ACUTE OTITIS MEDIA--ADJUVANT THERAPY TO IMPROVE OUTCOME

尽管有有效的抗生素治疗急性 中耳炎 (AOM)、治疗失败、持续渗出液和 复发很常见。 治疗效果不佳的相关因素之一 是并发病毒感染，我们已证明其与 中耳 (ME) 液体中炎症介质的水平增加。 我们建议炎症介质，特别是组胺和 白三烯在以下疾病的发病机制中发挥着重要作用： 从 AOM 中恢复，因此将测试辅助治疗是否旨在 抵消组胺作用（抗组胺），和/或抑制 白三烯和其他炎症物质的形成 （皮质类固醇），除抗生素外，还可改善急性和长期 通过降低初始炎症程度来达到 AOM 的长期结果。 辅助药物的功效将分 2 个单独进行测试， 使用随机、双盲、安慰剂的同步研究 4年的受控设计。 在研究 1 中，60 名患者将 在 AOM 开始时注册。 鼓膜穿刺术将在 治疗 5 天后测量组胺和白三烯水平 记录细菌和病毒病因。 这些患者将被跟踪 ME 积液持续时间。 各组将进行比较 细菌学和病毒学病因、ME 组胺和 白三烯水平和临床结果。 研究2是一项大型临床 对 2000 名 1 岁以下儿童进行的试验，有 2 名记录在案 既往有 OM 发作，但不存在 ME 积液。 他们将被跟随 通过家访进行鼓室测试和电话联系，直到下一次 急性发作，并分配到治疗组。 治疗结果 将比较各组之间的治疗失败率、治疗持续时间 积液和 OM 复发超过 9 个月。 对治疗的反应也会 与 OM 危险因素、诊断时症状的严重程度有关，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、炎症之间的关联 调解员。 如果这些药物被证明有效，它们的使用将产生 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成本和不便 父母。

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.