Project Summary/AbstractOver 2.2 million children aged 25 years have wheezing episodes that are severe enough to require EmergencyDepartment (ED) visits each year in the United States and 15% of these children require hospitalization. Thereis new evidence suggesting that harmful bacteria growing in the throat may play an important role in determiningwhich preschoolers will wheeze and then go on to develop asthma. Bacteria and viruses are equally associatedwith the risk of acute episodes of wheezing in preschoolers and antibiotics may be a potential treatment. Twolarge well-designed clinical trials performed in outpatient clinics recently showed a significant reduction in severesymptoms when children were treated with the antibiotic Azithromycin (AZ) either before or after they startedwheezing. Though these results are encouraging we are not sure how this benefit occurs since AZ has bothanti-bacterial and anti-inflammatory effects. In addition we do not know if AZ could be effective in more severecases like those requiring ED visits. The relatively underprivileged preschoolers who present to the ED for careof their severe wheezing episodes are usually sicker and with greater risk factors for bacterial infections. Theyare therefore the population that may get the greatest benefit if AZ is shown to be effective in this setting. Wepropose a trial in preschool age children coming to the ED with severe wheezing who will be treated with eitherAZ or placebo. We will also determine which bacteria are growing in the childrens pharynx. This will answer thequestion Does Azithromycin make children with severe wheezing better sooner and if so is that benefit seenin all the children treated or only in those with potentially harmful bacteria in their throats? There is concernthat excessive use of antibiotics may cause bacterial resistance to their effects. We will thus determine if geneticfactors or the populations of microbes present in the pharynx can identify children that are more likely to respondto AZ. This will allow us to target the use of AZ to these children in the future. By testing treatment of high riskchildren with severe wheezing in the ED with AZ and determining which bacteria are growing in their throats ourstudy may identify a new way to treat these severe frightening and difficult to treat illnesses.