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

原发性纤毛运动障碍和原发性免疫缺陷的上呼吸道表现特征

• 批准号: 10011877
• 负责人: Stephanie Duggins Davis
• 金额: $ 22.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-06 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011877
• 关键词: Adult; Affect; Airway Disease; Anatomy; Bacteria; Biological Markers; Characteristics; Child; Chronic; Clinical; Clinical Treatment; Clinical Trials; Conductive hearing loss; Congestive; Data; Defect; Development; Diagnosis; Disease; Ear; Endoscopy; Enrollment; Family; Functional disorder; Future; Genetic Diseases; Genetic Predisposition to Disease; Genotype; Goals; Hereditary Disease; Hospitals; Immune system; Immunologic Tests; Impairment; Individual; Investigation; Lead; Lung diseases; Measures; Morbidity - disease rate; Mucins; Mucociliary Clearance; Mucous body substance; Multicenter Studies; North Carolina; Nose; Otitis Media; Otitis Media with Effusion; Outcome Measure; Paranasal Sinus Diseases; Participant; Patients; Pattern; Phenotype; Positioning Attribute; Primary Ciliary Dyskinesias; Proteins; Quality of life; Recurrence; Reporting; Sensorineural Hearing Loss; Severities; Severity of illness; Sinus; Site; Smell Perception; Speech Development; System; Testing; Treatment Protocols; Universities; Visit; Washington; X-Ray Computed Tomography; base; chronic infection; chronic rhinosinusitis; clinical subtypes; cohort; congenital immunodeficiency; design; ear infection; early childhood; effusion; experience; genetic disorder diagnosis; genetic testing; hearing impairment; improved; infancy; inflammatory marker; middle ear; middle ear disorder; novel therapeutics; optimal treatments; primary endpoint; prospective; protein biomarkers; recruit; recurrent infection; respiratory; therapeutic target; treatment strategy

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.

抽象项目3 原发性纤毛运动障碍 (PCD) 和原发性免疫缺陷 (PID) 中上呼吸道疾病的发病率 没有明确定义。由于表型重叠，这些病症可能很难区分。这 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 最佳治疗方案尚未确定。该项目的主要目标是描述和描述 比较 PCD 和 PID 中的上呼吸道表型，并收集关键数据，为未来的设计提供信息 治疗上呼吸道和中耳疾病的临床试验。 该项目有三个主要具体目标： 在目标 1 中，我们将描述和比较 PCD 和 PCD 的影响。 使用三个主要终点来评估 PID 鼻窦疾病对患者体验的影响：临床特征、生活质量和 嗅觉功能的测量。子目标 1a 将描述鼻窦解剖结构和疾病严重程度 内窥镜检查和 CT 成像，采用经过验证的评分系统，而子目标 1b 将评估和比较 PCD 和 PID 中鼻窦的粘液成分（粘蛋白、蛋白质、炎症标记物、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、传导性和中耳炎的影响。 患有 PCD 和 PID 的儿童和成人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（在目标 1 和 2 中评估）和特定超微结构之间存在关系 PCD 参与者的缺陷和基因型。 在这项横断面、观察性、多中心研究中，将从四个联盟地点招募参与者： 北卡罗来纳大学 (UNC)、麦吉尔大学 (MU)、多伦多大学、病童医院 (UT- HSC）和圣路易斯华盛顿大学（WUSTL）。我们将招募200名参与者，平均分配 诊断患有 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、解剖学和病理生理学表型 与 PID 相比，PCD 中鼻窦疾病的影响，确定疾病终点和生物标志物 区分这两种重叠的疾病。这些研究的结果也将增强我们的理解 PCD 和 PID 患者横断面队列中的中耳疾病和相关听力损失。 最终，我们联盟的长期目标是阐明这些疾病的潜在表型和基因型 疾病，可能会导致新的治疗方法改善受影响个体的生活。