Characterizing the upper airway manifestations in Primary Ciliary Dyskinesia and Primary Immunodeficiencies

点击翻译按钮获取中文摘要

Abstract Project 3 The morbidity of upper airway disease in primary ciliary dyskinesia (PCD) and primary immunodeficiencies (PID) is not well defined. These conditions can be difficult to distinguish due to their overlapping phenotypes. The sinonasal and middle ear features are often identified as most problematic by patients and their families, and optimal treatment regimens have not been established. The main objective of this project is to characterize and compare the upper airway phenotypes in PCD and PID and to collect critical data to inform the design of future clinical trials of treatment of the upper airway and middle ear disease. This project has three main specific aims: In Aim 1, we will characterize and compare the impact of PCD and PID sinonasal disease on patient experience using three primary endpoints: clinical features, quality of life, and measures of olfactory function. Sub-aim 1a will characterize sinus anatomy and disease severity by nasal endoscopy and CT imaging, employing validated scoring systems, while Sub-aim 1b will evaluate and compare mucus composition (mucins, proteins, inflammatory markers, bacteria) of the sinuses in PCD and PID. In Aim 2, we will characterize and compare the impact of recurrent otitis media on clinical features, conductive and sensorineural hearing loss in children and adults with PCD and PID. In Aim 3, we will determine whether relationships exist between otolaryngological phenotypes (evaluated in Aims 1 and 2) and specific ultrastructural defects and genotypes in participants with PCD. In this cross-sectional, observational, multicenter study, participants will be recruited from four Consortium sites: University of North Carolina (UNC), McGill University (MU), University of Toronto, Hospital for Sick Children (UT- HSC) and Washington University at St. Louis (WUSTL). We will recruit 200 participants equally distributed between individuals diagnosed with PCD and PID; each participant will participate in a single study visit. We anticipate that these investigations will discern the clinical, anatomical, and pathophysiological phenotypes of paranasal sinus disease in PCD compared to PID, identifying disease endpoints and biomarkers that differentiate these two overlapping disorders. Findings from these studies will also enhance our understanding of middle ear disease and associated hearing loss in a cross-sectional cohort of patients with PCD and PID. Ultimately, the long-term goal of our Consortium is to elucidate underlying phenotypes and genotypes of these diseases, potentially leading to novel therapeutics that will improve the lives of affected individuals.