, Volume 64, Issue 21, pp 2417–2432 | Cite as

Aspirin-Induced Asthma

Clinical Aspects, Pathogenesis and Management
  • Ahmed M. Hamad
  • Amy M. Sutcliffe
  • Alan J. Knox
Review Article


Aspirin (acetylsalicylic acid)-induced asthma (AIA) consists of the clinical triad of asthma, chronic rhinosinusitis with nasal polyps, and precipitation of asthma and rhinitis attacks in response to aspirin and other NSAIDs. The prevalence of the syndrome in the adult asthmatic populations is approximately 4–10%. Respiratory disease in these patients may be aggressive and refractory to treatment.

The aetiology of AIA is complex and not fully understood, but most evidence points towards an abnormality of arachidonic acid (AA) metabolism. Cyclo-oxygenase (COX), the rate-limiting enzyme in AA metabolism, exists as two main isoforms. COX-1 is the constitutive enzyme responsible for synthesis of protective prostanoids, whereas COX-2 is induced under inflammatory conditions. A number of theories regarding its pathogenesis have been proposed. The shunting hypothesis proposes that inhibition of COX-1 shunts AA metabolism away from production of protective prostanoids and towards cysteinyl leukotriene (cys-LT) biosynthesis, resulting in bronchoconstriction and increased mucus production. The COX-2 hypothesis proposes that aspirin causes a structural change in COX-2 that results in the generation of products of the lipoxygenase pathway. It is speculated that this may result in the formation of mediators that cause respiratory reactions in AIA.

Related studies provide evidence for abnormal regulation of the lipoxygenase pathway, demonstrating elevated levels of cys-LTs in urine, sputum and peripheral blood, before and following aspirin challenge in AIA patients. These studies suggest that cys-LTs are continually and aggressively synthesised before exposure to aspirin and, during aspirin-induced reactions, acceleration of synthesis occurs. A genetic polymorphism of the LTC4S gene has been identified consisting of an A to C transversion 444 nucleotides upstream of the first codon, conferring a relative risk of ALA of 3.89. Furthermore, carriers of the C444 allele demonstrate a dramatic rise in urinary LTE4 following aspirin provocation, and respond better to the cys-LT antagonist pranlukast than A444 homozygotes.

AIA patients have an aggressive form of disease, and treatment should include combination therapy with inhaled corticosteroids, β2-adrenoceptor agonists and LT modifiers. Furthermore, recently developed inhibitors of COX-2 may be safer in patients with AIA.


Aspirin PGE2 Salmeterol Nasal Polyposis Zileuton 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dr Hamad is supported by a grant from the Wellcome Trust. No other sources of funding were used to assist in the prepration of this review. The authors have no conflicts of interest to declare.


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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Ahmed M. Hamad
    • 1
  • Amy M. Sutcliffe
    • 2
  • Alan J. Knox
    • 2
  1. 1.Department of Respiratory MedicineAl-Mansourah UniversityAl-DakahliaEgypt
  2. 2.Department of Respiratory MedicineUniversity of NottinghamNottinghamUK

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