Emergency Medicine Professor and Colleagues Report Medical Breakthrough in the New England Journal of Medicine

We congratulate Kurt R. Denninghoff, MD, professor of emergency medicine, as the lead author on a recent milestone article in the New England Journal of Medicine (NEJM), published May 18, 2026, to coincide with his research team’s presentation of their findings at the 2026 American Thoracic Society International Conference.

Their Phase 3 clinical study concluded that azithromycin, an antibiotic commonly used to treat certain bacterial infections, did not lead to a greater reduction in the severity of wheezing-related symptoms than a placebo in preschool-age children who presented to the emergency department with moderate-to-severe acute wheezing.

NEJM is one of the world’s premier peer-reviewed medical journals — out of approximately 16,000 submissions received annually, only about 5% are accepted for publication. It is known for publishing landmark studies and featuring practice-changing clinical trials, such as the one undertaken by Dr. Denninghoff and his colleagues. According to Samuel Keim, MD, MSc, professor and head of the University of Arizona Department of Emergency Medicine, this NEJM article is a significant scientific achievement for emergency medicine and our department, and it is a pinnacle goal for any researcher.

Dr. Denninghoff is one of three principal investigators on the clinical trial reported on in the recent NEJM article, “Azithromycin Therapy in Preschoolers with a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED),” which was funded in part by the National Heart, Lung, and Blood Institute (NHLBI), a division of the National Institutes of Health. Additional support was received from the Pediatric Emergency Care Applied Research Network (PECARN), which is supported by the Maternal and Child Health Bureau in the Health Resources and Services Administration of the U.S. Department of Health and Human Services under the Emergency Medical Services for Children program. The other principal investigators on the study are Fernando Martinez, MD, lead researcher, director of the Asthma and Airway Disease Research Center, Regents Professor and Swift-McNear Professor of Pediatrics, and T. Charles Casper, PhD, senior faculty member of the Utah Data Coordinating Center and biostatistician for PECARN.

As noted elsewhere, the AZ-SWED has provided more definitive answers to longstanding questions and inconclusive studies about the role of some types of bacteria in wheezing and asthma, and how to effectively treat these conditions. In the trial, 521 of the 840 children with moderate-to-severe acute wheezing who presented to eight different pediatric emergency departments across the United States tested positive for at least one kind of possibly harmful bacteria, but most of the children in the study (slightly more than 86%) also had a virus (72.5% were infected with a cold virus). By highlighting the importance of viral infections in wheezing and asthma in preschoolers, this finding explains the lack of benefit of antibiotic treatment. The trial was stopped early after the researchers found that azithromycin was useless in easing wheeze in those cases.

Dr. Denninghoff described how this multidisciplinary, transformative research developed.

“Fernando [Martinez] and I met together over a decade ago with the goal of taking advantage of his leadership in pediatric asthma and my role as one of the principal investigators for the HRSA-funded PECARN. By bringing his tremendous skills and knowledge to our world-leading pediatric emergency medicine research group, we were able to work together with Charlie [Casper, PhD] at the UDC as well as specific PECARN research sites to bring this definitive multi-center study to completion,” he said. “Today, about 25% of preschoolers who present to the ED with wheezing are treated with antibiotics. This number may be as high as 60% in the moderate-to-severe cases we studied, 50% of whom were admitted to the hospital. We are honored to have this work published in the NEJM and believe that these results will stop the ineffective use of antibiotics in children who wheeze without clear evidence of pneumonia.”