The Effect of Preterm Birth and RLN Damage on Airway Protection and Maturation

早产和 RLN 损伤对气道保护和成熟的影响

• 批准号: 9906065
• 负责人: Rebecca Z German
• 金额: $ 47.23万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906065
• 关键词: Abnormal coordination; Address; Age; Animal Model; Animals; Biomechanics; Birth; Breathing; Cardiovascular system; Caring; Collection; Data; Data Set; Deglutition; Development; Developmental Course; Ethics; Exhibits; Failure; Family suidae; Functional disorder; German population; Gestational Age; Growth; Human; Iatrogenesis; Incidence; Individual; Infant; Intervention; Knowledge; Larynx; Lesion; Lung; Measurement; Methods; Modeling; Oral; Pathology; Patients; Pattern; Pharyngeal structure; Physiological; Premature Birth; Premature Infant; Recommendation; Recovery; Recurrent Laryngeal Nerve; Respiration; Speed; System; Technology; Term Birth; Time; Treatment Efficacy; Weaning; Work; base; course development; experimental study; improved; individual variation; insight; kinematics; longitudinal course; model design; nerve injury; premature; prevent; repaired; respiratory; therapy design; translational model

Coordination among the functional components of the aerodigestive system, particularly between swallowing and respiration, is critical for successful airway protection in infants. Disruption of this coordination can produce failure of airway protection, manifest as pulmonary aspiration. Preterm birth is one cause of this disruption and subsequent aspiration. These problems may be compounded with damage to the recurrent laryngeal nerve (RLN) resulting from cardiovascular repairs necessitated by prematurity. Because the current understanding of the pathologies in these fragile patients is based largely on non-invasive technologies, the causal relationship between disordered coordination and airway protection, including how development impacts this system, is unknown. In particular, we do not know the biomechanical alterations that cause aspiration nor what, if any, longitudinal changes occur in biomechanics that may promote airway protection. We propose to investigate the longitudinal course of maturation of airway protection in preterm/term infants, with and without RLN damage. The use of a validated preterm animal model will permit the collection of detailed data, using invasive methods, including high-speed, biplanar videofluoroscopy, that are not appropriate for human patients. The work proposed here will determine how preterm birth effects the sensorimotor interactions that underlie successful airway protection as well as how RLN damage impacts those interactions through three specific aims: (SA1) Determine the longitudinal development of coordination between respiration and swallowing in control infant pigs born at term from birth through weaning; (SA2) Determine the longitudinal development of the coordination between respiration and swallowing after preterm birth using pigs delivered at the equivalent of human gestational age of 30-32 weeks; (SA3) Determine the interaction between the maturation of airway protection and RLN injury in both (SA3a) control term infants and (SA3b) preterm infants. By working with a proven and validated animal model of translational importance, the study proposed here will provide data on the underlying normal and pathophysiologic mechanisms that cause failure of airway protection in preterm infants. These data, collected longitudinally and in sufficient quantity to assess within individual variation and ontogenetic changes within individuals, will provide insight not possible from human patients. Such data will change our understanding of the potential for recovery and treatment recommendations. Furthermore these data can be the basis for designing intervention strategies based on understanding of the mechanisms underlying the pathophysiology.

气化系统的功能组件之间的协调，特别是 在吞咽和呼吸之间，对于婴儿的成功气道保护至关重要。 这种协调的破坏会导致气道保护失败，表现为肺部 抽吸。早产是这种破坏和随后攻击的原因之一。这些 问题可能会使对复发性喉神经（RLN）的损害更加复杂 从早产中需要的心血管维修。因为当前对 这些脆弱患者的病理主要基于非侵入性技术，即 无序协调与气道保护之间的因果关系，包括如何 开发影响该系统是未知的。特别是，我们不知道生物力学 引起抽吸的变化或生物力学中发生的纵向变化（如果有）发生了什么 这可能会促进气道保护。我们建议调查 在有没有RLN损害的情况下，早产/期限婴儿的气道保护成熟。使用 经过验证的早产模型将允许使用侵入性收集详细数据 方法，包括高速，双波拉型视频荧光镜检查，不适用于人类 患者。这里提出的工作将决定感觉运动的早产如何 成功的气道保护以及RLN损害如何影响的互动 通过三个特定目标进行的相互作用：（SA1）确定 呼吸与吞咽对照婴儿猪的协调从出生开始出生 通过断奶； （SA2）确定协调之间的纵向发展 早产后使用与人类等效的猪进行呼吸和吞咽 妊娠年龄为30-32周； （SA3）确定成熟之间的相互作用 （SA3A）控制术语婴儿和（SA3B）早产儿的气道保护和RLN损伤。 通过使用经过验证和经过验证的转化重要性模型，该研究 这里提出的将提供有关基本正常和病理生理机制的数据 这会导致早产儿的气道保护失败。这些数据，纵向收集 并有足够的数量评估在个体变异和内部发生变化之内 个人将提供人类患者不可能的见解。这样的数据将改变我们的 了解恢复和治疗建议的潜力。此外，这些 数据可能是根据对理解的理解设计干预策略的基础 病理生理学的基础机制。

项目成果

The pattern of brain-size change in the early evolution of cetaceans.

• DOI: 10.1371/journal.pone.0257803
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Waugh DA;Thewissen JGM
• 通讯作者: Thewissen JGM

Evolution, diversification and function of the maternal-infant dyad in mammalian feeding.

哺乳动物喂养中母婴二元的进化、多样化和功能。

• DOI: 10.1098/rstb.2022.0554
• 发表时间: 2023
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Mayerl,ChristopherJ;German,RebeccaZ
• 通讯作者: German,RebeccaZ

Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model.

• DOI: 10.1007/s00455-018-9881-z
• 发表时间: 2018-10
• 期刊: Dysphagia
• 影响因子: 2.6
• 作者: Ballester A;Gould F;Bond L;Stricklen B;Ohlemacher J;Gross A;DeLozier K;Buddington R;Buddington K;Danos N;German R
• 通讯作者: German R

Sucking versus swallowing coordination, integration, and performance in preterm and term infants.

早产儿和足月儿吸吮与吞咽的协调、整合和表现。

• DOI: 10.1152/japplphysiol.00668.2020
• 发表时间: 2020
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Mayerl,ChristopherJ;Edmonds,ChloeE;Catchpole,EmilyA;Myrla,AlexisM;Gould,FrancoisDH;Bond,LauraE;Stricklen,BethanyM;German,RebeccaZ
• 通讯作者: German,RebeccaZ

Does birth weight affect neonatal body weight, growth, and physiology in an animal model?

• DOI: 10.1371/journal.pone.0246954
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Adjerid K;Mayerl CJ;Gould FDH;Edmonds CE;Stricklen BM;Bond LE;German RZ
• 通讯作者: German RZ