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Published on: November 4, 2010
Aspirin-induced asthma: clinical aspects, pathogenesis and management
Ahmed M Hamad1, Amy M Sutcliffe, Alan J Knox
1Department of Respiratory Medicine, Al-Mansourah University, Al-Dakahlia, Egypt.
Drugs
|October 16, 2004
Summary
Aspirin-induced asthma (AIA) involves abnormal arachidonic acid metabolism, leading to increased cysteinyl leukotrienes and severe respiratory reactions. Genetic factors and LT modifiers play key roles in AIA pathogenesis and treatment.
Area of Science:
- Immunology
- Pharmacology
- Genetics
Background:
- Aspirin (acetylsalicylic acid)-induced asthma (AIA) is a clinical triad of asthma, chronic rhinosinusitis with nasal polyps, and NSAID-induced respiratory attacks.
- Affecting 4-10% of adult asthmatics, AIA can present as aggressive, treatment-refractory disease.
- The underlying cause is complex, with strong evidence pointing to dysregulated arachidonic acid (AA) metabolism.
Purpose of the Study:
- To explore the role of arachidonic acid (AA) metabolism in Aspirin (acetylsalicylic acid)-induced asthma (AIA) pathogenesis.
- To investigate the link between cyclooxygenase (COX) and lipoxygenase pathways in AIA.
- To identify genetic factors and therapeutic targets for AIA.
Main Methods:
- Review of existing literature on AIA pathogenesis, focusing on AA metabolism.
- Analysis of studies investigating cyclooxygenase (COX) and lipoxygenase pathways.
- Examination of genetic polymorphisms in the LTC4S gene and their association with AIA.
Main Results:
- Evidence suggests a shunting of AA metabolism from protective prostanoids towards cysteinyl leukotrienes (cys-LTs) upon COX inhibition.
- Elevated cys-LTs are found in AIA patients, with increased synthesis during aspirin challenges.
- A specific LTC4S gene polymorphism (C444 allele) confers a 3.89-fold increased risk of AIA and predicts better response to cys-LT antagonists.
Conclusions:
- AIA pathogenesis involves abnormal AA metabolism, particularly increased cys-LT production.
- Combination therapy including LT modifiers is recommended for AIA management.
- COX-2 inhibitors may offer a safer treatment option for AIA patients.
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