Acetaminophen and Asthma: A Bad Marriage

Acetaminophen and Asthma Prevalence and Severity: Should Prescribing Habits Change?

The Study

McBride JT. The association of acetaminophen and asthma prevalence and severity. Pediatrics. 2011;128:1181-1185.

This study was chosen as the subject of an interview because of its selection in the Medscape newsletter Practice-Changing Articles. This service ranks studies in 2 ways: by analyzing their statistical strength using a 15-item rating instrument and by assessing their clinical relevance as determined by an expert review panel.

Acetaminophen is among the most trusted medications to treat fever and pain, but epidemiologic studies have suggested that acetaminophen might be associated with a higher risk for asthma among both children and adults. However, limitations of the available data make it easy to discount any possible association between acetaminophen and asthma. The current review by Dr. McBride puts the issue of acetaminophen and asthma into the proper perspective so that clinicians can use this information to make everyday practice decisions.

The Background

Acetaminophen, or paracetamol, is one of the most commonly used medications worldwide, because it is considered effective for fever and pain and also has a relatively benign safety profile. The issue of safety is important particularly among children, who are more prone to adverse events associated with medications.

The primary reason for treatment with acetaminophen is fever, which is one of the most common acute symptoms among children and the most common reason for presentation to a pediatric emergency department. Many parents inappropriately give antipyretics to children, including at body temperatures less than 37°C.^[1]

The use of medications to treat pain and fever in children is fairly widespread. A large study from Germany found that nearly 9% of all children had been given some medication for one of these indications over a 1-week period, and this proportion rose to 17.5% among children with more regularly occurring pain.^[2] Acetaminophen, ibuprofen, and aspirin were the most commonly used analgesics.

Doubt regarding the safety of acetaminophen among children is increasing, however, particularly because risks for wheeze and asthma have been related to its use. Recent observational studies have found a significant link between acetaminophen use and asthma. In one study involving 322,959 adolescents in 50 countries, recent use of acetaminophen was associated with an odds ratio for current asthma symptoms of 1.49 (95% confidence interval [CI], 1.33-1.53).^[3] Recent acetaminophen use was also associated with higher risks for atopic disease, such as eczema and rhinoconjunctivitis.

Research in younger children from this same study cohort found that treatment with paracetamol during the first year of life increased the risk for asthma symptoms by 46%.^[4] Moreover, there was a dose-dependent positive association between current paracetamol use and asthma symptoms among these children; paracetamol use also was associated with higher risks for eczema and rhinoconjunctivitis.

These findings were corroborated by research from a population of children in Ethiopia. Acetaminophen use at age 1 year was associated with a dose-dependent positive increase in the risk for wheeze at age 1 to 3 years; the risk was more than 7-fold higher among children who received at least 4 acetaminophen tablets in 1 month.^[5]

Some studies suggest that acetaminophen can increase the risk for incident asthma among adults as well. An analysis of the Nurses' Health Study, which enrolled 121,700 women in the United States, found that the multivariate rate ratio for asthma among women who used acetaminophen for more than 14 days per month was 1.63 (95% CI, 1.11-2.39).^[6]

Systematic reviews also suggest that acetaminophen can promote asthma and wheeze. A review of 19 studies with a total of over 425,000 children and adults found a pooled odds ratio for asthma of 1.63 (95 CI, 1.46-1.77) among users of acetaminophen.^[7] The risk for asthma was similar among adults and children, and this study also demonstrated that prenatal use of acetaminophen increased the risk for asthma and wheezing among offspring.

Finally, a meta-analysis of data from randomized controlled trials only concluded that acetaminophen use was a significant risk factor for wheeze and asthma symptoms.^[8]

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