Hibbs -Association Between Intermittent Hypoxia and Later Respiratory Morbidity

希布斯 - 间歇性缺氧与后期呼吸系统疾病之间的关联

• 批准号: 9169707
• 负责人: Anna Maria Hibbs
• 金额: $ 18.82万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9169707
• 关键词: Age; Age-Months; Animal Model; Apnea; Asthma; Basic Science; Biochemical Markers; Biological Markers; Biomedical Engineering; Blood specimen; Breathing; Clinical; Clinical Trials; Cohort Studies; Collection; Data; Data Collection; Development; Disease; Enrollment; Environmental air flow; Event; Frequencies; Future; Gestational Age; Goals; Hospitalization; Hypoxia; Incidence; Infant; Intervention; Lead; Length; Length of Stay; Life; Link; Lung; Measurement; Measures; Morbidity - disease rate; Mus; Neonatal; Neonatal Apneic Attack; Outcome; Oxidative Stress; Oxygen; Oxygen Therapy Care; Pathway interactions; Pattern; Pharmaceutical Preparations; Population; Pregnancy; Premature Birth; Premature Infant; Process; Pulse Oximetry; Recovery; Research Personnel; Resistance; Resolution; Respiratory System; Retinopathy of Prematurity; Risk; Rodent; Role; Serotonergic System; Serotonin; Signal Transduction; Smooth Muscle Actin Staining Method; Staging; Structure; Symptoms; Time; Urine; Wheezing; Work; cohort; experience; falls; follow-up; high risk; improved; lung injury; meetings; novel; oxidant stress; oxidation; postnatal; premature; prospective; respiratory; respiratory smooth muscle; time interval

Project Summary Longer term respiratory morbidity remains a major consequence of preterm birth. We seek to characterize the association between immature respiratory control manifest as intermittent hypoxia [IH] and later respiratory morbidity in a cohort of preterm infants less than or equal to 30 weeks' gestation. Our hypotheses in Aims 1 and 2 are that IH episodes at one week and one month of life are significantly associated with prolonged duration of hospitalization and respiratory support, as well as a high incidence of wheezing disorders by six months adjusted age. In Aim 3 we hypothesize that low serotonin levels are associated with a high incidence of IH and a prolonged recovery of respiratory effort after onset of desaturation. Finally, in Aim 4 we hypothesize a temporal relationship between IH episodes and markers of oxidative stress determined by urine and blood samples. In prior studies we have demonstrated that apnea almost always precedes desaturation in preterm infants and have documented a novel association between retinopathy of prematurity, and both the duration of IH events and the time interval between IH events. From these data we speculate that it is both longer IH events and a distinct time interval of at least one minute between IH events that will be associated with respiratory morbidity and accompanying oxidative stress. This proposal provides a unique opportunity to quantify, for the first time, a relationship between IH and biomarkers of oxidation. We provide additional retrospective data that IH is associated with both increased length of stay and postnatal wheezing disorders, as well as a remarkable track record for both meeting enrollment goals and effective follow-up in prior clinical trials. Additionally, we have a strong track record for collection of continuous cardiorespiratory waveforms with bioengineering expertise in signal acquisition and processing that is ideally suited for multicenter data collection. In conclusion, our investigators' expertise in the measurement and analysis of respiratory and saturation waveforms, characterization of IH events, the basic science of respiratory control, and the measurement of clinical respiratory outcomes, makes us ideally poised to execute this single center, as well as multisite, proposal.

项目概要 长期呼吸道疾病仍然是早产的一个主要后果。我们力求 表征不成熟的呼吸控制之间的关联，表现为间歇性 小于或等于 30 岁的早产儿队列中缺氧 [IH] 以及随后的呼吸系统疾病 怀孕几周。我们在目标 1 和 2 中的假设是，IH 发作在一周和一周时发生。 生命月数与住院时间延长显着相关 呼吸支持，以及六个月调整后喘息疾病的高发生率 年龄。在目标 3 中，我们假设低血清素水平与高发病率相关 IH 和去饱和发生后呼吸努力的长时间恢复。最后，在目标 4 中，我们 假设 IH 发作和氧化应激标志物之间存在时间关系 通过尿液和血液样本确定。在之前的研究中，我们已经证明呼吸暂停 几乎总是发生在早产儿的去饱和之前，并记录了一项新颖的研究 早产儿视网膜病变与 IH 事件持续时间和时间之间的关联 IH 事件之间的间隔。根据这些数据，我们推测这既是较长的 IH 事件，又是一个 与相关的 IH 事件之间至少有一分钟的不同时间间隔 呼吸道疾病和伴随的氧化应激。该提案提供了一个独特的 首次有机会量化 IH 和氧化生物标志物之间的关系。 我们提供了额外的回顾性数据，表明 IH 与住院时间的延长有关 和产后喘息障碍，以及这两项会议的卓越记录 先前临床试验的入组目标和有效随访。此外，我们还有强大的 通过生物工程收集连续心肺波形的跟踪记录 信号采集和处理方面的专业知识非常适合多中心数据 收藏。总之，我们的研究人员在测量和分析方面的专业知识 呼吸和饱和波形、IH 事件的特征、基础科学 呼吸控制和临床呼吸结果的测量使我们成为理想的选择 准备执行这个单一中心以及多站点的提案。