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MEDIA BRIEFING
13th March 2008

Aspirin reduces the risk of developing asthma in women

Summary
Women who regularly take low dose aspirin have a lower risk of developing asthma, a new analysis of the Women's Health Study suggests.(1)

The study showed that, over a 10-year period, women who took aspirin 100 mg every other day had a 10 per cent lower risk of developing asthma compared with women taking placebo. This effect was the same regardless of age (over 45), smoking status and exercise levels but was not apparent in women who were obese.

This finding follows earlier evidence that aspirin is associated with a reduced risk of developing asthma in healthy men (in the Physicians' Health Study (2)) and in women (in the Nurses' Health Study (3)).

How was the new study carried out?
The Women's Health Study was a randomised, placebo-controlled, double-blind trial to evaluate the risks and benefits of taking aspirin (100 mg every other day) and/or vitamin E (600 IU every other day) in 39,876 American women. The trial began in 1993 and ended in 2004

Women who joined the study were health professionals aged at least 45 years. They were apparently healthy; women who already had asthma were excluded from this analysis, leaving a study population of 37,270.

What were the results?
This analysis compared the incidence of newly diagnosed asthma in women who were taking aspirin with those who were not.

During an average follow-up period of 9.7 years, a total of 1,835 new cases of asthma were identified. Of these, 872 occurred among women taking aspirin (4.68 per cent) and 963 among those taking placebo (5.17 per cent). This is equivalent to a 10 per cent reduction in the relative risk of asthma in women taking aspirin.(a)

The risk reduction among women taking aspirin became apparent after 6 years and was increasing continuously (that is to say, longer aspirin use was associated with a lower risk of asthma).

The risk reduction associated with aspirin was not affected by age, smoking status, levels of exercise, use of hormone replacement therapy, or vitamin E use. However, there was no risk reduction among women who were obese.(b)

Interpretation


The authors state:
In this large, randomised, double-blind, placebo-controlled trial in apparently healthy women, 100 mg aspirin every other day significantly reduced the relative risk of newly reported adult onset asthma diagnosis by 10 per cent. The magnitude of the reduction was similar across subgroups of age, smoking status, exercise, postmenopausal hormone intake and randomised vitamin E intake but was absent in those who were obese.

They conclude:

However, before public recommendations are provided, results from randomised trials are needed that are specifically designed to test whether low-dose aspirin reduces the risk of asthma.

They note that this is not the first study to find an association between taking aspirin and a reduced risk of asthma.

• The Physicians' Health Study(2) found that men who took aspirin 325 mg on alternate days had a 22 per cent lower risk of developing asthma compared with those taking placebo.
• The Nurses Health Study,(3) an observational study comparing women who reported taking aspirin on at least 15 days a month with those reporting no use, found that aspirin was associated with a 40 per cent lower risk of developing asthma.

The authors caution that aspirin may worsen symptoms in a minority of people who already have asthma.

How might aspirin affect the risk of developing asthma?
The mechanism by which aspirin reduces the risk of developing asthma is unknown. It is possible that aspirin alters the immunological events that affect the airways in people with asthma via its effects on the enzyme cyclo-oxygenase. Asthma is associated with a particular type of inflammatory reaction known as the Th2 response (due to the predominance of events associated with Th2 lymphocytes); aspirin may inhibit this and instead promote a Th1 response, reducing susceptibility to asthma. The authors say this theory is biologically plausible but there is currently no definitive evidence to support it and alternative mechanisms may also be important.

It is also unknown why aspirin appeared to have no effect in obese women. It may be because asthma is different in this group or because the dose of aspirin was proportionately smaller when expressed according to bodyweight.

What were the strengths and weaknesses of the trial?
The strengths of this trial were:

• its design (randomised, placebo-controlled, double-blind)
• the large number of women who participated
• the large number of cases of asthma identified

Its limitations were:
• the participants were apparently healthy, predominantly white women who were health professionals and it is uncertain whether the results can be extrapolated to other groups
• it was not specifically designed to test the effects of aspirin on the risk of asthma (though it had adequate statistical power to do so)
• asthma diagnoses were reported by the participants (though this would be random and not expected to favour aspirin)


References
1. Kurth T, Barr RG, Gaziano JM, Buring JE. Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study. Thorax 2008 doi:10.1136/thx.2007.091447

2. Barr RG, Kurth T, Stampfer MJ et al. Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians’ health study. Am J Respir Crit Care Med 2007;175:120–5.

3. Barr RG, Wentowski CC, Curhan GC et al. Prospective study of acetaminophen use and newly diagnosed asthma among women. Am J Respir Crit Care Med 2004;169:836–41.


Notes

a. The relative risk reduction was calculated as a hazard ratio of 0.90 with 95% confidence intervals of 0.82 to 0.99. This was statistically significant (p=0.027).

b. Obesity was defined as body mass index =30 kg/m2, which is the standard used in the UK.