DOES ACETAMINOPHEN CONTRIBUTE
TO ASTHMA MORBIDITY?

LONDON-- Frequent use of acetaminophen may be more common in adults with asthma, new research suggests. A team of British researchers recently found that frequent acetaminophen use was positively associated with asthma.[1] Furthermore, daily or weekly use of acetaminophen was also associated with more severe asthma, and in those without asthma, with rhinitis.

"This study showed that frequent--daily or weekly--use of acetaminophen was more common in adults with asthma (especially severe asthma) and rhinitis. There was no clear effect of less frequent use," Seif O. Shaheen, MD, PhD, said in a recent interview with RESPIRATORY REVIEWS. The findings suggest that acetaminophen (or paracetamol, as it is known in Europe) may play a role in asthma morbidity in adults, according to Dr. Shaheen, a senior lecturer in clinical epidemiology in the department of public health sciences at Guy's, King's, and St. Thomas' School of Medicine, King's College, London.

In their study, Shaheen et al assessed the frequency of acetaminophen and aspirin use in adults age 16 to 49 years who were enrolled in a population-based, case-control study designed to investigate the role of dietary antioxidants in asthma. Study subjects included 664 patients with asthma and 910 without asthma who completed a survey of asthma morbidity. Participants were asked to indicate how often they took acetaminophen and aspirin (daily, weekly, monthly, less than monthly, or never).

FREQUENCY OF USE

The researchers found that increasing acetaminophen use was strongly associated with asthma, particularly more severe cases. The association between acetaminophen and asthma remained even after the analysis was controlled for potential confounding risk factors (eg, sex, age, smoking status). In comparison with those who never used acetaminophen, weekly users had an odds ratio (OR) of 1.79 [95% confidence intervals (CIs), 1.21 to 2.65]; among daily users, it was 2.38 [CIs, 1.22 to 4.64]. The effect of acetaminophen was stronger in men than in women. In contrast, there was no clear relationship between aspirin use and asthma.

Shaheen et al also examined the relationship between acetaminophen use and rhinitis. Even after controlling for aspirin use and other possible confounding factors, they found an association between acetaminophen and rhinitis; in comparison with never-users of acetaminophen, weekly users and daily users had an increased prevalence of rhinitis (ORs, 1.80 [CIs, 1.11 to 2.91] and 2.33 [CIs, 1.09 to 4.96], respectively). The researchers noted that this relationship was found only in nonasthmatic subjects. No association was found between aspirin use and rhinitis.

UNDERLYING MECHANISM

The researchers offered a causal interpretation for the relationship between frequent acetaminophen use and asthma morbidity. "We do not think that aspirin avoidance can totally explain the results," Dr. Shaheen noted, "because the frequency of aspirin use was similar in the asthma patients and controls and the effect of acetaminophen was also seen in those taking aspirin. Rather, we believe that frequent acetaminophen use might make these conditions [asthma and rhinitis] worse by lowering levels of an important antioxidant in the lungs and nose," he added.

Evidence from animal studies indicates that acetaminophen can deplete the lung of the antioxidant glutathione (GSH), which is thought to play an important role in controlling airway inflammation in asthma. The researchers speculated that if acetaminophen use has similar effects in humans as in animals, "it could compromise pulmonary defenses against oxidative stress and contribute to asthma morbidity." In addition, acetaminophen has been shown to deplete immune cells of GSH, which may promote an atopic response.

Despite their findings, Shaheen et al cautioned that further research is necessary before a causal relationship between acetaminophen use and asthma is proved. They recommend that acetaminophen continue to be used in favor of other analgesics and antipyretics because of the potential risks associated with aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), including severe sensitivity reactions in those with asthma, gastrointestinal bleeding in adults, and Reye's syndrome in children.

"Acetaminophen, taken when necessary and in recommended doses, should be regarded as safe. However, individuals who are taking acetaminophen on a daily basis should try to reduce their usage and should ensure that they are not taking the drug unnecessarily or exceeding the recommended dosage," according to Dr. Shaheen. "Adults taking acetaminophen regularly should not switch to aspirin or NSAIDs, because of the potential risk of gastrointestinal bleeding and (in those with asthma) the potential risk of sensitivity reactions," he added.

--Deborah L. O'Connor

Reference
1. Shaheen SO, Sterne JAC, Songhurst CE, Burney PGJ. Frequent paracetamol use and asthma in adults. Thorax. 2000;55:266-270.