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

摘要项目3 原发性睫状肌运动障碍(PCD)和原发性免疫缺陷(PID)患者上呼吸道疾病的发病率 没有很好地定义。这些疾病可能很难区分，因为它们的表型重叠。这个 鼻窦和中耳特征通常被患者及其家人认为是最有问题的，并且 最佳治疗方案尚未建立。这个项目的主要目标是描述和描述 比较PCD和PID患者的上呼吸道表型，并收集关键数据为未来的设计提供参考 治疗上呼吸道和中耳疾病的临床试验。 该项目有三个主要的具体目标：在目标1中，我们将描述和比较PCD和 使用三个主要终点：临床特征、生活质量和 嗅觉功能的测量。分目标1a将通过鼻腔描述鼻窦解剖和疾病严重程度。 内窥镜检查和CT成像，采用经过验证的评分系统，而次级目标1b将进行评估和比较 PCD和PID的鼻窦粘液成分(粘蛋白、蛋白质、炎症标志物、细菌)。在目标2中， 我们将描述和比较复发性中耳炎对临床特征、传导性和 儿童和成人PCD和PID的感音神经性听力损失。在目标3中，我们将确定是否 耳鼻喉科表型(在AIMS 1和2中评估)和特定的超微结构之间存在联系 PCD患者的缺陷和基因分型。 在这项横断面、观察性、多中心研究中，参与者将从四个联合体站点招募： 北卡罗来纳大学(UNC)、麦吉尔大学(MU)、多伦多大学、患病儿童医院(UT- 华盛顿大学圣路易斯分校(WUSTL)。我们将平均招募200名参与者 在被诊断为PCD和PID的个体之间；每个参与者将参加一次研究访问。 我们预计，这些研究将辨别临床、解剖和病理生理表型。 比较PCD和PID的副鼻窦疾病，识别疾病终点和生物标志物 区分这两种重叠的障碍。这些研究的结果也将加深我们对 在PCD和PID患者的横断面队列中，中耳疾病和相关听力损失的风险。 最终，我们联盟的长期目标是阐明这些基因的潜在表型和基因类型 疾病，可能导致新的治疗方法，将改善受影响个人的生活。

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.