Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma

Abstract

Background: Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.

Methods: In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial.

Results: Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two 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=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events.

Conclusions: Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

Figure 1. Screening, Randomization, and Follow-up

“Study failure” was defined as asthma that was not controlled well enough (prespecified criteria are listed in the protocol) for the child to remain in the study.

Figure 2. Time to First Asthma Exacerbation

Shown are Kaplan–Meier curves for the cumulative risk of an asthma exacerbation during the course of the trial. In a Cox proportional-hazards regression analysis, no significant difference was seen between the treatment groups (P = 0.70). Tick marks indicate times at which data were censored owing to end of follow-up or dropout.

Figure 3. Number of Doses of Acetaminophen or Ibuprofen, According to the Number of Asthma Exacerbations That Led to Treatment with Systemic Glucocorticoids

Shown is the number of acetaminophen or ibuprofen doses that were administered in a blinded manner during the trial period, stratified according to the number of exacerbations that led to treatment with systemic glucocorticoids during the same period. P values for the comparison of treatments within each systemic glucocorticoid subgroup are based on the Wilcoxon rank-sum test. The horizontal lines in the boxes represent the median number of doses of trial medication (acetaminophen or ibuprofen); the top and bottom edges of the boxes represent the the first and third quartiles; the I bars extend to the lowest and highest data value that is not more than 1.5 times the interquartile range below and above the lower and upper end of the box, respectively, and the circles are individual data points that are more than 1.5 times the interquartile range above the top edges of the box.