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)
Dept of Medicine, Copernicus University School of Medicine, Cracow, Poland.
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Szczeklik
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D053818:Chymases; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D017999:Leukotriene E4; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D016210:Methacholine Chloride; D008875:Middle Aged; D012260:Ribonucleases; D013189:SRS-A / Q000031:analogs & derivatives* / Q000652:urine; D012697:Serine Endopeptidases / Q000097:blood; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D053802:Tryptases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D013189:SRS-A; D016210:Methacholine Chloride; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D012260:Ribonucleases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D001241:Aspirin