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NOTTINGHAM, England, May 2-Now it's Tylenol's turn in the revenge of the painkillers.

Frequent use of acetaminophen, the over-the-counter painkiller found in Tylenol and many other analgesics, has been associated with an increased risk for asthma, chronic obstructive pulmonary disease (COPD), and decreased lung function.

In a retrospective health survey of more than 13,000 Americans, which was analyzed here, researchers found that frequent acetaminophen users were more likely to have lung disease than those who never or seldom used it. In contrast, neither ibuprofen (Motrin, Nuprin) nor aspirin use was associated with lung problems in this study.

The report comes on the heels of an FDA public health advisory three weeks ago on the entire class of non-steroidal anti-inflammatory drugs (NSAIDs) for pain, with the exception of aspirin. Acetaminophens such as Tylenol, which are not NSAIDs, were not included in the FDA advisory.

In December the FDA said that acetaminophen is an active ingredient found in more than 600 over-the-counter and prescription medicines, such as pain relievers, cough suppressants and cold medications. "It is safe and effective when used correctly, but taking too much can lead to liver damage," the FDA said.

A link between acetaminophen and asthma, as well as aspirin, has been seen in other studies, but this is the first to detect a dose-related association between the popular painkiller and other serious lung diseases. The authors reported this in a study published in the May issue of the American Journal of Respiratory and Critical Care Medicine.

Acetaminophen has been shown in animal studies to reduce levels of the antioxidant glutathione, which is found in high concentrations in epithelial lung fluid. This could put users of the drug at risk for increased oxidative damage to lung tissues and subsequent respiratory disease, says Tricia M. McKeever, Ph.D., of the University of Nottingham and colleagues in the Netherlands and U.S.

"Increased use of acetaminophen was also associated with decreased lung function, although this effect was seen only in participants reporting either daily or greater use of acetaminophen," Dr. McKeever says.

The study drew on data from the Third National Health and Nutrition Examination Survey (NHANES III), and included information on more than 13,000 men and women between the ages of 20 and 80 years.

Participants who reported regular acetaminophen use (6-29 times per month), had a 40% greater risk (adjusted odds ratio =1.40) of having asthma, and daily users had a 75% greater risk. In contrast, no statistically significant differences were seen in asthma risk among aspirin or ibuprofen users.

Similarly, acetaminophen use, but not ibuprofen or aspirin use, was linked to higher risk of COPD, with daily users being at 72% increased risk, even when the data were adjusted for confounding variables such as smoking, race, and use of other pain medications.

Acetaminophen use was also seen to negatively affect lung function, as measured by forced expiratory volume (FEV₁). Daily users of acetaminophen had a mean adjusted FEV₁ that was 61.5 ml (95% CI, -97.5 to -25.4) lower than nonusers, and the regression coefficient was only slightly attenuated after adjusting for use of other pain medication (-54.0 ml; 95% CI, -90.3 to -17.7), and after exclusion of subjects with asthma (-46.9 ml; 95% CI, -89.4 to -4.5).

"The potential risk of acetaminophen must ultimately be estimated through a balanced consideration of the positive benefit and the potential harm if these medications were substituted with others. Nevertheless, this association provides further evidence of the broader importance of oxidant and antioxidant processes in the pathogenesis of asthma and COPD, and points to a possible overlap in the pathogenesis," the researchers wrote.

They acknowledge that their study results are limited by difficulties with the cross-sectional design, which relies on subject recall and assumes that reported drug use over one month in the survey is representative of long-term use.

Further research is required to confirm or debunk the findings, "particularly the novel findings of an association between acetaminophen use and lung function," the authors wrote.

Although the study did not find an effect with aspirin, aspirin-induced asthma has long been known. Studies have suggested that up to 20% of asthmatics are sensitive to aspirin, and aspirin intolerance is an independent risk factor for developing asthma.

"We found that increased acetaminophen use was associated with greater prevalence of both asthma and COPD, and with lowered lung function in this large, cross-sectional study," the authors wrote. "To put these results in context, aspirin avoidance is important in people who have severe, persistent asthma or a history of aspirin sensitivity, and aspirin avoidance in children is important to prevent Reyes syndrome. The potential risk of acetaminophen must ultimately be estimated through a balanced consideration of the positive benefit and the potential harm if these medications were substituted with others."

Related article:

• American Heart Association: Lengthy NSAID Use May Be Risky

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