Mechanisms of aspirin-sensitive asthma

Authors

  • Sun Ying,

    1. Department of Asthma, Allergy and Respiratory Science, Guy’s, King's and St Thomas’ School of Medicine, 5th Floor, Thomas Guy House, Guy's Hospital, London, UK
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  • Christopher J Corrigan,

    1. Department of Asthma, Allergy and Respiratory Science, Guy’s, King's and St Thomas’ School of Medicine, 5th Floor, Thomas Guy House, Guy's Hospital, London, UK
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  • Tak H Lee

    1. Department of Asthma, Allergy and Respiratory Science, Guy’s, King's and St Thomas’ School of Medicine, 5th Floor, Thomas Guy House, Guy's Hospital, London, UK
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Dr Sun Ying, Department of Asthma, Allergy and Respiratory Science, Guy’s, King's and St Thomas’ School of Medicine, 5th Floor, Thomas Guy House, Guy's Hospital, London, SE1 9RT, UK. Email: ying.sun@kcl.ac.uk

Abstract

It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs), may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte−macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C4 synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT1, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E2 (PGE2) serves as a ‘brake’ to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of drugs that inhibit cysteinyl leukotriene synthesis or block the action of cysteinyl leukotrienes on their receptors, recent data suggest that PGE2, and possibly lipoxin analogs, may also prove effective in the treatment of aspirin-sensitive asthma.

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