Abstract
After completing aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD), treatment with daily aspirin in sufficiently large doses (325-1,300mg/d) has been shown to significantly suppress inflammatory respiratory disease in most patients. Four clinical observations should be recalled. First, the dose of aspirin that maintains desensitization seems to be independent of the effects of aspirin treatment. For example, 81 mg/d aspirin maintains aspirin desensitization but does not have a measureable effect on disease control. Second, other nonsteroidal anti-inflammatory drugs (NSAIDs) can be used to desensitize and maintain desensitization in patients with AERD, but daily treatment with 400 mg of ibuprofen twice daily did not induce therapeutic benefit in 5 patients followed for 1 to 6 months (D. D. S., unpublished data). Third, daily aspirin treatment of aspirin-tolerant patients who also have nasal polyps pansinusitis, and asthma has not been associated with improvement of symptoms. Finally, about two thirds of patients with AERD also have a comorbid condition of IgE-mediated disease, making it difficult to unwind these dual pathogenic processes and asses efficacy of treatment if directed at only one of the 2 diseases. Investigation of AERD continues to advance our understanding of the underlying disease, reactions, desensitization, and the clinical benefit of aspirin treatment. Despite the fortuitous discovery of the beneficial effect of chronic aspirin therapy in patients with AERD some 30 years ago, a satisfactory unifying explanation for its benefit has largely eluded us. A few key observations about the mechanism of the disease and reactions that occur in patients with AERD have beenmade. Exposure to an inhibitor of COX-1 unleashed a variety of eicosanoid lipid mediators generated from membrane phospholipids. Of these mediators, thromboxane, a potent bronchoconstrictor, is synthesized in increasing amounts in monocytes from patients with AERD when compared with levels in healthy control subjects. Prostaglandin D2 levels are increased at baseline and increase further during reactions precipitated by any NSAID. Continued synthesis of leukotrienes, specifically leukotriene (LT) C4, LTD4, and LTE4, might also be important in the pathogenesis of
Published Version
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