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 as pirin but the mechanisms by which this happens are unknown. To test th e hypothesis that there may be a reduction in aspirin-induced leukotri ene release following aspirin densensitization, we studied nine patien ts 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 me asured before and after ingestion of a threshold dose of aspirin leadi ng to a 15% decrease in FEV(1), and then at intervals following desens itization, when a maintenance dose of 600 mg aspirin was ingested. Pri or to desensitization, the maximum decrease in FEV(1) following ingest ion 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 1,71 4 +/- 783 pg/mg creatinine at 3 h. Immediately after acute desensitiza tion, 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) i ncreased 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 ba sal level of 432 +/- 127 pg/mg creatinine to 749 +/- 257 pg/mg creatin ine 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, sub stantial amounts of LTE(4) were still produced without any significant change in lung function. Chronic aspirin ingestion continues to downr egulate urinary LTE(4) excretion in response to aspirin. Aspirin desen sitization is accompanied by a reduced aspirin-induced production of s ulfidopeptide leukotrienes.