The development and application of outcome measures and biomarkers for treatment of people with a mucociliary clearance disorder

Mucociliary clearance protects the host from pathogens by propelling them out of the airways via a layer of mucus. There are two key components to this process: proper mucus production and coordinated ciliary beating. If any or both of these components are not functioning properly, this can cause a mucociliary clearance disorder, such as cystic fibrosis (CF) or primary ciliary dyskinesia (PCD). This thesis discusses the development of outcome measures and biomarkers for the use of monitoring the effect of therapy and disease progression for people with a mucociliary clearance disorder. The thesis starts out on PCD and the challenges caused by the high heterogeneity of the disease. It discusses the challenges of designing proper clinical trials for people with PCD and CF and the phenotypes that are not included in those trials. A core outcome set is developed for PCD and one of the chapters shows the results of a real-life study including a severe CF phenotype, which was excluded from clinical trials. Next to outcomes in clinical trials, this thesis also focusses on biomarkers. Specifically, biomarkers in exhaled breath for the detection of pathogen infection. This thesis explores a novel route in validating these biomarkers. Finally, this thesis concludes that a hypothesis driven approach is key in monitoring disease progression and effectiveness of therapy, within people with a mucociliary clearance disease. Collaboration is extremely important for future development of new therapies and improving clinical care and quality of life for people with CF and PCD.