Study Shows Painkiller Raises Risk of Asthma; Manufacturer Says Drug Is Safe
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Reviewed By Louise Chang, MD
Nov. 5, 2009 -- The popular pain and fever reliever acetaminophen may be linked with an increased risk of asthma in children and adults, according to a new research review of previously published studies by Canadian researchers.
But the manufacturer of Tylenol -- the brand-name version of acetaminophen -- says the painkiller has a well-established safety record.
Researchers pooled the results of 19 clinical studies, with a total of more than 425,000 participants, to see if the association between the pain reliever use and asthma (and wheezing in children) held up. It did.
What triggered the review? "Concern over the risk of acetaminophen and asthma highlighted by the 2008 ISAAC study, published in The Lancet," says the review's lead author Mahyar Etminan, PharmD, a scientist at the Vancouver Coastal Health Research Institute in British Columbia and an assistant professor of medicine at the University of British Columbia.
In the ISAAC (International Study of Asthma and Allergies in Childhood) study, researchers looked at more than 205,000 children, ages 6 to 7, in 31 countries and found that acetaminophen use for fever in the first year of life was linked to increased risk of asthma symptoms in children 6 to 7 years old. Current use of acetaminophen was also linked to increased risk of asthma symptoms.
Other studies, Etminan says, have produced conflicting results, so the Canadian team conducted the review.
Sales of acetaminophen products in the U.S. are about $1 billion annually, the researchers estimate.
Calculating Asthma Risk
Etminan's team searched the medical literature to find high-quality published studies, trying to quantify the risk of asthma and wheezing among acetaminophen users, as well as the effect of prenatal exposure to the medicine.
After eliminating studies that weren't scientifically sound enough, the researchers focused on 19 studies. Overall, they found that acetaminophen users were 63% more likely to have asthma than nonusers. Other findings:
- The risk of asthma in children given acetaminophen in the year before their asthma diagnosis was increased by 60%.
- The risk of asthma in children who used acetaminophen in the first year of life was 47% higher than in those who didn't use it.
- The risk of asthma in adults who used acetaminophen was 74% higher than in those who did not.
- Prenatal use of acetaminophen boosted the risk of wheezing by 50% and the risk of asthma by 28% in children.
The researchers concede that children with severe asthma may be more likely to get acetaminophen for viral or other infections that may actually be due to asthma or may precede an asthma diagnosis.
The finding of acetaminophen use and asthma is an association, they say, but not necessarily a cause and effect.
The researchers say other mechanisms may explain the link. Acetaminophen, they say, may boost an enzyme involved in the anti-inflammatory response in asthma.
There are other possible mechanisms. "There isn't enough evidence to favor one over the other," Etminan says. He says more studies are needed to fully understand the association.
In a prepared statement, McNeil Consumer Healthcare, which makes Tylenol, says:
"TYLENOL® (acetaminophen) has over 50 years of clinical history to support its safety and efficacy and, when used as labeled, TYLENOL® has a superior safety profile compared with many other over-the-counter (OTC) pain relievers. The well-documented safety profile for acetaminophen makes it the preferred pain reliever for asthma sufferers."
The statement continues: "There are no prospective, randomized controlled studies that show a causal link between acetaminophen and asthma. The systematic review and meta-analysis published in Chest does not establish a definitive casual relationship between the therapeutic use of acetaminophen and an increased risk of asthma and wheezing in both children and adults. In fact, the study investigators admit that their systematic review is subject to several limitations, one of which is that diagnosis of asthma in most of the studies was through self-reporting and the possibility of misclassification of asthma with other respiratory conditions can't be excluded. The authors also stated that additional studies would be needed in order to verify their findings."
Another expert said the review is strong. "This is clearly synthesizing the studies that have been conducted over the past 10 years and is showing the emerging evidence that acetaminophen seems to be associated with the development of asthma and asthma-like symptoms in children and adults," says Matt Perzanowski, PhD, assistant professor of environmental health sciences at the Mailman School of Public Health at Columbia University in New York.
With his colleagues at Columbia, Perzanowski recently found that prenatal acetaminophen exposure boosts the risk of wheezing in inner city, minority children (who have high rates of asthma) at age 5.
They believe that children with a genetic mutation affecting an antioxidant that helps "detox" the body may be the ones at risk, Perzanowski tells WebMD.
A practicing allergist, Rebecca G. Piltch, MD, who cares for patients with asthma and allergies in Marin County, Calif., says the association is interesting but points out it does not prove cause and effect.
Perzanowski agrees, saying: "There is still a possibility the association is due to some other mechanism besides the acetaminophen."
Until more research is done, what's a parent or adult to do? "The American Academy of Pediatrics recommends acetaminophen as the drug of choice for controlling fever," Etminan says. "Parents should still follow these guidelines until the recommendations change."
"For adults, ibuprofen is an alternative drug that can be used," he says. "Unlike acetaminophen, ibuprofen has not been shown to be associated with asthma."
Following the recommended dose is important, he says. The question of whether a specific dose is linked with the risk of asthma needs to be studied, Etminan says.
Patients already diagnosed with asthma should check with their own doctor about acetaminophen use, Piltch says. Those who don't have asthma "but have concerns about acetaminophen should discuss them with their primary care provider."
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Etminan, M. Chest, November, 2009; vol 135: pp 1316-1323.
Beasley, R. The Lancet, Sept. 20, 2008; vol 372: pp 1039-1048.
Perzanowski, M. Thorax, published online Oct. 22, 2009.
Matt Perzanowski, PhD, assistant professor of environmental health sciences, Mailman School of Public Health, Columbia University.
Rebecca G. Piltch, MD, allergist and immunologist, Marin County, Calif.
Marc Boston, McNeil Consumer Healthcare.
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