Urinary 11-dTXB2 Research Articles

Effects of immunosuppressive agents on the hemostatic system in normal dogs.

BackgroundIn dogs, the effects of immunosuppressive medications on hemostasis are not well known.Hypothesis/ObjectivesThe objective was to determine the effects of immunosuppressive medications on primary and secondary hemostasis. Our hypothesis was that cyclosporine and prednisone would increase markers of hypercoagulability and thromboxane synthesis, while azathioprine, mycophenolate mofetil, and leflunomide would have minimal effects on hemostasis.AnimalsEight healthy dogs.MethodsA randomized, cross‐over study used aggregometry, the PFA‐100 platelet function analyzer, viscoelastometry, platelet count, and prothrombin and activated partial thromboplastin times to evaluate hemostasis during the administration of prednisone, azathioprine, cyclosporine, mycophenolate mofetil, and leflunomide for 1 week each at standard oral doses. Urine 11‐dehydro‐thromboxane‐B2 (11‐dTXB2) and 6‐keto‐prostaglandin‐F1α (6‐keto‐PGF1α) concentrations, normalized to urine creatinine concentration, were measured.ResultsThe aggregometry amplitude decreased from 51 ± 21 to 27 ± 14 (P = .002) during leflunomide treatment (ADP activation), but there were no differences in amplitude (P = .240) for any medications when platelets were activated with collagen. For all medications, there were no significant differences in viscoelastometry indices (ACT, P = .666; ClotRate, P = .340; and platelet function, P = .411) and platelet count (P = .552). Compared with pretreatment values, urinary 11‐dTXB2‐to‐creatinine ratio increased (P = .001) after drug administration (from 3.7 ± 0.6 to 5.6 ± 1.1). Cyclosporine was associated with an increase (P < .001) in the 6‐keto‐PGF1α‐to‐creatinine ratio (from 10.3 ± 4.6 to 22.1 ± 5.3).Conclusions and Clinical ImportanceMost immunosuppressive drugs do not enhance platelet function or coagulation in healthy dogs, suggesting that these medications might not predispose hypercoagulable dogs to thromboembolism. The results of our study need to be correlated with the clinical outcomes of hypercoagulable dogs.

Effects of aspirin dose escalation on platelet function and urinary thromboxane and prostacyclin levels in normal dogs.

Established "low" aspirin dosages inconsistently inhibit platelet function in dogs. Higher aspirin dosages consistently inhibit platelet function, but are associated with adverse effects. The objectives of this study were to use an escalation in dosage to determine the lowest aspirin dosage that consistently inhibited platelet function without inhibiting prostacyclin synthesis. Eight dogs were treated with five aspirin dosages: 0.5mg/kg q24h, 1mg/kg q24h, 2mg/kg q24h, 4mg/kg q24h and 10mg/kg q12h for 7days. Utilizing aggregometry and a whole-blood platelet function analyzer (PFA-100), platelet function was evaluated before and after treatment. Urine 11-dehydro-thromboxane-B2 (11-dTXB2 ) and 6-keto-prostaglandin-F1α (6-keto-PGF1α ), were measured. Compared to pretreatment, there were significant post-treatment decreases in the maximum aggregometry amplitude and increases in the PFA-100 closure times for all dosages expect 0.5mg/kg q24h. There was no difference in amplitude or closure time among the 2mg/kg q24h, 4mg/kg q24h, and 10mg/kg q12h dosages. Compared to pretreatment values, there was a significant decrease in urinary 11-dTXB2 -to-creatinine and 6-keto-PGF1α -to-creatinine ratios, but there was no dose-dependent decrease for either metabolite. An aspirin dosage of 2mg/kg q24h consistently inhibits platelet function without decreasing prostacyclin synthesis significantly more than lower aspirin dosages.

Metamizole and Platelet Inhibition by Aspirin Following On-Pump Coronary Artery Bypass Grafting

The purpose of the study was to evaluate the impact of intravenous metamizole on platelet inhibition by aspirin in patients with coronary artery disease early after on-pump coronary artery bypass grafting (CABG). Prospective, single-blind, randomized trial. Tertiary referal hospital. The study comprised 43 patients with multivessel coronary artery disease undergoing CABG. Patients were randomized to postoperative intravenous metamizole ± opioids (study group; n = 23) or opioids alone (control group; n = 20). Aspirin was withheld at least 7 days before the surgery and reinitiated (300 mg) immediately after the procedure prior to metamizole use, and continued daily thereafter (150 mg). Platelet function was evaluated using multielectrode impedance aggregometry (acid-induced platelet activation [ASPI] and collagen-induced platelet activation [COL] test), P-selectin expression and urinary 11-dehydro-thromboxane B2 (11-DTXB2) level at baseline, postoperative day (POD) 0, POD 1, POD 2, and POD 6. Residual platelet reactivity (RPR) was defined as ASPI test >400 AU*min. In all study participants, postoperative ASPI test value moderately decreased (1058.2 v 966.6 AU*min, p = 0.047), urinary 11-DTXB2 level increased (923.4 v 4367.3 pg/mg, p < 0.001), and P-selectin expression and COL test value remained stable postprocedure. The decreases of ASPI (p = 0.146) and COL test (p = 0.642), and P-selectin expression (p = 0.318) did not differ between both groups. Patients in the control group had higher postoperative increase of urinary 11-DTXB2 level (p = 0.001). The prevalence of RPR was high and comparable between study and control groups (day 1, 95.6% v 100%, p = 0.535; day 6, 100% v 90%, p = 0.21). Multivariate analysis revealed that metamizole use did not predict the fluctuations of ASPI and COL test values and P-selectin expression, yet it independently predicted postoperative change of 11-DTXB2 level (b = -0.518, p = 0.001). Intravenous metamizole preceded by a loading dose of aspirin did not modify platelet response to aspirin in the postoperative period after CABG.

The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs.

BackgroundCyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets.Hypothesis/ObjectivesOur hypothesis was that the concurrent administration of low‐dose aspirin and cyclosporine would inhibit cyclosporine‐associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis.AnimalsSeven healthy dogs.MethodsA randomized, crossover study utilized turbidimetric aggregometry and a platelet function analyzer to evaluate platelet function during the administration of low‐dose aspirin (1 mg/kg PO q24h), high‐dose aspirin (10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12h), and combined low‐dose aspirin and cyclosporine. The urine 11‐dehydro‐thromboxane‐B2 (11‐dTXB 2)‐to‐creatinine ratio also was determined.ResultsOn days 3 and 7 of administration, there was no difference in the aggregometry amplitude or the platelet function analyzer closure time between the low‐dose aspirin group and the combined low‐dose aspirin and cyclosporine group. On day 7, there was a significant difference in amplitude and closure time between the cyclosporine group and the combined low‐dose aspirin and cyclosporine group. High‐dose aspirin consistently inhibited platelet function. On both days, there was a significant difference in the urinary 11‐dTXB 2‐to‐creatinine ratio between the cyclosporine group and the combined low‐dose aspirin and cyclosporine group. There was no difference in the urinary 11‐dTXB 2‐to‐creatinine ratio among the low‐dose aspirin, high‐dose aspirin, and combined low‐dose aspirin and cyclosporine groups.Conclusions and Clinical ImportanceLow‐dose aspirin inhibits cyclosporine‐induced thromboxane synthesis, and concurrent use of these medications does not alter the antiplatelet effects of aspirin.

Comparison between urinary 11-dehydrothromboxane B2 detection and platelet Light Transmission Aggregometry (LTA) assays for evaluating aspirin response in elderly patients with coronary artery disease

Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. The aim of our study was to compare between two established methods of aspirin response, urinary 11-dehydrothromboxane B2 (11dhTXB2) and platelet Light Transmission Aggregometry (LTA) assays in elderly Chinese patients with coronary artery disease (CAD), and to investigate the clinical significance of both methods in predicting cardiovascular events. Urinary 11dhTxB2 assay and arachidonic acid-induced (AA, 0.5mg/ml) platelet aggregation by Light Transmission Aggregometry (LTAAA) assay were measured to evaluate aspirin responses. High-on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1500pg/mg or AA-induced platelet aggregation≥15.22%—the upper quartile of our enrolled population. The two tests showed a poor correlation for aspirin inhibition (r=0.063) and a poor agreement in classifying HAPR (kappa=0.053). With a mean follow-up time of 12months, cardiovascular events occurred more frequently in HAPR patients who were diagnosed by LTA assay as compared with no-HAPR patients (22.5% versus 10.6%, P=0.039, OR=2.45, 95% CI=1.06–5.63). However, the HAPR status, as determined by urinary 11dTXB2 measurement, did not show a significant correlation with outcomes.

Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin.

Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk.

Intermittent hypoxia-activated cyclooxygenase pathway: role in atherosclerosis

Intermittent hypoxia, the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to intermittent hypoxia-induced atherosclerosis remains to be determined. We studied the effects of 8-weeks of intermittent hypoxia exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of apolipoprotein E(-/-) mice. Urinary 11-dehydrothromboxane B2 (11-dTXB2) was assessed in 50 OSA subjects free of cardiovascular risk factor matched for age and body mass index with 25 controls, and 56 OSA with cardiovascular risk factor. Intermittent hypoxia significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r = 0.654, p = 0.0003) and TXBS (r = 0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in intermittent hypoxia mice only (p = 0.04). Urinary 11-dTXB2 was similar in OSA subjects free of cardiovascular risk factor and controls, but was increased by 13% (p = 0.007) in OSA subjects with cardiovascular risk factor compared with those without. Although OSA itself was not associated with increased urinary 11-dTXB2 concentration, the COX-1 pathway was activated in intermittent hypoxia-exposed mice and in OSA subjects presenting with cardiovascular risk factor, and may contribute to intermittent hypoxia-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA.

TCT-715 First Demonstration of dose Dependent Effect of Statin Therapy on Urinary 11-dehydrothromboxane B2 levels in Patients Undergoing Coronary Angiography

Background: Aspirin and statin therapy are primary treatment strategies in patients with cardiovascular disease. Heightened urinary 11-dehydrothromboxane B2(11-dTxB2) levels have been associated with an increased risk of adverse cardiovascular events. The aim of the study was to determine the effect of statin therapy on 11-dTxB2 levels in patients undergoing coronary angiography on 325 mg aspirin. Methods: Urinary 11-dTxB2 was measured in patients prior to coronary angiography with (n 155) and without (n 95) statin therapy. Lipoproteins by vertical density gradient ultracentrifugation technique and thrombin-induced platelet-fibrin clot strength(TIP-FCS), a marker for cardiovascular events by thrombelastography, were also measured. The dose dependent effect of statin therapy was analyzed according to atorvastatin equivalent dose, categorized as: 5-10mg, 20-40mg, 80mg. Results: Baseline demographics and cardiac risk factors were similar between groups. Statins significantly reduced urinary 11-dTxB2 levels in a dose dependent manner (Figure). There was a significant relation between quartiles of 11-dTxB2 and TIPFCS,(p 0.05 for ANOVA). Patients on statin therapy had significantly lower levels of LDL, triglycerides, VLDL, atherox and apo B100 (p 0.005 for all). However, Urinary 11-dTxB2 did not correlate with lipids and lipoproteins measurements. Conclusions: This is the first study to demonstrate the dose dependent response of statin therapy on urinary 11-dTxB2 levels, independent of lipid lowering effects.Clinical outcome studies are required to determine the utility of this novel marker for optimizing statin therapy. TCT-716

Aspirin Resistance in Children after Interventional Cardiac Catheterisation.

Several large trials have demonstrated the benefit of aspirin for the prevention of arterial thrombotic events in adults. Aspirin has also been increasingly used as an anti-platelet agent in children. However, very few well-designed clinical trials assessing the clinical efficacy and dosing of aspirin in children have been performed. In children, aspirin is usually administrated at a dose between 1 and 10 mg/kg/day. The term “aspirin resistance” (AR) describes the inability of aspirin to protect individuals from arterial thrombotic events (clinical AR) or the failure of aspirin to produce an expected response on laboratory measures of platelet activation and aggregation (laboratory AR). In adults, a prevalence of 5%–51% of AR had been reported, depending on the laboratory method used. A recent study using the platelet function analyser PFA-100 and levels of urinary 11-dehydrothromboxane B2 (11-dTXB2) excretion to define AR in paediatric cardiology patients, found a prevalence of 26% of laboratory AR (Heistein et al 2007). Here we studied the frequency of AR in children given aspirin at 3–5 mg/kg/d after interventional cardiac catheterization for atrial or ventricular septal defects or patent ductus arteriosus. Blood samples were taken 1–3 months after the initiation of aspirin therapy. Definition of AR was based on results from platelet aggregometry (% arachidonate-induced aggregation (AAG) of ≥ 20%) and results were compared with collagen/epinephrine closure times using the platelet function analyser PFA-100 and the levels of 11-dTXB2 excretion. As cyclooxygenase 1 (COX-1) is the primary target of aspirin and mutations could lead to a loss of functional protein, the presence of COX-1 was analyzed by western blot. Further, all children were followed clinically and side effects were monitored.Of 56 children included to date (median age: 10 y, range: 10 mo −20 y), 44 have completed the study. AR, was detected in 6 (14%) children. Of these 6 children, 3 had a normal response to aspirin (i.e. decreased AAG to <20%) after doubling the dose to 6–10 mg/kg, 1 child did not respond to a dose increase, and 2 were unavailable for further studies. Children under the age of 7 had higher urinary 11-dTXB2 levels initially compared to older children (323 vs 178 ng/mmol creatinine; p< 0.001). During aspirin therapy, 11-dTXB2 levels decreased to 38 ± 15 ng/mmol creatinine (mean ± SD). However, in 2 children, 11-dTXB2 decreased only minimally (81 and 84% of pre-aspirin level, respectively; results > mean+2SD ): Of these 2 children, one child had AR by the AAG definition even after aspirin dose increase and the other revealed AR by the PFA-100, with normal closure time, but not by AAG. While PFA-100 closure times were prolonged in 48% of children already prior to administration of aspirin, all children with AR according to AAG had prolonged closure times during aspirin-therapy. All 6 AR patients and 10 patients with a normal response to aspirin by AAG demonstrated equal amounts of COX-1 by western blot. While 6 children (14%) showed easy bruising and epistaxis during aspirin therapy, no severe bleeding or thrombotic complications were recordedIn conclusion, AR was detected in 14% of children after interventional cardiac catheterization by AAG and could be overcome in some patients by increasing the dose of aspirin. These results are in keeping with findings from adults. By the use of the PFA-100 a previous study found a prevalence of 26% of AR in children (Heistein et al 2007). However, the authors did not correlate these results to AAG. In our cohort, the assessment of AR by the PFA100 was hampered by a high rate of abnormal PFA results previous to the initiation of therapy. Although reduction of 11-dTXB2 excretion indicates an inhibition of the COX-1 pathway by aspirin therapy, 11-dTXB2 and AAG results were not always congruent.

Targeting the urine and plasma determinants of thromboxane A2 metabolism in detection of aspirin effectiveness

Detection of reduced aspirin effectiveness has gained significant importance since clinical consequences of aspirin resistance were reported. Nevertheless, due to differentiated molecular basis of aspirin resistance, the conflicting choice of referential method for detection of acetylsalicylic acid ineffectiveness has become troublesome. This study, using a rat model of antiplatelet therapy, examines the aptitude of selected TXB2 metabolism-based methods in the detection of acetylsalicylic acid effectiveness. We hypothesized that ex-vivo whole blood spontaneous TXB2 generation assay could be, contrary to basal TXB2 and urine 11-dTXB2, a novel surrogate measure for impaired acetylsalicylic acid-dependent inhibition of thromboxane synthesis. To address this hypothesis, we evaluated the sensitivity of TXB2 generation assay in hirudinized whole blood to detect acetylsalicylic acid-mediated inhibition of cyclooxygenase activity in healthy rats and diabetic rats treated with acetylsalicylic acid. In diabetic and control animals, both acetylsalicylic acid drenches in the dose-independent manner contributed to significant attenuation of basal plasma TXB2 and urinary 11-dTXB2 formation. Urinary concentrations of 11-dTXB2 were, contrary to basal TXB2, significantly higher, regardless of acetylsalicylic acid dose, among all diabetic groups, compared with corresponding control groups. Determination of TXB2 generation in whole blood enabled sensitive detection of dose-related acetylsalicylic acid effect in both groups, as well as increased TXB2 formation in diabetes. We showed for the first time that evaluation of spontaneous generation of TXB2 in hirudinized whole blood enables, contrary to basal plasma TXB2 and urine 11-dTXB2 concentrations, to sensitively determine the acetylsalicylic acid effect in healthy and diabetic subjects.

Measurement of urinary 11-dehydro-thromboxane B2 excretion in dogs with gastric dilatation-volvulus

To measure 11-dehydro-thromboxane B2 (11-dTXB2) in urine of healthy control dogs, dogs undergoing ovariohysterectomy, and dogs with gastric dilatation-volvulus (GDV) and assess the relationship between urinary 11-dTXB2 concentrations in dogs with GDV and postoperative outcomes. Urine samples from 15 nonsurgical control dogs, 12 surgical control dogs, and 32 dogs with GVD. Urine samples were obtained from healthy pet dogs (ie, nonsurgical control dogs), dogs undergoing ovariohysterectomy at anesthetic induction and 1 hour following surgery (ie, surgical control dogs), and dogs with GDV at hospital admission and 1 hour following surgical derotation of the stomach (ie, GDV dogs). Urinary 11-dTXB2 concentrations were determined with an ELISA and normalized to urinary creatinine (Cr) concentrations by calculation of the 11-dTXB2 -to-Cr ratio. Differences in median 11-dTXB2 -to-Cr ratios among dogs and before and after surgery were analyzed. Urinary 11-dTXB2-to-Cr ratios did not differ between nonsurgical control dogs and surgical control dogs before or after surgery. Urinary 11-dTXB2-to-Cr ratios were significantly higher in GDV dogs at the time of hospital admission and 1 hour after surgery, compared with those of nonsurgical control dogs. Postoperative urine samples from GDV dogs had significantly higher 11-dTXB2-to-Cr ratios than postoperative urine samples from surgical control dogs. Median urinary 11-dTXB2-to-Cr ratios increased significantly in GDV dogs that developed postoperative complications. Urinary 11-dTXB2 concentration is increased in GDV dogs at the time of hospital admission and after surgical derotation of the stomach, compared with that of healthy dogs. An increased urinary 11-dTXB2-to-Cr ratio following surgery is associated with an increased incidence of postoperative complications in dogs with GDV.

スポット尿中１１‐ｄｅｈｙｄｒｏ‐Ｔｈｒｏｍｂｏｘａｎｅ Ｂ２レベルによるアスピリン耐性患者のスクリーニングは可能か？

Thromboxane A2 (TXA2) is produced from arachidonic acid by cyclooxygenase-1 (COX-1) in thrombocytes and for the most part is converted to 11-dehydro-thromboxane B2 (11dTXB2), the final stable metabolite. Since daily excretion amounts of 11dTXB2 in urine are well correlated with the degree of inhibition of COX-1 by aspirin, inhibition is evaluated by measuring 11dTXB2 excretion and this is usually done through 24-hour urine collection. However, as this involves a lot of work, we examined the validity of using spot urine measurements for this purpose. The intra-day variation in urinary 11dTXB2 levels was studied in five patients who had been taking low-dose aspirin for an extended period. Urinary concentrations of 11dTXB2 were measured using a commercial enzyme immunoassay kit and the urinary excretion rate of 11dTXB2 was expressed as the ratio of the concentration of 11dTXB2 to that of creatinine. The results showed that there was no marked variation in intra-day urinary excretion rates and that the range of variation from 24-hour urine measurements was no more than about 15%. They therefore indicate that spot urine could be used in place 24-hour urine collection for measuring 11dTXB2 levels.

尿中１１‐ｄｅｈｙｄｒｏ‐Ｔｈｒｏｍｂｏｘａｎｅ Ｂ２の日内変動に関する検討

Thromboxane A2 (TXA2) is produced from arachidonic acid by cyclooxygenase-1 (COX-1) in thrombocytes and for the most part is converted to 11-dehydro-thromboxane B2 (11d-TXB2), the final stable metabolite.Daily excretion amounts of 11d-TXB2 in urine are well correlated with the extent of inhibition of COX-1 by aspirin. Since the collection of 24-hour urine that is generally used for such evaluation is a lot of work, we studied the validity of using spot urine for this purpose. The intra-day variation in urinary 11d-TXB2 levels was studied in six healthy volunteers. Urinary concentrations of 11d-TXB2 were measured using a commercial enzyme immunoassay kit. The urinary excretion rate of 11d-TXB2 was expressed as the concentration ratio of 11d-TXB2 vs. creatinine. The results showed that there was no marked variation in intra-day urinary excretion rates, the range being within of that for urine collected over 24 hours for each volunteer. However, the urinary excretion rate of 11d-TXB2 was slightly decreased at around 7 pm for almost all of the volunteers. These results indicated that spot urine could be used in place of 24-hours urine collection for evaluating 11d-TXB2 levels.

Correlation among urinary eosinophil protein X, leukotriene E4, and 11-dehydrothromboxane B2 in patients with spontaneous asthmatic attack.

Various kinds of cells and their mediators are thought to be involved in the pathogenesis of bronchial asthma. However, changes in each mediator or relationship among mediators during an asthmatic attack have not been well documented. In this study, to clarify whether eosinophil protein X (EPX) is a marker which is distinct from leukotriene E4 (LTE4), or 11-dehydrothromboxane B2 (11DTXB2), we measured the urinary excretion of EPX, LTE4, and 11DTXB2 in 14 asthmatics who were admitted to the hospital with either an acute asthmatic attack or status asthmaticus. These patients included eight atopic and six non-atopic types of bronchial asthma, with a median age of 34.0 years. Urinary excretion of EPX was significantly high on admission with the asthmatic attack, and returned to control levels 175 [122 -384] microg/day when the patients were in the improved state (1036-317 microg/day, P < 0.01). Similar findings were observed in LTE4 (155-59 ng/day, P < 0.01) and 11DTXB2 (991-442ng/day, P<0.01). No significant differences in values were observed between atopic and non-atopic types of asthma in all three substances. When the individual data during the attack state were analysed, a significant correlation was observed between changes (%) in urinary EPX and those in urinary LTE4, but no such relationship was observed between changes (%) in urinary EPX and those in urinary 11DTXB2. These results suggest that measuring urinary EPX levels may be a useful marker for the understanding and management of the disease.

Urinary leukotriene E4 and 11‐dehydrothromboxane B2 in patients with aspirin‐sensitive asthma

The objective of this study was to define the participation of cysteinyl leukotrienes (LTs) or thromboxane A2 in the pathogenesis of aspirin-sensitive asthma (ASA). Leukotriene E4 (LTE4) and 11-dehydrothromboxane B2 (11DTXB2) values in spot urine were measured in 22 asthmatics with a history of aspirin sensitivity and in 17 without such a history (non-aspirin-sensitive asthma [NASA]) in the outpatient clinic. The urinary LTE4 value was significantly higher in ASA patients than in NASA (340 +/- 47 vs 65 +/- 15 pg/mg.cr, P < 0.001), but there was no significant difference in urinary 11DTXB2 between the two groups (891 +/- 77 vs 657 +/- 90 pg/mg.cr). A high value of LTE4 was not associated with type of asthma, severity of disease, oral prednisolone treatment, sex, or age. A higher value of 11DTXB2 was observed in the atopic type than the nonatopic type in ASA (1086 +/- 111 vs 697 +/- 147 pg/mg.cr, P < 0.05). No correlation was observed between urinary LTE4 and 11DTXB2 in either ASA or NASA. In conclusion, LTs may play an important role in the pathogenesis of ASA, and TXA2 in the pathogenesis of the atopic type in ASA.