The Association Between Acetaminophen and Asthma

Should Its Pediatric Use Be Banned?

Antonio Martinez-Gimeno; Luis García-Marcos


Expert Rev Resp Med. 2013;7(2):113-122. 

In This Article

Weakness of the Case Against Acetaminophen as a Wheezing Disorders Promoter

Epidemiological association, however strong, does not guarantee a causal relationship. Moreover, there still remains the possibility that the whole epidemiological association between acetaminophen and wheezing disorders is just the product of large sources of bias, which could explain entirely the overwhelming epidemiological evidence against acetaminophen. Should this be the case, acetaminophen could be an innocent bystander falsely accused of something actually produced by some factor to which acetaminophen is associated. Three different types of explanatory bias have been proposed.

First, confounding by indication, in which the real culprit would be infections, mainly viral and respiratory in nature, which would trigger simultaneously the use of acetaminophen and the real causal relationship producing asthma. This source of bias has been defended, among others, by Lowe et al.,[28] supported by their results in the Melbourne Atopy Cohort Study,[4] in which the statistically significant OR against acetaminophen initially found in a first crude analysis disappeared after controlling for respiratory tract infections and stratifying for indication, not being significant for nonfever use of acetaminophen. The authors suggest that this would have happened in other studies if they had controlled for respiratory tract infections. Schnabel et al., in a prospective population-based birth cohort study, found that more than 95% of the participant children had been exposed to acetaminophen during the first year of life.[29] Those with a diagnosis of asthma had had more months with a course of acetaminophen during the first year of life compared with those without the diagnosis of asthma, but this difference was explained by a larger number of respiratory infections. The number of acetaminophen courses due to nonrespiratory causes was similar in children with or without asthma. The authors concluded that respiratory infections and not acetaminophen use were associated with asthma development.

However, Kreiner-Møller et al., in a prospective birth cohort study of newborns from asthmatic mothers, found that the epidemiological association between infant acetaminophen use and early asthmatic symptoms remained after controlling for respiratory infections.[30] Therefore, confounding by indication has not always been found when the research protocol has looked for it.

Second, confounding by reverse causation, asthma itself being the origin of symptoms that prompt acetaminophen use, creating a sort of vicious circle: asthma induces acetaminophen use, which in turn apparently (but falsely) induces asthma. This view is supported by some studies that have found that asthmatic children suffer more comorbidities prone to the use of acetaminophen, like headaches and low-back pain.[31]

Finally, preferential use of acetaminophen by children at greater risk of asthma due to fear that ibuprofen might increase asthma symptoms. Table 2 offers an overview of the arguments in the case against acetaminophen as a promoter of wheezing disorders in children.