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N Engl J Med. 2016 Aug 18;375(7):619-30. doi: 10.1056/NEJMoa1515990.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

Collaborators (158)

Mauger DT, Israel E, Phipatanakul W, Smith L, Solway J, Krishnan J, Pongracic J, Wechsler M, Szefler S, Sorkness C, Lemanske R, Wenzel S, Holguin F, Lazarus S, Cabana M, Castro M, Bacharier L, Kraft M, Martinez F, Peters S, Fitzpatrick A, Busse WW, Butler E, Maiolo J, Misplay S, Skoner D, Smith G, Flexas I, Kumar R, Makhija M, Qamar N, Szychlinski C, Bloss V, Brown M, Chee K, David S, Ehrman CS, Ezmigna D, Goodwin J, Grad R, Hiranratta A, Lopez S, Paco A, Priefert J, Provencio NS, Ryan E, Varela M, Vasquez M, Weese R, Wences J, Decker J, Harrison K, Long D, Meade K, Mok R, Nelson-Purdy C, Ren D, Stessel H, Bartnikas L, Bouzaher A, Burke C, Cavanaugh M, Chen J, Cunningham E, Cunningham A, Friedlander J, Hindi E, Kantor D, Kopel L, Permaul P, Rao D, Rossi M, Schierembergg D, Schneider L, Troung J, Umetsu D, Zhou J, Aujla S, Broyles J, Chong H, Dubin P, Finder J, Green TD, Holt L, Kufen A, Kurland G, Lanzo R, Nash D, Parente J, Smith C, Spahr J, Weiner DJ, Beaty T, Brown SW, Bruce AC, Dodds JC, Douglas S, Freedle K, Simon DM, Whitlock DM, Gleason M, Spears G, Sundstrom DA, White M, Batalla J, Littlefield M, Rutledge B, Seymour D, Brown S, OquendoFlores O, Doty L, Gern B, Merchlinski A, Nelson J, Schmidt J, Texter L, Updegrave A, Zeller J, Zimmerman R Jr, Craven D, DiMarino A, Hart M, Kerns LA, Logan L, Veri L, Codispoti C, Fu J, Li G, Munoz-Mendoza D, Stevens S, Thompson B, Zitzer S, Bowman J, Bowyer V, Gonzales-Vargas J, McKean M, Tran N, Batson C, Davies L, Kelly F, Morales E, Redway A, Spicher M, Kaminski L, Knutson MR, Olson S, Turcsanyi S, Watson T, Wilmoth C, Caldwell W, Dula C, Ellis A, Horner C, Kertz L, Norris T, Rivera-Spoljaric K, Rodriguez O, Strunk R.

Author information

From the Divisions of Allergy and Immunology (W.J.S., S.N.B., W.P.) and Respiratory Diseases (J.M.G.), Boston Children's Hospital and Harvard Medical School, and the Division of Allergy and Pulmonary Medicine, Brigham and Women's Hospital and Harvard Medical School (E.I.) - all in Boston; the Departments of Public Health Sciences (D.T.M., S.J.B.) and Pediatrics (I.M.P.), Penn State College of Medicine, Hershey, and the University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (F.H.) and the Department of Pediatrics, Allegheny General Hospital (D.A.G.), Pittsburgh - all in Pennsylvania; Stroger Hospital of Cook County and Department of Pediatrics, Rush University Medical Center (J.N.M.), Ann and Robert H. Lurie Children's Hospital of Chicago (J.A.P., R.G.R.), and University of Illinois at Chicago (H.V.K.) - all in Chicago; the Breathing Institute, Children's Hospital Colorado (S.J.S.), and the Departments of Pediatrics (S.J.S.) and Medicine (M.E.W.), University of Colorado School of Medicine, Aurora, and the Department of Pediatrics (R.C., J.T.O.) and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine (M.E.W.), National Jewish Health, Denver - both in Colorado; the Department of Pediatrics, Emory University, Atlanta (A.M.F.); the Section of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health (D.J.J., R.F.L.) and the School of Pharmacy, University of Wisconsin-Madison (C.A.S.) - both in Madison; Washington University School of Medicine in St. Louis and the Department of Pediatrics, St. Louis Children's Hospital (L.B.B., A.B.) - both in St. Louis; the Departments of Pediatrics (M.D.C.) and Medicine (S.C.L.) and the Airway Clinical Research Center (N.L.), University of California, San Francisco, San Francisco, Benioff Children's Hospital Oakland, Oakland (M.B., J.M.), and Olive View UCLA Medical Center and Department of Pediatrics, David Geff



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.


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.


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.


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 number, NCT01606319.).

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