Multidimensional phenotype classification in grade 3 BPD

3 级 BPD 的多维表型分类

基本信息

批准号：
10632887
负责人：
ERIK ALLEN JENSEN
金额：
$ 75.97万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10632887
关键词：
Affect Age Asthma Biological Bronchopulmonary Dysplasia Bronchoscopy Cardiac Cardiopulmonary Caring Characteristics Child Childhood Chronic Chronic Obstructive Pulmonary Disease Chronic lung disease Classification Classification Scheme Clinical Clinical Data Cluster Analysis Cognition Complication Counseling Cystic Fibrosis Data Dependence Development Developmental Disabilities Diagnosis Diagnostic Diagnostic Procedure Diagnostic tests Dimensions Disease Disease Outcome Enrollment Esophagus Evaluation Gastroesophageal reflux disease Health Heterogeneity Hospitals Hypoxemia Image Impairment Individual Infant Intervention Irrigation Life Lung Lung CAT Scan Lung diseases Masks Measures Mechanics Medical Records Medicine Modeling Monitor Morbidity - disease rate Neonatal Neonatology Neurodevelopmental Disability Neurodevelopmental Impairment Outcome Outcome Measure Oxygen saturation measurement Pathologic Pathology Patients Performance Phenotype Pregnancy Premature Birth Premature Infant Prognosis Prospective cohort Pulmonary Inflammation Quality of life Recurrence Reporting Research Research Personnel Selection for Treatments Severities Standardization Subgroup System Testing Therapeutic Intervention Ventilator chest computed tomography clinically relevant cohort cost diagnostic strategy diagnostic technologies disease classification disease heterogeneity disease phenotype disorder subtype dysbiosis effective therapy electric impedance evidence base extreme prematurity heart imaging high risk improved improved outcome lung imaging microbial novel novel diagnostics outcome prediction patient subsets personalized care premature prognostic value pulmonary arterial hypertension respiratory risk stratification targeted treatment ventilation

项目摘要

PROJECT SUMMARY/ABSTRACT Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease that develops over the first months of life in more than half of infants born less than 30wk of gestation. Infants who develop grade 3 BPD, the most severe disease form (defined as invasive ventilation at 36wk postmenstrual age), are at high risk for life-long deficits in health and cognition and poor quality of life. Unfortunately, rates of grade 3 BPD are increasing, and no therapies have been proven to treat this devastating disease. A key contributor to these care gaps is the nearly singular reliance on the prescribed respiratory support to define BPD presence and severity, select therapeutic interventions, and assess prognosis. Our data and others’ show that this subjective diagnostic approach masks significant heterogeneity in clinical presentation, treatment responsiveness, and outcomes. In other heterogenous chronic respiratory conditions such as COPD, cystic fibrosis, and asthma, evidence- based phenotyping (identification of patient subgroups based on shared characteristics) has become the new gold-standard to objectively classify distinct disease sub-types, improve patient counseling, identify novel disease mechanisms, and discover and implement more effective treatments. Our central hypothesis is that multidimensional phenotyping in grade 3 BPD is feasible, will accurately characterize disease heterogeneity, and will improve outcome prediction. Confirmation of this hypothesis will promote a frameshift towards an objective, systematic diagnostic approach in BPD and first-ever phenotype-specific trials in neonatology. Importantly, our motivating preliminary data support this hypothesis. Using retrospective results from chest CT, cardiac echo, and bronchoscopy, we showed that preterm infants with grade 3 BPD can be classified into phenotypes based on the presence or absence of severe parenchymal lung disease, abnormal large airways, and pulmonary arterial hypertension. This diagnostic approach correlated with pre-discharge outcomes and suggested possible phenotype-specific therapies. However, it relied on investigator chosen phenotypes rather than empirically derived subgroups, used qualitative results from only 3 diagnostic tests, and did not assess longitudinal phenotype stability or post-discharge outcomes. Our recent data indicate that serial quantitative cardiopulmonary imaging and evaluation of proven mechanistic contributors to BPD may improve disease phenotyping and outcome prediction. Our proposal builds on these preliminary data and will employ robust cluster analyses and longitudinal multidimensional imaging, biological, and clinical data in a large, prospective cohort of very preterm infants to accomplish the following Specific Aims: (1) define objective, evidence-based phenotypes in grade 3 BPD, and (2) define the strength of association between grade 3 BPD phenotypes and neurodevelopmental and pulmonary outcomes through 2 years’ corrected age using standardized development testing and validated outcome measures.

项目概要/摘要支气管肺发育不良 (BPD) 是一种严重的慢性肺部疾病，在出生后的头几个月内发生超过一半的妊娠期不足 30 周的婴儿会出现 3 级 BPD。严重疾病形式（定义为经后 36 周有创通气），终生面临高风险不幸的是，健康和认知缺陷以及生活质量差，3 级 BPD 的发病率正在上升。没有任何疗法被证明可以治疗这种毁灭性的疾病，造成这些护理差距的一个关键因素是。几乎完全依赖规定的呼吸支持来定义 BPD 的存在和严重程度，选择我们的数据和其他人的数据表明，这种主观诊断。方法掩盖了临床表现、治疗反应和结果方面的显着异质性。其他异质性慢性呼吸道疾病，如慢性阻塞性肺病、囊性纤维化和哮喘，证据- 基于表型分析（根据共同特征识别患者亚组）已成为新的方法客观分类不同疾病亚型、改善患者咨询、识别新疾病的金标准疾病机制，并发现和实施更有效的治疗方法我们的中心假设是： 3 级 BPD 的多维表型分析是可行的，将准确表征疾病异质性，并将改善结果预测。这一假设的确认将促进框架的转变。 BPD 的客观、系统的诊断方法和新生儿学中的首次表型特异性试验。重要的是，我们的初步数据支持了这一假设。胸部 CT、心脏超声和支气管镜检查，我们发现患有 3 级 BPD 的早产儿可以根据是否存在严重肺实质疾病、异常等分为表型该诊断方法与出院前相关。结果并建议可能的表型特异性疗法，但是，这取决于研究者的选择。表型而不是凭经验得出的亚组，仅使用 3 项诊断测试的定性结果，并且没有评估纵向表型稳定性或出院后结果。连续心肺成像和对已证实的 BPD 机制影响因素的评估可能会我们的建议建立在这些初步数据的基础上，并将改善疾病表型和结果预测。采用强大的聚类分析和纵向多维成像、生物和临床数据大型、前瞻性的极早产儿队列，以实现以下具体目标：(1) 定义客观的、基于证据的 3 级 BPD 表型，以及 (2) 定义之间的关联强度 3 级 BPD 表型以及 2 岁校正年龄期间的神经发育和肺部结局使用标准化的开发测试和经过验证的结果测量。