Coordination of Respiration with Deglutition & Phonation in Ataxia-Telangiectasia

描述（由申请人提供）：呼吸和吞咽之间的时间联系对于气道保护至关重要，因为这些功能共享咽作为共同的通路。这种联系的中断是口咽吞咽困难疾病的一个重要问题。共济失调-毛细血管扩张症（A-T）是一种单基因疾病，可导致进行性神经变性和延髓功能障碍，包括吞咽功能障碍（吞咽困难）。最常见的死亡原因是A-T患者的复发性肺部感染。我们将使用呼吸测量（RDT）仪器来表征A-T患者吞咽期间的呼吸。RDT仪器是非侵入性的，并且在健康受试者的整个生命周期中准确地定义了这种关系。此外，我们将开发A-T作为一个模型系统，用于量化没有重复辐射暴露的儿童吞咽困难的进展。为了实现这些目标，我们建议A-T临床中心（约翰霍普金斯医院，巴尔的摩MD）和研究人员之间建立伙伴关系，这些研究人员已经定义了健康受试者与RDT（伊利诺伊大学厄巴纳-香槟分校）的吞咽关系。该合作将通过常见的和先前验证的程序和数据分析方案来表征吞咽-吞咽关系，以（a）标准化用于评估A-T患者吞咽的临床评估工具，（B）提供提交全面研究资助所需的数据。我们假设A-T患者的呼吸-吞咽和呼吸-发声之间的时间关系会出现中断。具体目标：具体目标#1。阐明年龄和疾病进展对A-T患者横断面组中呼吸-吞咽关系的影响。具体目标#2。阐明年龄和疾病进展对A-T患者横断面组中发音-发声关系的影响。长期目标是使用呼吸和吞咽协调作为治疗性临床试验和吞咽治疗的结果测量。描述A-T患者的这些关系应有助于早期识别吞咽功能障碍，帮助跟踪吞咽困难模式的过程，并降低与吞咽困难相关的发病率。此外，发展A-T作为一个模型将成为将这种非侵入性技术应用于其他吞咽困难儿童的基础。

DESCRIPTION (provided by applicant): Temporal linkage between breathing and swallowing is critical for airway protection because these functions share the pharynx as a common pathway. Disruption of this linkage is a significant concern in diseases with oropharyngeal dysphagia. Ataxia-Telangiectasia (A-T) is a monogenic condition that causes progressive neurodegeneration and bulbar dysfunction, including swallowing dysfunction (dysphagia). The single most common cause of death is recurrent lung infections in patients with A-T. We will use Respirodeglutometric (RDT) instrumentation to characterize the respiration during deglutition in patients with A-T. RDT instrumentation is non-invasive and has accurately defined this relationship in healthy subjects across the life-span. Moreover, we will develop A-T as a model system for quantifying the progression of dysphagia in children without repeated radiation exposure. To accomplish these goals, we propose the creation of a partnership between the A-T Clinical Center (Johns Hopkins Hospital, Baltimore MD) and researchers who have defined respiratory-swallowing relationships in healthy subjects with the RDT (University of Illinois, Urbana-Champaign). This collaboration will characterize respiratory-swallow relationships with common and previously validated procedural and data analysis protocols to (a) standardize a clinic assessment tool for the evaluation of swallowing in patients with A-T and (b) provide data necessary for submission of a full- scale research grant. We hypothesize that patients with A-T will exhibit disruptions in the temporal relationships between respiration-deglutition and between respiration-phonation. The following specific aims will be addressed: Specific Aim #1. To elucidate the impact of age and disease progression on respiratory- swallow relationships in a cross-sectional group of patients with A-T. Specific Aim #2. To elucidate the impact of age and disease progression on respiratory-phonatory relationships in a cross-sectional group of patients with A-T. Long-term goals are to use respiration and deglutition coordination as an outcome measure for therapeutic clinical trials and swallowing therapies. Characterizing these relationships in patients with A-T should facilitate earlier identification of swallowing dysfunction, help track the course of dysphagic patterns, and decrease the morbidity associated with the dysphagia. Furthermore, developing A- T as a model will form the basis for applying this non-invasive technology to other children with dysphagia.