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

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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.