The main goal of our project is to characterize the clinical course and improve the diagnosis and treatment of PCD patients. To accomplish this, we propose 5 S&T Objectives:
- To perform an observational trial for answering pertinent questions on clinical phenotype of PCD, severity, prognosis and effect of treatments on outcomes. This will be an individual patient data (IPD) meta-analysis of all existing cross-sectional and longitudinal datasets (WP1).
- To establish an international prospective PCD registry for systematic data collection on incidence, clinical presentation, treatments and course of the disease. This will allow to monitor trends in incidence, management and outcomes and to recruit patients for studies (WP2).
- To improve clinical practice in PCD by introducing standardized diagnostic testing for PCD in European countries, where this is currently not available (WP3);
- To establish PCD-specific Health-Related Quality of Life Questionnaires (HRQOLQ) as an outcome measure (WP4);
- To perform a randomized controlled clinical trial on the use of azithromycin in PCD (WP5).
We will analyse currently available evidence in an observational trial (WP1), establish a prospective international PCD registry (WP2), standardize diagnostic tests for PCD and implement these tests in European countries with low health care expenditures to reach patients with delayed or missing diagnosis (WP3); establish HRQoLQs (WP4) as outcome measure for subsequent randomized trials (WP5); train clinicians on standardized PCD diagnostic tests (WP7).
There is no orphan drug for PCD and treatment is off label. We will analyse all available data in an observational trial data to evaluate effects of different treatment regimens (WP1) and address the clinical management of upper and lower respiratory tract infections with azithromycin or placebo in a randomized controlled study (WP5). Our protocol has been designed to carefully evaluate patient-centred measures of effectiveness (quality of life) and clinical measures (e.g. FEV1); We will specifically look for and report on adverse events (eg. antibiotic resistance).
We will: determine suitable outcome measures in an expert consensus/adapted Delphi process and evaluate suitability of outcomes measures in the observational trial (WP1); collect appropriate outcome measures prospectively in the registry (WP2); develop and validate HRQoL instruments (WP4); use carefully defined main and secondary outcome parameters in the randomized trial (WP5).
Respiratory tract infections are secondary to defective mucociliary clearance of the airways, and all genetic mutations of PCD identified thus far affect the molecular machinery of mucociliary clearance – to our knowledge, these mutations have no link to the primary etiology of cancer, infectious diseases, and nervous system diseases, and will not be considered further in our studies.
Our partners have discussed and planned our studies with patient organisations, most recently at the International PCD meeting 2011 in Muenster, Germany. The US PCD Foundation, the Dutch (PCD Belangengroep), the Polish (Ciliary Dyskinesia Society) and the German and Swiss PCD patient organisations (Kartagener Syndrom und Primäre Ciliäre Dyskinesie e.V.) all strongly support these studies and expect that patients will greatly benefit from the results. Stakeholder engagement will continue at all stages of the study.
The project will disseminate BESTCILIA objectives in a broad and efficient manner by targeting not only patients and their families, but a broader public; specifically medical caregivers, who are key targets of our dissemination activities as the nexus for building trust with and awareness to PCD patients. A webpage and brochure articulating BESTCILIA will be made publicly available, and we will ensure high-quality translation of both technical (e.g. diagnostic screening) and theoretical aspects of the project by hosting annual patient conferences and also workshops dedicated to clinicians; our goal is to have attendees act as multipliers for further dissemination of BESTCILIA objectives. Importantly, our partners will solicit expert opinion by intercalating with the ERS and US PCD task force to ensure the highest standard of hands-on training for pediatric and adult pulmonologists during our workshops. Our partners will disseminate results of the work packages by presenting seminars at conferences and jointly publishing data in peer-reviewed journals, and we will present our vision for better screening and treatment for PCD in an editorial in the European Respiratory Journal (WP7). Diagnosis and treatment in early childhood is central to this proposal to reduce morbidity and mortality associated with delayed management. Expert consensus is that early diagnosis and treatment of PCD will have the greatest health impact in this disorder. We will raise awareness of difficult to diagnose cases of PCD (e.g. no situs inversus), establish standardized diagnostic tools for PCD, and conduct observational and clinical trials with the aid of a PCD registry.