ACUTE OTITIS MEDIA--ADJUVANT THERAPY TO IMPROVE OUTCOME

急性中耳炎——改善疗效的辅助治疗

• 批准号: 2128073
• 负责人: Tasnee Chonmaitree
• 金额: $ 33.93万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2128073
• 关键词: antibiotics; antihistamines; bacterial disease; clinical trials; combination chemotherapy; combination therapy; corticosteroids; cytokine; ear disorder chemotherapy; histamine; human subject; human therapy evaluation; immunotherapy; infant human (0-1 year); leukotrienes; microorganism culture; otitis media; preschool child (1-5); prognosis; prostaglandins; virus diseases

Despite the availability for effective antibiotics for treatment of acute otitis media (AOM), treatment failures, persistent effusions and recurrences are common. One factor associated with poor treatment outcome is concurrent viral infection, which we have shown to be associated with increased levels of inflammatory mediators in the middle ear (ME) fluids. We propose that inflammatory mediators, particularly histamine and leukotrienes, play a significant role in both the pathogenesis of and recovery from AOM, and therefore will test whether adjuvant therapy aimed at counteracting histamine actions (antihistamine), and/or inhibiting formation of leukotrienes and other inflammatory substances (corticosteroid), in addition to antibiotic, will improve acute and long- term outcome of AOM by reducing the degree of the initial inflammation. The efficacy of the adjuvant drugs will be tested in 2 separate, simultaneous studies which use a randomized, double-blind, placebo- controlled design over a 4-year period. In Study 1, 60 patients will be enrolled at the onset of AOM. Tympanocentesis will be performed prior to and 5 days into therapy to measure histamine and leukotriene levels and document bacterial and viral etiology. These patients will be followed for the duration of ME effusion. Groups will be compared for bacteriologic and virologic etiology, changes in ME histamine and leukotriene levels, and clinical outcomes. Study 2 is a large clinical trial of 2000 children, enrolled under 1 year of age with 2 documented prior episodes of OM but not present ME effusion. They will be followed by home visits with tympanometry and telephone contacts until their next acute episode, and the assigned to treatment groups. Results of treatment will be compared among groups for rate of treatment failure, duration of effusion, and recurrences of OM over 9 mo. Response to therapy will also be related to OM risk factors, severity of symptoms at diagnosis, and evidence of concurrent viral infection of the respiratory tract. These studies should clarify the potential benefits of antihistamine and/or corticosteroid therapy, both for treatment of acute and possible prevention of recurrent and/or chronic OM in infants, and shed light on associations between adjuvant treatment, viral infection, inflammatory mediators. If the drugs are proven efficacious, their use would make a significant impact on health care. If they are inefficacious, discontinuation of their use will reduce costs and inconvenience to parents.

尽管有效的抗生素治疗急性 中耳炎（AOM）、治疗失败、持续性积液和 复发是常见的。 一个与不良治疗结果相关的因素 是并发病毒感染，我们已经证明这与 中耳（ME）液中炎症介质水平升高。 我们认为炎症介质，特别是组胺和 白细胞三烯，发挥重要作用，在发病机制和 从AOM中恢复，因此将测试辅助治疗是否旨在 对抗组胺作用（抗组胺剂），和/或抑制 白三烯和其他炎症物质的形成 （皮质类固醇），除了抗生素，将改善急性和长期- 通过降低初始炎症的程度来改善AOM的长期结局。 辅助药物的功效将在2个单独的， 使用随机、双盲、安慰剂的同步研究- 在四年的时间里进行控制设计。 在研究1中，将有60名患者 在AOM发作时登记。 鼓室穿刺术将在 治疗5天后测量组胺和白三烯水平， 记录细菌和病毒病因。 这些患者将接受随访 在ME积液期间。 将比较各组 细菌学和病毒学病因学，ME组胺变化， 白三烯水平和临床结果。 研究2是一项大型临床研究。 在2000名1岁以下儿童中进行的试验，其中2名记录 既往OM发作，但未出现ME积液。 他们会被跟踪 通过鼓室压测定和电话联系进行家访， 急性发作，并分配到治疗组。 治疗结果 将比较各组的治疗失败率、 渗出和OM复发超过9个月。 对治疗的反应也将 与OM风险因素、诊断时症状的严重程度相关，以及 呼吸道并发病毒感染的证据。 这些研究应该阐明抗组胺药的潜在益处 和/或皮质类固醇治疗，用于治疗急性和可能的 预防婴儿复发性和/或慢性OM，并阐明 辅助治疗、病毒感染、炎性 调解员 如果这些药物被证明有效，它们的使用将使 对医疗保健产生重大影响。 如果它们无效， 停止使用它们将减少费用和不便， 父母