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The pathogenesis of aspirin-sensitive asthma remains unknown. Using a new model of platelet activation, initially described as a response of platelets to IgE antibody-dependent stimuli, this study was designed to test the hypothesis of a possible involvement of platelets in aspirin-sensitive asthma. Washed platelets from 35 aspirin-sensitive asthmatics showed an abnormal in vitro response to cyclooxygenase inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs)--aspirin, indomethacin or flurbiprofen--characterized by the generation of a cytocidal supernatant and (14 patients explored) a burst of chemiluminescence; these drugs had no similar effect on platelets from 31 controls (p less than 0.0001). It was shown that the abnormal platelet response to NSAIDs was not mediated by IgE. In contrast to platelets, aspirin-sensitive asthmatic leukocytes generated neither cytocidal factors nor chemiluminescence in the presence of NSAIDs. Sodium salicylate and salicylamide, which, though structurally similar to aspirin, do not inhibit cyclooxygenase and are well tolerated by aspirin-sensitive asthmatics, did not activate their platelets to release cytocidal factors. Moreover, preincubation of platelets with sodium salicylate, salicylamide or prostaglandin endoperoxide PGH2, highly prevented their abnormal response to NSAIDs (greater than 80%; p less than 0.0001). Since several lipoxygenase inhibitors (NDGA, esculetin), including inhibitors of both cyclooxygenase and lipoxygenase (ETYA, BW755c), did not activate patient platelets and prevented the subsequent abnormal response to NSAIDs, it is suggested that the abnormal platelet activation by NSAIDs is not only the consequence of an inhibition of cyclooxygenase, but also involves generation of lipoxygenase metabolites of arachidonate. Besides, platelets from 4 aspirin-sensitive asthmatics undergoing aspirin desensitization were found to have completely lost their abnormal responsiveness to NSAIDs. These findings represent the first identification in aspirin-intolerant asthmatics of a specific abnormal cellular response to drugs inducing asthmatic attacks and open new perspectives into the pathogenesis, prevention and diagnosis of this disease. They also provide support to the concept of a role for platelets in asthma.
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
June 1992,
Nihon Kyobu Shikkan Gakkai zasshi,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
July 1977,
British medical journal,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
February 2001,
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
May 1954,
Medicinski glasnik,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
February 1992,
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
April 2005,
Internal medicine journal,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
March 1985,
Chest,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
December 1981,
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J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
August 2008,
Allergy,
J C Ameisen, and
A Capron, and
M Joseph, and
J Maclouf, and
H Vorng, and
V Pancré, and
E Fournier, and
B Wallaert, and
A B Tonnel
March 1996,
International archives of allergy and immunology,
