Is Acetaminophen Safe for Asthmatic Patients?

Sheehan WJ, Mauger DT, Paul IM, et al. Acetaminophen versus ibuprofen in young children with mild persistent asthma. N Engl J Med. 2016;375(7):619-630.

Acetaminophen is the most commonly used pediatric medication in the United States. Past studies have suggested an association between acetaminophen use and concurrent asthma symptoms and decreased lung function. The mechanism for this association was thought to be the reduction of glutathione in the lung, leading to greater oxidative stress and subsequent damage.

These findings came from observational studies and post hoc analyses, which are prone to bias and confounding. With this in mind, Sheehan and colleagues designed a blinded, randomized trial to determine whether the use of acetaminophen, when clinically indicated, was associated with higher morbidity in young children with mild persistent asthma when compared with ibuprofen.

The Acetaminophen versus Ibuprofen in Children with Asthma trial was a multicenter, randomized, double-blind, parallel-group trial that was conducted from March 2013 through April 2015. Patients were randomized to receive either acetaminophen or ibuprofen, and all patients received standardized asthma controller therapies. The caregivers gave the analgesics on an as-needed basis during the study period. Outcomes examined included the number of asthma exacerbations per participant, the percentage of asthma-controlled days, average use of rescue albuterol, and the frequency of sick visits for asthma. These details were captured by caregivers in an electronic diary.

The number of asthma exacerbations was not found to be significantly different between the 2 groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=.67). There was also no difference found between percentage of asthma-controlled days, use of albuterol rescue inhaler, unscheduled sick visits, or adverse events.

It was also seen that greater use of antipyretic, analgesic medications was associated with more apparent respiratory illnesses. These respiratory illnesses were associated with asthma exacerbations and the use of systemic glucocorticoids. That being said, there were no results that indicated the use of acetaminophen during these periods led to a more severe illness when compared with ibuprofen.

There are limitations to note when reviewing this study. The patients enrolled in this trial were classified as having mild persistent asthma, reducing the applicability for those with more severe disease or no diagnosis at all. This study does not address whether acetaminophen exposure leads to the development of asthma. This study did not compare acetaminophen to a placebo, as that was felt to be inappropriate care of the patients enrolled.

These results seem to suggest that the use of acetaminophen in usual, as-needed doses did not worsen asthma or wheezing in children. The observational studies that have suggested otherwise may be confounded by the idea that children with asthma may be more symptomatic during a respiratory tract infection, so antipyretics/analgesics are used more often. While more research needs to be conducted, it does seem safe for families of patients with mild persistent asthma to use acetaminophen as directed in appropriate situations. 

Jessica Tomaszewski, MD, is an assistant clinical professor of pediatrics at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania, and a hospitalist pediatrician at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware.

Charles A. Pohl, MD—Series Editor, is a professor of pediatrics, senior associate dean of student affairs and career counseling, and associate provost for student affairs at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania.