Balloon Dilation in Selected Subjects with Refractory Eustachian Tube Dysfunction

描述（由申请人提供）：咽鼓管（ET）是中耳（ME）和鼻咽（NP）之间的潜在沟通。ET的管腔通常是封闭的，但可以通过管旁肌的活动暂时打开。已知在患有渗出性中耳炎（OME）的患者中ET开放功能（ETF）受损，并且组成性ET功能障碍（ETD）可导致疾病作为慢性病症持续存在。没有标准的药物治疗可以有效改善ETF或解决长期持续性OME，通常的治疗方法是插入通气管（VT），绕过ET以保持ME与环境之间的开放式沟通。然而，成人VT的功能性半衰期约为4-9个月，当VT被挤出或变得无功能时，疾病经常复发。最近，一种可能更持久的ETD替代手术治疗方法，即ET球囊扩张术（BDET），被描述为相对容易执行，安全有效地解决OME，并正在积极推广给执业外科医生，以在他们的实践中采用。然而，评估该手术有效性的少数临床研究包括小样本量，“治愈”的弱定义，并且没有随机化，盲法或假对照。重要的是，没有一项研究评估了手术对ETF的直接影响。在这里，我们建议进行一项试点研究，以确定安全性和有效性方面的改善ETF的BDET。在2年的时间内，我们将确定年龄在18-50岁之间的其他健康患者，这些患者接受VT插入治疗ETD引起的OME。提供试验性单侧BDET知情同意书的40例患者将作为受试者入组研究。他们将进行基线ETF测试和内窥镜ET/NP评估，以记录是否存在ETD。将评价ETD受试者亚组的3种可降低ETF等级的常见疾病：过敏、鼻窦炎和胃食管反流病。如果诊断出疾病，受试者将接受适当的药物治疗;否则，将接受鼻内类固醇治疗。将重复ETF测试和鼻内窥镜检查，20名对药物治疗无反应的ETD受试者将在监测麻醉护理下进行单侧BDET。为了安全性和ET管腔几何形状的测量，将在手术前完成针对ET和ME的改良CT方案。将在1、3和6个月时重复ETF测试和内窥镜评价，并在BDET后3个月时重复CT扫描。将对数据进行分析，以确定OME成人患者ETD的频率和原因;确定是否可以使用合并症或炎症的短期药物治疗来取消受试者接受BDET的资格，确定与手术相关的并发症的类型和频率，描述手术对ETF和ET管腔几何形状的影响。这些结果将决定该手术是否需要进行多中心的II/III期临床试验。

DESCRIPTION (provided by applicant): The Eustachian tube (ET) is a potential communication between the middle ear (ME) and nasopharynx (NP). The lumen of the ET is usually closed but can be transiently opened by the activity of the paratubal muscles. It is known that the ET opening function (ETF) is impaired in patients presenting with otitis media with effusion (OME) and that constitutive ET dysfunction (ETD) can cause the persistence of the disease as a chronic condition. No standard medical therapy is effective in improving ETF or in resolving persistent OME long-term and the usual treatment is insertion of ventilation tubes (VTs) which bypasses the ET to maintain an open communication between the ME and environment. However, the functional half-life of a VT in adults is approximately 4-9 months and the disease often recurs when the VT is extruded or becomes non-functional. Recently, an alternative and perhaps more permanent surgical treatment for ETD, balloon dilation of the ET (BDET), has been described as being relatively easy to perform, safe and efficacious in resolving OME and is being actively promoted to practicing surgeons for adoption in their practices. However, the few clinical studies that evaluated the efficacy of the procedure included small sample sizes, a weak definition of "cure" and were not randomized, blinded or sham controlled. Importantly, none of the studies evaluated the direct effect of the procedure on ETF. Here, we propose to conduct a pilot study to define the safety and efficacy with respect to improving ETF of BDET. Over a 2-year period, we will identify otherwise healthy patients between 18-50 years of age who have VTs inserted as a treatment for OME caused by ETD. Forty of the patients who provide informed consent for experimental, unilateral BDET will be enrolled as subjects in the study. They will have baseline ETF tests and endoscopic ET/NP evaluations to document the presence or absence of ETD. The subset of subjects with ETD will be evaluated for 3 common conditions that can down-grade ETF: allergy, sinusitis and gastro-esophageal reflux disease. If a condition is diagnosed, the subject will be treated medically as appropriate; otherwise, they will be treated with intranasal steroids. ETF tests and nasal endoscopic examinations will be repeated and 20 subjects with ETD unresponsive to medical treatment will have unilateral BDET done under monitored anesthesia care. For safety and measurement of ET luminal geometry, a modified CT protocol focused on the ET and ME will be done prior to the procedure. ETF tests and endoscopic evaluations will be repeated at 1, 3 and 6 months and the CT scan will be repeated at 3 months after the BDET. The data will be analyzed to: define the frequency and cause of ETD in unselected adults with OME; determine if a short course of medical treatment for co-morbid conditions or for inflammation can be used to disqualify subjects from consideration for BDET, identify the type and frequency of complications associated with the procedure, describe the effect of the procedure on ETF and ET luminal geometry. These results will determine if a multi-center, phase II/III clinical trial ofthe procedure is warranted.