THE EFFECT OF ASPIRIN DESENSITIZATION ON URINARY LEUKOTRIENE E(4) CONCENTRATIONS IN ASPIRIN-SENSITIVE ASTHMA

Patients with aspirin sensitive asthma (ASA) can be desensitized to aspirin but the mechanisms by which this happens are unknown. To test the hypothesis that there may be a reduction in aspirin-induced leukotriene release following aspirin densensitization, we studied nine patients with ASA, 37 +/- 2.3 yr of age (mean +/- SEM) with a baseline FEV(1) of 94 +/- 3.5%. Urinary leukotriene E(4) (LTE(4)) and FEV(1) were measured before and after ingestion of a threshold dose of aspirin leading to a 15% decrease in FEV(1), and then at intervals following desensitization, when a maintenance dose of 600 mg aspirin was ingested. Prior to desensitization, the maximum decrease in FEV(1) following ingestion of a threshold dose of aspirin was 15.3 +/- 3.9%, and urinary LTE(4) rose from a baseline value of 235 +/- 79.4 pg/mg creatinine to 1,714 +/- 783 pg/mg creatinine at 3 h. Immediately after acute desensitization, which was performed over several days, 600 mg aspirin provoked a maximum decrease in FEV(1) of only 3.3 +/- 2.4%, and urinary LTE(4) increased from a baseline of 645 +/- 223 pg/mg creatinine to 1,256 +/- 456 pg/mg creatinine. Following ingestion of 600 mg aspirin for 9 +/- 3.2 mo (n = 5; chronic desensitization), urinary LTE(4) rose from a basal level of 432 +/- 127 pg/mg creatinine to 749 +/- 257 pg/mg creatinine at 3 h after 600 mg aspirin, and this was accompanied by a maximum decrease in FEV(1) of 7.4 +/- 4.5%. Although there was significantly less aspirin-induced LTE(4) excretion after acute desensitization, substantial amounts of LTE(4) were still produced without any significant change in lung function. Chronic aspirin ingestion continues to downregulate urinary LTE(4) excretion in response to aspirin. Aspirin desensitization is accompanied by a reduced aspirin-induced production of sulfidopeptide leukotrienes.