Clinical Reviews in Allergy & Immunology

, Volume 24, Issue 2, pp 169–187

Pathogenesis of aspirin-exacerbated respiratory disease



The underlying respiratory disease is activated by unknown mechanism and results in an intense infiltration of mast cells and eosinophils into the entire respiratory mucosa. These cells synthesize leukotrienes (LTs) at a very high rate and mast cells also release histamine and tryptase and synthesize PGD2 a vasodilator and bronchoconstrictor. Furthermore, AERD patients under synthesize from arachidonic acid (AA) a peculiar product called lipoxins, which opposes inflammation generated by leukotrienes. Finally, cysLT1 receptors are over expressed and highly responsive to LTE4, further augmenting the underlying inflammatory disease.

This inflammatory condition is partly inhibited by synthesis of PGE2 through COX-1. PGE2 partially inhibits 5-lipogygenase conversion of AA to LTA4 and blocks release of histamine and tryptase from mast cells. When COX-1 is inhibited by ASA or NSAIDs, PGE2 synthesis stops and an enormous release of histamine and synthesis of LTs occurs. The upper respiratory reaction is mediated by both histamine and LTs but the bronchospastic reaction is mediated by LTs. The systemic effects of flush, gastric pain and hives are mediated by histamine.

Aspirin desensitization can not be explained by disappearance of LT synthesis since urine LTE4 levels are still elevated at acute ASA desensitization. However, mast cell products such as histamine, tryptase and PGD2 are no longer released or synthesized at acute desensitization. It is more likely that a diminution in number or function of cysLT receptors accounts for the diminished inflammatory response found in ASA desensitization.

Index Entries

Aspirin-exacerbated respiratory disease (AERD) leukotrienes (LTs) leukotriene E4 (LTE4leukotriene A4 (LTA4Cysteinyl leukotriene receptors (cysLTR) prostaglandin E2 (PGE2prostaglandin G2 (PGD2arachidonic acid (AA) 


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Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  1. 1.Allergy and Immunology DivisionScripps Clinic and The Scripps Research InstituteLa Jolla
  2. 2.Department of Experimental and Molecular MedicineThe Scripps Clinic and Research InstituteLa Jolla

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