Predictive Modeling for Treatment of Upper Airway Obstruction in Young Children

描述（由申请人提供）：有上气道异常的婴儿和儿童存在缺氧、呼吸功能不全和长期发病的风险。这些疾病中遇到的多层次气道阻塞会导致危及生命的空气交换困难、吞咽协调、生长和语言发育问题。在这些气道疾病中，治疗通常由临床医生的经验和偏好来指导，而不是根据标准化的生理或解剖指标。定量方法评估和确定这些上气道异常的最佳管理将对改善临床护理和结果有巨大的好处。新的研究工具现在可以测量计算流体动力学。这些流固相互作用模型通过创建气道的虚拟模型，计算出气流、壁面剪切应力、压力分布和气道壁形状变化，从而将动态解剖学与生理测量相结合。该计算模型可以进行虚拟修改，以反映医疗干预、手术技术和正常生长，可以预测气道壁顺应性、新的气流模式、压力分布和其他生理变量的变化，从而在干预之前产生预期的临床结果。当计算建模工具用于儿科上呼吸道干预计划时，结果的改善是巨大的，特别是在复杂的临床情况下。为了模型开发的目的，我们专注于两个非常具体的，经常遇到的，在我们中心遇到的高风险异常，Pierre Robin序列和声门下狭窄。关于上气道生长发育的规范性数据将被研究。我们假设一个功能计算模型可以模拟患有Pierre Robin序列和喉部病变（如声门下狭窄）的儿童上呼吸道的力学和空气动力学行为，可以作为有效的诊断和治疗计划工具，减少初始治疗的失败，避免潜在的不必要的并发症和干预。本研究的具体目标是：（1a）建立儿童上气道的功能计算模型，该模型可用于诊断和预测10岁以下患有Pierre Robin序列和声门下狭窄的儿童的治疗结果；将获得正常气道的数据和模型，以帮助开发描述老化气道的儿科气道解剖图谱；还将开发一个集成的虚拟儿科气道工作台（1b）使用解剖学和生理学测量来验证功能性计算模型，该模型用于评估患有Pierre Robin序列和声门下狭窄的小于10岁儿童的气道通畅和上呼吸道气流限制；(2)将计算模型应用于患有Pierre Robin序列和声门下狭窄的儿童。并确定模型在解剖和生理指标上准确预测各种潜在干预结果的能力。公共卫生相关性：幼儿上呼吸道问题可能导致危及生命的呼吸困难、生长不良、误吸、语言发育迟缓和长期发病。两种常见的上气道异常是Pierre Robin序列（下颌小，腭裂，舌头向下移位）和声门下狭窄（声带以下气道狭窄）。这些儿童的管理通常由临床医生的经验和偏好来指导，而不是根据公布的方案或气道生理学和解剖学的定量测量。改进评估和确定最佳管理的方法将有利于临床护理和结果。新的研究工具，测量结构，气流和本质上创建气道的虚拟模型将显著改善这些儿童的护理。这些计算模型现在是可能的，并且可以修改以反映医疗或手术干预以及正常的生长和发育。通过计算建模改进的定量测量具有显著改善复杂上呼吸道患儿护理的巨大潜力。本研究的研究人员假设，可以开发一种功能计算模型，类似于具有复杂上气道的婴儿，特别是皮埃尔·罗宾序列和声门下狭窄的儿童上呼吸道的机械和空气动力学行为。研究人员还假设该模型可以用作有效的诊断/治疗计划工具；从而减少治疗失败，避免未来不必要的并发症或干预。本研究的具体目标是：（1a）建立儿童上气道的功能计算模型，该模型可用于诊断和预测10岁以下患有Pierre Robin序列和声门下狭窄的儿童的治疗结果；还将获得正常气道的数据和建模，以开发描述老化气道的儿科气道解剖图谱，还将开发儿科气道工作台，使医生能够听到气道声音并“虚拟”与气道交互（1b）。(2)将计算模型应用于正在评估Pierre Robin Sequence和声门下狭窄的婴儿和儿童，并确定该模型准确预测各种潜在干预措施对临床结果的影响的能力。对于整个气道，成人和儿童，以及更广泛的病理性气道问题的计算建模应用的长期影响有可能改变当前的管理方法。（摘要结束）

DESCRIPTION (provided by applicant): Infants and children with abnormalities of the upper airway are at risk for hypoxia, respiratory insufficiency and long term morbidity. Multiple levels of airway obstruction encountered in these disorders lead to life threatening difficulties in air exchange, problems with coordination of swallowing, growth, and speech development. In these airway disorders, therapy is typically directed by the clinician's experience and preference, rather than on normalized physiologic or anatomic metrics. Quantitative methods of evaluating and determining optimal management of these upper airway anomalies would be of tremendous benefit for improved clinical care and outcomes. New research tools can now measure computational fluid dynamics. These fluid-structure interaction models allow for the merger of dynamic anatomy with physiologic measures by creating a virtual model of the airway with computed measures of airflow, wall shear stress, pressure distribution, and airway wall shape change. This computational model can be virtually modified to reflect medical intervention, surgical techniques, and normal growth, which can predict changes in airway wall compliance, new airflow patterns, pressure distribution, and other physiologic variables to yield expected clinical results prior to intervention. Improvements in outcomes when computational modeling tools are used in pediatric upper airway intervention planning is enormous, particularly in complicated clinical scenarios. For purposes of model development, we focus on two very specific, commonly encountered, high risk anomalies encountered at our center, Pierre Robin sequence and subglottic stenosis. Normative data regarding growth and development of the upper airway will be studied. We hypothesize that a functional computational model that simulates the mechanical and aerodynamic behavior of the upper airway in children with Pierre Robin sequence and laryngeal lesions (e.g. subglottic stenosis) can be used as an effective diagnostic and treatment planning tool, reducing failures of initial treatment and avoiding potentially unnecessary future complications and interventions. Specific aims for this proposal are to: (1a) develop a functional computational model of the pediatric upper airway which can be used for diagnosis and to predict treatment outcomes in children < 10 years of age with Pierre Robin sequence and subglottic stenosis; data and modeling of normal airways will be obtained to help develop a Pediatric Airway Anatomical Atlas describing the aging airway; an integrated Virtual Pediatric Airway Workbench will also be developed (1b) validate the functional computational model using anatomic and physiologic measures that assess airway patency and airflow limitation in the upper airway in children < 10 years of age with Pierre Robin Sequence and subglottic stenosis and (2) apply the computational model to children being evaluated for Pierre Robin Sequence and subglottic stenosis, and determine the ability of the model to accurately predict results of various potential interventions on anatomic and physiologic metrics. PUBLIC HEALTH RELEVANCE: Upper airway problems in young children may lead to life threatening respiratory difficulties, poor growth, aspiration, delay in speech development and long term morbidity. Two common upper airway anomalies are Pierre Robin sequence (small jaw, cleft palate, downward displacement of the tongue) and subglottic stenosis (narrowing of the airway below the vocal cords). Management of these children is typically directed by the clinician's experience and preference, rather than on published protocols or quantitative measures of airway physiology and anatomy. Improved methods of evaluating and determining best management would benefit clinical care and outcomes. Novel research tools that measure structure, airflow and essentially create a virtual model of the airway would significantly improve care of these children. These computational models are now possible and can be modified to reflect medical or surgical intervention as well as normal growth and development. Improved quantitative measurements through computational modeling have enormous potential to significantly improve care in children with complicated upper airways. The researchers in this study hypothesize that a functional computational model may be developed that is similar to the mechanical and aerodynamic behavior of the upper airway in infants with complicated upper airways, specifically children with Pierre Robin Sequence and subglottic stenosis. The researchers also hypothesize that this model could be used as an effective diagnostic/treatment planning tool; thereby, reducing failed treatment and avoiding unnecessary future complications or interventions. Specific aims for this proposal are to: (1a) develop a functional computational model of the pediatric upper airway which can be used for diagnosis and to predict treatment outcomes in children < 10 years of age with Pierre Robin sequence and subglottic stenosis; data and modeling of normal airways will also be obtained to develop a Pediatric Airway Anatomical Atlas describing the aging airway and a workbench of the pediatric airway will also be developed allowing the physician to hear airway sounds and "virtually" interact with the airway (1b) validate the functional computational model using clinical, anatomic and physiologic measures that evaluate airway size and obstruction in the upper airway in children < 10 years of age with Pierre Robin Sequence and subglottic stenosis and (2) apply the computational model to infants and children being evaluated for Pierre Robin Sequence and subglottic stenosis, and determine the ability of the model to accurately predict the results of various potential interventions on clinical outcomes. The long term implications for the application of computational modeling for the entire airway, adult and pediatric, and to the broader range of pathologic airway problems has the potential to change the current approach to management. (End of Abstract)