Featured Research
Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults
Primary ciliary dyskinesia and some inborn errors of immunity (IEI) have significant phenotypic overlap. This multicenter, observational, cross-sectional study (NCT04702243), conducted through the Genetic Disorders of Mucociliary Clearance Consortium, utilizes a standard diagnostic approach to establishing a genetic diagnosis of PCD or IEI in children and adults with characteristic features. Diagnostic testing can include CT scans, nasal nitric oxide measurements, immunodeficiency screening labs, transmission electron microscopy of ciliary biopsies, genetic panels for PCD and IEI and, in some cases, whole exome sequencing.
Longitudinal Characterization of Respiratory Tract Exacerbations and Treatment Response in Primary Ciliary Dyskinesia
Interspersed with chronic symptoms, individuals with PCD experience frequent acute respiratory tract exacerbations characterized by symptoms such as increased cough, sputum production, nasal drainage, dyspnea and fatigue and commonly treated with oral, inhaled or intravenous antibiotics. As these exacerbations adversely affect quality of life and result in missed days of work or school and increased healthcare utilization, they are natural targets for clinical trials – yet they are poorly characterized and poorly understood.
This study (NCT05161858), led by Dr. Rosenfeld and Dr. Scott Sagel at the University of Colorado, is an ongoing prospective, multicenter observational study that leverages remote monitoring technologies and sample collection to characterize exacerbations in children and adults with PCD enrolled through the Genetic Disorders of Mucociliary Clearance Consortium. The primary objective is to provide critical data needed to inform the design of future interventional trials of exacerbation prevention and treatment in children and adults with PCD.
Clinical Trial Readiness – PCD (ancillary study)
Decentralized clinical trials offer the opportunity to “bring the trial to the patient,” minimizing or eliminating the need for in-person visits. This longitudinal multicenter trial evaluates home spirometry and an electronic patient-reported outcome (ePRO) as endpoints for future clinical trials in PCD. The objective of the study is to evaluate the feasibility and validity of weekly home spirometry and respiratory tract exacerbation detection through a simple ePRO to inform incorporation of these endpoints into clinical trials.
Validation of a State-of-the-Art Scoring System for Chest Computed Tomography (CT) Scans in Children and Adults With Primary Ciliary Dyskinesia
Chest computed tomography (CT) is a sensitive method to detect and monitor the progression of structural lung abnormalities in PCD, making it a promising clinical endpoint for future clinical trials. Our CT studies are aimed at describing the natural progression of structural lung disease – specifically bronchiectasis, or irreversible airway dilatation that impairs mucus clearance.
We are evaluating two novel chest CT scoring tools for evaluating structural lung disease in children with PCD: the manual Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD (MERAGMA-PCD) CT scoring system that evaluates airway changes in a hierarchical order, and the fully automated (AI) bronchial-artery (BA-LungQ) tool.
What have we learned so far?
- Bronchiectasis increases with age in children with PCD.
- Children with PCD and inner dynein arm defects with microtubular disorganization (IDA/MTD) have increased airway disease, predominately driven by mucus plugging in the small airways.
Future directions
We are collaborating with national and international centers to build a database of CTs from children and adults with PCD. We plan to utilize this database to validate these new CT scoring tools. Information gained from these studies will better inform utilizing CTs in clinical trials aimed at testing new therapeutics for children and adults with PCD.
PCD Foundation Registry: A Longitudinal Study of Patients With Primary Ciliary Dyskinesia
We are a site for the PCD Foundation Registry, a prospective, multicenter natural history observational study collecting clinical and demographic information as well as patient-reported data to improve PCD diagnostics, clinical care, quality of life and patient-important outcomes. Dr. Rosenfeld chairs the Access and Publications Committee of the Registry Oversight Committee.