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.

呼吸消化系统各功能部件之间的协调，特别是 在吞咽和呼吸之间，对于婴儿成功的气道保护至关重要。 这种协调的破坏可导致气道保护的失败，表现为肺功能障碍。 抱负早产是造成这种中断和随后的误吸的原因之一。这些 问题可能与喉返神经（RLN）的损伤相结合， 因为早产而进行的心血管修复因为目前对 这些脆弱患者的病理学主要基于非侵入性技术， 协调障碍和气道保护之间的因果关系，包括如何 这个系统的发展，是未知的。特别是，我们不知道生物力学 引起抽吸的改变，以及生物力学中发生的纵向变化（如果有的话） 可以促进气道保护。我们建议调查的纵向过程 有或无喉返神经损伤的早产儿/足月儿的气道保护成熟。使用 一个有效的早产动物模型将允许收集详细的数据，使用侵入性 不适合人类的方法，包括高速、双平面视频透视 患者这里提出的工作将确定早产如何影响感觉运动 成功的气道保护的基础相互作用以及RLN损伤如何影响 这些互动通过三个具体目标：（SA 1）确定纵向发展 对照仔猪出生后呼吸和吞咽协调性 通过断奶;（SA 2）确定纵向发展之间的协调 早产后的呼吸和吞咽，使用与人类相当的猪 胎龄30-32周;（SA 3）确定 （SA 3a）对照足月儿和（SA 3b）早产儿的气道保护和RLN损伤。 通过使用经过验证和验证的具有转化重要性的动物模型， 本文提出的方法将提供关于潜在的正常和病理生理机制的数据 导致早产儿呼吸道保护失败。这些数据是纵向收集的 并以足够的数量来评估个体内的变异和个体发育变化， 个人，将提供洞察力不可能从人类患者。这些数据将改变我们的 了解康复的潜力和治疗建议。此外这些 数据可以作为设计干预战略的基础， 病理生理学的潜在机制。

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