Bronchial aspirin challenge causes specific eicosanoid response in aspirin-sensitive asthmatics.
We have shown that inhalation of lysine aspirin enhances leukotriene production in the lungs of patients with aspirin-induced asthma (AIA). To assess the specificity of this reaction, we compared two well-matched groups of patients: eleven with AIA versus 14 asthmatics tolerant to aspirin (ATA). All subjects underwent bronchoalveolar lavage (BAL) with saline followed immediately by instillation of 10 mg of lysine aspirin, into a right middle lobe segmental bronchus, which was lavaged 15 min later. At baseline the two groups did not differ with respect to BAL fluid concentrations of cyclooxygenase products, peptido-leukotrienes, histamine, tryptase, interleukin-5 (IL-5), eosinophil cationic protein (ECP), or eosinophil number. Fifteen minutes after aspirin instillation, there was a statistically significant rise in peptido-leukotrienes, IL-5, and eosinophil number in AIA, but not in ATA, but not in ATA patients. In the former, but not in the latter group, mean histamine concentrations rose in response to aspirin, approaching the level of statistical significance. Tryptase and ECP levels showed no significant change. Aspirin significantly depressed PGE2 and thromboxane B2 (TXB2) in both groups, however PGD2, PGF2 alpha, and 9 alpha, 11 beta-PGF2 decreased only in ATA patients. A characteristic disturbance in eicosanoid balance, produced by aspirin in patients intolerant to this drug, might explain precipitation of asthma attacks.
Szczeklik
A
A
Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
Sladek
K
K
Dworski
R
R
Nizankowska
E
E
Soja
J
J
Sheller
J
J
Oates
J
J
D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D053818:Chymases; D015777:Eicosanoids / Q000096:biosynthesis*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D007958:Leukocyte Count; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D012260:Ribonucleases; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases
D001798:Blood Proteins; D015777:Eicosanoids; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D015289:Leukotrienes; D011453:Prostaglandins; D006632:Histamine; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D012260:Ribonucleases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D001241:Aspirin