Oral Aspirin Challenge Research Articles

Exhaled eicosanoids following oral aspirin challenge in asthmatic patients

Biochemical analysis of expiratory breath condensate is an emerging non-invasive technique for assessment of airway inflammation. We wondered whether application of expiratory breath condensate could facilitate diagnosis of aspirin-intolerant asthma and reproduce eicosanoids mediators' abnormalities described in this disease. We measured prostaglandins (PGs) E(2), F(2 alpha), 9 alpha 11 beta F(2) and iso-F(2) by gas-chromatography/mass-spectrometry and cysteinyl leukotrienes (cys-LTs) by radioimmunoassay in breath condensates of asthmatic patients undergoing oral aspirin challenge. Fourteen patients with aspirin-induced asthma and 20 aspirin-tolerating asthmatics, most of them on chronic inhaled corticotherapy, were studied and compared with 10 healthy subjects. Additionally, plasma 9 alpha 11 beta PGF(2), the metabolite of PGD(2) and urinary leukotriene (LT) E(4) were measured before and following the challenge. At baseline, PG did not differ between the groups, except for lower 9 alpha 11 beta PGF(2) in aspirin-intolerant asthma. Their concentrations were not changed by the challenge. Breath condensate cys-LTs were similar in the groups studied at base, and after aspirin challenge increased only in aspirin-intolerant patients. Elevated baseline urinary LTE(4) and its further increase following aspirin challenge was highly diagnostic for aspirin-intolerant asthma. The discriminatory value of cys-LTs increase in breath condensates was lower (72.8%) than either basal (99%) or post-challenge increase (94%) of urinary LTE(4). In asthmatic patients on chronic corticotherapy measurement of urinary LTE(4) excretion rather than cys-LTs in breath condensate is of greater value for diagnosis of aspirin hypersensitivity.

Jenkins et al. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ 2004;328:434

A review of a number of data sources showed that the frequency of aspirin-triggered asthma in groups of individuals with chronic asthma was considerably higher when determined by oral aspirin challenge (mean, 21% in adults and 5% in children) than when determined by positive patient verbal histories (3% for adults and 2% in children). Over-the-counter nonsteroidal anti-inflammatory drugs triggered asthma in most aspirin-sensitive individuals with asthma, but the incidence of cross-sensitivity to paracetamol (acetaminophen) in such patients was only 7%. Of note, studies by the Scripps Clinic group have shown that the occasional triggering of respiratory symptoms by acetaminophen in such patients might be related to the dose of acetaminophen ingested. A review of a number of data sources showed that the frequency of aspirin-triggered asthma in groups of individuals with chronic asthma was considerably higher when determined by oral aspirin challenge (mean, 21% in adults and 5% in children) than when determined by positive patient verbal histories (3% for adults and 2% in children). Over-the-counter nonsteroidal anti-inflammatory drugs triggered asthma in most aspirin-sensitive individuals with asthma, but the incidence of cross-sensitivity to paracetamol (acetaminophen) in such patients was only 7%. Of note, studies by the Scripps Clinic group have shown that the occasional triggering of respiratory symptoms by acetaminophen in such patients might be related to the dose of acetaminophen ingested.

Hypersensitivity to aspirin: Common eicosanoid alterations in urticaria and asthma

BackgroundAspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can precipitate adverse reactions in two apparently different clinical conditions: bronchial asthma and chronic idiopathic urticaria (CIU). Recent evidence indicates that the reactions are triggered by the drugs that inhibit cyclooxygenase-1 but not cyclooxygenase-2. ObjectiveTo assess whether patients with CIU and aspirin sensitivity share common eicosanoid alterations with patients who have aspirin-sensitive asthma. MethodsSeventy-four patients with CIU and a history of sensitivity to aspirin and NSAIDs underwent placebo-controlled oral aspirin challenge tests. Concentrations of urinary leukotriene E4 (uLTE4) were measured by ELISA and plasma stable prostaglandin D2 metabolite, 9α,11β prostaglandin F2 by GC/MS. All measurements were carried out at baseline and after aspirin dosing. Patients were genotyped for the leukotriene C4 synthase (LTC4S) promoter single nucleotide polymorphism. ResultsIn 30 of 74 patients, the aspirin challenge was positive, resulting in urticaria/angioedema. In these 30 patients, baseline uLTE4 levels were higher than in nonresponders and the healthy control subjects and increased further (significantly) after the onset of clinical reaction. No such increase occurred in subjects with negative aspirin challenge. Baseline uLTE4 levels correlated with severity of skin reactions. Plasma 9α,11β prostaglandin F2 levels rose significantly in both aspirin responders and nonresponders, although in the latter group the increase occurred later than in the former. In patients who reacted to aspirin, frequency of −444C allele of LTC4S was significantly higher than in patients who did not react. ConclusionsCIU with aspirin sensitivity is characterized by the eicosanoid alterations, which are similar to those present in aspirin-induced asthma.

Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria.

During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well-established non-immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimental setting. Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU. Microscopic analysis of tissue sections. 16 patients with CIU. Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occurring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare-like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case. Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug-specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response.

Exhaled eicosanoids following oral aspirin challenge in patients with asthma

Rationale Since eicosanoids are involved in pathogenesis of asthma we hypothesized that their exhaled pattern may differ in various asthma phenotypes. Methods We measured cysteinyl leukotrienes (CysLTs) using radioimmunoassay, and prostaglandins E 2 and F 2α using GC-MS, in exhaled air condensates from patients with aspirin-induced asthma (AIA; n=13, age=40.6 ± 14.1 y., M/F=6/7), aspirin-tolerant asthma (n=18, age=35.8 ± 11.3, M/F=4/14) and healthy subjects (n=10, age=31.7 ± 10.3, M/F=6/4). The measurements were carried out at baseline and following aspirin challenge, and were coupled with urinary leukotriene E 4 (uLTE 4) estimations by ELISA. Results At baseline, the eicosanoid content in exhaled air did not differ between the groups. Following aspirin challenge, a rise in exhaled CysLTs was observed only in AIA (from 10.0 ± 10.3 to 36.5 ± 33.5 pg/ml; p=0.005). Only AIA patients had elevated uLTE 4 at baseline (2.97 ± 1.7 ng/mg creatinine; p=0.001), which increased further following aspirin provocation (9.8 ± 9.0; p=0.002). In AIA patients, there was an inverse relationship (Spearman's ρ=-0.7, p=0.008) between magnitude of CysLTs response to aspirin measured in exhaled air, as compared to urine. Conclusions 1) Measurement of eicosanoids in expiratory air condensates, though sensitive to detect CysLTs increase during aspirin challenge in AIA patients, offers no additional clinical advantage over uLTE 4 estimation. 2) Unexpected negative correlation between breath and urinary CysLTs responses awaits further inquires.

Hypersensitivity to aspirin: Common eicosanoid alterations in urticaria and asthma

Rationale To assess whether patients with chronic idiopathic urticaria (CIU) and aspirin sensitivity share common eicosanoid alterations with patients suffering from aspirin-sensitive asthma. Methods 74 patients with CIU and a history of sensitivity to aspirin and NSAIDs underwent placebo-controlled oral aspirin challenge tests. Concentrations of urinary leukotriene E4 (uLTE4) were measured by ELISA, and plasma stable prostaglandin D2 metabolite, 9α,11βPGF2, by GC/MS. All measurements were carried out at base, and after aspirin dosing. Patients were genotyped for the leukotriene C4 synthase (LTC4S) promoter single nucleotide polymorphism. Results In 30 of 74 patients the aspirin challenge was positive, resulting in urticaria/angioedema. In these 30 patients baseline uLTE4 were higher than in non-responders and healthy controls, and increased further significantly after the onset of clinical reaction. No such increase occurred in subjects with negative aspirin challenge. Baseline uLTE4 levels correlated with severity of skin reactions. Plasma 9α,11βPGF2 levels rose significantly in both aspirin-responders and non-responders, although in the latter group the increase occurred later than in the former. In patients who reacted to aspirin, frequency of −444C allele of LTC4S was significantly higher than in patients who did not react. Conclusions CIU with aspirin sensitivity is characterized by the eicosanoid alterations which are similar to those present in aspirin-induced asthma.

Nasal versus bronchial and nasal response to oral aspirin challenge: Clinical and biochemical differences between patients with aspirin-induced asthma/rhinitis

Background Aspirin-induced asthma/rhinitis (AIAR) is characterized by the altered metabolism of leukotrienes and proinflammatory prostaglandins. The basal and postchallenge levels of eicosanoids might reflect the clinical and biochemical characteristics of patients with distinct types of hypersensitive responses to aspirin. Objective We compared clinical and eicosanoid profiles of patients with AIAR showing both bronchial and nasal versus isolated nasal responses to aspirin challenge. Methods Twenty-three patients with AIAR underwent the single-blind, oral, placebo-controlled aspirin challenge. The bronchial response (BR) was evidenced by dyspnea and spirometry, whereas the nasal response (NR) was evidenced by nasal symptoms and acoustic rhinometry and/or rhinomanometry. Urinary leukotriene E 4 (uLTE 4), serum and urinary stable prostaglandin D 2 metabolite, and 9α,11β-prostaglandin F 2 (9α,11β-PGF 2), were determined at baseline and after the aspirin challenge. Results Fifteen subjects showed BR and NR (BNR), whereas 8 showed NR only. Basal uLTE 4 in the BNR group was significantly higher than in the NR group. After aspirin challenge, it increased significantly in both groups. Serum 9α,11β-PGF 2increased after aspirin challenge in the BNR group only. The patients with BNR had more severe AIAR. Conclusions BNR to aspirin in AIAR indicates a more advanced disease and more profound underlying eicosanoid metabolism disturbances.

Adverse reactions to aspirin and nonsteroidal antiinflammatory drugs (NSAIDs).

Aspirin can provoke reactions ranging from respiratory to cutaneous in those susceptible individuals. There has been particular attention looking at the role of cyclooxygenase enzymes and 2 and their role in aspirin exacerbated respiratory disease. Patients who present with a spectrum of allergic and pseudoallergic reactions to aspirin pose a special challenge for the physician. This article discusses proposed classification system, clinical manifestations, pathogenesis of disease, and current treatment options of aspirin related disease. Relevant articles in the medical literature were. derived from searching the MEDLINE database. Sources also include review articles, randomized control trials, and standard textbooks of allergy and immunology. Aspirin-exacerbated respiratory disease remains a complex, heterogeneous disease with manvaried clinical presentations. There have been many advances in trying to elucidate the pathogenesis of this disease. The classification system presented will provide greater ease when reading the literature and communicating with one another. Oral aspirin challenge remains the diagnostic test of choice for both respiratory and cutaneous reactions. Aspirin desensitization is an option for those with refractory respiratory disease or who require aspirin for other medical conditions. This review discusses the challenges in classification, diagnosis and treatment of those patients with a sensitivity to aspirin. Special attention is made to the possible mechanisms mediating disease progression and how specific. Therapies, such as the leukotriene modifiers may be helpful.

Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma

Background: Patients with aspirin-sensitive respiratory disease experience cross-reactions to all nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase enzymes. With the introduction of antiarthritis drugs, which selectively inhibit cyclooxygenase-2, questions are raised as to whether cross-reactivity occurs between aspirin and these new cyclooxygenase-2 inhibitors. Objective: The goal of this study was to determine whether rofecoxib cross-reacts in aspirin-sensitive patients with asthma. Methods: Sixty patients with asthma underwent doubleblinded, placebo-controlled oral challenges with rofecoxib (12.5 mg, 25 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, aspirin sensitivity was proven in each of the 60 patients through use of single-blinded oral aspirin challenges. Results: None of the 60 patients experienced any symptoms, changes in nasal examination findings, or declines in FEV 1 values during their challenges with rofecoxib. All 60 patients experienced typical naso-ocular and asthmatic reactions to aspirin with a mean provoking dose of 61 mg. The exact 1-sided CI for the probability of rofecoxib inducing crossreactions in aspirin-sensitive patients with asthma is calculated to be between 0% and 0.05%. Conclusion: Given that none of the 60 patients reacted to rofecoxib and given the statistical power of this large sample size, we conclude that cross-reactivity between aspirin and rofecoxib does not occur in patients with aspirin-sensitive respiratory disease. This does not exclude rofecoxib from participating in other types of reactions, including immune recognition after prior treatment with the drug. From the standpoint of the mechanisms involved in aspirin-induced respiratory reactions, this study strongly supports inhibition of cyclooxygenase-1 as the essential initiator of these types of reactions. (J Allergy Clin Immunol 2001;108:47-51.)

Safety of a specific COX‐2 inhibitor in aspirin‐induced asthma

In a subset of patients with asthma, aspirin and several other non-steroidal anti-inflammatory drugs (NSAID) that inhibit simultaneously cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) precipitate dangerous asthmatic attacks. We tested the hypothesis that in patients with aspirin-induced asthma the attacks are triggered by inhibition of COX-1 and not COX-2. In twelve asthmatic patients (seven men, five women, average age 39 years) oral aspirin challenge precipitated symptoms of bronchial obstruction with fall in FEV1 > 20%, and a rise in urinary leukotriene E4 (LTE4) excretion; also in five patients the stable metabolite of PGD2, 9alpha11betaPGF2, increased in urine. The patients then entered a double-blind, placebo-controlled, cross-over study in which they received either placebo or rofecoxib in increasing doses 1.5-25.0 mg for 5 consecutive days, separated by a 1-week wash-out period. No patient on rofecoxib developed dyspnoea or fall in FEV1 > 20%; mean urinary LTE4 and 9alpha11betaPGF2 urinary levels, measured on each study day for 6 h post-dosing, remained unchanged. Two patients on placebo experienced moderate dyspnoea without alterations in urinary metabolites excretion. At least 2 weeks after completion of the study, all patients received on an open basis 25 mg rofecoxib without any adverse effects. NSAID that inhibit COX-1, but not COX-2, trigger asthmatic attacks in patients with asthma and aspirin intolerance. Rofecoxib can be administered to patients with aspirin-induced asthma.

Clinical features and diagnosis of aspirin induced asthma

Although for therapeutic reasons it has become convenient to consider asthma as a single disease entity, this clearly is not the case, with many variants occurring. From a clinical standpoint,...

Lack of effect of the 5-lipoxygenase inhibitor zileuton in blocking oral aspirin challenges in aspirin-sensitive asthmatics

Leukotrienes (LTs) have been implicated as major mediators of aspirin-(ASA)-induced respiratory reactions. It was therefore logical to assume that an inhibitor of 5-lipoxygenase (5-LO), such as zileuton, given before and during oral challenges with ASA, might prevent ASA-induced respiratory reactions. Indeed, in prior studies, pretreatment of ASA-sensitive respiratory disease patients with leukotriene modifiers eliminated or attenuated respiratory reactions upon re-challenge with the previously established provoking dose of ASA. However, doses higher than the provoking doses were not administered during these reported studies. We wished to determine whether zileuton pretreatment could prevent ASA-induced respiratory reactions in our six volunteers with aspirin-sensitive respiratory disease when ASA challenge doses were started below the usual provoking dose of 60 mg and then increased until a respiratory reaction occurred. Aspirin sensitivity was established previously in all six patients during a prior ASA oral challenge. In this study, pretreatment with zileuton 600 mg qid was initiated 7 days prior to, and continued during oral ASA challenges. Patients underwent single-blind oral ASA challenges with escalating doses of ASA, every 3 hours, according to our standard protocol. All six patients reacted to doses of ASA between 45 and 325 mg. Four patients experienced bronchospasm (FEV1 declined 19% to 53%) while receiving zileuton. All six had naso-ocular reactions. Concentrations of urine LTE4 also increased significantly (mean 334 pg/mg Cr at baseline, increasing to 1024 pg/mg Cr at respiratory reactions). During ASA challenges, zileuton, in standard doses of 600 mg qid was associated with increased synthesis of LTs in five of six patients and naso-ocular reactions in all six patients, as well as bronchospasm in four patients.

Hydrocortisone sodium succinate does not cross-react with aspirin in aspirin-sensitive patients with asthma

Background: Bronchospasm after intravenous hydrocortisone treatment has been reported in some patients with aspirin-sensitive respiratory disease. Objective: This study was designed to determine the prevalence of sensitivity to hydrocortisone among patients with aspirin-sensitive respiratory disease. Methods: We performed double-blind, placebo-controlled challenges with aspirin and 100 mg of hydrocortisone sodium succinate administered intravenously in 53 subjects. Results: Forty-five of the 53 subjects (85%) undergoing oral aspirin challenge experienced respiratory reactions to aspirin. Forty-four of these 45 patients had neither naso-ocular, cutaneous, nor respiratory reactions to hydrocortisone sodium succinate. One aspirin-sensitive subject had bronchospasm and a naso-ocular reaction to hydrocortisone sodium succinate and a naso-ocular reaction with minimal bronchospasm to methylprednisolone sodium succinate. After desensitization to aspirin, and while receiving maintenance aspirin therapy, this subject again reacted to hydrocortisone sodium succinate with bronchospasm and naso-ocular reaction. Conclusion: We conclude that aspirin-sensitive patients with asthma are not preferentially sensitive to hydrocortisone and that hydrocortisone sodium succinate does not cross-react or cross-desensitize with aspirin. ( J Allergy Clin Immunol 1995;96:545-8.)

Cysteinyl leukotrienes overproduction and mast cell activation in aspirin-provoked bronchospasm in asthma

In order to examine the hypothesis that in aspirin-induced asthma (AIA) cyclooxygenase inhibition is associated with enhanced release of leukotrienes (LTs), we measured urinary leukotriene E4 (LTE4) and 11-dehydro-thromboxane B2 (TXB2) (as a measure of cyclooxygenase production) following challenge with oral aspirin or inhaled methacholine, in 10 AIA patients. We also determined serum tryptase and eosinophilic catonic protein (ECP) levels, in order to evaluate mast cell and eosinophil activation. Urinary LTE4 excretion was increased sevenfold 4-6 h after aspirin challenge, while 11-dehydro-TXB2 decreased gradually reaching 50% baseline levels 24 h after challenge (p < 0.05). This was accompanied by a significant fall in blood eosinophil count at 6 h, and a tendency to a rise in ECP. The intensity of both LTE4 and 11-dehydro-TXB2 responses depended on the dose of aspirin used (p < 0.001, analysis of variance (ANOVA)). The accompanying maximum fall in forced expiratory volume in one second (FEV1) was not correlated with peak LTE4 levels. In contrast to aspirin, methacholine challenge producing comparable bronchial obstruction, did not alter eicosanoid excretion or serum tryptase or ECP levels. In a separate study, lysine-aspirin inhalation challenge was performed in seven AIA patients, four of whom had responded with a rise in serum tryptase to oral aspirin challenge. Challenge with inhaled aspirin led to similar bronchoconstriction as with oral challenge, but non-respiratory symptoms such as scarlet flush or rhinorrhea were absent, and serum tryptase levels remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic acid metabolism in monocytes of aspirin-sensitive asthmatic patients before and after oral aspirin challenge

Aspirin and nonsteroidal antiinflammatory drugs induce bronchospastic reactions in patients with aspirin-sensitive respiratory disease. Although the mechanism of this reaction is unknown, all drugs that induce the respiratory reaction also Inhibit the cyclooxygenase enzyme. The ensuing changes in arachidonate metabolism are presumed to play a role in the pathogenesis of the reaction. We measured generation of leukotrienes and thromboxane by calcium ionophore stimulated blood monocytes. Before aspirin challenge, monocytes released significantly more thromboxane B 2 in patients with aspirin sensitivity than in patients without aspirin sensitivity or in healthy control subjects ( p < 0.02). During aspirin-induced bronchospasm, release of leukotriene B 4 increased significantly (45.5%, p = 0.018), whereas release of thromboxane B 2 decreased (−46.9%, p = 0.028). Two hours after ingestion of 60 mg aspirin, normal monocyte release of thromboxane B 2 did not drop, whereas leukotriene B 4 release increased. Monocytes formed only minimal amounts of leukotriene C 4. We conclude that the profile of released eicosanoids from aspirin-sensitive monocytes is distinct from non-aspirin-sensitive subjects, and that these differences could contribute to the development of bronchospasm after aspirin ingestion.

Commentary: the American experience with aspirin desensitization for aspirin-sensitive rhinosinusitis and asthma.

The experience in the United States with aspirin sensitivity associated with rhinosinusitis and asthma is generally in agreement with the European perspective offered by Drs. Szczeklik and Kowalski, though our approach to challenging these patients is slightly different. Most aspirin-sensitive patients no not have a family history of aspirin sensitivity. Aspirin sensitivity is found in one third of patients having nasal polyps, rhinosinusitis, and asthma, the remaining two thirds of these patients having no adverse response to aspirin ingestion. In 85% of asthmatics who give a history of aspirin-induced bronchospasm, oral aspirin challenges are positive. Thus, a small group of patients have inappropriately assigned aspirin-sensitive asthmatic (ASA) as the cause of a prior asthmatic attack that in reality had been induced by an independent provoking factor.

Plasma Histamine After Methacholine, Allergen, and Aspirin Challenges

Plasma histamine levels were measured by radio-enzymatic technique in seven patients following 10 challenges: five methacholine challenge tests, four antigen inhalation challenge tests, and one oral aspirin challenge test. Baseline plasma histamine was the same in all patients except in the aspirin-challenged patient, who had a higher baseline histamine level. There was no statistical change in the level of histamine throughout the test in either the methacholine-challenged or the antigen-challenged patients, whereas there was a marked increase in histamine levels in the aspirin challenged patient. A possible explanation is that methacholine and antigen are inhaled and therefore have primarily local effects on the lung, whereas oral aspirin has a systemic effect with consequently systemic changes in histamine which are detectable as changes in plasma level.

The absence of detectable complement activation in aspirin-sensitive asthmatic patients during aspirin challenge

Activation of complement was sought by two independent assay methods, total hemolytic complement (CH 50) and C4 activation by rocket immunoelectrophoresis for C4d and C4 in plasma samples obtained from 16 aspirin-sensitive asthmatic patients and four control subjects during provocative oral aspirin challenges. No consistent evidence of significant complement activation was detected in either the asthmatic or control groups when serial measurements were performed. The measurements of CH 50 and C4 activation did not change in either arterial or venous samples. These findings indicate that oral aspirin given in dosages that provoke bronchospasm did not activate C4 or significantly decrease serum complement activity.

Aspirin-sensitive rhinosinusitis/asthma: spectrum of adverse reactions to aspirin

In order to determine the types of respiratory responses observed during aspirin-induced reactions, 50 consecutive asthmatic patients with -a history of aspirin sensitivity underwent prospective oral aspirin challenges between 1979 and 1981. Oral aspirin challenges produced 36 asthmatic responses (33 combined with rhinitis and three purely asthmatic) and six acute rhinoconjunetivitis responses (three combined with mild asthma and three purely rhinoconjunctivitis) but failed to stimulate any reaction in eight patients. The results produced by these challenges were then compared with results recorded during additional aspirin challenges in 28 of these patients, performed after the index challenge in 1979–1981 in 26 patients and in the case of two patients before 1979. The type of respiratory response to aspirin varied significantly in 11 (39%) of the 28 patients and included disappearance of aspirin reactivity in four patients.

Aspirin sensitive rhinosinusitis: the clinical syndrome and effects of aspirin administration

Nineteen aspirin sensitive adult patients were identified who experienced naso-ocular responses without associated bronchospasm during standardized oral aspirin challenge. These 19 patients exhibited the characteristics of the aspirin triad except asthma. These included hypertrophic rhinitis with or without associated nasal polyps, abnormal sinus roentgenograms, nasal eosinophilia, aspirin-provoked responses of the upper airway identical to those observed in aspirin-sensitive asthmatics, capacity of the upper airway to be desensitized to aspirin, and cross-reactivity andlor cross-desensitization of the upper airway to indomethacin. Of the 17 patients who were treated with daily aspirin after desensitization, 77% experienced improvement in their nasal symptoms.