Salivary miRNAs as Prognostic Markers of Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia in Extremely Low Gestational Age Infants

唾液 miRNA 作为极低胎龄婴儿支气管肺发育不良相关肺动脉高压的预后标志物

• 批准号: 10739639
• 负责人: Roopa Siddaiah
• 金额: $ 17.36万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739639
• 关键词: 1 year old; Admission activity; Age; Alveolar; Biological Markers; Biometry; Bronchopulmonary Dysplasia; Cell Proliferation; Cells; Cessation of life; Childhood; Clinical; Clinical Research; Clinical Trials; Complex; Complication; Correlation Studies; Data; Development; Development Plans; Diagnosis; Disease; Early identification; Echocardiography; Etiology; Extremely low gestational age newborn; Feasibility Studies; Foundations; Future; Gene Expression; Genes; Genetic; Genetic Risk; Goals; Growth Factor Gene; Home; Hypoxia; Incidence; Infant; Insulin; Intervention; Intubation; Journals; Learning; Life; Logistic Regressions; Lung; Master of Science; Medical; Mentors; MicroRNAs; Modeling; Molecular; Morbidity - disease rate; Neonatal Intensive Care Units; Outcome; Oxygen; Pathologic; Pathway Analysis; Pathway interactions; Pediatrics; Peer Review; Physicians; Population; Pre-Eclampsia; Predictive Value; Pregnancy; Premature Infant; Prevalence; Prognostic Marker; Prospective Studies; Publishing; Pulmonary Hypertension; Recording of previous events; Regression Analysis; Regulation; Research Project Grants; Risk; Saliva; Salivary; Sampling; Scientist; Small for Gestational Age Infant; Statistical Data Interpretation; Stratification; Subgroup; Testing; Trachea; Tracheostomy procedure; Training; Transforming Growth Factor beta; Translational Research; Untranslated RNA; Vascular Endothelial Growth Factors; Ventilator; Very Low Birth Weight Infant; Vulnerable Populations; Work; angiogenesis; aspirate; biological adaptation to stress; biomarker identification; biomarker panel; career; career development; classification trees; design; differential expression; experience; extreme prematurity; genomic data; high risk; hospital readmission; improved; improved outcome; in silico; interest; intraamniotic infection; longitudinal analysis; lung development; meetings; migration; molecular marker; mortality; multidisciplinary; multiple omics; neonatal care; neonate; predictive marker; pulmonary vascular disorder; recruit; regression trees; respiratory; risk prediction; risk stratification; routine screening; saliva sample; screening; tool; transcriptome sequencing; treatment response; vascular bed

PROJECT SUMMARY/ABSTRACT With recent advances in neonatal care, there is improved survival of extremely premature babies with very low birth weight, although the complications of bronchopulmonary dysplasia (BPD) remain. One of the most severe of these complications is pulmonary hypertension (BPD-PH). The true incidence of BPD-PH in preterm babies is unknown, but prevalence is estimated to range from 17-40%. BPD and BPD-PH are typically diagnosed at 36 weeks postmenstrual age (PMA). BPD-PH leads to more days in the neonatal ICU, increased days of ventilator and oxygen requirement, and the need for tracheostomy and home ventilator support. Furthermore, these infants continue to have high mortality and morbidity with increased hospital readmissions in their first 2 years of life. Some clinical parameters and qualitative markers help predict development of BPD-PH at 36 weeks PMA, such as infants born small for gestational age, maternal history of preeclampsia, chorioamnionitis, and early periods of ventilator support at 7 and 28 days of life. However, we lack quantitative markers to predict development or long-term outcomes such as death, re-hospitalization, or response to therapies. A non-invasive quantitative predictor would help stratify these infants early on and be appropriate for these frequently intubated and medically fragile infants. In our preliminary study among infants with BPD-PH, we non-invasively obtained tracheal aspirate and identified a specific panel of microRNAs (small noncoding RNAs) associated with hypoxic stress response and angiogenic pathways. We have further conducted preliminary studies correlating tracheal aspirate samples with that of saliva from extreme preterm infants. In this proposed K23 project, the Candidate (with advice from an outstanding multidisciplinary team of mentors) will study salivary samples of extreme preterm infants for early identification of target miRNAs that could predict development of BPD-PH and its long-term outcomes. This will be a prospective study of infants born <28 weeks of gestation; saliva samples will be collected at 7 and 28 days of age and analyzed for markers that could predict BPD-PH at 36 weeks of gestation. The Candidate will evaluate miRNA expression in infants with BPD-PH over the first year of life and identify markers that predict diagnosis and outcomes, based on their echocardiogram findings and oxygen requirements. By the end of this K23, the Candidate will have learned how to design and carry out future miRNA studies and analyze their results. She also will have completed selected relevant courses as part of her Master’s Degree in Clinical Research and received guidance on career development. Data will be disseminated at meetings and published in peer-reviewed journals. In summary, this project will provide a strong platform for future R01-type applications and help continue the Candidate’s positive career trajectory and ultimate goal to become an independent physician-scientist and nationally recognized expert in BPD-PH in premature infants.

项目摘要/摘要 随着新生儿护理的最新进展，极早的婴儿的生存率提高了 尽管支气管肺发育不良（BPD）的并发症仍然很低，但仍然存在。最重要的之一 这些并发症的严重是肺动脉高压（BPD-PH）。 BPD-PH在早产中的真实事件 婴儿是未知的，但估计患病率在17-40％范围内。 BPD和BPD-PH通常被诊断出 月经后36周（PMA）。 BPD-PH导致新生儿ICU的更多天，增加的天数 呼吸机和氧气需求，以及气管切开术和家庭呼吸机的需求。此外， 这些婴儿的死亡率和发病率仍然很高，医院的再入院增加了 生活年。一些临床参数和定性标记有助于预测36周的BPD-PH的发展 PMA，例如胎龄小的婴儿，先兆子痫，绒毛膜炎和 在生命的7和28天的早期通风支持。但是，我们缺乏预测的定量标记 发育或长期结局，例如死亡，重新住院或对疗法的反应。无创的 定量预测因子将有助于早期对这些婴儿进行分层，并适合这些婴儿经常插管 和医学上脆弱的婴儿。在我们对BPD-PH的婴儿的初步研究中，我们非侵入性获得 气管抽吸物，并鉴定出与低氧相关的一系列特定的microRNA（小非编码RNA） 压力反应和血管生成途径。我们进一步进行了初步研究，使气管相关 来自极端婴儿的抽吸样品与唾液的样本。 在这个拟议的K23项目中，候选人（在一个杰出的多学科团队的建议下 导师）将研究极端婴儿的唾液样本，以早日鉴定目标miRNA 可以预测BPD-PH及其长期结果的发展。这将是对婴儿的前瞻性研究 出生于妊娠28周；唾液样品将在7天和28天内收集，并分析标记 这可以预测妊娠36周的BPD-PH。候选人将评估婴儿的miRNA表达 BPD-PH在生命的第一年中，并确定预测诊断和结果的标记 超声心动图发现和氧气要求。到本k23结束时，候选人将了解如何 设计和进行未来的miRNA研究并分析其结果。她还将完成选择 相关课程是其临床研究硕士学位的一部分，并获得了职业指导 发展。数据将在会议上传播，并在同行评审期刊上发布。总而言之，这 项目将为未来的R01型应用程序提供强大的平台，并帮助候选人的积极 职业轨迹和最终目标是成为独立的身体科学家和全国认可 BPD-PH的专家早产婴儿。