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

1/2：阿奇霉素治疗在急诊科诊断出严重喘息发作的学龄前儿童 (AZ-SWED)

• 批准号: 10274820
• 负责人: KURT R DENNINGHOFF
• 金额: $ 176.52万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-11-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10274820
• 关键词: 17q; 5 year old; 6 year old; Accident and Emergency department; Acute; Admission activity; Age; Ambulatory Care Facilities; Anti-Bacterial Agents; Antibiotics; Antiinflammatory Effect; Applied Research; Asthma; Azithromycin; Bacteria; Bacterial Infections; Cephalosporins; Child; Clinical Trials; Clinical Trials Design; Diagnosis; Dose; Emergency Care; Emergency department visit; Event; Future; Gene Cluster; Genes; Genetic; Genetic Carriers; Genetic Polymorphism; Genomics; Guidelines; Haemophilus influenzae; Health Care Costs; Hospitalization; IL8 gene; Life; Longitudinal Studies; Lower respiratory tract structure; Macrolides; Microbe; Microbiology; Modernization; Moraxella catarrhalis; Multi-Institutional Clinical Trial; Nasopharynx; Nursery Schools; Outcome; Pathogenicity; Penicillins; Pharyngeal structure; Placebos; Play; Population; Preschool Child; Prevalence; Property; Randomized; Recommendation; Reporting; Resistance; Risk; Risk Factors; Role; Sampling; Schedule; Severities; Severity of illness; Source; Streptococcus pneumoniae; Symptoms; Technology; Testing; United States; Variant; Virus; Wheezing; age group; aged; airway obstruction; bacterial resistance; clinical research site; disability; experience; health care service utilization; high risk; hospitalization rates; microbial; microbial community; microbiota; novel therapeutics; pathogenic bacteria; pediatric emergency; predict responsiveness; predicting response; psychologic; respiratory; respiratory microbiome; response; social; symptomatic improvement; treatment guidelines

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.

项目摘要/摘要 超过220万2-5岁的儿童有喘息性发作，严重到需要紧急情况 在美国，每年有15%的儿童需要住院治疗。那里 是否有新的证据表明，咽喉中生长的有害细菌可能在决定 哪些学龄前儿童会喘息，然后继续发展为哮喘。细菌和病毒同样有关联。 学龄前儿童有急性喘息的风险，抗生素可能是一种潜在的治疗方法。二 最近在门诊进行的大型、精心设计的临床试验显示，严重的 儿童在开始使用抗生素阿奇霉素(AZ)之前或之后的症状 气喘吁吁。尽管这些结果令人鼓舞，但我们不确定这种好处是如何发生的，因为亚利桑那州既有 具有抗菌和消炎作用。此外，我们不知道AZ在更严重的情况下是否有效 个案，例如需要急症室探访的个案。向教育署求助的相对贫困学龄前儿童 他们严重的喘息发作通常病情更重，细菌感染的风险因素也更大。他们 因此，如果AZ被证明在这种情况下是有效的，那么可能会获得最大的好处。我们 建议在来急诊室的学龄前儿童中进行一项试验，他们患有严重的喘息，将接受以下两种药物之一的治疗 AZ或安慰剂。我们还将确定哪些细菌在儿童的咽部生长。这将回答 问题：阿奇霉素是否能使患有严重喘息的儿童更早好转？如果是，这种益处是否显现？ 在所有接受治疗的儿童中，还是只在喉咙中有潜在有害细菌的儿童中？令人担忧的是 过度使用抗生素可能会导致细菌对其作用产生抗药性。因此，我们将确定基因是否 咽部存在的因素或微生物种群可以识别更有可能做出反应的儿童 去亚利桑那州。这将使我们能够在未来针对这些儿童使用AZ。通过测试高风险的治疗 患有严重喘息的儿童在急诊室使用AZ并确定哪些细菌在他们的喉咙中生长，我们的 研究可能会找到一种新的方法来治疗这些严重、可怕和难以治疗的疾病。