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How prevalent is aspirin induced asthma?
  1. A J Knox
  1. University Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
  1. Correspondence to:
    Professor A J Knox, Division of Respiratory Medicine, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK;

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There is still much to be learned about the genetics and pathogenesis of aspirin induced asthma and the role of prostaglandins and leukotrienes in airways diseases.

The bark of the white willow Salix alba has been used in medicine for thousands of years and was described by Hippocrates in 400BC and by Dioscarides, a Greek surgeon to the Roman Army, in AD70. In the 1700s Edward Stone, the vicar of Chipping Norton, wrote that 20 grains of powered willow bark in a dram of water every 4 hours was an excellent cure for “agues”. It was only in 1829 that Leroux discovered that salicin was the active ingredient and in 1859 that Kolbe succeeded in the chemical manufacture of salicylic acid. Felix Hoffmann, a German chemist, added an acetyl group to the molecule in 1897 in an effort to increase its stability and to provide a more effective and safe treatment for his father who was crippled by rheumatism. Aspirin was born. Subsequently, benefits of aspirin have been reported in a wide range of ailments including fevers, inflammatory diseases, stroke, and heart disease. In 1971 Vane and colleagues identified the mechanism of action of aspirin as inhibition of cyclooxygenase, a key enzyme in the generation of prostaglandins from arachidonic acid.1

It has become clear, however, that not all the effects of aspirin are beneficial and this is particularly notable in the respiratory tract where a subset of patients with asthma develop an aggressive mucosal inflammatory disease within hours of ingesting aspirin and most other non-steroidal anti-inflammatory drugs (NSAIDs).2 Aspirin induced asthma forms part of a syndrome which includes rhinitis and nasal polyposis.3,4 Aspirin intolerance is associated with more severe forms of asthma and is more common in women.2 Although there are a number of theories regarding the pathogenic mechanisms involved in aspirin induced asthma, it seems to be related to inhibition of protective prostaglandins from cyclooxygenase causing an imbalance of pro-inflammatory leukotrienes.2–5 Genetic studies have shown that individuals with a polymorphism in leukotriene (LT) C4 synthase which causes them to produce larger quantities of cysteinyl leukotrienes are more prone to developing aspirin induced asthma.6,7 Most patients with asthma, however, do not bronchoconstrict to aspirin and, indeed, protective beneficial effects have been reported with both oral and inhaled cyclooxygenase inhibitors on a wide range of bronchoconstrictor challenges in patients with asthma.8

Studies of aspirin induced asthma in different populations have found prevalences ranging from 1% to 20%, with the differences being attributed either to the methods of diagnosis or differences in the populations being assessed.9–12 The study by Vally et al13 reported in this issue of Thorax looks at the prevalence of aspirin intolerant asthma in three populations of asthmatic subjects in Australia, one cohort recruited from hospital based sources, a second from the Asthma Association of Western Australia, and a third taken from a study of randomly selected individuals from a rural community. The prevalence of respiratory symptoms triggered by aspirin in all three populations was remarkably similar at 10–11%.

Estimates of the prevalence of aspirin induced asthma depend on the methods used, however. It has been suggested that the gold standard for diagnosing aspirin induced asthma should be either oral or inhaled challenge with aspirin.14 Challenge studies have suggested prevalences as high as 20% in some populations and it is possible that many patients are diagnosed who did not realise that aspirin made their asthma worse.15 Our own anecdotal experience in Nottingham of trying to identify asthmatic patients by oral challenge suggests that these patients are rather more difficult to find than one might expect, based on prevalence figures from questionnaire studies. Interestingly, in the study by Vally et al13 a number of individuals in the random cohort had not been diagnosed as asthmatic but reported respiratory symptoms with aspirin and other NSAIDs, which suggests that these individuals may suffer asthmatic symptoms when challenged with NSAIDs.

Cyclooxygenase, the enzyme responsible for production of prostanoids, exists in two isoforms—COX-1 (the constitutive form) and COX-2 (the inducible inflammatory form).16 There is evidence that the inflammatory form COX-2 is increased in both human asthma16 and in animal models of asthma.17,18 As COX-1 is predominantly involved in the production of protective housekeeping prostanoids, it has been thought that it is COX-1 inhibition which is responsible for the adverse effects of aspirin.19 If this is correct, the new selective COX-2 inhibitors should be less prone to induce aspirin induced asthma. Recent studies suggest that this is, indeed, the case and that adverse respiratory reactions are seen much less commonly with these drugs.20,21

There is clearly still much to be learned about both the genetics and pathogenesis of aspirin induced asthma and of the role of prostaglandins and leukotrienes in airways diseases. Reports such as the one from Australia13 suggest that aspirin induced asthma is an important problem for further study.

There is still much to be learned about the genetics and pathogenesis of aspirin induced asthma and the role of prostaglandins and leukotrienes in airways diseases.


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