1/2: AZithromycin Therapy in Preschoolers with a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)

Project Summary/Abstract Over 2.2 million children aged 2–5 years have wheezing episodes that are severe enough to require Emergency Department (ED) visits each year in the United States, and 15% of these children require hospitalization. There is new evidence suggesting that harmful bacteria growing in the throat may play an important role in determining which preschoolers will wheeze and then go on to develop asthma. Bacteria and viruses are equally associated with the risk of acute episodes of wheezing in preschoolers, and antibiotics may be a potential treatment. Two large, well-designed clinical trials performed in outpatient clinics recently showed a significant reduction in severe symptoms when children were treated with the antibiotic Azithromycin (AZ) either before or after they started wheezing. Though these results are encouraging, we are not sure how this benefit occurs since AZ has both anti-bacterial and anti-inflammatory effects. In addition, we do not know if AZ could be effective in more severe cases, like those requiring ED visits. The relatively underprivileged preschoolers who present to the ED for care of their severe wheezing episodes are usually sicker and with greater risk factors for bacterial infections. They are, therefore, the population that may get the greatest benefit, if AZ is shown to be effective in this setting. We propose a trial in preschool age children coming to the ED with severe wheezing who will be treated with either AZ or placebo. We will also determine which bacteria are growing in the children’s pharynx. This will answer the question “Does Azithromycin make children with severe wheezing better sooner and, if so, is that benefit seen in all the children treated or only in those with potentially harmful bacteria in their throats?” There is concern that excessive use of antibiotics may cause bacterial resistance to their effects. We will thus determine if genetic factors or the populations of microbes present in the pharynx can identify children that are more likely to respond to AZ. This will allow us to target the use of AZ to these children in the future. By testing treatment of high risk children with severe wheezing in the ED with AZ and determining which bacteria are growing in their throats, our study may identify a new way to treat these severe, frightening, and difficult to treat illnesses.