Acetaminophen and Asthma: A Bad Marriage

A Cautionary Review

Dr. McBride focuses on these results in providing a stern caution regarding the use of acetaminophen among children. Moreover, he notes a temporal association between the rising use of acetaminophen among children, probably due to the fear of Reye syndrome associated with aspirin use, and a more than 60% increase in the prevalence of asthma between 1980 and 2003.

A direct causal link between wider use of acetaminophen and the epidemic of asthma worldwide over the past 30 years cannot be proved. In addition, most of the research that demonstrates an association between acetaminophen and asthma is limited by confounding factors. Children receive acetaminophen when they are ill and more prone to wheeze and asthma symptoms, and children with asthma are more likely to acquire viral upper respiratory infections and need treatment with antipyretics and analgesics. It is also possible that physicians and parents have been more likely to use acetaminophen instead of aspirin or ibuprofen among children with wheeze and asthma because of a perceived reduced risk for adverse effects with acetaminophen.

In fact, acetaminophen does not seem to be safer than ibuprofen among children, particularly with regard to wheeze and asthma symptoms. In a randomized trial of 1879 children with asthma, treatment with ibuprofen was associated with a significantly lower rate of outpatient visits for asthma compared with treatment with acetaminophen, and there was a nonsignificant trend toward a lower risk for asthma hospitalizations in the ibuprofen group.^[9]

Nonsteroidal anti-inflammatory drugs, such as ibuprofen, are associated with several other potential adverse events, including gastrointestinal bleeding and renal complications. However, a meta-analysis of 24 randomized controlled trials found that ibuprofen and acetaminophen were not associated with a significant increase in the overall rate of adverse events compared with placebo or with each other.^[8]

Given this research and the sum of data suggesting that acetaminophen may promote wheeze and asthma, ibuprofen may be strongly considered a safer option for treatment compared with acetaminophen. There have been multiple randomized trials of acetaminophen and ibuprofen, alone or in combination, for treating fever among children.

Adding acetaminophen to ibuprofen does not seem to have a profound benefit in the management of pediatric fever. In one trial, the combination of ibuprofen plus acetaminophen resulted in nearly 1 hour less of fever compared with acetaminophen alone during the 4 hours after dosing, but the total time with fever was similar in the combination therapy vs ibuprofen-only treatment groups.^[10] Time to resolution of fever was also similar with ibuprofen alone compared with combined therapy.

A review of studies comparing ibuprofen, acetaminophen, and combined treatments for fever in children found little evidence that combined treatment substantially improved clinical outcomes.^[11] Combined therapy seemed to be more effective in reducing fever after 4 hours compared with ibuprofen or acetaminophen alone, and children's discomfort may have improved slightly with combined therapy. Also, the rate of acute adverse events was similar with combined vs individual-drug treatment.

Dr. McBride concludes that the burden of proof has shifted from establishing that acetaminophen is harmful to confirming that it does not in fact promote a higher risk for asthma. Further research may yet exonerate acetaminophen of this charge, but it would take large clinical trials with years of follow-up to best assess this relationship.

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