Oral Aspirin Challenge Research Articles

Diagnostic Value of Clinical Parameters in the Prediction of Aspirin-Exacerbated Respiratory Disease in Asthma

PurposeAspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with increased asthma severity. However, oral aspirin challenge (OAC) to diagnose AERD is a time-consuming procedure, and some patients experience serious complications. Thus, we evaluated diagnostic values of non-invasive clinical parameters to predict AERD in asthmatic patients.MethodsA total of 836 Korean subjects were recruited from an asthma cohort. They underwent OAC, and clinical parameters including the history of aspirin hypersensitivity, nasal polyposis, and chronic sinusitis of aspirin-tolerant asthma (ATA) and AERD asthmatic patients were compared.ResultsSignificant differences (P<0.01) were found in eight parameters: age at diagnosis, body mass index, FEV1%, PC20, history of urticaria, nasal polyps, chronic sinusitis, and history of aspirin hypersensitivity. After logistic regression analysis based on the eight clinical parameters, nasal polyps, history of aspirin intolerance, sinusitis, and log [PC20 methacholine] remained significantly associated with AERD (P<0.05). The sensitivity and specificity of the history of aspirin hypersensitivity to predict AERD were 64.7% and 92.0%, respectively, and the positive and negative predictive values were 56.9% and 94.1%, respectively. Overall, the accuracy of the test was 88.2%. The accuracy of the tests for nasal polyps and chronic sinusitis were 67.3% and 60.4%, respectively.ConclusionsAmong clinical parameters associated with AERD, the history of aspirin hypersensitivity has the best positive and negative predictive values for the oral aspirin challenge test. Because the false-positive and -negative rates were still high, additional non-invasive methods are needed to reduce the rate of false outcomes.

Coxibs strike back

Coxibs strike back

Use of intranasal ketorolac and modified oral aspirin challenge for desensitization of aspirin-exacerbated respiratory disease

Intranasal ketorolac challenges can induce respiratory reactions in patients with aspirin-exacerbated respiratory disease (AERD). To determine whether intranasal ketorolac challenges might be used for aspirin desensitization. One hundred patients with suspected AERD who were referred to Scripps Clinic from May 1, 2007 to December 31, 2009 were challenged with 4 increasing doses of ketorolac intranasally at 30-minute intervals. Symptoms, objective changes in the results of their nasal examination, peak nasal inspiratory flow rates, and forced expiratory volume in 1 second (FEV(1)) values were recorded. After nasal ketorolac dosing, patients were given oral aspirin as part of the challenge and desensitization. A control group consisted of 100 patients who had previously undergone our standard oral aspirin challenges and desensitization. Both groups were consecutively enrolled and had similar clinical characteristics. Compared with the standard oral aspirin challenge and desensitization, intranasal ketorolac and modified aspirin challenge significantly attenuated the mean percentage decrease in FEV(1) values (8.5% vs 13.4%; P = .01) and decreased the percentage of extrapulmonary reactions (23% vs 45%; P = .002), particularly laryngospasm (7% vs19%; P = .02) and gastrointestinal reactions (12% vs 33%; P = .001). This new protocol was significantly shorter, lasting an average of 1.9 vs 2.6 days (P = <.001). In fact, 83% of the patients completed the new protocol in less than 48 hours compared with only 20% in the oral challenge control group (P < .001). Intranasal ketorolac challenge and desensitization followed by rapid oral aspirin challenges is effective, safe, and less time-consuming than our standard oral aspirin desensitization protocol.

Airway Responsiveness to Inhaled Aspirin is Influenced by Airway Hyperresponsiveness in Asthmatic Patients

Background/AimsMany patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin.MethodsThe clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus.ResultsForty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 ± 0.02) than in the oral responders (1.36 ± 0.03, p < 0.01) and in non-responders (n = 141, 1.37 ± 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR.ConclusionsA considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.

Predicting outcomes of oral aspirin challenges in patients with asthma, nasal polyps, and chronic sinusitis

Predicting outcomes of oral aspirin challenges in patients with asthma, nasal polyps, and chronic sinusitis

Association Analysis of Peroxisome Proliferator-activated Receptors Gamma Gene Polymorphisms with asprin hypersensitivity in Asthmatics

PurposePeroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARγ regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA.MethodsBased on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His).ResultsLogistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04).ConclusionsThe +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.

Rational approach to aspirin dosing during oral challenges and desensitization of patients with aspirin-exacerbated respiratory disease

Aspirin desensitization improves clinical outcomes in most patients with aspirin-exacerbated respiratory disease. Most protocols for desensitization are time-consuming. Our objective was to use historical information about the course of aspirin desensitization to enhance the efficiency of the desensitization protocol. Four hundred twenty subjects with suspected aspirin-exacerbated respiratory disease underwent oral aspirin challenges. Their clinical characteristics were analyzed in relation to features of reactions during aspirin challenges. Large (FEV(1) decrease >30%) and moderate (FEV(1) decrease 21% to 30%) bronchial reactions occurred in 9% and 20% of subjects, respectively. Multivariate analysis identified risk factors associated with these larger reactions, including lack of leukotriene modifier use, baseline FEV(1) of less than 80% of predicted value, and previous asthma-related emergency department visits. Seventy-five percent of patients reacted to a provoking dose of either 45 or 60 mg. Only 3% of initial reactions occurred after 150- or 325-mg provoking doses, and none occurred after the 650-mg dose. Most bronchial and naso-ocular reactions during oral aspirin challenges occurred within a narrow dosing range (45-100 mg). Only 1 of 26 patients without risk factors had a moderate reaction.

Association of TNF-α promoter polymorphisms with aspirin-induced urticaria

Although the pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)-alpha, a potent pro-inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF-alpha promoter polymorphisms in the development of AIU, we performed an association study of TNF-alpha promoter polymorphisms with AIU phenotype. Two hundred thirty-nine patients with AIU consisting of 120 patients with aspirin intolerant chronic urticaria (AICU) and 119 with aspirin-intolerant acute urticaria (AIAU), and 524 normal controls were enrolled. AIU was confirmed by oral aspirin challenge test. Five SNPs in the TNF-alpha gene (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) were genotyped by a single-base extension method. Haplotype analyses were done. The genotype frequencies of TNF-1031T>C and TNF-863C>A were significantly higher in the AIU patients than in the normal controls in both co-dominant (P = 0.014, P = 0.007) and dominant (P = 0.007, P = 0.004) models. The frequency of TNF-ht2[CACGG] containing a genotype in the AIU group was significantly higher in the normal controls with both co-dominant (P = 0.004, Pc = 0.02) and dominant models (P = 0.002, Pc = 0.01). These findings suggest that the two promoter polymorphisms of TNF-alpha at -1031T>C and -863C>A may contribute to the development of AIU.

Predicting outcomes of oral aspirin challengesin patients with asthma, nasal polyps, andchronic sinusitis

A definitive diagnosis of aspirin-exacerbated respiratory disease (AERD) requires a positive oral aspirin challenge (OAC), but predicting which patients will have positive challenges is often difficult. To analyze information about historical aspirin- and nonsteroidal anti-inflammatory drug (NSAID)-associated respiratory reactions and clinical characteristics as potential markers to predict positive OACs. A total of 243 patients underwent OACs. Data related to previous reactions and clinical characteristics of patients were correlated with the result of the OACs. Without prior exposure to aspirin or NSAIDs, the chance of a positive OAC was 5 in 12 (42%) but was 198 in 231 (86%) for those with a history of aspirin- and NSAID-associated asthma attacks. Sex, atopy, number of sinus infections per year, and number of sinus surgical procedures were not associated with positive OACs. Patients with 2 or more prior aspirin- and NSAID-associated respiratory reactions had an 89% chance of having a positive OAC vs single reactors (80%; P = .04). Mild or moderate prior reactions were associated with 84% or 80% positive OACs, whereas 100% of the 45 patients with severe prior reactions had positive OACs (P = .007). Except for hospitalizations, treatment locations of prior reactions (home or emergency department) did not seem to make any difference. Logistic regression identified age, sense of smell, and multiple prior reactions as independent risk factors associated with positive OACs. Age younger than 40 years, poor sense of smell, multiple prior respiratory reactions, and severe prior asthmatic reactions associated with aspirin and NSAIDs significantly increased the chances of a positive OAC.

Safety of triflusal (antiplatelet drug) in patients with aspirin‐exacerbated respiratory diseases

Aspirin, a cyclo-oxygenase (COX)-1 and COX-2 inhibitor, is the antiplatelet drug of choice to prevent serious vascular events. Adverse reactions to aspirin are frequent particularly among patients with asthma, chronic rhinosinusitis and nasal polyps. COX-1 inhibitors but not COX-2 inhibitors precipitate asthma attacks. Triflusal is a preferential COX-2 inhibitor antiplatelet agent that is as effective as aspirin in the prevention of serious vascular events. The aim of the study was to assess the tolerability of triflusal in patients with aspirin-exacerbated respiratory disease (AERD). We studied 26 asthma patients [11 males, aged 52 (23-75) years] who had suffered asthma episodes triggered by one or more (23% of patients) nonsteroidal anti-inflammatory drugs. Aspirin sensitivity was confirmed by either intranasal or oral aspirin challenge. All subjects underwent a single-blind, placebo-controlled oral challenge with three doses of triflusal separated by 1 week (first cumulative dose = 225 mg; second cumulative dose = 450 mg; third cumulative dose = 900 mg). Cutaneous, respiratory, general symptoms and lung function were monitored for 4 h in the laboratory and for 24 h at home. No clinical reactions to triflusal were observed. There were no significant changes in lung function measurements. Our study appears to demonstrate that triflusal is a suitable alternative to aspirin as antiplatelet agent to prevent AERD.

Prostaglandin E2 systemic production in patients with asthma with and without aspirin hypersensitivity

Background:A special regulatory role for prostaglandin E2 has been postulated in aspirin-induced asthma. A study was undertaken to investigate the effects of aspirin on the systemic production of prostaglandin E2...

The relationship between historical aspirin-induced asthma and severity of asthma induced during oral aspirin challenges

Historical aspirin- or nonsteroidal anti-inflammatory drug (NSAID)-induced reactions might provide predictive information about the severity of reactions in patients with aspirin-exacerbated respiratory disease (AERD) undergoing oral aspirin challenge (OAC). We sought to assess the relationship between historical aspirin- or NSAID-induced bronchial reactions and the severity of bronchial reactions during OAC in patients with AERD. Data regarding the provoking doses, treatments, and treatment settings of historical aspirin/NSAID-induced reactions were recorded, analyzed, and compared with the provoking doses, maintenance regimens, and observed decreases in FEV(1) that occurred during OAC in 210 consecutive patients referred with suspected AERD. Of 147 patients who reported seeking acute medical care for their historical aspirin/NSAID-induced asthma attacks, 101 (69%) were treated in an emergency department and released, and 46 (31%) required hospitalization. During OAC in these 147 subjects, 23 (16%) had a 20% to 29% decrease and 14 (10%) had a 30% or greater decrease in FEV(1) values from baseline. Of the 46 patients previously hospitalized for aspirin/NSAID-induced asthma attacks, 9 (20%) had a 20% to 29% decrease and 6 (13%) had a 30% or greater decrease in FEV(1) during OAC. By contrast, of the 63 patients who treated their prior aspirin/NSAID-induced reactions at home, 5 (8%) had a 20% to 29% decrease and 5 (8%) had a 30% or greater decrease in FEV(1) during OAC (P = not significant for both). The severity of the historical aspirin/NSAID-induced asthma attack was not predictive of asthma severity during OAC. These data provide further reassurance regarding the safety of outpatient aspirin desensitization.

Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: a practice paper

Aspirin desensitization is indicated for patients who have aspirin-exacerbated respiratory disease and whose asthma and/or rhinosinusitis is suboptimally controlled with inhaled corticosteroids and leukotriene-modifying drugs. In this practice paper, the general requirements for aspirin desensitization are presented, the locations where desensitizations can be safely performed are outlined, prechallenge patient preparation is discussed, an oral aspirin challenge protocol is presented, treatment of adverse reactions is reviewed, and maintenance of aspirin desensitization is discussed.

Effect of leukotriene modifier drugs on the safety of oral aspirin challenges

Aspirin-exacerbated respiratory disease can be diagnosed with oral aspirin challenges and treated with aspirin desensitization. To evaluate whether controller medications, particularly leukotriene modifier drugs, taken during oral aspirin challenges can reduce the risk of severe asthmatic responses. The medical records of 676 patients who had undergone oral aspirin challenges, followed by aspirin desensitization, were reviewed. Asthmatic responses were stratified based on severity of bronchospastic response or lack of response. The effect of pretreatment with controller medications on the outcome of oral aspirin challenges was measured. Leukotriene modifier drugs had the most significant effect in protecting the lower airways from severe reactions (P = .004). The protective effect of leukotriene modifier drugs was observed in patients already taking systemic corticosteroids, where the addition of leukotriene modifier drugs significantly shifted the response toward a milder asthmatic response (P < .001). Protection from significant aspirin-induced bronchospasm during oral aspirin challenge can be accomplished with leukotriene modifier drugs. The use of a combination of inhaled corticosteroids, long-acting beta-agonists, systemic corticosteroids, and leukotriene modifier drugs stabilized underlying airways in preparation for a reasonably safe and accurate oral aspirin challenge. However, only pretreatment with leukotriene modifier drugs enhanced the safety of oral aspirin challenge in patients with aspirin-exacerbated respiratory disease by significantly decreasing the degree of asthmatic responses. Therefore, outpatient oral aspirin challenges in most well-selected patients appear to be a reasonable decision.

Intranasal ketorolac challenge for the diagnosis of aspirin-exacerbated respiratory disease

Intranasal administration of aspirin-lysine has been used in Europe for the diagnosis of aspirin-exacerbated respiratory disease. It has a low adverse effect profile and is believed to be safer for asthmatic patients, particularly those with a low baseline forced expiratory volume in 1 second, in whom oral aspirin challenge would be contraindicated. Ketorolac, a nonsteroidal anti-inflammatory drug useful for severe pain, is available in the United States in parenteral form. To determine whether ketorolac nasal challenge has acceptable specificity and sensitivity for diagnosing aspirin-exacerbated respiratory disease. Twenty-nine patients with suspected aspirin-exacerbated respiratory disease were challenged with nasal ketorolac before oral challenge and desensitization with aspirin. Symptoms, objective changes in nasal examination findings, and peak nasal inspiratory flow values were recorded. Nasal lavage fluid for cysteinyl leukotriene analysis was collected. Ketorolac doses of 2.1, 5.2, or 7.8 mg were administered and compared with the results of oral aspirin challenge. Eighteen patients had a positive challenge reaction to oral aspirin. Ketorolac nasal inhalation had a sensitivity of 78% and a specificity of 64%. Patients in the reactor group had significantly higher levels of cysteinyl leukotrienes after ketorolac challenge than in the nonreactor group. Mild bronchospasm occurred in 3 patients, and 2 of these occurred at higher starting doses of ketorolac. Nasal ketorolac administration is a reasonably accurate and safe method for diagnosing aspirin-exacerbated respiratory disease.

Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease

In patients with aspirin-exacerbated respiratory disease (AERD), pretreatment with asthma controller medications (leukotriene modifiers, inhaled or systemic corticosteroids, and salmeterol) partially modifies the severity of aspirin-induced asthmatic reactions. A recent study showed that pretreatment with tacrolimus completely prevented aspirin-induced respiratory reactions and might allow silent aspirin desensitization. Ten patients with rhinosinusitis, nasal polyps, and asthma had a history of asthma attacks after ingesting aspirin and nonsteroidal anti-inflammatory drugs. All underwent baseline oral aspirin challenges and had typical respiratory reactions. They were then randomized to receive tacrolimus (0.1 mg/kg weight; 8 patients) or placebo (2 patients) in a double-blind protocol before rechallenge with aspirin using the previous provoking dose of aspirin. In addition, respiratory reactions sustained by 50 consecutive patients with AERD during 2004 were recorded, analyzed, and compared with the tacrolimus/placebo-treated patients to determine whether there were any differences. Tacrolimus pretreatment failed to block respiratory reactions to provoking doses of aspirin in 5 of 8 patients with AERD, and in the other 3 patients did not block higher doses of aspirin. The results of oral aspirin challenges in the control population of 50 patients were compared with either the baseline or postchallenge data from the tacrolimus-pretreated or placebo-pretreated patients with AERD, and there were no significant differences. Use of tacrolimus as add-on pretreatment to prevent reactions to aspirin in patients with AERD or to achieve the goal of silent aspirin desensitization could not be accomplished.

Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity

Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs) but there is no consensus on a standardized protocol. As a prior clinical history of adverse reactions to aspirin is poorly predictive of a positive result from formal aspirin challenge, many patients have an OAC performed. We retrospectively identified and prospectively validated how a 1-day OAC protocol could be modified, and patient selection improved, to deliver a safe and more efficient service. In a retrospective audit of 45 OACs using a 2 h dose interval, all reactions occurred within 90 min of the threshold dose. Forty OACs were then performed using a 90-min dose interval. This reduced the mean duration of a positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively. Histories of multiple manifestations of AHs were found in 91.6% (11) of those with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6% (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5% (1) with angiooedema, with a positive OAC, had a history of a single manifestation of AHs. The efficiency of an OAC service can safely be improved by reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient selection, as the likelihood of a positive OAC increases among patients with a history of asthma, angiooedoema or anaphylaxis with multiple manifestations of AHs.

Oral aspirin challenges in patients with a history of intolerance to single non‐steroidal anti‐inflammatory drugs

Summary Background In the clinical practice patients with a history of acute urticaria induced by a single non-steroidal anti-inflammatory drug (NSAID) and seeking for safe alternative drugs generally undergo tolerance tests with alternative NSAIDs that have little or no cyclooxygenase-1 (COX-1) enzyme inhibitory activity. This practice does not allow for the detection of single NSAID reactors and may lead to unnecessary avoidance of many potentially useful NSAIDs. Evaluate aspirin challenge as a means to distinguish single from multiple NSAID intolerance in patients with a clinical history of acute urticaria induced by a single NSAID. Methods One hundred and seventeen otherwise normal subjects with a history of acute urticaria following the ingestion of a single NSAID (pyrazolones (n=58), nimesulide (n=17), propionic acid derivatives (n=13), aryl acetic acid derivatives (n=14), acetaminophen (n=9), piroxicam (n=5), and indometacin (n=1)) underwent single-blind placebo-controlled oral challenges with aspirin. Aspirin-intolerant subjects underwent further tolerance tests drugs exerting little or no inhibitory activity on COX-1 enzyme (including paracetamol, nimesulide, rofecoxib, tramadol, and floctafenine). Results Aspirin induced urticaria in 28/117 (24%) patients. Five out of 28 (18%) aspirin reactors did not tolerate alternative NSAID on subsequent oral challenges. Conclusion In subjects with a history of urticaria induced by a single NSAID (other than aspirin) the diagnostic workup should start with an aspirin challenge in order to detect single/multiple NSAID reactors.

The human leucocyte antigen‐DRB1*1302‐DQB1*0609‐DPB1*0201 haplotype may be a strong genetic marker for aspirin‐induced urticaria

Urticaria/angioedema is a common aspirin-induced allergy; however, its pathogenic mechanism is not understood. In order to uncover the genetic mechanism, we studied the associations of the human leucocyte antigen (HLA) genotypes in patients with aspirin-induced urticaria compared with aspirin-intolerant asthma and normal control in a Korean population. Ninety-four aspirin-induced urticaria patients presenting urticaria/angioedema-induced by both ASA and NSAID (50 had underlying chronic urticaria) and showing positive responses on oral aspirin challenge test, 76 aspirin-intolerant asthmatics with positive responses on lysine-aspirin bronchoprovocation test, and 185 normal healthy controls were enrolled. HLA-DRB1, DQB1, and DPB1 genotypings were performed by direct DNA sequencing analysis. The allele frequencies of HLA-DRB1(*)1302 (18.1%) and HLA-DQB1(*)0609 (10.1%) in aspirin-induced urticaria were significantly higher than in aspirin-intolerant asthma (5.3%, P=0.0004; 2.0%, P=0.0024) and in normal controls (8.1%, P=0.0005; 3.2%, P=0.0008), and they remained significant after correcting for multiple comparisons. The patients with these two HLA markers had a significantly younger age than patients without, while no associations were found in with respect to atopic status, a history of previous allergic diseases, total IgE level, or presence of underlying chronic urticaria (P>0.05, respectively). In haplotype analysis, the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 was significantly higher in the aspirin-induced urticaria (8.0%) than in the aspirin-intolerant asthma (0.7%, P=0.0014) and normal controls (2.0%, P=0.0006). These findings suggest that the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 may be a strong genetic marker to determine the aspirin-induced urticaria phenotype.

Pathogenesis and Management of Aspirin-Intolerant Asthma

In 2-23% of adults with asthma, and rarely in children with asthma, aspirin (acetylsalicylic acid) and non-steroidal anti-inflammatory drugs (NSAIDs) cause asthma exacerbations. Within 3 hours of ingestion of aspirin/NSAIDs, individuals with aspirin-intolerant asthma (AIA) develop bronchoconstriction, often accompanied by rhinorrhea, conjunctival irritation, and scarlet flush. In severe cases, a single therapeutic dose of aspirin/NSAIDs can provoke violent bronchospasm, loss of consciousness, and respiratory arrest. In order to diagnose AIA, oral, inhaled, nasal or intravenous aspirin challenge tests are performed in facilities where experienced physicians are present and emergency treatment is available. The exact differences in the pathogenesis of AIA and other types of asthma are not fully understood. The interference of aspirin/NSAIDs with arachidonic acid metabolism in the lungs plays an important role in the mechanism of AIA; inhibition of cyclo-oxygenase is accompanied by overproduction of cysteinyl leukotrienes (cys-LTs). It has been proposed that overproduction of cys-LTs, together with removal by aspirin/NSAIDs of the 'brake' imposed by the bronchodilator prostaglandin E2, may cause an asthma attack in patients with AIA. Development of a suitable animal model to investigate the pathogenesis of AIA would help to clarify this question. Although it is still controversial whether leukotriene modifiers are more effective in patients with AIA compared with other types of asthma, because LT plays an important role in the pathogenesis of AIA, leukotriene modifiers are the preferred medication for the long-term control of AIA. Add-on efficacy of leukotriene modifiers has been confirmed in patients with AIA already treated with inhaled corticosteroids. However, this does not mean that aspirin/NSAIDs can be safely taken by aspirin-sensitive patients treated with leukotriene modifiers. To prevent attacks of AIA, sensitive patients should avoid the use of aspirin/NSAIDs or use selective cyclo-oxygenase 2 inhibitors when required. When patients with AIA need aspirin for specific situations they should receive aspirin desensitization therapy or treatment with selective cyclo-oxygenase 2 inhibitors.