Effects of cysteinyl-leukotriene receptor antagonist, thromboxane A2 receptor antagonist, and thromboxane A2 synthetase inhibitor on antigen-induced bronchoconstriction in patients with asthma.
BACKGROUND
Leukotriene (LT) and thromboxane A2 (TXA2) receptor antagonists have been used in the treatment of asthma.


OBJECTIVE
We examined the effects of an LT receptor antagonist, TXA2 receptor antagonist, and TXA2 synthetase inhibitor on bronchoprovocation test (BPT) in patients with mild-to-moderate atopic asthma.


METHODS
BPT was performed four times in each of six asthmatics. Development of the immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) was confirmed on the first BPT (BPT1). After a 7-day washout period, an LT receptor antagonist (pranlukast, 450 mg/d), TXA2 receptor antagonist (seratrodast, 80 mg/d), or TXA2 synthetase inhibitor (ozagrel, 800 mg/d) was administered orally over 7 days at random using a cross-over method (BPT2-4). Blood levels of LTB4, LTC4, LTD4, 11-dehydrothromboxane B2, eosinophil cationic protein, and histamine were measured at reaction phases of pre-BPT, IAR, and LAR.


RESULTS
Administration of pranlukast suppressed IAR by 80.5% (p < 0.0001) and LAR by 54.6% (p = 0.0391). Ozagrel significantly suppressed IAR by 39.5% (p = 0.0413), but the fall in FEV1 was >20% (21.56+/-4.173%). Seratrodast did not suppress IAR or LAR. Blood levels of chemical mediators did not correlate with the suppressive effects of the tested drugs.


CONCLUSIONS
The LT receptor antagonist was considered to be the most effective. LT might play a more important role in the pathogenesis of asthma than TXA2. Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma.
Obase
Y
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan. obadann-ngs@umin.u-tokyo.ac.jp
Shimoda
T
T
Matsuo
N
N
Matsuse
H
H
Asai
S
S
Kohno
S
S
D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000941:Antigens / Q000009:adverse effects; D001249:Asthma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D016227:Benzoquinones / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002867:Chromones / Q000627:therapeutic use*; D018592:Cross-Over Studies; D047091:Eosinophil Granule Proteins; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006632:Histamine / Q000097:blood; D006801:Humans; D020024:Leukotriene Antagonists; D008297:Male; D008565:Membrane Proteins; D008689:Methacrylates / Q000627:therapeutic use*; D018077:Receptors, Leukotriene / Q000097:blood; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000097:blood; D012260:Ribonucleases; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; D000941:Antigens; D016227:Benzoquinones; D001798:Blood Proteins; D002867:Chromones; D047091:Eosinophil Granule Proteins; D006538:Heptanoic Acids; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D008689:Methacrylates; D018077:Receptors, Leukotriene; D017482:Receptors, Thromboxane; C060230:seratrodast; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D006632:Histamine; C412375:cysteinyl leukotriene receptor 2; D012260:Ribonucleases; D013930:Thromboxane-A Synthase; C034364:ozagrel; C083169:leukotriene D4 receptor; C047681:pranlukast