The effect of aspirin desensitization on urinary leukotriene E4 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 desensitization, we studied nine patients with ASA, 37 +/- 2.3 yr of age (mean +/- SEM) with a baseline FEV1 of 94 +/- 3.5%. Urinary leukotriene E4 (LTE4) and FEV1 were measured before and after ingestion of a threshold dose of aspirin leading to a 15% decrease in FEV1, and then at intervals following desensitization, when a maintenance dose of 600 mg aspirin was ingested. Prior to desensitization, the maximum decrease in FEV1 following ingestion of a threshold dose of aspirin was 15.3 +/- 3.9%, and urinary LTE4 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 FEV1 of only 3.3 +/- 2.4%, and urinary LTE4 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 LTE4 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 FEV1 of 7.4 +/- 4.5%. Although there was significantly less aspirin-induced LTE4 excretion after acute desensitization, substantial amounts of LTE4 were still produced without any significant change in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)
Nasser
S M
SM
Department of Allergy and Allied Respiratory Disorders, Guy's Hospital, London, United Kingdom.
Patel
M
M
Bell
G S
GS
Lee
T H
TH
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy* / Q000652:urine; D003404:Creatinine / Q000652:urine; D003888:Desensitization, Immunologic; D004342:Drug Hypersensitivity / Q000628:therapy* / Q000652:urine; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged
D017999:Leukotriene E4; D003404:Creatinine; D001241:Aspirin