Longitudinal Characterization of Respiratory Tract Exacerbations and Treatment Responses in Primary Ciliary Dyskinesia

在原发性睫状体运动障碍(PCD)中，与其他化脓性肺部疾病类似，患者经历发作性 呼吸道恶化(RTES)，以咳嗽、痰增多等症状为特征 生产、发烧和疲劳，通常使用抗生素和增加呼吸道清除量来治疗。已定义 由于呼吸道症状的急性变化而开始进行新的治疗，rtes引起显著的 发病率和相当大的医疗保健利用率、缺课/缺勤，并可能加速结构性 呼吸道损伤和呼吸道阻塞。鉴于其对PCD患者生活的负面影响，rte是 干预试验的明显目标，旨在建立以证据为基础的预防和治疗指南 RTES的处理。 在开始对PCD中的RTE进行干预性试验之前，必须解决知识中的关键差距。我们 提出一项纵向、多中心研究，利用创新的移动健康监测工具， 包括家庭肺活量测定以及患者直接反馈和质量控制，一种新开发的和 经过验证的疾病特定健康相关生活质量量表和新型床边数字咳嗽监测器，以 描述PCD患者一年内的RTE和治疗反应。这项研究将是 根据患者和家庭利益相关者的关键意见实施，并包括对PCD有意义的终端 社区。拟议研究的总体目标是提供设计所需的关键数据 对儿童和成人PCD的RTE预防和治疗的未来干预性试验。目标 包括1)描述RTES的主要特征；2)研究RTES的可行性、可靠性和分析性 家庭肺活量测定、患者报告结果调查管理和咳嗽监测的影响；3) 确定候选临床试验的短期(最长一个月)和长期(最长一年)效应大小 在研究访问和家庭中监测终点；4)评估1年以上RTE率的潜在预测因素 到第一个RTE的时间了。该项目的顺利完成将为设计提供必要和充足的数据 针对PCD中RTES预防和治疗关键问题的试验，并为 涉及移动医疗设备的以患者为中心的临床试验设计。未来的干预试验可能会评估 延迟首次RTE的时间或降低RTE发生率的慢性疗法，或抗生素的类型和持续时间 RTES。此外，如果家庭监控被证明是可行和可靠的，我们的结果可以作为一个范例 用于其他罕见疾病人群的创新临床试验设计，这些人群传统上被限制在 由于需要经常进行办公室访问，因此需要参加试行。

In primary ciliary dyskinesia (PCD), similar to other suppurative lung diseases, patients experience episodic respiratory tract exacerbations (RTEs), characterized by symptoms such as increased cough, sputum production, fever and fatigue, that are typically treated with antibiotics and increased airway clearance. Defined as acute changes in respiratory symptoms for which new treatment is initiated, RTEs cause significant morbidity and substantial health care utilization, school/work absenteeism and likely accelerate structural airway damage and airway obstruction. Given their negative impact on the lives of people with PCD, RTEs are obvious targets for interventional trials designed to establish evidence-based guidelines for the prevention and treatment of RTEs. Prior to embarking on interventional trials of RTEs in PCD, critical gaps in knowledge must be addressed. We propose a longitudinal, multicenter study that takes advantage of innovative mobile health monitoring tools, including home spirometry coupled with direct patient feedback and quality control, a newly developed and validated disease-specific health-related quality of life instrument and a novel bedside digital cough monitor, to characterize RTEs and response to treatment in PCD patients over a one year period. The study will be implemented with key input from patient and family stakeholders and include endpoints meaningful to the PCD community. The overall objective of the proposed study is to provide critical data needed to inform the design of future interventional trials of RTE prevention and treatment in children and adults with PCD. The aims include 1) describing the key characteristics of RTEs; 2) investigating the feasibility, reliability and analytic impact of home spirometry, patient reported outcome survey administration and cough monitoring; 3) determining short-term (up to one month) and long-term (up to one year) effect sizes of candidate clinical trial endpoints monitored at study visits and at home; 4) evaluating potential predictors of RTE rate over 1 year and time to first RTE. Successful completion of this project will provide necessary and sufficient data for designing trials addressing key questions in the prevention and treatment of RTEs in PCD and lay the groundwork for patient-centered clinical trial designs involving mobile health devices. Future interventional trials might evaluate chronic therapies to delay time to first RTE or reduce RTE rates, or type and duration of antibiotics to treat RTEs. In addition, if home monitoring proves to be feasible and reliable, our results could serve as a paradigm for innovative clinical trial designs in other rare disease populations that have traditionally been restricted from trial participation due to the requirement for frequent office-based visits.