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

在原发性纤毛运动障碍（PCD）中，与其他化脓性肺部疾病相似，患者会经历间歇性纤毛运动障碍。 呼吸道急性加重（RTE），特征为咳嗽、咳痰增加等症状 生产，发烧和疲劳，通常用抗生素和增加气道清除治疗。定义 作为呼吸道症状的急性变化，开始新的治疗， 发病率和大量使用保健服务、旷课/旷工以及可能加速结构性 气道损伤和气道阻塞。鉴于其对PCD患者生活的负面影响，RTE 干预性试验的明显目标，旨在建立预防和治疗的循证指南， 治疗RTE。 在开始PCD中的RTE干预性试验之前，必须解决知识方面的关键差距。我们 提出一项纵向、多中心研究，利用创新的移动的健康监测工具， 包括家庭肺活量测定，加上直接的病人反馈和质量控制，一个新开发的， 经验证的疾病特异性健康相关生活质量仪器和新型床边数字咳嗽监测仪， 描述PCD患者在一年内的RTE和治疗反应。本研究将 在患者和家庭利益相关者的关键输入下实施，并包括对PCD有意义的终点 社区拟议研究的总体目标是提供设计所需的关键数据 未来在PCD儿童和成人中进行RTE预防和治疗的干预性试验。目标 包括1）描述RTE的关键特征; 2）调查RTE的可行性、可靠性和分析性， 家庭肺功能测定、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1个月）和长期（最长1年）效应量 在研究访视和家中监测终点; 4）评价1年内RTE率的潜在预测因素， 首次RTE的时间。该项目的顺利完成将为设计提供必要和充分的数据 解决PCD中RTE预防和治疗的关键问题，并为 涉及移动的医疗器械的以患者为中心的临床试验设计。未来的干预性试验可能会评估 延迟至首次RTE时间或降低RTE率的慢性治疗，或治疗抗生素的类型和持续时间 RTE。此外，如果家庭监测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 由于需要经常到办公室进行访问，因此无法参加审判。

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.