 2003, 58: 1064-6. 10.1034/j.1398-9995.2003.00267.x.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Kalyoncu AF, Karakaya G, Sahin AA: Occurrence of allergic conditions in asthmatics with analgesic intolerance. Allergy. 1999, 54: 428-35. 10.1034/j.1398-9995.1999.00963.x.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    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: 432-6. 10.1034/j.1399-3003.2000.016003432.x.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Lockey RF: Aspirin-improved ASA triad. Hosp Pract. 1978, 13 (8): 129, 131, 133.

    Google Scholar 

  31. 31.

    Pierzchalska M, Mastalerz L, Sanak M: A moderate and unspecific release of cysteinyl-leukotrienes by aspirin from peripheral blood leukocytes precludes its value for aspirin-sensitivity testing in asthma. Clin Exp Allergy. 2000, 30: 1785-91. 10.1046/j.1365-2222.2000.00953.x.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Gray PA, Warner TD, Vojnovic I: Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors. Br J Pharmacol. 2002, 137: 1031-8. 10.1038/sj.bjp.0704927.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  33. 33.

    Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G: Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. Br Med J. 1975, 1: 67-9. 10.1136/bmj.1.5949.67.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  34. 34.

    Szczeklik A: The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J. 1990, 3: 588-93.

    CAS  PubMed  Google Scholar 

  35. 35.

    Szczeklik A, Sanak M: The role of COX-1 and COX-2 in asthma pathogenesis and its significance in the use of selective inhibitors. Clin Exp Allergy. 2002, 32: 339-42. 10.1046/j.1365-2222.2002.01333.x.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Vane SJ: Aspirin and other anti-inflammatory drugs. Thorax. 2000, 55 (Suppl 2): S3-9. 10.1136/thorax.55.suppl_2.S3.

    PubMed Central  Article  PubMed  Google Scholar 

  37. 37.

    Vane JR, Botting RM: The mechanism of action of aspirin. Thromb Res. 2003, 110: 255-8. 10.1016/S0049-3848(03)00379-7.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971, 231: 232-5.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Smith JH, Willis AL: Aspirin selectively inhibits prostaglandin production in human platelets. Nature. 1971, 231: 235-7.

    CAS  Google Scholar 

  40. 40.

    Vane JR, Botting RM: Mechanism of action of aspirin-like drugs. Semin Arthritis Rheum. 1997, 26: 2-10. 10.1016/S0049-0172(97)80046-7.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Vane JR, Bakhle YS, Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998, 38: 97-120. 10.1146/annurev.pharmtox.38.1.97.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Nasser SM, Pfister R, Christie PE: Inflammatory cell populations in bronchial biopsies from aspirin-sensitive asthmatic subjects. Am J Respir Crit Care Med. 1996, 153: 90-6.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Nasser S, Christie PE, Pfister R: Effect of endobronchial aspirin challenge on inflammatory cells in bronchial biopsy samples from aspirin-sensitive asthmatic subjects. Thorax. 1996, 51: 64-70. 10.1136/thx.51.1.64.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  44. 44.

    Sousa AR, Lams BE, Pfister R: Expression of interleukin-5 and granulocyte-macrophage colony-stimulating factor in aspirin-sensitive and non-aspirin-sensitive asthmatic airways. Am J Respir Crit Care Med. 1997, 156: 1384-9.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Cowburn AS, Sladek K, Soja J: Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest. 1998, 101: 834-46. 10.1172/JCI620.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  46. 46.

    Antczak A, Montuschi P, Kharitonov S: Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin induced asthma. Am J Respir Crit Care Med. 2002, 166: 301-6. 10.1164/rccm.2101021.

    Article  PubMed  Google Scholar 

  47. 47.

    Chandrasekharan NV, Hu Dai, Lamar Turepu Roos K: COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA. 2002, 99: 13926-31. 10.1073/pnas.162468699.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  48. 48.

    Picado C, Fernandez-Morata JC, Juan M: Cyclooxygenase-2 mRNA is down-expressed in nasal polyps from aspirin-sensitive asthmatics. Am J Respir Cell Mol Biol. 2000, 160: 291-6.

    Google Scholar 

  49. 49.

    Kowalski ML, Pawliczak R, Wozniak J: Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients. Am J Respir Crit Care Med. 2000, 161: 391-8.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Mullol J, Fernandez-Morata JC, Roca-Ferrer J: Cyclooxygenase 1 and cyclooxygenase 2 expression in abnormally regulated in human nasal polyps. J Allergy Clin Immunol. 2002, 109: 824-30. 10.1067/mai.2002.123534.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Szczeklik A: Prostaglandin E2 and aspirin-induced asthma. Lancet. 1995, 345: 1056-10.1016/S0140-6736(95)90799-8.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Pavord ID, Tattersfield AE: Bronchoprotective role for endogenous prostaglandin E2. Lancet. 1995, 345: 436-8. 10.1016/S0140-6736(95)90409-3.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Adamjee J, Suh YJ, Park HS: Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps of patients with aspirin-intolerant asthma. J Pathol. 2006, 209: 392-9. 10.1002/path.1979.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    El Miedany Y, Youssef S, Ahmed I, El Gaafary M: Safety of etoricoxib, a specific cyclooxygenase-2 inhibitor, in asthmatic patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2006, 97: 105-9. 10.1016/S1081-1206(10)61378-6.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Sanak M, Kielbasa B, Bochenek G, Szczeklik A: Exhaled eicosanoids following oral aspirin challenge in asthmatic patients. Clin Exp Allergy. 2004, 34 (12): 1899-904. 10.1111/j.1365-2222.2004.02123.x.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Sestini P, Armetti L, Gambaro G: Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma. Am J Respir Crit Care Med. 1996, 153: 572-5.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Szczeklik A, Mastalerz L, Nizankowska E, Cmiel A: Protective and bronchodilator effects of prostaglandin E and salbutamol in aspirin-induced asthma. Am J Respir Crit Care Med. 1996, 153: 567-71.

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Lockey RF, Rucknagel DL, Vanselow NA: Familial occurrence of asthma, nasal polyps and aspirin intolerance. Ann Intern Med. 1973, 78: 57-63.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Miller FF: Aspirin-induced bronchial asthma in sisters. Ann Allergy. 1971, 29: 263-5.

    CAS  PubMed  Google Scholar 

  60. 60.

    Von Maur K, Adkinson NF, Van Metre TE: Aspirin intolerance in a family. J Allergy Clin Immunol. 1974, 54: 380-95. 10.1016/0091-6749(74)90028-1.

    Article  Google Scholar 

  61. 61.

    Szczeklik A, Sanak M: Genetic mechanisms in aspirin-induced asthma. Am J Respir Crit Care Med. 2000, 161 (2 Pt 2): S142-6.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Kennedy BP, Diehl RE, Boie Y: Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP). J Biol Chem. 1991, 266: 8511-6.

    CAS  PubMed  Google Scholar 

  63. 63.

    Lam BK, Penrose JF, Freeman GJ, Austen KF: Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci USA. 1994, 91: 7663-7. 10.1073/pnas.91.16.7663.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  64. 64.

    Sanak M, Pierzchalska M, Bazan-Socha S, Szczeklik A: Enhanced expression of the leukotriene C4 synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma. Am J Respir Cell Mol Biol. 2000, 23 (3): 290-6.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Kawagishi Y, Mita H, Taniguchi M: Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma. J Allergy Clin Immunol. 2002, 109: 936-42. 10.1067/mai.2002.124466.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Nizankowska E, Duplaga M, Bochenek G, Szczeklik A, on behalf of the AIANE Project : Clinical course of aspirin-induced asthma: results of AIANE. Eicosanoids, aspirin and asthma. Edited by: Szczeklik A, Gryglewski R, Vane J. 1998, New York: Marcel Dekker, 451-71.

    Google Scholar 

  67. 67.

    Berges-Gimeno MP, Simon RA, Stevenson DD: The natural history and clinical characteristics of aspirin exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2002, 89: 474-8. 10.1016/S1081-1206(10)62084-4.

    Article  PubMed  Google Scholar 

  68. 68.

    Szczeklik A, Nizankowska E, Bochenek G: Safety of a specific COX-2 inhibitor in aspirin-induced asthma. Clin Exp Allergy. 2001, 31: 219-25. 10.1046/j.1365-2222.2001.01075.x.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Yoshida S, Ishizaki Y, Onuma K: Selective cyclo-oxygenase 2 inhibitor in patients with aspirin-induced asthma. J Allergy Clin Immunol. 2000, 106: 1201-2. 10.1067/mai.2000.110926.

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Woessner KM, Simon RA, Stevenson DD: The safety of celecoxib in aspirin exacerbated respiratory disease. Arthritis Rheum. 2002, 46: 2201-6. 10.1002/art.10426.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Baldassarre S, Schandene L, Choufani G, Michils A: Asthma attacks induced by low doses of celecoxib, aspirin and acetaminophen. J Allergy Clin Immunol. 2006, 117: 215-7. 10.1016/j.jaci.2005.10.021.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Zeiss CR, Lockey RF: Refractory period to aspirin in a patient with aspirin-induced asthma. J Allergy Clin Immunol. 1976, 57: 440-8. 10.1016/0091-6749(76)90059-2.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Pleskow WW, Stevenson DD, Mathison DA: Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol. 1982, 69 (1 Pt 1): 11-9. 10.1016/0091-6749(82)90081-1.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Sclano G: Refractory period to aspirin after aspirin-induced asthma. J Allergy Clin Immunol. 1982, 70: 220-1. 10.1016/0091-6749(82)90046-X.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Micheletto C, Tognella S, Visconti M: Changes in urinary LTE(4) and nasal functions following nasal provocation test with ASA in ASA-tolerant and -intolerant asthmatics. Respir Med. 2006, 100 (12): 2144-50. 10.1016/j.rmed.2006.03.017. Epub 2006.

    Article  PubMed  Google Scholar 

  76. 76.

    White A, Bigby T, Stevenson D: Intranasal ketorolac challenge for the diagnosis of aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2006, 97: 190-5. 10.1016/S1081-1206(10)60012-9.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G: Clinical patterns of hypersensitivity to nonsteroidal antiinflammatory drugs and their pathogenesis. J Allergy Clin Immunol. 1977, 60: 276-84. 10.1016/0091-6749(77)90106-3.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Setipane RA, Stevenson DD: Cross-sensitivity with acetaminophen in aspirin sensitive subjects with asthma. J Allergy Clin Immunol. 1989, 84: 26-33. 10.1016/0091-6749(89)90174-7.

    Article  Google Scholar 

  79. 79.

    Dahlen S-E, Malmstrom K, Nizankowska E: 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.

    Article  PubMed  Google Scholar 

  80. 80.

    Yoshida S, Sakamoto H, Ishizaki Y: Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma. Clin Exp Allergy. 2000, 30: 64-70. 10.1046/j.1365-2222.2000.00797.x.

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Mastalerz L, Nizankowska E, Sanak M: Clinical and genetic features underlying the response of patients with bronchial asthma to treatment with a leukotriene receptor antagonist. Eur J Clin Invest. 2002, 32: 949-95. 10.1046/j.1365-2362.2002.01088.x.

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    Fuji : Effect of endoscopic sinus surgery on aspirin-induced asthma. Jpn J Rhinol. 2004, 43 (2): 175-81.

    Article  Google Scholar 

  83. 83.

    McFadden EA, Woodson BT, Fink JN, Toohill RJ: Surgical treatment of aspirin triad sinusitis. Am J Rhinol. 1997, 11: 263-70. 10.2500/105065897781446702.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Hosemann W: Surgical treatment of nasal polyposis in patients with aspirin intolerance. Thorax. 2000, 55 (Suppl 2): S87-90. 10.1136/thorax.55.suppl_2.S87.

    PubMed Central  Article  PubMed  Google Scholar 

  85. 85.

    Amar YG, Frenkiel S, Sobol SE: Outcome analysis of endoscopic sinus surgery for chronic sinusitis in patients having Samter's triad. J Otolaryngol. 2000, 29: 7-12.

    CAS  PubMed  Google Scholar 

  86. 86.

    Stevenson DD, Simon RA, Mathison DA: Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges. J Allergy Clin Immunol. 1980, 66: 82-8. 10.1016/0091-6749(80)90143-8.

    CAS  Article  PubMed  Google Scholar 

  87. 87.

    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: 180-6. 10.1067/mai.2003.7.

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Sousa AR, Parikh A, Scadding G: Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med. 2002, 347 (19): 1493-9. 10.1056/NEJMoa013508.

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Berges-Gimeno MP, Simon RA, Stevenson DD: The effect of leukotriene-modifier drugs on aspirin-induced asthma and rhinitis reactions. Clin Exp Allergy. 2002, 32: 1491-6. 10.1046/j.1365-2745.2002.01501.x.

    CAS  Article  PubMed  Google Scholar 

  90. 90.

    White AA, Stevenson DD, Simon RA: The blocking effect of essential controller medications during aspirin challenges in patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2005, 95: 330-5. 10.1016/S1081-1206(10)61150-7.

    CAS  Article  PubMed  Google Scholar 

  91. 91.

    Wong JT, Nagy CS, Krinzman SJ: Rapid oral challenge-desensitization for patients with aspirin-related urticaria-angioedema. J Allergy Clin Immunol. 2000, 105: 997-1001. 10.1067/mai.2000.104571.

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    Stevenson DD, Mehra PK, White AA: Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2005, 116: 755-60. 10.1016/j.jaci.2005.05.020.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Mathew Varghese MD.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Varghese, M., Lockey, R.F. Aspirin-Exacerbated Asthma. All Asth Clin Immun 4, 75 (2008).

Download citation


  • aspirin desensitization
  • aspirin exacerbated asthma
  • aspirin exacerbated respiratory disease
  • aspirin sensitive asthma
  • cysteinyl leukotriene
  • leukotriene
  • leukotriene C4
  • leukotriene C4 synthase